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Advances in

OPHTHALMOLOGY

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Advances in
OPHTHALMOLOGY

Ashok Garg

Suresh K Pandey

MS PhD FIAO (Bel) FRSM ADM FICA FAIMS FICS

MD

National and International Gold Medalist


Medical Director
Garg Eye Institute and Research Centre
235, Model Town
Dabra Chowk
Hisar (India)

Instructor, John A Moran Eye Center


Department of Ophthalmology and
Visual Sciences
University of Utah, 50, North Medical Drive
Salt Lake City, Utah (USA)

David J Apple
Vidushi Sharma

MD

MD FRCS (Edin)

John A Moran Professor of Ophthalmology


Co-Director
David J Apple
Laboratories for Ophthalmic Devices
Research, John A Moran Eye Center
Department of Ophthalmology and
Visual Sciences
University of Utah, 50, North Medical Drive
Salt Lake City, Utah (USA)

Sr Resident
Dr Rajendra Prasad Center for
Ophthalmic Sciences
All India Institute of Medical Sciences
Ansari Nagar
New Delhi (India)

Foreword

Illustrations

Jairo E Hoyos

Ashok Garg

JAYPEE BROTHERS
MEDICAL PUBLISHERS (P) LTD
New Delhi

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Published by
Jitendar P Vij
Jaypee Brothers Medical Publishers (P) Ltd
EMCA House, 23/23B Ansari Road, Daryaganj
New Delhi 110 002, India
Phones: 23272143, 23272703, 23282021, 23245672, 23245683
e-mail: jpmedpub@del2.vsnl.net.in
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Advances in Ophthalmology1
2003, Ashok Garg, Suresh K Pandey, Vidushi Sharma, David J Apple
All rights reserved. No part of this publication should be reproduced, stored in a retrieval
system, or transmitted in any form or by any means: electronic, mechanical, photocopying,
recording, or otherwise, without the prior written permission of the editors and the publisher.
This book has been published in good faith that the material provided by contributors
is original. Every effort is made to ensure accuracy of material, but the publisher, printer
and editors will not be held responsible for any inadvertent error(s). In case of any
dispute, all legal matters are to be settled under Delhi jurisdiction only.
First Edition : 2003
Publishing Director: RK Yadav
ISBN 81-8061-098-5
Typeset at JPBMP typesetting unit
Printed at Gopsons Papers Ltd., A-14, Sector 60, Noida

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Dedicated to
My Respected Guru
Sant Gurmeet Ram Rahim Singh Ji
Param Pujya Agam Muni Ji and
Sthir Muni Ji for their blessings
All my respected teachers specially
Prof IPS Parmar
Prof CS Dhull
Prof D Randell and
Prof Wanberg
for their invaluable guidance
My respected parents, my wife
Dr Aruna Garg and my son and
daughter for their endless support
My dear friend Dr Amar Agarwal for his
timely advice and whole hearted support

Param Pujya Gurudev


Pt Shri Ram Sharma Acharya and
Mata Bhagawati Devi Sharma
Shantikunj, Hardwar, India
for their blessings
My respected parents
(Shri Kameshwar Prasad Pandey and
Smt Maya Devi Pandey)
for helping me to set higher goals
All my teachers and colleagues
(particularly, Dr Liliana Werner
Prof David J Apple,
Prof Jagat Ram and Dr Amar Agarwal)
for the constant encouragement and
for transmitting their skills and
expertise with passion and enthusiasm

Ashok Garg

My respected parents for


their constant support
All my respected teachers for
their endless guidance
All the countless patients who repose
their total trust in us, and without
whom modern ophthalmic science
would never be possible

Suresh K Pandey
Sir Harold Ridley
the inventor of intraocular lens
and the man who cured aphakia
All my fellows, the Apple Korps
for their valuable contribution
to advance the science of Ophthalmology
My wife Ann Apple
for sharing my journey and
making it worthwhile

Vidushi Sharma
David J Apple

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Contributors
Alice Handzel
Augenarztin
Zeigelhuttenweg 1-3
D-60598, Frankfurt (Germany)

Athiya Agarwal
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)

Amar Agarwal
Director
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)

Clement K Chan
Retina, Consultants
Southern California Desert
PO Box 2467,Palm Springs
CA 92263 (USA)

Anand A Bagmar
Aditya Jyot Eye Hospital
Mumbai (India)

Clive O Peckar
Consultant Ophthalmic Surgeon
Department of Ophthalmic Surgery
Warrington Hospital
United Kingdom (UK)

Andrea M Izak
Department of Ophthalmology
Storm Eye Institute
Charleston SC (USA)
Anjli Hussain
Macular Clinic
Aditya Jyot Eye Hospital
Mumbai (India)
Asha B
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)
Ashish Doshi
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)
Ashish Mahobia
Retina Foundation
Aso Palov Eye Hospital
Ahmedabad (India)
Ashok Garg
Medical Director
Garg Eye Institute and Research
Centre, 235, Model Town
Dabra Chowk
Hisar-125005 (India)

Cyres Mehta
Mehta International Eye Institute
Sea Side, 147 Colaba Road
Mumbai-400005 (India)
David J Apple
Co-Director
John A Moran Eye Centre
University of Utah
50, North Medical Drive
Salt Lake City, Utah (USA)
Dimitrii D Dementiev
San Babila Day Hospital
Via Stoppani, 36, Milano, Italy
Fernando Rodriquez-Mier
Instituto Oftalmologico De
Sabadell, Barcelona (Spain)

Guillermo Avalos
Guadalajara
Mexico
Guillermo L Simn-Castellvi
Clinica Oftalmologica Simon
Simon Eye Clinic, Barcelona (Spain)
Jagat Ram
Professor
Department of Ophthalmology
PGI, Chandigarh (India)
J Agarwal
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai -600086 (India)
Jairo E Hoyos
Director
Instituto Oftalmologico De
Sabadell, Barcelona(Spain)
Jes Mortensen
Lonnholmsgatan 9D
Jonkoping, Sweden
Jaya Thakur
Tilganga Eye Centre
Kathmandu (Nepal)
Kamal Nagpal
Retina Foundation, Aso Palov
Eye Hospital
Ahmedabad (India)

Francisco J Gutirrez-Carmona
Department of Ophthalmology
Carmona Hospital General De
Segovia, Segovia (Spain)

Kenneth J Hoffer
St Marry Eye Centre
1441, Broadway, Santa Monica
CA 90404 (USA)

Gerald RS Schultz
Asst. Clinical Professor
Department of Ophthalmology
Lomalinda University
Lomalinda, California (USA)

Keiki R Mehta
Medical Director
Mehta International Eye Institute
Sea side,147, Colaba Road
Mumbai (India)

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viii

Advances in Ophthalmology1

Liliana Werner
Centre for Research on Ocular
Therapeutics & Biodevices
Storm Eye Institute
Charleston SC (USA)

PN Nagpal
Director
Retina Foundation
Aso Palov Eye Hospital
Ahmedabad (India)

Manish Nagpal
Retina Foundation
Aso Palov Eye Hospital
Ahmedabad (India)

R Rajalakshmi
Dr Agarwals Eye Hospital
India

Marta Marson
Instituto Oftalmologico De
Sabadell, Barcelona (Spain)
M Edward Wilson
Professor and Chairman
Storm Eye Institute
Charleston SC (USA)
Melania Cigales
Instituto Oftalmologico De
Sabadell
Barcelona (Spain)
Nazimul Hussain
Vitreoretinal Surgery Clinic
Aditya Jyot Eye Hospital
Mumbai (India)
Nilesh Kanjani
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)

Reena M Choudhry
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)
Robert Stegmann
Professor
University of Pretoria
Department of Ophthalmology
Pretoria (South Africa)
Sandeep Arora
Retina Foundation
Aso Palov Eye Hospital
Ahmedabad (India)
Saurabh Choudhry
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)
Shahana Mazumdar
Aditya Jyot Eye Hospital
Mumbai (India)

Nishanth Patel
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)

Sonika Doshi
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)

Norbert Krber
Ophthalmic Surgeon
Ambulatory Outpatient Care
Cologne (Germany)

Soosan Jacob
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)

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S Natrajan
Medical Director
Aditya Jyot Eye Hospital
Mumbai (India)
Steve Charles
Charles Retina Institute
6401, Poplar Ave. Suite 190
Memphis, Tennessee (USA)
Sunita Agarwal
Dr Agarwals Eye Hospital,
15, Eagle Street
Langford Town
Bangalore (India)
Villa No. 2, Round House 3
Alwasl Road, Dubai PB 9168
Dubai
Sundaram
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)
Suresh K Pandey
John A Moran Eye Centre
University of Utah
50, North Medical Drive
Salt Lake City, Utah (USA)
Tahira Agarwal
Dr Agarwals Eye Hospital
19, Cathedral Road
Chennai-600086 (India)
Tobias Neuhann
Founder and Medical Director
Aam Augenklinik AM
Marienplatz, Marienplatz 18
Munich (Germany)
Vidushi Sharma
Dr RP Centre for Ophthalmic
Sciences, All India Institute of
Medical Sciences
New Delhi (India)

Contents ix

Foreword
During my twenty five years of professional experience, I have had the opportunity to
directly witness the huge leap forward that ophthalmic surgery has taken over these last
years of the XX century. These developments in surgical techniques are the consequence of
both recent technological breakthroughs and the quest of professionals of ophthalmology
who have dedicated their lives to sciences.
The first significant advance I was able to experience was the change in cataract surgery,
from the intracapsular to the extracapsular technique and on to the implant of the first
intraocular lenses. This transition yielded some highly positive results and for years we
lived through the perfecting of extracapsular surgery and improvements in intraocular
lenses. This was followed by the rebirth and perfecting of phacoemulsification, a technique
that had been dormant for years, which accompanied the evolution of the new intraocular
lenses that can be implanted through a small incision. We are presently at the threshold of
being able to extract the cataract and perform the implant through an incision as small as 1 millimeter.
Improvements in anesthesia techniques have paralleled technological advances, passing from general and
retrobulbar to peribulbar, subtenonian and todays topical anesthesia, allowing the patients immediate recovery of
vision.
The work undertaken by Prof Jos Ignacio Barraquer in modifying or sculpturing the shape of the cornea, the
so-called technique of keratomileusis, is probably the most revolutionary development in recent years. The marriage
between keratomileusis and excimer laser technology in the form of LASIK, has provided us with the tool to rapidly
and safely correct refractive errors such as myopia, astigmatism and hyperopia. A multitude of ophthalmologists
worldwide have contributed to perfecting this technique and today we correct the optical defects of our patients by
a procedure that was simply unimaginable in the not so distant past. The range of correction in refractive surgery has
been completed with the appearance of anterior and posterior chamber phakic lenses, increasing the ophthalmologic
tools available to deal with these defects.
Simultaneous to these advances in cataract and refractive surgery, new techniques have emerged for the
treatment of glaucoma. Posterior pole surgery has also evolved, with the perfecting of the vitrectomy and diode laser
therapy for macular degeneration. An array of technological changes has also helped us diagnose and treat eye
pathologies.
These advances have surpassed the barriers of our imagination and now our efforts are not only directed
towards the diagnosis and treatment of eye disease, but also aim to prevent, correct and improve vision with
techniques that are ever less invasive and achieve the ever increasingly rapid rehabilitation of our patients. Studies,
investigations and the exchange of scientific knowledge will allow us to continue this advance. This book by
Dr Ashok Garg and colleagues describes the therapeutic strategies in the different fields of ophthalmology and we
hope it will be a stimulus for the ophthalmology of the XXI century to continue developing for the benefit of us all.
Dr Jairo E Hoyos
MD PhD

Director, Instituto Oftalmologico Hoyos


Rambla de Sabadell 62-1, Sabadell (08201), Spain
Fellow, Department of Prof Ramon Castrovieji, New York (USA)
Organiser, Director of Refractive Surgery Courses, Barcelona (Spain)
Founder and President of KM Study Group
Coordinator, KMSG Hotline International Internet

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Advances in Ophthalmology1

Dr Jairo E Hoyos is an International Eye Surgeon of repute. Having done

his first degree in Medicine and Surgery from Zaragoza (Spain), he did his
specialization in ophthalmology from Barcelona (Spain) and Doctorate in
Medicine and Surgery from Autonomous university Barcelona (Spain). Dr
Hoyos is fellow of department of Professor Ramon Castroviezo, New York
(USA). He is organiser Director and Teacher of intensive courses on Extra
Capsular Surgery and the Artificial lens (1984-1986), of Refractive Surgery
courses (KM study group 1989, 1994-1999) and update in Phakic Lenses course
(Colombia 2002). Dr Hoyos performed in July 1993 the first Lasik Surgery in
Spain. He is founder and president of the KM Study Group and coordinator of
the KMSG Hotline. He works as Director Instituto Oftalmologico Hoyos,
Sabadell (08201) Spain. He can be reached by e-mail: jairoca@iohoyos.com.

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Contents xi

Preface
In last one decade tremendous advances have taken place in ophthalmology specially in the field of Phacoemulsification, Lasik Surgery and Ocular Therapeutics.
In todays high tech scenario the main focus of every ophthalmologist is to keep abreast of latest acquired skills,
equipments and ocular pharmacokinetics. One of the best way to get latest knowledge is through books and
Journals. This book on recent advances has been written through a team effort after thorough research of the matter
with the sole aim of providing latest knowledge to ophthalmologists. This book has been designed to incorporate all
recent advances in the fields of Cataract, Refractive Surgery, Glaucoma, Retina and Ocular Therapeutics. Every
effort has been made to include all the latest advancements of practical interest in this book. A special chapter on
Quick Look Ocular Therapeutics has been added to provide complete product information and specific formulation
availability a necessity in day-to-day ophthalmic practice. We are thankful to contributors who are masters in their
specific field at an International level, family members and friends who have extended every cooperation to prepare
this useful book.
Our special thanks to Mr Jitendar Vij (Chairman and Managing Director ) Jaypee Brothers Medical Publishers (P)
Ltd., a leading International name in medical publication field who extended full cooperation to prepare this high
quality book and published it in a short time.
Each author in this book has worked hard and shared his/her experiences to make this book a valuable
companion to our dear readers. We shall work tirelessly for future editions of this book with your valuable
comments, suggestions and blessings.
Editors

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Contents
SECTION I: CATARACT
1. Anesthesia in Cataract Surgery An Update
Ashok Garg

2. No Anesthesia Clear Corneal Phacoemulsification


Suresh K Pandey, Amar Agarwal, Liliana Werner, Sunita Agarwal, Athiya Agarwal

16

3. Corneal Endothelium and its Protection in Phacoemulsification


Keiki R Mehta

26

4. Phacoemulsification with CryoanalgesiaA New Approach


Francisco J Gutirrez Carmona

35

5. No Anesthesia Cataract Surgery


Tobias Neuhann

39

6. Phakonit
Amar Agarwal, Athiya Agarwal, Sunita Agarwal

44

7. Phakonit with Acritec IOL


Sunita Agarwal, Athiya Agarwal, Amar Agarwal

54

8. Endocapsular Lensectomy
Steve Charles

62

9. Phaco in Subluxated Cataracts


Nishanth Patel, Vikas Lal, Amar Agarwal, Athiya Agarwal, Sunita Agarwal

66

10. Update on Pediatric Cataract Management


Suresh K Pandey, M Edward Wilson, David J Apple, Liliana Werner, Jagat Ram

74

11. Favit A Technique for Removing Dropped Nucleus during Phacoemulsification


Amar Agarwal, Sunita Agarwal, Athiya Agarwal, Suresh K Pandey, Clement K Chan

104

12. Management of Dislocated Implants by the Vitreoretinal Approach


Clement K Chan, Gerald RS Schultz

109

13. Air Pump to Prevent Surge


Sunita Agarwal, Amar Agarwal, Athiya Agarwal

118

14. Trypan Blue in the Management of Mature Cataracts


Amar Agarwal, Athiya Agarwal, Sunita Agarwal

121

15. My Personal Technique of Vertical Hubbing Phacoemulsification


Keiki R Mehta

127

16. The Prevention of Complications and their Management in Phacoemulsification


Keiki R Mehta, Cyres Mehta

137

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xiv Advances in Ophthalmology1

17. Laser Phaco Cataract Surgery


Amar Agarwal, Sunita Agarwal, Athiya Agarwal, Suresh K Pandey, Clement K Chan

151

18. Corneal Topography in Phakonit


Amar Agarwal, Soosan Jacob, Athiya Agarwal, Sunita Agarwal

159

19. Attacking Childhood Cataract Blindness in the Economically Emerging Countries


Suresh K Pandey, M Edward Wilson, Jaya Thakur, Vidushi Sharma

164

20. Update on Capsular Dye Enhanced Cataract Surgery


Suresh K Pandey, Liliana Werner, David J Apple

179

21. Update on Ophthalmic Viscosurgical Devices


Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak, Vidushi Sharma

198

22. Update on Twenty First Century CataractIntraocular Lens Surgery


Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak,
Vidushi Sharma, Amar Agarwal

214

23. Update on Posterior Capsule Opacification: Etiopathogenesis, Clinical


Manifestations, Pharmacological and Surgical Prevention
Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak

220

24. Pediatric CataractIOL Surgery: Past, Present and Future


Suresh K Pandey, M Edward Wilson, Liliana Werner, David J Apple, Vidushi Sharma

238

25. Update on Delayed Postoperative Opacification of Rigid and


Foldable, Intraocular Lenses
Suresh K Pandey, Liliana Werner, Andrea M Izak, David J Apple

245

26. Corneal Topography in Cataract Surgery


Athiya Agarwal, Sunita Agarwal, Amar Agarwal, Nilesh Kanjani

261

SECTION II: REFRACTIVE SURGERY


27. AberropiaA New Refractive Entity
Soosan Jacob, Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Tahira Agarwal

271

28. Presbyopic LASIK


Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Guillermo Avalos

278

29. Zyoptix
Amar Agarwal, Nilesh Kanjani, Ashish Doshi, Sonika Doshi, Sunita Agarwal,
Athiya Agarwal, J Agarwal, T Agarwal

282

30. Ocular Pharmacokinetics in Refractive Surgery


Ashok Garg

287

31. Phakic Refractive Lens (PRL)Indications and Techniques


Dimitrii D Dementiev, Kenneth J Hoffer

295

32. Visual Acuity with Contact Lenses Vs LASIK in Myopia


Melania Cigales, Fernando Rodriquez-Mier, Marta Marsan, Jairo E Hoyos

305

33. Contact Lens Fitting in Refractive Surgery


Ashok Garg

315

34. Primary Posterior Corneal Elevation


Amar Agarwal, Nilesh Kanjani, Ashish Doshi, Sonika Doshi,
Sunita Agarwal, Athiya Agarwal, J Agarwal, T Agarwal

323

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Contents xv

SECTION III: GLAUCOMA


35. Modern Glaucoma Surgery
Jes Mortensen

331

36. Laser Sclerotomy, Laser Phakonit and IOL Implantation


Sunita Agarwal, Sundaram, Asha B

338

37. Viscocanalostomy
Norbert Krber, Robert Stegmann, Clive O Peckar, GL Simn-Castellvi

342

38. Update on Antiglaucoma Therapy


Ashok Garg

348

39. Triple ProcedureTrabeculectomy with Phaco and IOL Implantation


Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Anand A Bagmar, R Rajalakshmi

380

SECTION IV: RETINA


40. Update on Photodynamic Therapy (Verteporfin) in Age-related Macular Degeneration
S Natrajan, Anand A Bagmar, Nazimul Hussain, Anjli Hussain, Shahana Mazumdar

389

41. Indocyanine Green Angiography


S Natrajan, Shahana Mazumdar, Nazimul Hussain, Anjli Hussain, Anand A Bagmar

393

42. Perfluorocarbon Liquids in Vitreoretinal Surgery


Amar Agarwal

400

43. Trypan Blue Assisted Epiretinal Membrane Removal


Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Saurabh Choudhry, Reena M Choudhry

409

44. Diabetic RetinopathyCurrent Concepts and Recent Advances


Ashish Mahobia, Manish Nagpal, PN Nagpal, Kamal Nagpal, Sandeep Arora

412

45. Advances in the Management of Age-related Macular Degeneration


Sandeep Arora, Manish Nagpal, PN Nagpal, Kamal Nagpal, Ashish Mahobia

436

SECTION V: OCULAR THERAPEUTICS


46. Update on Routes of Administration and Drug Delivery Systems in Ophthalmology
Ashok Garg

451

47. Update on Antibacterial Therapy


Ashok Garg

459

48. Update on Anti-inflammatory Therapy


Ashok Garg

480

49. Update on Ophthalmic Dyes


Ashok Garg

497

50. Quick Look Ocular TherapeuticsAn Update


Ashok Garg

510

51. Future Drugs in Ophthalmology


Ashok Garg

537

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xvi Advances in Ophthalmology1

SECTION VI: MISCELLANEOUS


52. Dry Eye and Its ManagementAn Update
Ashok Garg

543

53. Update on Toric Contact Lenses


Ashok Garg

552

54. Plastic Surgery and Laser Treatment in Ophthalmology


Alice Handzel

562

55. Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update


Ashok Garg

586

Index

599

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Section I

Cataract
1. Anesthesia in Cataract Surgery An Update
Ashok Garg
2. No Anesthesia Clear Corneal Phacoemulsification
Suresh K Pandey, Amar Agarwal, Liliana Werner, Sunita Agarwal, Athiya Agarwal
3. Corneal Endothelium and its Protection in Phacoemulsification
Keiki R Mehta
4. Phacoemulsification with CryoanalgesiaA New Approach
Francisco J Gutirrez Carmona
5. No Anesthesia Cataract Surgery
Tobias Neuhann
6. Phakonit
Amar Agarwal, Athiya Agarwal, Sunita Agarwal
7. Phakonit with Acritec IOL
Sunita Agarwal, Athiya Agarwal, Amar Agarwal
8. Endocapsular Lensectomy
Steve Charles
9. Phaco in Subluxated Cataracts
Nishanth Patel, Vikas Lal, Amar Agarwal, Athiya Agarwal, Sunita Agarwal
10. Update on Pediatric Cataract Management
Suresh K Pandey, M Edward Wilson, David J Apple, Liliana Werner, Jagat Ram
11. Favit A Technique for Removing Dropped Nucleus during Phacoemulsification
Amar Agarwal, Sunita Agarwal, Athiya Agarwal, Suresh K Pandey, Clement K Chan
12. Management of Dislocated Implants by the Vitreoretinal Approach
Clement K Chan, Gerald RS Schultz
13. Air Pump to Prevent Surge
Sunita Agarwal, Amar Agarwal, Athiya Agarwal
14. Trypan Blue in the Management of Mature Cataracts
Amar Agarwal, Athiya Agarwal, Sunita Agarwal
15. My Personal Technique of Vertical Hubbing Phacoemulsification
Keiki R Mehta
16. The Prevention of Complications and their Management in Phacoemulsification
Keiki R Mehta, Cyres Mehta
17. Laser Phaco Cataract Surgery
Amar Agarwal, Sunita Agarwal, Athiya Agarwal, Suresh K Pandey, Clement K Chan

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18. Corneal Topography in Phakonit


Amar Agarwal, Soosan Jacob, Athiya Agarwal, Sunita Agarwal
19. Attacking Childhood Cataract Blindness in the Economically Emerging Countries
Suresh K Pandey, M Edward Wilson, Jaya Thakur, Vidushi Sharma
20. Update on Capsular Dye Enhanced Cataract Surgery
Suresh K Pandey, Liliana Werner, David J Apple
21. Update on Ophthalmic Viscosurgical Devices
Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak, Vidushi Sharma
22. Update on Twenty First Century CataractIntraocular Lens Surgery
Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak, Vidushi Sharma, Amar Agarwal
23. Update on Posterior Capsule Opacification: Etiopathogenesis, Clinical Manifestations,
Pharmacological and Surgical Prevention
Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak
24. Pediatric CataractIOL Surgery: Past, Present and Future
Suresh K Pandey, M Edward Wilson, Liliana Werner, David J Apple, Vidushi Sharma
25. Update on Delayed Postoperative Opacification of Rigid and Foldable, Intraocular Lenses
Suresh K Pandey, Liliana Werner, Andrea M Izak, David J Apple
26. Corneal Topography in Cataract Surgery
Athiya Agarwal, Sunita Agarwal, Amar Agarwal, Nilesh Kanjani

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Anesthesia in Cataract
SurgeryAn Update
Ashok Garg

INTRODUCTION
ANESTHESIA FOR CATARACT
SURGERY
GENERAL ANESTHESIA
PROCEDURE
METHODS OF ANESTHESIA
ANESTHESIA FOR CHILDREN
COMPLICATIONS OF GENERAL
ANESTHESIA
COMPLICATIONS OF
RETROBULBAR INJECTION
PERFORATION OF THE GLOBE
RETINAL VASCULAR
OBSTRUCTION
SUBARACHNOID INJECTION
PERIBULBAR (PERIOCULAR)
TECHNIQUE
TOPICAL ANESTHESIA
HOW TO ACHIEVE SURFACE
ANESTHESIA FOR INTRAOCULAR
SURGERY
CAN ONE CONVERT HALF WAY
THROUGH SURGERY UNDER
TOPICAL ANESTHESIA
NO ANESTHESIA CATARACT
SURGERY

INTRODUCTION
Anesthesia for Cataract Surgery has undergone tremendous changes and
advancements in last century. In 1846 general anesthesia techniques were
developed which were not found suitable and satisfactory for ophthalmic
surgery. In 1884 Koller discovered surface anesthesia techniques using
topical cocaine for cataract surgeries which found favor with the
ophthalmologists. However due to significant complications and side
effects of cocaine Herman Knopp in 1884 described retrobulbar injection
as local anesthetic technique for ocular surgery. He used 4 percent cocaine
solution injected into the orbital tissue close to posterior part of the globe
to achieve adequate anesthesia but in the subsequent injections patients
experienced pain. In 1914 Van Lint introduced orbicularis akinesia by local
injection to supplement subconjunctival and topical anesthesia. However
this technique found favor only after 1930 when procaine (Novocaine) a
safer injectable agent made it feasible.
With the development of hyaluronidase as an additive to the local
anesthetic solution Atkinson (1948) reported that large volumes could be
injected with less orbital pressure and improved safety injections into the
cone (retrobulbar) were recommended and gained rapid favor becoming
anesthetic route of choice among ophthalmologists.
In Mid 1970s, Kelman introduced an alternative technique of local
anesthesia for ocular surgery known as peribulbar injection. However till
1985 this new technique was not published in ophthalmic literature. In
1985 Davis and Mandel reported local anesthetic injection outside the cone
into the posterior peribulbar space (periocular). Further modifications of
both retrobulbar and periocular injection techniques were made by
Bloomberg, Weiss and Deichaman, Hamilton and colleagues, whitsett,
Murdoch Shriver and Coworkers. These modifications consisted of more
anterior deposition of anesthetic solution with shorter needles and smaller
dosages.
With the introduction of small incision cataract surgery, Phaco emulsification and other microsurgical procedures in ophthalmology, use of
shorter needles with smaller dosages became more common. Fukasawa
and Furata et al reintroduced subconjunctival anesthetic techniques.
Fichman in 1992 first reported the use of topical tetracaine anesthesia for
phacoemulsification and intraocular lens implantation starting an era of
topical anesthesia in ocular sugery.
With the advent of many ocular anesthetic techniques in past two
decades indicates the need for the development of an ideal anesthetic and

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Section I: Cataract

technique for ocular surgery. Every existing technique


has its own advantages and disadvantages. General
anesthesia for cataract surgery is virtually out of favor
with ophthalmologists. Retrobulbar anesthesia,
periocular (peribulbar, subconjunctival, orbital and
epidural) and topical anesthesia or a combination of
peribulbar and topical are being used in present day
ocular sugery. Now with the advent of below 1 mm
incision technique, foldable and Rollable intraocular
lenses, no anesthesia cataract surgery is becoming
popular with increased frequency.

patient to undergo a safe procedure with the benefit of a


general anesthetic.

ANESTHESIA FOR CATARACT SURGERY

Diabetes Mellitus

Cataract extraction may be performed under general


anesthesia, local anesthesia or topical anesthesia,
depending upon condition of patient cataract status and
surgeon choice.

Diabetes mellitus is commonly found in those for whom


cataract surgery is indicated. Preadmission stabilization
is necessary, and when this is in doubt, a longer period
of preoperative inpatient assessment and management
is required to eliminate any ketonuria or gross hyperglycemia. Oral diabetic medication should be omitted
on the day of surgery because the effects may persist for
up to 24 hours. During surgery and throughout the early
postoperative period, control is effected by using 5
percent glucose intravenously and insulin as required,
as shown by the blood glucose levels. When the patient
resumes normal oral intake postoperatively, the normal
regimen is rapidly resumed.

General Anesthesia
Usually for cataract surgery general anesthesia is not
given. It is advisable only in highly anxious/nervous
patient or when cataract surgery requires a long time for
completion. Patients who are extremely apprehensive,
deaf, mentally retarded, unstable or cannot communicate
well with the surgeon are more suitable for general
anesthesia. General anesthetic facilities with expert
anesthetist are mandatory.
GENERAL ANESTHESIA PROCEDURE
Preoperative Preparation
A patient who is to be given a general anesthetic needs
proper preoperative assessment and examination,
preferably on the day before the anesthetic is to be
administered, although preparation earlier on the day
of surgery may be acceptable in many cases. Patients with
cataracts are often elderly and not infrequently have other
medical problems that must be considered before
anesthesia is induced. These are
Chronic (Obstructive) Respiratory Disease
These patients require more careful assessment. Their
condition in severe cases can be adversely affected by
anesthetic drugs and muscle relaxants. On the other
hand, the inability to control obstructed respiration can
lead to hazardous cataract surgery and a high incidence
of failure. Preoperative preparation with antibiotics,
bronchodilators, and physiotherapy often enable a sick

Cardiovascular Disease
Because many patients with cardiovascular disease will
already be on diuretic treatment, preoperative assessment to detect and treat cardiac failure or hypokalemia
is most important. The adequate control of hypertension
is also an essential safety requirement, especially for the
middle-aged.

Dystrophia Myotonica
These patients frequently require cataract surgery while
they are quite young. They are particularly sensitive to
anesthetic drugs and subject to prolonged respiratory
depression. Suxamethonium is contraindicated; minimal
doses of other drugs such as atracurium should be used.
Premedication
The aim of premedication is to allow a smooth induction
of anesthesia. Most patients appreciate some sedation to
alleviate the natural anxiety associated with any eye
surgery. Opiates, however, are to be avoided because of
their association with respiratory depression and postoperative vomiting. For the aged and anxious, oral
premedication with diazepam, 5 to 10 mg, according to
fitness and size or Lorazepam, 1 to 2 mg, works well. An
antiemetic can then be administered during surgery.
For the younger and more robust, one can use a
combination of pethidine, promethazine hydrochloride,
and atropine. This is also a helpful combination for those
with established respiratory disease.
Children over 1 year of age required sedation with
trimeprazine tartrate syrup (3 to 4 mg per kg) 2 hours

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Chapter 1: Anesthesia in Cataract SurgeryAn Update 5


preoperatively. Younger babies should not require
sedation. Atropine may be given either intramuscularly
(0.2 to 0.6 mg 30 minutes preoperatively) or intravenously
(0.015 to 0.02 mg with induction).
METHOD OF ANESTHESIA
Induction
A smooth induction avoids the problems of increased
central nervous pressure with its consequent adverse
effect on the intraocular pressure.
The drug most commonly used is thiopentone, which
produces a rapid loss of consciousness. When it is used
in doses of 3 to 4mg per kg, the onset is relatively slow in
the elderly, who frequently have a slower circulation
time. For the very frail, methohexitone is useful,
producing less change in blood pressure. More recently
disoprofol (Diprivan) has been found to be useful; it also
has a rapid onset of action and induces little nausea and
vomiting.
Intubation of the trachea with a non-kinking endotracheal tube is achieved with suxamethonium. Its use
is associated with a transient rise in the intraocular
pressure due to choroidal expansion. Ventilation with
nitrous oxide and oxygen with 0.5 to 1 percent halothane
is continued until the effects of the suxamethonium have
subsided.
More recently techniques have been described for
rapid sequence induction with vecuronium. These
methods do not seem to be associated with a significant
rise in the intraocular pressure and they avoid the
problems of suxamethonium.
Maintenance
A nondepolarizing muscle relaxant is used throughout
the surgical procedure, dosages depending on the size,
age, and health of the patient. Available drugs include
tubocurarine, which is inclined to produce hypotension
(occasionally severe), pancuronium, and more recently
vecuronium and atracurium. Vecuronium has been
demonstrated to lower intraocular pressure. Because
both atracurium and vecuronium act and subside
rapidly, their effectiveness must be monitored regularly
by a peripheral nerve stimulator.
Intermittent positive pressure ventilation is maintained by nitrous oxide, oxygen, and an anesthetic drug.
One-half percent halothane has long been considered
effective and also lowers the intraocular pressure. Other
anesthetic drugs include enflurane (associated with more
postoperative vomiting and restlessness, though less

hypotension) and isoflurane. The latter does not appear


to adversely affect the stability of the cardiovascular
system. Its effect on intraocular pressure has not been
reported.
Throughout the procedure the pulse, blood pressure,
electrocardiographic record, and arterial oxygen saturation must be regularly monitored, along with the nerve
stimulation needed for the nondepolarizing muscle
relaxant being used. All ventilators should be fitted with
an alarm to warn of malfunction.
Completion of recovery from anesthesia after cataract
surgery must be as smooth as the induction, care being
taken to avoid gagging, coughing, and of course vomiting. Modern ophthalmic sutures are good but not
foolproof! The neuromuscular blockade is reversed
with atropine and pros-tigmine. Gentle extubation is
associated with careful pharyngeal suction. Patients are
encouraged to resume normal activity as soon as the
effects of the anesthetic drugs have worn off.
ANESTHESIA FOR CHILDREN
Adequate premedication and careful handling should
insure a calm quiet child and allow a smooth induction.
Because the cataract is dealt with by using a closed
system, the surgical risks of a rise in intraocular pressure
are not so severe. Inhalational anesthesia using nitrous
oxide and oxygen with halothane is usually sufficient.
COMPLICATIONS OF GENERAL ANESTHESIA
The complications associated with a general anesthetic
range from death to the less serious but irritating
nuisances of protracted nausea and vomiting or sore
throats. This chapter covers only those complications
producing serious morbidity or mortality and those
peculiar to the patient with eye disease.
1. Hypoxemia (insufficient oxygen in the arterial blood
to sustain life) is the most common cause of disaster,
and failure to ventilate is the most common cause of
hypoxemia. Unrecognized esophageal intubation,
ventilator disconnection, and, most distressing of all,
inability to ventilate after unconsciousness and
paralysis have been obtained are all possible causes
of failure to ventilate. Delivery of an inadequate
oxygen concentration is a less common cause of
hypoxemia. Most but not all of the foregoing are
preventable with the monitoring and fail-safe devices
available today, provided a competent anesthetist is
monitoring the devices.
2. Aspiration of gastric contents remains a common
complication despite such preventive measures as

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Section I: Cataract

overnight fasting, the use of metoclopramide to


enhance gastric emptying, and rapid sequence
induction with cricoid pressure in emergency
procedures. The two life-threatening results of
aspiration are airway obstruction from large food
particles and chemical pneumonitis from acidic
gastric contents.
3. The two most serious cardiovascular complications,
aside from cardiovascular collapse secondary to
hypoxemia and acute anaphylaxis, are myocardial
infarction and cerebrovascular accident. Surgery
performed under general anesthesia within 3 months
after a myocardial infarction carries a 40 percent
incidence of repeat infraction. This figure decreases
to about 10 percent at 6 months, after which the
incidence is approximately the same as in the general
population. All elective surgery is delayed until after
3 months, and a 6 month wait is encouraged unless
poor visual acuity seriously limits activities.
4. Renal and hepatic toxic effects from anesthetic drugs
are seldom seen in our practice. Careful preanesthetic
screening identifies all patients with renal and hepatic
disease. Halothane, which gained notoriety because
of its hepatotoxicity, especially when administered
repeatedly, is not used in adults and is usually used
for induction only in children. The metabolic
byproducts of methoxyflurane and enflurane are
inorganic fluorides, which can produce nephrogenic
diabetes insipidus. We no longer use these drugs
because so many of our patients have diabetes and
severe renal disease in our population.
5. Failure to resume respiration at the end of the surgery
occurs often enough to merit mention. The most
common causes are simple respiratory depression
from the anesthetic drugs or narcotics, electrolyte
disturbance (i.e., hypokalemia), hypothermia
(particularly in infants), and the use of the combination of mycin antibiotics and nondepolarizing
muscle relaxants. It also may occur after the administration of succinylcholine when there is a pseudocholinesterase deficiency. Respirations are maintained until the cause is found and remedied.
Cardiovascular complications are the most commonly
seen events in our practice. If diagnosed and treated
properly, they need not result in a disaster. Hypertension
is the most prevalent problem. The usual causes are
apprehension, neo-synephrine eyedrops, pain, distended bladder if mannitol was given, and autonomic
nervous system imbalance secondary to the general
anesthetic. Apprehension can be allayed with intravenous injections of 1 to 3 mg of Valium or 0.5 to 2 mg
Zolpidem. Nitropaste applied to the skin and sublingual

doses of nifedipine have proved invaluable, but an


intravenous line should be in place before their use.
Hypotension must be treated immediately and
vigorously because it is tolerated less well than hypertension. Arrhythmias are the most frequent cause of
cancellation on the day of surgery in the elderly patient
with eye disease. The sudden onset of atrial fibrillation
is the most common arrhythmia. An electrocardiographic
monitor is mandatory for eye surgery.
Extrusion of ocular contents during administration
of a general anesthetic is a serious complication in eye
surgery. The entire anesthetic process is geared to
minimize this possibility. Once the eye is opened, patients
are kept deeply anesthetized or paralyzed with nondepolarizing relaxants to insure immobility.
Local Anesthesia
Local ocular anesthesia is the mainstay of cataract
surgery. Local anesthesia minimises the risk of wound
rupture a complication frequently associated with
coughing during extubation and postoperative nausea
and vomiting (in General Anesthesia) (Fig. 1.1). Generally
the use of 1:1 mixture of 2 percent Xylocaine and 0.50
percent Bupivacaine along with adrenaline and
Hyaluronidase in facial, retrobulbar and peribulbar
blocks achieve rapid anesthesia, akinesia and postoperative analgesia for several hours.
Care should be taken to avoid intravascular injections
of anesthetic agents because refractory cardiopulmonary
arrest may result from an inadvertent intravenous or
intra-arterial injections.

Fig. 1.1: Diagrammatic surface distribution of sensory nerves.


Note branches derived from ophthalmic nerve (V 1) and
maxillary nerve (V2) a division of the trigeminal nerve

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Chapter 1: Anesthesia in Cataract SurgeryAn Update 7


Many patients express pain of facial and retrobulbar
injections so proper preoperative sedation and good
rapport with the surgeon make them quite comfortable.
Following techniques are used for giving local anesthesia. These include:
Orbicularis Oculi Akinesia
Temporary paralysis of the orbicularis oculi muscle is
essential before making section for the cataract surgery
to prevent potential damage from squeezing of the lids.
Following methods are used, for getting orbicularis oculi
akinesia.
a. O Briens technique Usually 10 ml of mixture of 2
percent Lidocaine solution (5 ml) and 0.5 percent
bupivacaine solution (5 ml) with 1:100,000 epinephrine and 150 units of hyaluronidase are infiltrated for
local anesthesia.
OBriens method is the injection of above mentioned local anesthetic solution down to the
periosteum covering the neck of the mandible where
the temporofacial division of facial nerve passes
forwards and upwards (Fig. 1.2). A 10 ml syringe with
preferably No. 17 or 18 needle and 2.5 cm in length is
used. The patient is asked to open his mouth and the
position of the condyle and temporomandibular joint
is located by the forefinger of the operators left hand.
After closing the jaw, the injection is given on a
horizontal line through the junction of the upper and
middle third of the distance between the zygoma and
angle of the mandible. The needle should pass
straight down the periosteum. 2-3 ml of local
anesthetic solution is injected and after withdrawing
the needle firm pressure and massage are applied.
Paralysis of orbicularis oculi should occur normally
within 7 minutes. The injection is unlikely to injure

Fig. 1.2: Diagrammatic presentation of OBrien technique of


local anesthesia

Fig. 1.3: Needle position for Van Lint Akinesia


(Courtesy: Ciba Geigy Clinical Symposia)

the external carotid artery which lies posterior and


at a deeper level. However damage may be done to
posterior facial vein and the transverse facial artery.
Movement of jaws is sometime painful for few days
after this injection.
b. Van Lints akinesia Van Lints method is a better
alternative. The injection of local anesthetic solution
is made across the course of branches of the seventh
nerve as they pass over the zygomatic bone (Fig. 1.3).
In this technique a 5 cm in length and 25 gauge
needle is passed through the wheal down to the
periosteum of the zygomatic bone. The needle is than
passed upward towards the temporal fossa without
touching the periosteum (as it may be painful) and 4
ml of solution is injected and then forwards medially
and downwards towards the infraorbital foramen to
inject 2ml and downwards and backwards along the
lower margin of the zygoma for 2.5 cm where 3 ml of
solution is injected. It is essential to massage the
infiltrated area with a gauze swab. Motor nerves are
less susceptible than sensory nerves to a block with
local anesthetic agents.
The advantage of Van Lints method is that it
provides regional anesthesia as well as paralysis of
the orbicularis muscle. After waiting for 5-7 minutes
akinesia is tested by holding the eyelids open with a
small swab on to a holder and asking the patient to
close his eyelids. If slightest action is observed then
injection may be repeated to obtain adequate akinesia.
c. Atkinson block The needle enters through a skin
wheal at the inferior border of the zygoma just inferior
to the lateral orbital rim. The path of the needle is
along the inferior edge of the zygomatic bone and
then superiorly across the zygomatic arch, ending at

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Section I: Cataract

Fig. 1.6: Spaeth block (facial nerve is blocked where it


crosses the posterior edge of the mandible)
Fig. 1.4: Atkinson akinesia (Intercepting the facial nerve
fibers as they cross the zygomatic arch)

Fig. 1.5: Diagrammatic presentation of OBrien and Atkinson


techniques (A) Classic OBrien technique (B) Modified OBrien
technique (C) Atkinson technique

the top of the ear. 3 to 4 ml of the anesthetic is injected


as the needle is advanced (Figs 1.4 and 1.5).
d. Spaeth block The Spaeth block avoids the inconsistencies of the OBrien block as well as the postoperative discomfort caused by going through the
parotid gland and entering the temporomandibular
joint. An injection is made into the back of the
mandibular condyle just below the ear, catching the
facial nerve before it divides (Fig. 1.6). To locate the
landmarks, the fingers are placed along the posterior

border of the mandible as superiorly as possible. The


needle is placed just anterior to the most superior
finger. Bone should be reached shortly. If not, the
needle is withdrawn and the position rechecked
before a second attempt is made. After the bone is
reached, the needle is pulled back slightly and suction
is placed on the syringe to make sure that a vessel
has not been punctured; 5 ml of anesthetic is then
injected. Although rarely required, the needle can be
redirected superiorly towards the outer canthus for
1.5 inches and an additional 5ml is injected. After 30
seconds, nearly complete facial palsy should be
evident.
e. Nadbath block An injection is made into the cavity
between the mastoid process and the posterior border
of the mandibular ramus. The skin is pierced, and a
skin wheal is made 1 or 2 mm anterior to the mastoid
process and inferior to the external auditory canal. A
12 mm, 26 gauge needle is used, with the injection of
anesthetic extending from the skin wheal, passing
through a taut membrane midway, to the full depth
of the needle; 3 ml is injected (Fig. 1.7).
The Nadbath block insures ease of performance,
and there are few complaints relating to the original
injection or subsequent pain in the jaw area. The most
common side effect is a bitter taste as the parotid
gland secretes the anesthetic. Other problems
reported are dysphonia, swallowing difficulty, and
respiratory distress. Judging from the fact that these
complications are seen predominantly in very thin
patients and most certainly are secondary to the
diffusion of anesthetic to the jugular foramen, 1 cm
deeper than the stylomastoid foramen, the length of
the needle i.e., the depth of injection is critical.

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Chapter 1: Anesthesia in Cataract SurgeryAn Update 9

Fig. 1.7: Needle positions for OBrien and Nadbath ocular


akinesia. (Courtesy: Ciba Geigy Clinical symposia)

Preexisting unilateral oropharyngeal or vocal cord


dysfunction is a definite contraindication, as bilateral
vocal cord paralysis could result. The Nadbath block
should never be done bilaterally. If, after a unilateral
Nadbath block, dysphonia or difficulty with swallowing or respiration occurs, lateral positioning will allow
the paralyzed vocal cord to fall out of the way, clearing
the airway.
Proper administration of local anesthesia requires
knowledge of orbital anatomy, various anesthetic
techniques, and the properties of the drugs used.
Prompt recognition of side effects and complications
following injection results in the best possible patient
care.
f. Retro-ocular (retrobulbar) injection Anesthesia and
akinesia of the eye are achieved by injecting a local
anesthetic solution into the retrobulbar space within
the muscle cone (Fig. 1.8).
I. In this method patient is asked to look upwards
and to the opposite side. A 3.5 cm length 23 gauge
sharp edge round tipped needle is inserted in the
quadrant between the inferior and the lateral
rectus muscles and directed posteriorly until the
resistance of orbital septum is encountered. After
it has penetrated the orbit the needle is directed
towards the apex of the orbit and advanced until
it meets the resistance of the inter-muscular
septum. When this structure is penetrated, the
needle tip is in the retrobulbar space. About 3-4
ml of local anesthetic mixture solution is injected

Fig. 1.8: Local anesthesia techniques (A) Van Lint akinesia


(dotted arrows) (B) Nadbath facial nerve block (C) Retrobulbar
needle position

taking care, to minimize the needle movement to


prevent possible vessels lacerations. Following the
injection the globe should be intermittently
compressed for several minutes for distributing
the anesthetic solution and to ensure hemostasis.
A properly placed retrobulbar injection is effective
within seconds. It blocks all extraocular muscles
except superior oblique muscle, affects the ciliary
ganglion and anesthetize the entire globe (Fig. 1.9).
Gills-Loyd Modified Retrobulbar Block
Before the anesthetic is administered, the patients vision
is checked and the A scan is done. Then, prior to the first
injection, 2 drops of proparacaine 0.5 percent are given
topically. The eyes are either fixed in primary gaze or
directed slightly superiorly, avoiding the superonasal
position. With sharp 27 gauge needle, enter is effected at
LE 4:00, RE 8:00, 5 mm medial to the lateral canthus. The
needle is inserted parallel to the optic nerve. A preretrobulbar injection of 1.5ml of pH adjusted Xylocaine is
administered subconjunctivally. After 30 seconds, a 5 ml
retrobulbar injection of pH adjusted bupivacaine and
hyaluronidase is injected with a 25 gauge, 1 inch needle.
After 8 to 9 minutes, the eye is checked for akinesia. A

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10

Section I: Cataract

Fig. 1.9: Needle positions for retrobulbar and peribulbar anesthesia (frontal view) (Courtesy: Ciba Geigy clinical symposia)

1 to 3 ml supplemental injection of full strength anesthetic is given as needed to complete the block. 1.0 ml
bolus is administered subdermally into the inferolateral
lid to anesthetize the distal branches of the seventh
cranial nerve; this technique does not require a total
seventh nerve block. Next 0.5 ml of cefazole is injected
subconjunctivally, and gentle eye compression is
administered for 30 to 60 minutes with a Super Pinky
Decompressor prior to surgery.
COMPLICATIONS OF RETROBULBAR INJECTION
A number of complications can occur as a result of retrobulbar injection, among them retrobulbar hemorrhage,
perforation of the globe, retinal vascular obstruction, and
subarachnoid injection.
Retrobulbar Hemorrhage
Retrobulbar hemorrhage probably occurs in 1 to 5 percent
of the cases. It seems to occur less frequently if a blunt
tipped needle is used, but this has not been demonstrated
in any controlled study.
Retrobulbar bleeding may occur at a number of sites.
The four vortex veins leave the globe approximately 4
mm posterior to the equator and could well be subjected
to the shearing forces of an inserted needle, as could the
central retinal or ophthalmic vein. An arterial source of
bleeding must be postulated to explain severe hemorrha-

ges that produce the rapid onset of proptosis, hemorrhage, chemosis, and immobility of the globe. The
posterior ciliary arteries supplying the choroid, the
central retinal artery, and other ophthalmic artery
branches are all subject to damage. Even the ophthalmic
artery can be reached in the area of the optic foramen
with a 11/2 inch needle.
Most instances of retrobulbar hemorrhage resolve
without complication, but should a complication arise,
particularly during elective surgery, it is prudent to
postpone the operation for at least 3 to 4 weeks and then
consider general anesthesia if the patient can tolerate it.
Even when general anesthesia is employed, severe
positive pressure can develop in an open eye if the
operation is performed within several days after the
hemorrhage.
Vision may be permanently decreased following a
retrobulbar hemorrhage. This probably occurs as a result
of closure of the central retinal artery or damage to the
smaller vessels that supply the retrobulbar optic nerve.
If examination reveals that the central retinal artery
has closed because of increased intraorbital and
intraocular pressures, a lateral canthotomy should be
performed. Other possible therapeutic modalities include
anterior chamber paracentesis and orbital decompression. Prior of decompression of the orbit, computed
tomographic scanning of the region should be undertaken to help localize the blood and rule out the possibility of bleeding within the optic nerve sheath, which
also might have to be decompressed.
PERFORATION OF THE GLOBE
This is another sight threatening complications of
ophthalmic surgery with retrobulbar anesthesia. Highly
myopic eyes are particularly suscepticle to this complication because of their long axial lengths. General
anesthesia should be considered as an alternative in such
eyes.
The scleral perforation should be repaired as soon as
possible. Cryopexy or laser treatment of the break(s) may
suffice, although vitreous traction that develops along
the needle tract through the vitreous gel is better negated
by a scleral buckling procedure. If the fundus view is
obscured by vitreous hemorrhage, a pars plana vitrectomy is warranted to visualize the break(s). Although
double scleral perforations probably have a worse
prognosis than the single variant, the latter also can be
devastating. I have seen one case in which the retina in
the posterior pole was partially aspirated through the
needle following a scleral perforation anterior to the
equator.

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Chapter 1: Anesthesia in Cataract SurgeryAn Update 11


Inadvertent injection of lidocaine into the vitreous
cavity appears to be tolerated by the globe. However, it
can cause an extreme elevation of the intraocular pressure
and rapid opacification of the cornea.
RETINAL VASCULAR OBSTRUCTION
Retinal vascular obstruction has been reported after
retrobulbar anesthesia. The most common types are
central retinal artery obstruction and combined central
retinal artery-central retinal vein obstructions. Central
retinal artery obstruction seems to occur more commonly in conjunction with diseases that affect the retinal
vasculature, such as diabetes mellitus and sickling
hemoglobinopathies. Nevertheless, it also can be seen
in people with good health. Fortunately, the condition
more often than not reverses spontaneously and the
central retinal artery reperfuses within several hours. The
causes are uncertain, but spasm of the artery, direct
trauma to the vessel from the needle, and external
compression by blood or an injected solution are possible
mechanisms that could cause obstruction. Ophthalmic
artery obstruction also can be induced, possibly by
injection and subsequent compression within the optic
foramen.
Therapy is directed towards relieving the obstruction
and keeping the retina viable. Anterior chamber paracentesis may help, the aim being to lower the intraocular
pressure and decrease the resistance to blood through
the central retinal artery. Although paracentesis widens
vessels narrowed by artery obstruction, fluorescein
angiography shows that the filling occurs in a retrograde
fashion, via the retinal veins. Hence its value is questionable.
Combined obstruction of the central retinal artery and
central retinal vein is a much more serious complication.
Ophthalmoscopically a cherry-red spot is seen, as well
as numerous intraretinal hemorrhages and dilated retinal
veins. The Mechanisms of obstruction include direct
trauma to the central retinal vessels from the needle or
compression from blood or fluid injected into the nerve
sheath. Blood within a dilated optic nerve sheath has
been demonstrated in these cases.
The visual prognosis of these eyes is generally grim.
Computed tomography of the retrobulbar optic nerve
may be used to determine whether a nerve sheath hemorrhage is present. If an optic nerve sheath hematoma is
discovered, decompression of the nerve sheath may be
of limited benefit.
Neovascularization of the iris may develop after
combined central retinal artery-central retinal vein
obstruction. If the anterior chamber angle is not yet

closed by a fibrovascular membrane, aggressive,


full scatter panretinal photocoagulation treatment
should be administered in an attempt to prevent neovascular glaucoma.
Injecting with the eye in the primary position may
help prevent this complication. In contrast, injecting with
the eye looking up and in, places the optic nerve and
central retinal vessels more in the pathway of the needle
and thus probably should be avoided.
Multiple emboli with the retinal arterial system have
caused vascular obstruction following retrobulbar
corticosteroid injection. No therapy is available for this
visually devastating complication which likely results
from injection into the central retinal or ophthalmic artery.
In theory, the use of a needle shorter than 11/2 inches
may help to prevent the complication, as can having the
patient gaze in the primary position during the injection.
SUBARACHNOID INJECTION
Among the most recently recognized complications of
retrobulbar, anesthesia, inadvertent injection into the
subarachnoid space may be the most serious. The
subarachnoid space extends around the retrobulbar optic
nerve up to the globe and can be violated with a
retrobulbar needle at any point along its course.
Optic atrophy and blindness have also been reported
following retrobulbar blocks but they are fortunately rare.
Due to these potential complications retro-ocular
injection is out of favor with eye surgeon worldwide.
PERIBULBAR (PERIOCULAR) TECHNIQUE
Since the exit of retrobulbar akinesia, peribulbar akinesia
is considered a safe and effective technique of local
anesthesia for cataract surgery. It is method of choice with
eye surgeons for giving local anesthesia in cataract
surgery. As the name indicates, peribulbar anesthesia is
a technique in which a local anesthetic is injected into
peribulbar space and is not aimed at blocking a perticular
nerve.
Technique
Periocular anesthesia is administered at two site in lower
temporal quadrant and nasal to caruncle (Fig. 1.10).
The required local anesthetics are Lidocaine 1 percent
and Bupivacaine 0.75 percent with hyaluronidase.
Bupivacaine is preferred as it is a longer acting anesthetic
agent which can provide prolonged anesthesia and
analgesia.
In the first stage, injection of 0.5 cc of 1 percent lidocaine with a 26 gauge needle is done under the skin at
about 1 cm away from the lateral canthus in the lower

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12

Section I: Cataract

Fig. 1.10: Needle positions for peribulbar and retrobulbar akinesia (Courtesy: Ciba Geigy clinical symposia)

lid, along the orbital rim. The same needle is passed


deeper to inject 0.5 cc of lidocaine into the orbicularis
muscle and 1.0 cc into the muscle sheath. A second
injection is done in the similar fashion in the upper
eyelid just below the supraorbital notch. Pressure is
applied at both for a minute using gauze pieces.
In the second stage, combination of 6.0 ml of 0.75
percent bupivacaine, 3 ml of 1 percent lidocaine and 0.25
cc of hyaluronidase is filled into a 10 ml Disposable
syringe fitted with a, 1-1/4 inch 23 gauge, hypodermic
needle. The needle is first introduced deep into the orbit
through the anesthetized site in the lower eyelid. One
ml is injected just beneath the orbicularis muscle and then
the needle is advanced upto the equator of the globe to
inject 2 to 3 ml of the solution. The same procedure is
followed in the upper nasal quadrant through the
preanesthetised site to inject 1ml and another 1 ml may
be injected around superior orbital fissure, by deeper
penetration.
At the end of the procedure, fullness of the lids is
noted due to the volume of the injected solution. Firm
pressure with the flat of the hand is applied over the globe
and is maintained for a minute. Then, before surgery, any
pressure device as per the surgeons choice like Honans
balloon, super pinky ball, balance weight or simple padbandage is applied for 20 to 30 minutes, to achieve the
desire response of hypotony.
The efficacy of the anesthesia is evaluated after about
10 minutes of injection and if inadequate, 2 to 4 ml more

can be injected. In case of persistent inferior or lateral


movement injection lower temporal quadrant and in case
of persistent movements upwards of nasally, the upper
quadrant could be infiltrated in the same fashion.
Hyaluronidase is essential as it helps in the spread of
the drug. Otherwise, there are chances of the eye being
proptosed due to high orbital pressure induced by the
large quantity of the fluid injected.
Single injection of 5 to 6 ml of anesthetic mixture
injected from any site posterior to equator of the globe
also achieves same results. For convenience, however, it
may be done through lower lid the junction of lateral
and middle one third, along the floor of the orbit.
Adequacy of akinesia is determined by the absence
of ocular movements in all directions.
This technique is certainly better than retro-ocular
technique and has least complications.
Advantages
The advantages reported are:
1. The injection is done outside the muscle cone and so,
the inherent complications of passing the needle into
the muscle cone is completely eliminated.
2. It does not enter the retrobulbar space and thereby
avoids retrobulbar hemorrhage, injury to optic nerve
and entry of anesthetic agents into subarachnoid space and other complications like respiratory
arrest.

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Chapter 1: Anesthesia in Cataract SurgeryAn Update 13


3. Since the needle is constantly kept parallel to the bony
orbit, it avoids injury to globe and entry of anesthetic
agents into the eyeball.
4. It causes less pain on injection.
5. The procedure is easier and can be performed without
causing damage to vital structures.
6. It does not reduce vision on table.
7. No facial block is required.
Drawback
The possible drawbacks of this procedure are:
1. Chemosis of conjunctiva.
2. Delayed onset of anesthetic effect and
3. Potential risk of orbital hemorrhage. Though it occurs
rarely, the magnitude of the problem is comparable
to retrobulbar hemorrhage and necessitates postponement of surgery.
Mechanism
The exact mechanism is not known but this procedure
may best be described as Infiltration anesthesia where
nerve endings in all tissues in the area of injection get
anesthetised.
Peribulbar anesthesia is a safe and reliable technique
for achieving akinesia and anesthesia of the globe. In case
of inadequate anesthesia, repeat injections in the similar
manner can be safely used to achieve the purpose.

Fig. 1.11: Parabulbar (flush) local anesthesia


(cross section view)

Superior Rectus Injection


The induction of temporary paralysis of the superior
rectus muscle is essential for any intraocular operation
where the surgical field is upper half of the eye. This
injection also affects the action of levator palpabrae
superioris.
In this injection patient is asked to look down. The
upper lid is retracted and 2.5 cm long needle is passed
into Tenons capsule at the temporal edge of the superior
rectus muscle. The needle is directed posteromedially
and about 1 ml of anesthetic mixture of 2 percent
Xylocaine is injected around the muscle belly behind the
equator. This injection can also be made through the skin
of the upper orbital sulcus.

Fig. 1.12: Parabulbar (flush) local anesthesia


(surgeon view)

Parabulbar (Flush) Akinesia

Tenons Capsule Injection


The injection of anesthetic mixture can be given into
Tenons capsule around the upper half of the eyeball and
into the belly of superior rectus muscle. It is considered
safer than the retro-ocular injection across the postganglionic fibers of the ciliary body and may be effective
in inducing extraocular muscle akinesia.

Parabulbar (flush) administration is a new route for local


anesthesia which is highly useful, safe, effective and
technically easier (Figs 1.11 and 1.12). This method
consists of a limbal sub-tenon administration of Retrobulbar anesthesia using a blunt irrigating cannula. This
technique can be used for anterior and posterior segment
surgery.

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14

Section I: Cataract

TOPICAL ANESTHESIA
Since the advent of retrobulbar and peribulbar techniques in the early part of this century, both procedures
are mainstay of local anesthesia for intraocular surgery
till today. They do carry the risk of perforation of globe,
optic nerve and the inadvertent injection of anesthetic at
wrong places.
These accidents are mainly due to:
Carelessness on the part of ophthalmologist who
considers the procedures lightly and occurs more
often with senior eye surgeons.
Using long needles for these techniques endangers
the perforation of globe, piercing the optic nerve and
entering crowded retrobulbar space and even
touching the intracranial space on forceful injection
of copious amounts.
Anesthetics given through local injection with little
knowledge of anatomy of this area.
Retrobulbar hemorrhage with its adverse effects on
nerve and globe is very common complication of this
technique.
Injury caused by perforation of globe can lead to hole
formation, retinal detachment, vitreous hemorrhage
and central and branch vein occlusions.
To overcome all these practical difficulties use of
topical anesthesia in intraocular surgery has been widely
suggested and used at an International ophthalmic level.
Topical anesthesia meaning topical application of 4
percent Xylocaine or 0.5-0.75 percent proparacaine one
drop 3-4 times at regular intervals) in the eye has become
increasingly popular and accepted. In present day high
tech intraocular surgery specially phaco surgery topical
anesthesia is the anesthesia of choice with the eye
surgeons worldwide.
Indications to use Topical Anesthesia
Its indications in intraocular surgery are mainly when
performing phacoemulsification and IOL implantation through a clear corneal tunnel and corneoscleral
incisions.
Topical anesthesia is ideally suited for small incision
and stitchless cataract surgery. However, it is not a
advocated to perform standard/manual extracapsular cataract extraction and IOL implantation.
Proper selection of patient is of great importance in
this technique. It is important to have a patient who
will comply with the instructions given during
surgery.
Patients who are non-cooperative, hard of hearing,
with language problem and anxious patients are poor

candidates for surgery under topical anesthesia.


Capsulorrhexis requires the maximum cooperation
of the patient.
Intraocular surgery likely to be problematic in
patients with rigid small pupils responding poorly
to dilating drops and eyes with lenticular subluxation
and high grade nuclear sclerosis are relative contraindications for topical anesthesia.
Eye surgeon operating with topical anesthesia should
be proficient and experienced at phacoemulsification.
This procedure requires the use of foldable IOL either
as a silicone lens or an acrylic lens. This is essential
because corneal tunnel suture lens incision cannot be
larger then 3.5mm. Otherwise corneal complications
may arise and the incision would not be self-sealing.
HOW TO ACHIEVE SURFACE ANESTHESIA FOR
INTRAOCULAR SURGERY
Generally 3 applications of 4 percent Xylocaine or 0.4
percent Benoxinate HCL or 0.5-0.75 percent proparacaine
10 minutes apart starting 30 minutes before surgery are
recommended. A drop is thereafter instilled prior to the
incision. 1 CC of 4 percent Xylocaine or 0.4 percent
Benoxinate HCI or 0.5-0.75 proparacaine (from fresh vail)
is drawn into sterile disposable syringe and OT staff
person is asked to instil a few drops of the same prior to
cauterisation of bleeders and if required during surgery
conjunctival anesthesia is used (pinpoint and mini
pinpoint surface anesthesia)
Apart from giving topical anesthesia one has to give
systemic analgesia. Besides it, surgeon should have a
commanding hypnotic voice (vocal local anesthesia).
Most surgeons doing corneal tunnel incision under
topical anesthesia prefer to do it from temporal side.
CAN ONE CONVERT HALF WAY THROUGH
SURGERY UNDER TOPICAL ANESTHESIA
Intraoperative conversion from topical to peribulbar
anesthesia can definitely be achieved if surgical situation.
Warrants it. Since corneal tunnel incision is sutureless
and self-healing a peribulbar injection can safely be given
during the surgery.
Advantages of Topical Anesthesia
1. Phacoemulsification experts feel that use of topical
anesthesia with a clear corneal tunnel self-healing
incision is a significant advancement in intraocular
surgery. With topical anesthesia visual recovery is
immediate.

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Chapter 1: Anesthesia in Cataract SurgeryAn Update 15


2. It prevents the well-known complications of retrobulbar and peribulbar injections as mentioned in the
early part of this chapter.
3. It lessens the time of operating room use thereby
lowering costs.
4. There is no immediate postoperative ptosis as seen
in retrobulbar or peribulbar and Van Lint, O Brien
infiltrations lasts for 6-8 hours due to temporary
akinesia of the lids.
5. With topical anesthesia photon laser intraocular
surgery can be OPD procedure.
6. In practice we have seen the anxiety of patients to
peribulbar and retrobulbar injections prior to surgery.
With topical anesthesia this problem is over and
patient compliance will be better during intraoperative period.
7. The need of qualified anesthesiologist is over in
operation theater during the operation as a number
of ophthalmologists have been seen to prefer
anesthesiologist by their side for local anesthesia
(retrobulbar and peribulbar anesthesia).
8. No risk of postponement of intraocular surgery as
seen in cases of retrobulbar hemorrhage.
Again its main advantage is that it provides for
immediate postoperative visual recovery.
Disadvantages of Topical Anesthesia
1. Only a highly experienced surgeon can operate with
topical anesthesia. The eye can move which makes
the operation more difficult. If the eye movement
occurs when capsulorrhexis is being done, an
undesirable capsular tear may take place leading to
failure of this important step of the operation.
2. The chances of intraoperative complications with
topical anesthesia can be high if the surgeon is not
highly skilled. If such complications arise surgeon
should be ready to convert to other methods of local
anesthesia during the intraoperative stage, because
topical anesthesia along may not be adequate to
handle intraoperative complications. Surgeon should
be of cool temperament who can handle such a
situation without anxiety.
3. Topical anesthesia is not indicated in all patients
specially in anxious stressed patients, people with
hearing difficulties, children and very young patients.
4. As in our country a large number of patients come
from rural areas who are illiterate and poor. Their
compliance remains very poor and they do not
respond adequately to the command during surgery
with topical anesthesia.

5. The presence of very opaque cataract is a contraindication to the use of topical anesthesia. This is
because surgeon depends on the patient ability to
visually concentrate on the operating microscope light
in order to avoid eye movement during the operation.
Patients, who are not able to fix the eyes, may lead to
complications.
6. Some patients may feel pain during surgery with
topical anesthesia. One patient observed a lot more
pain and felt as if a sword was being used to cut him
up. The pain continued postoperatively for quite
sometime.
7. In principle, adequate selection of patients is fundamental when considering the use of topical anesthesia.
In spite of these hurdles topical anesthesia will be a
safe and common technique for local anesthesia during
intraocular surgery in the near future.
NO ANESTHESIA CATARACT SURGERY
This is the latest technique of cataract surgery in which
no anesthesia is required (whether local or topical).
Neither the topical or intracameral anesthetics agents are
used. This techniques is devised by Dr Amar Agarwal
(India) and has been acclaimed and accepted worldwide
and is being used routinely in phacoemulsification
surgery.
FURTHER READING
1.

Arora R et al. Peribulbar anesthesia, J Cataract Ref Surg 1991;


17:506-08.
2. Bloomberg L. Administration of periocular anesthesia. J
Cataract Ref Surg 1986; 12: 677-79
3. Bloomberg L. Anterior peribulbar anesthesia. J Cataract Ref
Surg 1991; 17: 508-11.
4. Davis DB. Posterior peribulbar anesthesia. J Cataract Ref Surg
1986; 12: 182-84.
5. Fichman RA: Topical anesthesia, Sanders DR, Slack 1993; 166172.
6. Furuta M et al. Limbal anesthesia for cataract surgery. Ophthalmic Surg 1990; 21: 22-25.
7. Garg A. Topical anesthesia: Current trends in ophthalmology.
New Delhi: Jaypee Brothers Medical Publishers (P) Ltd., 1997;
1-5.
8. Hay A et al. Needle perforation of the globe during retrobulbar
and peribulbar injection. Ophthalmology 1991; 98: 1017-24.
9. Kimble JA et al. Globe perforation from peribulbar injection.
Arch Ophthalmol 1987; 105: 749.
10. Shriver PA et al. Effectiveness of retrobulbar and peribulbar
anesthesia. J Cataract Ref Surg 1992; 18: 162-65.
11. Zahl K et al. Ophthalmol Clin North Am. Philadelphia: WB
Saunders, 1990.

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16

Section I: Cataract

No Anesthesia Clear
Corneal Phacoemulsification
Suresh K Pandey, Amar Agarwal, Liliana Werner, Sunita Agarwal, Athiya Agarwal

BACKGROUND
PROSPECTIVE RANDOMIZED
DOUBLE-MASKED STUDY
OUR STUDY AND OTHER
SURGEONS EXPERIENCE
WORLDWIDE
NO ANESTHESIA
CLEAR CORNEAL
PHACOEMULSIFICATION
SURGERY: WHY
DOES IT WORK?

BACKGROUND
Ophthalmic surgeons have witnessed a significant evolution in surgical
techniques for cataract extraction in the 20th century.1 The most remarkable
advance is, of course, the considerable decrease in the size of the wound
incision. Small-incision cataract surgery using phacoemulsification through
clear corneal self-sealing incisions avoids cauterization, suturing and
intraocular pressure fluctuations. Moreover, this is faster, more controlled
and less traumatic when compared with conventional large-incision
extracapsular cataract extraction (ECCE). With the advent of the phaconit
technique today it is possible to remove the cataract through a 0.9 mm
incision.2,3 The evolution in surgical techniques for cataract extraction is
summarized in Figure 2.1.
Anesthetic techniques for cataract surgery have also advanced significantly (Fig. 2.2). 4,5 General anesthesia was preferred in past years,
followed by various techniques of injectable anesthesia including
retrobulbar, peribulbar, sub-Tenon, and subconjunctival anesthesia. Due
to marked improvements in surgical techniques, it is no longer essential
to ensure complete akinesia of the eye and as a consequence, the technique
of topical anesthesia has been popularized as phaco anesthesia.6-22 This
includes eyedrops application, sponge anesthesia, eyedrops plus
intracameral injection, and most recently gel application.6,7,11-15,18-21,23,24
Topical anesthesia is the preferred technique for the members of American
Society of Cataract and Refractive Surgery (ASCRS) in the United States
(49%; range 37%-63%) according to a survey conducted by David Leaming
in 2000.25 It revealed that as high as 82 percent respondents using topical
anesthesia preferred eyedrops in association with intracameral injection
of lidocaine. In a recent, prospective, randomized, double-masked clinical
trial, Gillow and coworkers26 evaluated the efficacy of supplementary
intracameral lidocaine in routine phacoemulsification under topical anesthesia. There was no significant relationship between the use of
intracameral lidocaine and either intraoperative or postoperative pain
scores. The authors concluded that the routine use of intracameral lidocaine
as a supplement to topical anesthesia did not have any clinically useful
role.
Clear corneal phacoemulsification has the advantage of avoiding
touching any superficial sensitive ocular tissue (other than the peripheral
cornea) during the surgery. Preserved ocular motility can be used to
improve the operating conditions by optimizing the red reflex and wound

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Chapter 2: No Anesthesia Clear Corneal Phacoemulsification

17

Evolution of Techniques for Cataract Surgery


Technique

Year

Author/Surgeon

Couching
ECCE* (inferior incision)
ECCEE (superior incision)
ICCE** (tumbling)
ECCE with PC-IOL***
ECCE with AC-IOL****
Phacoemulsification
Foldable IOLs
Capsular surgery
Accommodating IOLs
Phaconit
Dye-enhanced cataract surgery

800
1745
1860
1880
1949
1951
1967
1984
1992
1997
1998
2000

Susutra
Daviel
von Graefe
Smith
Ridley
Strampelli
Kelman
Mazzocco
Apple/Assia
Cummings/Kamman
Agarwal
Pandey/Werner/Apple

*ECCE:

extracapsular cataract extraction.


ICCE: intracapsular cataract extraction.
***PC-IOL: posterior chamber intraocular lens.
****AC-IOL: anterior chamber intraocular lens.
**

Fig. 2.1: Evolution of techniques for cataract surgery


Evolution of Anesthetic Techniques for Cataract Surgery
Technique

Year

Author

General anesthesia
Topical cocaine
Injectable cocaine
Orbicularis akinesia

1846
1884
1884
1914

Hyaluronidase
Retrobulbar (4% cocaine)
Posterior peribulbar
Limbal
Anterior peribulbar
Pinpoint anesthesia
Topical
Topical plus intracameral
No anesthesia
Cryoanalgesia
Xylocaine jelly
Hypothesis, no anesthesia

1948
1884
1985
1990
1991
1992
1992
1995
1998
1999
1999
2001

Koller
Knapp
Van Lint, OBriens
Atkinson
Atkinson
Knapp
Davis and Mandel
Furata and coworkers
Bloomberg
Fukasawa
Fichman
Gills
Agarwal
Gutierrez-Carmona
Koch, Assia
Pandey and Agarwal

Fig. 2.2: Evolution of anesthetic techniques


for cataract surgery

access. Compared to regional anesthetic techniques such


as peribulbar anesthesia, the topical approach does not
increase the vitreous pressure, and there is no effect on
the optic nerve blood flow. Postoperative recovery is
quicker, postoperative pain is reduced, and the
patient may prefer this technique. Recently, various
authors reported their experience concerning topical
anesthesia.11-13,15,18-21
However, neither injectable nor topical anesthetics are
completely safe. Injectable techniques of these agents can

lead to various complications which can be non-sightthreatening, sight-threatening and very rarely, lifethreatening.3,4,6,8,26 Topical anesthesia prevents these complications but it can lead to corneal epithelial, corneal
endothelial, and/or retinal toxicity, mostly due to the
preservatives in the anesthetic solutions.28-32 Moreover,
topical anesthetic agent and its vehicle may serve as
reservoir of microbial contamination with the potential
for causing an infection. Some of these agents (e.g. proparacaine) can lead to allergic and idiosyncratic reactions.
Manifestations of such reactions include periocular
swelling, erythema, and the typical rash of contact
dermatitis. Further, preoperative instillation of some of
the topical anesthetics (e.g. lidocaine) may cause burning
and stinging sensations and multiple applications
sometimes lead to mild haziness of the cornea during
the surgical procedure. There is a potential for cumulative
toxicity on account of need for administration of several
doses. Recent reports suggested that cataract surgeons
should be aware of the potential for endothelial injury if
anesthetic agents are injected into the eye.30-32 This is not
surprising because the intraocular concentration of the
anesthetic agent after intracameral injection can be 250
times higher than the concentration after topical
application. 33 Complications can be associated with
topical anesthesia are summarized in Figure 2.3.
The clear corneal phacoemulsification and intraocular
lens (IOL) implantation without the use of anesthetic
agent was recently performed in India (Agarwal A, MD,
FRCS, Agarwal A, MD, Agarwal S, MD, Comparison of
Cataract Surgery with No, Topical, or Intracameral Anes-

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Section I: Cataract

Side Effects and Complications of


Topical Ocular Anesthetics
1. Alteration of the stability of lacrimal and tear
films.
2. Delayed healing of the epithelium in presence
of epithelial defects.
3. Toxicity to corneal endothelium secondary to
preservative benzalkonium.
4. Surface keratopathy.
5. Retinal and macular toxicity
Fig. 2.3: Side effects and complications of
topical ocular anesthetics

thesia, Presented at the ASCRS Symposium on Cataract,


IOL and Refractive Surgery, Boston, MA, USA, April
2000), Germany (T. Neuhann, MD, No Anesthesia
Cataract Surgery can be an option, Ocular Surgery News;
September 2000) and Spain (F. J. Gutierrez-Carmona, MD,
PhD, Phacoemulsification with Cryoanalgesia: A New
Approach for Cataract Surgery, Video Presented at the
American Academy of Ophthalmology annual meeting,
Dallas, Texas, USA, October 2000) and Brazil (V.
Centurion, MD, No Anesthesia cataract surgery Defies
Conventional Wisdom, Ocular Surgery News, January
15, 2001, pages 9-15).
We recently completed a collaborative study on no
anesthesia cataract surgery in comparison to topical and
topical plus intracameral anesthesia.35,36 The aim of the
study was to avoid the use of topical anesthesia during
cataract surgery and to evaluate the efficacy of this
technique. We also compared the comfort of the patient
and the stress for the surgeon during the surgery in the
3 groups.
PROSPECTIVE RANDOMIZED
DOUBLE-MASKED STUDY
Patients
Seventy-five patients were enrolled in this prospective,
randomized, double blind study as reported by Pandey
et al.35 Informed consent was obtained from the patients
after explaining in detail the outline of the study, which
was reviewed and approved by the ethics committee of
the hospital. All patients were randomized to one of the
three groups: group I - no anesthesia, 25 patients; group
II - topical anesthesia, 25 patients; group III - topical plus
intracameral anesthesia, 25 patients. The patients

included in the study were between 38 and 79 years of


age. The density of the cataracts varied from grade 2 to 4
(Emery-Little classification).37
Excluded were patients with barrier to communication or cooperation during surgery (extreme anxiety,
language and/or hearing impairment, mental
retardation, dementia, Parkinsons disease, very young,
etc). Monocular patients and those with hard, mature
cataracts (grade 5 Emery-Little classification), shallow
anterior chamber(s), pupil(s) less than 5 mm in diameter
(when fully dilated), and inability to understand a visual
analogue pain scale were also excluded.
The patients were prepared for cataract surgery
without preoperative (or intraoperative) sedation. The
pupils were preoperatively dilated using phenylephrine
(5%), cyclopentolate (0.5%) and tropicamide (1%) eyedrops. Nonsteroidal anti-inflammatory drugs (NSAIDs)
were not used.
Anesthetic Techniques
Patients in group I received, while still in the preoperative
area, two drops of balanced salt solution (BSS Alcon,
Forth Worth, TX) every 5 minutes three times, beginning
10-15 minutes before the procedure. After the corneal
endothelium was coated with viscoelastic, before
performing the capsulorhexis, an intracameral injection
of BSS via a 25 gauge Rycroft cannula (Beaver and
Visitec Products, Bidford on Avon, England) was
performed. Patients randomized to group II received
lidocaine (4%) eyedrops preoperatively, and an intra
cameral injection of BSS, as described above. Patients
in group III received both, preoperative 4 percent
lidocaine eyedrops and intracameral injection of
preservative-free lidocaine (1%), using the same methods
as in the other 2 groups.
The protocol established for the supplemental
anesthesia for breakthrough pain during the surgery, if
it should occur, was as follows: if the patient was in pain,
two additional drops of lidocaine (4%) would be placed
in the eye. If the pain persisted, a peribulbar or
retrobulbar block would be used.
Surgical Technique
All cataract surgical procedures in this study were
performed in a referral institute of South India by the
same surgeon (Dr Amar Agarwal). A solid speculum with
a screwing mechanism was placed. No superior rectus
sutures were used in any group. Patients were informed
that they would be aware of the sensation of touch and
would be able to move their eyes. First of all, viscoelastic

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Chapter 2: No Anesthesia Clear Corneal Phacoemulsification

19

Fig. 2.4: Clear corneal incision. Note the straight rod


in the left hand to stabilize the eye

Fig. 2.5: Rhexis being performed. Note once again the left
hand holding the straight rod to stabilize the eye

was injected into the anterior chamber using a needle


through the area where the second (paracentesis) site was
made. This was important in order to distend the eye to
create a good self-sealing corneal valve. A straight rod
was then used to enter within the anterior chamber
through the same opening of the needle to stabilize the
eye. With the right hand, a 3.2 mm groove was made in
clear temporal cornea using a diamond knife (Fig. 2.4).
During the entire surgical procedure care was taken to
avoid grasping of the conjunctiva or sclera by tooth
forceps. The globe was stabilized by the straight blunt
rod during the entire surgery. A 5.0-5.5-mm wide
capsulorhexis (Fig. 2.5) was performed using a 26 gauge
bent needle cystotome. Hydrodissection was performed
with BSS. Nuclear emulsification (Alcon, Universal 2,
Fort Worth, TX) was performed using the Karate chop
technique using less ultrasound power. Cortical
aspiration was then done. The capsular bag was filled
with viscoelastic. Foldable one-piece plate lenses were
then implanted (STAAR Surgical Co, Monrovia, CA).
Intracameral miotics were not used in any of the patients.
The viscoelastic was removed from the anterior chamber
and the capsular bag by irrigation. The corneal incisions
were secured by performing stromal hydration.
The operating microscope light was kept at its lowest
level and gradually increased in intensity. The level was
up to the usual operating levels after hydrodissection
and the patient was encouraged to fix the eye toward
the microscope light during the surgery. All of the patients

neither receive subconjunctival injections nor an eyepad


was applied at the completion of the surgery.
Parameters Assessed
After the surgery, the patients were taken to the postoperative area where vital signs were obtained. There, one
constant observer also collected patient assessment
responses. Questions were presented to the patients in a
standardized written form. Each patient was shown a
10-point visual analogue graphic pain scale with numeric
and descriptive ratings where 0 represented no pain and
10 represented severe, unbearable pain.38 They were
asked to grade the level of discomfort or pain during the
surgery and postoperatively, on separate scales. If the
patient was unable to see the scale or read the
accompanying text, the scale was described and verbal
score was obtained. They were also asked to differentiate
pain or discomfort from touch or movement
sensation. The degree to which the patients were
bothered due to ability to move their eyes, sense of
touching their eyes and by the operating microscope light
was also assessed. This was graded as not at all (0),
not very much (1) and very much (2). If the surgeon
was bothered by the patients eye movement, it was also
graded as not at all (0), not very much (1) and very
much (2). Stress for the surgeon during the surgery
(from 0-2) and total surgical time (minutes) were also

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Section I: Cataract
Table 2.1: Characteristics of the patients included in each group

Number of cases
Average age
Males/females
Nuclear density
Operating time (min.)
Race (% nonwhite)

*Group I

**Group II

***Group III

25
59.66+/-9.54
18/7
2.50+/-1.10
8.25+/-1.78
100

25
56.80+/-9.35
15/10
2.64+/-0.90
8.88+/-2.24
100

25
60.00+/-10.17
14/10
2.28+/-0.79
8.38+/-1.70
100

*:No anesthesia.
**:Topical anesthesia.
***:Topical + intracameral anesthesia.

noted. The patients were kept in the recovery area for a


minimum of 30 minutes. The surgeon also completed a
questionnaire on the surgical conditions, complications
and need for supplemental anesthesia.
Comparison of various parameters between the
aforementioned three groups was performed using
analysis of variance (ANOVA). A P value inferior to 0.05
was considered statistically significant.
Results
A total of 75 patients were recruited into the study. No
patient refused to take part. Patients data are listed in
Table 2.1. There was no significant difference in age (Fig.
2.6) and density of cataracts (Fig. 2.7) of the patients from
the three groups. Therefore, the patients included in the
study were comparable. The average surgical time (Fig.
2.8) was 8.25 1.78 minutes for the no anesthesia group
(group I), 8.88 2.24 minutes in the topical anesthesia

Fig. 2.7: Results of no anesthesia cataract


surgery study: Cataract density

Fig. 2.8: Results of no anesthesia


cataract surgery: Surgical time
Fig. 2.6: Results of no anesthesia cataract
surgery study: Mean age

group (group II) and 8.38 1.70 minutes in the topical


plus intracameral anesthesia group (group III). The

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21

Table 2.2: Parameters (and scores) evaluated in the three groups

Pain (0-10)
Discomfort due to
microscope light (0-2)
Discomfort due to
ability to move the eye (0-2)
Discomfort due to
sense of touch (0-2)
Surgeons discomfort
during surgery (0-2)
Stress for surgeon
during surgery (0-2)

Group I*
(N = 25)

Group II**
(N = 25)

Group III***
(N = 25)

P Value

1.54+/-1.84
0.20+/-0.41

1.44+/-1.04
0.04+/-0.20

1.16+/-1.17
0.16+/-0.37

0.6106
0.2115

0.25+/-0.44

0.40+/-0.20

0.40+/-0.20

0.0235****

0.37+/-0.64

0.20+/-0.40

0.28+/-0.45

0.0629

0.30+/-0.57

0.12+/-0.33

0.28+/-0.45

0.158

0.40+/-0.58

0.08+/-0.27

0.16+/-0.37

0.0206****

*: No anesthesia
**: Topical anesthesia
***: Topical + Intracameral anesthesia
****: Statistically significant (P<0.05)

Fig. 2.9: Results of no anesthesia cataract surgery:


Scale of pain

surgical time was slightly higher in the topical anesthesia


group when compared to the no anesthesia or topical
plus intracameral anesthesia groups, but this difference
was not significant (P=0.3562). No patients in any group
required supplemental anesthesia.
The results from the questionnaires are summarized
in Table 2.2. The mean score of intraoperative pain (scale
from 0 to 10) in the no anesthesia group (Fig. 2.9) was
slightly superior than in the topical and topical plus
intracameral groups. However, this difference was not
statistically significant (P=0.6101). In other words, there
was no significant difference in the subjective sensation
of pain during cataract surgery either with or without
topical anesthesia. The mean score of patient discomfort

Fig. 2.10: Results of no anesthesia cataract surgery:


Patients discomfort due to microscope light

due to the microscope light was slightly higher in the no


anesthesia group, but this difference was again (Fig. 2.10)
not statistically significant (P=0.2115). Patient discomfort
due to ability to move the eyes had a significantly higher
mean score in the no anesthesia group (P=0.0235) when
compared (Fig. 2.11) to the two other groups. Regarding
patient discomfort due to sense of touching the eyes the
mean score was higher in the no anesthesia group (Fig.
2.12). However this difference was not statistically
significant (P=0.0629). Concerning surgeon discomfort
due to the ability of the patients to move the eyes, the
difference between the three groups (Fig. 2.13) was also
not statistically significant (P=0.1580). However, the
stress for the surgeon during the surgery was

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Section I: Cataract

Fig. 2.11: Results of no anesthesia cataract surgery:


Surgeons discomfort due to patients ability to move the eye

Fig. 2.13: Results of no anesthesia cataract surgery:


Patients discomfort due to ability to move the eye

Fig. 2.12: Results of no anesthesia cataract surgery:


Patients discomfort due to sense of touching the eye

Fig. 2.14: Results of no anesthesia cataract surgery: Stress


for the surgeon during surgery

significantly greater in the no anesthesia group (Fig. 2.14)


when compared to the topical or topical plus
intracameral group (P=0.0206 ).
In summary, the only two parameters that differed
significantly in the 3 groups were patient discomfort due
to ability to move the eyes and stress for the surgeon
during the entire surgical procedure.

anesthesia combined with intracameral lidocaine was not


associated with significantly lower intraoperative and
early postoperative pain scores.
Assessments of other parameters in the 3 groups
besides the pain scores revealed that only patient
discomfort due to ability to move the eyes and stress for
the surgeon during the procedure were significantly
different.
No anesthesia cataract surgery has been currently
performed by other surgeons in various countries.
Dr Francisco J Gutierrez-Carmona performed no anesthesia cataract surgery on 50 patients in Spain.39 He used
cooled balanced salt solution in the operating eye and
termed this technique as cryoanalgesia. Dr Tobias

OUR STUDY AND OTHER SURGEONS


EXPERIENCE WORLDWIDE
This is the first randomized, double-masked, controlled
trial comparing three techniques, namely no anesthesia,
topical anesthesia and topical plus intracameral
anesthesia. The use of either topical anesthesia or topical

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Chapter 2: No Anesthesia Clear Corneal Phacoemulsification


Neuhann performed no anesthesia cataract surgery on
16 cases in Germany (T. Neuhann, MD, No anesthesia
cataract surgery can be an option, Ocular Surgery News;
September 2000). He performed it mostly on patients
over 50 years, but interestingly some of the patients less
than 50 years of age also asked for the no anesthesia
technique. This is due to a trend of no medical treatment, which is common in very selective group of
peoples in Germany. The use of 2 percent hydroxypropyl
methyl cellulose (HPMC) to cover the cornea, helped in
avoiding corneal dryness during the surgery. Although
motivation is important, according to Dr Neuhanns
experience no anesthesia cataract surgery works better
in older patients. Dr Keiki R Mehta from Mumbai, India
also performed more than 450 cases using this technique
(Mehta KR, MD, personal communication). The need for
supplemental anesthesia in his series was about 10-12
percent. He believes that the limbus is a watershed area
for tactile sensations and therefore the corneal sensitivity
in the peripheral cornea is significantly lower than the
central cornea (see below: anatomical factors). Other
surgeons currently performing this technique include Drs
Heidi Fischer, Cordelia N Uddoh and Eli-Marcovici
(USA), Martin Zand (Sweden) (Zand M, No anesthesia
catartact surgery, presented at the All India Ophthalmology Congress, Chennai, India, January, 2000) and
Mohan Rajan (India) (Rajan M, How no anesthesia
cataract surgery works? presented at the All India Ophthalmology Congress, Chennai, India, January 2000).
NO ANESTHESIA CLEAR CORNEAL
PHACOEMULSIFICATION SURGERY:
WHY DOES IT WORK?
It seems surprising that cataract surgery can be
performed through one of the most sensitive structures
(cornea) without using any anesthesia. The precise
explanation(s) for this fact is still unknown to us.
However, some hypotheses related to surgical factors and
anatomical factors as proposed by Pandey and
associates,35,36 are discussed here.
Surgical Factors
The skill and experience of the surgeon is one of the most
important factors for the no anesthesia cataract surgery.
While using this technique, it is important to avoid
grasping the conjunctiva or sclera with tooth forceps. The
surgeon should use a straight and relatively blunt rod to
stabilize the eye during the entire procedure. Also, the
use of a clear corneal incision avoids the use of cautery,
necessary to achieve hemostasis with scleral tunnel

23

incisions. In addition, gradual increase in the microscope


luminance, minimization of the iris-lens diaphragm
movement and iris manipulations are important factors
for topical as well as no anesthesia techniques. The phaco
power should be used minimally to avoid excessive
heating of the phaco tip, which in turn can produce pain.
Anatomical Factors
The cornea is supplied by the medial and lateral long
ciliary nerves, which are branches of the trigeminal nerve.
It is sensitive to touch, pain and temperature.40 However,
there are marked topographical variations in the corneal
sensitivity. Besides the diurnal variations, corneal sensitivity also varies according to age, sex and race.40-42 The
central part of the cornea is the most sensitive. There is
an overall reduction in the corneal sensitivity from the
center to the periphery. The superior part of the cornea
is the least sensitive, probably because of a decreased
concentration of acetylcholine.
Concerning the diurnal variations, corneal sensitivity
is the lowest in the morning and highest in the evening.
This decreased sensitivity in the morning must be
attributed to the reduction in oxygen tension at the
epithelium surface when the eye is closed.41
Corneal sensitivity remains practically unchanged
from 10 to about 50 years of age. Beyond that age, the
decline is significant reaching a half beyond 65 years of
age. The precise mechanism is not clear, however, some
authors relate it to the formation of arcus senilis and to a
decreased concentration of acetylcholine. In females,
corneal sensitivity decreases during the premenstrual
and menstrual periods.
The role of racial factors should not be underestimated.42 It was documented during contact lens fitting
and many studies confirmed that corneal sensitivity in
non-white (dark-brown eyed: Indians, Chinese, and
Negroes) peoples is 4 times less than in white (blue-eyed:
Caucasians) peoples. As reported by Michel Millodot in
1975, this phenomenon is obviously relevant to the
wearing of contact lenses. 42 It may also have some
bearing on problems of anesthesia as it is possible that
different quantities of anesthetics may be needed
according to eye color. This is similar to the clinical fact
that more ocular drugs are needed for people with dark
rather than light-pigmented irises to obtain the same
effect (for example cycloplegia). The reason for this is
not known, although it may be related to the amount of
melanin pigment present in the iris. Since the cornea does
not contain any pigment, however, it is not easy to explain
the diminution of corneal sensitivity with darker
pigmentation of the iris. It is not known whether the

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Section I: Cataract

thickness of the cornea varies with eye color. It has been


shown that thicker corneas, as a result of edema, are less
sensitive than normal corneas. It is also unknown
whether nerve supply density varies widely among these
different peoples. Another possibility is that the
difference in sensitivity arises in the central nervous
system and not at the periphery. The difference in tactile
sensitivity may also be relevant to understand that the
practice of acupuncture may be more acceptable in China
than it is in countries inhabited by blue-eyed people.
Finally, recent studies have documented that frequent
exposure to ultraviolet rays (between 280 and 310 nm)
may give rise to a loss in corneal sensitivity, as high as 73
percent.40 Also, decrease in temperature can lead to
reduction in corneal sensitivity, which have been
documented up to nine folds.40
Thus, no anesthesia cataract surgery works due to
atraumatic surgical techniques in suitable patients by a
very experienced and confident surgeon. The speed and
dexterity of the surgeon are paramount to the successful
use of this technique, as it is the proper patient selection.
Incision and manipulations through the least sensitive
(superior) part of the cornea are probably the most important factors. Further decrease in corneal sensation due
to the dark iris of patients in India, and aged patients
exposed to ultraviolet rays probably accounted for the
results obtained in our study.
As mentioned earlier, the reasons for the racial
variations are still unknown. However, the differences
may be important in adapting the technique for more
sensitive corneas in white patients, as did Dr Francisco
Gutierrez-Carmonas in Spain by using cooled balanced
salt solution (cryoanalgesia) for corneal desensitization.39
CONCLUSION
In conclusion, we demonstrated that clear corneal
phacoemulsification surgery could be performed without
the use of anesthetic agents. The advantage is that it
avoids any toxicity associated with topical and/or
intracameral anesthetic solutions. However, no
anesthesia cataract surgery certainly not suitable for
every cataract surgeon or every patient and its real
benefits have to be measured carefully, in a case-by-case
basis. Alternatively, the use of cooled eyepad, irrigating
solution and viscoelastics (cryoanalgesia) may also be
helpful to reduce patient pain and discomfort during the
cataract surgery without having any possible adverse
effects from topical and/or intracameral anesthetic
agents.

REFERENCES
1. Linebarger EJ, Hardten DR, Shah GK, Lindstrom RL. Phacoemulsification and modern cataract surgery. Surv Ophthalmol
1999; 44:123-47.
2. Agarwal A, Agarwal S, Agarwal A et al. Phakonit: Phacoemulsification through a 0.9 mm corneal incision. J Cataract Refract
Surg 2001; 27:1548-52.
3. Agarwal A, Agarwal S, Agarwal A, Bagmar A, Patel N, Pandey
SK, Shah S. PhakonitLens removal through a 0.9 mm corneal
incision. J Cataract Refract Surg 2001; 27:1531-32.
4. Greenhalgh D. Anesthesia for cataract surgery. In Yanoff M,
Ducker JS (Ed). Ophthalmology. St Louis, Mosby-Yearbook,
1998, PP 21.5-21.6.
5. Ram J, Pandey SK. Anesthesia for cataract surgery. In Dutta LC
(Ed): Modern Ophthalmology. New Delhi, India: Jaypee
Brothers. 2000, PP 325-30.
6. Koch PS. Anterior chamber irrigation with unpreserved lidocaine 1% for anesthesia during cataract surgery. J Cataract
Refract Surg 1997; 23:551-54.
7. Patel BCK, Burns TA, Crandall A et al. A comparison of topical
and retrobulbar anesthesia for cataract surgery. Ophthalmology
1996; 103:1196-1203.
8. Gills JP, Cherchio M, Raanan MG. Unpreserved lidocaine to
control discomfort during cataract surgery using topical
anesthesia. J Cataract Refract Surg 1997; 23:545-50.
9. Zehetmayer M, Radax U, Skorpik C et al. Topical versus
peribulbar anesthesia in clear corneal cataract surgery. J Cataract
Refract Surg 1996; 22:480-84.
10. Manners TD, Burton RL. Randomized trial of topical versus
sub-tenons local anaesthesia for small-incision cataract surgery.
Eye 1996; 10:367-70.
11. Roman S, Auclin F, Ullern M. Topical versus peribulbar anesthesia in cataract surgery. J Cataract Refract Surg 1996; 22:112124.
12. Crandall AS, Zabriskie NA, Patel BCK et al. A comparison of
patient comfort during cataract surgery with topical anesthesia
versus topical anesthesia and intracameral lidocaine. Ophthalmology 1999; 106:60-66.
13. Masket S, Gokmen F. Efficacy and safety of intracameral
lidocaine as a supplement to topical anesthesia. J Cataract
Refract Surg 1998; 24:956-60.
14. Martin RG, Miller JD, Cox CC III et al. Safety and efficacy of
intracameral injections of unpreserved lidocaine to reduce
intraocular sensation. J Cataract Refract Surg 1998; 24:961-63.
15. Garcia A, Loureiro F, Limao A et al. Preservative-free lidocaine
1% anterior chamber irrigation as an adjunct to topical
anesthesia. J Cataract Refract Surg 1998; 24:403-06.
16. Tseng H-S, Chen FK. A randomized clinical trial of combined
topical-intracameral anesthesia in cataract surgery. Ophthalmology 1998; 105:2007-11.
17. John T. Simplified anesthesia technique for scleral tunnel
phacoemulsification. J Cataract Refract Surg 1998; 24: 1562-65.
18. Gills JP, Cherchio M, Raanan MG. Unpreserved lidocaine to
control discomfort during cataract surgery using topical
anesthesia. J Cataract Refract Surg 1997; 23:545-50.
19. Koch P. Anterior chamber irrigation with unpreserved lidocaine
1% for anesthesia during cataract surgery. J Cataract Refract
Surg 1997; 23:551-54.
20. Carino NS, Slomovic AR, Chung F, Marovich AL. Topical
tetracaine versus topical tetracaine plus intracameral lidocaine
for cataract surgery. J Cataract Refract Surg 1998; 24:1602-08.

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Chapter 2: No Anesthesia Clear Corneal Phacoemulsification


21. Garcia A, Loureiro F, Limao A et al. Preservative-free lidocaine
1% anterior chamber irrigation as an adjunct to topical
anesthesia. J Cataract Refract Surg 1998; 24:403-06.
22. Claoue C. Simplicity and complexity in topical anesthesia for
cataract surgery (editorial). J Cataract Refract Surg 1998;
24:1546-47.
23. Koch PS. Efficacy of lidocaine 2% jelly as a topical agent in
cataract surgery. J Cataract Refract Surg 1999; 25:632-34.
24. Assia EI, Pras E, Yehezkel M et al. Topical anesthesia for
lidocaine gel for cataract surgery. J Cataract Refract Surg 1999;
25:635-39.
25. Leaming DV. Practice styles and preferences of ASCRS members2000 Survey. J Cataract Refract Surg 2001; 27:948-55.
26. Gillow T, Scotcher SM, Deutsch J et al. Efficacy of supplementary
intracameral lidocaine in routine phacoemulsification under
topical anesthesia. Ophthalmology 1999; 106:2173-77.
27. Davis DB, Mandel MR. Anesthesia for cataract extraction. Int
Ophthalmol Clin 1994; 34:13-30.
28. Rosenwasser GOD. Complications of topical ocular anesthetics.
Int Ophthalmol Clin 1989; 29:153-58.
29. Maloney WF. Intraocular lidocaine causes transient loss in small
number of cases. Ocul Surg News 1996; 14:32.
30. Werner L, Legeais JM, Obsler C et al. Toxicity of xylocaine to
rabbit corneal endothelium. J Cataract Refract Surg 1998;
24:1371-76.
31. Liang C, Peyman GA, Sun G. Toxicity of intraocular lidocaine
and bupivacaine. Am J Ophthalmol 1998; 125:191-96.
32. Judge AJ, Najafi K, Lee DA, Miller KM. Corneal endothelial
toxicity of topical anesthesia. Ophthalmology 1997; 104:
1373-79.

25

33. Behndig A, Linden C. Aqueous humor lidocaine concentrations


in topical and intracameral anesthesia. J Cataract Refract Surg
1998; 24:1598-1601.
34. Agarwal A, Agarwal A, Agarwal S, No anesthesia cataract
surgery with karate chop. In Phacoemulsification, Laser
Cataract Surgery and Foldable IOLs- Second edition. India:
Jaypee 2000, 195-203.
35. Pandey SK, Werner L, Agarwal A, No anesthesia cataract
surgery. In Phacoemulsification, Laser Cataract Surgery
and Foldable IOLs- Second edition. Jaypee India., 2000,
217-25.
36. Pandey SK, Werner L, Apple DJ, Agarwal A, Agarwal A,
Agarwal S. A randomized clinical trial comparing no anesthesia
clear corneal phacoemulsification surgery with topical and
topical plus intracameral anesthesia. J Cataract Refract Surg
2001; 27:1643-50.
37. Emery JM, Little JH. Phacoemulsification and Aspiration of
Cataracts; Surgical Techniques, Complications, and Results. St
Louis: CV Mosby, 1979, 45-48.
38. Scott J, Huskisson EC, Graphic representation of pain. Pain 1976;
2:175-84.
39. Gutierrez-Carmona FJ. Phacoemulsification with cryoanalgesia:
A new approach for cataract surgery. In Agarwal S, Agarwal A,
Apple DJ, Buratto L, Ali JL, Pandey SK, Agarwal A (Eds): Text
book of Ophthalmology (volume II). Thorofare, Slack Inc., 2000
(in press).
40. Millodot M, A review of research on the sensitivity of the cornea.
Ophthal Physiol Opt 1984; 4:305-18.
41. Millodot M, Do blue-eyed people have more sensitive cornea
than brown-eyed people? Nature 1975; 8:151-52.
42. Millodot M, Diurnal variation of corneal sensitivity. Br J
Ophthalmol 1972; 56:844.

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Section I: Cataract

Corneal Endothelium and


its Protection in Phacoemulsification
Keiki R Mehta

THE IMPORTANCE OF THE


ENDOTHELIUM
EVALUATION OF THE
ENDOTHELIUM: THE
ENDOTHELIAL MICROSCOPE

THE IMPORTANCE OF THE ENDOTHELIUM


The transparency of the cornea depends on its lack of blood vessels, on a
grate-like distribution of the collagen fibers of corneal stroma, and its
relative lack of water. Deturgence of the cornea is maintained by the
endothelium and the epithelium. Damage to the epithelium only leads to
a light localized swelling of the cornea, which disappears as soon as
epithelium re-generates through cell division.
For the clarity of the cornea the endothelium has a far greater significance. The endothelium is a single layered structure of flat, hexagonal/
cuboidal cells, applied to the posterior layer of the Descemets membrane.
According to Maurice 1972, the endothelium dehydrates the cornea by
pumping the water against the hydrostatic pressure into the anterior
chamber. As an intact cell layer the endothelium passively prohibits the
diffusion of the molecules into the corneal stroma. This fact further
contributes to the low water content of the cornea.
The cornea normally has a relative constant thickness of 500 microns
and has water content of 75 to 80 percent (Cotlier 1970). If the endothelium
is badly damaged, water enters the stroma, causing it to swell; thus the
collagen fibers separate from each other, and loose the crystal-like
distribution. Clinically this means clouding of the cornea. This stromal
change leads to edema of the corneal epithelium.
EVALUATION OF THE ENDOTHELIUM:
THE ENDOTHELIAL MICROSCOPE
In 1968 Morris described a specular microscope for observation of the
endothelium of the enucleated eye. Laing in 1975 and Bourne and Kaufman
in 1976 subsequently modified this instrument, so that one could examine
the patient in the sitting position. The procedure was subsequently termed
as clinical endothelium microscopy.
Endothelial (Specular) microscopes can be of two types: Contact and
Non-contact.
Contact Endothelial Microscope
The advantage of a contact system is that you can examine a larger area
with sharper and better illumination. However, these units are commonly
utilized for clinical research and are comparatively costly. A good example

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Chapter 3: Corneal Endothelium and its Protection in Phacoemulsification 27


of the contact endothelial specular microscope is the
Konan-Keeler microscope. In Contact microscopy, the
objective of the instrument is brought in direct touch with
the cornea which it applanates. The applanation to some
extent, controls the fine movement of the eye, so that the
picture sharpness is enhanced. Without the contact
element, the image quality diminishes. This is due to a
higher difference between the refractive index of the
cornea and the air (difference = +0.376). In addition there
is much more pronounced scattering of light by the
inhomogeneitis of the tear film and by the unevenness
of the epithelial surfaces. Bigar 1982.
Non-contact Endothelial Microscope
They can be fully dedicated units like the Topcon specular
microscope, which can automatically change focus and
take the flash photograph to get the best possible picture.
These units are much more economical and far faster to
use and, being non-contact, are very patient friendly.
The other alternatives are the simple attachments on
to a Slit Lamp or, better still a Photo Slit Lamp. The early
specular attachments were made by both Zeiss and
Nikon, but were designed to specifically fit only their
own slit lamps. Bio-Optics EMH 1000 made a small
attachment, very much like the barrel of a regular microscope, which could be fitted on any slit lamp. McIntyre
made a reticule, which could be introduced into the Zeiss
slit lamp. Used at a fixed 40X magnification it could grade
the cells into four categories of 4000, 2000, 1000 and 500
cells mm2.
The limitations of all these instruments are that it is
never possible to exactly photograph the same area again
and hence serial photographs become very difficult.
Hence, there is always a statistical variation, which has
to be taken into account in considering these cell counts.
The wide field endothelial microscope by increasing the
area of photographs, diminishes this problem, enhances
accuracy, permits a more meanful analysis of cell
morphology and density, and is a more sensitive indicator
of endothelial cell changes and stress (Glasser DB et al
1985).
Variations in Endothelial Cell Count
The total endothelial cell count at birth is highin the
range of 6500-7000 cell/mm2. While mitosis may occur
in the very young endothelium, it is infrequent in adults
(Bron and Tripathy 1997). There is great individual
variation in cell counts. A gradual decrease in density
and increase in shape variation (polymegathism) occurs
with age (Shaw 1978). In youth the cells are predominantly hexagonal, but become more polymorphic with
increasing age. Sherand Novakovics and Speedwell

(1987) suggest that the endothelial density is around 6000


cell/mm2 at birth and falls by 26 percent in the first year.
A further 26 percent is lost over the next 11 years but the
rate of cell loss decreases and stabilizes around middle
age, especially in polymegathous endothelium (Blatt,
Rao, Aquavella 1979).
Healing of Lost Endothelial Cell Areas
Hoffer KJ, Philippi G (1978, 1982) in their cell membrane
theory gave a very lucid hypothesis on cell movement
of the endothelium. The stimulus for the endothelial cells
begins with an area of cell loss. It is within the defect
that the loss of contact between the neighboring cells
leads to spreading of the cells, which become quantitatively larger. When through spreading, the cells make
contact again, the movement of the cell protoplasm in
that direction stops. If the defect is greater, the cells may
loose contact on the side opposite the defect. Now the
cells lining the secondary gap in cell continuity will
respond to this loss of contact by following the first cells.
As soon as all the cells are in contact with each other the
process stops. This hypothesis therefore explains the
findings of the uneven cell size and cell shape (poikilocytosis) that one finds in older patients.
Minimal Cell Density
The minimum cell density required for corneal clarity is
still unknown. It is certain that even after a great reduction of endothelial cells, the cornea is still able to stay
clear. Clear corneas were noted with cell counts of 380
(Forstot 1977), 442 (Binkhorst 1978) 480 (Kraff 1978), it
would thus appear that cells of 400-500 cell/mm2 are
adequate to maintain dehydration (Alpar 1986). On the
other hand corneal decompensation has also been noted
at a higher cell count level.
Late Corneal Decompensation
A presently clear cornea with a low cell count does not
really mean that the cornea will remain clear for the rest
of the patients life. It would only require the subsequent
addition of insult, iritis, glaucoma or surgery to precipitate a barely stable cornea into an unstable one, which
would lead to decompensation.
Steps to Prevent Cell Loss
Prevent IOL Contact
From the earlier days it was well known that certain steps
led to significant corneal loss. Even the momentary
contact of a PMMA lens with the endothelium, led to

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28

Section I: Cataract

severe damage to the endothelium. The cells were lifted


off (sheared off). The Descemets (Kaufmanns 1976),
Worst( 1984) studies showed that in addition to the
contact, movement was also needed. On the other hand,
the surface of the natural lens on the endothelium was
practically harmless. Contact with the silicone IOL led
to a mild loss but contact with a fully hydrated HEMA
IOL had hardly any cell loss (Mehta 1989, 1992).
Care with Irrigating Solutions
Intracameral and irrigating solutions also can lead to
extensive endothelial cell loss. Physiologic salt solution
is quite toxic . Ringer Lactate is a little better than plain
Ringers solution. Balanced salt solution seems to be
better, but the ideal solution is BSS plus (BSS with
oxidized glutathione) . In the clinical studies comparing
BSS to BSS Plus, Klein et al in 1983 found significantly
less endothelial cell loss will BSS Plus (15.4%) than with
BSS (22.7%) in other patients after ECCE and an P/C
implant performed without a visco-elastic. Benson 1981
in a well-designed prospective study found significantly
less corneal edema on the first day with BSS Plus than
with lactated ringer.
There is a paucity of studies comparing BSS with BSS
Plus. Kline (1982) showed that there was significantly
less loss of endothelial cells using BSS Plus (15.4%), as
compared to BSS (22.7%). Despite many studies which
show that the endothelial cell count is different, BSS with
BSS Plus, one has to clearly appreciate that simple
endothelial cell loss does not demonstrate the subtle
changes which can be depicted in the early postoperative
period. We know that endothelial cell loss continues
throughout life and the cornea remains clear by virtue
of the endothelial cell reserve, which, with its vital
function, maintains deturgescence. Any surgical or nonsurgical insult tends to shift the endothelial cell loss curve
towards progressive decompensation (Mishima 1982).
Thus even a slight increase in the rate of endothelial cell
loss can significantly reduce the clarity lifespan of the
corneal endothelium.
Patients with low endothelial cell densities of the
endothelium (diabetics) are known to be more susceptible
to surgical stress. Even stresses such as contact lens wear;
persistent iritis or glaucoma can lead to corneal decompensation. In cases where the endothelium has already
been compromised it would make sense that the most
physiological, non-traumatic, endothelial cell viable,
irrigating solution should be utilized to give the endothelial cells the maximum chances to survive.
The question often asked is why does BSS Plus
maintain better structure and functional integrity of

intraocular tissues as compared to ordinary BSS or Ringer


Lactate. This question had been answered by Winkler
(1977) who felt that the difference was essentially in the
buffer, bicarbonate in BSS Plus, which is the major buffer
present in aqueous and effective in the physiological pH
range of 6.00 to 8.00. Bicarbonate is also important for
normal retinal function (Moorhead 1979). The citrateacetate in BSS is effective only at non-physiologic pH
levels of 3.6-6.2. Citrate may also chelate calcium, which
would disrupt Endothelial cell functions and barrier
functions (Stern 1981). On the other hand Ringer lactate
lacks a buffer altogether. Other chemical differences
between the solutions too play an important role. Glutathione is needed for maintenance of Endothelial cell
junctions and barrier function and also plays an essential
role in endothelial fluid transport (Whikehart DR 1978).
Glucose is an essential energy source for maintenance of
aerobic metabolism. It is also used for ATP production
for the Na/K pump and NADPH production to reduce
glutathione and prevent oxidative damage to endothelial
cells.
Another factor that is often not taken into account is
the time, the solution stays in contact with the endothelium. Often one seems to consider the contact time is
only the surgery time, thinking erroneously, that aqueous
replenishes itself virtually immediately. McDermott and
Edelhauser in 1988 calculated that it takes over four hours
for the aqueous to replace the fluid left in the anterior
chamber at the end of surgery. However an important
consideration also is that the aqueous fluid production
is nearly always reduced by surgery with a 50 percent
reduction being normal, thus the irrigating solution
would remain in the postoperative eye for almost 8 hours.
Use Preservative Free Intracameral Solutions
Preservative in the solutions can do gross endothelial
damage. Especially antioxidants like sodium hydrogen
sulfite, bacteriostatic substances like benzylchonium
chloride (normally added to solutions as a preservative).
Sterilizing solutions like cetrimonium chloride, Hibitane
(Chlorhexidine), Epinephrine with its preservative,
sodium bisulphite, are very toxic, but intracardiac epinephrine (without preservative) at a very low concentration of 0.5 ml in 500 ml of BSS seems to be well
tolerated.
Use Iced (4oC ) Irrigating Solutions
Another important consideration when the solution is
utilized with Phacoemulsification is the temperature of
the solution. Although 37o C is considered physiological
it would seem more likely that the temperature would

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Chapter 3: Corneal Endothelium and its Protection in Phacoemulsification 29


be much higher than that especially since the irrigating
solution is also utilized to cool the Phacoemulsification
tip. Accelerated metabolic activity with increased
glucose/oxygen consumption and even denaturation of
some proteins may occur if the temperatures rises just a
few degrees about 37oC (Edelhauser 1987). It is for this
reason that the use of cooling solutions has been
recommended, by running the tube through an icy bath.
Reduced temperatures would reduce the rate of
biochemical reactions and reduce inflammation and in
addition reduce the risk of a scleral burn from the hot
phaco needle especially when hard cataracts are being
tackled by phacoemulsification.
Why Endothelial Cell Loss with Phaco?
More often than not, phaco is now done using only
topical anesthesia. Sometimes, when the case is predicted
to take longer, as when a hard cataract is being done,
many surgeons will utilize intracameral 1 percent Xylocard (preservative free Xylocaine utilized by cardiologists). Though Xylocard is considered innocuous the
normal corneal endothelial long-term studies still have
not shown total safety in corneas, which show some
degree of stress.
Phacoemulsification is characterized by the use of
ultrasound energy coupled with a high quantum of
irrigation fluid usage. In addition, a fair amount of movement occurs in the anterior chamber, which is required
to prepare the nucleus for removal.
Unfortunately, the corneal dome has inadequate space
for gymnastics. The surgeon invariably visualizes the
critical central area of the cornea, forgetting that the
periphery is as important, for injury in the periphery has
to heal the same way, namely by cells enlarging and
sliding over to close the gap left by the injury. The cells
for this healing process naturally have to be provided
from the adjacent areas and from the center.
As far as possible try to minimize multiple entry in
and out of the eye, as it will invariably lead to inadvertent
corneal touch with grave results.
The Surgeon has to Take Special Care
1. During tunnel construction At the time of making a
corneal tunnel, after dimpling the endothelium at the
time of entry, the chamber is well formed and
preserved. The problem only occurs at the time of
removal of the diamond knife. One needs to remove
it without any pressure on the posterior lip to keep
the chamber formed. Any undue pressure on the
posterior lip will lead to a chamber collapse. Now

when the knife is being removed it will rub all over


the endothelium.
2. Introduction of the phaco tip in the chamber The corneal
periphery is affected every time the surgeon enters
the eye as some level of trauma is induced. Particular
care needs to be taken at the time of entry of the phaco
instrument. In an effort to enter without touching the
iris, the surgeon looses sight of the fact that the phaco
will invariably, for 1 mm or so slide over the inner
edge of the cornea, affecting the endothelium.
3. With the insertion of the capsulorhexis forceps The
moment the rhexis forceps is opened, it becomes a
race between the instrument entering, and the gradual oozing out of the viscoelastic, leading to a
gradual collapse of the chamber which once again
needing refilling. In this race, the surgeon tends to
turn the rhexis forceps in an inadequate chamber and
is likely to touch the endothelium.
4. Doing peripheral rhexis in tight eyes Similarly, doing
rhexis with a forceps in the extreme periphery, care
has to be taken that the surgeon concentrating on
doing a good rhexis accidentally, does not lift the
capsule forceps inadvertently touching the cornea.
5. Time of insertion of the IOL If forceps are being used,
care should be taken, that the chamber is fully
distended with viscoelastic substance. The IOL should
be carefully inserted. It is better to slightly scrape
against the iris rather than scrape the corneal endothelial cells off. If an injector is being utilized, after
the tip of the injector enters the corneal tunnel, prior
its exit the tip should be slightly deflected down (in a
similar maneuver as when the cornea is dimpled for
entry during making of the tunnel). This simple
maneuver prevents the damage to the endothelial
cells.
Since the cornea, with either the aqueous or BSS
slightly distorts the view (objects seem slightly bent
forwards). Unless the perception of depth with the
microscope is exceptional, it may lead the surgeon to
miscalculate his actual position in the anterior chamber
leading to accidental touch.
A panicky surgeon leads to a lost eye. Nothing
panics a surgeon as much as a non-cooperative lens in a
phaco surgery. I still remember Professor Federov, the
Great Russian Implant specialist being asked at a meeting
in Mumbai, as to what he would do if he got into trouble
during an IOL insertion, He had replied. I would sit
back, have a shot of Vodka, and then decide what to do.
It is important when a complication occurs, to sit back,
reflect on it for a few minutes (not necessarily with
Vodka), plan a line of action and only then proceed. It is
not the complication, which affects the eye, but often the

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30

Section I: Cataract

surgeon who complicates the complication by trying to


do everything at the same time, loosing his cool and
compounding the problematic situation.
One must make sure that the IOL does not come into
intimate contact with the endothelium in the late postoperative period. Virtually all phaco surgery is now done
with corneal tunnels. A properly constructed tunnel gives
an excellent result. The problem with a tunnel, which
has inadequate length or has a badly designed inner flap,
is that it does not seal itself. If the surgeon is unhappy
with a tunnel and feels that it may not self-seal, it is better
to place a single horizontal mattress or an infinity stitch
rather than leaving it untended. A leaking corneal tunnel
will lead to a flat chamber and has the propensity for
late infection. The fundamental rule should be that a
tunnel not sealing on the table will not seal by itself. It
must be sutured.
Protection of the corneal endothelium has always
been a critical requirement for successful phacoemulsification. Protection is particularly important in
endothelially-compromised corneas as in Fuchs dystrophy and in all cases where the cell count is inadequate.
A good cell count and even more, a proper analysis of
the cell configuration is essential prior undertaking
phaco. One must be very careful if the second eye of the
patient has gone in for decompensation. Some ethnic
races have a predilection for decompensation even with,
what one would feel, really minimal trauma. In India,
Parsis in particular, as a race, do have this problem.
Endothelial Cell Protection Techniques in
Phacoemulsification
Decrease Fluid Input Coupled with Zero Suction
It is a well-established fact that prolonged irrigation;
coupled with excess aspiration, tend to lead to cell loss.
It can be minimized by: (i) altering the irrigation solution
used (BSS Plus is the most innocuous), (ii) usage of zero
suction by disconnecting the suction line from the
machine. However, zero suction is a problem with the
new techniques of chop, which require a firm, hold on
the cortical nucleus to be able to chop it successfully.
Present day phaco, unless it is being performed on a
very hard cataract usually is a short procedure and hence
the fluid exchange in the chamber is rarely more than
150 ml.
Viscoelastic Protection
The use of dispersive viscoelastics is supposed to significantly diminish the propensity towards endothelial cell

loss (e.g. Viscoat). It must however be clearly understood


that the primary aim of viscoelastic substances (VES for
short) is that they are space occupying, and maintain the
chamber.
Steve Arshinoff, divided viscoelastic substances into
two basic groups. An understanding of these groups goes
a long way in appreciation of their protection abilities.
He divided viscoelastic substances into:
a. High viscosity and cohesive ability with zero shear
rate and possessing a high molecular weight
(examples are Healon, Healon GV, Provisc, Amvisc
and Biolon)
b. Lower viscosity with low cohesive ability but with
exceptional dispersive ability, possessing a low
molecular weight (examples are Viscoat, Vitrax,
HPMC).
The high cohesive viscoelastic substances with high
viscosity are very useful for the creation and maintenance
of space in the anterior chamber. In addition they enable
stabilization of the nucleus and the torn capsule during
the capsulorhexis procedure. They can also be used as a
tool to separate and dissect tissue like re-opening
adhesions or reforming a flat chamber. They also act as a
inertial energy control when the IOL is shot out of an
injector and the viscoelastic substances damps down the
speed of silicone unfolding, preventing damage to the
tissues. In addition they act as a tamponade for the
vitreous in the unlikely event of a capsular rupture.
The high cohesive viscoelastic substances have the
advantage that they are very easy to remove during the
final irrigation/aspiration phase.
The high dispersive viscoelastic substances have the
advantage that they break down (or disperse) into their
components (hence the term dispersive). This group of
products forms an adherent layer, which clings onto the
endothelium, literally acting as a second skin, and
protects the endothelium from the effect of deleterious
substances. It is this group which is very useful in performing phacoemulsification on eyes with a poor
endothelial cell count. It also has the advantage that it
traps the nuclear fragments, preventing them from
bouncing off the endothelium during phacoemulsification.
The dispersive viscoelastic substances have the
disadvantage that at the end of the procedure, they have
to be literally, vacuum aspirated.
A combination of these substances is now available
Amvisc Plus (Bausch and Lomb). It is said to combine
the advantages of both, and is moderately cohesive as
well as dispersive.

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Chapter 3: Corneal Endothelium and its Protection in Phacoemulsification 31


Use of Freezing Solutions
Both the viscoelastic as well as the infusion solutions, if
used ice-cold are said have a preservative action on the
endothelium (Edelhauser 1998). In addition the use of
freezing solutions also minimizes the incidence of corneal
burns from the phaco tips, especially when high ultrasound energies are used with the very hard (Suprahard)
cataracts.
Pulse Phaco Usage
Diminishing the phaco power by using the pulsed phaco
method, and a more sensitive control with better tuning
capabilities have both helped to diminish the cell loss.
The only problem with pulsed phaco is that it is difficult
to really get a good hold on the lens for chopping and
thus can only be used after the primary phaco procedure
of nuclear chopping is over. A modified version of pulse
mode is the Burst mode (the AMO Diplomax and the
Alcon Legacy), which, in essence, gives a fixed series of
pulses and stops so that the lens can be held. It however
has the problem that if attempted, just a bit carelessly,
the burst will, in a medium cataract, go all the way
through, promptly rupturing the capsule.
Proper Tip Placement

The obvious solution in providing a physical


protection for the endothelium is the Hema Hood. Here
a Hema membrane is used to protect the endothelium of
the cornea by placing it in direct contact with the
endothelium. Thus, in essence, it functions as an endocorneal contact lens. The method devised acts as a physical barrier literally like a corneal endothelial umbrella.
Hema Intracameral Endothelial Contact Lens
The Hema material used in the Hood has also been used
by the author for fashioning Hema soft IOL from 1977
onwards and has been in usage for over 18 years, first as
an Iris Clip lens and later as a Disc P/C. It is a proven
concept that a soft IOL touching the endothelium of the
cornea lead to virtually no deleterious effect (Packer 1978,
Mehta 1997, 1998).
The Design of the Hema Hood
The Hema Hood is designed with a front surface curve
of 8.20 mm, of Plano power, 9.00 mm total diameter. The
central thickness is 0.18 mm. The edge is made with a
reverse bevel, which prevents the hood from being
dislodged by a stream of BSS from the phaco needle.
The Material of the Hema Hood

Though newer techniques like tangential/vertical chop


have helped further, by decreasing operative time and
diminishing intracameral acrobatics, the modern
techniques of phacoemulsification depend much more
on the ability to properly position the tip to be in an
optimal position to hold a lens and chop it down into
smaller parts, permitting easy emulsification using
negligible ultrasound energy. The problem only comes
about if the cataract is very hard. Now the number of
times the lens has to be held with bursts of ultrasound
power increases. Since the fragments are very hard, the
energy required to engulf and emulsify them also
increases. Naturally the endothelium exposure to U/S
energy will increase.
The Advent of the Concept of Physical
Endothelial Cell Protection

Wohlk (German) soft contact lens material


Hexamethyl methacrylate with cross polymers and
EGDA
Refractive Index
1.44
Elasticity at break
1.40
Oxygen permeability
4.43*10.9
Hydration:
Saline content
38.8 percent
Water uptake
62.3 percent
Saline uptake
63.6 percent
Temperature resistance: No change in parameters
after boiling for 24 hours
Light Transmission 400-800 nM
Ash Content 0.1 mg in 3.00 gm ashed
The Surgical Technique of using the Hema Hood

The obvious answer is to protect the endothelium from


the deleterious effects of ultrasound, the turbulence of
the irrigation fluid, the noxious effects of the irrigating
solution and/or intracameral injections (like Xylocard)
on the cornea and the accidental touch with the endothelium during intracameral maneuvers. The barrier
should be for functional reasons, a physical barrier.

Preparation of the Hood for Usage


The endothelial hood is presented in a metal foil sealed
bottle filled with BSS, sterilized by autoclaving, and
sealed in a sterile, (ETO gas) double pouch. The surgeon
takes the bottle on the table utilizing full sterile facilities.
The hood is removed from the bottle using a toothless

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32

Section I: Cataract

forceps or simply floated out. It is then put in the jaws of


a box folder, normally used for folding silicone lenses
prior insertion. Using a standard silicone lens insertion
forceps the hood is grasped making sure that the entire
lens is engulfed in the lips of the holder. It is imperative
that the lens be always kept moist. It is then coated with
viscoelastic solution prior insertion.
Insertion of the Hood
The correct time for insertion of the hood in the anterior
chamber is after completing the rhexis, finishing the
hydrodissection and making sure the nucleus rotates
well. The anterior chamber is inflated with viscoelastic.
(HPMC works best).
The Hood is now inserted in a folded stage, held in
the holder. Once the lens crosses the mark of the hood,
the forceps is released which permit the hood to unfold.
Be sure to release the hood keeping the convex side
towards the dome of the cornea. Next, viscoelastic is
again injected between the hood and the iris, thus
pushing the hood into intimate contact with the
endothelium. The hood sticks by itself to the
endothelium. Wait for about 30 seconds, which allows
the hood to settle itself, and the phaco procedure may be
commenced.

syringe filled with BSS with a blunt 26 G bent cannula.


Insert it into the anterior chamber and squirt at the edge
of the Hema Hood. As the jet of BSS impacts at the edge
of the hood, it dislodges the Hema Hood off the endothelium of the cornea. The hood then simply floats onto the
iris. Using straight, plain forceps, the Hood is held and
simply removed. The Hood being a pure Hema material
oozes out with no problem. Though the Hood is supplied
as a single use, disposable item, it can be washed
carefully, placed in BSS, and the re-autoclaved.
Postsurgical Evaluation
The eye is always very quiet. In over 775+ cases done
over the last 2 years, no problem has been encountered.
The case selection is based on whether it is a hard cataract,
which will need more ultrasound time and if the cell
counts is poor.
It is used as a routine
a. If the cell count is 1500 or less.
b. If the other cornea has suffered decompensation
for any reason.
c. When students are being taught phacoemulsification in a firm or hard cataract as it protects the
endothelium very significantly.
d. In all cases of Suprahard cataracts (6+ or over).

Phacoemulsification Procedure with the Hood


Phaco is allowed to proceed normally with no restriction
of technique for the primary phaco or, the subsequently
following, I/A or IOL insertion. Any technique can be
used, four quadrant technique to chopping or the newer
vertical phacoemulsification. There is no problem if the
HEMA hood is accidentally touched, it simply moves
and then automatically slides back into position. Even
with full irrigation/aspiration, there is no discernible
movement of the hood.
The IOL can be injected or simply inserted with
forceps. The only additional care needed, is at the time
of inserting the IOL. When the injector is placed in the
tunnel, just prior its exit from the tunnel into the anterior
chamber, remember to enter at a slightly steeper angle,
tilting the IOL towards the iris to prevent the edge of the
hood from being nudged. Again, even if it occurs, the
hood will only slide away, like a decentering soft contact
lens and then shift back into position smoothly.
Removal of the Hood following Surgery
On the completion of the surgery, after the IOL has been
inserted, as a last step, take out the Hema Hood. The
technique for removal is simplicity itself. Take a 5.00 ml

Endothelial Cell Analysis


Analysis of the Endothelial Cells with the Hema Hood
has been carried out in detail in the last 14 months with
the Topcon Non-Contact Specular Microscope SP-2000P.
The data is transferred to a Pentium III computer and
analyzed with the Topcon ImageNet Cell Analysis
software which give good, reproducible, stable readings.
Initial data would seem to confirm what we had
originally conceived. The cell protection ability of the
Hood seems very good.
To really know if the system works, two independent
observers did a series of evaluation of the authors cases.
All cell counts were done with the Topcon Non-Contact
Specular Microscope SP-2000P. The data being analyzed
with the Topcon ImageNet Cell Analysis software.
The authors average cell loss, using the tangential
chop for medium cataracts, vertical phacoemulsification
for hard cataracts, and the Side chop/Saddle-hump
technique for suprahard cataracts. WITHOUT the use of
the endothelial cell protection device, the Hema hood
were:
Soft cataracts
02.2 percent
Medium cataracts
1.2-4.4 percent

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Chapter 3: Corneal Endothelium and its Protection in Phacoemulsification 33


Table 3.1: Endothelial cell difference in MEDIUM density cataracts with the Hema Hood
Sr No Patient
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

HB
CG
MB
DR
AS
HM
RT
CD
SM
DC

Pre-Op

Post Op

3880
2464
2658
3668
3348
4014
4340
3964
2884
4432

3768
2386
2600
3633
3264
3872
4450
3856
2800
4318

Difference

Percent variation

112
78
58
35
84
142
10
108
84
114

2.88
3.16
2.18
0.95
2.50
3.53
0.23
2.72
2.9
2.57

Endothelial Cell loss as evaluated by a Topcon Non-Contact Endothelial camera: Average Variation
= 2.36 percent.

Table 3.2: Endothelial cell difference in HARD cataracts with the use of the Hema Hood
Sr No Patient
1.
2.
3.
4.
5.
6.
7.
8.

WC
RC
DS
FD
TH
HR
CU
YD

Pre-op
3448
2868
4226
3086
5062
3838
3862
4208

Post-op
3320
2764
4142
3012
4956
3760
3770
4052

Difference

Percent variation

128
104
84
74
106
78
92
158

3.71
3.62
1.98
2.39
2.09
2.03
2.38
3.75

Endothelial Cell loss as evaluated by a Topcon Non-Contact Endothelial camera: Average


Variation = 2.74 percent
Table 3.3: Endothelial cell difference in SUPRA-HARD cataracts with Hema Hood
Sr No Patient
1.
2.
3.
4.
5.
6.
7.
8.

SH
DK
NR
TD
FT
RK
FN
TC

Pre-op
2864
2874
4148
3864
4006
2884
3286
4428

Post-op
2720
2722
3960
3736
3842
2798
3158
4236

Difference

Percent variation

144
154
188
128
164
86
128
192

5.03
5.35
4.53
3.32
4.09
2.98
3.89
4.33

Endothelial Cell loss as evaluated by a Topcon Non-Contact Endothelial camera: Average


Variation = 4.19 percent

Hard cataracts
2.4- 6.4 percent
Supra hard cataracts
5.8- 12.3 percent
Note: The accuracy of the Topcon Non-Contact Endothelial Camera technique has a maximum accuracy of
(+/-) 2 - 3 percent.

With the usage of the Hema Hood, three types of cataracts were considered and analyzed; Medium density,
Hard Cataracts and Suprahard cataracts and their cell
counts were done individually. Representative analyses
are displayed above in Table 3.1 to 3.3.

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34

Section I: Cataract

Hema Intracameral Contact Lens


Endothelial Cell Loss: Average Cell
Loss in Phaco with the Hema Hood
With any type of lens density, irrespective of the length
of the procedure, the cell loss stays in the narrow range
of 3-5 percent.
Subsequently, endothelial cells evaluations were done
using the Hood. The cells differences showed that
whether a hard or a suprahard cataract was done the
difference remained virtually identical. Even in
suprahard cataract, which in the authors own series
showed a gross variation, in the Hood series showed a
very stable cell count, which hardly varied. With any type
of lens density, irrespective of the length of the procedure,
the cell loss stays in the narrow range of 3-5 percent.
Note: The accuracy of the Topcon Non-Contact
Endothelial Camera technique has a maximum accuracy
of (+/-) 2 - 3 percent.
Interestingly in a number of cases of suprahard
cataracts after the surgery was over, and the hood was
removed a clear demarcation line, almost like a

watermark was left. The area protected by the Hood was


very clear but a diffuse haze was visible outside the
boundaries of the hood. The haze was there the next day
and then gradually faded off.
It would thus seem that the Hema protection device
is functional. It is particularly useful where the cells are
compromised either in quantity or even quality and
where the surgeon feels that the endothelium is at risk.
It is particularly useful to use when phaco is been done
on a case, which has been grafted before.
It also makes for an excellent teaching device, as even
with prolonged ultrasound power being used in the
chamber the endothelium is not at any risk.
In Summary
In the long Odyssey of Phaco, the Hema Hood is an
effective technique in preserving the vital endothelial
cells in the Phaco procedure. Usage of the Hood permits
phaco even in endothelially-compromised corneas, with
safety.

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Chapter 4: Phacoemulsification with CryoanalgesiaA New Approach

35

Phacoemulsification with
CryoanalgesiaA New Approach
Francisco J Gutirrez Carmona

INTRODUCTION
INTRODUCTION
SURGICAL TECHNIQUE
COMMENT

With the passing of time we see rapid changes in advances in all fields of
medicine, and especially in surgery. As far as ophthalmology is concerned,
it is perhaps the specialty in which most changes have been developed, as
is the case of ocular anesthesia.
Cataract surgery is currently carried out, in the majority of cases, with
local anesthetic via retrobulbar, peribulbar or subconjunctival injection,
or also with topical anesthesia. The tendency is to reserve general
anesthetic mainly for patients with senile dementia, deafness, in cases of
non-collaboration of the patient and in pediatric surgery.
The use of local anesthetic in cataract surgery has superseded general
anesthesia due to its great advantages, such as the possibility of ambulatory
surgery, rapid recovery and the elimination of the complications derived
from general anesthesia.
Nevertheless, local anesthetic surgery, whether with the retrobulbar or
peribulbar technique, is not without its complications, such as the possible
perforation of the eyeball with retinal detachment and severe intraocular
hemorrhage, retrobulbar hematoma, diplopia, direct trauma to the optic
nerve by the retrobulbar needle, increased intraocular pressure (IOP),
postoperative ptosis, or the systemic complications due to the accidental
transfer of anesthetic into the bloodstream, or by impregnation of the
nervous system.
New cataract surgery techniques through a small incision, using
manual phacofragmentation or phacoemulsification have facilitated the
reintroduction of topical anesthesia. This kind of anesthesia was first used
in 1910 by Hirschberg, who routinely operated on cataracts using a 2
percent cocaine solution. More recently, in 1985, Smith used a combination
of topical anesthesia and subconjunctival injection of lidocaine for
extracapsular cataract extraction (ECCE). However, in 1992, Fichman was
the first author to reintroduce topical anesthesia in cataract surgery by
means of phacoemulsification and the implantation of an intraocular lens
(IOL).
Afterwards, in June of 1998, Agarwal in India carried out the first
cataract operation without the use of pharmacological anesthesia.
Later, in February of 1999, the author in Spain carried out the first
cataract operation using cryoanalgesia, modifying Agarwals method. This
technique was presented at the 14th SECOIR Congress (Zaragoza, Spain),
at the 17th European Society of Cataract and Refractive Surgeons (ESCRS)

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36

Section I: Cataract

Congress (Vienna, Austria), and at the Video Cataratta


99 (Milan, Italy).
In this way, we see that it is possible to carry out
treatment or surgery using the analgesia caused by
coldcryoanalgesia. For example, it has been used in
this way in thoracic surgery for lung lobectomy through
a minithoracotomy or in the treatment of postoperative
pain after thoracotomy. Cryoanalgesia is also used in the
pain units of anesthesia departments, for hip adductor
spasticity and obturator neuralgia as postoperative
treatment for chronic pain.
In ophthalmology, about 30 years ago, a Polish
ophthalmologist, Dr. Tadeusz Krwawicz, performed the
first cataract operation with cryoextraction of the lens.
This ophthalmologist not only opened a new branch of
ophthalmologycryoophthalmologyfor the treatment of certain ocular diseases, but also demonstrated
the possibilities of the use of low temperatures in
medicine.
SURGICAL TECHNIQUE

Fig. 4.1: The cornea is cooling in the area where


we carry out the paracentesis

Clear-corneal Incision

In order to perform surgery, it is necessary previously


to cool all fluids to be used in the operation to around 4
degrees, except for the povidone drops, which should
be at normal temperature for optimum effect.
Before the operation, a bag of cold gel can be placed
over the eye, which will afford a degree of analgesia to
the eyelids, facilitating the insertion of the lid speculum.
We carry out ocular asepsis before surgery with 5
percent povidone drops. Next, a drop of cold methylcellulose is instilled into the eye before placing the
ophthalmic drape to isolate the eyelids. The cold
methylcellulose reduces the stinging sensation of the
povidone.
It is important to perform phacoemulsification
through a clear-corneal incision, not to touch the
conjunctiva or sclera and not to use forceps to hold the
eyeball. For the blepharostaxis, we use a Barraquer
speculum, although a Castroviejo one is also very
useful.

We inject cold viscoelastic material through the paracentesis into the AC, and subsequently we introduce a
lens manipulator to stabilize the eyeball. Then we
continuously cool the cornea with BSS in the area in
which we are to perform the clear-corneal incision. The
corneal tunnel incision is performed at 90 to the
paracentesis with the help of a 45 stab incision knife
(Fig. 4.2), an angled crescent knife and a 3.2 mm phaco
knife (Fig. 4.3).

Paracentesis
The cornea is previously cooled by continuous irrigation with the flask of cold BSS in the area in which we
carry out the paracentesis. To perform the paracentesis
we hold the eyeball still with a spatula or lens
manipulator placed on the corneal periphery opposite
the area where we enter the anterior chamber (AC) with
a paracentesis knife (Fig. 4.1).

Fig. 4.2: At 90 from the paracentesis, the clear-corneal


incision is performed, with the help of a 45 stab incision
knife, having previously cooled the corneal surface

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Chapter 4: Phacoemulsification with CryoanalgesiaA New Approach

Fig. 4.3: The anterior chamber is entered with 3.2 mm


phaco knife, having previously cooled the corneal area

37

Fig. 4.4: The nuclear phacoemulsification is performed


using irrigation with cold balanced salt solution (BSS)

IOL Implantation and Incision Closure


Capsulorhexis and Nuclear Hydrodissection
Cold viscoelastic is injected into the AC. Next, we chill
the corneal incision in order to perform a continuous
circular capsulorhexis (CCC) with capsular forceps.
The lens nucleus is hydrodissected with cold BSS
using a Binkhorst cannula introduced at 12 Oclock, or
with a straight Rycroft cannula.

Cold viscoelastic is injected into the capsular bag and


the corneal incision is enlarged to 4.1 mm, after chilling
it. Next, after cooling the corneal incision with BSS, a
foldable IOL is implanted (Fig. 4.5).
Closure of the incision is performed with stromal
hydration using cold BSS (Fig. 4.6).
COMMENT

Phacoemulsification
Depending on the surgeons preferences, our method can
accommodate the use of either the peristaltic pump
system or the venturi pump.
The process of phacoemulsification can be carried out
by any surgical techniquechip and flip, divide and
conquer, chop techniques, etc. modifying the parameters
of the phacoemulsifier according to the type of cataract,
type of apparatus and preferences of the surgeon.
We perform phacoemulsification using irrigation with
cold BSS during linear and pulsed phaco (Fig. 4.4).
During phacoemulsification, the cornea must be
kept chilled with cold BSS. When the tip of the phacoemulsifier is inserted into the anterior chamber, the
corneal incision is cooled by continuous irrigation with
the flask of cold BSS.

With this new method of phacoemulsification using


cryoanalgesia, we have obtained very good results as
regards analgesia in the patient and surgeon comfort.

Cortical Aspiration
The cortical aspiration is performed with cold irrigation and according to the parameters of each phacoemulsifier.

Fig. 4.5: After cooling the corneal incision with BSS,


a foldable IOL is implanted

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Section I: Cataract
Furthermore, we believe that phacoemulsification
with cold fluids will reduce postoperative inflammation and the presence of endophthalmitis, as well
as the endothelial trauma caused by the heat of the
phacoemulsifier tip. Ancillary advantages is a quieter
eye, with significantly less redness, both during and
after surgery, with less prostaglandin response.
FURTHER READING

Fig. 4.6: Closure of the wound is performed by


stromal hydration with cold BSS

An important point to emphasize in this new method


of performing cataract phacoemulsification without
pharmacological anesthesia, is the continuous cooling
by irrigation of the corneal surface before carrying out
paracentesis and corneal incision, and also before the
introduction of any probe or instrument, etc. into the
anterior chamber.
Given that the iatrogenia derived from pharmacological anesthesia has been reduced by the use of
topical anesthesia, we think that this new method is a
further step towards avoiding the secondary effects of
topical anesthesia, such as allergic reactions to
anesthetic, corneal epithelial damage, etc.

1. Agarwal A, Agarwal S, Sachdev MS et al (Eds): No anesthesia


cataract surgery with karate chop. Phacoemulsification Laser
Cataract Surgery and Foldable IOLs (1st ed), New Delhi: Jaypee
Brothers , 1998;19:144-54.
2. Gutierrez-Carmona FJ: Cirugia de la catarata sin anesthesia. Es
posible by aceptable? (video) 14 Congreso SECOIR Zaragoza,
Spain, 1999.
3. Gutierrez-Carmona FJ: No anaesthesia cataract surgeryis it
possible and acceptable? (video). XVIIth Congress of the
European Society of Cataract and Refractive Surgeons Vienna,
1999.
4. Gutierrez-Carmona FJ: No anaesthesia cataract surgeryis it
possible and acceptable? (video). Video Cataratta99 Milan, Italy,
1999.
5. Kim PS, Ferrante FM: Cryoanalgesiaa novel treatment for hip
adductor spasticity and obturator neuralgia. Anesthesiology
1998;89(2):534-36.
6. Pastor J, Morales P, Cases E et al: Evaluation of intercostal
cryoanalgesia versus conventional analgesia in postthoracotomy
pain. Respiration 1996;63(4):241-45.
7. Toczolowski J: Thirty years of cryo-ophthalmologywork
dedicated to the memory of Dr Tadeusz Krwawicz. Klin Oczna
1994;96(4-5):129-31.
8. Tovar EA, Roethe RA, Weissig MD et al: Muscle-sparing
minithoracotomy with intercostal nerve cryoanalgesiaan
improved method for major lung resections. Am Surg 1998;
64(11):1109-15.
9. Tovar EA, Roethe RA, Weissig MD et al: One-day admission
for lung lobectomyan incidental result of a clinical pathway.
Ann Thorac Surg 1998;65(3):803-06.

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Chapter 5: No Anesthesia Cataract Surgery 39

No Anesthesia Cataract Surgery


Tobias Neuhann

INTRODUCTION
INCISION
CAPSULORHEXIS
PHACOEMULSIFICATION
TECHNIQUES
INTRAOCULAR LENS
IMPLANTATION
NO ANESTHESIA CLEAR LENS
EXTRACTION
SPECIFIC PRECAUTIONS IN NO
ANESTHESIA CATARACT
SURGERY
DISCUSSION

INTRODUCTION
As we all know, the surface of the human eye is highly sensitive. A quick
approach, a dust particle, a gust of air to dry out the ocular surfacethe
eyelids will close immediately in a protective reflex. To operate an eye
without any anesthesia? The mere idea seems to be absurd. However,
disregarding all that we know, it is possible.
On June 13, 1998, Amar Agarwal successfully performed the first no
anesthesia cataract operation during the Phaco and Refractive Surgery
conference in Ahmedabad, India, in front of an audience of 250 persons,
applying the karate chop technique.1,2 On the occasion of the 1999 ASCRS
convention in Seattle, live surgery was performed in India by Sunita
Agarwal, Amar Agarwal and Mahipal S Sachdev and communicated via
satellite to the meeting in Seattle. All these operations were performed
under no anesthesia. The cataracts were removed through a sub 1 mm
incision by Sunita Agarwal and Amar Agarwal using a technique called
phakonit. Sunita Agarwal demonstrated laser phacoemulsification, while
Mahipal S. Sachdev performed high vacuum phacoemulsification.3
On the 1999 AIOS conference, I had the opportunity to personally attend
live no anesthesia cataract surgery by Amar Agarwal. He kindly offered
me to perform a live no anesthesia cataract operation, myself. It was a
fascinating experience, and even during the operation itself, it was hard
to believe that it was really possible.
Back in Munich, I successfully operated two patients under the age of
40 using this astounding new methodboth upon their own request.
Fourteen other cases followed. However, the specific preconditions of this
particular group of patients will be discussed later on in this chapter.
INCISION
Without any anesthesia, naturally the incision is much more critical than
in routine cataract surgery under topical (retrobulbar, parabulbar or surface
anesthesia) or even general anesthesia.4 The entire procedure is only
possible if neither the sclera nor the conjunctiva are touched. In addition,
no one-toothed forceps is used to stabilize the eye. Instead, a straight rod
is inserted into the eye to guarantee a stable position during the operation.
The first step is essential. A side port is created with a diamond and
viscoelastic is injected. This incision is then used to insert a straight rod to
stabilize the eye. This is followed by a clear corneal incision.1,2
CAPSULORHEXIS
The capsule is opened using capsulorhexis, like in any routine cataract
surgery. The capsulorhexis can be performed alternatively using the needle
or the forceps technique.

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Section I: Cataract

Fig. 5.1: The ideal capsulorhexis

Fig. 5.2: Stellate burst

The needle technique first requires an initial puncture


of the anterior capsule within the central area to be
removed, which is then extended in a curve-shaped
manner to the targeted eccentric circle to be described.
The circular tear is started by either pushing or pulling
the central anterior capsule in either direction, while the
flap to be created is gently lifted. The next step is to turn
over the flap and apply the vectorial forces in tearing
with the needle in such a way that a more or less concentrical opening originates. Once the full circle is almost
completed the end will automatically join the beginning
of the curve outside in (Fig. 5.1). It is also possible to
place the first puncture directly within the planned
curvature and start the rhexis with a curved enlargement
of this tiny hole. With this approach, the tear is brought
around on both sides, until finally the ends join together.5
Advantages of the needle technique are that it is
economical, since it can be performed with application
of BSS as well as viscoelastics and the cost of the needles
is neglectable. The following factors are essential for the
success of the needle capsulorhexis: I highly recommend
the use of a 23 gauge needle, because the lumen of this
type of needle is just sufficient to produce a pressure
exchange between anterior chamber and BSS irrigating
bottle and the metal of such a cannula supplies just
enough rigidity to provide the necessary resistance for
difficult manipulations. A higher, that is positive pressure

in the anterior chamber compared to the intracapsular


pressure is mandatory. This becomes especially
noticeable with intumescent lenses, where the lens
protein is hydrated resulting in a volume increase inside
the capsular bag, so that also the endocapsular pressure
is considerably increased. Only if the anterior chamber
pressure is greater than or equal to that inside the
capsular bag can a successful capsulorhexis be
performed. The pressure in the anterior chamber can be
adjusted by varying the height of the infusion bottle. In
addition, the needle tip should be as sharp as possible,
since a blunt needle may create stellate burst (Fig. 5.2).5
The forceps technique is easier. For this reason it is
also the most frequently applied capsulorhexis technique,
which, however, can only be performed after viscoelastic
instillation. The principle of the forceps capsulorhexis
exactly corresponds to the principle of the needle
technique. In addition to the known Utrata forceps there
are mini forceps which are similar in construction to the
forceps developed for the posterior segment of the eye.
The advantage of these newly designed forceps is that
they can be inserted into the anterior chamber via a
paracentesis, so that the incision is not exposed to
needless strain.5
To point out the difference between the needle and
the forceps technique, the following example might be
appropriate: To turn over a page of a book you can take
the sheet between two fingers and turn it from one side

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Chapter 5: No Anesthesia Cataract Surgery 41


to the other (this is what you do with the forceps), or
you take a moistened finger, press the page a bit down
and then turn it over (that is what you do with the needle;
the counterhold is the cortex). With this in mind the
consequences appear quite clear cut. I will always use a
needle technique, the initial puncture peripheral or
central, for the great majority of my cases. The forceps I
will use in situations where the needle so to say lacks
the other branch. This is mainly the case when liquefied
cortex is apparent or secondary enlargement of the
capsulorhexis diameter is necessary.5
PHACOEMULSIFICATION TECHNIQUES
A variety of phacoemulsification techniques has been
developed with the aim to disintegrate the nucleus in
the safest and most efficient way. When Howard Gimbel
introduced his divide and conquer technique, it was
adopted enthusiastically by ophthalmologists throughout the world.6 For many years after, divide and conquer
remained the outstanding technique for all nuclei hard
enough not to be simply aspirated, until Nagahara
presented his new technique, phaco chop, the big brother
of divide and conquer. Other than in divide and conquer,
the nucleus is no longer divided with the phaco tip, but
with a second instrument, the chopper, so that hardly
any manipulations with the tip itself were necessary any
longer, thus reducing the risk to damage the sensitive
intraocular structures with the tip to a minimum.7
The phaco chop technique has remained one of the
most efficient methods in phacoemulsification until
today. The advantages are obvious. The lens can be
divided up mechanically into 4, 6 and 8 or more pieces.
In this process, the originating forces counteract, since
the force exerted by the chopper is directed against the
phaco tip. The result is that all force vectors go centrally,
so that there is no hazard for the lens capsule or the
corneal endothelium.
The phaco chop technique is especially suitable for
mature cataracts or cataracta nigra, where mostly weak
zonulas are found. A beneficial side effect for the surgeon
is the ease of work, because the nucleus can always be
rotated into the most favorable position. However, an
important aspect of phaco chop is that it is only a
technique for experienced surgeons, whereas beginners
should start with divide and conquer to develop a feeling
for the consistency of the nucleus to stay on the safe side.
For the first chopping attempt, a medium nuclear
sclerosis should be selected.
To understand the mechanism of phaco chop, you
have to consider the anatomic structure of the nucleus,

where the crystalline lens fiber runs from one side of the
equator towards the opposite side through the center of
the nucleus. As a logical consequence, the natural
cracking direction follows the lens fiber. As is usual in
modern cataract surgery, the capsule is opened with the
CCC and hydrodissection is carried out. Then the
epinucleus is aspirated inside the CCC with weak phaco
energy. For your first chop, you have to catch the lens
with your phaco tip at the 12 hours position, advance
the phaco tip until you have firm hold of the nucleus
and then insert the chopper into the space between the
equator and the capsule at the 6 hours position. As the
chopper is gradually brought closer to the tip, the nucleus
will crack into two halves. Then the nucleus is rotated
90 and the inferior heminucleus is cracked into
quadrants applying the same principle. If the nucleus is
relatively soft, the quarters can be aspirated and
emulsified with the phaco tip. In this process, the tip
opening should remain in the center of the lens capsule
not to increase the hazard of damaging either the
posterior capsule or the corneal endothelium unnecessarily. When aspiration and emulsification of the inferior
heminucleus are completed, the superior heminucleus
is rotated 180 and disintegrated accordingly. In the case
of harder nuclei, a subdivision of the nucleus into 8 or
more pieces may be required to exclude that residual
fragments escape into the anterior chamber and damage
the corneal endothelium with their sharp edges.
Experience in phacoemulsification shows that it is
beneficial to reduce the overall phaco time and power to
the necessary minimum. An additional advantage of the
phaco chop technique is that here the nuclear matter is
first aspirated and then emulsified. In this way, the entire
phaco energie is used for emulsification of the nucleus,
the aspiration volume concentrates on the nucleus, and
less phaco energie and time are required, thus reducing
strain for the incision as well as for the corneal endothelium.
The initial phaco chop technique has been modified
several times by different ophthalmologists including
Nagahara, its inventor. He uses his karate chop technique,7,8 which was also applied in the first live no
anesthesia cataract surgery by Amar Agarwal,1,2 for
cases with poor mydriasis to be able to perform the whole
phacoemulsification procedure within the range of the
pupil or the CCC. Other than in the initial phaco chop
technique, karate phaco chop goes from the anterior pole
to the posterior pole of the crystalline lens. For hard
nuclei with a thin epinucleus and the typical dual
structure of soft periphery and hard core Nagahara
suggests the crater phaco chop technique. To be able to

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42

Section I: Cataract

Fig. 5.3: Ring-haptic fixation; computer animation

Fig. 5.4: Ring-haptic fixation; clinical case

grab hold of the hard core of the nucleus with the phaco
tip, first a crater is excavated providing enough space
for easy insertion of the tip.
My personal method of choice is the quick-chop
technique when performing no anesthesia cataract
surgery because of the above mentioned advantages,
such as stress- and pain-free intraocular manipulations.

Depending on the specific case, an IOL is then implanted


or in cases of extremely high myopia, the patient is left
aphakic. The operation follows the same procedure as
no anesthesia cataract surgery. For less experienced
surgeons, a parabulbar anesthesia is recommended
instead of a peribulbar block to avoid the hazard of globe
penetration with the needle.1,2

INTRAOCULAR LENS IMPLANTATION

SPECIFIC PRECAUTIONS IN NO
ANESTHESIA CATARACT SURGERY

Using no anesthesia cataract surgery, I recommend an


implantation of a soft, foldable silicone or acrylic IOL to
be able to make use of the advantages of small incision
surgery, especially under the aspect that a clear corneal
incision is inevitable, because the sclera as well as the
conjunctiva must not even be touched. For both intraocular lens families, acrylic as well as silicone, a large
variety of IOL models and types from the different
manufacturers is available in the market. In this way it
is easy to find a lens to meet the specific requirements of
the individual patient. As one of the newest developments, even a foldable toric IOL can be implanted using
a ring-haptic-fixation with a capsular tension ring (Figs
5.3 and 5.4).9 Foldable IOLs can be implanted with
forceps or with an injector, which is mostly the easier
alternative.
NO ANESTHESIA CLEAR LENS EXTRACTION
At the Agarwal eye hospitals in Chennai and Bangalore,
India, clear lens extractionalso without anesthesiais
applied for the surgical treatment of high refractive errors
as an alternative to PRK or LASIK, especially in
hyperopic or high myopic patients (more than 15 D).

Experience shows that it is beneficial to cover the cornea


with HPMC 2.4 percent to reduce the surface sensitivity
of the eye. In addition, it is essential to maintain the
moisture of the cornea throughout the operation.
It is important, not to inform the patient prior to the
operation to exclude the danger of increased sensitivity
caused by the patients fear of pain. In addition, it is very
important to exclude any sharp or pointed instrument,
such as Colibri forceps. However, the use of diamond
knives is appropriate.
Furthermore, utmost care with the eyelid is required,
because it is experienced as highly disturbing by the
patients.
During phacoemulsification, it is very important to
only apply low amounts of ultrasound power to avoid
the origination of heat, which would be painful for the
patient. In addition, the anterior chamber should be wellmaintained throughout the procedure.1
DISCUSSION
No anesthesia cataract surgery is a surprising new
development in our highly refined techniques in
ophthalmic surgery that have been achieved todate.

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Chapter 5: No Anesthesia Cataract Surgery 43


Without any doubt, the mere existence of this new option
is very exciting and also might be very helpful in cases
with specific indications. However, in my opinion, the
different preconditions of the patient goods in different
areas of the world need to be briefly discussed. As we all
know, a series of amazing phenomena exists in India.
Which other country on earth has been able to produce
individuals who are able to stick knives and sabers
through their bodies and faces and pull them out again
without a drop of blood dripping down and without any
wound remaining? On the other hand, documentations
of almost unbelievable practices also exist from other
areas in the world, like in parts of Africa, where trepanation is performed without any anesthesia, too, and the
patients maintain not to feel too much pain when their
skulls are opened without any anesthetic relief. On this
basis, the no anesthesia approach should be further
investigated in terms of its introduction in suitable
countries, also taking into account the poverty in large
parts of the world, where no anesthesia cataract surgery
might be a step into the right direction to improve health
care for the population by lovering the costs of treatment.
Generally, in the Western World this method is only
suitable for especially old patients, where the surface
sensitivity of the eye is already considerably reduced or
for highly motivated patients. In my own practice, I
operated a total of six patients without anesthesia todate. All of these patients had a particular mental attitude
in common, which enabled them to undergo this kind of
procedure, and which considerably differs from that the
majority of the population in any of our industrialized
countries. All of these patients asked me to perform no
anesthesia cataract surgery, while the larger majority
especially of the younger patients rather tend to consider
the advantages of general or topical anesthesia, instead,

and would not even dream of having an operation


performed without any anesthesia. In this way, the
special motivation of my 16 cases formed the only
possible basis for this new approach.
No anesthesia cataract surgery is a highly fascinating
new alternative. It is certainly not designed for routine
practice. However, it remains an excellent method for
patients with specific indications, where our common
forms of anesthesia are not possible, for example in
hemophilics.
REFERENCES
1. Agarwal A, Agarwal S, Agarwal A. No anesthesia cataract/clear
lens extraction. Refractive Surgery. Jaypee Brothers Medical
Publishers (P) Ltd: New Delhi, 2000;487-98.
2. Agarwal A, Agarwal S, Agarwal A. No anesthesia cataract
surgery. Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs. Jaypee Brothers Medical Publishers (P) Ltd: New
Delhi, 1998;139-43.
3. Azim Siraj A. Dr Agarwals homepage. Issues Conference and
Seminars: 1999;2.
4. Lang GK. Operative Therapie. Augenheilkunde Georg Thieme
Stuttgart: Verlag, 1998;190-93.
5. Neuhann T. Capsulorhexis. Phacoemulsification, Laser Cataract
Surgery and Foldable IOLs. Jaypee Brothers Medical Publishers
(P) Ltd: New Delhi, 1998;81-88.
6. Gimbel HV, Anderson PE. Divide and conquer nucleofractis
techniques. Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs. Jaypee Brothers Medical Publishers (P) Ltd: New
Delhi, 1998;97-109.
7. Nagahara KB. Phaco chopdevelopment and recent advances.
Atlas of Cataract Surgery. Martin Dunitz Ltd: London, 1999;
98-109.
8. Agarwal A, Agarwal S, Agarwal A. Karate chop. Phacoemulsification, Laser Cataract Surgery and Foldable IOLs. Jaypee
Brothers Medical Publishers (P) Ltd: New Delhi, 1998;144-54.
9. Neuhann T: New Foldable IOLs. Atlas of Cataract Surgery.
Martin Dunitz Ltd: London, 1999;169-80.

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44

Section I: Cataract

Phakonit
Amar Agarwal, Athiya Agarwal, Sunita Agarwal

HISTORY
PRINCIPLE
TERMINOLOGY
TECHNIQUE OF PHAKONIT
FOR CATARACTS
INCISION
RHEXIS
HYDRODISSECTION
PHAKONIT
ANTI-CHAMBER COLLAPSER
SURGE
TECHNIQUE
DISCUSSION
PHAKONIT THINOPTX
ROLLABLE IOL
LENS INSERTION TECHNIQUE
ROLLECTOR
TOPOGRAPHY
LASER PHAKONIT
THREE PORT PHAKONIT

HISTORY
On August 15th 1998 the author (Amar Agarwal) performed the first sub
1 mm cataract surgery by a technique called PHAKONIT.1,2 In this the
cataract was removed through a 0.9-mm incision. Since Charles Kelman
started phacoemulsification, various new modalities have developed
which have made this technique more refined. One problem still persists
which is the size of the incision. The normal size of the incision is 3.2 mm.
With time and more advances in phaco machines and phaco tips this
reduced to 2.8 mm and then to 2.6 mm. Today certain phaco machines like
the Alcons Legacy and the Staar phaco machine have produced a 1.9-mm
phaco probe. In other words cataract surgery has become a sub 2-mm
incision. The authors (Sunita Agarwal) worked on Laser cataract surgery
and had achieved cataract removal through an incision below 2-mm (1.8mm) using laser phaco energy coupled with high aspiration. But the
problem of the incision still remained and the 1-mm barrier could not be
broken. The authors have started a new technique called PHAKONIT in
which the size of the incision is below 1 mm. In other words the size of the
incision through which the cataract is removed is 0.9 mm. The authors
(Amar Agarwal) performed this technique for the first time in the world
on August 15th 1998. It was performed without any anesthesia. No
anesthetic drops were instilled in the eye nor was any anesthetic given
intracamerally. The first live surgery in the world of Phakonit was
performed on August 22nd 1998 at Pune, India by the authors (Amar
Agarwal) at the Phako and Refractive Surgery Conference. This was done
in front of 350 ophthalmologists. This technique will revolutionize cataract
surgery because now the foldable Intraocular lenses which pass into the
eye through a size of below 2 mm (1.9 mm) will have to pass through a
below 1 mm incision.1,2 They will have to pass through a 0.9-mm incision.
The problem with this technique was to find an IOL, which would
pass through such a small incision. Then on October 2nd 2001 the authors
(Amar Agarwal) did the first case of a Phakonit Rollable IOL. This was
done in their Chennai (India) hospital. The lens used was a special lens
from Thinoptx. This was the first Rollable IOL, which was implanted after
a Phakonit procedure, and as it was a rolled IOL the authors called it the
Phakonit Thinoptx Rollable IOL. This is a special lens with a 5 mm optic.
PRINCIPLE
The problem in phacoemulsification is that we are not able to go below an
incision of 1.9 mm. The reason is because of the infusion sleeve. The infusion
sleeve takes up a lot of space. The titanium tip of the phaco handpiece has

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Chapter 6: Phakonit 45
a diameter of 0.9 mm. This is surrounded by the infusion
sleeve which allows fluid to pass into the eye. It also cools
the handpiece tip so that a corneal burn does not occur.3
The authors separated the phaco tip from the infusion
sleeve. In other words, the infusion sleeve was taken out.
The tip was passed inside the eye and as there was no
infusion sleeve present the size of the incision was
0.9 mm. In the left hand an irrigating chopper was held
which had fluid passing inside the eye. The left hand
was in the same position where the chopper is normally
held, i.e. the side port incision. The assistant injects fluid
(BSS) continuously at the site of the incision to cool the
phaco tip. Thus the cataract is removed through a 0.9
mm opening.
TERMINOLOGY
The name PHAKONIT has been given because it shows
phaco (PHAKO) being done with a needle (N) opening
via an incision (I) and with the phako tip (T).

Fig. 6.1: A 26 gauge needle with viscoelastic making an entry


in the area where the side port is. This is for entry of the
irrigating chopper

TECHNIQUE OF PHAKONIT FOR CATARACTS


Anesthesia
All the cases done by the authors have been done without
any anesthesia. But the technique of Phakonit can be
done under any type of anesthesia also. In the cases done
by the authors no anesthetic drops were instilled in the
eye nor was any intracameral anesthetic injected inside
the eye. The authors have analyzed that there is no
difference between topical anesthesia cataract surgery
and No anesthesia cataract surgery. They have stopped
using anesthetic drops totally in all their hospitals in
India (Bangalore and Chennai) and Dubai (UAE). But
Phakonit can be done with any type of anesthesia.
INCISION
In the first step a needle with viscoelastic is taken and
pierced in the eye in the area where the side port has to
be made. Then a special knife to create an incision of 0.9
mm is made (Fig. 6.1). The viscoelastic is then injected
inside the eye. This will distend the eye so that the clear
corneal incision can be made. Now a temporal clear
corneal incision is made. The problem here is that the
diamond knives are all 2.6 mm or larger. Since our aim is
to make only a 0.9-mm opening these diamond knives
are not sufficient. So a special blade is used (Fig. 6.2).
This creates an opening of 0.9 mm. When this incision is
made it should be done in such a fashion that a clear

Fig. 6.2: Clear corneal incision made with the keratome (0.9mm). Note the left hand has a straight rod to stabilize the eye
as the case is done without any anesthesia. These instruments
are made by Katena (USA)

corneal valve is made. The authors have devised a


keratome of 0.9 mm which they now use. This keratome
creates a good valve. This keratome and other instruments for Phakonit are made by Katena (USA) and
Gueder (Europe).
RHEXIS
The rhexis is then performed. This is done with a needle
(Fig. 6.3). In the left hand a straight rod is held to stabilize
the eye. The advantage of this is that the movements of
the eye can get controlled as one is working without any
anesthesia.

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Section I: Cataract

Fig. 6.3: Rhexis started with a needle

HYDRODISSECTION
Hydrodissection is performed and the fluid wave passing
under the nucleus checked. Check for rotation of the
nucleus.
PHAKONIT
After enlarging the side port a 20 gauge irrigating
chopper connected to the infusion line of the phaco
machine is introduced with foot pedal on position 1. The
phaco probe is connected to the aspiration line and the
phaco tip without an infusion sleeve is introduced
through 0.9-mm incision (Fig. 6.4). Using the phaco tip
with moderate ultrasound power, the center of the
nucleus is directly embedded starting from the superior
edge of rhexis with the phaco probe directed obliquely
downwards towards the vitreous. The settings at this

Fig. 6.5: Phakonit started. Note the phako needle in the right
hand and an irrigating chopper in the left hand.
Phakonit being performed. Note the crack created by karate
chopping. The assistant continuously irrigates the phaco probe
area from outside to prevent corneal burns

stage is 50 percent phaco power, flow rate 24 ml/min


and 110 mm Hg vacuum. When nearly half of the center
of nucleus is embedded, the foot pedal is moved to
position 2 as it helps to hold the nucleus due to vacuum
rise. To avoid undue pressure on the posterior capsule
the nucleus is lifted a bit and with the irrigating chopper
in the left hand the nucleus chopped. This is done with a
straight downward motion from the inner edge of the
rhexis to the center of the nucleus and then to the left in
the form of an inverted L shape (Fig. 6.5). Once the crack
is created, the nucleus is split till the center. The nucleus
is then rotated 180 and cracked again so that the nucleus
is completely split into two halves.
The nucleus is then rotated 90 and embedding done
in one half of the nucleus with the probe directed horizontally (Fig. 6.6). With the previously described technique, 3 pie-shaped quadrants are created in one half of
the nucleus. Similarly 3 pie-shaped fragments are created
in the other half of the nucleus. With a short burst of
energy at pulse mode, each pie-shaped fragment is lifted
and brought at the level of iris where it is further
emulsified and aspirated sequentially in pulse mode.
Thus the whole nucleus is removed (Fig. 6.7). Note in
Figure 6.7 no corneal burns are present. Cortical washup is done with the bimanual irrigation aspiration
technique (Figs 6.8 and 6.9).
ANTI-CHAMBER COLLAPSER

Fig. 6.4: Phakonit irrigating chopper and phako


probe without the sleeve inside the eye

One of the real bugbears in Phakonit when we started it


was about the problem of destabilization of the anterior
chamber during surgery. This was solved to a certain

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Chapter 6: Phakonit 47

Fig. 6.6: Phakonit continued. The nuclear pieces are


chopped into smaller pie-shaped fragments

Fig. 6.9: Bimanual irrigation aspiration completed

Fig. 6.7: Phakonit completed. Note the nucleus has been


removed and there are no corneal burns
Fig. 6.10: Anti-chamber collapser

Fig. 6.8: Bimanual irrigation aspiration started

extent by using an 18 gauge irrigating chopper. A


development made by us (SA) was to use an anti-chamber collapser 4,5 which injects air into the infusion bottle
(Fig. 6.10). This pushes in more fluid into the eye through
the irrigating chopper and also prevents surge. Thus we
were not only able to use a 20 gauge irrigating chopper
but also solve the problem of destabilization of the
anterior chamber during surgery. This increases the
steady-state pressure of the eye making the anterior
chamber deep and well maintained during the entire
procedure. It even makes phacoemulsification a relatively safe procedure by reducing surge even at high
vacuum levels. Thus this can be used not onlyin Phakonit
but also in Phacoemulsification.

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Section I: Cataract

SURGE
When an occluded fragment is held by high vacuum and
then abruptly aspirated, fluid rushes into the phaco tip
to equilibrate the built up vacuum in the aspiration line,
causing surge. This leads to shallowing or collapse of the
anterior chamber. Different machines employ a variety
of methods to combat surge. These include usage of
noncomplaint tubing,4 small bore aspiration line tubing,4
microflow tips,4 aspiration bypass systems,4 dual linear
foot pedal control4 and incorporation of sophisticated
microprocessors4 to sense the anterior chamber pressure fluctuations.
The surgeon dependent variables to counteract surge
include good wound construction with minimal leakage5 and selection of appropriate machine parameters
depending on the stage of the surgery.5 An anterior
chamber maintainer has also been described in literature
to prevent surge, but an extra side port makes it an
inconvenient procedure. Another method to solve surge
is to use more of phacoaspiration and chop the nucleus
into smaller pieces.
TECHNIQUE
Two balanced salt solution (BSS) bottles are used instead
of one. A Y shaped trans-urethral resection (TUR) set
is used to connect the two BSS bottles to the irrigation
tubing of the handpiece (Fig. 6.10). The TUR set has three
pinch valves, one on each limb to prevent the back flow.
The internal diameter of the TUR set is 4.5 millimeters
compared to 2.5 millimeters of the intravenous (IV)
irrigation set routinely used. This increases the amount
of fluid passing from the infusion bottle to the phacoemulsification handpiece. The bottles are kept at a height
of about 65 centimeters above the operating field. The
automated air pump, which is similar to the pump used
in fish tanks to supply oxygen to the fish, is utilized to
forcefully pump air into the irrigation bottle at a
continuous rate. The air pump is connected to one of the
BSS bottles through an IV set. A micropore air filter is
used between the air pump and the infusion bottle so
that the air pumped into the bottle is sterile. Sterile air is
pumped into the infusion bottle, pressurizing it to force
fluid into the anterior chamber, thereby neutralizing
surge and maintaining a deep anterior chamber through
out the procedure.
Free flow irrigation volume through the handpiece
was measured using IV set, TUR set and TUR set with
the air pump. The fluid volume in milliliters per minute
with the IV and TUR set were 48 and 60 respectively. It
increased to 160 milliliters per minute with the air pump

and TUR set. With this increased fluid volume we were


able to maintain a deep anterior chamber and no surge
was observed in our routine Phakonit or phacoemulsification cases.
DISCUSSION
Surge is defined as the volume of the fluid forced out of
the eye into the aspiration line at the instant of occlusion
break. When the phacoemulsification handpiece tip is
occluded, flow is interrupted and vacuum builds up to
its preset values. Additionally the aspiration tubing may
collapse in the presence of high vacuum levels. Emulsification of the occluding fragment clears the block and
the fluid rushes into the aspiration line to neutralize the
pressure difference created between the positive pressure
in the anterior chamber and the negative pressure in the
aspiration tubing. In addition, if the aspiration line tubing
is not reinforced to prevent collapse (tubing compliance),
the tubing, constricted during occlusion, then expands
on occlusion break. These factors cause a rush of fluid
from the anterior chamber into the phaco probe. The fluid
in the anterior chamber is not replaced rapidly enough
to prevent shallowing of the anterior chamber.
The maintenance of intraocular pressure (steadystate
IOP) during the entire procedure depends on the
equilibrium between the fluid inflow and outflow. In
most phacoemulsification machines, fluid inflow is
provided by gravitational flow of the fluid from the
balanced salt solution (BSS) bottle through the tubing to
the anterior chamber. This is determined by the bottle
height relative to the patients eye, the diameter of the
tubing and most importantly by the outflow of fluid from
the eye through the aspiration tube and leakage from
the wounds.
The inflow volume can be increased by either
increasing the bottle height or by enlarging the diameter
of the inflow tube. The intraocular pressure increases by
10 mm Hg for every 15 centimeters increase in bottle
height above the eye.5 High steady-state IOPs increase
phaco safety by raising the mean IOP level up and away
from zero, i.e. by delaying surge related anterior chamber
collapse. Air pump increases the amount of fluid inflow
thus making the steady-state IOP high. This deepens the
anterior chamber, increasing the surgical space available
for maneuvering and thus prevents complications like
posterior capsular tears and corneal endothelial damage.
The phenomenon of surge is neutralized by rapid inflow
of fluid at the time of occlusion break. The recovery to
steady-state IOP is so prompt that no surge occurs and
this enables the surgeon to remain in foot position 3
through the occlusion break. High vacuum phacoemulsi-

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Chapter 6: Phakonit 49
fication can be safely performed in hard brown cataracts
using an air pump. Phacoemulsification under topical
or no anesthesia6 can be safely done neutralizing the
positive vitreous pressure occurring due to squeezing of
the eyelids.
As we tend to use two bottles instead of one, the cost
is a bit more expensive and the TUR set is slightly more
expensive than a normal IV set. The air pump is a new
device, which helps to prevent surge. This helps to
prevent posterior capsular rupture, helps deepen the
anterior chamber and one can work comfortably even in
hard cataracts. The air pump pumps air into the infusion
bottle thus tending to push more of fluid into the eye
and with greater force. Now, we routinely use the air
pump in all our cases.

Fig. 6.13: The rollable IOL in the capsular bag

Fig. 6.11: The phakonit thinoptx rollable IOL when


removed from the bottle
Fig. 6.14: Viscoelastic removed using bimanual
irrigation aspiration probes

PHAKONIT THINOPTX ROLLABLE IOL

Fig. 6.12: The rollable IOL inserted through the incision

Thinoptx the company that manufactures these lenses


has patented technology that allows the manufacture of
lenses with plus or minus 30 dioptres of correction on
the thickness of 100 microns. The Thinoptx technology
developed by Wayne Callahan, Scott Callahan and Joe
Callahan is not limited to material choice, but is achieved
instead of an evolutionary optic and unprecedented
nano-scale manufacturing process. The lens is made from
off-the-shelf hydrophilic material, which is similar to
several IOL materials already on the market. The key to
the Thinoptx lens is the optic design and nano-precision
manufacturing. The basic advantage of this lens is that

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Section I: Cataract

Fig. 6.15: Phako foldable and phakonit thinoptx IOL. The figure on the left shows a case of phako with a foldable
IOL and the figure on the right shows phakonit with a thinoptx rollable IOL

Fig. 6.16: Phako foldable IOL orbscan results. The figure on the left is the preoperative orbscan. The
figure on the right is the one day postoperative orbscan. Note the difference between the two orbscan
pictures. This is the site where the clear corneal temporal incision was made

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Chapter 6: Phakonit 51

Fig. 6.17: Phakonit thinoptx rollable IOL orbscan results. The figure on the left is the preoperative
orbscan. The figure on the right is the one day postoperative orbscan. Note the similarity between
the two orbscan pictures. This shows the minimal astigmatism created even on one day postoperative

they are Ultra-Thin lenses. Thinoptx has made a special


lens for Phakonit which has a 5 mm optic.
LENS INSERTION TECHNIQUE
The lens is taken out from the bottle. The lens is then
held with a forceps (Fig. 6.11). The lens is then placed in
a bowl of BSS solution that is approximately body
temperature. This makes the lens pliable. Once the lens
is pliable it is taken with the gloved hand holding it
between the index finger and the thumb. The lens is then
rolled in a rubbing motion. It is preferable to do this in
the bowl of BSS so that the lens remains rolled well.
The lens is then inserted through the incision carefully
(Fig. 6.12). One can then move the lens into the capsular
bag (Fig. 6.13). The natural warmth of the eye causes the
lens to open gradually. Viscoelastic is then removed with
the Bimanual irrigation aspiration probes (Fig. 6.14). The
tips of the footplates are extremely thin which allow the
lens to be positioned with the footplates rolled to fit the
eye.

ROLLECTOR
We have now devised a special injector to implant the
Rollable IOL after Phakonit and called it the Agarwal
Rollector. This is being made by Katena (USA). The
advantage of this rollector is that it not only rolls the lens
but also inserts the lens inside the eye.
TOPOGRAPHY
We also perfomed topography with the orbscan to
compare cases of phakonit and phaco and we found that
the astigmatism in phakonit cases is much less compared
to phaco (Figs 6.15 to 6.18). Stabilization of refraction is
also faster with Phakonit compared to phaco surgery.
LASER PHAKONIT
Laser Phakonit uses laser energy (coupled with
ultrasound energy in hard nuclei) to remove the nucleus.
This technique was started first time in the world by the

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Section I: Cataract

Fig. 6.18: Phakonit thinoptx rollable IOL orbscan results. The figure on the left is the pre-operative
orbscan. The figure on the right is the one day post-operative orbscan. Note the similarity between
the two orbscan pictures. This shows no astigmatism created even on one day post-op. Do note the
astigmatism pre-op is 0.8 d and post-op on day one is 0.7 d

author (Sunita Agarwal). The laser machine used is the


Paradigm Laser Photon. In these cases, two ports are
used. One port has fluid (BSS) flowing through an
irrigating chopper of 20 gauge and in the other hand is
the phaco probe without a sleeve. In the center of the
phaco probe is passed the laser probe. The diameter of
the phaco probe is 900 microns. The laser probe reduces
the orifice opening to 550 microns. Thus the nucleus can
be removed through a very small 0.9 mm opening.

There are pros and cons in every technique. The


problem in three port phakectomy is that it is too cumbersome. Surgeons prefer to have two ports only. Some
surgeons prefer three ports as an anterior chamber
maintainer is present in the eye and thus the anterior
chamber is always formed. At present it is easier to
perform Phakonit using a 20 gauge irrigating chopper
with the anti-chamber collapser.
SUMMARY

THREE PORT PHAKONIT


Another technique by which one can perform Phakonit
is to use an anterior chamber maintainer. The authors
started this technique. They call it THREE-PORT
PHAKONIT. Just as a three port vitrectomy, here also
we have three ports, hence the name- Three-Port
Phakonit.

There are various problems, which are encountered, in


any new technique and so also with Phakonit. With time
these will have to be solved. The important point is that
today we have broken the 1 mm barrier for cataract
removals. This can be done easily by separating the phaco
needle from the infusion sleeve. As the saying goesWe have miles to go before we can sleep.

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Chapter 6: Phakonit 53
REFERENCES
1. Agarwal S, Agarwal A, Sachdev MS, Mehta KR, Fine IH,
Agarwal A: Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs; (2nd edn) New Delhi: Jaypee Brothers, 2000.
2. Boyd BF, Agarwal S, Agarwal A. Lasik and Beyond Lasik;
Highlights of Ophthalmology; 2000; Panama.
3. Laura J Ronge. Clinical Update; Five Ways to avoid Phaco Burns;
1999.

4. Fishkind WJ. The Phaco Machine: How and why it acts and
reacts? In: Agarwals Four volume textbook of Ophthalmology.
New Delhi: Jaypee Brothers, 2000.
5. Seibel SB. The fluidics and physics of phaco. In: Agarwals et
al. Phacoemulsification, Laser Cataract Surgery and Foldable
IOLs (2nd edn). New Delhi: Jaypee Brothers, 2000; 45-54.
6. Agarwal et al. No anesthesia cataract surgery with karate chop;
In: Agarwals Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs (2nd edn) New Delhi: Jaypee Brothers, 2000; 21726.

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Section I: Cataract

Phakonit with Acritec IOL


Sunita Agarwal, Athiya Agarwal, Amar Agarwal

HISTORY
PRINCIPLE
TERMINOLOGY
TECHNIQUE OF PHAKONIT FOR
CATARACTS
INCISION

HISTORY
On August 15th 1998 the authors (Amar Agarwal) performed the first sub
1 mm cataract surgery by a technique called PHAKONIT.1,2 The authors
(Sunita Agarwal) also worked on Laser cataract surgery and achieved
cataract removal through the laser phaco machine of Paradigm. Today
companies have started manufacturing IOLs that can pass through ultrasmall incisions of 1.5 mm or less. One such IOL is the Acri.Lye IOL made
by the Acritec company (Berlin, Germany).

RHEXIS
PHAKONIT
ACRITEC IOL
LENS LOADING TECHNIQUE
LENS INSERTION TECHNIQUE
LASER PHAKONIT

PRINCIPLE
The problem in phacoemulsification is that we are not able to go below an
incision of 1.9 mm. The reason is because of the infusion sleeve. The infusion
sleeve takes up a lot of space. The titanium tip of the phaco handpiece has
a diameter of 0.9 mm. This is surrounded by the infusion sleeve which
allows fluid to pass into the eye. It also cools the handpiece tip so that a
corneal burn does not occur. With whitestar technology of Allergan or the
cold phaco from Staar corneal burns do not occur.
The authors separated the phaco tip from the infusion sleeve. In other
words, the infusion sleeve was taken out. The tip was passed inside the
eye and as there was no infusion sleeve present the size of the incision was
0.9 mm. In the left hand an irrigating chopper was held which had fluid
passing inside the eye. The left hand was in the same position where the
chopper is normally held, i.e. the side port incision. The assistant injects
fluid (BSS) continuously at the site of the incision to cool the phaco tip.
Thus the cataract is removed through a 0.9 mm opening.
TERMINOLOGY
The name PHAKONIT has been given because it shows phaco (PHAKO)
being done with a needle (N) opening via an incision (I) and with the phako
tip (T).
TECHNIQUE OF PHAKONIT FOR CATARACTS
Anesthesia
All the cases done by the authors have been done without any anesthesia.3
But the technique of Phakonit can be done under any type of anesthesia
also. In the cases done by the authors no anesthetic drops were instilled in

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Chapter 7: Phakonit with Acritec IOL 55

Fig. 7.1: A 26 gauge needle with viscoelastic making an entry


in the area where the side port is. This is for entry of the
irrigating chopper

Fig. 7.2: Clear corneal incision made with the keratome (0.9mm). Note the left hand has a rod to stabilize the eye as the
case is done without any anesthesia. These instruments are
made by Katena (USA)

the eye nor was any intracameral anesthetic injected


inside the eye. The authors have analyzed that there is
no difference between topical anesthesia cataract surgery
and No anesthesia cataract surgery. They have stopped
using anesthetic drops totally in all their hospitals in India
(Bangalore and Chennai) and Dubai (UAE). But Phakonit
can be done with any type of anesthesia.
INCISION
In the first step a needle with viscoelastic is taken and
pierced in the eye in the area where the side port has to
be made (Fig. 7.1). A special keratome (Katena, USA) is
then used to create an incision of 0.9 mm (Fig. 7.2). The
viscoelastic is then injected inside the eye.
RHEXIS
The rhexis is then performed. This is done with a needle
(Fig. 7.3). In the left hand a straight rod is held to stabilize
the eye. The advantage of this is that the movements of
the eye can get controlled as one is working without any
anesthesia. Hydrodissection is performed and the fluid
wave passing under the nucleus checked.

Fig. 7.3: Rhexis started with a needle

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Section I: Cataract

Fig. 7.4: Phakonit irrigating chopper and phako probe


without the sleeve inside the eye

PHAKONIT
After enlarging the side port a 20 gauge irrigating
chopper connected to the infusion line of the phaco
machine is introduced with foot pedal on position 1. The
phaco probe is connected to the aspiration line and the
phaco tip without an infusion sleeve is introduced
through 0.9-mm incision (Fig. 7.4). Using the phaco tip
with moderate ultrasound power, chopping of the
nucleus is done (Fig. 7.5). The whole nucleus is finally
removed (Fig. 7.6). Note in Figure 7.6 no corneal burns
are present. Cortical wash-up is done with the bimanual
irrigation aspiration technique (Figs 7.7 and 7.8).
ACRITEC IOL
The Acry.Lyc IOL is manufactured by the Acri.Tec
company in Berlin, Germany. This lens is a sterile foldable
intraocular lens made of hydrophobic acrylate. The
intraocular lens consists of highly purified biocompatible
hydrophobic acrylate with chemically bonded UVabsorber. It is a single piece foldable IOL like a platehaptic IOL. The lens is sterilized by autoclaving. The lens

Fig. 7.5: Phakonit started. Note the phako needle in the right
hand and an irrigating chopper in the left hand.
Phakonit being performed. Note the crack created by karate
chopping. The assistant continuously irrigates the phaco probe
area from outside to prevent corneal burns

comes in a sterile vial, filled with water and wrapped in


a sterile pouch.
LENS LOADING TECHNIQUE
To remove the IOL one should open the Medipeel pouch
at the defined spot. The lens vial or bottle (Fig. 7.9) is
then taken out and placed on the sterile tray. The lens is
like a plate haptic IOL (Fig. 7.10). The next step is to
prepare the injector (Fig. 7.11). First of all the injector tip
is fitted with a sponge tip (Figs 7.12 and 7.13) which
comes with the cartridge. This will prevent the injector
tip from damaging the lens while inserting it inside the
eye. The lens is then taken out from the bottle /vial. The
lens is then held with a forceps. The lens is then placed
in the cartridge (Fig. 7.14). Viscoelastic is injected in the
cartridge and once the flanges of the IOL are in the groove
of the cartridge the cartridge is closed and then inserted
in the injector (Fig. 7.15). Once the cartridge is fixed onto
the injector the injection of the lens is done by the spongy
tip (Fig. 7.16) till one can see the lens coming into the
nozzle of the cartridge (Fig. 7.17).

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Chapter 7: Phakonit with Acritec IOL 57

Fig. 7.6: Phakonit completed. Note the nucleus has been


removed and there are no corneal burns

Fig. 7.8: Bimanual irrigation aspiration completed

Fig. 7.7: Bimanual irrigation aspiration started

Fig. 7.9: The Acri. Lye foldable IOL in the sterile vial

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Section I: Cataract

Fig. 7.10: The Acri. Lye foldable IOL

Fig. 7.12: The soft spongy tip being fixed onto


the tip of the Acri. Tec injector

Fig. 7.13: Tip of the injector with the spongy tip. This will
prevent any damage to the lens when inserting the lens
Fig. 7.11: The Acri. Tec injector

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Chapter 7: Phakonit with Acritec IOL 59

Fig. 7.16: The tip of the injector with the spongy tip ready in
place to push the IOL

Fig. 7.14: The Acri. Lye IOL placed in the cartridge

Fig. 7.17: The IOL coming out into


the noozle of the cartridge

LASER PHAKONIT

Fig. 7.15: The cartridge fixed onto the injector

LENS INSERTION TECHNIQUE


After the Phakonit procedure is completed, the incision
is increased to 1.5 mm. Then the tip of the cartridge is
kept at the site of the incision (Fig. 7.18). Remember the
cartridge is not inserted inside the anterior chamber.
Now, the lens is gradually inserted through the incision
(Fig. 7.19). One can watch the lens unfolding inside the
capsular bag. The inferior haptic goes into the bag (Fig.
7.20) and the superior haptic is gradually tucked inside
the capsular bag. Viscoelastic is then removed with the
Bimanual irrigation aspiration probes (Fig. 7.21).

Laser Phakonit uses laser energy (coupled with ultrasound energy in hard nuclei) to remove the nucleus. This
technique was started first time in the world by the
authors (Sunita Agarwal). The laser machine used is the
Paradigm Laser Photon. In these cases, two ports are
used. One port has fluid (BSS) flowing through an
irrigating chopper of 20 gauge and in the other hand is
the phaco probe without a sleeve. In the center of the
phaco probe is passed the laser probe. The diameter of
the phaco probe is 900 microns. The laser probe reduces
the orifice opening to 550 microns. Thus the nucleus can
be removed through a very small 0.9 mm opening.
SUMMARY
With the advent of Phakonit the size of the incision has
drastically reduced. Now with more companies moving

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Section I: Cataract

Fig. 7.18: The tip of the noozle of the cartridge is at the


incision site but not inside the anterior chamber

Fig. 7.20: The IOL being inserted inside the bag

Fig. 7.19: The IOL inserted through a 1.5 mm incision

Fig. 7.21: Viscoelastic removed using bimanual irrigation


aspiration probes

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Chapter 7: Phakonit with Acritec IOL 61


into manufacturing ultra-small incision IOLs which can
pass through 1.5 mm incisions or less the advantage of
Phakonit becomes even more. With time more surgeons
will move into this technology thus benefiting more
patients.

REFERENCES
1. Agarwal S, Agarwal A, Sachdev MS, Mehta KR, Fine IH,
Agarwal A. Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs (2nd edn) New Delhi: Jaypee Brothers, 2000.
2. Boyd BF, Agarwal S, Agarwal A, Agarwal A. Lasik and Beyond
Lasik; Highlights of Ophthalmology; 2000; Panama.
3. Agarwal et al. No anesthesia cataract surgery with karate chop;
In: Agarwals Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs (2nd edn) New Delhi: Jaypee Brothers, 2000; 21726.

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62

Section I: Cataract

Endocapsular Lensectomy
Steve Charles

INTRODUCTION
CONVENTIONAL TECHNIQUES
WITH THE FRAGMENTER
INFUSION OPTIONS
LENS CAPSULE REMOVAL
FRAGMENTER OPTIONS
PHACOEMULSIFICATION WITH
PARS PLANA VITRECTOMY
ANTERIOR LENS CAPSULE
RETENTION AND LENS
IMPLANTATION IN THE SULCUS
ENDOCAPSULAR LENSECTOMY

INTRODUCTION
The development of vitrectomy and phacoemulsification have an
intertwined and interesting history. The first vitrectomy cutter was patented
by Banko in 1968 in response to vitreous complications of early phacoemulsification. Banko had apparently learned of the need for a vitreous
cutter because he developed the fluidics for Kelmans early phacoemulsifier. Machemer developed the trans pars plana vitrectomy procedure
in 1970 and shortly thereafter performed lensectomy with the vitreous
infusion suction cutter (VISC). It was soon discovered that the vitreous
cutter would not handle denser nuclear sclerosis. Girard developed the
fragmenter in 1972 as a phacoemulsifier without the coaxial infusion sleeve.
The author was an early advocate of trans pars plana lensectomy using
the Girard fragmenter with aspiration. Girard advocated vitrectomy with
his unit and later recommended using the fragmenter for routine cataract
surgery. The author believes that ultrasonic vitrectomy and pars plana
lensectomy for routine cataract surgery are unsafe. Shock adapted a dental
unit to cataract surgery just as Kelman had at an earlier date, but like Girard
could not use a coaxial infusion sleeve which had been patented by Kelman.
The shock technique required a large, leaky wound and was used with
infusion through the fragmenter needle rather than suction. The shock
system was used by Machemer in this manner but through the pars plana
for cases with nuclear sclerosis too great for the VISC.
CONVENTIONAL TECHNIQUES WITH THE FRAGMENTER
Current practice for trans pars plana lensectomy with the fragmenter begins
with placement of the infusion cannula. The cannula is then inspected to
ascertain that it has penetrated the choroid and nonpigmented ciliary
epithelium. The author strongly recommends that this is done with the
operating microscope. It is very dangerous to inspect with the naked eye
even with the endoilluminator.
The next step is typically to incise the equatorial lens capsule with the
massive vitreous retractor (MVR) blade. The author has also used the
fragmenter to incise the lens capsule. The fragmenter method offers no
real advantage but was initiated to avoid the stress that capsular incision
with the MVR blade creates on the zonules. Many surgeons advocate
penetration of the nucleus with the MVR blade. This step is unnecessary if
the nucleus is soft but creates excessive stress on the zonules if the nucleus
is hard.
After incising the lens capsule, the fragmenter is used in what phaco
surgeons would call a sculpting mode to remove lens material. The author

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Chapter 8: Endocapsular Lensectomy 63


has advocated sculpting in a plane parallel to the iris
starting on the temporal side adjacent to the entry site.
An initial thick sheet of cortex and nucleus is removed
while being careful to avoid the cortex near the anterior
and posterior lens capsule. The posterior capsule is much
weaker than the anterior capsule and is usually not intact
by the time the posterior cortex has been removed.
Many surgeons recommend alternating aspiration
and sonification. Many surgeons use pulsating mode as
well. Unlike the phacoemulsifier, the fragmenter has no
infusion sleeve and must rely on fluid flow through the
lumen for cooling. The needle has approximately 0.003
in of longitudinal movement and generates significant
frictional heat. In contrast, the author has always
recommended continuous and simultaneous sonification
and aspiration. The constant fluid flow cools the needle
and therefore the sclera. If white, particulate matter (lens
milk) appears at the needle, the surgeon must release
the foot pedal immediately to avoid scleral burns. If the
needle becomes clogged, it should be back flushed with
a syringe filled with balanced salt solution (BSS) with
the ultrasound activated after double checking to
determine that the needle is out of the eye. Aspiration of
saline from a cup is never effective, and it is unnecessary
to remove, clean with a stylet, or replace the needle if it
becomes plugged.
INFUSION OPTIONS
Many surgeons recommend placing a separate infusion
into the lens rather than using the pars plana infusion
cannula. If the lens is soft, infusion directly into the lens
is not necessary. If the lens is hard, infusion into the lens
will not reach the temporal side where the sculpting
necessarily must begin. Infusion into the lens tends to
force lens material through ever present defects in the
posterior capsule. For this reason, the author uses only
the pars plana infusion cannula for lensectomy cases
except during hydrodissection.
LENS CAPSULE REMOVAL
Most surgeons use the vitreous cutter to remove the
capsule. The author has recommended end-opening
Grieshaber forceps to remove the capsule for over a
decade. The author has used the diamond-coated forceps
developed with Grieshaber since they became available.
The capsule is stripped from the zonules in a circular
motion identical to capsulorhexis. Care must be taken to
avoid engaging the vitreous so as to prevent force on the
retina. Using the vitreous cutter to remove lens capsule
frequently damages the iris, causes miosis, prolongs
operating time and leaves lens material behind.

FRAGMENTER OPTIONS
The fragmenter handpieces sold by Berkley Bioengineering, Coopervision, Sparta, Fiber sonics, MidLabs, Storz,
and Alcon were all made by Fiber sonics. These
fragmenters were very useful but had less power than
the phacoemulsifier and hence had more difficulty with
dense nuclear sclerosis. Alcon introduced a titanium
fragmenter several years ago that uses the same
ultrasonic driver as the Legacy phacoemulsifier. The
alcon titanium fragmenter will handle dense nuclear
sclerosis just as well as the phacoemulsifier. The Alcon
Accurus system supports this fragmenter and has
advanced fluidics and vitreous cutters.
PHACOEMULSIFICATION WITH
PARS PLANA VITRECTOMY
Many surgeons now recommend using a phacoemulsifier
to remove visually significant cataract through a
conventional cataract incision before initiating vitreous
surgery. If this is done as a separate operation, it adds
risk and cost. If a cataract surgeon is brought in to operate
with the vitreous surgeon, it adds cost and operating
time. Phaco at the time of vitrectomy frequently causes
miosis, viscoelastics in the anterior chamber, and may
cause slight corneal haze, striate keratopathy, and
pigment in the anterior chamber. Viscoelastics are
contraindicated if silicone is to be used because they
decrease the interfacial tension from 42 dyne/cm2 to
about 30 dyne/cm2 and increase emulsification. If iris
clips or sutures are used because of miosis created by
transpupillary phaco, there is more postoperative
inflammation and operating time as well as increased
cost.
ANTERIOR LENS CAPSULE RETENTION AND
LENS IMPLANTATION IN THE SULCUS
The late Ron Michels was long an advocate of preserving the anterior lens capsule until the end of the
vitrectomy to reduce damage to the endothelium and
trabecular meshwork induced by erythrocytes, infusion
fluid, and turbulence. Kokame and Blankenship reported
retention of the anterior lens capsule to permit
implantation of a posterior chamber lens in the ciliary
sulcus at the end of the vitrectomy. They recommended
performing a posterior capsulotomy after lens
implantation. Some phaco surgeons have been critical
of this procedure because endocapsular implantation has

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64

Section I: Cataract

better results than ciliary sulcus placement. The author


has had very good results with this method with no cases
of decentration or capsular fibrosis. The author has found
that polishing the capsule has a significant chance of
preserving a clear capsule. The author has recently
started using the Acrysoft foldable acrylic lens from
Alcon through a 3.1 mm keratome incision at the end of
the vitrectomy. This lens is implanted in the sulcus,
anterior to the retained anterior capsule.

ENDOCAPSULAR LENSECTOMY
Conventional lensectomy as described above, is essentially an endocapsular phaco except that it starts with an
equatorial capsular incision. This equatorial defect
frequently leads to capsular tears that extend into the
anterior capsule. Extension of capsular tears was a
frequent problem in phaco surgery until the circular
capsulorhexis was developed.

Figs 8.1 to 8.6: Technique of endocapsular lensectomy

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Chapter 8: Endocapsular Lensectomy 65

Figs 8.7 and 8.8: Technique of endocapsular lensectomy

Cataract surgery has seen a progression from intracapsular to extracapsular surgery, followed by phacoemulsification. Phaco has evolved from anterior chamber
to nuclear elevation, to endocapsular surgery. Circular
capsulorhexis, if well-executed, has dramatically reduced
problems with capsular tears for the cataract surgeon.
The author has done posterior capsulorhexis, hydrodelineation and hydrodissection and sculpting and has
found these techniques to be of great value in endocapsular lensectomy.
The current technique (Figs 8.1 to 8.8) begins with
conventional placement and inspection of the infusion
cannula. All sclerotomies are made with the MVR blade,
3.0 mm posterior to the limbus, unless pars plana
pathology demands a more anterior location. The second
sclerotomy is made superonasally for the endoilluminator. The endoilluminator is essential to stabilize the
eye and provide a red reflex. The endoilluminator can
be touched to the lens capsule in various locations to aid
in visualization without the light toxicity associated with
reflective red reflex methods. The third sclerotomy is
made superotemporally for the capsulorhexis, sculpting,

and capsule polishing tools. The capsulorhexis is made


with vitreous cutter after a limited anterior vitrectomy.
Hydrodelineation and hydrodissection is the next step.
A blunt 27 gauge cannula attached with a short length of
tubing to a 5 cc syringe operated by the assistant is used
for this step. Sculpting is then initiated centrally to avoid
damaging the capsule with the fragmenter. The Alcon,
20 gauge, titanium fragmenter is used to sculpt the
nucleus, epinucleus, and finally the cortex. The anterior
cortex is avoided to prevent damaging the anterior
capsule. The anterior capsule is polished with the
vitreous cutter. Any posterior chamber lens could
theoretically be utilized, but foldable IOLs offer the
advantage of a smaller incision. The Alcon Acrysof lens
is currently being evaluated and shows promise.
SUMMARY
Endocapsular lensectomy combines the best aspects of
advanced phacoemulsification, lens implant surgery, and
fragmentation. It is hoped that better management of
visually significant cataract in conjunction with indicated
vitrectomy will evolve from these concepts.

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Section I: Cataract

Phaco in Subluxated Cataracts


Nishanth Patel, Vikas Lal, Amar Agarwal, Athiya Agarwal, Sunita Agarwal

INTRODUCTION
HISTORY
ADVANTAGES
DESIGNS AND DESCRIPTIONS
INDICATIONS
APPLICATIONS

INTRODUCTION
The surgical management of cataract associated with zonular dialysis is a
real challenge for the ophthalmic surgeon. Due to recent advances in equipment and instrumentation, better surgical techniques and understanding
of the fluidics, the surgeon is able to perform relatively safe cataract surgery
in presence of compromised zonules. Implantation of a capsular tension
ring can stabilize a loose lens and allow the surgeon to complete phacoemulsification and IOL implantation.

TECHNIQUE
INCISIONS
CAPSULORHEXIS
HYDRODISSECTIONHYDRODELINEATION
IMPLANTATION OF
CAPSULAR RING
PHACOEMULSIFICATION
CORTICAL ASPIRATION
IMPLANTATION OF THE
INTRAOCULAR LENS
SPECIAL CONDITIONS

HISTORY
Insertion of a ring into the capsular bag fornix (equator) to support the
zonular apparatus was first described by Hara and coauthors in 1991.1
Hara et al introduced the concept of equator ring, endocapsular ring
or capsular tension ring(CTR). In 1993, the first capsular tension ring
(CTR) for use in humans was designed.2 In 1994, Nagamoto and Bissen
Noiyajima 3 suggested using an open PMMA ring to provide adaptability.
ADVANTAGES
The use of an endocapsular flexible PMMA ring in cases of subluxated
cataract, introduced by Ulrich Legeir in 1993, has changed the surgical
approach to complicated situations. This technique offers four main
advantages:
1. The capsular zonular anatomical barrier is partially reformed, so that
vitreous herniation to the anterior chamber during surgery in reduced
or even avoided.
2. A taut capsular equator offers counter traction for all traction
maneuvers, making them easier to perform and decreasing the risk of
extending the zonular dialysis. The great advantage of using the
capsular ring during the phacoemulsification rather than after, just to
center the lens is a great deal safer. Any force that is transmitted to the
capsule is not applied directly to the adjacent zonules, but rather
distributed circumferentially to the entire zonular apparatus.
3. The necessary capsular support for an in the bag, centered implant is
obtained.
4. The capsular bag maintains its shape and does not collapse, which can
lead to proliferation and migration of epithelial cells, development of
capsular fibrosis syndrome and late IOP decentration.

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Chapter 9: Phaco in Subluxated Cataracts 67

Fig. 9.1: Capsular tension ring or endocapsular ring. Note


the eyelets at the ends of the ring

DESIGNS AND DESCRIPTIONS


The capsular tension ring (Fig. 9.1) is made of one piece
polymethylmethacrylate (PMMA) and is available in
different sizes depending on their use in patients with
emmetropia, low or high myopia. The original capsular
tension ring, with characteristic islets on both ends is
marketed by Morcher company in co-operation with Dr
Mitchel Morcher. Meanwhile, various similar products
are being marketed (e.g. by ophtec physiol, corneal, IOL
tech, Acrimed, Rayner, Hanita, Lens Tec). As a standard
capsular tension ring, 12.0/10.0 mm diameter ring
(Morcher type 14) and the 13.0/11.0 mm diameter ring
(ophtec 13/11) are the most commonly used by surgeons.
Morcher type 14 for normal axial length eyes, while type
14A and 14C are for myopic eyes.
The modifications used, as by Morcher, include 2
types of capsular tension rings with iris shields (Type L
and G, with integrated iris shields of 60 and 90 degrees,
respectively) and 2 types of capsular bending rings
(CBRs) designed to prevent capsule opacification (type
E and F). These modified versions incorporate fixation
elements that allow the surgeon to suture the ring to the
scleral wall, through the ciliary sulcus, without violating
the capsular ring.4
Special designs for suturing in severe zonular dehiscence:
In cases where severe or progressive zonular
dehiscence is present implantation of the capsular tension
ring alone may not be adequate. This may lead to severe
postoperative capsular bag shrinkage as well as IOL
decentration and pseudophakodonesis.5 Also complete

luxation of the bag along with the capsular tension ring


and the IOL cannot be excluded.
A modified design developed by Cionni with a
fixation hook for severe or progressive cases of zonular
deficiency6 solves this problem. The hook is kept opposite
to the meridian of decentration and is pulled peripherally using a trans-scleral fixation suture, to counteract
capsular bag decentration and tilt. In severe cases two
such rings or the two hooked model can be used. However the Cionni ring has its limitations like difficulty to
implant if the capsulorhexis is small and in such cases
the hook may even drag on the edge of the anterior capsule, and as the fixation plane is anterior to the anterior
capsule, it may lead to iris chafing leading to pigment
dispersion and chronic uveitis.
An alternative is to fix the ring by guiding the needle
of the scleral suture through the equator of the capsular
bag, just inside the capsular tension ring.7 This technique
has to be completed as a one step procedure because the
suture may cheese-wire through both capsules leaving
along the equator.
Another alternative in cases of severe decentration is
to make a small equatorial capsulorhexis through which
a standard capsular tension ring can be inserted. A scleral
suture can then be passed around the exposed capsular
tension ring which is then used to center the lens before
capsulorhexis.
INDICATIONS
The indication for use of capsular tension ring is in all
cases of subluxation of lens (Table 9.1) ranging from the
common ones like traumatic displacement (mechanical
or surgical), Marfans syndrome, pseudoexfoliation
syndrome and hypermature cataract to the rare ones like
aniridia and intraocular tumors.
The indications for use of the capsular ring, in the FDAmonitored study include:
Pseudoexfoliation syndrome
Marfans syndrome
Loss of zonular integrity
Ocular trauma (Blunt or surgical trauma)
High myopia
Previous vitrectomy
The best surgical technique for removing the subluxated cataract depends on the extent of the zonular dialysis.
With a zonular defect of less than 90 degree (3 clock
hours), endocapsular phacoemulsification within the bag
IOL implantation can be accomplished. The haptics of
the IOL should be placed in the meridian of the zonular
dialysis.
When the zonular tear is larger than 90 degrees, all
tractional surgical maneuvers are difficult and increase

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Section I: Cataract
Table 9.1: Etiology of subluxated lenses

A. Isolated ocular abnormality


Simple ectopia lentis
Simple microsherophakia
Spontaneous,late subluxation of lens
B. Associated with other ocular abnormality
Aniridia
Ectopia lentis et pupillae
Uveal coloboma
Cornea plana
C. Associated with heritable systemic syndromes
Marfans syndrome
Homocystinuria
Weill-Marchesani syndrome
Ehlers-Danlos syndrome
Reigers syndrome
Hyperlysinemia
Sulfite oxide deficiency
Sturge-Weber syndrome
Pflanders syndrome
Crouzons syndrome
Sprengels anomaly
Oxycephaly
D. Associated with other ocular conditions
Mature or hypermature cataract
Mechanical stretching of zonules
Buphthalmos
Staphylomas
Ectasias of globe
High myopia
Perforation of large central corneal ulcer
Pull on zonules
Cyclytic inflammatory adhesions
Ealesdisease
Persistent hyperplastic primary vitreous
Intraocular tumors
Retinal detachment
Degeneration of zonules
Uveitis
Retinitis pigmentosa
Chalcosis
Prolonged silicone oil tamponade
High myopia
Hypermature cataract
E. Traumatic subluxation/dislocation and surgical trauma

the chance of further zonular disinsertion. Moreover, the


defect in the capsular-zonular barrier allows hydration
and herniation of the vitreous into the anterior chamber
during surgery. In addition, insufficient capsular support
may make necessary either the suturing of at least one
haptic of a posterior chamber IOL or the placement of an
anterior chamber IOL. Endocapsular introduction of a
flexible PMMA ring has changed the surgical manage-

ment of such cases, allowing safe aspiration of lens


material and implantation of an in the bag IOL.
APPLICATIONS
Zonular Dehiscence
The efficacy of the capsular tension ring in managing
zonular dialysis has been demonstrated in vitro 8,9
depending on where the zonular defect presents. The
capsular tension ring may be inserted at an stage of
cataract procedure. By re-establishing the capsules
contour, the capsular tension ring protects the capsular
fornix from being aspirated, avoiding consecutive
zonular dialysis extension, irrigation fluid running
behind the capsular diaphragm with the posterior
capsule bulging, and vitreous prolapse into the anterior
chamber with possible aspiration. With preexisting
zonular defects such as those caused by blunt trauma,
the capsular tension ring is inserted before phacoemulsification is started.
Zonular Weakness
Ocular and systemic conditions may result in a zonular
weakness that may be profound and progressive.
Pseudoexfoliation syndrome with or without glaucoma
and Marfans syndrome are the most common causes. If
zonular weakness is profound the capsular tension ring
is implanted before the cataract is emulsified and a 10-0
nylon anchoring suture may be temporarily threaded
through the eyelets so as to remove the capsular tension
ring if the zonules fail during surgery.
In pseudoexfoliation syndrome, the anterior capsule
may contract excessively after in the bag IOL placement
(capsular phimosis). This can be prevented by providing
a locking mechanism that would prevent the islets from
overlapping, suturing together the two islets together or
by using two larger implants. This can be supplemented
by meticulously polishing the anterior capsule leaf
overlapping the implant.
In case of Marfans syndrome the zonules may be
disintegrated or elongated while the remaining may be
still functional, giving rise to lens decentration, which
may be progressive. In case of Weill-Marchesani syndrome, microsherophakia and zonular degeneration may
occur. Secondary scleral suturing to remedy IOL
decentration and tilt may be useful in such cases.7
Use of prolonged silicone oil tamponade may lead to
progressive zonular atrophy and emulsified oil or oil
bubble gaining access into the anterior chamber spontaneously or during the cataract surgery. In such cases a

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Chapter 9: Phaco in Subluxated Cataracts 69


large capsular tension ring should be implanted before
phacoemulsification is done.
TECHNIQUE
Anesthesia
Both general and peribulbar anesthesia are suitable for
creation of scleral windows and trans-scleral suturing
of the capsular ring or of the IOL if necessary. Special
mention is required about 1 percent intracameral
lidocaine. There is a risk of its passage through the zones
lacking zonular fibers, and transitory loss of sight
resulting from retinal toxicity, as described in cases of
capsular ruptures.10
INCISIONS
The first step is to make an incision in the eye (Fig. 9.2).
A needle with viscoelastic is injected inside the eye in
the area where the second site is made (Fig. 9.3). This
will distend the eye so that when you make a clear
corneal incision, the eye will be tense and one can create
a good valve. In Figure 9.3 note the subluxation seen to
the right. Now use a straight rod to stabilize the eye with
the left hand. With the right hand make the clear corneal
incision (Fig. 9.4).

Fig. 9.3: Needle with viscoelastic entering the eye to inject the
viscoelastic. This gives an entry into the eye through which a
straight rod can be passed to stabilize the eye. Note no forceps
holds the eye. Note also the subluxation seen to the right

CAPSULORHEXIS
Commencing capsulorhexis (Fig. 9.5) is difficult because
of capsular instability. It is better to begin the capsulorhexis in the area where the zonules is whole and where
the capsule offers sufficient resistance. If vitreous is
present in the anterior chamber, the gel must be first

Fig. 9.4: Clear corneal incision. Note the straight rod inside
the eye in the left hand. The right hand is performing the clear
corneal incision. This is a temporal incision and the surgeon
is sitting temporally

isolated and vitrectomy should be performed if required.


After the vitreous has been removed from the anterior
chamber, a viscoelastic preferably dispersive is inserted
by first covering the zone. Capsulorhexis can be performed after the zone of zonular dehiscence and iridocrystalline diaphragm have been stabilized.
HYDRODISSECTIONHYDRODELINEATION

Fig. 9.2: Eye with subluxated cataract

Hydromaneuvers should be performed meticulously to


ensure correct freeing of the lens nucleus. The hydrodissection cannula should be inserted in the direction of the
zone of disinsertion rather than in the opposite direction,
which would enlarge the disinsertion. Viscoelastic may

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Section I: Cataract

Fig. 9.5: Rhexis being done with a needle

Fig. 9.6: Injector for the capsular tension ring.


Note the hook at the end of the injector

be required to separate the nucleus and cortical material


and also to separate the cortex from the lens capsule.
IMPLANTATION OF CAPSULAR RING
Mostly capsular tension rings can be easily inserted in
the capsular bag if it is well-expanded with viscoelastic.
The instruments used to implant a capsular tension ring
include Kelman-McPherson type forceps, special
injectors (marketed by Ophtec and Geuder suitable for
both Ophtec and Morcher CTRs and the one developed
by Menapace and Nishi for use with CBR, Geuder Co. )
and last but not the least a guiding suture.
In Figure 9.6 one can see the injector made by
Ophtec. This has a small hook (Fig. 9.6) in it which hooks
on to the islets of the capsular tension or endocapsular
ring. The injector is brought close to the islet of the
capsular tension ring (Fig. 9.7) and once the hook locks
onto the islet, the plunger of the injector is released

Fig. 9.7: The hook of the injector locks onto


the eyelet of the capsular tension ring

Fig. 9.8: The caspular tension ring is


withdrawn into the injector

which makes the capsular tension ring move into the


injector (Fig. 9.8). Then the capsular tension ring is
inserted by the injector into the capsular bag through
the rhexis (Fig. 9.9).
PHACOEMULSIFICATION
Nuclear phacoemulsification can be performed (Fig. 9.10)
in the bag or out of the bag, depending on the surgeons
preference. In general, phacoemulsification in these
situations may be considered a safe proposition if
performed in a proper way.
CORTICAL ASPIRATION
When performing automated aspiration (Fig. 9.11),
movements of the tip should not be radial because of the
risk of traction on the ring and the capsular bag.

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Chapter 9: Phaco in Subluxated Cataracts 71

Fig. 9.12: Allergan foldable IOL in the unfolder


Fig. 9.9: The capsular tension ring is then inserted inside
the capsular bag by the injector

Fig. 9.13: Foldable IOL in capsular bag. Viscoelastic


removed with the irrigation aspiration probe
Fig. 9.10: Phacoemulsification performed

IMPLANTATION OF THE INTRAOCULAR LENS


It is desirable to implant a larger diameter lens to
minimize symptoms if lens decentration were to occur.
The foldable lens (Fig. 9.12) is loaded and implanted in
the capsular bag (Fig. 9.13) followed by viscoelastic
removal. In either case, rotational maneuvers must be
avoided or minimized.11
Figure 9.14 shows the first postoperative day photograph of the same patient. Figure 9.15 shows the
postoperative photograph of another patient in whom a
Staar plae haptic foldable IOL was implanted with the
capsular tension ring.
Key Points with the Use of Capsular Tension Rings

Fig. 9.11: Cortical aspiration. Note the straight rod in the


left hand which helps control the movements of the eye

1. Use a high viscosity viscoelastic.


2. Make the incision at a meridian with no zonular
dialysis, in order to avoid damage to zonular fibers
with the movement of the phaco tip.

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Section I: Cataract

Fig. 9.14: Capsular tension ring and the allergan foldable


IOL in the bag. One day postoperative photo

Fig. 9.15: Capsular tension ring and a staar plate haptic


foldable IOL in the capsular bag. Note the eyelets seen clearly
in the capsular bag

3. Perform slow-motion phaco, with low flow rate, low


vacuum, and low infusion bottle height.
4. Emulsification can be done in the bag when the
nucleus is soft and in the anterior chamber if the
nucleus is hard thereby avoiding as much stress as
possible to the already damaged zonular apparatus.
5. Perform a careful two port anterior vitrectomy with
lax infusion bottle and low aspiration pressure when
necessary.
6. Try to place IOL haptics in the meridian of the zonular
disinsertion.
7. IOL stability must be checked at the end of the surgery,
both in the frontal and sagittal plane in order to
consider if suturing one haptic to the sulcus is
necessary.6

3. Anterior eye wall resection for uveal melanoma or


other intraocular malignancy: A combined use of a
standard and coloboma capsular tension ring is
advocated in cataract surgery after anterior eye wall
resection for intraocular malignancy like uveal
melanoma. Uveal tumors involving the anterior
segment of the eye may need uveal resection resulting
in large iris coloboma and zonular dehiscence. The
crystalline lens may be cataractous or may become
opaque after the surgery of the tumor requiring its
removal sooner or later. For technical approach
intracapsular cataract extraction was considered
previously, but the combined use of a standard and
coloboma capsular tension ring may help preserve
the capsular bag and cover the iris defects.
4. Along with primary posterior capsulorhexis: for
preexisting central capsule fibrosis or as a general
preventive measure against capsule opacification has
been advocated.12 As the capsular tension ring is in
place, vector forces during primary posterior capsulorhexis can be controlled in a better way as the ring
stretches the posterior capsule, giving uniform radial
vector forces. As the capsular tension ring is in place
distortion in shape of the primary posterior
capsulorhexis can be avoided and folds on the capsule
caused by traction due to oversized and rigid lens
loop can be prevented, which allows closer and
perfect apposition of the posterior capsule with the
optic of the IOL thereby preventing lens epithelial
cells (LECs) from entering the retrolental space in the
posterior capsulorhexis margin and thus preventing
the secondary primary posterior capsulorhexis
closure.

SPECIAL CONDITIONS
1. Coloboma shield for large sector iris defects or
iridodialysis: Tinted capsular tension ring with an
integrated 60 to 90 degree sector shield designed by
Rasch can be used to protect against glare and /or
monocular diplopia.(Morcher L and G ).The capsular
tension ring can be placed to cover sector iris defects
and /or coloboma. If more than 90 degrees of defect
is present then more than one capsular tension ring
can be used.4
2. Multisegmented coloboma ring for aniridia: This
multisegmented ring designed by Rasch (Morcher
type 50 C) is used in combination with the one of the
same kind so that the interspaces of the first ring are
covered by the sector shields of the second forming a
contiguous artificial iris.

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Chapter 9: Phaco in Subluxated Cataracts 73


5. In combined cataract and vitreous surgery: When the
capsular tension ring is in place, the posterior capsule
remains uniformly distended and a perfect peripheral
view is possible. Also as the capsular tension ring is
in place silicone oil can be removed through the same
phaco incision from the primary posterior capsulorhexis, which can be performed in a controlled
manner with the capsular tension ring in place.
6. As a tool to measure capsular bag circumference: The
capsular tension ring in vivo can be visualized
goniscopically from a well-dilated pupil .The distance
between the islets can be determined by adjusting the
width of the slitbeam of the slitlamp to fill in the space
between the eyelets which can be readout on the
slitlamp directly. This capsular bag biometry can be
used for quantifying in vivo capsular bag circumference13 and capsular bag shrinkage dynamics.14
7. For prevention of posterior capsular opacification:
Theoretically the lesser the space in between the lens
optic and the posterior capsule the lesser are the
chances of lens epithelial cells from migrating behind
the optic, i.e. no space no cells. When the capsular
bending ring is in place, this interspace is less
common and if present less in amount as compared
to without a capsular bending ring. Also by keeping
the anterior capsule away from the posterior capsule,
myofibroblastic transdifferentiation of lens epithelial
cells on the anterior capsule edge and back surface
can be prevented. The capsular bending ring is an
open, band-shaped polymethylmethacrylate ring
measuring 11 mm in diameter with pretension (13 mm
diameter when open), 0.2 mm in thickness, and 0.7
mm in thickness.
The ring is minimally polished to keep the edges
sharp and rectangular, facilitating the creation of a sharp,
discontinuous band in the equatorial capsule. A crooked
islet is located at both the ring ends to prevent spearing
of the capsular fornix and to facilitate manipulation
during insertion. The capsular bending ring reduces
anterior capsular fibrosis and shrinkage as well as
posterior capsular opacification. The ring may be useful
in patients who are at high risk of developing eye
complications from opacification that require Nd:YAG
laser capsulotomy, in those expected to have vitreoretinal
surgery and photocoagulation, and in cases of pediatric
cataract.15

SUMMARY
Capsular tension rings or endocapsular rings have solved
the problems of phaco in subluxated cataracts. They have
made life much easier for the cataract surgeon.
REFERENCES
1. Hara T, Hara T, Yamada Y.Equatorial ring for maintainance
of the completely circular contour of the capsular bag equator
after cataract removal. Ophthalmic Surg 1991; 22; 358-59.
2. Hara T, Hara T, Sakanishi K, Yamada Y.Efficacy of equator rings
in a experimental rabbit study. Arch Ophthalmol 1995; 113:106065.
3. Nagamoto T, Bissen-Noiyajima H. A ring to support the capsular
bag after continuous curvilinear capsulorhexis. Cataract Refract
Surg 1994; 20:417-20.
4. Rupert Menapace, Oliver Findl, Michael Georgopoulos, Georg
Rainer, Clemens Vass, Karin Schmetter. The capsular tension
ring: Designs, applications, and techniques. J Cataract Refract
Surg 2000; 898-912.
5. Nishi O, Hishi k,Sakanishi K, Yamada Y. Explantation of endocapsular posterior chamber lens after spontaneous posterior
dislocation.J Cataract Refract Surg 1996,22:272-75.
6. Groessl SA, Anderson CJ. Capsular tension ring in a patient
with Weill-Marchesani syndrome. J Cataract Refract Surg 1998;
24:1164-65.
7. Fischel JD, Wishart MS. Spontaneous complete dislocation of
the lens in pseudoexfoliation syndrome. Eur J Implant Refract
Surg 1995;7:31-33.
8. Sun R, Gimbel HV.In vitroevaluation of the efficacy of the
capsular tension ring for managing zonular dialysis in cataract
surgery. Ophthalmic Surg Lasers 1998; 29:502-05.
9. Gimble HV, Sun R, Heston JP.Management of zonular dialysis
in phacoemulsification and IOL implantation using the capsular
tension ring. Ophthalmic Surg Lasers 1997;28:273-81.
10. Gills J, Fenzil R. Intraocular lidnocaine causes transient loss of
vision in small number of cases. Ocular Surgery News 1996.
11. Agarwal S, Agarwal A, Sachdev MS, Mehta KR, Fine IH,
Agarwal A. Phacoemulsification, Laser Cataract Surgery and
Foldable IOLs; (2nd edn) New Delhi: Jaypee Brothers, 2000.
12. Van Cauwenberge F, Rakic J-M,Galand A. Complicated poserior
capsulorhexis: Etiology, management, and outcome. Br J
Ophthalmol 1997;81:195-98.
13. Vass C, Menapace R, Schametter K et al. Prediction of pseudophacic capsular bag diameter on biometric variables. J Cataract
Refract Surg 1999; 25: 1376-81.
14. Strenn K, Menapace R, Vass C. Capsular bag shrinkage after
implantation of an open loop silicone lens and a polymethyl
methacrylate capsule tension ring. J Cataract Refract Surg 1997;
23: 1543-47.
15. Okihiro Nishi, Kayo Nishi, Rupert Menaopace, Junsuke Akura.
Capsular bending ring to prevent posterior capsule opacification:2 year follow up. J Cataract Refract Surg 2001;27:1359-65.

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Section I: Cataract

10

Update on Pediatric Cataract Management


Suresh K Pandey, M Edward Wilson, David J Apple, Liliana Werner, Jagat Ram

INTRODUCTION
DIAGNOSIS OF PEDIATRIC
CATARACTS
CATARACT SURGERY IN
CHILDREN
SURGICAL TECHNIQUES
DYE-ENHANCED PEDIATRIC
CATARACT SURGERY
PEDIATRIC TRAUMATIC
CATARACTS AND THEIR
MANAGEMENT
PERIOPERATIVE AND
POSTOPERATIVE TREATMENT
POSTOPERATIVE
COMPLICATIONS AND
MANAGEMENT
RESIDUAL REFRACTIVE ERROR
MANAGEMENT OF AMBLYOPIA

INTRODUCTION
Congenital, early developmental and traumatic cataracts are common
ocular ailments and represent an important cause of visual impairment in
childhood.10 Managing cataracts in children remains a challenge; treatment
is often difficult, tedious and requires a dedicated team effort by the parents,
pediatrician, surgeon, anesthesiologist, orthoptist and community health
workers. The surgeon plays a significant role in achieving a good visual
outcome following the treatment of childhood cataracts.16 This chapter
will focus on the management of pediatric cataracts with an emphasis on
the various surgical techniques, intraocular lens (IOL) implantation and
postoperative complications.
DIAGNOSIS OF PEDIATRIC CATARACTS
Congenital, developmental and traumatic cataracts can have different
morphological characteristics (Figs 10.1A to 10.5 and Table 10.1). These
have extensively been reviewed by several authors.124,125,151 A thorough
ocular and systemic examination is mandatory in every child for the
accurate diagnosis of type of the cataract. Ocular examination should
include the visual acuity assessment, ocular motility, pupillary response,
and posterior segment evaluation. When feasible, biomicroscopic
examination of the anterior segment should be performed to evaluate the
size, density, and location of the cataract in order to plan the surgical
procedure and to determine the visual outcome. Fundus examination
should be carried out after pupillary dilatation. A scan ultrasound helps
to measure the axial length for calculating the IOL power and monitoring
the globe elongation postoperatively. For an eye with total cataract, a B
scan evaluation is useful for detection of vitreoretinal pathology. A history
from the parents is useful to determine whether the cataract could be
congenital, developmental or traumatic in origin. One must ascertain if
there is any history of maternal drug use, infection or exposure to radiation
during pregnancy. Each child should be thoroughly examined by a
pediatrician to rule out systemic associations, anomalies or congenital
rubella. This is essential as the cataract surgery in children is usually
performed under general anesthesia.
CATARACT SURGERY IN CHILDREN
How does Pediatric Cataract Surgery Differ from Adult?
Difficulties are encountered during pre, intra and postoperative periods.
Preoperative difficulties include late diagnosis, associated conditions like

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Chapter 10: Update on Pediatric Cataract Management 75

Figs 10.1A to C: Slit-lamp photographs of zonular cataracts,


taken from 3 different cases. Note that the lenticular opacity is
occupying the central visual axis

Figs 10.2A to C: Clinical photographs showing 3 different


examples of bilateral total infantile cataracts. As opposed to
the usual age-related cataract of adults, untreated cataracts
of childhood are especially unfortunate since the individual is
often doomed to immediate long-term suffering. An early
surgical intervention and prompt optical rehabilitation is
mandatory in order to prevent irreversible deprivational
amblyopia (A) Bilateral total cataract in a 2-month-old male
child (B) Bilateral total cataract in a 5-month-old male child
(C) Bilateral total cataract in a 9-month-old female child

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Section I: Cataract

Figs 10.4A and B: Pediatric uniocular cataracts following blunt


and penetrating trauma (A) Slit-lamp photograph of the anterior
segment of a 6-year-old male child showing traumatic cataract
after blunt trauma (firecracker injury). Note the formation of a
posterior synechia at 3 oclock position (B) Slit-lamp photograph of the anterior segment of a 7-year-old female child after
the repair of penetrating (bow and arrow) injury. Note the formation of a traumatic cataract associated with an irregular pupil

Figs 10.3A to C: Examples of unilateral total pediatric cataracts


in 3 different children (A) Unilateral congenital cataract in a 2month-old male child. Note the convergent squint in the left
eye probably secondary to deprivational amblyopia
(B) Unilateral traumatic cataract in a 2-year-old male child
(C) Unilateral developmental cataract in a 5-year-old female
child

prematurity and systemic disorders. Risk factors for


general anesthesia need a serious consideration.
Intraoperative difficulties are caused as a result of
smaller size of the eye, sometimes poorly dilating pupil,
highly elastic anterior capsule, low scleral rigidity and
dense vitreous giving rise to raised intravitreal and
lenticular pressure. Postoperative examination requires
repeated short anesthesia. Propensity for increased
postoperative inflammation and capsular opacification,
a refractive state that is constantly changing due to
growth of the eye, difficulty in documenting anatomic

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Chapter 10: Update on Pediatric Cataract Management 77


pathways in the central nervous system. In addition to
causing amblyopia, visual deprivation can disrupt the
process of emmetropization. Abnormal axial growth
has been reported even in the absence of amblyopia as a
result of the effects of unequal visual inputs to the two
eyes.
Despite these differences, the improved surgical
techniques that are largely a reflection of the adult
cataract surgery and the advances in postoperative
optical rehabilitation has significantly improved the
prognosis of cataract surgery in children.156
Indications for Treatment
Fig. 10.5: Bilateral congenital cataract in a 10-year-old male
child associated left convergent squint. Note the associated
ocular anomalies (microphthalmos and microcornea)

and refractive changes due to poor compliance, and a


tendency to develop amblyopia are the factors that make
the cataract surgery in the child different from that in
the adult.24,100,178-181
In sharp contrast to the treatment of adult cataracts,
the timing of cataract surgery in children is of paramount
importance. It affects the visual result to a much greater
extent than the surgical technique or method of postoperative optical correction utilized by the surgeon. In a
young child, a cataract blurs the image received by the
retina and disrupts the development of the visual

In order to avoid the development of deprivational


amblyopia, prompt diagnosis and treatment are
necessary for visually significant cataract in neonate,
infants or toddler.56 Indications for surgery in these eyes
include: cataracts of more than 3 mm in diameter
(visually significant), dense nuclear cataracts, cataracts
obstructing the examiners view of fundus or preventing
refraction of patient, if the contralateral cataract has been
removed and cataracts associated with strabismus and/
or nystagmus.81,82,101,178,179
When children beyond infancy present with dense,
central opacities of uncertain duration and Snellen visual
acuity cannot be accurately measured, surgery is
indicated within a few weeks of detection. Non-surgical
methods as patching or pharmacological pupillary
dilation can be useful to manage partial cataracts.

Table 10.1: Characteristics of pediatric cataracts


CONGENITAL/DEVELOPMENTAL
Total/Diffuse Uncommon; Rubella Cataracts, Bilateral; Variable
Visual Prognosis.
Anterior Polar:
Unilateral or bilateral; Sporadic; Opacity < 3 mm; Usually Nonprogressive; Good Visual Prognosis.
Lamellar/Zonular:
Bilateral; Partial; Opacity 5-6 mm; Good Visual Prognosis.
Nuclear:
Autosomal Dominant in many; Bilateral (80%); Non-progressive;
Opacity 3.5 mm; Moderate Visual Prognosis.
Posterior Lentiglobus: Unilateral; Good Visual Prognosis.
Persistent Hyperplastic Primary Vitreous (PHPV): Unilateral;
Sporadic and Progressive; Poor Visual Prognosis (when posterior
segment involvement present).
ETIOLOGY
Idiopathic, Hereditary, Congenital Rubella Syndrome, Galactosemia,
Lowes Syndrome, TORCH Infection
Associated Ocular Findings
Strabismus, Amblyopia, Anisometropia, Microphthalmia,
Microcornea, Peters Anomaly, Excessive Elongation of the Globe.

TRAUMATIC

Total/Diffuse
Anterior Subcapsular
Posterior Subcapsular
Intumescent
Ruptured Anterior Capsule with
Flocculent Lens Matter in
Anterior Chamber
Partially Absorbed
ETIOLOGY
(Blunt/Penetrating trauma)
Sport related
Firecracker
Bow and Arrow
Thorn
Sticks
Associated Ocular Findings
Corneal Laceration (s), Hyphema, Angle Recession,
Vitreous Hemorrhage, Posterior Capsule, Rupture,
Retinal Detachment,

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The threshold for surgical removal of a partial cataract


in a child capable of Snellen visual acuity has often been
stated to be 20/70 or 20/80. Use of vision charts, e.g. Lea
Hyvarinen symbol charts, is extremely useful in assessment of the visual status in a young child unable to read.
However, individual judgments need to be made (especially in children too young for Snellen visual acuity
testing) based on documented progression of the partial
cataract and on the childs visual functioning, visual
needs, and expected best visual outcome. When possible,
low contrast sensitivity testing may provide a helpful
guideline for deciding either the need of cataract surgery
or treatment for posterior capsule opacification (PCO).
Optical Rehabilitation
Correction of pediatric aphakia can be accomplished with
spectacles, contact lenses, epikeratophakia or IOL
implants (Figs 10.6 and 10.7).1,2,128 Currently the contact
lenses (in infants) and IOLs (in older children) are preferred. In infants, whichever method of optical correction
is chosen, it is important to get a reasonably well-focused
image on the retinas as early as possible.
Aphakic Glasses
Spectacle correction is safest and their power can be
readily changed to compensate for ocular growth. They
can be worn at any age and not unduly expensive. Their

Fig. 10.7: Use of rigid gas permeable (RGP) contact lens for
aphakic correction after surgery for traumatic cataracts in a 9year-old child. Note the traumatic corneal scar inferonasally
extending from 7 o clock to 1 oclock and a large sector iridectomy from 4 oclock to 10 oclock. The visual acuity of the eye
was 20/40 with the RGP contact lens (Courtesy: Ashok
Sharma, MD, Post Graduate Institute, Chandigarh, India)

magnifying effect may improve the childs acuity and


make microphthalmic eyes appear normal size.
Spectacles can be the only form of optical correction that
is available in a community and most children using
contact lenses should have a pair of aphakic glasses as a
spare, for when they are not able to use contact lenses.
A child wearing contact lenses, or with an IOLs, will need
bifocals if his or her acuity is not good enough. Spectacles,
however, have the disadvantage of poor cosmesis and
inferior optics (Fig. 10.6). They cause alteration in the
peripheral field of vision by inducing distortion and
prismatic effects. An infants ear and nose are often too
insubstantial to support aphakic glasses. In addition,
obtaining centration with heavy aphakic glasses is
difficult and the optical center of the lens does not move
with the eye. Although they provide a satisfactory
correction for many children with bilateral aphakia,
aphakic spectacles are generally not suitable for children
with unilateral aphakia because of marked retinal image
size disparity (approximately 30% magnification).
Contact Lenses

Fig. 10.6: Visual rehabilitation in an infant after bilateral


cataract surgery using aphakic glasses. Thick and heavy
aphakic glasses are not suitable for the infants nose and facial
structure. They are also cosmetically inferior to other modalities
(contact lenses/IOLs) of optical corrections

There are three choices of contact lens type for pediatric


patients: the hard lens, including polymethylmethacrylate (PMMA) and rigid gas-permeable (RGP) lenses (Fig.
10.7), the hydrogel extended-wear or daily wear lens,
and the silicone lens. Most of the problems of aphakic
spectacles can be overcome by the use of contact lenses,
their power can also be easily adjusted according to the
growth of the eye.20,158

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Chapter 10: Update on Pediatric Cataract Management 79


The RGP contact lenses have the advantage of low
cost and can be customized in regards to power and base
curve. Their disadvantage is that they must be removed
daily and are more difficult for the parents to insert. The
hydrogel or soft contact lenses have comfort as their main
advantage. These lenses are tolerated in a wide range of
base curvatures and thus they are easily fitted. However,
insertion difficulties coupled with instability and fragility
lead to high damage and lens loss rates. Extended wear
poly HEMA lenses have proven to be the lenses of choice
for children with unilateral aphakia. They are fairly stable
with reduced lens loss rates.
Silicone contact lenses (Silsoft, Bausch and Lomb,
Rochester, NY) combine the best features of hard and
soft lenses. They are reported to mask up to 2 diopter
(D) of astigmatism in the adult. Like the hard lenses, they
are easy to handle, have a relatively low loss rate, and
can be fitted using either measurement or trial
techniques. Most children under the age of one year can
be fitted with a lens of 7.50 base curve. Older children
are most often fit with a base curve of 7.70. A fluorescein
pattern may be used during the fitting sequence as
needed. Lens movement with blinking is the most critical
and important factor to evaluate during fitting. If too
much movement is seen, a steeper lens can be tried. If
little or no movement is seen, a flatter lens is indicated.
Unique problems facing the fitter of contact lenses in
young aphakic children include their small eyes, steep
corneas, and high hyperopia. Their continuously
changing refraction, primarily related to an increasing
axial length and progressive corneal flattening provides
an additional challenge. Repeated insertion and removal
of a contact lens can be psychologically traumatic to the
child. The major disadvantage of contact lenses for the
correction of aphakia is the frequency of lens loss.180 In
addition to lens loss, noncompliance is a major problem
particularly in children using contact lenses for correction
of monocular aphakia. Assaf and co-workers13 reported
that only 44 percent of children with unilateral aphakia
were wearing their contact lens during their follow-up
visits. Loss of lenses, conjunctival erythema and poor fit
were reasons for noncompliance in these cases. With
noncompliance comes increased amblyopia and sensory
strabismus. Other problems associated with contact lens
use, more commonly encountered in developing country
patients, who often come from rural communities with
poor socio-economic and educational background,
include infective keratitis, corneal vascularization, hypoxic corneal ulcerations, red eye without ulcerations.196
Epikeratophakia
Epikeratophakia was introduced in the early 1980s as an
alternative means of optically correcting aphakic eyes.

It is a refractive corneal surgical technique in which a


lathed lamellar corneal disc is sutured to the front surface
of the recipients cornea after removal of the recipients
epithelium. Epikeratophakia corrects the refractive error
by changing the anterior curvature of the cornea.
Advantages of this technique are that no damage occurs
to the recipients central cornea, it is reversible, entirely
extraocular, and may be employed with cataract extraction or as a secondary procedure. Problems like graft
failure due to persistent epithelial defects, infections or
mechanical trauma are common with this technique. In
addition, sutures must be removed after 3 weeks, often
necessitating another anesthetic procedure. Amblyopia
therapy is generally delayed until 4 to 6 weeks after the
initial operation. Epikeratophakia for correcting pediatric
aphakia has fallen into disuse due to the difficulty in
achieving the target refracting power and the prolonged
haziness of the host donor interface.
Intraocular Lens Implantation
Problems such as contact lens intolerance, downward
displacement of the lens with induced vertical diplopia,
aniseikonia (approximately 6% with contact lenses), and
traumatic corneal scars have prompted some investigators to advocate IOL implants for pediatric aphakia.
IOL implantation in children during the early years of
implant use in adults resulted in frequent complications
secondary to poor lens design and poor quality control
but also to lack of present refinements in the surgical
technique.64,67,68,70,85,107-116,130,168,169,257 There continues to
be some hesitation of some ophthalmologists to implant
IOLs in the pediatric population because of fear of the
long-term effects of synthetic material, the changing
refractive status of the developing eye and the increased
inflammatory response that occurs in pediatric eyes. As
late as 1991, IOL implantation in children was not well
accepted, especially by the pediatric ophthalmic community. However, the 1990s brought major improvements
in IOL designs and surgical techniques better suited for
childrens eyes. In 1994, 46 percent of 234 pediatric
ophthalmologists responding to a survey conducted by
Wilson et al.248, indicated that they were currently
implanting IOLs in children. In addition, 27 percent of
1,039 adult cataract specialists were implanting pediatric
patients. The numbers are undoubtedly greater today.
Many surgeons who remained skeptical in the recent
past, have now become advocates of selective IOL use in
children. A growing number of case series have now been
published supporting the safety and effectiveness of IOLs
for children beyond infancy. 21,22,33,34,45,47,49,51-53,63,66,
69,73,75,84,87,89,93,96,99,120,134-139,140,149,161,163-164,171,183,
184-191,201,202,207,209,211-221,225,229-234,237,243,249,255,258,260,261,264

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Why are IOLs preferred for pediatric cataract surgery?


Several reasons can be cited for the increased use of IOLs
in children. The three most important are:
First, appropriately sized (11.5-12.0 mm), more flexible implants made from PMMA and acrylic foldable
materials are now available and can be inserted much
more easily into the capsular bag of the child. Despite
their increased flexibility, newer lens designs retain
enough memory to resist the intense equatorial
capsular fibrosis seen in children after implantation.
In addition, PMMA as an implant material now has a
tract record of biocompatibility that extends to thirty
or more years. Heparin surface modification of PMMA
has increased its biocompatibility even more.22 Also,
copolymerization of different acrylate and methacrylate acids had resulted in foldable lenses that have
retained the biocompatibility features of PMMA. As
an example, foldable acrylic lenses, such as the
AcrySof are also being implanted into childrens
eyes with greater frequency. The biocompatibility of
the acrylic lenses may be equal or exceed the tried
PMMA lenses. The foldable acrylic lenses are easier
to insert in a small eye, and the squared edge of the
AcrySof IOL optic design result in delayed PCO in
young eyes (D. Stager, Foldable Acrylic Intraocular
Lenses in Children, presented at the annual meeting
of the American Academy of Ophthalmology, San
Francisco, California, USA, October 1997; M.E. Wilson,
D.R. Holland, In-the-bag Secondary Intraocular Lens
Implantation in Children, presented at the
symposium on Cataract, IOL, and Refractive Surgery,
San Diego, California, USA, April 1998; and L. Shastri,
R. Trivedi, A. Vasavada, AcrySof implantation in
Congenital Cataract Surgeryan update, presented
at the symposium on Cataract, IOL, and Refractive
Surgery, Boston, MA, USA, May 2000). Pavlovic and
coworkers190 reported that foldable silicone IOL
implantation in children is also a safe procedure with
stable short-term anatomic results.
The second reason for the increased use of IOLs in
children is the improved understanding of the
surgical principles and refinements in surgical
techniques that have ensured capsular fixation of an
IOL even over the extended life span of a child. Capsular fixation provides sequestration of the implant
away from vascularized tissues. Although ciliary
sulcus fixation of the IOL may also be safe with short
follow-up, uveal contact for a lifetime is not desirable. In addition, complications such as pupillary
capture and IOL decentration are more common with
ciliary sulcus fixation. The preference for capsular
fixation over ciliary sulcus placement has resulted in

more IOLs being implanted in children at the time of


cataract extraction, even at very young ages.
Finally, customized management of the anterior and
posterior capsules for the pediatric eyes at the time
of implantation has improved outcomes and decreased complications.
IOL implantation at the time of cataract surgery is
rapidly becoming the commonest means of optical correction for children beyond infancy. An IOL can provide
a full time correction with optics that closely simulates
those of the crystalline lens.151 However, concern still
remains about the unknown risks of an IOL over the long
life span of a child. In addition, predicting the refractive
change of even older children is difficult since individual
variation is common.
Is IOL implantation feasible for infantile cataracts? In
contrast to older children, there is no consensus about
when, if ever, to implant an IOL in the first 1 or 2 years of
life.50,204 Increased tissue reactivity and marked axial
length and refractive changes have been cited as contraindications to IOL use in the first 2 years of life. However,
Dahan and Salmenson66 reported 13 patients who had
posterior chamber IOLs implanted at age 18 months or
younger. With follow-up ranging from 1.2 years to 4.5
years, the IOLs were well-tolerated with no additional
surgical intervention needed. Primary posterior capsulectomy and anterior vitrectomy were performed in these
patients at the time of IOL placement. Vasavada and
Chauhan230 evaluated 21 eyes of 13 infants between 2
and 8 months of age who had primary posterior chamber
IOL implantation for congenital cataracts. Twelve eyes
had a posterior capsulorhexis or plaque peeling at the
time of IOL implantation and 1 eye had a vitrectomy.
Follow-up ranged from 6 months to 5 years. All eyes
developed one or more posterior synechiae and all,
except one, required secondary capsulectomy and
vitrectomy between 1 month and 1 year. Twenty eyes
attained stable IOL fixation and a clear visual axis in their
series. Patients with bilateral cataracts had greater visual
improvement than those with a cataract in 1 eye only.
Their findings revealed the benefits of posterior
capsulectomy and anterior vitrectomy if done in early
postoperative period. Oliver and co-workers182 included
patients as young as 10 months of age in their posterior
chamber lens implantation series. Other than a greater
propensity for PCO, the IOLs were as well-tolerated in
the infants and toddlers as they were in the older
children. Metge and co-workers171 reported placing
posterior chamber (PC) IOLs bilaterally in six patients
aged 4 to 6 months. With a mean follow-up of 2.5 years,
no complications related to the surgery were seen.

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Chapter 10: Update on Pediatric Cataract Management 81


More recently, Knight-Nanan and co-authors134 reported that 6 eyes with congenital cataracts implanted with
IOLs between 4 and 28 weeks of age had central steady
and maintained fixation postoperatively with a mean
follow-up of 66.4 weeks. Hutchinson and co-workers,120
in a series of 22 eyes of 17 children, evaluated the outcomes and ocular growth after IOL implantation in the
first 2 years of life. The follow-up ranged from 2 to 36
months. Although postoperative refractive error showed
a mean of 1.5 diopters, pseudophakic eyes demonstrated
a normal rate of growth when compared with their fellow
phakic eyes. No significant difference was seen in the
complication rates between pseudophakic patients and
the age-matched aphakic group. However, in 14 of 32
aphakic eyes (44%), a notation in the chart indicated that
the patient had stopped wearing glasses or contact lenses
for at least 2 months. According to the authors, IOL
implantation in younger children is not only a safe and
effective alternative to contact lens or spectacle correction
of aphakia but it also aids amblyopia treatment by eliminating periods of uncorrected aphakia. Dahan et al65
evaluated the lens choice and dioptric power in 156
pseudophakic eyes of 99 children aged 1 month to 8 years.
According to them, the younger the child at time of
implantation, the greater the myopic shift. To reduce the
necessity of the IOL exchange they suggested that an
infant should receive 80% of the IOL power need for
emmetropia, while in a toddler or a young child the IOL
power should correct 90 percent of the aphakia. This
leads to initial hypermetropia but it gradually moves to
emmetropia or moderate myopia in adulthood.
IOL power selection Although aforementioned reports
indicate that IOL implantation is technically feasible even
in early infancy, problems remain. Since the axial growth
of the eye is dramatic in early infancy, IOL power
selection is much more difficult. Keratometry, usually
very stable after eighteen months of age, is still
undergoing rapid change in early infancy. A multi-center
randomized clinical trial is being planned in hopes of
answering the question of whether primary intraocular
lens implantation or the use of contact lenses with
secondary intraocular lens implantation at an older age
produces better outcomes in unilateral congenital
cataracts.
Knight-Nanan et al,134 recommend the use of an IOL
which is lower by 6.00 diopters than one needed for
emmetropia to compensate for the expected myopic shift
when implanting infants younger than one year of age.
The residual refractive errors are managed with spectacles. However, when an IOL is implanted in the first
month of life, we are often faced with residual hyperopia

as high as 10 diopters. A contact lens may be needed for


a few months until the residual hyperopia decreases to
the 4 to 6 diopters range. Spectacles can then be more
easily used. Since contact lens wear is easiest in early
infancy and much more difficult as the toddler age is
approached, this treatment scheme has been successful.
For children beyond age 2, data are available to help
the surgeon predict the growth of the eye on average.95,165167,194 When operating on children between the ages of 2
and 8 years, many surgeons have advised selecting an
IOL power that will leave mild to moderate hyperopia,
milder with increasing age.63,230,254 Awner and associates19 have suggested aiming for a postoperative refraction of +4.00 for children younger than age two, +3.00
diopters for children age two to four, +2.00 diopters for
age four to six, +1.00 diopters for age six to eight, and
emmetropia for children older than eight years of age at
the time of implantation. Other authors have advocated
aiming for emmetropia regardless of age when operating
beyond age two. This approach avoids potentially
amblyogenic residual hyperopia but is likely to lead to
the development of significant myopia later.
Modern theoretical IOL formulas are usually used in
adults to calculate the IOL power most likely to achieve
the desired postoperative refraction. In a recent study4
we applied the Sanders-Retzlaff-Kraff (SRK) II, SRK-T,
Holladay, and Hoffer Q formulas to measurements from
47 consecutive IOL implantation in children. The eyes
were divided into short (less than 22 mm in axial length)
medium (axial length > 22 mm but less than 24 mm) and
long (> 24 mm) groups. While the average error (1.2 to
1.4 diopters for all formulas) was larger than usually
expected in adults, no formula outperformed any other.
The errors were as often below the target refraction as
above it. All axial length and keratometry measurements
were made under anesthesia to avoid error from poor
patient cooperation.
How important is IOL sizing? The mean axial length of
a newborns eye is 17.0 mm compared to 23 to 24 mm in
an adult. The pediatric eye, especially in the first 1 to 3
years of life, is significantly smaller than the adult. This
has led to concerns with implantation of adult-sized IOLs
in these patients. In an effort to determine the size of the
pediatric lens, Bluestein et al 44 examined 50 fresh,
nonpreserved autopsy eyes from patients ranging in age
from 1 day to 16 years. A variety of measurements were
made, including the anteriorposterior, vertical, and
horizontal lengths of the globe, corneal diameter, lens
diameter and the diameter of the zonular free zone. The
most rapid lens growth occurred from birth to 2 years of
age.

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82

Section I: Cataract

To evaluate the stretching of the capsular bag, implantation of rigid PMMA and foldable acrylic IOLs was
performed in 2 postmortem eyes obtained from six and
21 days old infants (J. Ram, S.K. Pandey, A. Hutchinson,
M.E. Wilson, D.J. Apple, Infantile cataract surgery: How
important is IOL sizing? Video presented at the ASCRS
Symposium of Cataract, IOL and Refractive Surgery,
April 1999, Seattle, WA, USA). After excising cornea and
iris, both eyes were prepared using the posterior video
technique of Miyake-Apple.9,173 A capsulorhexis of 3.5
to 4.0-mm size was performed using the Utrata forceps.
Cortical cleaving hydrodissection was performed and
this was followed by aspiration of the lens substance.
The soft cortex and lens epithelial cells were removed
from the anterior and equatorial capsules. A one-piece,
all PMMA IOL with a 5-mm optic and 12 mm overall
size was implanted into the capsular bag. This was
followed by implantation of a foldable hydrophobic
acrylic IOL with a 5.5-mm optic size and 12-mm overall
length. The vertical and horizontal capsular bag
diameters were measured before and then parallel and
perpendicular to the haptics after the IOL implantation.
Marked ovaling of the capsular bag, parallel to the IOL
haptic, was noticed in both eyes after implantation of
adult sized IOLs. The mean capsular bag stretching was
found to be 42 percent (six days old) and 40 percent (21
days old). Figures 10.8A and B show ovaling of the
capsular bag after implantation of the PMMA and acrylic
IOLs.
Wilson and coworkers246 conducted an experimental
IOL implantation study in 50 pediatric eyes obtained
postmortem to determine the biomaterials, designs, and
sizes that may be appropriate for pediatric implantation.
Based on this study, using the Miyake-Apple posterior
video technique, these researchers recommended the
following guidelines:
Clinical trials of capsular IOLs, downsized to approximately 10.0-mm diameter, are appropriate for children under two years of age. Capsular IOLs are defined
as flexible open loop, one-piece, all PMMA, modified
C-loop designs made especially for in-the-bag
placement.
Because the rapid growth phase of the lens is complete
by the age of two, downsizing the IOL is not necessary
after this age unless axial length measurements indicate an unusually small eye. Standard flexible 12.0
to 12.5-mm diameter capsular IOLs can be safely
implanted. Such lenses could be tolerated throughout
the life, obviating the need for later IOL exchange.
Changes in ocular and refractive growth In addition to
the lens size and selection decisions arising from normal
pediatric eye growth, implantation of a device into the

Figs 10.8A and B: Anterior (surgeons view) of a 5.5 mm optic


posterior chamber IOL fixated in the capsular bag, of the eye
of a 21-day-old infant, obtained postmortem. Note the ovaling
of the capsular bag parallel to the IOL haptics (A) Foldable
AcrySof IOL (B) Rigid PMMA IOL

newborn eye can in itself induce changes in ocular development.83,98,152-154,159,199,242,243,245, In studies published by
Kugelberg et al,144-147 implantation of large-sized capsular tension rings (10 mm) and adult-sized PMMA
IOLs in young rabbits resulted in significant reduction
in eye growth compared to aphakic eyes. Interestingly,
implantation of smaller capsular tension rings (7 mm)
and silicone IOLs did not seem to result in as much axial
growth retardation. The authors speculated that this
might occur via a mechanism similar to that noted in
patients experiencing ocular growth retardation
following peripheral retinal ablation.

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Chapter 10: Update on Pediatric Cataract Management 83


In a multicenter, retrospective observational case
series, McClatchey and co-workers165 compared the rate
of refractive growth (according to a logarithmic model
used to predict future refractions of a childs pseudophakic eye) in pseudophakic childrens eye to that of
aphakic eye. One hundred eyes of 83 pseudophakic
patients and 106 eyes of 74 aphakic patients, aged at
3 months and 10 years were evaluated for age at surgery,
IOL power, IOL A-constant, initial postoperative refraction, final refraction, and final age. The follow-up period
was 3 years or more, depending on the age at surgery.
They noted that overall, pseudophakic eyes showed a
lesser rate of refractive growth than aphakic eyes.
Nevertheless, the mean quantity of myopic shift was
greater in pseudophakic eyes than in aphakic eyes,
despite of shorter follow-up time in aphakic eyes. This
is due to the optical effects of a constant IOL power in a
growing eye. These authors concluded that pediatric
pseudophakic eyes have a slightly lesser rate of refractive
growth than aphakic eyes.
SURGICAL TECHNIQUES
Historical Perspective
The initial reluctance of the pediatric ophthalmic community to endorse primary implantation of PC-IOLs in

children was related in part to the perceived need for an


intact posterior capsule. Surgeons experienced in removing neonatal and infantile cataracts feared returning to
the days of dense secondary membranes and frequent
repeat surgeries. 150 Technical advances have now
resulted in several options for opening the posterior
capsule without eliminating the possibility of IOL
placement within the capsular bag. In addition, even
when the posterior capsule is left intact, the combination
of more complete cortical removal and the presence of
an intraocular lens in the capsular bag have resulted in a
lower incidence of, or at least a delay in posterior capsule
opacification.
Table 10.2 summarizes the major advances
influencing the pediatric cataract surgery procedure
during the last three decades that considerably popularized the use of IOL implantation in children.100,104,105,250
Scheie206 popularized the technique of manual aspiration
of congenital and juvenile cataracts. After a successful
implantation of an IOL in an adult by Herold Ridley200
in 1949, Peter Choyce57 reported the implantation of an
IOL in a 10-year-old child as early as 1958. Binkhorst35-40
first implanted iridocapsular fixated IOLs in children in
1959. Hiles, BenEzra and coworkers27-31 have extensively
studied the use of intraocular lens in pediatric cataract
and their complications. Use of a vitreous suction cutter

Table 10.2: Evolution of pediatric cataract surgery


ADVANCES

YEAR

AUTHOR(S)

ADVANCES

First Implant in a
Child for the
Aphakic Correction
Manual Aspiration of
Congenital/Juvenile
Cataract
Iridocapsular Implant
Binkhorst Intraocular
Lenses (IOLs)
Posterior Chamber
IOLs
Iris-Claw Lenses
Pathophysiology
of Amblyopia
Posterior Chamber
IOLs
Posterior Capsulotomy
Anterior Vitrectomy
Epikeratophakia
Epilenticular
IOL/Pars Plana
Endocapsular
Lensectomy

1958

Choyce

1960

Scheie

1969
1977-82

Binkhorst
Hiles

1982

Hiles

1983
1977-85

Singh
Weisel/Raviola

1983-93

Sinskey/Hiles

1983

Parks

Retropseudophakic
1991
Vitrectomy via Limbus
Retropseudophakic
1993
Vitrectomy + Posterior
Capsulectomy via Pars Plana
Primary Posterior
1994
Capsulorhexis/Optic Capture
IOL Biomaterials/
Designs/Sizing
1994
in Children
Primary Posterior
1994-96
Capsulotomy and Ant
Vitrectomy
Anterior Capsulotomy
1994
for Pediatric Cataract
Surgery

1986
1988

Morgan
Tablant

YEAR

Heparin in BSS to Decrease 1995


Postoperative Inflammation
Dye-Enhanced Pediatric
2000
Cataract Surgery

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AUTHOR(S)
Mackool/
Chhatiawala
Buckley et al

Gimbel/DeBroff

Wilson et al
Ben Ezra/Cohen
Koch/Kohnen
Wilson et al
(Vitrectorhexis)
Auffarth et al
(Rabbit Model)
Brady et al
Pandey/Werner

84

Section I: Cataract

to perform a posterior capsulectomy and vitrectomy


while removing a congenital or juvenile cataract was
advocated by Parks in 1983.188 This represents one of the
major advances revolutionizing the cataract surgery in
infants. Although recurrent membrane formation had
been very common after the infantile cataract surgery,
second surgeries became rare. Removal of all but 2 mm
of the peripheral posterior lens capsule with a vitreous
suction cutter was recommended as well as a generous
anterior vitrectomy. While this procedure reduced the
risk of amblyopia by virtually eliminating secondary
membranes, it was incompatible with primary in-the-bag
fixation of an IOL or secondary sulcus fixation of an IOL.
In consideration of secondary sulcus fixated posterior
chamber IOL at an older age, most pediatric ophthalmic
surgeons today modify the Parks procedure to leave
enough residual capsule to support the IOL when it is
later placed in the ciliary sulcus.
Anesthesia
Most pediatric cataract surgeries are done under general
endotracheal anesthesia. Thus, the occurrence of
vomiting in the early postoperative period is not
uncommon. This, along with inevitable rubbing of eyes,
helps to justify the use of sutures to close the surgical
wound even if it appears to be self-sealing. Children also
have a very active Bells phenomenon if they become
somewhat light under anesthesia. For this reason, many
pediatric surgeons still use a superior rectus traction
suture during cataract surgery.
Wound Construction
Children have thin sclera and markedly decreased scleral
rigidity when compared with adults. Scleral collapse
results in increased vitreous upthrust (positive vitreous
pressure). Collapse of the anterior chamber and prolapse
of iris tissue are also much more common when operating
on pediatric eyes. Pediatric cataracts can be removed
through a relatively small wound, as the lens can be
removed in toto since there is usually no formed nucleus.
Therefore, wounds should be constructed to provide a
snug fit for the instruments that pass into the anterior
chamber. When an IOL is not being implanted, two stab
incisions are usually made at or near the limbus. These
incisions should not be larger than necessary for the
instruments being used. For instance, a microvitreoretinal
(MVR) blade creates a 20-gauge opening that is ideal for
a 20-gauge vitrector/aspirator to enter the anterior
chamber. A 20-gauge blunt tipped irrigating cannula can
also be used through a separate MVR blade stab incision.

If the instrument positions need to be reversed, the snug


fit is maintained. An anterior chamber entry of 3 mm or
less can facilitate manual anterior capsulotomy and
cortical aspiration with a phacoemulsification or irrigation/aspiration handpiece. When a rigid IOL is being
implanted, a scleral tunnel wound is utilized most often.
A half thickness scleral incision is made initially
approximately 2 or 2.5 mm from the limbus and dissected
into clear cornea. It is enlarged to the size necessary for
IOL insertion. Scleral tunnel wounds decrease the incidence of iris prolapse into the wound during surgery and
assist the surgeon in preventing collapse of the anterior
chamber, which occurs with greater frequency in the soft
eyes of children. Unlike adults, scleral tunnel incisions
do not self-seal in children.91 According to the study by
Basti et al25 self-sealing wounds failed to remain watertight in children below 11 years of age, especially when
an anterior vitrectomy was combined with cataract
extraction. In older (> 11 years) children the wounds
remained self-sealing. The authors attributed this to low
scleral rigidity resulting in fish mouthing of the wound
leading to poor approximation of the internal corneal
valve to the overlying stroma. Closure is recommended
using a synthetic absorbable suture such as 10-0 Biosorb
or Vicryl. When a foldable IOL is being implanted, a corneal tunnel is preferred since it leaves the conjunctiva
undisturbed. The corneal tunnel should begin near the
limbus (so-called near clear incision) for maximum
healing and should be sutured with a synthetic
absorbable suture.
While the temporal wound presents the same advantages in children as it does in adults, the location is more
easily traumatized by children. The superior approach
allows the wound to be protected by the brow and the
Bells phenomenon in the trauma prone childhood years.
Both scleral tunnels and corneal tunnels can be easily
made from a superior approach since children rarely have
deep set orbits or overhanging brows. Locating the site
of tunnel according to the pre-existing astigmatism (e.g.
temporally in against-the-rule astigmatism) can help in
reducing the astigmatic component in the postoperative
treatment of amblyopia.
Viscoelastic Substances
A high molecular weight viscoelastic substance such as
sodium hyaluronate 14 mg/per ml (Healon GV,
Pharmacia Corp. Peapack, NJ, USA) is most commonly
used in pediatric cataract surgery to effectively resist the
increased tendency for anterior chamber collapse due to
decreased scleral rigidity and a positive vitreous
pressure. This viscoelastic helps to maintain a deep

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Chapter 10: Update on Pediatric Cataract Management 85


anterior chamber and a lax anterior capsule, facilitating
attempts at manual anterior capsulorhexis. Also, the
initially convex posterior capsule is effectively held back
during IOL insertion. We have also recently evaluated
the use of viscoelastic with even higher viscosity, sodium
hyaluronate 23mg/per ml (Healon 5, Pharmacia Corp.
Peapack, NJ, USA) during pediatric cataract surgery. This
viscoadaptive appears to be useful during various steps
of pediatric cataract surgery (R. Trivedi, A. R.Vasavada,
D. J. Apple, J. Ram, L. Werner, S.K. Pandey, et al Healon
5: helping hand to congenital cataract surgeon? Video
Presented at the ASCRS Symposium of Cataract, IOL and
Refractive Surgery, San Diego, CA, USA, April/May
2001). Without a high molecular weight viscoelastic, an
IOL inserted in a manner acceptable for an adult eye will
result in inadvertent sulcus placement secondary to the
posterior vitreous pressure and posterior capsule
convexity. The trabecular meshwork of children clears
viscoelastic substances more easily, on average, than in
adults. However, efforts should still be made to remove
all of the viscoelastic material since postoperative
intraocular pressure spikes have been documented when
Healon GV is inadequately removed.76
Anterior Capsule Management
Manual Continuous Curvilinear Capsulorhexis
The ideal anterior capsulectomy technique in pediatric
patients would be one that is easy to perform and yet
results in a low incidence of radial tears.6,18 While a
manual continuous curvilinear capsulorhexis (CCC) is
ideal for adults,90 it is more difficult to perform in young
eyes. The pediatric capsule is very elastic and requires
more force before tearing begins.131 When performing a
CCC, control of the capsulectomy and prevention of
extensions out toward the lens equator are inversely
related to the force needed to generate the tear. Despite
these difficulties, manual CCC, when it can be controlled
and completed, remains the gold standard since it creates
an edge that results in the lowest incidence of radial tears.
As in adults, radial tears extending outward from the
anterior capsulectomy margin can promote decentration
of the IOL by allowing one of the haptics to exit the
capsular bag. This is known as the pea pod
effect. 14,15,241 Since children have a greater tissue
reactivity and more intense capsular fibrosis, asymmetric
loop fixation may result in an even higher rate of
decentration in children than in adults.
Vitrector-cut Anterior Capsulectomy (Vitrectorhexis)
Wilson and coworkers have tested a mechanized circular
anterior capsulectomy in both laboratory and clinical

settings. It had proven to be a very good alternative to


CCC for young children where the CCC may be difficult
to control. 3,247,252,253,256 This technique, known as
vitrectorhexis, is best performed using a vitrector tip
attached to a Venturi pump irrigation and aspiration
system. The capsulectomy is not started with a bent
needle cystotome. Rather, the vitrector tip is placed
through a tight fit stab incision at the limbus or through
a scleral tunnel. Irrigation is provided with a sleeve
surrounding the vitrector or through a separate stab incision. A cut rate of 150 cycles per minute is recommended.
With the cutting port oriented posteriorly, the center of
the anterior capsule is aspirated into the cutting port to
create an initial opening. Any nuclear or cortical material
that spontaneously exits the capsular bag anteriorly is
easily aspirated without interrupting the capsulectomy
technique.256 The capsular opening is enlarged using the
cutter in a gentle circular fashion. The cutter is kept just
anterior to the capsular edge, aspirating the capsule up
into the cutting port rather than engaging the capsular
edge directly. Visualization of the capsular edge during
enlargement of the capsulectomy is excellent because the
aspirating capability of the vitrector continuously
removes lens cortex as it enters the anterior chamber. A
smooth round capsulectomy can be produced that resists
radial tearing. One of us (MEW) has performed more
than 150 successful anterior capsulectomies in children
using this technique.253
Bipolar Radiofrequency Capsulotomy
A continuous curvilinear capsulotomy can also be created
by a high frequency endodiathermy. Although designed
to produce an anterior capsulotomy in adults, it is
well-suited for the elastic pediatric anterior capsule.61,62,141,142,174 The instrument was invented by Kloti133
and is manufactured by Oertli (Berneck, Switzerland).
The handpiece is 0.6 mm in diameter. The platinum tip
is insulated. A high frequency modulation (500 kHz)
signal is delivered with amperage and voltage
preselected and fixed within the unit by the
manufacturer. A low mean energy is delivered which
minimizes the cutting energy and decreases heat
generation. The base of the needle tip is placed in contact
with the anterior capsule as the tip is activated by
pressing the foot pedal. The capsulotomy size and shape
are controlled by the surgeon as the tip is moved along a
circular path. Gas bubbles form as the capsule is cut but
they do not usually interfere with visualization of the
capsulotomy edge. The procedure is performed under
viscoelastic. The capsular edge tends to roll up slightly
which creates a slightly larger capsulotomy than initially
cut with the instrument tip.224

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86

Section I: Cataract

Lens Substance Removal


Pediatric cataracts are soft. Phacoemulsification is rarely
if ever needed. Lens cortex and nucleus usually easily
aspirated with an irrigation/aspiration or vitrectomy
handpiece. When using the vitrector, bursts of cutting
can be used intermittently to facilitate the aspiration of
the more gummy cortex of young children. The
phacoemulsification handpiece can also be very useful
when aspirating pediatric lens material. Hydrodissection78,80 has been thought to be less useful in children
than in adults. However, a recent study has shown the
intraoperative benefits of performing multiquadrant
hydrodissection. The benefits are: overall reduction in
the operative time, and the amount of irrigating solution
used and facilitation of lens substance removal (R.
Trivedi, A.R. Vasavada, D.J. Apple, J. Ram, S.K. Pandey,
L. Werner. Cortical cleaving hydrodissection in congenital cataract surgery, Presented at the ASCRS Symposium
on Cataract, IOL and Refractive Surgery, San Diego, CA,
USA, May 2001). A fluid wave can sometimes be
generated in older children but not reliably in infants
and toddlers. Cortical material strips easily from the
pediatric capsule even in the absence of hydrodissection.
Attempts at hydrodelineation should be discouraged in
children since it does not aid in lens removal and may
lead to capsular rupture.
Primary Intraocular Lens Implantation
Capsular fixation of the IOL is strongly recommended
for children.78,184,250 Care should be taken to avoid asymmetric fixation with one haptic in the capsular bag and
the other in the ciliary sulcus. In contrast to adults, dialing
of an IOL into the capsular bag can be difficult in
children. An oversized IOL (adult IOL - 12 to 12.5 mm)
along with the vitreous upthrust often cause the IOL
to vault forwards which results in its dialing out of the
capsular bag. On the other hand, sulcus fixation of an
IOL in a child appears to be easy but the long-term
consequences of contact with vascularized uveal tissue
is a cause for concern. To minimise the iris-optic contact,
lens decentration and to reduce the possibility of erosion
into the ciliary body, prolapse of the optic through an
intact anterior or posteior capsulotomy is suggested
when sulcus fixation of an IOL in a child is necessary.

implant is placed into the ciliary sulcus.67 Since the sulcus


is only 0.5 to 1.0 mm larger than the evacuated capsular
bag, most IOLs designed for capsular fixation can also
be placed in the ciliary sulcus. Viscodissection is often
all that is needed to break synechia between the iris and
residual capsule. Both the AcrySof acrylic lens and the
all-PMMA lenses have been used by the authors for
sulcus fixation in the child (M.E. Wilson, D.R. Holland,
In-the-bag Secondary Intraocular Lens Implantation in
Children, presented at the symposium on Cataract, IOL,
and Refractive Surgery, San Diego, California, USA, April
1998). Our current recommendations are to place an allPMMA heparin-surface-modified IOL rather than an
acrylic lens when sulcus placement is required.
Prolapsing the IOL optic through the fused anterior and
posterior capsule remnants is useful in preventing
pupillary capture and assuring lens centration. In some
cases, the anterior and posterior capsular remnants can
be dissected apart allowing the IOL to be placed in the
capsular bag. 207 An exuberant Soemmerings ring
formation will often separate the anterior and posterior
capsule leaflets and maintain the peripheral capsular bag.
This material can be aspirated cleanly after the anterior
capsule edge is lifted off of the posterior capsular edge
to which it is usually fused.
When inadequate capsular support is present for
sulcus fixation in a child, implantation of an IOL is not
recommended unless every contact lens and spectacle
option has been fully explored. Although their long-term
safety is unknown, modern flexible open loop anterior
chamber lenses seem to be well-tolerated in children
when their anterior segment is developmentally normal.
Scleral fixation of posterior chamber IOLs in children
have been well-tolerated according to some recent
studies, but complications such as pupillary capture,
suture erosion and refractive error from lens tilt or
anterior/posterior displacement have been reported.149,209,261 The ab-externo approach is recommended
for trans-scleral suture placement in children.
Management of the Posterior Capsule
Management of the pediatric posterior capsule,
especially when implanting an IOL at the time of the
primary surgery remains controversial. 160 Several
surgical techniques have been used by various surgeons
to maintain the long-term clear visual axis.

Secondary Intraocular Lens Implantation


The vast majority of children undergoing secondary
intraocular lens implantation have had a primary
posterior capsulectomy and anterior vitrectomy. If
adequate peripheral capsular support is present, the

Primary Posterior Capsulotomy and


Anterior Vitrectomy
Primary posterior capsulectomy and anterior vitrectomy
during pediatric lensectomy were popularized by Parks

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Chapter 10: Update on Pediatric Cataract Management 87


in the early 1980s.188 This led to a dramatic decrease in
the need for secondary surgery for congenital cataracts.
Pediatric ophthalmologists are accustomed to removing
a portion of the posterior capsule and the anterior
vitreous at the time of lensectomy. An increase in late
complications from primary capsulectomy and
vitrectomy has not been reported. Adult cataract
surgeons are often more reluctant to perform a primary
capsulectomy and vitrectomy for fear that the risk of
retinal detachment or cystoid macular edema will be
increased. In point of fact, these complications are
exceedingly rare after pediatric cataract surgery with or
without a primary capsulectomy and vitrectomy.
Neodymium: YAG laser posterior capsulotomy is usually
necessary in children when the posterior capsule is left
intact. This procedure also carries a risk of retinal
detachment and cystoid macular edema. In addition,
larger amounts of laser energy are often needed when
compared to adults and the posterior capsule opening
may close requiring repeated laser treatments or a
secondary pars plana membranectomy.
Dahan and Salmenson 66 have recommended
posterior capsulotomy and anterior vitrectomy in every
pediatric cataract patient younger than eight years.

Vasavada and Desai231 also advise anterior vitrectomy


along with primary posterior continuous circular
capsulorhexis (PCCC) in children younger than 5 years
of age. Metge and co-workers171 have shown that a
posterior capsulectomy without a central vitrectomy did
not prevent the development of a secondary membrane.
The opacification rate was not significantly decreased
by a posterior capsulectomy alone. Only when an
anterior vitrectomy was added did the opacification rate
fall. Vasavada and Trivedi, 232 in a prospective and
randomized study, have also shown that visual axis
obscuration by reticular fibrosis of the anterior vitreous
phase occurred in 70 percent of those eyes in which
vitrectomy was not done following PCCC. As opposed
to this, no eye developed visual axis obscuration when a
PCCC was combined with anterior vitrectomy (Figs
10.9A and B). Also, these eyes performed better for low
contrast sensitivity testing. All these results suggest that
anterior vitrectomy is not only beneficial but also
necessary in children aged 5 to 12 years.233
Posterior Capsulorhexis with
Intraocular Lens Optic Capture
Gimbel and DeBrof 88,92,93 recommend performing a
posterior capsulorhexis with IOL optic capture. This tech-

Figs 10.9A and B: Two different cases of in-the-bag IOL fixation in combination with primary posterior capsulotomy and
anterior vitrectomy. This procedure is helpful to maintain a clear visual axis in younger children (courtesy: A. R. Vasavada, MD,
FRCS, Ahmedabad, India) (A) Clinical photograph post implantation of an all PMMA IOL in which a primary posterior capsulotomy
with anterior vitrectomy were performed at the time of primary surgery. The posterior capsule within the visual axis remained
clear 1-year postoperatively. Note however the presence of some cell deposits on the IOL surfaces (B) Acrylic (AcrySof) IOL
implanted in the capsular bag of a 4-year-old child. A primary posterior capsulorhexis and anterior vitrectomy were performed.
This photograph was taken 1-year postoperatively. There are several Elschnig pearls outside the IOL optic, but the visual axis
is clear

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88

Section I: Cataract
of cataract extraction. They recommended a primary
posterior capsulectomy and anterior vitrectomy at the
time of primary lens implantation in children who are
not expected to be suitable candidates for awake
Neodymium: YAG capsulotomy within 18 months of
surgery. IOL exchange, if needed later, will be more
difficult if optic capture has been used.

Fig. 10.10: Photograph of an eye implanted with an acrylic


(AcrySof) IOL in the capsular bag. IOL optic capture through
a posterior capsulorhexis was performed during the primary
procedure. This photograph was taken at 1 month
postoperatively and shows well centered IOL and anterior and
posterior capsulorhexis edges (courtesy: A. R. Vasavada, MD,
FRCS, Ahmedabad, India)

nique is designed to help prevent secondary membrane


formation without necessitating a vitrectomy. 79 It
also ensures centration of the posterior chamber IOL
because the haptics remain in the capsular bag and the
optic is captured in the posterior capsular opening (Fig.
10.10). Vasavada and Trivedi232 also reported a better
centration of the IOL following optic capture. However,
they have also expressed concern regarding the resultant
increased predisposition to uveal inflammatory sequelae.
The same authors,232 along with other surgeons135,136
have reported opacification of the visual axis despite
optic capture. Thus they recommend performing an
anterior vitrectomy even when optic capture is utilized
through the posterior capsulorhexis.
Neodymium (Nd): YAG Laser Posterior Capsulotomy
Atkinson and Hiles,17 on the other hand, recommended
leaving the posterior capsule intact even in very young
children and performing Neodymium: YAG capsulotomy
under a second general anesthesia in the early postoperative period. Subsequently, however, the same group
reported a 41 percent need for repeating laser capsulotomy when this protocol was followed. Interestingly,
Plager et al194 reported that in their patients, the incidence
of PCO began to increase markedly at approximately 18
months after surgery, independent of the age at the time

Options for primary posterior capsulotomy When a


decision is made to perform a primary posterior capsulotomy, several options are available.26,92,240 The posterior
capsular opening can be made using a manual PCCC
technique or using an automated vitrector or the Kloti
radiofrequency bipolar unit. The manual technique and
the mechanized vitrector technique can each be performed either before or after the intraocular lens has been
placed in the eye. When the vitrector is used after the
IOL has been placed, it is usually done via the pars plana.
The radiofrequency bipolar unit is not easily manipulated
beneath an IOL and is therefore usually performed on
the posterior capsule from an anterior approach prior to
IOL insertion. In most instances, an anterior vitrectomy
is performed simultaneously with the posterior
capsulectomy.
DYE-ENHANCED PEDIATRIC CATARACT SURGERY
Use of capsular dyes such as 2 percent fluorescein
sodium, 0.5 percent indocyanine green (ICG), and 0.1
percent trypan blue for staining the anterior capsule,
while performing CCC in white/advanced adult cataract
cases is well known. We recently reported our experience
of anterior capsule staining for performing CCC in postmortem human eyes with advanced/white cataracts.185
We also reported the use of capsular dyes to enhance
visualization to learn and perform other critical steps of
the phacoemulsification procedure, and posterior capsulorhexis, respectively 186,243b (S.K. Pandey, MD;
L. Werner, MD, PhD; D.J. Apple, MD, et al. Anterior
Capsule Staining in Advanced Cataracts: A laboratory
study using postmortem human eyes, presented at the
annual meeting of the American Academy of Ophthalmology, Orlando, Florida, October 1999; S.K. Pandey,
MD; L. Werner, MD, PhD; D.J. Apple, MD, et al. Dyeenhanced Cataract Surgery in Human Eyes Obtained
Postmortem: A Laboratory Study to Learn and Perform
Critical Steps of Phacoemulsification, prize winning
video (second place, Scientific Value), presented at the
ESCRS Symposium on Cataract, IOL, and Refractive
Surgery, Vienna, Austria, September 1999). Learning the
posterior continuous curvilinear capsulorhexis (PCCC)
procedure (and achieving a consistent size of posterior
capsule opening for performing the optic capture) can

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Chapter 10: Update on Pediatric Cataract Management 89


be difficult for the beginning surgeon due to the thin and
transparent nature of the posterior capsule. According
to our experimental studies, posterior capsulorhexis
(with or without the optic capture) is relatively easy to
perform after staining of the otherwise transparent
posterior capsule (Figs 10.11A and B). The procedure of
optic capture with or without anterior vitrectomy can
also be accomplished easily after staining the posterior
capsule.186 It is easier to localize an inadvertant tear of
the posterior capsule when staining of the posterior
capsule has been utilized (Fig. 10.11C).
PEDIATRIC TRAUMATIC CATARACTS AND
THEIR MANAGEMENT
Epidemiology and Etiology
Traumatic cataract in children is a common cause of
unilateral loss of vision.60 Incidence of traumatic cataract
in children is reported as high as 29 percent of all childhood cataracts.72 Penetrating injuries are usually more
common than blunt injuries. Eighty percent of traumatic
cataract cases occur in children while playing or when
they are involved in sport-related activities. Injuries are
also caused by thorns, firecrackers, sticks, bow and
arrows.143
Surgical Management
At the time of presentation after the trauma to the eye,
primary repair of the corneal or scleral wound is usually
preferred. Cataract surgery with IOL implantation is
performed later following complete evaluation of
damage to the intraocular structures (e.g., posterior
capsule rupture, vitreous hemorrhage, and retinal
detachment) by ancillary methods such as B-scan
ultrasonography. 102 Some authors report PC-IOL
implantation at the same time as primary repair of
corneal lacerations and removal of traumatic cataract.5
We think repair of corneal or scleral wounds combined
with primary IOL implantation should be considered in
younger children at the risk of developing amblyopia.
Implantation of IOL is preferred in the cases of traumatic
cataracts with corneal injuries, because contact lenses
may be difficult to fit.123
Visual Results and Postoperative Complications
In sharp contrast to congenital and developmental cataracts, traumatic cataracts are mostly unilateral and often
associated with good visual prognosis in absence of
associated ocular trauma32,106,122 (M.M. Peterseim, S.K.
Pandey, L.E. Elliot, R. Saunders, M. E. Wilson, Intraocular

Figs 10.11A to C: Photographs of a pediatric eye obtained


postmortem, taken from anterior (surgeons view) illustrating
the use of the capsular dye to enhance visualization during
various steps of the pediatric cataract surgery (A) Posterior
capsulorhexis after the staining of the capsular bag with trypan
blue (B) Posterior capsulorhexis and optic capture of a foldable
IOL after the staining of the capsular bag with trypan blue
(C) Visualization of a posterior capsule tear after staining of
the capsular bag with indocyanine green

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Section I: Cataract

lens implantation in unilateral traumatic cataract in


children, poster presented at Annual congress of
American Association of Pediatric Ophthalmology and
Strabismus, Orlando, FL, USA, March 2001).
We recently reported our experience on the implantation of posterior chamber (PC) IOLs in 20 children (20
eyes) with traumatic cataracts.183,184,184a Capsular bag
fixation of a PC-IOL was performed in 10 eyes (group A)
and in other 10 eyes (group B) ciliary sulcus fixation was
performed (Figs 10.12A and B). Traumatic cataracts

associated with large corneal lacerations (10-mm or


more), hyphema, angle recession, or posterior segment
involvement were excluded. A best-corrected visual
acuity (BCVA) of 20/40 or better was achieved in 9 of 10
eyes (90%) in the group A and in 8 of 10 eyes (80%) in the
group B at the end of the mean follow-up period (24.6
10.6 months). The residual refractive error did not exceed
3.50 diopters in either group. In this prospective, randomized study, capsular bag fixation of PC-IOLs provided
similar visual results as was noted with ciliary sulcus
fixation but was associated with fewer postoperative
complications, particularly uveitis and pupillary capture.
In a comparable series of 8 cases of traumatic cataracts
in children Koenig et al137 reported 20/40 or greater visual
acuity in 87 percent (7 out of 8) eyes undergoing PC-IOL
implantation for pediatric traumatic cataracts. The
average follow-up in their series was 10 months. Gupta
et al99 reported that 9 (50%) of 18 children with unilateral
traumatic cataract achieved 20/40 (or greater) visual
acuity after IOL implantation, with an average followup of 12 months. In many cases corneal leucomata contributed for decreased postoperative visual acuity. Similarly,
Anwar et al,19 Bustos and co-authors,53 BenEzra and coauthors,27 and Eckstein et al73 reported visual acuity of
20/40 or better in 73.3 percent, 79.0 percent, 65.2 percent
and 67.0 percent of cases after traumatic cataract surgery
with PC-IOL implantation in children respectively. Table
10.3 summarizes the visual results and postoperative
complications concerning recent studies of PC-IOL
implantation in pediatric traumatic cataracts.
PERIOPERATIVE AND
POSTOPERATIVE TREATMENT

Figs 10.12A and B: Cataract surgery and in-the-bag fixation


of posterior chamber IOLs in pediatric traumatic cataracts
(A) Preoperative photograph of the anterior segment of a
6-year-old male child showing traumatic cataract and formation
of posterior synechia at 2.30 oclock position. The visual acuity
on presentation was 20/60 (B) Same eye 4 weeks postoperatively, showing the clear visual axis after cataract extraction
and capsular bag fixation of a posterior chamber intraocular
lens. The best-corrected visual acuity was 20/20

The perioperative routine includes a drop of 5 percent


povidone iodine at the beginning and at the end of the
surgical procedure. It is better to avoid using a miotic at
the completion of surgery since this can create increased
anterior segment inflammation. Topical steroid/
antibiotic and atropine ointment are put in the eye, and
a light patch and fox shield placed over the eye.
Beginning the next morning, topical steroid drops six
times a day and atropine 1 percent eyedrops once per
day for four weeks are recommended. A topical antibiotic
is added for the first several days. The atropine eyedrops
regimen is stopped at four weeks and the topical steroid
tapered and discontinued. The atropine is sometimes
avoided when an IOL is placed in the ciliary sulcus to
reduce the chances of pupillary capture. Glasses or an
eye shield is worn over the eye continuously for the first
week.

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Chapter 10: Update on Pediatric Cataract Management 91


Table 10.3: Studies of posterior chamber intraocular lens implantation in children with traumatic cataracts
Study

Number of Age range Mean


patients
(years) follow-up
(years)

Bienfait et al
Gupta et al***
Koenig et al
Anwar et al
Bustos et al
BenEzra et al
Eckstein et al
Pandey et al
*
**
***
****

23
22
8
15
19
23
52
20

04-11
3-11
4-17
3-8
3-15
2-13
2-10
4-10

6.5
0.9
0.8
3.2
0.7
6.2
2.9
2.5

BCVA*
(=/>6/12)
(%)
70.1
45
87
73.3
79
65.2
67
85

Fibr. ant.
uveitis
0
81.8
NR ****
NR
26
NR
19
45

Complications %
Pupillary
PCO**
capture
9
9
NR
NR
10.5
26
41
20

83
27
37
40
21
100
92
60

BCVA = best-corrected visual acuity


PCO = posterior capsule opacification
Four patients had an anterior chamber IOL
NR = not reported

POSTOPERATIVE COMPLICATIONS
AND MANAGEMENT
Complications associated with pediatric cataract surgery
continue to be a major concern for the ophthalmic surgeon. The risk of postoperative complication is higher
due to greater inflammatory response after pediatric
intraocular surgery.150 In many cases, these complications
may be the primary reason for a poor visual outcome.208
In some cases, the complications appear to be intrinsically
related to associated ocular anomalies that coexist with
the developmental cataract. Close follow-up, early
detection and management of the complications are
mandatory.
Early Onset
Uveitis

Fig. 10.13: Slit-lamp photograph of a young child after ciliary


sulcus fixation of a PMMA IOL. Note the formation of a membrane and multiple posterior synechiae

Postoperative anterior uveitis (fibrinous or exudative) is


a common complication due to increased tissue reactivity
in children. In a series of 40 eyes with congenital or developmental cataracts, incidence of fibrinous uveitis was
seen in as high as 57.5 percent eyes (S. K. Pandey,
J. Ram, L. Werner, D. J. Apple, Intraocular lens implantation in pediatric cataracts, presented at the symposium
on Cataract, IOL, and Refractive Surgery, Boston, MA,
USA, May 2000). In comparative studies, the reported
incidence of postoperative fibrinous anterior uveitis was
81.8 percent, 26.0 percent and 19.0 percent.99,130,283 Uveitis
results in fibrinous membrane formation, pigment
deposits on the IOL and posterior synechia formation
(Fig. 10.13).196,197 Frequent topical steroids and even syste-

mic steroids may be needed in selected cases to reduce


uveitis-related complications. Brady et al47 recommend
five units of intravenous heparin in 500 ml of irrigating
solution. According to recent studies, implantation of
heparin-surface-modified PMMA IOLs in children
reduces postoperative inflammation. Mullaney et al177
reported dissolution of pseudophakic fibrinous exudates
with the use of intraocular streptokinase (500-1000 IU)
without any adverse effect. Similarly, Klais and coworkers132 performed fibrinolysis in 11 eyes of 10 children
who developed severe fibrin formation despite intensive
topical steroid therapy. A complete resolution of fibrin
formation was seen in 90 percent of children after using
10 micrograms of recombinant tissue plasminogen

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Section I: Cataract

activator (rt-PA).155 Besides incomplete resolution and


recurrence of membranes, other complications of rt-PA
use include hyphema, dysfuction of corneal endothelial
cells and corneal band keratopathy. Other possibilities to
treat fibrin formation after pediatric IOL surgery are Nd:
YAG laser discission, simple mechanical discission, and
intraocular steroid (e.g. dexamethasone) delivery system
(Surodex).155 However, modern surgical techniques that
limit iris manipulation and ensure capsular bag fixation
of the IOL, have resulted in less postoperative inflammation even in small children.

clinically apparent in the postoperative period is between


48 and 96 hours postoperatively. Postoperative schedules
for evaluating these patients should be drafted with this
fact in mind in this era of ambulatory surgical therapy.
The risk of endophthalmitis may be lower than the
risks associated with general anesthesia in some
neonates. Therefore, some ophthalmologists have opted
to perform bilateral cataract surgery under one general
anesthesia in medically unstable infants. This point
remains controversial.
Noninfectious Inflammation

Corneal Edema
Transient corneal edema may occur in pediatric cataract
surgery but bullous keratopathy is a rare complication.203
Cataract surgery does not cause significant endothelial
cell loss in children. Reports on corneal endothelial cell
count in pediatric aphakia and IOL implantation have
shown no significant loss of endothelial cells.20,103,230
Corneal decompensation may occur if detergents (e.g.
glutaraldehyde) are used for sterilization of cannulas or
instruments and are not rinsed thoroughly before use in
the anterior chamber. Indeed, cannulas or tubing should
not be sterilized in glutaraldehyde solution as, even after
thorough rinsing, residual chemicals may remain.

Jameson and colleagues126 have described a benign syndrome of excessive noninfectious postoperative inflammatory response in young aphakic children. This
syndrome presents with excessive photophobia, tearing,
and even the inability to open the eyes postoperatively.
It may persist for days or even weeks and may preclude
the early contact lens fitting that initiates amblyopic
therapy. It is not clear whether steroids applied topically
or injected into the sub-Tenons space are efficacious in
shortening this benign inflammatory process.
Intermediate/Late Onset
Capsular Bag Opacification

Endophthalmitis
Endophthalmitis does occur after cataract extraction in
children. It is a rare complication and appears to occur
with the same frequency as in adult cataract patients.
The prevalence of endophthalmitis reported by Wheeler
and associates244 was 7/10,000 cases, after pediatric
cataract surgery. Common organisms are Staphylococcus
aureus, Staphylococcus epidermidis and Staphylococcus
viridence. Nasolacrimal duct obstruction, periorbital
eczema and upper respiratory tract infections are
important risk factors.94
Techniques to avoid the complication of endophthalmitis remain controversial in all cataract procedures.
Authorities advise the use of topical antibiotic
ophthalmic solutions applied to the cataractous eye for
24 hours preoperatively. Other authorities emphasize the
need to use an undiluted povidone-iodine (Betadine)
solution not only applied to the skin but also instilled in
the eye at the time of the operation to reduce the bacterial
flora in the operative field.
Identifying endophthalmitis in the young child is
often much more difficult than in the adult aphakic
patient. Careful slit-lamp examination may not be possible, even with a hand-held device. It should be recalled
that the most likely time for endophthalmitis to become

Opacification of the capsular bag universally occurs


following pediatric cataract surgery. It includes opacification of the anterior, equatorial and posterior capsules.
Excessive anterior capsule fibrosis and shrinkage of the
CCC opening can lead to difficulty in examining the
retinal periphery and occasionally the decentration of
the IOL.243a Figures 10.14A to C shows examples of
capsular bag opacification in 3 different pediatric cases.
PCO is the most common complication after pediatric
cataract surgery with or without IOL implantation.11,100
A recent report has indicated an age independent
dramatic rise in the incidence of PCO beginning at 18
months after surgery and reaching nearly 100 percent
overtime.194 PCO is amblyogenic if it occurs during the
critical period of visual development in the younger
children. In cases of dense, thick PCO, surgical posterior
capsulotomy combined with anterior vitrectomy may be
required to prevent amblyopia. Nd: YAG laser can also
be used to perform posterior capsulotomy when PCO is
not dense (Fig. 10.15). 17 The use of newer surgical
techniques such as primary posterior capsulotomy and
anterior vitrectomy, posterior capsulorhexis with optic
capture or posterior capsulotomy performed with endodiathermy of capsule have shown encouraging results
in maintaining a clear visual axis.24,26,30

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Chapter 10: Update on Pediatric Cataract Management 93

Fig. 10.15: Slit-lamp photograph of the anterior segment of a


7-year-old-male child 18 months following capsular bag fixation
of a posterior chamber intraocular lens. This patient required
Nd: YAG laser posterior capsulotomy for posterior capsule
opacification. There was also an opacification of the anterior
capsule including the capsulorhexis margin

Secondary Membrane Formation

Figs 10.14A to C: Clinical photographs showing examples of


delayed postoperative capsular bag opacification (and its
sequelae) after pediatric cataract surgery (A) Anterior capsule
opacification after phacoemulsification and implantation of an
AcrySof IOL in a 7-year-old child. Both eyes had a bestcorrected visual acuity of 20/40 (B) Dense anterior capsule
opacification after phacoemulsification and in-the-bag
implantation of a PMMA IOL in a 8-year-old child (C) Superior
decentration of in-the-bag fixated posterior chamber IOL 5
months following cataract surgery secondary to asymmetrical
capsular bag fibrosis in a 5-year-old child

Formation of secondary membranes is a common


complication of pediatric cataract surgery, particularly
after infantile cataract surgery.148,176,187,259 Nd: YAG laser
capsulotomy may be sufficient to open them in the early
stage. More dense secondary membranes usually need
membranectomy and anterior vitrectomy.170 Pupillary
membranes can occur postoperatively in children
whether an intraocular lens has been implanted or not.
Microphthalmic eyes with microcoria operated in early
infancy are at greatest risk, especially when mydriatic/
cycloplegic agents have not been used postoperatively.
When an IOL is in place, secondary membranes may form
over the anterior and/or posterior surface of the implant.
The incidence of secondary membranes after neonatal
or infantile cataract surgery has been reduced
dramatically by the no-iris-touch aspect of the closed
chamber surgery, by applying topical corticosteroids and
cycloplegic agents at frequent intervals postoperatively
and by performing posterior capsulectomy and an
adequate anterior vitrectomy.
Pupillary Capture
Placing the IOL in the capsular bag helps to prevent pupillary capture, a complication that is much more common
in children. It is associated with posterior synechia
formation and PCO. Incidence of pupillary capture after
pediatric cataract surgery varies from 8.5 to 41 percent.

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This was reported by several authors: Vasavada and


Chouhan230 in 33 percent (7 of 21 eyes), Basti et al26 in 8.5
percent (7 of 82 eyes), Brady et al47 in 14.2 percent (3 of 20
eyes) and Bustos et al53 in 10.5 percent (2 of 19 eyes).
Pupillary capture occurs most often in children younger
than 2 years of age, when an optic size less than 6 mm is
used and the lens is placed in the ciliary sulcus. In a series
of 20 cases of traumatic cataracts with PC-IOL
implantation in children, Pandey et al184 reported an
incidence of pupillary capture as high as 40 percent in
ciliary-sulcus fixated IOLs while none of the eyes with
in-the-bag fixation of the PC-IOL had this complication
(Figs 10.16A and B). Pupillary capture can be left
untreated if it is not associated with decreased visual
acuity, IOL malposition or glaucoma. However, surgical
repair recreates a more round pupil shape and IOL
centration. Fixation of PC-IOLs in the capsular bag
(whenever possible) is recommended to decrease the
incidence of this complication. Prolapsing the optic of a
secondary sulcus fixated IOL through the anterior
capsulorhexis opening can also prevent pupillary capture.
Deposits on IOL Surface
Precipitates composed of pigments, inflammatory cells,
fibrin, blood breakdown products and other elements,
are often seen during the immediate postoperative period
on the surface of an IOL optic implanted in a child (Figs
10.17A and B). The deposits can be pigmented or nonpigmented but are usually not visually significant. They
occur much more commonly in children with a dark iris,
and when compliance with postoperative medications
has been poor. Heparin-surface-modified IOLs have been
reported to decrease the incidence of these deposits. The
site of IOL implantation can also influence the formation
of deposits. Vasavada and Trivedi232 have found that the
incidence of deposits was higher in eyes with the IOL
optic captured through the PCCC in comparison with the
bag fixated IOLs.
IOL Decentration
Decentration of an IOL can occur because of traumatic
zonular loss and/or inadequate capsular support.
Capsular bag placement of the IOL is the most successful
way to reduce this complication. Posterior capture of the
IOL optic also resulted in better centration of the implanted IOL. Incidence of lens malposition in pediatric eyes
following posterior chamber IOL implantation was
reported as high as 40 percent.109 Asymmetric IOL fixation, with one haptic in the capsular bag and the other in
the ciliary sulcus can also lead to decentration and should

Figs 10.16A and B: Pupillary capture and posterior capsule


opacification after pediatric cataract surgery and IOL
implantation (A) Slit-lamp photograph of the anterior segment
of a 12-year-old-female child 13 months after ciliary sulcus
fixation of a posterior chamber intraocular lens. Note the
marked pupillary capture of the IOL optic, extending from 12
oclock to 5 oclock associated with pupillo-capsular synechia
and marked posterior capsule opacification. Best-corrected
visual acuity was 6/24 in this eye due to posterior capsule
opacification. It required Nd: YAG laser posterior capsulotomy
(B) Clinical photograph of the eye of a 10-year-old girl, post
PMMA posterior chamber intraocular lens implantation. There
is a marked pupillary capture. This is associated with marked
posterior capsule opacification. Attempt to perform Nd: YAG
laser failed, resulting in multiple pits on the IOL optic. This
type of dense PCO is an indication of surgical posterior
capsulotomy with anterior vitrectomy

therefore be avoided. Complete IOL dislocation can occur


after trauma. Explanation or repositioning of the IOL may
be necessary in some cases presenting with significant
decentration/dislocation.

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Chapter 10: Update on Pediatric Cataract Management 95

Figs 10.17A and B: Slit-lamp photographs showing pigment


deposition surface of 2 different IOLs. This complication is not
uncommon after the pediatric cataract surgery and usually
dont cause a decrease in visual acuity (courtesy: A. R.
Vasavada, MD, FRCS, Ahmedabad, India)

Glaucoma
Pediatric aphakic/pseudophakic glaucoma remains a
challenge. Its etiology, pathogenesis, incidence, onset,
diagnosis, and successful treatment often confuses the
surgeon. The incidence of glaucoma varies from 3 to 32
percent.12,48,59,74a,210,239 Although microphthalmic eyes
appear to be at the highest risk, cataract surgery before
one year of age, congenital rubella, and poorly dilated
pupils are other important risk factors and should alert
the treating ophthalmologist.

Glaucoma occurring soon after surgery is usually due


to pupillary block or peripheral anterior synechia
formation. This form of glaucoma is rare in children.
Vajapyee and coworkers228 reported the development of
pseudophakic pupillary block glaucoma in 16 children
after PC-IOL implantation leading to irreversible visual
loss in two of their patients. These authors emphasized
the necessity of stringent and frequent follow-up for
pseudophakic children. Peripheral iridectomy may
prevent pupillary block pseudophakic glaucoma. For this
reason, some authors recommend that all children having
PC-IOLs undergo peripheral iridectomy when there is
rupture of the posterior capsule or zonular dehiscence,
which may predispose to vitreous plugging. The majority
of pediatric cataract surgeons, however, dont routinely
perform peripheral iridectomy at the time of cataract
surgery.
The most common type of glaucoma to developing
after pediatric cataract surgery is open-angle glaucoma.
Unlike angle-closure glaucoma, which usually develops
soon after surgery, open angle glaucoma is usually seen
later, emphasizing the need for a life-long follow-up of
these children. The reported mean interval from the time
of cataract surgery until the detection of glaucoma ranged
from 6 years to as long as 56 years.193a A deep anterior
chamber, increased pigmentation of the trabecular
meshwork, and the iris inserting into the posterior aspect
of the trabecular meshwork are generally seen during
the gonioscopic examination. Cataract surgery may
accelerate the development of glaucoma in certain eyes
that are predisposed to develop open angle glaucoma.
The diagnosis of glaucoma may be difficult to
establish in children after cataract surgery.238 Intraocular
pressure should be periodically recorded to detect and
treat this vision threatening complication. This may be
difficult to measure with the child awake, and view of
the optic disk may be compromized by lens remnants,
miosis, and nystagmus. Further, it is difficult to assess
the visual field until later in childhood. An excessive loss
of hyperopia may be the sign of glaucoma in children
following cataract surgery as noted by Egbert and
Kushner.74a Asrani and Wilsensky12 have recommended
a screening examination for glaucoma after pediatric
cataract surgery every 3 months during the first
postoperative year, twice yearly until the tenth year, and
annually thereafter. Medical treatment should be tried
first to lower the intraocular pressure, but a glaucoma
filtering surgery with antimetabolites or a drainage
implant are often required to control the intraocular
pressure.

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Section I: Cataract

Retinal Detachment
The incidence of retinal detachment following pediatric
cataract surgery has been reported between 1 to 1.5
percent. The interval from infantile cataract surgery to
retinal detachment ranged from 23 to 34 years according
to some authors.121,127,226 The significant risk factors for
occurrence of retinal detachment are high myopia and
repeated surgeries. Retinal detachments following
infantile cataract surgery are usually secondary to oval
or round holes along the posterior vitreous base. These
are difficult to repair in children due to poor visualization
and retinal degeneration. Most reported cases have a
history of multiple reoperations performed in the years
prior to the introduction of automated lensectomy and
vitrectomy. The incidence appears to be decreasing as
surgical techniques advance and evolve.
Cystoid Macular Edema
Cystoid macular edema (CME) is a rare complication
following pediatric cataract surgery probably due to
healthy retinal vasculature.175,193 Because of the difficulty
of performing fluorescein angiography during infancy,
surgeons seldom evaluate children for this complication.
Hoyt and Nickel117 in 1982 reported that the development
of CME was common in infantile eyes after lensectomy
and anterior vitrectomy, but the appearance of the lesions
was atypical and they were not documented
photographically. The following year, Gilbard and
coworkers86 reported no CME in 25 eyes after pars plicata
removal of congenital cataracts. No subsequent paper
has documented clinically significant CME after pediatric
cataract surgery even when an anterior vitrectomy is
performed.
Hemorrhagic Retinopathy
This complication may occur following infantile cataract
surgery in up to one-third of eyes as reported by Mets
and Del Monte.172 It presents with flame-shaped retinal
hemorrhages and may be associated with concurrent
vitreous hemorrhage.58 The hemorrhages develop during
the first 24 hours following surgery, are non-progressive
and resolve within few weeks.

lenses are not worn. Even short intervals of uncorrected


aphakia are potentially very damaging to the
prognosis.41-43,46,54 When an IOL is implanted, a smaller
amount of residual hyperopia may be present. Correction
of residual hyperopia and any significant astigmatic error
is necessary to optimize visual development and
recovery from amblyopia. Some surgeons prefer to
correct children to emmetropia with an IOL even at
young ages to minimize the amblyogenic effects of
residual hyperopia. Since young childrens eyes continue
to grow axially after cataract surgery and IOL implantation, significant late myopia will be more and more
common as the years pass, especially if emmetropia is
achieved early in life with an IOL.77,118,119 Glasses or
contact lenses will be used for correction of secondary
myopia in most cases. However, the development of new
corneal and intraocular refractive procedures will
provide new options for correcting significant late
myopia.
Piggy-back foldable intraocular lenses in infants
Polypseudophakia (piggy-back IOLs) has been used as
a means to provide appropriate optical correction for
patients requiring high IOL power or for secondary
correction of an undesirable postoperative refraction after
cataract surgery. It has been successfully used in adult
patients since it was first reported by Gayton and
Sanders, and Gills.82a One of us (MEW), implanted piggyback AcrySof TM lenses in infantile eyes to manage the
changing refractive status of these patients. This
procedure, called temporary polypseudophakia, may
help in the prevention and treatment of amblyopia by
avoiding residual hyperopia.251 The posterior lens is
implanted in the capsular bag and the anterior lens is
placed in the ciliary sulcus. Within 12 to 24 months after
the primary surgical procedure, the lens implanted in
the ciliary sulcus is explanted/exchanged. To date, 15
infantile eyes have had this procedure successfully. (M.E.
Wilson, Pseudophakia and polypseudophakia in first
year of life, Presented at the ASCRS Symposium on
Cataract, IOL and Refractive Surgery, May 2000, Boston,
MA, USA). Long-term results would help us to further
evaluate this modality of refractive correction after
pediatric cataract surgery.
MANAGEMENT OF AMBLYOPIA

RESIDUAL REFRACTIVE ERROR


Uncorrected aphakia after pediatric cataract surgery can
cause or worsen amblyopia. When a child is left aphakic,
every effort should be made to minimize time intervals
when the prescribed aphakic glasses or aphakic contact

The postoperative compliant occlusion therapy of the


normal eye in cases of unilateral congenital, developmental or traumatic cataract may be needed to reverse
or prevent amblyopia in visually immature children.97,129,157,222,223,227,235,242 Pharmacological penalization

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Chapter 10: Update on Pediatric Cataract Management 97


may be useful in children with amblyopia secondary to
unilateral aphakia. Wheeler et al 243 found poor
compliance of amblyopia therapy in onethird of the
children having PC-IOLs. A best-corrected visual acuity
of 20/40 or better was achieved only in 33 percent of
eyes in their series. Noncompliance of occlusion therapy
appears to be a major barrier in achieving satisfactory
visual outcome during the treatment of amblyopia.

4.

5.

6.

SUMMARY AND CONCLUSIONS


Pediatric cataracts are common and represent one of the
most treatable causes of visual impairment in this population. Management of cataract in children is different
from the adult, because of increased intraoperative
difficulties, propensity of postoperative inflammation,
changing refractive state of the eye, difficulty in
documenting anatomic and refractive changes due to
poor compliance, and a tendency to develop amblyopia.
Adoption of different techniques for cataract surgery in
children is a must due to a low scleral rigidity, increased
elasticity of the anterior capsule, and positive vitreous
pressure. Early surgical intervention and adequate visual
rehabilitation is necessary to avoid irreversible visual
damage secondary to amblyopia. Aphakic glasses are not
desirable for the long-term correction of pediatric
aphakia because of many disadvantages associated with
their use. Although contact lenses offer many advantages
over aphakic spectacles, there are problems of infection,
lens loss, and a low compliance. Current practice for
providing full time correction of pediatric aphakia is
shifting toward implantation of intraocular lenses due
to refined and perfected microsurgical techniques, as well
as the availability of suitable rigid and foldable implant
designs. Main postoperative complications noted
following pediatric cataract surgery include fibrinous
uveitis, pupillary capture, aphakic glaucoma, pigment
and cellular deposits on the implants, posterior capsule
opacification or secondary membrane formation, and
residual refractory error. These side effects may develop
after many years. Therefore, it is crucial to follow children
closely on a long-term basis after pediatric cataract
surgery.

7.
8.
9.
10.
11.
12.
13.
14.

15.

16.
17.
18.
19.
20.
21.

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158. Lorenz B, Worle J, Visual results in congenital cataract with the
use of contact lenses. Graefes Arch Clin Exp Ophthalmol 1991,
229: 123-32.

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Chapter 10: Update on Pediatric Cataract Management 101


159. Lorenz B, Worle J, Friedl N, et al, Ocular growth in infant
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216. Sinskey RM, Patel J, Posterior chamber intraocular lens implants
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217. Sinskey RM, Stoppel JO, Amin PA, Long-term results of
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218. Sinskey RM, Stoppel JO, Amin PA, Ocular axial length changes
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219. Spierer A, Desantik H, Refractive status in children after longterm follow-up of cataract surgery with intraocular lens
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221. Tablante RT, Cruz EDG, Lapus JV, Santos AM, A new technique
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222. Taylor D, Monocular infantile cataract, intraocular lenses and


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237. Wagners RS, Nelson LB, Problems in pediatric cataract
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238. Wallace DK, Plager DA, Corneal diameter in childhood aphakic
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243 b. Werner L, Pandey SK, Escobar-Gomez M, Hoddinott DSM,
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Cataract Refract Surg 2000, 26: 1060-65.

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243. Wheeler DT, Mullaney PB, Awad A, et al, Pediatric IOL
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244. Wheeler DT, Stagger DR, Weakley DR, Jr, Endophthalmitis
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253. Wilson ME. Anterior capsule management for pediatric


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104 Section I: Cataract

11

FavitA Technique
for Removing Dropped
Nucleus during Phacoemulsification
Amar Agarwal, Sunita Agarwal, Athiya Agarwal, Suresh K Pandey, Clement K Chan

FAVIT
INTRODUCTION
SURGICAL TECHNIQUE
DISCUSSION

FAVIT
Favit is a new technique for removing FAllen nucleus from the VITreous,
one of the biggest bugbears for an ophthalmic surgeon. In Favit, a 2-port
vitrectomy with a 3-function probe is performed through the same limbal
incisions used for phacoemulsification, while a contact lens is applied on
the cornea to allow visualization of the posterior segment. This is followed
by utilizing a phaco handpiece in an aspiration mode to impale the dropped
nucleus with a minimal burst of ultrasonic energy. The engaged nucleus is
brought to the anterior chamber for removal. Favit is a safe, effective, and
technically simple procedure, associated with minimal complications and
good surgical results and visual outcome.
INTRODUCTION
Use of phacoemulsification has markedly increased within the past 3
decades, especially in the industrialized world and urban setting of the
developing world. Many modifications, including the use of capsulorhexis,
hydrodissection and hydrodelineation have been added to it. It has evolved
into a common and effective surgical method that allows implantation of
foldable lenses through a small incision. Therefore, there is substantial
interest among surgeons practicing extracapsular cataract extraction
(ECCE) and residents-in-training to learn phacoemulsification. The
transition to phacoemulsification can be difficult, with a relatively high
incidence of intraoperative complications (posterior capsular tear, vitreous
loss, dislocation of nucleus in the vitreous cavity, etc.) in the early learning
period.1
The rupture of the posterior capsule with loss of the nucleus into the
vitreous is one of the most intriguing complications in phacoemulsification.
The removal of the nucleus is mandatory, as severe inflammation will follow
if the nucleus is left in vitreous cavity.2
A variety of options are available to retrieve the dislocated nucleus
from the vitreous. Common techniques include anterior floatation of the
nucleus with perfluorocarbon liquids3,4,13,14,17 using a vitrector 5,7,10,12 threeport vitrectomy combined with mid vitreous phacofragmentation,9,11,15 and
fragmatome dissolution of the lens. We herein describe a new technique,
Favit, for the management of dropped lens nuclei, and report its associated

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Chapter 11: FavitA Technique for Removing Dropped Nucleus during Phacoemulsification 105

Following nucleus dislocation, the cortical remnants are


first removed with the phaco probe set at the irrigationaspiration mode. A vitrectomy probe, connected to the
peristaltic pump of an Alcon Universal phacoemulsification unit (Alcon Inc., Fort Worth, Tx, USA), is passed
through the previously made clear corneal or scleral
tunnel incision. An anterior vitrectomy is performed
while using the operating microscope light. A hand-held
contact lens is placed on the cornea to allow visualization
of the posterior segment during the procedure. The
operating microscope light is then turned off after
introducing an endoilluminator through the same sideport incision previously used for inserting the chopper.

This is followed by an adequate mid and posterior


vitrectomy (Fig. 11.1A). Care is taken to clear all vitreous
fibers around the dropped nucleus. Free mobility of the
nucleus is confirmed, indicating adequate vitreous clearance. The phacoemulsification probe with an infusion
sleeve, is then introduced through the clear corneal/
scleral tunnel with the endoilluminator remaining in the
side port. The setting for the phaco probe consists of 50
percent emulsification power, 50 mm Hg aspiration and
18 ml per min flow rate. When the phaco probe is placed
over the nucleus, suction is applied to engage the nucleus.
After the nucleus comes up to the phaco tip, a short burst
of phaco energy16 is activated to embed the nucleus into
the tip (Fig. 11.1B). The phaco probe is lifted anteriorly
to bring the nucleus above the iris and into the anterior
chamber (Fig. 11.2A). This is accomplished with the foot
pedal in position 2. Position 3 is only used once for a
fraction of the second while impaling the nucleus. As
the nucleus is brought anteriorly, the endoilluminator
held with the surgeons left hand is used to guide the

Fig. 11.1A: Vitrectomy being performed with a vitrector and


an endoilluminator with a contact lens. After completing the
anterior lenticular cortical clean up and anterior vitrectomy a
two-port posterior vitrectomy is performed. The vitrectomy
probe and endoilluminator are inserted through separate clear
corneal or scleral tunnel incisions created at the start of
cataract surgery and a vitrectomy contact lens is applied firmly
on the cornea by the surgical assistant to allow adequate
viewing of the posterior fundus for the surgeon

Fig. 11.1B: Embedding of the phaco tip in the nucleus and


bringing it towards the anterior chamber. The vitrectomy probe
is replaced with the phacoemulsification probe after completion
of the posterior vitrectomy to engage the posteriorly dislocated
nuclear lens fragment. Suction only mode is activated to elevate
the lens fragment and the phaco tip is then embedded into
the elevated lens fragment with a small burst of ultrasonic
energy

benefits, complications, and visual outcome. The term


FAVIT, is an acronym for a technique to remove FAllen
nucleus from the VITreous, while performing phacoemulsification procedure.
SURGICAL TECHNIQUE

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106 Section I: Cataract

Fig. 11.2A: Nucleus brought at the iris plane and stabilized


with the endoilluminator. The lens fragment is lifted anteriorly
with the phaco probe while the endoilluminator is used at the
same time to guide the lens fragment above the iris and into
the anterior chamber

Fig. 11.2B: Nucleus phacoemulsified in the anterior chamber.


Emulsification is performed on the lens fragment in the anterior
chamber, while chopping and pulsing are avoided to prevent
dropping smaller lens fragments back into the vitreous cavity

nucleus above the iris. At this stage, the grade of the


nucleus is re-assessed. If the nucleus is not hard, phacoemulsification is performed in the anterior chamber (Fig.
11.2B). Pulse mode and phaco chop techniques are
avoided to prevent the dropping of nuclear fragments
back into the vitreous cavity. If the nucleus is hard, the
entire nucleus is manually removed after extending the
limbal incision.
Next, the vitrector is reintroduced into the posterior
segment to search for and remove any resident small
cortical and nuclear fragments. A superior peripheral
iridectomy is then created with the vitrectomy probe. For
all the eyes, a 6.5 mm rigid posterior chamber intraocular
lens is implanted within the ciliary sulcus The corneal
wound was sutured using 10-0 nylon sutures.

technique in managing a dislocated lens nucleus is the


anterior floatation of the lens nucleus with perfluorocarbon liquids, 3,4,13,14 a particularly advantageous
method for managing hard nuclei. The high specific
gravities of the perfluorocarbon liquids and their inherent
property of insulating the retina from injury allow the
safe anterior displacement of the dislocated lens nucleus
for removal with minimal complications.4,14 However
their disadvantages include high cost, the need for a third
infusion port, as well as the risk of potential ocular
toxicity (retinal damage, corneal decompensation, and
glaucoma) due to incomplete oil removal. A vitrectomy
probe5,7,10,12 is an effective instrument for removing
retained lens fragments and preventing lens particleinduced uveitis and glaucoma. However, using the threeport pars plana vitrectomy probe remove hard lens nuclei
is time-consuming and frequently associated with the risk
of inducing corneal decompensation from the prolonged
irrigation of intraocular infusion fluid and creating retinal
breaks from the bouncing lens fragments.8
A three-port vitrectomy combined with mid-vitreous
phacoemulsification is currently the standard technique
for removing dislocated lens fragments.9,11,12 Although
it is a safe and effective technique, it is associated with
certain disadvantages, such as the following: the require-

DISCUSSION
Dropping the lens nucleus is a common complication for
the beginning cataract surgeon learning the techniques
of phacoemulsification.9 The dropped nucleus should not
be left in the vitreous cavity because it may incite a
chronic inflammatory reaction, glaucoma, as well as
phaco-toxic or phacoanaphylactic reactions, resulting in
subsequent visual loss.2,5,6,10-12 One commonly utilized

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Chapter 11: FavitA Technique for Removing Dropped Nucleus during Phacoemulsification 107
ment of creating three new sclerotomy ports different
from the original cataract incision ports, potential retinal
damage from multiple dropped lens fragments during
the emulsification process in the vitreous cavity, and the
induction of marked intraocular inflammation including
cystoid macular edema in the event of prolonged
ultrasonic maneuvers.4,15
Favit provides several advantages over currently
used techniques. Unlike all of the above techniques, it
requires only two entry ports (the same as the original
cataract surgical incisions: corneal/scleral tunnel entry
and the chopper side port). The avoidance of separate
conjunctival and scleral incisions and the use of the
original limbal incisions for retrieving the dropped
nucleus are convenient features for an expedient
handling of the dropped nucleus for the cataract surgeon
faced with a sudden devastating complication with
potentially serious consequences. The avoidance of a
separate infusion port also decreases the chance of
infusion complications, e.g. subretinal and choroidal
effusion.
Another major advantage of Favit is the requirement
of only limited additional instrumentation by adaptation
of the existing equipment, thus allowing a quick changeover in managing the complication. Instead of using a
probe connected to a vitrectomy machine with a venturi
pump associated with the standard three-port pars plana
technique, we use a three-function probe (cutting,
aspiration, and infusion through a sleeve) connected to
the existing phacoemulsification machine with a
peristaltic pump. We ensure that the formed vitreous
fibers are first eliminated with a two-port limbal core
vitrectomy, in order to prevent unwanted vitreous
incarceration and vitreoretinal traction during the
retrieval of the dropped nucleus.6,8 By applying only a
short burst of phaco power to engage the dropped
nucleus and avoiding any phacoemulsification in the
vitreous cavity, there is less chance of retinal injury with
multiple dropped nuclear fragments, a common occurrence with the standard techniques. The dropped nucleus
is elevated en bloc from the retinal surface into the
anterior chamber for controlled phacoemulsication or
removal as a whole through a widened limbal incision.
Expensive agents such as perfluorocarbon liquids are also
not necessary.
One relative disadvantage of this technique is the
need of the surgical assistant to apply sufficient
compression of the hand-held contact lens on the cornea
in order to neutralize the corneal distortion induced by
the passing of surgical instruments through the two
limbal incisions by the surgeon. Another potential
complication is the increased chance of corneal endo-

thelial damage from the phacoemulsification of the


nuclear fragment in the anterior chamber. Corneal
decompensation can be minimized by the liberal use of
viscoelastics in the anterior chamber during phacoemulsification and the removal of a hard lens fragment
through an enlarged limbal incision instead of phacoemulsification. In our series, only two eyes developed
corneal decompensation. For both eyes, the primary
cataract surgeon was still going through his learning
curve for the phacoemulsification technique, which likely
contributed to the subsequent corneal problem.
CONCLUSION
We find Favit to be a safe and effective technique for the
removal of retained lens fragments in our hands. The
complication rate is extremely low and the postoperative
visual outcome is generally excellent. It allows a rapid
changeover from the original cataract surgical setup to
one conducive for expeditious removal of the lens
fragments without sacrificing any safety measures
associated with the currently accepted methods of
vitreous surgery. It is a particularly convenient alternative
technique for the cataract surgeon familiar with
vitreoretinal surgical methodology, when suddenly faced
with the dreaded complication of a sizable dropped
nucleus during the primary phacoemulsification surgery.
REFERENCES
1. Mathai A, Thomas R. Incidence and management of posteriorly
dislocated nucear fragments following phacoemulsification.
Indian J Ophthalmol. 2000;48(2): 159-61.
2. Stenkula S, Byhr E, Crafoord S, Carlsson JO, Jemt M, Shanks G,
Stenevi U. Tackling the dropped nucleus. Acta Ophthalmol
Scand. 1999;77(2):242-43
3. Michael J Shapiro, Kenneth I. Resnik, Sang H. Kim, Aaron
Weinberg. Management of the dislocated crystalline lens with
a perfluorocarbon liquid. Am J Ophthalmol 1991;112:401-05.
4. Hilel Lewis, Mark S. Blumenkranz, Stanley Chang. Treatment
of dislocated crystalline lens and retinal detachment with
perfluorocarbon liquids. Retina 1992;12:299-304.
5. Raymond R. Magherio, Alan R. Magherio, Scott D. Pendergast
et al. Vitrectomy for retained lens fragments after phacoemulsification. Ophthalmology 1997;104:1426-32.
6. David M Fastenburg, Peter L Schwartz, Jeffrey L Shakin, Barry
M Golob. Management of dislocated nuclear fragments after
phacoemulsification. Am J Ophthalmol 1991;112:535-39.
7. Michael J Borne, William Tasman, Carl Regillo et al. Outcomes
of vitrectomy for retained lens fragments. Ophthalmology
1996;103:971-76.
8. Fred H Lambrou, Jr., Michael W Stewart. Management of dislocated lens fragments during phacoemulsification. Ophthalmology 1992;99:1260-62.
9. Michael A Kapsuta, John C Chen, Wai-Ching Lam. Outcomes
of dropped nucleus during phacoemulsification. Ophthalmology 1996;103:1184-87.

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108 Section I: Cataract


10. Grant D Gilland, William L Hutton, Dwain G Fuller. Retained
Intravitreal lens fragments after cataract surgery. Ophthalmology 1992;99:1263-69.
11. Discussion by Trexler M. Topping. Retained intravitreal lens
fragments after cataract surgery. Ophthalmology 1992;99:1268.
12. Barbara A. Blodi, Harry W. Flynn, Jr., Christopher F. Blodi,
et al. Retained nuclei after cataract surgery. Ophthalmology
1992;99:41-44.
13. Neil J Rowson, Annette S Bacon, Paul H Rosen. Perfluorocarbon
heavy liquids in the management of posterior dislocation of
the lens nucleus during phakoemulsification. Am J Ophthalmol
1992;76:169-70.

14. Alexander Movshovich, Maria Berrocal, Stanley Chang. The


protective properties of liquid perfluorocarbons in phacofragmentation of dislocated lenses. Retina 1994;14:457-62.
15. Charles S. Vitreous microsurgery, 2nd ed. Baltimore: Williams
and Wilkins, 1987;48-51.
16. Rover J. Augenklinik der Stadt, Krankenstalten Bielefeld-Mitte.
Phacoemulsification of the dislocated lens nucleus in the
vitreous body [Article in German] Klin Monatsbl Augenheilkd.
1995;206(6):456-9.
17. Verma L, Gogoi M, Tewari HK, Kumar A, Talwar D. Comparative study of vitrectomy for dropped nucleus with and without
the use of perfluorocarbon liquid. Clinical, electrophysiological
and visual field outcomes. Acta Ophthalmol Scand 2001
Aug;79(4):354-8

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Chapter 12: Management of Dislocated Implants by the Vitreoretinal Approach 109

12

Management of Dislocated
Implants by the Vitreoretinal Approach*

Clement K Chan, Gerald RS Schultz

ANTERIOR CHAMBER
INTRAOCULAR LENS (ACIOL)
POSTERIOR CHAMBER
INTRAOCULAR LENS (PCIOL)

ANTERIOR CHAMBER INTRAOCULAR LENS (ACIOL)


Dislocation of the ACIOL into the vitreous cavity is relatively infrequent
in comparison to the posterior chamber IOL (PCIOL). However, the ACIOL
may dislocate during trauma, particularly in the presence of a large sector
iridectomy. A subluxated or posteriorly dislocated ACIOL may be simply
repositioned into the anterior chamber.1,2 If the dislocated ACIOL is attached to formed vitreous or is sitting deep in the posterior vitreous cavity,
an initial partial vitrectomy to eliminate the vitreoretinal traction is
preferred before the repositioning or removal of the ACIOL.2 If there is
any substantial anterior segment injury associated with the dislocation
(e.g. marked iridodialysis, large hyphema, excessive angle damage, etc.),
it is best to remove the dislocated ACIOL through a limbal incision.
POSTERIOR CHAMBER INTRAOCULAR LENS (PCIOL)
Location of PCIOL Fixation
A dislocated PCIOL may occasionally be left undisturbed without causing
a problem.3 However, it is usually best to remove or reposition a posteriorly
dislocated PCIOL to avoid a sight-threatening retinal injury. The removal
of the dislocated PCIOL represents a simple and direct approach. Mittra et
al reported favorable visual results and minimal complications with the
removal of the dislocated PCIOL, and the implantation of an open-loop,
flexible ACIOL at the same time.4 Proper PCIOL repositioning provides
the best potential for optimal visual rehabilitation. Past reports have
described the repositioning of the PCIOL at various intraocular locations.
McCannel first introduced the idea of a retrievable suturing technique for
anchoring an IOL on the iris in 1976.5 Stark described the anchoring of the
subluxated PCIOL on the iris in 1982,6 and Sternberg reported the
attachment of the posteriorly dislocated PCIOL to the iris with the pars
plana technology in 1986.7 Girard advocated anchoring the PCIOL at the
pars plana,8 or imbricating the haptic loops into the sclerotomies with
sutures.9 Smiddy,10 Campo,11 and Anand12 presented their versions of
repositioning the dislocated PCIOL in the ciliary sulcus with a pars plana
approach. The repositioning at the ciliary sulcus allows the dislocated
PCIOL to be restored to a position most similar to the original state.

* The authors have no proprietary interest in any of the commercial products in the text

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110 Section I: Cataract


Opened Eye or External Approach
This approach involves modifications of various suturing techniques for inserting an external primary or
secondary PCIOLsometimes in association with aphakic penetrating keratoplasty, or with an IOL exchange,
in the absence of appropriate capsular or zonular
support.13-23 The suture material can be easily tied to the
externally located IOL before its reinsertion. A relatively
large limbal incision is required for the externalization
and the subsequent reinsertion of the dislocated PCIOL.
Closed Eye or Internal Approach:
Pars Plana Techniques
This approach avoids the making of a large surgical
incision that may induce undesirable astigmatism or
tissue injury. The integrity of the globe is maintained,
and the fluctuation of the intraocular pressure (IOP) is
minimized throughout the case. However, many of the
internal techniques require the passage of sharp
instruments or needles into the eye, which sometimes
can be associated with the risk of an injury to the
intraocular structures. Relatively intricate intraocular
maneuvers may also be involved. In recent years, a
number of internal techniques for the repositioning of
the PCIOL with a pars plana approach have become
increasingly popular.24-36
Scleral Loop Fixation
In 1991, Maguire and Blumenkranz et al described the
preparation of a 9-0 or 10-0 polypropylene suture loop
by making a simple knot or a series of twists on the suture
with a pair of microforceps.24 The same microforceps are
used to grasp the suture adjacent to the suture loop for
insertion through an anterior sclerotomy corresponding
to the location of the ciliary sulcus, after a partial pars
plana vitrectomy to eliminate the vitreoretinal traction.
The inserted suture loop is then used to engage one of
the dislocated haptics for anchoring at the anterior
sclerotomy. The same maneuver is repeated for the
opposite haptic (Fig. 12.1).
The Grieshaber Snare
Grieshaber first manufactured a snare designed by Packo
in the early 1990s. It consists of a 20 gauge tube and
handle with a movable spring-loaded finger slide for
adjusting the size of a protruding polypropylene loop.
The distal portion of the tube with the polypropylene
loop is inserted through an anterior sclerotomy for
engaging a dislocated haptic in the vitreous cavity. Once

Fig. 12.1: The scleral loop fixation technique involves engaging the haptics of the dislocated PCIOL with a 9-0 or 10-0
polypropylene loop prepared by making a series of twists on
the suture with forceps, followed by fixation in the ciliary
sulcus (Maguire et al: Arch Ophthalmol 109:1754-58,1991)

the looped haptic is pulled up against the anterior


sclerotomy, the external portion of the polypropylene
loop is cut free and guided through a 30 gauge needle
for anchoring by the anterior sclerotomy (Fig. 12.2). Little
et al reported the successful transscleral fixation of the
dislocated PCIOL with the snare method in a series of
cases in 1993.27
Use of Perfluorocarbon Liquid
Various authors reported the removal of the dislocated
crystalline lens or the management of the dislocated
PCIOL with the aid of perfluorocarbon liquids in the early
1990s.28-33 In 1993, Lewis and Sanchez described the
following maneuver:33 The perfluorocarbon liquid is first
used to float the dislocated PCIOL anteriorly; then 9-0
polypropylene sutures are inserted through the
horizontal anterior sclerotomies to engage the positioning
holes of the optics at 90 degrees from the haptics, which
are anchored in the ciliary sulcus along the vertical
meridians (Fig. 12.3). This maneuver allows a four-point
fixation associated with the proper centering of the IOL.
However, not all of the optics have positioning holes.
Care must also be taken to avoid infusing a large amount
of the perfluorocarbon liquid, which tends to induce a
convex meniscus, and can cause the floated IOL to glide
toward the peripheral retina or the vitreous base. A layer
of viscoelastic may be placed on the surface of the
perfluorocarbon liquid to neutralize the convex

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Chapter 12: Management of Dislocated Implants by the Vitreoretinal Approach 111

Fig. 12.2: The Grieshaber snare consists of a 20 G tube and


handle with a movable spring-loaded finger slide for adjusting
the amount of a protruding polypropylene suture loop. The
suture loop is inserted posteriorly to engage a dislocated
haptic. The external portion of the suture loop is then cut free
and guided through a 30 G needle for anchoring at the sclera,
after the engaged haptic is pulled up against the anterior
sclerotomy

meniscus, and allow the recentering of the dislocated


IOL.34
The 25 Gauge IOL Forceps
In 1994, Chang introduced the 25 gauge IOL forceps. The
passive-action forceps have smooth platforms at the
distal end for grasping tissue or holding a suture, and a
small groove at the proximal end for gripping
a haptic.35 After a partial vitrectomy, a sharp 25 gauge,
5/8 inch needle is inserted through a scleral groove at
0.8 mm posterior to the corneoscleral limbus, to create a
tract for the 25 gauge forceps. The forceps holding a slip
knot (lasso) on a 10-0 polypropylene suture is then
inserted through the grooved scleral incision into the eye
for engaging an IOL haptic. After looping the haptic, the
forceps are released from the suture and are used to
regrasp the end of the haptic, thus, preventing the suture
from slipping off the haptic. After tightening the slip
knot, the IOL is repositioned in the ciliary sulcus by
anchoring the needle of the 10-0 polypropylene suture
within the scleral groove (Fig. 12.4). The same maneuver
may be repeated for the opposite haptic, if necessary. The
scleral groove is closed with an interrupted 10-0 nylon
suture.

Fig. 12.3: The perfluorocarbon liquid is used to float the


dislocated PCIOL anteriorly (A). The haptics are anchored in
the ciliary sulcus along the vertical meridians, while the 9-0
polypropylene sutures are inserted through the horizontal
anterior sclerotomies to engage the positioning holes of the
optic (B); resulting in a stable 4-point fixation (C). (Lewis et al:
Ophthalmol 100:1055-59,1993)

Temporary Haptic Externalization


Chan first described this method in 1992. Its main
features involve the temporary haptic externalization for
suture placement after a pars plana vitrectomy, followed
by the reinternalization of the haptics tied with 9-0 or
10-0 polypropylene sutures for secured anchoring by the
anterior sclerotomies.
Detailed method36,37
A 3-port pars plana vitrectomy is performed for the
removal of the anterior and central vitreous adjacent
to the dislocated IOL, in order to prevent any vitreoretinal traction during the process of manipulating
the IOL.
Two diametrically opposed limbal-based partial
thickness triangular scleral flaps are prepared along
the horizontal meridians at 3 and 9 Oclock. Anterior
sclerotomies within the beds under the scleral flaps
are made at 1 to 1.5 mm from the limbus (Figs 12.5A
and B). As an alternative to the scleral flaps, the
anterior sclerotomies may be made within the scleral
grooves at 1 to 1.5 mm from the horizontal limbus
(Fig. 12.5C).
A fiberoptic light pipe is inserted through one of the
posterior sclerotomies, while a pair of fine non-angled

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112 Section I: Cataract

Fig. 12.4: The 25 G Chang passive-action IOL forceps have


smooth distal platforms for grasping tissues or sutures, and a
proximal groove for gripping a haptic. A slip knot is inserted
through a paralimbal scleral groove incision to engage the
haptic of the IOL. The forceps are then used to regrasp the
distal end of the haptic to prevent the slippage of the suture
loop. After tightening the slip knot, the needle of the 10-0
polypropylene suture is anchored within the scleral groove for
the implant fixation in the ciliary sulcus. (Chang et al: Am J
Ophthalmol 119:165-74,1995)

positive action forceps (e.g. Grieshaber 612.8) is


inserted through the anterior sclerotomy of the
opposing quadrant to engage one haptic of the
dislocated IOL for the temporary externalization (Fig.
12.6A). A double-armed 9-0 (Ethicon TG 160-8 plus,
Somerville NJ) or 10-0 polypropylene suture (Ethicon
CS 160-6 Somerville NJ) is tied around the
externalized haptic to make a secured knot. The same
process is repeated for the other haptic after the
surgeon switches the instruments to the opposite
hands (Fig. 12.6B).
The externalized haptics with the tied sutures are
reinternalized through the corresponding anterior
sclerotomies with the same forceps (Fig. 12.7). The
internalized haptics are anchored securely in the
ciliary sulcus by taking scleral bites with the external
suture needles on the lips of the anterior sclerotomies.
By adjusting the tension of the opposing sutures while
tying the polypropylene suture knots by the anterior
sclerotomies, the optic is centered behind the pupil,
and the haptics are anchored in the ciliary sulcus (Figs
12.8A and B).

Figs 12.5A to C: Temporary haptic externalization method:


(Step 1): Anterior sclerotomies at 1 to 1.5 mm from the
horizontal limbus are made under partial thickness scleral
flaps (A and B). Instead of scleral flaps, anterior sclerotomies
may also be made within scleral grooves (C). (Chan:
Ophthalmol 99:51-57,1992)

Important features The horizontal meridians are chosen


for the location of the anterior sclerotomies for easier
manipulation of the forceps, haptics and sutures during
the repositioning process. The location of the anterior
sclerotomies determines the final position of the IOL.
Previous anatomic studies have reported the ciliary
sulcus to be between 0.46 to 0.8 mm from the limbus.38
Thus the distance of 1 to 1.5 mm from the limbus places
the anterior sclerotomies close to the external surface of
the ciliary sulcus. Making the anterior sclerotomies at
less than 1 mm from the limbus increases the risk of
injuring the anterior chamber angle or the iris root.
The following steps are taken to ease the passage of
the haptics through the anterior sclerotomies and reduce
the chance of haptic breakage: (i) The anterior sclerotomies should have adequate sizeif necessary, they may
be widened before the haptic reinternalization, and (ii)
Fine non-angled positive action intraocular forceps are
used for the haptic manipulation to give the surgeon the
maximal feel and control. Excessive pinching of the
haptics is avoided during the passage of the haptics.
Several measures may also be taken to prevent the
decentering and tilting of the IOL:
The anterior sclerotomies are made at 180 from each
other.

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Chapter 12: Management of Dislocated Implants by the Vitreoretinal Approach 113

Figs 12.6A and B: Temporary haptic externalization method:


(Step 2): After a partial pars plana vitrectomy, a doublearmed 9-0 or 10-0 polypropylene suture is tied around the
haptic which has been externalized with fine non-angled
positive action forceps through one of the two anterior sclerotomies (A). The same process is repeated for the opposite
haptic (B) (Chan)

Figs 12.8A and B: Temporary haptic externalization method:


After adjusting the tension of the polypropylene sutures tied
to the reinternalized haptics (A), the implant is fixated in the
ciliary sulcus by anchoring the sutures by the anterior sclerotomies (B) (Chan)

A four-point-fixation optionto enhance more


stability, two separate polypropylene sutures can be
tied on each haptic, and the associated needles are
anchored on the two corners of each anterior
sclerotomy (Fig. 12.9). This results in the stable
configuration of a four-point fixation of the IOL.
After the initial report of 12 eyes, additional 22 eyes
successfully undergoing this method of repositioning
between 1992 and 1999 were presented.37 Thach et al also
reported 57 patients undergoing IOL repositioning with
this technique at the 1998 AAO meeting in New
Orleans.39 In Chans series, the average age of the patients
was 74. The average follow-up time was 17.5 months.
The average preoperative best-corrected visual acuity
Fig. 12.7: Temporary haptic externalization method (Step 3): (BCVA) was 20/400 (rangelight perception to 20/30),
The haptics tied with the polypropylene sutures are and the average postoperative BCVA was 20/50 (range
reinternalized through the corresponding anterior sclerotomies
of no light perception to 20/20). There were no major
with the same forceps (Chan)
complications, e.g. retinal breaks or detachment, macular
pucker, endophthalmitis, ocular ischemia, etc. Despite
The sutures are tied at equal distance from the ends fixating the scleral sutures along the horizontal
of both haptics.
meridians, there were no signs of any injury to the ciliary

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114 Section I: Cataract

Fig. 12.9: Temporary haptic externalization method: To


enhance the centering and prevent the tilting of the IOL, two
9-0 or 10-0 polypropylene sutures are tied on each haptic
which has been externalized with fine non-angled forceps,
and then anchored on the 2 corners of each anterior sclerotomy after the reinternalization of the haptics. This results in
a stable 4-point fixation associated with the appropriate centering of the IOL (Chan)

arteries or nerves. The following minor complications


were encountered:37
Cystoid macular edema (CME)20.4 percent (10
eyes); most resolved after topical and/or periocular
therapy
Mild IOL decentration14.7 percent (5 eyes)nonsight threatening
Suture erosion through the conjunctiva1 eye, no
scleral flaps for covering the sutures were made for
this eye
Recurrent IOL dislocation1 eye, the IOL was too
small for the involved eye.
This repositioning technique combines the best
features of the external and the internal approaches,
while avoiding any intricate and cumbersome intraocular
manipulations. With the easy placement of the anchoring
sutures in an opened environment and the
maintenance of the integrity of the globe in a closed
environment, this technique allows the secured and
precise fixation of the dislocated IOL in the ciliary sulcus
on a consistent basis.36,37

The slippery surface of the one-piece silicone plate


implant makes it relatively mobile, even years after its
placement. The silicone plate implant is fixated in the
capsular bag by capsular contraction. 37-40 After its
implantation, there is fibrotic fusion of the anterior and
posterior capsules as well as capsular purse-stringing due
to the anterior capsular contraction.38-41 These effects
induce the posterior bowing of the silicone plate implant
against the posterior capsule, resulting in the posterior
capsular tightening and stretching. 40-44 Thus any
dehiscence of the capsular bag outside of the capsulorhexis allows the release of the built-up tension, and
the expulsion of the implant through the dehiscence.38-41
Frequently, further capsular contraction after a posterior
YAG capsulotomy may then vault the one-piece silicone
plate implant through the opening into the vitreous
cavity, in a delayed fashion.38-41
Previous reports have advocated the repositioning of
the dislocated silicone plate implant anterior to the
capsular remnants or in the ciliary sulcus. Schneiderman
and Johnson described the technique of picking the
slippery silicone plate implant off the retinal surface with
a lighted pick.40,41 The surgeon extends the tip of the pick
under the edge of the silicone plate implant to gently
elevate it off the retinal surface. The elevated edge is then
grasped with the intraocular forceps for the repositioning
or removal of the implant. Alternatively, the plate implant
may be brought anteriorly by hooking the lighted pick
through one of its positioning holes, and then grasped
with forceps at the anterior or midvitreous cavity (Fig.
12.10). Another method is to aspirate the plate implant
with a soft-tip cannula. The perfluorocarbon liquid may
also be used to float the dislocated plate implant. The
one-piece silicone plate implant is designed for insertion
into the capsular bag. Thus the silicone plate implant
repositioned anterior to the capsular remnants or in the
ciliary sulcus tends to be unstable, particularly without
the support of sutures. None of the suturing methods
work well for the one-piece silicone IOL with plate
haptics. The temporary externalization of the bulky plate
haptics of the silicone plate implant is awkward, and the
suture placement through its floppy surface tends to
result in the cheese-wiring of the implant. Frequently,
the best approach for managing the dislocated one-piece
silicone plate implant is its removal.
Managing Eyes with Two Intraocular Implants

One-piece Silicone Plate IOL


There is a lack of fibrous adhesion between the lens
capsule and the one-piece silicone IOL with plate haptics
even years after its insertion into the capsular bag.37-40

The presence of two intraocular implants complicates the


surgical management. This usually occurs when the
anterior segment surgeon inserts a second implant
(usually an ACIOL) without removing the posteriorly

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Chapter 12: Management of Dislocated Implants by the Vitreoretinal Approach 115

Fig. 12.10: The slippery silicone plate implant may be lifted


on its edge or hooked through a positioning hole with a
lighted pick, and then grasped with intraocular forceps for its
repositioning or removal. (Schneiderman et al: Am J
Ophthalmol 123: 629-35, 1997)

dislocated implant. When the dislocated implant is soft


and consists of relatively inert material (e.g. one-piece
silicone implant with plate haptics), it may be left alone
with a minimal chance of causing a retinal injury,
although the movement of the implant may create a
visual disturbance. Mobile dislocated implants with hard
surfaces and sharp edges may induce an intraocular
injury, and therefore should be removed. The association
of vitreous hemorrhage, glaucoma, uveitis, retinal breaks,
or a retinal detachment with the dislocated implant also
requires surgical intervention. The presence of the second
intraocular implant eliminates the option of repositioning
the dislocated implant, and it also interferes with the
removal of the dislocated implant. A number of
techniques have been described in the removal of the
dislocated implant in the presence of a second implant.
The dislocated implant may be treated as an intraocular
foreign body, and removed through a pars plana incision
with standard vitreoretinal techniques, as reported by
Williams et al.42 The dislocated implant may also be
removed through a limbal incision with or without the
simultaneous removal of the second implant.42 Wong
recently described a technique of temporarily suspending the dislocated implant at the anterior vitreous cavity

by passing a 6-0 nylon suture through one of the IOL


positioning holes, followed by gently tilting up the edge
of the second implant to allow the delivery of the
dislocated implant out of the eye through a limbal
incision.43 Another option is the removal of the second
implant followed by the repositioning of the dislocated
implant. This option may be chosen if there is marked
anterior segment pathology associated with the second
anterior chamber implant (marked iridodialysis or
hyphema, progressive corneal edema, etc.), and the
dislocated posterior chamber implant can be safely
fixated in the ciliary sulcus. The final option is the
removal of both implants, particularly when the presence
of any implant may aggravate the ocular condition; such
as poorly controlled glaucoma, or an advanced retinal
detachment with severe proliferative vitreoretinopathy.
Whether there is the removal of one or both implants
through a limbal or a pars plana opening, a relatively
large incision is required, and complex maneuvers are
necessary. This leads to a high chance of ocular morbidities. Thus the placement of a second implant should
be avoided in the setting of a posteriorly dislocated
implant.
SUMMARY
A dislocated AC or PCIOL may be removed, exchanged,
or repositioned. The repositioning of the dislocated
PCIOL in the ciliary sulcus with modern vitreoretinal
techniques provides an optimal environment for visual
recovery. The implant repositioning techniques may be
broadly divided into the external and the internal
approaches. The former involves modifications of the
suturing techniques for a primary or secondary implant
in the absence of appropriate capsular or zonular
support, while the latter is best accomplished with the
pars plana technology. Some of the recent vitreoretinal
methods of PCIOL repositioning gaining wide acceptance
include the scleral loop fixation, 24 the snare approach, 27
the use of perfluorocarbon, 30,32,33 the 25 gauge implant
forceps,35 and the temporary haptic externalization.36 The
temporary haptic externalization method combines the
best features of the external and the internal approaches,
avoids difficult maneuvers, and allows the consistent IOL
fixation in the ciliary sulcus. Unique features are
associated with the silicone plate implants. The capsular
contraction after a posterior YAG capsulotomy often
leads to a delayed posterior dislocation of the plate
implant. Special techniques can be used to pick up the
slippery plate implant from the retinal surface for its
removal or repositioning. The plate implant repositioned
anterior to capsular remnants or in the ciliary sulcus may

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116 Section I: Cataract


be unstable, and it is often best to remove the dislocated
plate implant. The placement of a second implant in the
presence of a dislocated implant is ill advised, as it
complicates subsequent surgical management. Surgical
options include the removal of the dislocated implant
through a pars plana or a limbal incision with special
techniques, the repositioning of the dislocated implant
after removing the second implant, or the removal of both
implants. Surgical maneuvers in the setting of double
implants are associated with increased morbidities and
complications.
REFERENCES
1. Flynn HW Jr: Pars plana vitrectomy in the management of
subluxated and posteriorly dislocated intraocular lenses.
Graefes Arch Clin Exp Ophthalmol 1987;225:169-72.
2. Flynn HW Jr, Buus D, Culbertson WW: Management of
subluxated and posteriorly dislocated intraocular lenses using
pars plana vitrectomy instrumentation. J Cataract Refract Surg
1990;16:51-56.
3. Jacobi KW, Krey H: Surgical management of intraocular lens
dislocation into the vitreouscase report. J Am Intraocul
Implant Soc 1983;9:58-59.
4. Mittra RA, Connor TB, Han DP et al: Removal of dislocated
intraocular lenses using pars plana vitrectomy with placement
of an open-loop, flexible anterior chamber lens. Ophthalmol
1998;105:1011-14.
5. McCannel MA: A retrievable suture idea for anterior uveal
problems. Ophthalmic Surg 1998;7(2): 98-103.
6. Stark WJ, Bruner WE: Management of posteriorly dislocated
intraocular lenses. Ophthalmic Surg 1980;11:495-97.
7. Sternberg P Jr, Michels RG: Treatment of dislocated posterior
chamber intraocular lenses. Arch Ophthalmol 1986;104:
1391-93.
8. Girard LJ: Pars plana phacoprosthesis (aphakic intraocular
implanta preliminary report. Ophthalmic Surg 1981;12:19-22.
9. Girard LJ, Nino N, Wesson M et al: Scleral fixation of a subluxated posterior chamber intraocular lens. J Cataract Refract
Surg 1988;14:326-27.
10. Smiddy WE: Dislocated posterior chamber intraocular lens. A
new technique of management. Arch Ophthalmol 1989;107:
1678-80.
11. Campo RV, Chung KD, Oyakawa RT: Pars plana vitrectomy in
the management of dislocated posterior chamber lenses. Am J
Ophthalmol 1989;108:529-34.
12. Anand R, Bowman RW: Simplified technique for suturing
dislocated posterior chamber intraocular lens to the ciliary
sulcus [letter]. Arch Ophthalmol 1990;108:1205-06.
13. Stark WJ, Goodman G, Goodman D et al: Posterior chamber
intraocular lens implantation in the absence of posterior
capsular support. Ophthalmic Surg 1988;19:240-43.
14. Hu BV, Shin DH, Gibbs KA et al: Implantation of posterior
chamber lens in the absence of posterior capsular and zonular
support. Arch Ophthalmol 1988;106:416-20.
15. Shin DH, Hu BV, Hong YJ et al: Posterior chamber lens
implantation in the absence of posterior capsular support
[letter]. Ophthalmic Surg 1988;19:606-07.
16. Dahan E: Implantation in the posterior chamber without
capsular support. J Cataract Refract Surg 1989;15:339-42.

17. Pannu JS: A new suturing technique for ciliary sulcus fixation
in the absence of posterior capsule. Ophthalmic Surg 1988;19:
751-54.
18. Spigelman AV, Lindstrom RL, Nichols BD et al: Implantation
of a posterior chamber lens without capsular support during
penetrating keratoplasty or as a secondary lens implant.
Ophthalmic Surg 1988;19:396-98.
19. Drews RC: Posterior chamber lens implantation during keratoplasty without posterior lens capsule support. Cornea 1987;6:
38-40.
20. Wong SK, Stark WJ, Gottsch SD et al: Use of posterior chamber
lenses in pseudophakic bullous keratopathy. Arch Ophthalmol
1987;105:856-58.
21. Waring GO III, Stulting RD, Street D: Penetrating keratoplasty
for pseudophakic corneal edema with exchange of intraocular
lenses. Arch Ophthalmol 1987;105:58-62.
22. Shin DH: Implantation of a posterior chamber lens without
capsular support during penetrating keratoplasty or as a
secondary lens [letter]. Ophthalmic Surg 1988;19:755-56.
23. Lindstrom RL, Harris WS, Lyle WA: Secondary and exchange
posterior chamber lens implantation. J Am Intraocul Implant
Soc 1982;8:353-56.
24. Maguire AM, Blumenkranz MS, Ward TG et al: Scleral loop
fixation for posteriorly dislocated intraocular lenses. Operative
technique and long-term results. Arch Ophthalmol 1991;109:
1754-58.
25. Bloom SM, Wyszynski RE, Brucker AJ: Scleral fixation suture
for dislocated posterior chamber intraocular lens. Ophthalmic
Surg 1990;21:851-54.
26. Friedberg MA, Pilkerton AR: A new technique for repositioning
and fixating a dislocated intraocular lens. Arch Ophthalmol
1992;110:413-15.
27. Little BC, Rosen PH, Orr G: Trans-scleral fixation of dislocated
posterior chamber intraocular lenses using a 9-0 microsurgical
polypropylene snare. Eye 1993;7:740-43.
28. Lewis H, Blumenkranz MS, Chang S: Treatment of dislocated
crystalline lens and retinal detachment with perfluorocarbon
liquids. Retina 1992;12:299-304.
29. Shapiro MJ, Resnick KI, Kim SH: Management of the dislocated
crystalline lens with a perfluorocarbon liquid. Am J Ophthalmol
1992;112:401-05.
30. Liu K, Peyman GA, Chen M: Use of high density vitreous
substitute in the removal of posteriorly dislocated lenses or
intraocular lenses. Ophthalmic Surg 1991;22:503-07.
31. Rowson NJ, Bacon AS, Rosen PH: Perfluorocarbon heavy liquids
in the management of posterior dislocation of the lens nucleus
during phakoemulsification. Br J Ophthalmol 1992;176(3): 16970.
32. Greve MD, Peyman GA, Mehta NJ: Use of perfluoroperhydrophenanthrene in the management of posteriorly dislocated
crystalline and intraocular lenses. Ophthalmic Surg 1993;24(9):
593-97.
33. Lewis H, Sanchez G: The use of perfluorocarbon liquids in the
repositioning of posteriorly dislocated intraocular lenses.
Ophthalmol 1993;100:1055-59.
34. Elizalde J: Combined use of perfluorocarbon liquids and viscoelastics aOL by temporary externalization of haptics, [poster
#132]. The Vitreous Society 17th Annual Meeting, Rome, 1999.
35. Duffey RJ, Holland EJ, Agapitos PJ et al: Anatomic study of
transsclerally sutured intraocular lens implantation. Am J
Ophthalmol 1999;108:300-09.

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Chapter 12: Management of Dislocated Implants by the Vitreoretinal Approach 117


36. Thach AB, Dugel PU, Sipperley JO et al: Outcome of sulcus
fixation of dislocated PCIOLs using temporary externalization
of the haptics. [paper] AAO Annual Meeting, New Orleans,
Louisiana, 1998.
37. Milauskas AT: Posterior capsule opacification after silicone lens
implantation and its management. J Cataract Refract Surg
1987;13:644-48.
38. Milauskas AT: Capsular bag fixation of one-piece silicone lenses.
J Cataract Refract Surg 1990;16:583-86.
39. Joo CK, Shin JA, Kim JH: Capsular opening contraction after
continuous curvilinear capsulorhexis and intraocular lens
implantation. J Cataract Refract Surg 1996;22:585-90.

40. Schneiderman TE, Johnson MW, Smiddy WE et al: Surgical


management of posteriorly dislocated silicone plate haptic
intraocular lenses. Am J Ophthalmol 123:629-35, 1997.
41. Johnson MW, Schneiderman TE: Surgical management of
posteriorly dislocated silicone plate intraocular lenses. Curr
Opin Ophthalmol 9:11-15, 1998.
42. Williams DF, Del Piero EJ, Ferrone PJ et al: Management of
complications in eyes containing two intraocular lenses.
Ophthalmol 105:2017-22, 1998.
43. Wong KL: Simplified technique to remove a posteriorly
dislocated PCIOL with a coexistent PCIOL [poster 133]. The
Vitreous Society 17th Annual Meeting, Rome, 1999.

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118 Section I: Cataract

13

Air Pump to Prevent Surge


Sunita Agarwal, Amar Agarwal, Athiya Agarwal

INTRODUCTION
SURGE
NEW TECHNIQUE
METHOD
CONTINUOUS INFUSION
ADVANTAGES
TOPICAL OR NO ANESTHESIA
CATARACT SURGERY
DISADVANTAGES

INTRODUCTION
One of the main bugbears of phacoemulsification is surge.1 The problem is
that as the nuclear piece gets occluded in the phaco tip and we emulsify it,
surge occurs. Many people have tried various methods to solve this
problem. Some phaco machines like the Sovereign have been devised with
the help of I Howard Fine, Barry Seibel and William Fishkind to solve this
problem. Others have tried to use an anterior chamber maintainer to get
more fluid into the eye. The problem with the anterior chamber maintainer
is that another port has to be made. In other words, now we have three ports
and if you are doing the case under topical or no anesthesia (as we do in our
hospital) it becomes quite cumbersome. Another method to solve surge is
to use more of phacoaspiration and chop the nuclear pieces with the left
hand (non-dominant hand). The problem by this is the surgical time
decreases and if the case is of a hard brown cataract, phacoaspiration will
not suffice.
SURGE
Surge1 occurs when an occluded fragment is held by high vacuum and is
then abruptly aspirated with a burst of ultrasound. What happens is that
fluid from the anterior chamber rushes into the phaco tip and this leads to
collapse of the anterior chamber.
NEW TECHNIQUE
One of us (Sunita Agarwal), then thought of a method to solve surge using
an air pump. We got this idea as when we were operating cases with
Phakonit (a new technique in which cataract is removed through a 0.9 mm
opening), we wanted more fluid entering the eye. Now we, routinely use
the air pump to solve the problem of surge.
METHOD
First of all (Fig. 13.1), we use two balanced salt solution (BSS) bottles
and not one. These are put in the IV stand.
Instead of using an IV set for the fluid to move from the bottle to the
phaco handpiece, we use a TUR set. This is a transurethral tubing set,
which is used by urologists. The advantage of this is that, the bore of
the tubing is quite large and so more fluid passes from the infusion
bottle to the phaco handpiece. The TUR set has two tubes, which go
into each infusion bottle, and then the TUR set becomes one, which
then passes into the phaco handpiece.

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Chapter 13: Air Pump to Prevent Surge 119

Fig. 13.1: Diagrammatic representation of the air pump and


infusion bottle. Note two infusion bottles connected to a TUR
set. Also note the air pump connects to one of the infusion
bottles

Now we take an air pump. This air pump is the same


air pump, which is used in fish tanks to give oxygen
to the fishes. The air pump is plugged on to the
electrical connection.
An IV set now connects the air pump to the infusion
bottle. The tubing passes from the air pump and the
end of the tubing is passed into one of the infusion
bottles (Fig. 13.2).
What happens now is that when the air pump is
switched on, it pumps air into the infusion bottle. This
air goes to the top of the bottle and because of the
pressure, it pumps the fluid down with greater force.
With this, the TUR set also is in place and so the fluid
now flows from the infusion bottle into the TUR set
to reach the phaco handpiece. The amount of fluid
now coming out of the handpiece is much more than
what would normally come out and with more force.
One can use an air filter between the air pump and
the infusion bottle so that the air which is being
pumped into the bottle is sterile.
This extra amount of fluid coming out compensates
for the surge which would occur.
CONTINUOUS INFUSION
Before we enter the eye, we fill the eye with viscoelastic.
Then once the tip of the phaco handpiece is inside the

Fig. 13.2: Air pump connected to the infusion bottle. Note two
infusion bottles. The black box on the left over the phaco
machine is the air pump. On the right is the phaco handpiece
lying in a tray

anterior chamber we shift to continuous irrigation. This


is very helpful especially for surgeons who are starting
phaco. This way, the surgeon, never comes to position
zero and the anterior chamber never collapses. Even for
excellent surgeons this helps a lot.
ADVANTAGES
With the air pump, the posterior capsule is pushed
back and there is a deep anterior chamber.
The phenomenon of surge is neutralized. This prevents the unnecessary posterior capsular rupture.
Striate keratitis postoperatively is reduced, as there
is a deep anterior chamber.
One can operate hard cataracts also quite comfortably,
as striate keratitis does not occur postoperatively.
The surgical time is shorter as we can go quite fast in
removing the nuclear pieces, as surge does not occur.

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120 Section I: Cataract


One can easily operate cases with the Phakonit
technique as quite a lot of fluid now passes into the
eye. Thus, the cataract can be removed through a
0.9 mm opening.
It is quite comfortable to do cases under topical or no
anesthesia.
TOPICAL OR NO ANESTHESIA
CATARACT SURGERY

words, there is a lot of space between the posterior


capsule and the cornea, preventing striate keratitis.
DISADVANTAGES
As we tend to use two bottles instead of one, the cost
is a bit more expensive
The TUR set is slightly more expensive than a normal
IV set.
SUMMARY

When one operates under topical or no anesthesia, the


main problem is sometimes the pressure is high especially if the patient squeezes the eye. In such cases, the
posterior capsule comes up anteriorly and one can
produce a posterior capsular rupture. To solve this
problem, surgeons tend to work more anteriorly, performing supracapsular phacoemulsification. The disadvantage of this is that striate keratitis tends to occur.
With the air pump, this problem does not occur. When
we use the air pump, the posterior capsule is quite back,
as if we are operating a patient under a block. In other

The air pump is a new device, which helps to prevent


surge. This helps to prevent posterior capsular rupture,
helps deepen the anterior chamber and one can work
comfortably even in hard cataracts. The air pump pumps
air into the infusion bottle thus tending to push more of
fluid into the eye and with greater force. Now, we
routinely use the air pump in all our cases.
REFERENCE
1. Agarwal S, Agarwal A et al: Phacoemulsification, Laser Cataract
Surgery and Foldable IOLs. New Delhi: Jaypee Brothers, 1998

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Chapter 14: Trypan Blue in the Management of Mature Cataracts

121

14

Trypan Blue in the


Management of Mature Cataracts
Amar Agarwal, Athiya Agarwal, Sunita Agarwal

INTRODUCTION
RHESIX IN MATURE CATARACTS
TRYPAN BLUE
TECHNIQUE
ADVERSE EFFECTS
STERILIZATION
INDOCYANINE GREEN DYE

INTRODUCTION
One of the biggest bugbears for a phaco surgeon is to perform a rhexis in a
mature cataract. Once one performs rhexis in mature and hypermature
cataracts, then phaco can be done in these cases and a foldable IOL
implanted.
RHEXIS IN MATURE CATARACTS
Various techniques are present which can help one perform rhexis in mature
cataracts.
1. One should use a good operating microscope. If the operating
microscope is good one can faintly see the outline of the rhexis.
2. Use of an endoilluminator. While one is performing the rhexis with the
right hand (Dominant hand), in the left hand (non-dominant hand)
one can hold an endoilluminator. By adjusting the endoilluminator in
various positions, one can complete the rhexis as the edge of the rhexis
can be seen.
3. Use of a forceps. A forceps is easier to use than a needle especially in
mature cataracts. One can use a good rhexis forceps to complete the
rhexis.
4. Use of paraxial light.
But with all these techniques, still one is not very sure of completing a
rhexis in all cases. Many times if the rhexis is incomplete, one might have
to convert to an extracapsular cataract extraction (ECCE) to prevent a
posterior capsular rupture or nucleus drop.
TRYPAN BLUE
The solution to this problem is to have a dye, which stains the anterior
capsule. This dye is TRYPAN BLUE. It is marketed as Blurhex made by Dr
Agarwal Pharma Ltd. Each ml of Blurhex contains 0.6 mg trypan blue 1.9
mg of sodium monohydrogen orthophosphate, 0.3 mg of sodium
dihydrogen orthophosphate, 8.2 mg of sodium chloride, sodium hydroxide
for adjusting the pH and water for injection.
TECHNIQUE
We always tend to perform a temporal clear-corneal incision. If the
astigmatism is plus at 90 degrees then the incision is made superiorly. First
of all, a needle with viscoelastic is injected inside the eye in the area where

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122 Section I: Cataract

Fig. 14.1: Left hand injects viscoelastic


using a 26 gauge needle

Fig. 14.2: Clear-corneal incision

the second site is made (Fig. 14.1). This will distend the
eye so that when you make a clear-corneal incision, the
eye will be tense and one can create a good valve. Now
use a straight rod to stabilize the eye with the left hand.
With the right hand make the clear-corneal incision (Fig.
14.2).
Now inject air into the anterior chamber (Fig. 14.3).
This prevents water-like dilution of the trypan blue. Then
the trypan blue is withdrawn from the vial into a syringe.
This is then injected by a cannula into the anterior
chamber between the air-bubble and the lens capsule
(Fig. 14.4). It is kept like that for a minute or two for
staining of the anterior capsule to occur. Next viscoelastic
is injected into the anterior chamber (Fig. 14.5) to remove
the air-bubble and the trypan blue.
Now, rhexis is started with a needle (Fig. 14.6). One
can use a forceps also. We prefer to use a needle as it
gives better control on the size of the rhexis. Note the

Fig. 14.3: Air injected inside the anterior chamber

Fig. 14.4: Trypan blue injected between the air-bubble and


the anterior lens capsule

Fig. 14.5: Viscoelastic injected to remove the airbubble and the trypan blue

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Chapter 14: Trypan Blue in the Management of Mature Cataracts

123

Fig. 14.6: Rhexis started with the needle. Note a straight


rod in the left hand to stabilize the eye

Fig. 14.9: Rhexis completed

Fig. 14.7: Rhexis continued. Note the contrast between the


stained anterior capsule and the unstained cortex

Fig. 14.10: Note the stained anterior capsule lying


in the anterior chamber

Fig. 14.8: Rhexis nearing completion

left hand holding a rod stabilizing the eye while the rhexis
is being performed. The rhexis is continued with the
needle (Fig. 14.7). Note the contrast between the capsule,
which has been stained, and the cortex, which is not
stained. The rhexis is continued (Fig. 14.8) and finally
completed (Fig. 14.9). When the rhexis is complete, we
can see the stained anterior capsule lying in the anterior
chamber (Fig. 14.10).
Hydrodissection is then done (Fig. 14.11). One will
not be able to see the fluid wave in such cases as the
cataract is very dense. In such cases a simple way is to
see if the lens comes up anteriorly a little bit. This will
indicate hydrodissection being completed. One can also
test this by rotating the nucleus before starting phaco.
We then insert the phaco probe through the incision
slightly superior to the center of the nucleus (Fig. 14.12).

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124 Section I: Cataract

Fig. 14.11: Hydrodissection

Fig. 14.13: Phaco probe embedded in the nucleus

Fig. 14.12: Phaco probe at the superior end of the rhexis.


Left hand holds the chopper

Fig. 14.14:Left hand holding the chopper chops the nucleus

At that point apply ultrasound and see that the phaco


tip gets embedded in the nucleus (Fig. 14.13). The
direction of the phaco probe should be obliquely
downwards toward the vitreous and not horizontally
towards the iris. Then only the nucleus will get
embedded. The settings at this stage are 80 percent phaco
power, 24 ml/minute flow rate and 101 mm of Hg
suction. By the time the phaco tip gets embedded in the
nucleus the tip would have reached the middle of the
nucleus. Now, with the chopper cut the nucleus with a
straight downward motion (Fig. 14.14) and then move
the chopper to the left when you reach the center of the
nucleus. In other words, your left hand moves the
chopper like an inverted L. Do not go to the periphery
for chopping but do it at the center. Once you have
created a crack, split the nucleus till the center (Fig. 14.15).

Fig. 14.15: The two halves of the nucleus are split

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Chapter 14: Trypan Blue in the Management of Mature Cataracts

125

Fig. 14.16: Embed the probe in one-half of the nucleus. Go


horizontally and not vertically as you have now a shelf of
nucleus to embed

Fig. 14.18: Final bits of nucleus being removed

Fig. 14.17: Using pulse phaco the pieces of


nuclei are emulsified

Fig. 14.19: Cortical aspiration done

Then rotate the nucleus 180 degrees and crack again so


that you get two halves of the nucleus.
Now that you have two halves, you have a shelf to
embed the probe. So, now place the probe with
ultrasound into one-half of the nucleus (Fig. 14.16) and
chop. Like this create three quadrants in one-half of the
nucleus. Then make another three halves with the second
half of the nucleus. Thus, you now have 6 quadrants or
pie-shaped fragments.
Once all the pieces have been chopped, take out each
piece one by one and in pulse phaco mode (Figs 14.17
and 14.18) aspirate the pieces at the level of the iris. Do
not work in the bag unless the cornea is preoperatively
bad or the patient is very elderly.
The next step is to do cortical washing (Fig. 14.19).
Always try to remove the subincisional cortex first, as
that is the most difficult. Note that everytime the left hand

has the straight rod controlling the movements of the


eye. If necessary use a bimanual irrigation-aspiration
technique. Then inject viscoelastic and implant the IOL
(Fig. 14.20). At the end of the procedure, inject the BSS
inside the lips of the clear-corneal incision. This will
create a stromal hydration at the wound. This will create
a whiteness, which will disappear after 4 to 5 hours. The
advantage of this is that the wound gets sealed better.
ADVERSE EFFECTS
1. One is still not sure if extended contact of trypan blue
with the corneal endothelium produces corneal
damage. At present, no cases have been reported as
the trypan blue is washed off with the viscoelastic
and the BSS fluid.

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126 Section I: Cataract


4. During animal experiments, a teratogenic and/or
mutagenic effect has been reported after repeated
and/or high dose intraperitoneal or intravenous
injections with trypan blue. So, one should not use
trypan blue in pregnant women.
STERILIZATION
Sterilization is done by autoclave.
INDOCYANINE GREEN DYE
Indocyanine green dye (ICG) has also been tried for staining of the anterior capsule. It does not have any
mutagenic effects but it is costlier.

Fig. 14.20: IOL being implanted

2. Postsurgical inflammatory reactions and some


bullous keratopathy have been known to occur after
using vital staining agents.
3. Extreme care must be taken when using trypan blue
on patients who are hypersensitive to any of its
components.

SUMMARY
Trypan blue can make life much easier for the phaco
surgeon, especially in cases of mature and hypermature
cataracts by staining the anterior capsule. Another dye,
which has been tried, is ICG, which is much costlier.

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Chapter 15: My Personal Technique of Vertical Hubbing Phacoemulsification

127

15

My Personal Technique of
Vertical Hubbing Phacoemulsification
Keiki R Mehta

PREOPERATIVE PREPARATION
ANESTHESIA TECHNIQUE
PREFERRED PHACOEMULSIFIER
DRAPING AND PREOPERATIVE
PREPARATION OF THE EYE
MONITORING PATIENTS IN THE
THEATRE
OPERATIVE PROCEDURE
THE INCISIONS
CORNEAL ENTRY
THE CAPSULORHEXIS
HYDRODISSECTION AND
HYDRODELAMINATION
PHACOEMULSIFICATION
TECHNIQUE
TECHNIQUE OF VERTICAL
HUBBING
PHACOEMULSIFICATION
INDICATIONS

PREOPERATIVE PREPARATION
The patient is dilated with 5 percent NeoSynephrine eyedrops with 1
percent Homatropine eyedrops. Both the drops are commenced 40 minutes
prior to surgery. In case the pupil is tardy in dilatation, place a drop of
methylcellulose on the cornea, instill a drop of Neosynephrine and
Homatropine on it, lift the lid and shut it over the methylcellulose, tape
the eye shut for 5 minutes. Usually after that period the pupil is well dilated.
Another alternate technique to dilate a tardy pupil is to instill a drop of
Xylocaine 4 percent, and then to instill the dilating drops. It functions as
the epithelial cells closed junctions become tenuous, permitting easier
diffusion into the anterior chamber of the dilating drops.
I also favor preoperatively treating the patient with an topical antibioticNSAID combination for a day prior surgery. The rationale for it is that
surgical insult is much less likely to demonstrate any postoperative
inflammation. In addition the use of preoperative antibiotics to reduce the
risk of postoperative endophthalmitis.
ANESTHESIA TECHNIQUE
Topical anesthesia is my choice for 98 percent of all cataract surgeries. I
use topically, Xylocaine 4 percent eyedrops (Lidocaine). The Xylocaine is
drawn in two syringes through a Millipore (20 micron) filter.One syringe
is left outside the operating field to be used prior draping and washing
the patient, and kept with the circulating nurse. The second sterile syringe
is left on the operating trolley after clearly labeling it.
A drop is instilled three minutes prior surgery so that the eye may be
washed out with Betadine solution (5% Betadine mixed with distilled water
in a 50% dilution). After washing the eye out, a final drop of Xylocaine is
instilled on the cornea prior commencing the case.
Normally topical anesthesia is all that I use in virtually all cases.
However if intraoperatively the patient has a problem and the case is likely
to take longer (inadvertent vitreous loss, a complaining patient, one who
keeps rotating his eye like a metronome, etc) I also keep a 5 ml syringe
with 2 percent Xylocard (intravenous Xylocaine, preservative free,
normally used by the cardiologists) with a blunt parabulbar cannula. All
syringes are plastic, disposable and Luer Lock type. At that stage it is a
simple procedure to give 1.00 ml as a parabulbar injection. It is virtually
painless, no pressure needs to be applied to the eye to diffuse the anesthetic
agent, and takes effect almost immediately. Though the movement of the

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128 Section I: Cataract


eye will take about a minute or so to decrease and
stabilize down, the anesthetic agent takes effect almost
immediately.
I normally like to instill a final drop of 4 percent
Xylocaine after the lid retractor has been placed, just prior
starting. I lift the retractors just a little to enable the drop
to go all the way up to the fornix. Wait for about 30
seconds, wash off the eye with BSS and commence
surgery. I normally do not use the Xylocaine 4 percent
drops again at all.
In the younger anxious patients or in those in whom
Im not sure of achieving their full cooperation, a little
sedation is given intravenously. The amount of sedation
being such that the patient does not drop of to sleep but
just becomes a little more amenable to control. I like my
patients to be able to respond to commands during the
surgery. In those cases which need further supplementation, I/V Propofol administered in 10 mg increments
induces a transient hypnosis with amnesia which clears
rapidly in minutes.
In cases where the papillary dilatation is inadequate,
despite best efforts at dilatation of the pupil, and where
intracameral surgical manipulations will involve iris
touch, or in cases where I would intend to use iris
retractors (Greishaber), I like to inject little Xylocard 2
percent (preservative free Xylocaine) diluted 50 percent
with BSS,to convert it to Xylocard 1 percent, 0.5 ml
injected immediately after the side port opening is made,
prior injection of viscoelastic. Wait for a minute, wash
out the chamber, and proceed with the surgery. It reduces
the iris sensitivity and reduces ciliary proprioception
(Grabow). I also like to use Intracameral Xylocard in cases
where the cataract is very hard and where the surgery is
likely to last much longer with more ultrasound energy
in the anterior chamber and much more lens
manipulation.
I am a little hesitant to use Topical anesthesia with
patients who I cannot converse with during the surgery,
like mentally retarded patients, or even patient speaking
a language which Im not familiar with. In these patients,
I prefer to give a peribulbar injection of 2 percent Xylocaine with 150 units of hyluronidase admixed, a single
injection administered through a 24 G, 1 inch disposable
needle, the injection given through the upper lid. I feel it
is important when giving the peribulbar block to insert
the tip of the index finger between the orbital ridge of
the frontal bone and the eye, which deflects the eyeball
away. The patient is requested to look straight upwards
at the operating microscope light (visible through the
closed lid), and the injection of 3.00 ml is given at the
point 1/3 towards the nasal point of a line drawn between
the two canthii. No massage is given. The eye is taped

shut (to prevent accidental corneal abrasion) and the


balancing weights (Tony Fernandez 1992) are placed on
the eye. I personally do not prefer to use either Honan
Oculopressor, the Super Pinky ball as I feel that in cases
of an inadvertent venous leak by a slow hemorrhage in
the socket, the pressure induced is likely to compromise
the ocular circulation. The balancing weights balls are
safer since they are not a constrictive device.
The pressure from the balancing balls, is kept on the
eye for 5 minutes, the IOP is checked with the Schiotz
tonometer.The ideal pressure should be a minimum of
10 deflection using no weight (5.5 gm).
The patient should be made comfortable on the
operating table. It is preferable that the hands be loosely
restrained so that accidentally during the procedure in
case the patient falls asleep and suddenly awakes, he
should not move is hands up and make an unexpected
moment.
PREFERRED PHACOEMULSIFIER
My present personal choice is the Legacy 20,000 (Alcon).
The Alcon Legacy has exceptional fluidics, maintains the
chamber well, has excellent ultrasound power, with a
sensitive, balanced, stable, 4 crystal handpiece, rarely
induces bubble formation and works very well. I usually
use the Max-Vac setup with a, 30 degree, 0.9 mm diameter, straight tips which work very well on the hard
cataracts common to India. The Kelman 30 degree bent,
0.9 mm tip also works well but sometimes are a bit
unpredictable. Perhaps the biggest advantage of the
Kelman is that, since the tip is curved down, the surgeon
does not need to hold the handpiece at a steep angle.
The Legacy has superior followability making the
procedure much simpler. In addition the dynamic range
of fluidics allow the surgeon to really individualize
settings at every single phase of cataract removal depending upon the grade of the nucleus.
DRAPING AND PREOPERATIVE
PREPARATION OF THE EYE
The patients eye is washed out with 10 ml of Betadine 5
percent solution diluted with distilled, sterile water (not
tap), half and half (50% dilution), taken in a 10 ml plastic
syringe. The assistant keeps the lids open widely to
permit a proper wash. Subsequently cotton swabs soaked
in full strength Betadine, are swept along the lash line to
be sure that the lashes are clean and properly prepared.
Next the entire area of the eye is again flushed out with
distilled water, dried with a sterile towel. Two drops of
an antibiotic solution are instilled in the eye (at present I
use Tobramycin eyedrops).

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A highly adherent plastic drape, termed as Opsite
(Johnson and Johnson) Tegaderm (3M) which is commonly used to isolate the skin for surgical procedures, is
placed over the fully opened Eye such that it drapes the
lashes, deflected outwards and away from the field, and
drapes all crevices around the Eye and the surrounding
area.
It is important that there should be adequate oxygenation under the drapes. An ideal device to maintain it
are silicone nasal prongs. The tubes are looped around
the ear to stabilize them and the prongs placed in the
nostrils. Oxygen (if not available, even normal air) at a
flow rate of 8 volumes/minute. It is very reassuring to
the patient to feel air under the drapes which otherwise may make a patient very apprehensive and
asphyxiated. In addition it assures adequate oxygenation
which is very useful to a patient who has limited respiratory ability (asthmatics or those with chronic pulmonary conditions).
Over the draped eye, a second self-adhesive drape
can be utilized, and over that a sterile, absorbent, thick
cotton drape with a small hole is fitted over. The head is
draped in a double layer of cloth to isolate the forehead
and the face away from the site to be operated. It is
important to tape a piece of rolled absorbent gauze just
in front of the ear on the operating side so accidentally
water does not trickle in the ear during surgery, leading
to discomfort and sudden head movement. The normal
eye (the one not to be operated) is taped shut, gauze
placed on it and a protective plastic shield taped over it.
The tape directly on the eye is to prevent the gauge from
irritating it, and the shield is to protect the eye in case,
accidentally the surgeon does apply inadvertent
pressure, which may cause the patient discomfort and
again may be the cause for the patient fidgeting under
the drapes.
MONITORING PATIENTS IN THE THEATRE
I strongly feel that all patients, even if they are under
topical anesthesia must be suitable monitored in the
theatre. All my patients have a finger- probe oxygen
saturation monitor with simultaneous cardiac monitoring. A safety intravenous line is commenced with a 23G
Vent-Flo (silicone indwelling venous catheter) which is
much more stable and safer than a butterfly venous
needle, which tends to be displaced at the slightest
movement. I use a anesthesiologist as a standby in all
cases. He normally only gives the I/V antibiotics on the
table and monitors the patient, but gives supplementary
sedation and analgesics if required.
In the balance salt solution (BSS plus, considering its
high cost, is not really required for short procedures

129

unless the endothelial cell count is significantly low) is


added ml of a cardiac, preservative free, epinephrine
1/1000 (without Sodium bisulphate) instilled in a
500 ml bottle to maintain the dilatation of the pupil, and
to keep a good clean, bloodless field. In addition to the
500 ml bottle of balanced salt solution add 10 mg of
Vancomycin or 40 mg of Garamycin. The use of these
antibiotics, in my opinion, significantly reduces the risk
of endophthalmitis. Other authorities too concur. Linda
Strong 1999, Kraff,Gills 1999.
A final drop of Xylocaine is added and the procedure
is now commenced. I do not like to utilize more drops as
Xylocaine 4 percent used excessively will lead to punctate
epithelial keratitis, corneal erosion and a delayed postoperative rehabilitation, and is said to lead to endothelial
cell damage (Marr WG, Wood R 1957).
I prefer also to connect dual BSS bottles, connected
to each other and to the phacomachine by a thick walled
cm bored, plastic tubing (Normally used by Urologists,
it is known as a TUR set). The advantage of using this
tubing is that it gives a good flow and cuts down on surge
developing which is critical in the high flow techniques
used (Bangkok system). In addition in the BSS bottles
the airways are special long needles which reach right
up to the clear air space on top rather than being put in
below. It is important for the suction generated in a glass
bottle to suck in the air very often leads to fluidic
imbalance and suction variables especially if one is
operating at low suction near the capsule or in removing
the final little bit of cortical or cortex material.
OPERATIVE PROCEDURE
The patient is requested to look into the operating light
and advised that he keeps his eye stable and fixed at the
light. It is clearly explained to him that at the time phaco
is done he must not move at all. The operating light
intensity is kept low until such time that Phacoemulsification is commenced.
The plastic drape is incised, and a reversible spring
speculum is utilized to give the eyes open. An ideal
speculum is the Kratz modified, Barraquer speculum.
The spring speculum is preferable to fixed screw speculums, because it has a certain amount of give which
enhances patient comfort. Another advantage is that with
a flexible spring retractor the patient does not fight it.
He blinks a few times, tiring the orbicularis, and then
keeps the eye wide open.
THE INCISIONS
A side port incision is made with a Alcon V-lance blade
(1.2 mm spear), made with the blade as parallel to the

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130 Section I: Cataract

Fig. 15.1: Tunnel incision with a 2.8 mm diamond knife

cornea as possible to get a good self-sealing shelf. The


chamber is refilled with BSS from a 3 ml syringe to reform
the chamber and repressure the eye in preparation for
the main phaco incision.
Almost all my implants utilized are flexible and in
most of the cases a SI40 Allergan silicone foldable lens
inserted via an injector (Unfolder in Allerganese), which
goes through a 2.8 mm incision (Fig. 15.1). Hence virtually all my cases have a pure corneal tunnel. In case I
will put in a PMMA 5.25 mm IOL, I prefer to do a semiscleral incision in a curved V or chevron incision after
reflecting back the conjunctival flap.
CORNEAL ENTRY
The correct point of entry is posterior to the clear cornea,
utilising the perilimbal capillary plexus as a landmark
and slightly anterior to the insertion of the conjunctiva. I
always prefer to see a faint capillary bleed where I make
my entry. Since the incision is into a slightly vascular
area, better long-term wound healing can be expected
rather than a incision into clear cornea.
The clear corneal entry can be done in a two plane
incision or in a single plane incision. However the single
plane incision is best done with the special diamond knife
which has a bevel on the blade which is more pronounced
anterior than posterior (Fine). Here the diamond knife is
placed on the cornea, and following the corneal plane
inserted straight in without any attempt at dimpling the
cornea. Due to the variance in the front and back bevel
of the knife, it enters in smoothly, at the proper plane,
and gives an excellent corneal valve. I normally utilize
this 2.8 mm diamond, angled keratome (3-D Rheim).
In the two plane entry system, the first incision is
placed perpendicular to the corneal plane. I prefer to

place the first plane of entry at 10.00 oclock position.


Rather than directly entering into the cornea I prefer to
make a shallow groove with the sharp edge of the knife
and equal in length to the blades width. Care is taken
not to incise the conjunctiva, as this will result in
conjunctival ballooning during phacoemulsification and
during irrigation-aspiration, markedly reducing
visibility.
The second plane, which essentially creates the
cleavage in the corneal stroma and creates the corneal
flap valve, is created by placing the haft (the flat surface)
of the blade in apposition with the conjunctiva and
advancing in the plane of the cornea. When one had
advanced by 2.0 to 2.5 mm, the tip of the diamond knife
is turned forwards till it dimples the deeper layer of the
cornea. The knife is then allowed to go its full depth
creating a perfect rectangular and almost square incision.
Dimpling is not required with the Rheim 3D knife with
the anterior differential bevel as it automatically enters.
Removal of the knife from the eye is equally important. Many a good valve has been ruined by incising the
edge during removal of the knife. It is important not to
lift the knife during removal but to gradually slide it out
in the same plane that it was inserted.
It is important to try and attain a perfect square inner
entry zone. The characteristics of the flap valve stability
depend more on the construction of the inner corneal
valve and less on the total width or length of the incision
as is commonly thought.
If premature tip entry takes place, do not let it
continue. Remove the knife and change the position of
the entry. Alternatively even the same site can be used
but make the knife enter a corneal plane more superficial
than the last one. The new incision will tamponade
the old one. The incision when finally made, should be
2.8 mm in width and 2.00 mm in length which gives
exceptionally good stability.
If a 5.25 mm width narrow profile phaco PMMA IOL
lenses is to be used, ideally the incision should be a
square, but a 5.25 by 4.00 mm length incision usually
suffices. The position of the placement of the main phaco
incisions is identical in both eyes, namely at the 10.00
oclock position. If for any reason this site is not appropriate due to a very deep set eye or a prominent forehead
or nose, I like to shift to a temporal approach. The big
advantage of a fixed sitting position at the head of the
patient is that the position of my surgical assistant, the
microscope, anesthesiologist, and instruments or lie in
their fixed places and do not need to be shifted which
often leads to confusion and slows down the pace of
surgery.
I have found the use of an aspirating speculum
(Liebermans) to be a great help. The aspirating speculum

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is connected to a small dental vacuum pump which gives


a low vacuum of 5-7 mm of Hg which is more than
adequate.
THE CAPSULORHEXIS
My personal preference is to utilize a sharp tipped
forceps to do the rhexis in preference to a needle. (26G,
length) with its tip bent at a 45 angle. The sharp
tipped needle (26G, inch length, with tip of the bevel
bent to 45 degrees), though it has the advantage that one
can enter through a closed chamber, lacks control in
hypermature cataracts, marbled cataracts (where the
anterior capsule has a differentially thickened capsule,
as typically occurs in old, neglected cataracts), or in eyes
where the pupil is not fully dilated. On the other hand,
where the capsule is thick and leathery, especially in
young children, or is lax where there is doubt about
zonular integrity, it would make more sense to do a
needle rhexis.
Via the phaco corneal tunnel entry zone, the anterior
chamber is re-formed with viscoelastic. I normally like
to use methylcellulose which is frozen. Methylcellulose
kept in the compartment just below the freezer increases
its density by a factor of three. The frozen methylcellulose
compresses the capsule making rhexis extremely easy.
In addition frozen Methylcellulose (HPMC) does not leak
or ooze out easily, and is fantastic for use in children
where even Healon does not stay in long. Methylcellulose
is available as Occucoat (Storz) in USA and other
countries, and in India as Visilon, Hyprosol, Moisol and
a host of others. AmVisc Plus (Alcon) is also a good
viscoelastic which can be utilized, however it is quite
costly for the Indian situation. Healon, by itself has no
place in phacoemulsification surgery as it promptly
jumps out the moment the phaco tip goes in. However
Healon 5, functions well, and is very useful, though
prohibitively priced.
In doing a forceps capsulorhexis, I prefer to make
the incision in the capsule using the sharp pointed tips
itself. The initial opening is made at 5.00 oclock, about
2.5 mm inferior, measuring from the center of the lens
simply opening a mm in size. Closing the rhexis sharp
pointed forceps makes a beautiful little nick in the
capsule. Once the nick is made, the capsule is caught in
the tips of rhexis forceps, which are then moved to the
left in a counterclockwise direction, towards the 11.00
oclock position (Fig. 15.2). The forceps leaves the
previous hold and takes a fresh hold at the tip of the
rhexis tear, and the forceps is then swung to towards the
6.00 oclock position, until it reaches the 8. 00 oclock
position when it is re-held and then gradually swung in

Fig. 15.2: Rhexis commenced. Size ideally 6.00 mm

such a way that it meets the previous rhexis opening from


out. On an average three holds and re-holds are adequate
for a good, well controlled rhexis peripherally. Doing a
rhexis is like taking a dog for a walk. One needs to pull
its direction at right angle to the prompt direction to
change it to the new line.
If a needle rhexis is desired, I prefer to make the initial
capsular opening with a 26G, inch needle, performing
the initial capsular opening at the 6. 00 oclock position
about 3.00 mm peripherally to the center. The initial
opening is made by impaling the needle tip and pulling
down, to the 12.00 oclock position for about a mm and
then swinging it to the right to the 3.00 oclock position,
in one smooth maneuver. This simple arc-shaped
movement will give rise to a well-positioned flap.
The next step is to lay the flap onto the capsule, the
point of the needle must be used to move the detached
flap in a plane with the residual capsule. Try not to dig it
in the capsule. The whole secret is to nudge the capsule
along. Since the flap lies in apposition there is no chances
of a sudden breakout and often control is better. Be sure
to turn the flap, around till it reaches more peripheral to
the place where it began and turn it in the meet the origin
of the rhexis. The correct shape after completion would,
thus resembles an apple.
Ideally rhexis is best done under a viscoelastic though
it can also be done under BSS and even under air.
Viscoelastic has the advantage that it keeps the chamber
well formed and tamponades the capsule. If methylcellulose (HPMC) is used as a viscoelastic substance, it works
even better as frozen methylcellulose (kept in the last
shelf, below the freezer compartment) as it does not flow
out easily, and tamponades the capsule perfectly,
maintaining the chamber deep, even in a tight eye.

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132 Section I: Cataract


Both air and BSS based rhexis can only done with the
needle. Using a forceps and opening up the chamber lead
to a disastrous collapse of the chamber and even
inadvertent contact of the delicate endothelium and the
rhexis instrument. In both BSS and an Air-based rhexis,
the rhexis has to be done before the phaco corneal tunnel
is made, so that it is complicated in a totally sealed
chamber.
If the Phaco entry incision has been made prior rhexis,
it is safer and better, to use a third incision site for doing
the rhexis. Using BSS filled chamber during rhexis is easy,
provided a third port is made with a continuous infusion
of BSS (Blumenthal cannula),while the procedure is being
done. The only problem is that often the flaps floats
around and makes it difficult to carry out the procedure.
Though, in theory, air is better in an over-mature cataract, and the use of BSS based rhexis avoids the use
of the viscoelastic, it is always a bit dicey. The author
always uses frozen methylcellulose assisted, forceps
based, rhexis.
HYDRODISSECTION AND HYDRODELAMINATION
Hydrodissection is done utilising a fine, 24-26 G flattened
cannula with rounded edges, mounted on a Luer Lock
3.00 ml plastic disposable syringe. I always specify Luer
Lock since the time I shot a blocked needle in the eye.
Fortunately only the capsule broke with no other problems and the patient retained full vision, but it was an
experience, difficult to forgot.
Hydrodissection should be commenced at a point just
below the edge of the capsulorhexis. The tip of the
hydrodissection cannula should go just under the edge
of the rhexis, slightly lift it up, and then inject. This
technique is termed as Cortical cleaving hydrodissection.
Fine 1992. Hydrodissection should be commenced first
at 4.00 oclock position and subsequently at the 7.00
oclock and finally at 2.00 oclock position (Fig. 15.3).
Usually by this time the lens seems to move slightly
upwards, indicating that the nuclear zone has been
hydrodissected off. It is important after every injection
to gently compress the center of the nucleus to enable
better hydrodissection and prevent central pooling of the
liquid and allow the excess liquid to flow out again.
It is important to appreciate that hydrodissection in
a hard cataract can sometimes give trouble. The surgeon
injects, and the moment the fluid is injected, the chamber
shallows and, the intraocular pressure rises sharply.
What has happened is that the fluid has pooled at the
back of the lens, as it has no way to exit, and is now
pushing the nucleus forward. Any pressure on the lens
in an effort to push it back and deepen the chamber will

Fig. 15.3: Hydrodissection at two planes

lead to a posterior capsule rupture. At this stage the


correct management is to utilize a thin blade iris repositor and insert it under the capsular edge at 4.00 oclock
(the site of the primary injection) and sweep it sideways
to 8.00 oclock on the right and to 2.00 oclock on the left
side. Immediately the fluid will gush out and the eye
becomes soft and the chamber automatically deepens.
Hydrodelamination as a procedure is now rarely
utilized. It was originally conceived as the technique of
delineating the hard nucleus and the peripheral epinuclear material. It was in vogue during the four
quadrant grooving technique and was utilized as a
method to know how far one could groove in the
periphery without accidentally touching the capsule.
Since the advent of Nagaharas chopping techniques, and
its multiple variants, hydrodelamination is no longer
required. It is however still utilized as a means of
inducing a soft nucleus to break it into its component
parts and permit it to be aspirated easily, especially in
young adults.
Once the hydrodissection has been done, the nucleus
is rotated utilising a lens rotator. It should rotate freely
with no hesitation. If it does not rotate, it is important
that you hydrodissect once again.
The next step depends on whether the surgeon wishes
to either flip the lens out of the bag and on its front side
(Supracapsular tumble) or enable the lens to stand
vertically (Vertical phacoemulsification) or the float the
entire lens out (Anterior chamber phacoemulsification)
(Visco levitation) Mehta (1995) Kelman (1997). All three
technique are done by injecting viscoelastic under the
lens capsule, at 9.00 oclock, irrespective whether it is
the right or left eye. Injecting at this site leads the 3.00
oclock position of the lens (temporal in the left eye, nasal

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Chapter 15: My Personal Technique of Vertical Hubbing Phacoemulsification

133

in the right eye) to tip forwards. Using the same cannula


which is being used to inject the viscoelastic, gently
nudge the inferior pole of the lens. A small nudge will
make it stand up vertically (Lens salute Mehta 1997), if
more is injected, the lens will flip over and can be rotated
out of the bag supracapsularly (Maloney 1997). If one
injects without tipping the inferior pole, it will, if the
rhexis is 7.00 mm or more in size, float vertically upwards
or visco levitate (Mehta/Kelman).
PHACOEMULSIFICATION TECHNIQUE
There are two methods which I use the first is the
Tangential Phaco chopping technique a method which
was popularized in 1996 (Mehta). The second which I
prefer is the vertical nuclear hubbing phacoemulsification.
In 1996 I developed the tangential chopping technique
whereby the chop rather than going vertically through
the substance of the lens, would go obliquely. One had
merely to tip an edge of the nucleus out, impact the
nucleus in the middle with a phaco tip and using a sharp
edged but blunt tipped chopper obliquely the lens is plot
from the periphery to the center. The advantage was that
rather than trying to split the lens vertically literally
shards of the lens were removed. The lens was rotated
and then chopped again, once again obliquely. Ultimately
only the thin central shard was remaining which could
be flipped out and phacod. It proved very effective
especially in hard cataracts. The big advantage was that
the capsule was never at risk.
In 1998, I conceived of the concept of Vertical Phacoemulsification whereby the nucleus was tilted vertically.
Considering that the maximum density of the nucleus is
on the middle, common sense dictated that if one could
remove the hard central core, one would literally convert
the entire nucleus into a simple doughnut. The peripheral
ring composed off much softer nucleus and epinucleus
would come out easily.
I therefore designed the system of Hubbing Phacoemulsification, where the nucleus could be hubbed or
removed by coring out the middle of the lens.
TECHNIQUE OF VERTICAL HUBBING
PHACOEMULSIFICATION
It is a very simple technique. So simple in fact that when
I demonstrate it to visitors in my theatre, the first
comment usually is, Looks easy..why has no one thought
of it?.
The technique involves a 6.00 mm rhexis, following
a full hydrodissection placing the nucleus vertical

Fig. 15.4: Lens tilt or better known as Lens Salute

viscodissection at the 9.00 oclock position with the nucleus at 3.00 oclock position standing out of the capsule
bag (Lens salute) (Fig. 15.4).
The steps of the surgery are as under:
Nuclear Stabilization
Viscoelastic is inject from the side port incision. This
manages to stabilize the nucleus and prevent it flopping
back. From the side port, enter with the blunt tipped,
but sharp sided chopper and support the nucleus.
Coring the Nucleus
The next step is to core out the center of the lens. In this
technique termed hubbing, I like to use the Kelman
bent 0.9 dia phaco tip as it penetrate easily in the nuclear
matter. The phaco settings are now altered to 70 percent
Phaco power, vacuum is reduced to the minimum. Thus
when energized, the phaco tip can penetrate, and move
out of the nucleus without displacing it since no suction
is involved.
Supporting the nucleus from the left with the phaco
chopper held flat against the nuclear surface to stabilize
it, the phaco tip is placed squarely in the middle of the
lens and literally allowed to penetrate virtually all the
way through (Figs 15.5 and 15.6). The first core, made
in the middle of the nucleus is called the primary core
(Fig. 15.7). Subsequently make three, one secondary core
just above, and two, one at each side of the primary core.
The next step is to rotate the nucleus by 90o and make
the final core (Figs 15.8 and 15.9). In any lens up to Grade
4 in density, a total of five cores (one central primary
and four secondary cores) will literally, eliminate the

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134 Section I: Cataract

Fig. 15.5: Tip of the phaco bared for 1.5 mm to


permit better penetration

Fig. 15.8: The final core being completed

Fig. 15.9
Fig. 15.6: Lens supported from the left side phaco tip
impaled in the middle of the lens

hard central nuclear matter. If it is harder cataract,


another set of four cores (termed tertiary cores) are placed
a little peripherally and in between the previous four
secondary cores.
Snapping the Periphery
The lens is now converted into a doughnut. To aspirate
the final rim, it needs to be snapped. The chopper, which
till the present was only supporting the nucleus for the
coring is now allowed to slip in-between the cored
nucleus. Using a phaco in the right hand, the ring is split
open using the sharp inner curve of the chopper. After
snapping the ring, it is slightly widened (Figs 15.10 and
15.11).
Pulse Aspiration of the Ring

Fig. 15.7: Initial core made, phaco tip retracted,


second core planned

The open end of the doughnut ring is allowed to impact


onto the phaco tip. The settings now change. Ultrasound

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Chapter 15: My Personal Technique of Vertical Hubbing Phacoemulsification

135

Fig. 15.10: Edge of the chopper engaged into the


hole cored into the nucleus

Fig. 15.12: Shift to pulse phaco: let edge of the nucleus


impact onto the tip so as to carrousel it around

Fig. 15.11: Core snapped open. Now the


nucleus is open edged

Fig. 15.13: Final bit being pulse phacod into the phaco tip

power is kept at 20-30 percent depending in the density


of the lens, set Pulse at 8 pulses per second. Vacuum is
set at 400 mmHg, Flow rate at 18 ml/min, energizing
the tip will lead the entire rim of the lens to rotate
(carrousel) till it is fully removed (Figs 15.12 and 15.13).
An average phacoemulsification, from beginning to
end, done with no haste, in a medium dense Grade 4
cataract, with this technique can be completed easily in
6 minutes (Figs 15.14 to 15.16).
INDICATIONS
Though it is an exceptional technique and can be used in
virtually any type of density of nucleus, it however does
require a little care. It is difficult to tumble the lens
through a rhexis smaller than 6.00 mm in size. It is
possible to enlarge the rhexis using the split rotation
technique described elsewhere. Since the quantum of

Fig. 15.14: I/A to remove the residual cortex

ultrasound energy liberated in the anterior chamber is


very low, it can be used safely in Fuchs dystrophy,
patients with a low endothelial cell count, or prior keratoplasty, where the regular options do not apply.

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136 Section I: Cataract

Fig. 15.15: Silicone IOL injected into the bag

phacoemulsification shows any disparity in endothelial


cell loss. It is often thought that since, in coring U/S
energy is used more, the endothelial cells may be affected,
but in fact the extra energy is masked off the cells by the
fact that a phaco needle buried in the substance of a lens
does not radiate any energy out. A Topcon endothelial
specular non-contact microscope coupled with its own
special ImageNet software, showed no cell loss of any
significance in a series of 125 consecutive cases. Though,
in theory, endothelial cell changes must occur in any
surgery, in practice there is hardly a +/- 3.00 percent
variation change in the endothelial cell count.
Perhaps the greatest application of this technique is
that it is an exceptional transition technique for teaching
residents, fellows and young pledging surgeons the art
of Phacoemulsification without inducing any complications. It is easy to do, minimizes the risks of capsular
damage, removes the chances of inadvertent iris contact,
and enables even a hard cataracts be done with safety in
a short period of time. It is thus the technique of choice
in Eye Camps where, I am sure, it will supplant the
regular technique in time.
REFERENCES

Fig. 15.16: A perfect result

The important question, often asked is whether doing


a regular phacoemulsification as compared to a vertical

1. Edelhauser HF, Van Horn DL, Hynduiuk RA, Schultz RO.


Intraocular irrigating solutions: Their effect on the corneal
endothelium.Arch Ophthalmol 1975;93:648-57.
2. Marr WG, Wood R, Senterfit L. Effect of topical anesthesia on
regeneration of corneal epithelium. Am J Ophthalmol 1957;21:
302.
3. Fine IH, Finchman RA, Grabow HB (Eds). Clear Corneal cataract
surgery and topical anaesthesia, Thorofare: NJ Slack Inc, 1993.
4. Fine IH. The Rheim 3-D diamond knife.EyeWorld 1996;1:224.
5. Fine IH. Cortical cleaving hydrodissection. J Cataract Refract
Surg 1992;18:5,508-12.

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Chapter 16: The Prevention of Complications and their Management in Phacoemulsification

137

16

The Prevention of Complications and


their Management in Phacoemulsification
Keiki R Mehta, Cyres Mehta

PREVENTIVE ASPECTS
PRIOR COMMENCING
PHACOEMULSIFICATION
COMPLICATIONS AT VARIOUS
PHASES OF
PHACOEMULSIFICATION
SURGERY

Phacoemulsification is a superb procedure however it needs to be done


with care and caution. In the hands of a skilled surgeon, phacoemulsification can give exceptional vision, rapid rehabilitation, in a virtually
painless procedure
For the less experienced surgeon, if the selection of cases is not appropriate, there is always a possibility of having problems. In phacoemulsification every single step commencing from the preparation and positioning
of the instrument, to the proper construction of the corneal tunnel, the
capsulorhexis, and the completion of the procedure, have to be accurate
and well completed. A mistake in one step will snowball into problems,
which will complicate the steps to follow.
In this chapter, let us take problems as they arise. Some of them may
seem very small and steps to prevent them would seem to be insignificant,
but experience has taught that the smallest steps, if ignored can precipitate
situations, which are best avoided.
PREVENTIVE ASPECTS PRIOR COMMENCING
PHACOEMULSIFICATION
Positioning of the Patient
Proper positioning of the patient is very important as it permits stability
with adequate access to the eye. The brow and the chin of the patient should
be on the same horizontal plane and at right angles to the operating
microscope. It is important to keep a number of small rubber pillows, of
different thickness, ( 1/2 inch, 1 inch, 2 inch, 3 inch, 4 inch) which can be
added to get the best possible position of the forehead. It is important that
a rubber ring be inserted under the head on the final rubber pillow, which
will prevent the rolling of the head during surgery stabilizing it further.
The pre-made trough pillows (a section cut into them to fit the head) are
quite inadequate. Either they are too large, permitting excessive rotation,
or too small, in which case the head sits on the edges and does not fit into
the groove, making it very unstable.
Checking the Intraocular Pressure
It is mandatory prior commencing surgery, whether a retrobulbar, a
peribulbar, or topical anesthesia is being utilized that the intraocular
pressure must be checked with an Schiotz tonometer on the table. Many

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138 Section I: Cataract


surgeons will check the pressure digitally (using the
digits of two fingers) after giving a retrobulbar, or a
peribulbar block. The block merely relaxes the muscles
and a digital check-up merely indicates the softness of
the retro-orbital tissues and does not reflect the softness
of the eye. Checking intraocular pressure with an Schiotz
tonometer, immediate pre-op routinely is important.
Often surprises will occur when an eye, thought to be
soft digitally, will turn out to have a high pressure with
the tonometer.
In topical anesthesia, what must be remembered is
that the eyes are being maximally dilated, using a combination of Neo-Synephrine 5 percent with Homatropine
2 percent. Thus, there is always the chance of an angleclosure glaucoma developing, even more so considering
that the cataract, being advanced, is likely to have
swollen. A pressure up to 21 mmHg would be taken as
acceptable, while the surgery may need to be put off for
some time and an effort made to reduce the intraocular
pressure by I/V Mannitol or pressure with a Honans
balloon or Buys bag or the balancing balls. Ideal pressure
for phacoemulsification is 15 mmHg or below. Doing
Phaco surgery with a high intraocular pressure is asking
for trouble. The chamber will tend to collapse and will
remain shallow. There is always the likelihood of
endothelial damage. The chances of capsular break are
significantly increased, and God forbid, if the capsule
breaks, vitreous loss is virtually inevitable.
Oxygen or Fresh Air Under the Drapes
It makes sense to use a digital oxygen saturation monitor
in all cases. Fresh air provided under the drapes (fresh
air, since oxygen is not truly required, though preferable)
washes out the carbon dioxide, which induces air hunger
and makes a patient extremely restive. Patients, in the
older age group, already have compromised pulmonary
function and go into oxygen deprivation extremely
readily. The presence of fresh air whistling under the nose
gives the patient a comfortable feeling. If the surgery is
being done under topical anesthesia, adequate oxygenation is vitally important for a peaceful patient, which
would lead to peaceful surgery by a peaceful surgeon.
The ideal technique of introducing the air/ oxygen is by
using soft silicone nasal prongs, which enables the air to
whistle comfortably in the nostrils. The plastic tube
should be fixed so it does not move and irritate the patient
during surgery. The ideal technique is to loop the plastic
tube around the ears and then fix them under the chin.
Fixed in this manner, the tube remains stable no matter
how the patient moves. This particular technique termed
as the Santa Barbara method.

Placement of the Lid Retractor


The lid retractor should be able to properly open the eye
to achieve good access without causing any discomfort.
Essentially retractors can be divided into two categories.
a. Fixed retractors can be opened and fixed at a required
lid retraction or opening, using a ratchet arrangement
or a screw attachment. The advantage of the fixed
retractors is that the quantum of the opening can be
varied as per requirement. On the other hand, the
disadvantage is that the patient often tries to fight
the offending retractor, which causes pain, leads to
an uncooperative patient.
b. Spring retractors utilize a spring mechanism to keep
the eye open. The spring retractors only open to the
level at which the tension of the lid is offset by the
tensile strength of the spring. Thus the quantum of
opening is dependent on the tension of the lids vis a
vis the spring elasticity. The big advantage is that as
the patient tries to forcibly close the eye the spring
retractor automatically closes and then reopens. After
some time of this closing and opening cycles the
orbicularis tires and the eye remains open. However,
the advantage is that the patient is comfortable and
the cooperation of the patient is assured.
Aspiration of Excess Fluid
In a deep-set eye or in one that has prominent bony
configuration the BSS and secretions tends to accumulate
in the eye and reflect like a mirror back into the operating
microscope literally blurring the surgeons vision. It is
thus important that the fluid be aspirated or drained off.
There many types of drains available. Merocell is a close
mesh plastic which allows the fluid to flow out of the
eye. Built in aspirators is a benefit with retractors. Usually
the suction line is in built and the openings in the tines
of the retractors suffice to suck out the excess BSS and
secretion from the eye. This is an ideal type and is to be
recommended. Connect the aspirating retractor to a small
suction unit. Usually the suction units available in the
hospital are much too powerful and tend to suck and
not only the fluid but also the conjunctiva. A small gentle
dental suction unit that has a suction of 2-4 mmHg is
ideal. This little suction unit should be connected via a
silicone, autoclavable tube to the aspirating retractor or
alternatively, a small hand suction tip so the assistant
can do the suction. It keeps the field dry, prevents
merocell or cotton swabs from being used continuously
near the fornices. This continuous swabbing predispose
to redness and small sub-conjunctival hemorrhages the
next day. It also increases the possibility of accidental

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Chapter 16: The Prevention of Complications and their Management in Phacoemulsification


pressure on the eye, especially after the attendant
becomes in attentive, after long list of surgical cases,
typically at the end of the day.
COMPLICATIONS AT VARIOUS PHASES OF
PHACOEMULSIFICATION SURGERY
The incision is the most important part of the phacoemulsification surgery.
Clear Corneal Incision
To be a self-sealing incision, the tunnel must be of an
adequate length. The incision at the entry point on the
cornea and the exit point at the Descemets membrane
should be a straight line if the valve is to really function
well. The ideal instrument is a diamond knife where there
is a deferential bevel between the front and the back. This
type of a diamond knife, conceived by Dr Fine, made by
Rheim, called a 3D blade, and gives almost perfect tunnel
formation time after time after time. However, a metal
keratome or knife would also work well but would need
a lot more experience to achieve perfect tunnels. The
diamond knife does it effortlessly. Many surgeons prefer
to use a round beveled blade to dissect a pocket, and
then use a 15-degree sharp knife to enter into the anterior
chamber. Though in the hands of an expert this technique
would seem to be adequate, its ability to do consistent
corneal tunnels is limited.
With phacoemulsification, it is important that the
width of the incision must exactly mimic the width of
the phaco tip used. Some machines require 3.00 mm for
the phaco tip introduction in the anterior chamber while
in others 2.8 mm may be ideal. In the authors machine,
an Alcon Legacy with the 0.9 mm diameter tips, a 2.8
mm incision is required. If incision is too narrow, it is
difficult to insert the phaco tip, which is liable to brush
against the Descemets and even detach the Descemet is
as the phaco tip enters the anterior chamber. The other
problem being that if it is too narrow the sleeve tends to
get compressed in the lips of the tunnel, choking off the
inflow of irrigating solution. A phaco tip remains cool
by the flow of irrigating solution over the phaco tip under
the sleeve and by the outflow of aspirating solution
through the needle. It is, however, the irrigation flow
which does the main work. If the sleeve is too tight in
the incision, it chokes off the irrigating flow allowing the
temperature of the phaco tip to build-up which is liable
to produce corneal burns. The biggest disadvantage of
corneal burns is that it makes the cornea at the burnt
area shrink slightly, which retracts creating a bridge over
the incision, no longer functioning as a self sealing

139

incision and even requiring sutures to close the incision


adequately on completion of the surgery.
The problem of a proper size incision can be solved
by using the appropriate blade, calibrated precisely for
that incisions requirement. One of the advantages of a
diamond blade is that a 2.8 mm blade will give you an
exact 2.8 mm incision. Since no pressure needs to be
applied on a diamond blade during entry, the width of
the incision remains a constant.
If on the other hand the incision is too wide, fluid
tends to escape from the sides, disproportionately, with
the result that the chamber depth tends to fluctuate and
is even liable to collapse. If the intraocular pressure of
the patient is high, more so if the vitreous pressure is
also high as occurs in myopes, a fluctuant chamber is
liable to lead to a break in the posterior capsule. In
addition the outflow from the leakage sites coupled with
the outflow from the bore of the needle would mean that
during phaco one can be saddled with an unstable, ever
changing anterior chamber depth with a bouncing
(trampoline) posterior capsule. A single mistake will lead
to a rupture of the posterior capsule with a vitreous break.
The Problem with Side Port Incision
A side port incision is very important . It is the entry
zone for the chopper to enter into the eye and the port
utilized to refill the anterior chamber at the end of the
surgery. An incision made too close to the limbus will
tend to impinge on the iris. In addition BSS escaping,
will tend to cause the conjunctiva adjacent to the site to
balloon up, making phacoemulsification difficult. In case
the tunnel is of inadequate length, it will tend to leak.
An easy way to get a proper length side-port incision is
to use an MVR blade (Alcon, or any other manufacturers,
1.2 mm width blade) and insert it at a horizontal plane
to the cornea. If the incision is made accidentally, too
wide, there will be continuous leakage, which would lead
to unstable anterior chamber. In case the incision leaks
excessively, it would be safer to place a suture and then
continue the surgery via a new side port, as it will prevent
problems.
Complications During Capsulorhexis
The capsulorhexis is a basic requirement for good
phacoemulsification as it allows the formation of a proper
capsule bag, which permits phacoemulsification to be
done within the confines of the back. It also has the
advantage that it permits a perfect placement of the
intraocular lens without any pressure on the sulcus. It
is the bag, which permits intracameral gymnastics

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140 Section I: Cataract


permitting the easy and safe removal of the nucleus. It is
important that the capsulorhexis have a perfect round
circle, which is not broken, nor has any nicks, which
would permit the capsule to tear when stretched.
To do a proper capsulorhexis one needs to have
perfect visibility, a good chamber filled with viscoelastic
and either a sharp bent needle or fine pointed capsulorhexis forceps.
It is always important to keep chamber well inflated
with viscoelastic. Healon is best but is costly. Iced methylcellulose seems to work extremely well and maintains a
constant compression on the surface, and most important
of all, being highly viscous (icing makes the methylcellulose increase by in viscosity almost three times) does
not readily come out of the chamber, keeping it well
inflated at all times.
Problems with the Capsulorhexis
Among the problems, which can occur during a capsulorhexis, the most frequent is a rhexis, which escapes of
into the periphery. The reason is not hard to see. The
anterior zonular fibers fan inserts onto the anterior
capsule usually at 8.59.00 mm from the lens center,
however, some aberrant fibrils will extend anteriorly up
to the 7.0 mm from the lens center ( Eisner 1975). If a
rhexis extended out to this level and reaches the zonular
insertion on the anterior capsular membrane, rather than
turning smoothly the rhexis will be deflected along the
zonular path, literally, running off into the periphery.
It is possible to shift it in again, using a forceps, but
be sure to use a repositor to sweep the anterior capsule
free of zonular adhesions prior continuing the rhexis.
With the rhexis forceps, grasp the edge of the capsule
and swing it sharply inwards. Usually it is more than
adequate to get the rhexis going again.
Another easy way to tame a rhexis, which has run
away from you, is to redirect it using a fine scissors, (a
long bladed Vanas scissor is ideal). Make a small fresh
cut in the direction you want the rhexis to go and, holding
the edge of the freshly cut capsule, complete the rhexis.
Be very certain not to exert stress at the place where you
have reverted the flap, as the initial extension is likely to
go to the periphery with problematical consequences.
Another method is to place a repositor under the edge
of the rhexis where you wish it to go, use a sharp pointed
needle and nick the capsule, Holding the inner nicked
part of the capsule, complete the rhexis, bringing the
advancing flap over the initial cut edge from the out, in.
This will once again restore the capsular bag integrity
(Vasavada 1997).

Prevention of Complications with


Hydrodissection
To prevent complications occurring it is important to use
a proper technique.
The technique involves injecting a small amount of
fluid (Ringer Lactate or BSS) under the anterior capsule
with a fine blunt cannula connected to a 3.00 ml syringe.
Because of the fluid pressure and the dissecting ability
of the fluid to take the path of least resistance, the fluid
separates the cortex and the epinucleus and partly separates the capsule and the cortex. During the hydrodissection, unless it is a very hard cataract or an opaque
one, the fluid wave can be seen clearly to separate the
cortex from the nucleus, and is indicative of a successful
hydrodissection. Hydrodissection is usually carried out
in three sites commencing with the 4.00 oclock position
followed by the 2.00 oclock position and finally followed
by hydrodissection at 8.00 oclock position. It is important
that small aliquots of fluid be utilized, as excess fluid
especially in a hard brown cataract is liable to balloon
the capsule posteriorly, rather than spreading as a wave,
and may, if more fluidic pressure is applied, rupture the
capsule.
It is important to visualize while injecting the fluid
diffusion wave. The ideal syringe is a Luer-Lock, plastic,
disposable, Teflon-coated or siliconized, of 3.00 ml
capacity. This type of a syringe permits a better control,
prevents application of too much pressure. Being Teflon
coated, or siliconised, the piston moves very smoothly,
and does not stick. Too thin a cannula, (ideal is 24-26G,
flat cannula), even if blunt is liable to puncture the
capsule if accidentally inserted too far into the periphery.
In addition, a thin cannula permits the fluid to emerge
in a sharp jet, at high velocity, which is not required. The
one way to be sure the hydrodissection is complete is to
check whether the nucleus rotates freely in the bag.
The ideal technique of cannula placement for effective
hydrodissection is to place the cannula just within the
capsulorhexis edge, slightly tenting it or lifting it
upwards. This technique termed as cortical cleaning
hydrodissection was originally conceived by Dr. Howard
Fine injecting the fluid along the rhexis edge permits the
fluid wave, literally to shear close to the capsule, thus
significantly diminishing the quantum of cortical remnants which will need to be aspirated after the primary
nucleus is removed by phacoemulsification.
In all cases, hydrodissection should be followed by
mechanical rotation of the nucleus to be sure the nucleus
rotates freely and that all adhesions have broken down.
It is important to appreciate that the lens does not rotates

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141

freely one must do hydrodissection again, and again,


until smooth rotation is achieved.
It is important that after every injection of fluid the
lens should be gently pressed backwards. This technique
is termed as compression hydrodissection and works
by causing the fluid to disperse and spread out as a flat
lamellar zone at the back of the nucleus and thereby
enhance the hydrodissection. This technique should
conduct gently with each injection of fluid under the
capsular flap. Compression hydrodissection thus decompresses a filled capsular bag, and at the same time shears
off any adhesions.
Managing Complications in Hydrodissection
Fig. 16.1

It is imperative that the quantity of BSS injected under


the capsule should never exceed 0.5 ml at a time. In addition, to prevent the risk of inadvertent perforation of the
anterior capsule, always use a 24 -26 G blunt cannula.
Always lift up the edge of the capsule. Besides doing a
good fluid wave, this technique also prevents accidental
puncture of the capsule, which will nick and weaken the
rhexis.
It is important to always press on the nucleus after
every injection to be sure that the fluid is dispersing well
and not accumulating below the nucleus, which may lead
to a rupture of the distended posterior capsule.
Impending Rupture of the Posterior Capsule
Every surgeon, at some time or the other is liable to break
the posterior capsule during hydrodissection. If one
learns to identify the signs of an impending rupture, it
can be handled safely. In case rupture does occur, it is
important to identify it early, as soon as it occurs, so that
the problem can be managed smoothly with minimal
complications (Figs 16.1 and 16.2).
The earliest signs of an impending rupture is to have
the iris/lens diaphragm move forwards reducing the
anterior chamber to a thin chink. At this stage if the
surgeon panics and tries to force the reformation of the
anterior chamber by injecting viscoelastic under pressure
or, worse still, tries to push on the nucleus, in a backward
direction, it will immediately lead to a rupture of the
posterior capsule.
The method of handling it at this stage is simple. All
on needs to do is to take a thin blade iris repositor and
introduce it under the capsule in the 5.00 oclock position
and then sweep in, under the capsule to 3.00 oclock
position and then to the 7.00 oclock position. Almost

Fig. 16.2

immediately, the surgeon will be rewarded with a gush


of fluid indicating that the block has broken
Managing the Ruptured Capsule
after Hydrodissection
Rupture is detected by the tight eye suddenly going soft,
and the iris and the nucleus moving backwards with the
chamber deepening. At this stage though the posterior
capsule has ruptured, the nucleus and the cortical
material stay in the same place in the posterior chamber.
Inadvertent and inopportune surgical movements will
now precipitate a problem with the nucleus luxating into
the vitreous (Figs. 16.3 and 16.4).
If the nucleus is likely to drop into the vitreous or has
luxated into the vitreous, its technique of management
has been discussed later in this chapter.

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142 Section I: Cataract

Fig. 16.3

Fig. 16.4

Problems and their Management During


Phacoemulsification of the Nucleus
Essentially phacoemulsification can be divided roughly
into two eras. The Pre-Chop and the Post-Chop era.
The Pre Chop era was dominated by the methods of
grooving and splitting and then finally flipping. It is still
a common technique in use today in India and thus is
being evaluated in detail.
Problems with Nucleo-fractis and In Situ
(Four Quadrant) Phaco Fracture Technique
Nucleo fractis or divide and conquer was first commenced by Gimbel 1986 subsequently modified as a 4 quadrant or in situ method are perhaps some of the most
common techniques being used in India. They were the
precursor to the Nagahara Chop technique, which has
literally revolutionized the phaco surgical scene.
Hydrodelineation in this procedure is very useful as
it tell the surgeon how far he can go in the periphery

without any risk. The phaco settings should set at 75


percent power but with minimal aspiration and a low
flow rate.
Be always sure to have a perfect hydrodissection. The
nucleus should spin like a top in the bag. In both the
nucleo-fractis as well as the 4 quadrant technique, the
problem always has been, the depth of the grooving
should be adequately deep to get to the thickness level
for a proper split to develop. For a proper groove, one
needs to shave off the nucleus, layer by layer. Taking care
not to bury the tip, making sure only the lower third of
the tip is occluded. The bottom of the groove is typically
at the level of the posterior Y suture. The red reflex can
also be used to gauge the depth of the groove. It gets
progressively brighter as the midline is passed. Care
should as always be exercised that the grooving is done
in a bowl fashion, deeper in the middle but shallower in
the periphery.
As a routine make, all the four grooves meet in the
middle and communicate with each other prior splitting.
This will make sure that the crack or split goes all the
way to the bottom. It is important if one is to achieve a
good split that the surgeon places the tips of both his
cracking instruments at the base of the groove. The
cracking or splitting can be done effectively in two ways.
a. A direct split, i.e. the instruments, placed at the base
of the groove (a blunt dissector or chopper in the left
hand, the phaco tip in the right hand), is separated.
b. In a contra-lateral split, the two instruments at the
base of the groove cross themselves. I.e. the phaco
tip, though held in the right hand, presses the left
sides of the groove and vice-versa.
In a soft cataract, a direct split is easier. In a hard
cataract, better leverage is obtained with the contra lateral
split.
Cracking the lens through both the grooves fully,
convert the round grooved nucleus into a four-piece pie.
Now, rather than trying to pull out the piece with the
phaco, (a dangerous and often futile maneuver), lever
out the tip of one piece using the left hand held, blunt
probe. Let the tip impinge onto the phaco tip; turn on
U/S and phaco it out. The phaco settings at this time
should be changed, high aspiration rate, a high flow rate
and moderate phaco power.
Most surgeons now a days, who are still utilizing this
technique, make only a single groove, split the nucleus
apart and then at this stage turn the nucleus high around,
using the phaco chopper in the left hand impale the
nucleus, and the chop it into two or more parts. Its saves
a great deal of time and works equally well.
For harder cataracts Gimbel had in 1992, devised the
Downslope technique. The technique involved pushing

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Chapter 16: The Prevention of Complications and their Management in Phacoemulsification


the nucleus downwards towards 6.00 oclock with the
spatula while the grooving is done. It had many advantages. It was a safer, better-controlled maneuver and could
get the groove done longer, and deeper and thus making
splitting hard cataracts easier.
A further modification of the above technique was
the Crack and Flip technique ( Fine, Maloney and
Dillman 1992). Once again a variation of an established
technique done to compensate for the problems in the
previous methods. The grooving and cracking as per the
previous techniques, the residual epinucleus is flipped
out by gently holding it low aspiration with the phaco
and with the other hand rolling it out. This solved the
often-problematical epinucleus removal.
The Flip method enhancing safety for epinuclear
removal, is a useful technique, and should be in every
surgeons armamentarium.
Complications with the Phaco Chop Techniques
The Post- Chop era of Phacoemulsification commenced
with Nagahara describing at the ASCRS meeting at
Seattle in 1993. A novel, new approach by chopping a
nucleus into its component parts directly. The entire
concept was that the nucleus is held firm by the phaco
tip while a sharp tipped chopper is used to score the
surface of the nucleus and the split it down. It made a
world of difference as grooving was unnecessary and
there was no need to go into the depths of the groove for
the cracking. The risk to the capsule dropped drastically.
In addition, the surgery became, more predictable and
faster. Even the hardest lens could now be chopped (at
least partially).
Managing Problems with the
Phaco Chop Technique
Fixation of the Nucleus
Unless it is properly fixated, the nucleus would slide off
the phaco tip. It makes it easier to use the tip with the
bevel forwards rather than down. Place the tip on
the surface of the nucleus just within the rhexis at the
12.00 oclock position, turn the phaco power on so that
the tip sinks into the nucleus and wait till the suction
builds up to its maximum pre set limit. Keep the tip
pressed down gently and only then position your
chopper for the next step.
Selection of the Chopper
The chopper has to be sharp to score the nucleus. The tip
has to be at least 1.5 mm long. It is preferable if the tip is

143

slightly flattened so that resistance will be encountered


with side movement, which will make the chopping
easier. The novice often errs on the side of using a short,
blunt chopper, a guaranteed recipe for failure. If possible,
the chopper should have its flat side slightly skewed by
20 degrees. Since the chopper and the phaco tip will be
separated by an angle of usually 30 degrees, skewing
the angle of the flat sharp side of the chopper makes for
easier chops especially in hard cataracts. A single point
of caution: To keep the tip of the chopper sharp always
leave it covered by a silicone tip when not in use.
There are places where a blunt chopper proves useful
a. Tangential chop technique. The chop goes tangentially against the substance of the lens.
b. When the fragment are small, but the cataract is
hard, a sharp sided, blunt tip chopper is preferable
as it can repeatedly make into thin slivers the hard
cataract and allow easy aspiration with the phaco
tip.
c. In soft cataract where there is a risk of the chopper
sinking through the substance of the lens. Here if
the chopper tip is sharp, the capsule is at risk.
d. In anterior chamber phaco. When the lens is
rotated into the a/c, one goes from the side and
does a peripheral chop to prevent accidental
corneal touch. The lens is spilt from the sides; the
blunt tip prevents entanglement and injury to the
iris.
Placement of the Chopper Tip
The chopper is inserted flat through the side port incision,
taking care that the iris does not entangle in the sharp
chopper tip during insertion. Once the nucleus is fixated,
go back from the tip by 3.00 mm and impact your chopper
in the nucleus. This distance of 3.00 mm from the phaco
tip is usually enough. It is unnecessary to go under the
capsule to the equator of the nucleus,
Now place the sharp edge of the chopper against the
nucleus, press gently downwards and pull towards the
phaco tip, While the Phaco tip holds the nucleus steady,
the chopper first scores the nucleus, and then buries itself
deeper, in the manner of a plough. When close to the
phaco tip, the chopper is moved to the left, while the
phaco tip moves to the right, splitting the nucleus into
two. The action is almost like splitting a log of wood after
embedding an axe into it. The important step is to keep
the downwards pressure on the chopper as it moves
towards the phaco tip. That particular movement buries
the chopper deep in the nucleus. Also remember to
allow both the instruments to separate so that the cleft
deepens.

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144 Section I: Cataract


Proper Holding of the Nucleus for a Chop
One of the common complaints is that the nucleus shifts
off the phaco tip preventing proper chop. This is because
an inadequate impalement of the phaco tip has taken
place. To get a proper impalement the phaco tip must be
buried in the depths of the nucleus. To get a proper depth,
two steps are important. First as one enter s the eye, in
the idle of the nucleus, swirl the tip around without
ultrasound. This will remove the superficial epinucleus
exposing the harder nucleus below. Now in a second step,
with a little ultrasound power make a shallow saucerised
space in the middle. Now with your phaco tip bevel
facing forwards apply the phaco tip just ahead of the
upper (12.00 oclock) edge of the rhexis and with a single
burst of ultrasound bury it in the nucleus. Wait until the
suction rises to its preset limit and then proceed with the
chopping.
Rather than doing it directly, many authorities (Koch
et al) Stop and chop) recommend that a shallow groove
be first prepared, turn the lens at 90 degrees to the groove
and then impale in the substance. In this way, the nucleus
is held firmly and with hard lenses, the chop can be done
with adequate force.
Rotation Following the Phaco Chop
Rotation of the nuclear fragments in the bag can be a
problem sometimes as after dismantling the pieces the
place in the capsule bag becomes very, limited. A simple
technique is to lever out one tip of the chopped piece
with the tip of the chopper, and to phaco it off. Automatically space is increased, and it makes more room
for better rotation and more place for the segment to
move when they are being chopped which leads to better
and deeper chops.
Chopping very hard nuclei (6 +) is very difficult. This
is because of the harder central nuclear zone, which has
a different density and therefore does not chop through.
To remove it, many new techniques have been developed.
The Shelling technique (Mehta 1997) is perhaps the
easiest. Make a central chop, and then extend it to the
side. This will expose the central nucleus. Phaco this
central nuclear zone separately with simple aspiration
and ultrasound. This part of the nucleus is a homogeneous material and does not need to be chopped. This
now leaves an empty bag of nucleus, which is flipped
over, and phacod,
Another, more innovative method is the Saddle
rump technique. It is based on the concept, that if one
breaks the binding of a book, the pieces come apart and
then can be easily tackled. In the Saddle rump technique,

(Mehta 1999) the edges of the nucleus are clipped or lifted


off with a special chopper, and gradually the lens is
unraveled. The surface is phacod separately as is the
central area. The deeper posterior nuclear material id
flipped over and then phacod. Both techniques have
been described in the Chapter on Managing Suprahard
Cataracts.
To Convert or not to Convert into ECCE
that is the Question
Whether it makes sense to continue a difficult case, or to
call it a day and convert to a standard ECCE, is a decision
every surgeon needs to make for himself. He has to
consider the patient, the density of the cataract, the state
of the corneal endothelium. (Consideration is even more
critical if this is the only eye of the patient). Against this
has to be balanced the surgeons knowledge, his faith in
his own skills, his confidence in himself and his ability
to handle a complication if it precipitates.
Another important point to consider is the machine,
which is being used by the surgeon. Some machines have
very good fluidic control and exceptionally fine
ultrasound and aspiration ability, and automated antisurge controls. (The Alcon Legacy, the Allergan Sovereign
and Diplomax and the Storz Millennium). Tacking a
difficult case with these units will naturally be far easier
than doing it with a small economical machine, which
does not have the appropriate capabilities. That is not to
decry some of the smaller machines, which work
perfectly well, but in a difficult situation the better the
machine the more superior are your chances of staying
on the top a difficult phaco situation.
In a hard cataract, an intact, well-designed, capsulorhexis is mandatory. No rhexis abort and convert, for
inevitably, in a majority of cases you will land up in
trouble.
The moment for conversion is when the surgeon starts
feeling unhappy with the situation - too hard a lens, a
nucleus refusing to chop and fragment, a rhexis which is
inadequate, an eye not responding as it should, a patient
who is becoming difficult, all tell the surgeon that it is
time he reconsidered his options. It makes more sense to
convert. If any doubt exists regarding the integrity of the
zonular or even, the bag, in a very hard cataract it is
grounds for immediate conversion.
Problems in Conversion to ECCE
A hard nucleus is also unfortunately a large nucleus, with
negligible buffering epicortical material. Hence, if it is
to be extruded from the bag, you will need to cut the
edge of the rhexis in at least three locations, two clock

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Chapter 16: The Prevention of Complications and their Management in Phacoemulsification


hours apart. Failure to do so will lead to an inadvertent
intracapsular extraction and/or a vitreous break. Do also
remember that with an intact capsule, the hydrodynamics
of nuclear expression are quite different and simple
pressure/ counter pressure will not work. You will need
to manually shift the lens into the anterior chamber by
rotating it out and only then expressing it out or hydro
expressing by a side port retainer ( Blumenthal). At this
stage, the use of visco-elevation is very useful. Inject
viscoelastic at the edge of the nucleus. If the bag is intact,
the nucleus will float (Visco-levitate; Kelman: Mehta) into
the anterior chamber. Another simple way is to do a
supracapsular tumble ( Maloney 1998), following a rhexis
multiple cuts, and shift the lens in front of the anterior
capsule. At this point, one can phaco it or extrude it out
of the a/c in a sliding ECCE technique.
Managing the Intact Posterior Capsule
It is important than that the posterior capsule remains
clear so that the visual axis is not impaired by any opacity.
A certain percentage of capsules will always opacify.
The younger the patient the quicker the capsule opacifies.
In a young child of 2-4 years, the capsules will opacity
in just a few months. Between the ages of 5 and 15, the
average opacification time is about 10-15 months. A
young adult between the ages of 20 to 40 years will
opacity in about 2-3 years. Those between the ages of
40 and 60 are likely to opacify in about 4-6 years while
those over the age of 60 many last for many years before
the need arises for the capsule is to be managed. Lest
it be misinterpreted that all capsule opacify, the average
percentage runs between 30 and 50 percent depending on age. The younger patients capsule all opacify,
while in the older + 60 age group hardly 8 to 10 percent
opacify. It would therefore make sense that the capsule
is managed to as soon as it tends to start becoming
opaque.
Treatment of this opacity can be during surgery
(intraoperative capsulotomy) or as a secondary procedure, done at a later date (postoperative capsulotomy).
There are some patients in whom the capsule should
always be left intact even subsequently. Those with high
myopia especially with retinal changes or who have had
a past history of retinal detachment, either in that eye or
even the other eye, those over had cytoid macular edema
in the other eye and those in whom there is a possibility
of a future fistulizing operation.
Though for practical purposes a capsulotomy may
be needed in future, the surgeon must try minimizing
the possibility of capsular thickening by leaving the
capsule as clear as possible. Among the methods, which

145

can be utilized, are to do an excellent irrigation/aspiration to remove all cortical material, which may reduce
the spontaneous re-absorbance. Polish the capsule to
eliminate as many proliferative cells as possible to avoid
the secondary opacification of the posterior capsule. It is
also imperative that all viscoelastic substances, which
had been utilized during surgery especially at the time
of implantation, be meticulously removed as this leads
to opacification.
Cleaning the capsule can be done in two ways.
1. With a hand blasted or a diamond tipped irrigating cannula.
2. With a ring polisher, which will permit, polish of
the posterior as well as the anterior capsule.
3. With the automated capsule polisher and in which
the vacuum is kept at 5 mmHg.
4. With an ultrasound polisher, which has rounded,
tipped and which can be moved over the capsule
shake the cells loose.
Intraoperative Primary Posterior Capsulotomy
It can be done in a variety of instruments, however, the
most frequently used is a fine needle (26G), which can
be attached on a syringe filled with viscoelastic.
Method of Usage of Polishing Cannula
The Kratz cannula is a simple irrigation cannula that is
blunt at the tip. The roughening has been generated by
sandblasting the tipped end. It is important that in using
this cannula, the flat surface be kept parallel to the
capsule, and it should be moved gently so that it doesnt
fold or ruck the capsule and tear it.
Diamond impregnated polishers should be used with
great caution as they go through the capsule very easily.
They are to be used only when the encrustation on the
capsule is very thick and one needs to polish the encrustation.
Vacuum capsule polishers are essentially the standard
irrigation/aspiration handpieces, with a 0.3 mm port. The
irrigation is diminished to 30 cm and the vacuum is kept
very low at 5 to 10 mmHg with a very low flow rate of 5
to 8 ml/min. The orifice is oriented onto the capsule and
while aspirating, it is gently moved over the surface of
the capsule. It is important not to ruck the capsule. The
secret of using this technique is to take your time. It works
well and all the fragments from the anterior capsule as
well the posterior capsule can be gently removed. It is
important that the tip be kept moving when the suction
is on. If it is left stationary for any length of time, the
capsule is liable to be trapped in the orifice and may be

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146 Section I: Cataract


torn if suddenly pulled. In addition the irrigating bottle
are kept low at the level where the capsule becomes flat,
and does not bulge backwards.
The ultrasound polisher is essentially a blunt needle
with tip rounded and roughened, connected to the
ultrasound hand piece. It must be used only after the
manual vacuum polishing of the capsule is complete as
by itself it is unable to complete the entire job. It shakes
off the final loose cells and is like a mopping up type of
operation. The U/S needs to be set to the minimum of
5 percent (depends from machine to machine).
It is important that the maximum possible magnification be utilized with which the surgeon feel is comfortable so that the small deposits, and areas of opacified
cortex can be identified and removed. If the cortex is very
transparent, avoid trying to polish it as it only puts the
integrity of the capsule to risk. The pressure exerted by
the polishing/cleaning instrument should be such as to
encourage only blunt dissection and should be able to
abrade off the particles without damaging the capsule.
The key to evaluate the quantum of pressure applied
to the capsule during the polishing phase is by looking
for the circular reflex on the capsule around the tip of
the polishing instrument. Normally the circular halo
should not exceed 3-4 mm any more and you are
applying too much pressure. Looking at the halo will also
tell you how clean the capsule is and if there are any
residual debris left, or if it is uniform and regular, and
free of any deposits
In case of any resistance encountered while polishing
the capsule, immediately desist from polishing further
because the polisher may have insinuated itself into the
capsule. The watchword for capsule polishing is caution.
The capsule is best kept under slight tension by
raising the irrigation bottle until the capsule is perfectly
flat. The risks was breaking of the capsule increase in
case the pressure of the irrigation fluid is kept too high,
which will make the capsule deeply concave, or if the
irrigation is too low, make the capsule convex.
Causes for Rupture of the Posterior Capsule
a. Accidental momentary touch with the ultrasound
phaco tip. This should, in theory, have no effect as
contact of the posterior capsule with a smooth
rounded phaco tip, with the ultrasound on, provided
it is not moved, should cause no damage .In practice
however, no phaco tip is perfectly smooth. After some
usage (In most countries, tips are used till they
literally die out), the tip is scratched and has multiple
sharp edges at the tip. If the suction is not too high
one may still get away with a small round hole with

an intact hyaloid membrane, but invariably, due to


the high suction combined with the high volume of
infusate, complicated with tip movement, the tear
invariably is complicated by the presence of vitreous.
b. The laceration of the capsule during chopping. It
occurs when the chopper is taken too far into the
periphery and the chop includes the edge of the
rhexis. If the chopper is very sharp, only a capsular
edge tear will occur, but if, as is frequent, it is slightly
blunt it will avulse the capsule. It also occurs when
splitting the pie sectors into smaller bits prior aspiration with minimal ultrasound. It can be prevented
by more attention on part of the surgeon with better
light and sharper visibility with higher magnification.
c. Discontinuity of the anterior capsule with a tear that
extends backwards involving the posterior capsule
invariably occurs when the capsulorhexis has been
made improperly, or the edge of the rhexis has run
off into the periphery. In these patients, any intracameral gymnastics leads to tear extension with a
posterior capsular tear in consequence.
d. Zonular disinsertion especially when the zonules are
weak as in cases of pseudoexfoliation or in cases of
hypermature old neglected cataracts or following
injury. However, not technically a posterior capsular
rupture it behaves in an identical manner.
Signs of a Posterior Capsular Rupture
The most common sign is deepening of the anterior
chamber and shift of the iris-lens diaphragm backwards.
The chamber is likely to become deep irregularly; In
addition, the nucleus and the cortical fragments seem
to move slowly by themselves. Nuclear rotation if
attempted will show restriction of movement. When left
after rotation the fragments partially creep back to their
initial places. These changes are because of the admixture
of the vitreous in the anterior chamber.
Another important sign is that the phaco will stop
working because of vitreous in the phaco tip. If the
capsule ruptures towards the end of the phaco procedure, this may even be the earliest sign. Occasionally a
small piece or even, if the surgeon is unfortunate, a large
piece of nucleus will luxate or drop into the vitreous
cavity.
The moment there is doubt about a posterior capsule
rupture, even if little, it is important to immediately stop
the phaco, take the phaco tip out of the anterior chamber.
Continuance of the phaco procedure will lead to extension of the tear with severe complications with a dropped
nucleus and admixture of the cortical remnants in the
vitreous with vitreous in the anterior chamber.

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Chapter 16: The Prevention of Complications and their Management in Phacoemulsification

Fig. 16.5

Managing the Broken Posterior Capsule


The rupture of the posterior capsule with its attending
complications is one of the most feared complications of
Phacoemulsification.
The management is dependant on whether the
hyaloid face is intact, the size of the tear, the stage at
which the phacoemulsification procedure has reached
and the complications which have ensued prior the
surgeons recognition of the posterior capsular rupture
Rupture of the Posterior Capsule
without Hyaloid Face Rupture
If the capsule gives way at an early stage of the nuclear
phacoemulsification, it is important to inject viscoelastic
below the nuclear fragment and gently try to maneuver
the fragments in to the anterior chamber (Fig. 16.5). If
Viscoat is available, it is an ideal material, but in its
absence frozen (iced) methylcellulose will work. If the
nucleus is hard and the size is big or the rhexis size is
small, you may need to give two relaxing cuts at the edge
of the rhexis to permit the nucleus to float out with a
little help from a spatula. Never inject viscoelastic under
the lens as the pressure of the viscoelastic will rupture
the hyaloid face and complicate matters. It is best not to
exert any pressure on the hyaloid face, nor on the
posterior capsule, as it will cause the tear to enlarge in
size. A spatula in one hand and a sharp chopper in the
other will coax the nucleus in the chamber.
Once the nucleus is brought in the anterior chamber,
we have three alternatives.
a. The simplest is to remove the nucleus by extending
the incision. Again, apply no counter pressure. Work
the nucleus out, under cover of a little viscoelastic,
with the edge of the sharp chopper to maneuver it,

147

and roll it out sideways. Following its removal a


gentle irrigation/aspiration to remove the cortical
remnants. The IOL can be fitted in front of the anterior
capsule as a sulcus fixated IOL.
b. In case the surgeon is confident of his own abilities
and the nucleus is not too hard, he may continue
phacoemulsification in the anterior chamber. The
nucleus once again needs to be maneuvered into the
anterior chamber and a lens glide needs to be slid
between the nucleus and the posterior capsule. You
may also utilize Michael or injectable (unpreserved)
Pilocarpine 0.5 percent. Lower the bottle, cut down
the aspiration rate to 12 mm Hg, decrease the suction
to 100 mmHg (in the Alcon Legacy with the 0.9 mm
tips), An Ultrasound power to 40 percent and gently
do a phacoemulsification. Chop the nuclear fragments into little bits and phaco them off.
c. If most of the nuclear material had already been
removed prior the break, continue with the phacoemulsification, after placing a bolus of iced methylcellulose or Viscoat at the broken site and after
lowering the bottles ( 1/2 meter above the patients
eye), gently proceed with the cortical remnants
removal and implant in the sulcus.
If one is confident of ones abilities to do the I/A in
these circumstances, dry (under viscoelastic) cortical
aspiration can be carried out. Inject viscoelastic form the
side port and at the same time continue to gently aspirate
out all the cortical remnants. Be extremely careful. No
sudden surge in pressure must occur, as the hyaloid is
very fragile
Rupture of the Posterior Capsule, with
Hyaloid Face Rupture, but without Luxation
of Nuclear Material into the Vitreous
Immediately stop any irrigation in the eye. The entire
secret of handling the situation is to use, as far as possible,
zero fluid. We can consider three situations,
1. If the opening is small and the lens fragments are not
too big, (i.e. we had almost reached the end of
phacoemulsification when the tear occurred, inject
viscoelastic under the fragments to support them.
Next, try to work the fragments one by one into the
anterior chamber. If the fragments are not coated with
vitreous and the surgeon was alert and responded
immediately to the capsular break, the Viscoat or
methylcellulose will force the fragments gradually up
in the anterior chamber. Try to work as many of the
nuclear fragments as possible up into the anterior
chamber. Next, place more viscoelastic and then insert
your phaco tip, with only aspiration, irrigation should

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148 Section I: Cataract


be very minimal and via the side port and only
allowed in when the phaco tip U/S functions and
when the suction is gently on. sucks. Gently suck with
only an occasional burst of low intensity ultrasound.
There is always the question of a corneal burn
occurring with little or no irrigation, but remember a
burn only occurs if the intensity of ultra sound is over
30 percent and is a continuous burst.
2. Alternatively, you may open the incision to 6 mm and
gradually with a thin blade wire vectis and spatula
remove the fragments. Subsequently again inject
viscoelastic and do a dry vitrectomy, remove all the
fragments and let your vitrectomy go 5 mm deep in
the vitreous, under the opening and again do a little
dry vitrectomy. Keep a BSS filled syringe in your hand
and only replenish the chamber if the chamber starts
to collapse and fill in just enough so that the chamber
fluctuation is minimized and the chamber is well
maintained. This semi dry vitrectomy works great
and you will be able to remove virtually all the
remnants and the cortical material with no problems
(Figs 16.6 to 16.11).
3. If the fragments are very large, i.e. the break occurred,
but the fragments do not show signs of an incipient
luxation, it is important to first inject viscoelastic
under the fragment and support it with a thin blade
spatula and gradually maneuver it into the anterior
chamber. The Incision is now widened to accommodate the lens nucleus for its removal. Using the
sandwich method (spatula or wire vectis below, a flat
broad blade iris repositor in front. The entire lens or
the fragment is supported and then slid out of the
chamber. Again, viscoelastic is filled and dry aspiration of the cortical fragments can be carried out. It
is important to do vitrectomy within minimal BSS
irrigation but with more of viscoelastic and do a

Fig. 16.7

Fig. 16.8

Fig. 16.9

Fig. 16.6

vitrectomy. Subsequently the IOL is placed on the


anterior capsule in the sulcus.
4. If the fragments are large, i.e. the break occurred, and
the large fragments are showing signs of an eminent
luxation
The method of handling this problem is termed the
Cruciate technique. A slightly different technique, but

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Chapter 16: The Prevention of Complications and their Management in Phacoemulsification

149

pupillary area. Now that the nucleus has been stabilized


one can open the chamber and using the sandwich technique remove the fragment, or if the nucleus fragment
seems soft and the surgeons very sure of his ability, he
may try to gently phaco the fragment out.
Lower the bottle height to 1/2 meters above the
patients eye. Reduce flow rate to 12 mmHg . Minimize
the quantity of fluid entering the eye and do a dry phaco
using viscoelastic, the BSS being only used to replenish
the chamber in case it looks as if it is liable to collapse.
This will slow down the pace in the chamber. Reduce
your ultrasound energy to pulse phaco with a maximum
setting of 40 percent power. Reduce aspiration rate.
Maneuver the nucleus into the anterior chamber
ahead of the iris. Now proceed with a slow phaco using
a phaco chop technique. Use minimum ultrasound
power. Move slowly. There is no hurry. You should
manage to complete the phaco with no difficulty.
Now insert your IOL, preferably foldable. Place it in
the anterior chamber. Do not remove the slide yet.
Maneuver each of the loop into the sulcus, in front of the
anterior capsule. Only then, remove the slide. Gentle
rinse out the chamber. Inject BSS via the side port and let
the viscoelastic gently wash out of the main phaco entry
port.
Remove the MVR blades only as a final step. Done
carefully the results are exceptional the next day. The eye
is very quiet (Figs 16.12 to 16.15).

Fig. 16.10

Fig. 16.11

essentially similar has also been described by Charles


Kelman (1998). All one does is to take two MVR blades
(Alcon) and insert them 5.00 mm from the limbus through
the conjunctiva and the sclera via the pars plana into the
vitreous and out the same way from the opposite side.
Place the first one at 7.00 oclock position; emerging again
at 2.00 oclock. The second one is placed at 4.00 oclock
and emerging at 10.00 oclock position. The assumptions
being that you are operating at the 12.00 oclock position.
In case you are operating temporally, change the position
of the MVR blades so that they do not interfere with your
routine surgery.
The next step is to introduce visco elastic and then,
using dry dissection, first aspirate out all the cortical
material, leaving behind only the hard nucleus.
Narrow the pupil with Miochol or with pilocarpine
1 percent eye drops.
The next step is to insert a plastic 3.00 mm size plastic
slide. This slide can be made from the sterile plastic over
wrap, which comes with the intraocular implants. Slide
it below the nucleus so that it occludes the narrowed

Rupture of the Posterior Capsule, with


Hyaloid Face Rupture, with Luxation of
Nuclear Material into the Vitreous
Unless the surgeon is very confident of his ability to do a
good 3 port posterior vitrectomy and to handle a contact

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Fig. 16.12

150 Section I: Cataract

Fig. 16.15

Fig. 16.13

Fig. 16.14

lens on the cornea, common sense would dictate that he


does a little anterior vitrectomy, removes, using dry
aspiration, as much of the cortical remnants and closes
up. It does not make sense to place an IOL, as it would
need to be removed by the retina surgeon when he gets
the fragment out. The only time it is considered permissi-

ble to place the IOL in is when the material that has


luxated is soft and the surgeon feels that with a phacofragmentor the retina surgeon will get the pieces out.
Never try and sweep the vitreous with a vectis as this is
almost a guarantee of either a massive retinal detachment
with the eye immediately filling up with blood, if
accidental retinal touch occurs, or a late detachment due
to the gross disturbance of the vitreous at a later date.
There are three ways the retina specialist may choose to
remove the lens.
a. Using PFC (perflurocarbon), after doing a full fledged
core vitrectomy, the nucleus can be floated up.
Though it looks a very simple technique, the perfluorcarbon needs to be completely removed or else
a severe reaction ensues and total removal is not
within the province of the anterior segment surgeon.
b. Following a good three port vitrectomy, the nucleus
is speared and then gradually using a bimanual technique with the light pipe in one hand and a diamond
coated forceps or a the spear in the other. The nucleus
is gradually lifted to the anterior chamber where it is
then removed after opening the chamber.
c. In an identical manner, following a vitrectomy, a
phacofragmentor is introduced through one port and
the lens fragmented in the vitreous itself .

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Chapter 17: Laser Phaco Cataract Surgery 151

17

Laser Phaco Cataract Surgery


Amar Agarwal, Sunita Agarwal, Athiya Agarwal, Suresh K Pandey, Clement K Chan

INTRODUCTION
HISTORY
LASER CATARACT SURGERY
PIONEERS
INSTRUMENTATION
THE SUNITA AGARWAL LASER
PHACO PROBE
ANATOMY OF DR SUNITA
AGARWAL LASER
PHACOEMULSIFICATION PROBE
COMPARISON
LASER PHOTON
IN-BUILT
USES
SURGICAL PROCEDURE
ADVANTAGES
HOW SMALL WILL OUR
INCISIONS GO

INTRODUCTION
From the time of its inception in 1949 with Meyer Schwickerath in Germany
the concept of lasers has caught the imagination of child and adult alike,
scientist and the public in general. Science fiction movies are made with
the concept of the laser as the ultimate weapon against all evil. Little wonder
then as eye surgeons we are always trying to better the techniques of
cataract removal over the years, thus today with lasers we find ourselves
equipped with one more wonderful tool in the armamentarium of the
operating room.
We are in the midst of a paradigm shift in cataract surgery today. We
must either become a part of the shift or we will be blind-sided by it. Today,
one of the latest developments in ophthalmology is the laser cataract
surgical system. The laser cataract surgery system would entail less trauma
and better rehabilitation of the patient.
HISTORY
Cataract the bane of old age has been known as a disease process to human
civilization for many years. Earliest records of its treatment were carried
out by Sushruta 500 BC the famous Indian surgeon who practiced a form
of medicine called Dhanvantri. He used a needle with no anesthesia,
through a bloodless route entered the eye through the cornea and dislodged
the cataract. The needle would stick into the cataract like a lollipop and
small movement of the cataract to and fro would break its zonular
attachments. Then the cataract would be made to fall into the deep vitreous.
This saved many a eye in that era and times, however many fell prey to
the adversities of the posterior segment. Yet today we have come a full
circle by bringing in the concept of no anesthesia, bloodless, painless, laser
phaconit (needle surgery) cataract surgery.
This idea of couching traveled the silk route into the Arab world and
reached the far corners of Europe. However somewhere along the 11th
century an Arabian scientist Ammar came up with the methodology of
removing the cataract enbloc out of the eye. Thus, started the road of
intracapsular cataract and extracapsular cataract extraction. For many years
the cataract would need to be rippend before the surgeon would go to
remove it.
Somewhere along the last two centuries sutures came into being and
cataract surgery became more and more safe where the eye and life were
concerned. However it was the remarkable discovery by Sir Harold Ridley
of PMMA pieces of plastic broken from the windshield of planes, lying
inert in the eyes of pilots of the Royal Air Force during the Second World

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152 Section I: Cataract


War. This led him to believe and rightly so that pieces of
plastic could be permanently placed in the eye to replace
the lost condensing power of the eye. Thus started the
saga of intraocular lens in 1949.
However it was the conception of the ultrasound
power by Charles Kelman in 1970 that made it really
possible to make cataract surgery as atraumatic an
experience as we see it today. It was also this ideology,
which made industry look around and give us the
foldable intraocular lens.
With the last two decades research into the idea of
lasers removing cataracts grew stronger and stronger. We
had some surgeons carrying out Nd:YAG laser capsulotomy preoperatively over a slit lamp delivery and then
taking the patient immediately to the operation theatre
to remove the cataract and replace with an intraocular
lens.
Around the latter part of the 80s a few patent applications were accepted for laser cataract surgery per se.
Here Dr. Eichenbaum created history by teaming up with
Paradigm Laser Photon and bringing out the first
commercially available laser cataract surgery system.
It was the authors (SA) good fortune to acquire such
a machine way back in 1995 and with continuous efforts
from the parent principal company and the experience
handed over through patients, evolution of this
methodology for cataract surgery has increased ever
more.
LASER CATARACT SURGERY
At the time when I first got the laser photon machine
from Paradigm (Fig. 17.1) all I could see was it was a
powerful machine. The laser fiber optic actually could
burn a hole in steel, thus I wondered if such a machine
can make a hole in steel a cataract tissue would be childs
play for it.
However, there were many barriers to this thinking
and soon I realized that evolution of a better system was
needed. The fluidics which make such an important part
of cataract surgery today was in its infantile phase. We
were actually holding vacuum levels at less than 100 mm
of Hg and this was not fast enough to remove cataract
tissue.
The major problem that all high-energy source have
is, even though they may disintegrate the tissue
instantaneously they also have the repulsion to push
away the piece from the aspirating porthole. Combating
this element with another physical capacity of the laser
being heat was another ball game altogether.
Nd:YAG laser was carried to the tip of the probe
through a fiberoptic and instilled inside the suction arena

Fig. 17.1: Laser photon machine from paradigm (USA)

with a sleeve outside bringing in the fluids. The laser


has the capacity to ablate solid tissue on coming into
contact, to about 20 microns tissue space. However a
small part of the tissue around this area of action would
get caseated due to the high protein content, slow
aspiration rate and high temperatures. This caseating
mass would then plug the aspirating porthole and the
surgery would have to wait till the mass was deluged.
This kind of method continued for sometime until I
realized this was not going to be effective enough.
Another aspect of laser cataract surgery is due to the
probe fashioned in the manner of a spoon. With the
aspiration in the deep part of the spoon, occlusion was
next to impossible.
We had learned till then the cataract was to be divided
and conquered, if occlusion was not possible then divide
and conquer was not possible. So started our road of
incorporating the laser with the ultrasound. The patents
for this probe were filed that same year, because we had
understood this was the wonderful link between
ultrasound and lasers.
This became the method of choice for tackling hard
and soft cataracts alike. Today we are slowly moving
away and away from ultrasound because we understand
the endothelial damage in an already compromised
cornea. Thus the increased interest in the laser that can
remove the cataract with the ease of an irrigation
aspiration handpiece yet the power of the ultrasound
vibrating needle.
We have much better fluidic control, our aspiration
rates can touch 350 to 400 mm of Hg, and this allows the
cataract to get sucked in before it has time to caseate on
the tip. The laser is much better centered in the probe
allowing all the laser energy to be targeted along the
cataractous tissue.

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Chapter 17: Laser Phaco Cataract Surgery 153


We have developed newer technologies for cataract
removal without having to subject the cataract into a
divide and conquer routine we are able to remove the
cataract with a carouselling technique
Like each temple to its own deity and each
monastery to its own monk so is each technique to its
own master. From the words of Jackie Chan, this relates
so to in our advanced laser phaco techniques, where each
surgeon has their own techniques.
PIONEERS
For decades now we have known benefits of the ultrasound energy. Incorporated with Dr.Kelmans path
breaking in roads of using this energy for the removal of
cataracts has indeed reduced rehabilitation of the cataract
patient.1-7
Four top ophthalmologists have been working
independently on the system of developing a laser to help
in cataract removal. The first has been Dr.Daniel
Eichenbaum from USA. It has been basically due to
Dr.Daniel Eichenbaum and Paradigm that the laser
cataract removal system could be started. They have
developed a machine called the Laser Photon. This laser
photon uses the Yag laser for cataract removal.
The second ophthalmologist Dr.Jack Dodick
introduced the use of the Yag:YLF laser for surgical
cataract removal. A laser beam is a fibre-optically directed
toward a titanium mirror target. The reflection produces
waves of optical breakdown power, resulting in
photoablation of the surface down to any depth desired.
Succeeding generations of instrumentation for this
technique have been modified and refined. The probes
are getting thinner and thinner compared to a phacoemulsification tip.
The third ophthalmologist is Dr. Michael Colvard. The
Erbium laser is being used by Michael Colvard to ablate
ocular tissue and its advantage is that it has maximal
absorption in water. When properly directed and
mirrored, as in Dodicks approach, the laser beam is kept
away from the posterior pole and the retina. safety seems
to be built into reflected laser ablation, allowing ablation
without thermal injury. In Colvards technique, the laser
beam is placed directly in contact with the nucleus of
the cataract for nonpercusssive cutting. By directing the
beam much as one would use an eraser to wipe over the
surface, the tip of the beam is directed over the ablation
zone, causing optical breakdown just at the beams tip.
The nuclear material is then removed with irrigation and
an IOL is implanted.
The fourth ophthalmologist was from India
Dr. Sunita Agarwal who designed a new probe which
incorporates laser and ultrasound in the same pico
second (Fig. 17.2).

Fig. 17.2: Sunita Agarwals laser phaco probe

In 1995 we acquired our first laser machine for cataract surgery. Soon we realized the potential of capitalizing
on both the energy sources together, something not
thought of by any cataract surgeon at that time. And we
developed a probe now capable of utilizing at the same
pico second laser and ultrasound energies.
INSTRUMENTATION
An ordinary phaco unit would contain three functional
elements, the phaco power delivered through a vibrating
titanium needle of 900 microns diameter, aspiration
through the needle, and irrigating fluid pump into the
eye through a silicon sleeve.
The laser unit consists of a key switch screwed into
the laser head unit that allows the laser light to pass
through a glass fiber optic delivery and the aiming beam
is also passed through the same system. This fibre is of
380 microns in diameter .
The laser phaco probe developed by Sunita Agarwal
is patent pending as the idea of incorporating laser with
ultrasound in the removal of cataracts was first developed by us and after going through many experimentations and variations we now plough the laser fibreoptic
through the phaco probe making any phaco probe into a
SA (Sunita Agarwal) laser phaco probe (Fig. 17.3).
The instrumentation is thus in two parts . One is the
Phaco part that most of us are accustomed too, and the
second is the laser part. These may come from the same
machine or from two different machines.
THE SUNITA AGARWAL LASER PHACO PROBE
All probes used before this (Fig. 17. 4) were thus designed
that used laser or ultrasound in the innermost

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154 Section I: Cataract

Fig. 17.3: Comparison between a phaco probe and


the laser phaco probe

laser fibre optic through the aspiration end of a regular


phaco probe. This version of the laser phaco probe gives
the advantage of using the laser, ultrasound, irrigation
and aspiration. Based on the ablation power of the laser
of water containing tissues four main have be evaluated
of which Nd:YAG has the lowest capacity for water
absorption. It has been further qualified with being near
perfect in effect and holds its place in the industry for
over two decades. The laser beam is focused onto grades
of high tensile glass fibre optic which carry the same and
release it on the cataractous tissue on contact and hence
the name contact laser. The laser photoablates 20 microns
of cataractous tissue on contact and liquefies a further
200 microns cataractous tissue around it.
COMPARISON

Fig. 17.4: Comparison between other companies and


Sunita Agarwals laser phaco probe

circumferential ring, with aspiration and irrigation


flowing on the outer ring. This was modified by special
intermediary equipment that would allow that
phacoemulsification machine to still function with a laser
fiberoptic delivery system in its midst. Around this is
the ultrasound waves pounding along with irrigation and
aspiration flowing on the outside. Thus the whole system
consists of a four function probe. The use and utilization
of both energy sources makes it easier for the cataract to
be blasted out of the eye in shorter time span, with less
energy sources used in the eye. The machine we used
was the laser photon machine.

Let us compare the phaco probe with the laser phaco


probe. There is a slight embarrassment to outflow using
the laser fiber optic (Fig. 17.6) in comparison with a
phaco probe. This is because the phaco probe is of 900
microns. The laser probe is 380 microns. This is placed
inside the phaco probe. So we get only 520 microns of
space left. Still the cataract is removed faster and much
more safely.
The laser has the capacity to photoablate 20 microns
of tissue space in contact and another 200 microns is
liquified reducing the solid cataract into liquid and gas.
The incision size is thus reduced as the phaco handpiece
gets hot and can burn the corneal tissue (Fig. 17.5). We
are able to perfom laser phaco in an incision of 2 mm
(Fig. 17.6). The phaco incision in the cornea can get
ragged with corneal burns. This rarely occurs in laser
phaco as the phaco energy used is comparatively very
small (Fig. 17.7).

ANATOMY OF DR SUNITA AGARWAL LASER


PHACOEMULSIFICATION PROBE
The author has designed this patent pending SA laser
phaco probe and it utilizes both, the laser to a maximum
extent and ultrasound to a lesser extent for cataract
removal. This probe can be developed by passing the

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Fig. 17.5: Phaco incision

Chapter 17: Laser Phaco Cataract Surgery 155

Fig. 17.8: Laser phaco probe


Fig. 17.6: Laser phaco incision

Fig. 17.7: Comparison of incision between


phaco and laser phaco

As the needle held in the hand is not vibrating anymore it can reach further into the eye without any
complications of iris capture or Posterior capsule capture.
Moreover, the laser is ineffective 500 microns away from
the posterior capsule and can be used very close to the
capsule.
The laser used is an ND:YAG with fiber optic delivery
and only the cataractous tissue needs to be removed thus
leaving behind an epinucleus and cortex that can be
easily aspirated .

designed that energy used to emulsify the cataract is


contained in a photovaporization chamber. The energy
used to remove the cataract does not expose the contents
of the eye to this energy. This gives the laser cataract
removal system an advantage over conventional phacoemulsification systems, with which the ultrasonic energy
can vibrate throughout the anterior chamber and involve
other ocular tissues.
The laser cataract surgery entails this specially
designed probe that combines fluid handling and
systems controls of ultrasonic cataract systems, now
fortified with the laser energy from a solid state pulsed
laser. All three major features of the system irrigation,
aspiration and laser are simultaneously transmitted
through a precise location in the eye through a single
small incision.
The laser is capable of ablating high water containing
tissues without pigmented chromophore. This is done
causing thermal injury. Its capability of performing these
functions through smooth cutting makes utilization
inside the eye very favourable. Most ocular tissues are
very high in their water content and the laser acts best in
these surroundings. Also its high absorption by the
cataractous lens makes its unwanted transmission and
scatter of laser energy to adjacent and underlying tissues
more controlled and precise.
The laser energy is generated through a solid state
crystal and its care and service come down to a minimum.
The laser is air cooled and does not require any special
installation practices. Hence it can be transported easily
to the end user facility with no untoward engineering
practices.

LASER PHOTON
In the Laser Photon (Fig. 17.8) pulsed laser energy is used
to vaporise and aspirate the lens material out of the eye
(Table 17.1). The most important feature of the Laser
Photon is its containment of laser energy. The probe is so

IN-BUILT
The laser photon machine has an in-built:
1. Laser,
2. Phacoemulsification system,

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156 Section I: Cataract


Table 17.1: Paradigm photon laser phaco system
specifications
Laser system

Specification

Type

Nd:Yag q-switched

Wavelength

1064 nanometers

Mode structure

Fundamental temoo

Pulse duration

Less than 4 nano seconds

Burst mode

One, two or three pulses per


burst

Pulse interval

20 microseconds

Energy (max)

20 ml per pulse

Energy selector

0.5 to 20 ml variable

Cone angle

16 degrees

Aiming beam

HENEintensity variable to
5 mw

Ultrasonic system

Specification

Ultrasonic capsule
probe-frequency

40 KHz

Ultrasonic phaco
probe-frequency

40 KHz

Ultrasonic phaco
probe-stroke

5 to 90 micron linear variable

General system

Specification

Fluidics

Peristaltic paraflow vacuum


system

Smartpac reusable
cassette system

Automated, programmable
Irrigation pole

Vitrectomy cutter

Pneumatic guillotine- 50-70


cuts per minute

Bipolar diathermy

On demand

Programmable

100 surgeon case programs

Display and indicators

Video crt and computer touch


panel Audio prompts for all
surgical operations

Cooling

Air quiet laminar flow base

Weight

175 lbs (79.4 kg)

Overall dimensions

21w-26d-53h inches

Power requirements

100-240 vac 20 a 50/60 Hz

3. Vitrectomy system and


4. Diathermy.

2. To remove the nucleus: A combination of laser and


aspiration helps remove the nucleus. This is aided
by the technique of nuclear chopping. If the cataract
is very hard a combination of laser followed by
emulsification can be done to make the cataract
removal through a 3 mm incision.
3. To remove cyclitic membranes: In such cases even a
vitrectomy is difficult as the membrane does not get
removed with the help of the vitrectomy probe. But
with the help of the laser one can create a central
opening in these membranes.
4. To create an opening in glaucoma cases. This is less
traumatising than other routine anti-glaucoma
surgeries.
5. To make an inferior iridectomy in cases when
vitrectomy is completed and one has to inject silicone
oil. In such cases, we normally make the iridectomy
with the vitrectomy probe which can by mistake
convert a small iridectomy to a complete iridectomy.
But with the laser photon one good controlled
iridectomy can be created.
SURGICAL PROCEDURE
The technique is basically the same as in normal phacoemulsification proceduresthe only difference being that
here instead of ultrasound power one uses the laser
energy and very rarely the ultrasound energy also. In
the first step a needle with viscoelastic is injected inside
the eye to distend the eye. Then a clear corneal incision
is done with a diamond knife The rhexis can be done
with the laser also. We prefer to do it with a needle. After
hydrodissection, the laser phaco probe (Fig. 17.9) is
passed through the incision, with the phaco chopper in
the other hand through the side port opening. The
nucleus is circumferentially removed (Fig. 17.10) and
gradually aspirated out, followed by cortical aspiration,
implantation of a foldable IOL and stromal hydration
(Fig. 17.11). In stromal hydration the BSS or saline is
injected at the lips of the clear corneal wound hydrating
the cornea and making it white. This helps make a better
wound closure.
ADVANTAGES

USES
The laser cataract system is used for many purposes:
1. To do a capsulorhexis: This can be done with the help
of the laser. One can get a neat round rhexis even in
cases of mature cataracts.

There is no corneal burns or ragged edges at site of


the incision as only minimal ultrasound is used in
laser phaco as compared to phacoemulsification.
A smaller incision is enough than that used for
Phacoemulsification for cataract removal.
The titanium needle has a diameter of 900 microns.
After threading the laser fibre optic of 380 microns

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Chapter 17: Laser Phaco Cataract Surgery 157


through the phaco probe, only 520 microns of space
is left inside the titanium needle for the rest of the
lens material to be removed. But inspite of this embarrassment in space the cataract extraction takes less
time than a regular phacoemulsification.
The laser is ineffective 500 microns away from the
posterior capsule and can hence be relied upon while
working close to the posterior capsule.
Capsulorhexis can be safely and neatly performed
with the laser
This laser has been used in performing laser sclerotomy in cases suffering from glaucoma, to remove
cyclitic membranes and to perform iridectomy.
Fig. 17.9: Laser phaco probe with the he ne beam

Fig. 17.10: Circumferential laser phaco technique

HOW SMALL WILL OUR INCISIONS GO


Today, with more and more new technology, the Laser
Photon will get better and better. It will make the incision
size smaller and smaller so that the astigmatism amount
becomes much less. By 2000 AD lasers will have become
a major force in cataract removal. Foldable IOLs have
definitely come to stay and they will improve day by
day. Today with the Rollable IOLs the lenses are going
through 1 mm incisions.
Any ophthalmologist who wants to put large lenses
in large incisions is bucking the tide of history. Small
incisions offer the best chance for most rapid, stable visual
rehabilitation of the cataract patient at the least cost,
including time of impaired vision following surgery, the
need for follow-up care, the attendance of relatives to
take care of them to the doctor and the like.
It is unclear as to how small will our incisions go
perhaps down to 0.1 mm. With laser phakonit the size
has gone to the sub 1 mm incision level. In laser phaconit
the laser probe is passed through the titanium tip and
the sleeve of the phaco probe is removed. Increasingly,
sophisticated laser equipment is capable of giving us
better utilization of energy. With the advent of the lasers,
the size of the incisions will decrease.
CONCLUSION

Fig. 17.11: Cortical aspiration completed

Lasers would revolutionize cataract surgery. This is the


modality by which one can go real small in the incision.
With this, new techniques and instruments will allow us
to put IOLs through these small incisions.
What the human mind can achieve as it marshals the
basic and clinical sciences will continue to amaze us. Look
how far we have come regarding IOLs and just imagine
how far we will go and can go.

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158 Section I: Cataract


REFERENCES
1. Thornton SP: IOLs, knives and lasers: A new commitment to
the cataract patient. Proceedings of Ocular Surgery News
Symposium; 1994;15:3.
2. Daniel Eichenbaum: Phaco is easier to do with the new laser
system. Ophthalmology Times; 1994;19(13).
3. Daniel Eichenbaum: New laser phaco. Eye Care Technology;
1994.

4. Jack M Dodick: New laser phaco. Eye Care Technology; 1994.


5. Vance M Thompson: A perspective on balancing the knife with
the laser. Ocular Surgery News; 1993;11(13).
6. Daniel Eichenbaum: Laser probes for cataract surgery. Ophthalmology World news; 1995.
7. Daniel Eichenbaum: First computer-aided laser cataract removal
system ready for clinical trials. Ocular Surgery News; 1995;
13(9).

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Chapter 18: Corneal Topography in Phakonit 159

18

Corneal Topography in Phakonit


Amar Agarwal, Soosan Jacob, Athiya Agarwal, Sunita Agarwal

INTRODUCTION

INTRODUCTION

ROLLABLE IOL

Cataract surgery and intraocular lenses (IOL) have evolved greatly since
the time of intracapsular cataract extraction and the first IOL implantation
by Sir Harold Ridley1. The size of the cataract incision has constantly been
decreasing from the extremely large ones used for ICCE to the slightly
smaller ones used in ECCE to the present day small incisions used in
phacoemulsification. Phacoemulsification and foldable IOLs are a major
milestone in the history of cataract surgery. Large postoperative againstthe-rule astigmatism were an invariable consequence of ICCE and ECCE.
This was minimized to a great extent with the 3.2 mm clear corneal incision
used for phacoemulsification but nevertheless some amount of residual
postoperative astigmatism was a common outcome. The size of the corneal
incision was further decreased by Phakonit2-4 a technique introduced for
the first time by one of us (Am.A), which separates the infusion from the
aspiration ports by utilizing a sleeveless phaco probe and an irrigating
chopper. The only limitation to thus realizing the goal of astigmatism
neutral cataract surgery was the size of the foldable IOL as the wound
nevertheless had to be extended for implantation of the conventional
foldable IOLs.

SURGICAL TECHNIQUE
TOPOGRAPHIC ANALYSIS AND
ASTIGMATISM
DISCUSSION

ROLLABLE IOL
With the availability of the ThinOptX rollable IOL (Abingdon, VA, USA),
that can be inserted through sub-1.4 mm incision, the full potential of
Phakonit could be realized. A special ultrathin 5 mm optic rollable IOL
was designed by one of us (Am.A) to make the incision size smaller.
SURGICAL TECHNIQUE
Five eyes of 5 patients underwent Phakonit with implantation of an ultrathin 5 mm optic rollable IOL at Dr Agarwals Eye Hospital and Eye Research
Centre, Chennai, India.
The name PHAKONIT has been given because it shows phacoemulsification (PHAKO) being done with a needle (N) opening via an incision (I)
and with the phaco tip (T). A specially designed keratome, an irrigating
chopper, a straight blunt rod and a 15 degree standard phaco tip without
an infusion sleeve form the main prerequisites of the surgery. Viscoelastic
is injected with a 26 gauge needle through the presumed site of side port
entry This inflates the chamber and prevents its collapse when the chamber
is entered with the keratome. A straight rod is passed through this site to
achieve akinesia and a clear corneal temporal valve is made with the

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160 Section I: Cataract

Fig. 18.1A: Clear corneal incision made with a specialized


keratome. Note the left hand has a straight rod to stabilize the
eye

keratome (Fig. 18.1A). A continuous curvilinear capsulorhexis (CCC) is performed followed by hydrodissection
and rotation of the nucleus. After enlarging the side port
a 20 gauge irrigating chopper connected to the infusion
line of the phaco machine is introduced with foot pedal
on position 1. The phaco probe is connected to the
aspiration line and the phaco tip without an infusion
sleeve is introduced through the main port (Fig. 18.1B).
Using the phaco tip with moderate ultrasound power,
the center of the nucleus is directly embedded starting
from the superior edge of rhexis with the phaco probe
directed obliquely downwards towards the vitreous. The
settings at this stage are 50 percent phaco power, flow
rate 24 ml/min and 110 mm Hg vacuum. When nearly
half of the center of nucleus is embedded, the foot pedal
is moved to position 2 as it helps to hold the nucleus due
to vacuum rise. To avoid undue pressure on the posterior
capsule the nucleus is lifted slightly and with the
irrigating chopper in the left hand the nucleus chopped.
This is done with a straight downward motion from the
inner edge of the rhexis to the center of the nucleus and
then to the left in the form of an inverted L shape. Once
the crack is created, the nucleus is split till the center.
The nucleus is then rotated 180 and cracked again so
that the nucleus is completely split into two halves. With
the previously described technique, 3 pie-shaped
quadrants are created in each half of the nucleus. With a
short burst of energy at pulse mode, each pie shaped
fragment is lifted and brought at the level of iris where it
is further emulsified and aspirated sequentially in pulse
mode. Thus the whole nucleus is removed. Cortical washup is then done with the bimanual irrigation aspiration
technique.

Fig. 18.1B: Agarwals Phakonit irrigating chopper and


sleeveless phaco probe inside the eye

Fig. 18.1C: The rollable IOL inserted through the incision

The lens is taken out from the bottle and placed in a


bowl of BSS solution of approximately body temperature
to make the lens pliable. It is then rolled with the gloved
hand holding it between the index finger and the thumb.
The lens is then inserted through the incision carefully
(Fig. 18.1C). The teardrop on the haptic should be
pointing in a clockwise direction so that the smooth optic
lenticular surface faces posteriorly. The natural warmth
of the eye causes the lens to open gradually. Viscoelastic
is then removed with the bimanual irrigation aspiration
probes (Fig. 18.1D). Figure 18.1 shows different steps of
the surgery.
TOPOGRAPHIC ANALYSIS AND ASTIGMATISM
The preoperative best corrected visual acuity (BCVA)
ranged from 20/60 to 20/200. The mean preoperative

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Chapter 18: Corneal Topography in Phakonit 161

Fig. 18.4: Table showing pre- and postoperative


mean astigmatism

Fig. 18.1D: viscoelastic removed using bimanual


irrigation aspiration probes

astigmatism as detected by topographic analysis was 0.98


D 0.62 D (range 0.5 to 1.8 D).
The postoperative course was uneventful in all cases.
The IOL was well-centered in the capsular bag. There
were no corneal burns in any of the cases.
Four eyes had a best-corrected visual acuity of 20/30
or better. One eye that had dry ARMD showed an
improvement in BCVA from 20/200 to 20/60. Figure 18.2
shows a comparison of the pre- and postoperative BCVA.
The mean astigmatism on postoperative day 1 on
topographic analysis was 1.1 0.61 D (range 0.6 to 1.9
D) as compared to 0.98 D 0.62 D (range 0.5 to 1.8 D)
preoperatively. The mean astigmatism was 1.02 0.64 D
(range 0.3 to 1.7 D) by 3 months postoperatively. Figures
18.3 and 18.4 shows mean astigmatism over time. Figures

Fig. 18.5A: Comparison of pre- and postoperative


day 1 cylinder

Fig. 18.5B: Comparison of 1 day postoperative and


3 months postoperative astigmatism

18.5A and B show a comparison of the astigmatism over


the pre- and postsurgical period.
DISCUSSION

Fig. 18.2: Comparison of pre- and postoperative BCVA

Fig. 18.3: Mean astigmatism over time

Cataract surgery has witnessed great advancements in


surgical technique, foldable IOLs and phaco technology.
This has made possible easier and safer cataract extraction utilizing smaller incision. With the advent of the
latest IOL technology which enables implantation
through ultrasmall incisions, it is clear that this will soon
replace routine phacoemulsification through the
standard 3.2 mm incisions. The ThinOptX IOL design
is based on the Fresnel principle. Flexibility and good
memory are important characteristics of the lens. It is
manufactured from hydrophilic acrylic materials and is
available in a range from 25 to +30 with the lens thickness ranging from 30 m up to 350 m. One of the authors
(Am.A) has modified the lens further by reducing the
optic size to 5 mm to go through a smaller incision. The

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162 Section I: Cataract


lens is now undergoing clinical-trials in Europe and the
USA.
In this study, no intraoperative complications were
encountered during CCC, phacoemulsification, cortical
aspiration or IOL lens insertion in any of the cases. The
mean phacoemulsification time was 0.66 minutes.
Previous series by the same authors showed more than
300 eyes where cataract surgery was successfully
performed using the sub-1 mm incision.3 Our experience
and that of several other surgeons suggests that with

existing phacoemulsification technology, it is possible to


perform phacoemulsification through ultrasmall
incisions without significant complications.2-6 In a recent
study from Japan, Tsuneoka and associates6 used a
sleeveless phaco tip to perform bimanual phacoemulsification in 637 cataractous eyes. All cataracts were safely
removed by these authors through an incision of 1.4 mm
or smaller that was widened for IOL insertion, without a
case of thermal burn and with few intraoperative
complications. Furthermore, ongoing research for the

Figs 18.6A and B: Topographical comparison during different surgical periods

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Chapter 18: Corneal Topography in Phakonit 163


development of laser probes7,8 cold phaco, and microphaco confirms the interest of leading ophthalmologists
and manufacturers in the direction of ultrasmall
incisional cataract surgery (Fine IN, Olson RJ, Osher RH,
Steinert RF. Cataract technology makes strides. Ophthalmology Times, December 1, 2001, 12-15).
The postoperative course was uneventful in all the
cases. The IOL was well-centered in the capsular bag.
There were no significant corneal burns in any of the
cases. Final visual outcome was satisfactory with 4 of
the eyes having a BCVA of 20/30 or better. One eye that
had dry ARMD showed an improvement in BCVA from
20/200 to 20/60. Thus the lens was found to have
satisfactory optical performance within the eye. In our
study, the mean astigmatism on topographical analysis
was 0.98 0.62 D (range 0.5 to 1.8 D) preoperatively, 1.1
0.61 D (range 0.6 to 1.9 D) on postoperative day 1 and
1.02 0.64 D (range 0.3 to 1.7 D) by 3 months post
operatively. Figures 18.5A and B showing a comparison
of the pre- and postoperative astigmatism indicate clearly
that Phakonit with an ultrathin 5 mm rollable IOL is
virtually astigmatically neutral. Figures 18.6A and B
depicting the topography comparison in different
surgical periods show clearly the virtual astigmatic
neutrality of the procedure and stability throughout the
postoperative course.
There is an active ongoing attempt to develop newer
IOLs that can go through smaller and smaller incisions.
Phakonit ThinOptX modified ultrathin rollable IOL is
the first prototype IOL which can go through sub-1.4 mm
incisions. Research is also in progress to manufacture this
IOL using hydrophobic acrylic biomaterials combined

with square-edged optics to minimize posterior capsule


opacification.
CONCLUSION
Phakonit with an ultrathin 5 mm optic rollable IOL
implantation is a safe and effective technique of cataract
extraction, the greatest advantage of this technique being
virtual astigmatic neutrality.
REFERENCES
1. Apple DJ, Auffarth GU, Peng Q, Visessook N. Foldable intraocular lenses: Evolution, clinicopathologic correlations,
complications. Thorofare, NJ, Slack , Inc., 2000.
2. Agarwal A, Agarwal A, Agarwal S et al. Phakonit: Phacoemulsification through a 0.9 mm corneal incision. J Cataract
Refract Surg 2001; 27:1548-52.
3. Agarwal A, Agarwal A, Agarwal A et al. Phakonit: Lens removal
through a 0.9 mm incision. (Letter). J Cataract Refract Surg 2001;
27:1531-32.
4. Agarwal A, Agarwal S, Agarwal A. Phakonit and laser phakonit:
Lens removal through a 0.9 mm incision. In: Agarwal S, Agarwal
A, Sachdev MS, Fine IH, Agarwal A, (Eds): Phacoemulsification,
Laser Cataract Surgery and Foldable IOLs. New Delhi, India:
Jaypee Brothers Medical Publishers (P) Ltd, 2000; 204-16.
5. Tsuneoka H, Shiba T, Takahashi Y. Feasibility of ultrasound
cataract surgery with a 1.4 mm incision. J Cataract Refract Surg
2001; 27:934-40.
6. Tsuneoka H, Shiba T, Takahashi Y. Ultrasonic phacoemulsification using a 1.4 mm incision: Clinical results. J Cataract
Refract Surg 2002;28:81-86.
7. Kanellpoupolos AJ. A prospective clinical evaluation of 100
consecutive laser cataract procedures using the Dodick photolysis neodymium: Yittrium-aluminum-garnet system.
Ophthalmology 2001;108:1-6.
8. Dodick JM. Laser phacolysis of the human cataractous lens. Dev
Ophthalmol 1991; 22:58-64.

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164 Section I: Cataract

19

Attacking Childhood Cataract


Blindness in the Economically
Emerging Countries
Suresh K Pandey, M Edward Wilson, Jaya Thakur, Vidushi Sharma

CHILDHOOD BLINDNESS,
PEDIATRIC CATARACTS:
A GLOBAL PERSPECTIVE
THE FINANCIAL BURDEN
CHILDHOOD CATARACT
MANAGEMENT
PEDIATRIC CATARACT SURGERY
IN THE ECONOMICALLY
EMERGING COUNTRIES
SURGICAL MODALITIES FOR
PEDIATRIC CATARACT
PEDIATRIC CATARACT SURGERY
IN THE ECONOMICALLY
EMERGING COUNTRIES:
SPECIAL ISSUES
EYE-CARE MODEL FOR
PEDIATRIC CATARACT
MANAGEMENT IN THE
ECONOMICALLY EMERGING
COUNTRIES
SIMULTANEOUS BILATERAL
PEDIATRIC CATARACT SURGERY
OR IMMEDIATELY SEQUENTIAL
CATARACT SURGERY
ROLE OF OPHTHALMOLOGISTS
FROM INDUSTRIALIZED NATIONS
PEDIATRIC CATARACT SURGERY
IN THE ECONOMICALLY
EMERGING COUNTRIES

CHILDHOOD BLINDNESS, PEDIATRIC CATARACTS:


A GLOBAL PERSPECTIVE
A child becomes bilaterally blind every minute, primarily within developing nations. Of the 1.5 million blind children in the world, 1.3 million live
in Asia and Africa, and 75 percent of all causes are preventable or curable.
The prevalence of blindness varies according to socioeconomic development of the country and the mortality rate of those under 5 years-of-age.
In developing countries the rate of blindness can be as high as 1.5 per
1,000 population. Compared to industrialized countries, this figure is tentimes higher.1-9 Table 19.1 summarizes some of the studies regarding
prevalence of childhood blindness in various developing countries.10-13
As reported by Foster and Gilbert,14 about 0.5 million children become
blind each year. For those who survive childhood, the burden of disability
in terms of blind-years is huge because of their visual disability. The
child who goes blind today is likely to remain with us into 2050.7
Presently, approximately 7 million adult cataract surgeries are performed annually in the world.15 We must break the trend of rapidly growing
cataract blindness. Precise data related to the total number of pediatric
cataract surgeries performed annually is not available. However, pediatric
cataract blindness presents an enormous problem in the developing world
in terms of human morbidity, economic loss and social burden (Table
19.2).16-20 It can be argued that restoring the sight of one child blind from
cataracts, is equivalent to restoring the sight of 10 elderly adults.7
Irrespective of the cause, childhood blindness has far reaching effects
on the child and family throughout life. It profoundly influences educational, employment, personal, and social prospects. The control of childhood blindness has been identified as a priority of the World Health
Organizations (WHO) global initiative for the elimination of avoidable
blindness by the year 2020.21
THE FINANCIAL BURDEN
Solely measuring disease frequency offers but a limited understanding of
the public health significance of childhood blindness. Both adult and
*This chapter is prepared after modification of our original article: Wilson ME, Pandey SK,
Thakur J. Pediatric cataract surgery in the developing world. Br J Ophthalmol 2002 (in press)

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Chapter 19: Attacking Childhood Cataract Blindness in the Economically Emerging Countries
Table 19.1: Prevalence of childhood blindness in
developing countries
Study

Country

Prevalence
per 1000 Children
(age range)

Cohen (1985)

Bangladesh

1.09 (0-5 yrs, urban)

Cohen (1985)

Bangladesh

0.64 (0-5yrs, rural)

Brilliant (1985)

Nepal

0.63 (0-14 yrs)

Chirambo (1986)

Malawi

1.1 (0-5 yrs)

Faal (1989)

Gambia

0.7 (0-19 yrs)

Table 19.2: Cataract as a cause of childhood blindness


Study

Country

Percentage of Blindness

165

in industrialized countries, the prevalence of blindness


is less, but life expectancy and earning capacity is greater
than in developing countries. However, these financial
costs alone provide only one perspective of the public
health burden of blindness. Improved understanding and
quantification require the application of indicators that
measure the impact of blindness in terms of morbidity
(years of disability suffered) as well as mortality (years
of life lost through premature blindness-associated
death). Such indicators are useful in identifying those in
the population in greatest need, and for setting priorities
in the provision of health services. These indicators are
also important in the assessment of the effectiveness of
interventions and their economic evaluation. A south
Asian study revealed that 85 percent of the men and 58
percent of the women who regained their sight, returned
to work with a financial return of 1,500 percent during
the first year following surgery.24

Moriarty (1988)

Jamaica

39 percent

Pottor (1991)

Central African
Republic

13.5 percent

Eckstein (1995)

Sri Lanka

17 percent

CHILDHOOD CATARACT MANAGEMENT

Rahi (1995)

India

12 percent

Waddell (1998)

Uganda

30.7 percent

Management of congenital and childhood cataracts


remains a challenge. Increased intraoperative difficulties,
propensity for increased postoperative inflammation,
changing refractive-state of the eye, more common
postoperative complications and a tendency to develop
amblyopia, all add to the difficulty in achieving a good
visual outcome in the pediatric patient. Adaptation of
techniques for cataract surgery specific to children is
necessary due to low scleral rigidity, increased elasticity
of the anterior capsule, and high vitreous pressure. Also,
microphthalmia and pupillary miosis often add to the
surgical complexity. Finally, surgical timing and adequate
visual rehabilitation are paramount to avoiding
irreversible visual damage secondary to amblyopia
(Wilson ME, Pandey SK, Werner L, Apple DJ. Pediatric
Cataract Surgery: Past, present and future, Third Prize
for Special Cases, Annual Video Festival, XXth Congress
of the European Society of Cataract and Refractive
Surgeons, Nice, France, September 2002).25-29

pediatric cataract blind-cases are emerging as a major


financial burden for several developing countries. The
regional burden of blindness (RBB) is the ratio of the
number of blind persons in a particular region to the
global number of blind, and the proportion of the regional
population to the world population. A RBB ratio greater
than unity identifies those regions where the burden of
blindness is to be taken into urgent consideration in terms
of establishing priorities on a global scale. In the
industrialized world the RBB is 0.42, while in India the
RBB is 1.46, in sub-Saharan Africa it is 1.93, and in Asia
it is 1.18.15-21 In a recent study, Shamanna et al,22 reported
that the economic burden of blindness in India during
1997 was US$4.4 billion, with the cumulative loss over a
lifetime of blindness was US$77.4 billion. Surprisingly,
these authors estimated the cost for treating all cases of
cataract blindness in India as only US$150 million.22 No
support for the blind exists in under-developed countries,
which makes effective surgery even more essential. These
figures have been estimated for adult cataract cases. In
terms of blind-years, the economic loss will be even
higher for childhood cataracts. The future of any society
lies with its children; therefore, they deserve special
attention.
The global financial cost of blindness with an onset
during childhood, in terms of loss of earning capacity
(i.e., per capita GNP), has recently been estimated to be
between US$6 billion and $27 billion.23 For children living

Industrialized Nations versus Developing Nations


A high incidence of pediatric cataracts exists in the
economically emerging countries, possibly due to such
factors as malnutrition, lack of immunization for rubella,
and consanguineous marriages. Further, late diagnosis
and late treatment of children with cataracts occurs more
frequently in the developing than the industrialized
world. Safe general anesthesia must be provided for
young children, even those less than 3 months of age.
Difficulty also arises in the purchase of high-quality

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166 Section I: Cataract


surgical microscopes, vitrectomy equipment, viscoelastic
materials and intraocular lenses (IOLs) needed to perform surgery, all due to inadequate financial resources.
A lack of operating room instrumentation, such as the
handheld keratometer and the A-scan ultrasound,
exacerbate the difficulty in selecting the appropriate IOL
power for the pediatric cataract patient. Late diagnosis
and treatment can lead to amblyopia, which will further
exaggerate the problem. The lack of low-vision rehabilitation centers and the limited availability of Nd:YAG
laser equipment for posterior capsulotomy, further
jeopardize the successful long-term functional visualoutcome following pediatric cataract surgery.30
Several articles and book chapters have been published regarding adult and pediatric cataract management in the industrialized world.25-29,31-35 In this chapter,
we address some of the major issues related to the surgical treatment of childhood cataracts by surgeons of the
developing or economically emerging countries. Interested readers can also refer to our another article on this
subject. 29
PEDIATRIC CATARACT SURGERY IN THE
ECONOMICALLY EMERGING COUNTRIES
Anesthetic Methods
Most pediatric cataract surgeries in the industrialized
world are done under general anesthesia, which is
induced by an anesthesia provider. Such specialists are
available only in urban centers and tertiary-care referral
centers in the economically emerging countries. General
anesthesia in economically emerging countries centers
are primarily for adults, and pediatric anesthetic risks
should be kept in mind and the number of anesthetic
exposures reduced to as few as possible. Some authors
have proposed simultaneous bilateral pediatric cataract
surgery in order to avoid repetition of the general
anesthesia. We will discuss the topic of simultaneous
bilateral cataract surgery elsewhere in this article.
General Anesthesia via Endotracheal (ET)
Intubation or Laryngeal Mask Airway (LMA)
A comprehensive summary of the techniques of general
anesthesia in ophthalmic care centers in the economically
emerging countries is beyond the scope of this article.
Cost and effectiveness are both very important when
choosing anesthetic agents in a developing world-setting.
We recommend that pediatric cataract surgery be performed under general anesthesia with constant monitoring
of the vital signs. Ophthalmic surgeons in Guatemala
have utilized modern inhalation agents via LMA
combined with peribulbar lidocaine and marcaine in

children to facilitate anesthesia maintenance on as little


inhalation agent as possible. In India, some centers get
equally good results from thiopentone induction, ET
intubation after giving suxamethonium with maintenance of anesthesia with nitrous oxide, oxygen, and
intermittent pancuronium.
The occurrence of vomiting in the early postoperative
period is not uncommon after general anesthesia. This,
along with inevitable rubbing of the eyes, helps to justify
the use of sutures to close the surgical wound even if it
appears to be self-sealing. Children also have a very
active Bells phenomenon if they become somewhat light
under anesthesia. For this reason, many pediatric
surgeons still use a superior rectus traction suture during
cataract surgery.
Ketamine Anesthesia
Due to limited resources and availability of anesthetists
in remote areas of the economically emerging countries,
ketamine provides a safe and potent intravenously
administered anesthetic of short duration for pediatric
populations. Ketamine combines analgesic and sleepproducing effects without significant cardiovascular and
respiratory depression.36 The most common side effects
are the so called emergence phenomenon which
include disorientation, vivid dreams, and sensory or
perceptual illusion.
Ophthalmic surgeons in Nepal have used ketamine
in combination with peribulbar lidocaine when performing pediatric cataract surgery. While an anesthetists is
not always available, the anesthesia is always administered by a person trained in pediatric airway management and resuscitation. A pulse oximeter is used as part
of the vital sign monitoring. This technique has the
advantage of ketamine as the dissociative anesthesia, and
peribulbar lidocaine (combined with ocular massage) as
the local anesthetic agent to anesthetize the ocular tissues
and to counter the effect of increased intraocular pressure
caused by ketamine. It also minimizes the oculocardiac
reflex.37 For children over two years of age, diazepam is
given before the administration of ketamine to reduce
the incidence of hallucinatory emergence phenomenon.
Ketamine does not eliminate eye and body movements
as well as general ET or LMA anesthesia. These movements may increase substantially, the difficulty of
operating these small soft eyes under an operating
microscope.
SURGICAL MODALITIES FOR PEDIATRIC CATARACT
The aim of pediatric cataract surgery is to provide and
maintain a clear visual axis and a focused retinal image.
This is accomplished by timely removal of the opacified

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Chapter 19: Attacking Childhood Cataract Blindness in the Economically Emerging Countries
crystalline lens and appropriate optical rehabilitation.
Modalities for pediatric cataract surgery used in the
developing world setting are needling, needling and
aspiration, or extracapsular cataract surgery with or
without IOL implantation. The long-term visual outcome
is often negatively affected by the development of amblyopia secondary to the cataract itself, or due to
postoperative re-opacification of the ocular media.26,27
Extracapsular cataract extraction (ECCE) techniques
described in the literature for the pediatric cataract
management include automated lensectomy with anterior vitrectomy (LAV); extracapsular cataract extraction
with intraocular lens implantation ([ECCE + IOL] manual
or automated with an intact posterior capsule), and
ECCE, primary posterior capsulotomy, anterior
vitrectomy with intraocular lens implantation ([ECCE +
PPC+AV+IOL], manual or automated posterior capsulectomy with automated vitrectomy). Variations on the latter
technique have been proposed in hopes of eliminating
the vitrectomy, while still performing the posterior
capsulotomy at the time of surgery. However, to the best
of our knowledge, the available literature does not
provide clear-cut guidelines about when to use these
various techniques. This is especially important in
developing countries since microsurgical equipment is
expensive and experience with pediatric ophthalmic
surgery and anesthesia are spread unevenly throughout
many regions.
The results of using the various surgical techniques
mentioned above have been reported in studies concerning pediatric cataract management (Table 19.3).38-43 In a
prospective, non-randomized trial,41 three methods of
pediatric cataract management were evaluated. The
surgical procedures performed included: lensectomy
anterior vitrectomy (LAV); extracapsular cataract
extraction with intraocular lens implantation (ECCE +
IOL); and ECCE, primary posterior capsulotomy, anterior
vitrectomy with intraocular lens implantation (ECCE +
PCC+AV+IOL). Aphakia in the LAV group was corrected
with spectacles or contact lenses. One hundred and
ninety-two eyes were included in the study. No statistically significant difference in intraoperative complication
was demonstrated. Post-operative obscuration of visual
axis was reported in 43.7 percent of eyes in the ECCE +
IOL group and in 3.7 percent of eyes in ECCE + PPC +
AV + IOL group. Based on this study,41 the authors concluded that out of the three approaches, ECCE + PPC +
AV + IOL was the most conducive to at least short-term
maintenance of a clear visual axis in children.
Based on the published studies38-43 and our experience so far, we agree that extracapsular cataract surgery,
primary posterior capsulectomy and anterior vitrectomy

167

(ECCE, PPC and AV) provide the best chance of longterm clear visual axis. When long-term follow-up is not
likely and Nd:YAG laser treatment is not available, we
recommend ECCE, PPC and AV with IOL implantation
for all children regardless of age, even those older than
age 8 years.
ECCE, PPC, AV and IOL
With the proper precautions ECCE, PPC, AV and IOL is
the most versatile technique for pediatric cataract
surgery. Manual anterior capsulotomy and manual lens
aspiration with IOL and without primary posterior
capsulotomy can be utilized in older children; but we
recommend this approach only where follow-up is likely
and Nd:YAG laser technology is available. Even when
these criteria are satisfied, Nd:YAG laser capsulotomy
may require a repeat anesthesia, and repeat laser
capsulotomies will be needed in more than 1/3 of those
treated. Alternatively, ECCE, PPC, AV and IOL requires
automated vitrectomy equipment, which may be difficult
to maintain in some settings. This obstacle can be
overcome by selecting equipment that requires fewer
repairs, and by developing organized biomedical repair
training sessions at sites where this equipment is to be
used. Also, tubing and vitrector handpieces that are
reusable and resterilizable must be available for use with
vitrectors, to reduce disposable costs. We recommend that
every clinical center where pediatric cataract surgery is
to be done be equipped with a Venturi-pump driven
mechanized vitrectomy unit. Phacoemulsification
machine (peristaltic-pump driven) often have a
vitrectomy attachment but do not cut capsule or vitreous
as efficiently or easily during pediatric procedures. If
these peristaltic pump machine must be relied upon, the
capsule must be opened manually and the unit used only
for the vitrectomy. Visitrec (Sarasota, Fl, USA) has
developed a bettery-powered portable vitrectomy system
(Visitrec) equipped with a guillotine cutter and manual
syringe aspiration. It can be used after manual aspiration
of the lens and manual posterior capsulectomy. Like the
peristaltic-pump machines, the Visitrec will not cut
capsule as described under surgical steps below. Also, it
has a maximum cutting speed of only 300 cycles per
minute. Despite these limitations, we recommend that
the Visitrec be available as a battery powered back-up
for completion of the vitrectomy in the event of power
failure or machine malfunction. The 20-gauge vitrector
with a 10 cc syringe is preferred over the 23-gauge vitrector and 3 cc syringe. Both are made by Visitec for disposable use with the Visitrec handpiece. Resterilization of
the cutter can reduce per case costs.

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168 Section I: Cataract


Table 19.3: Studies on pediatric cataract surgery
Study

No. of
Age Range
Patients
(mean)
(no. of eyes)

Taylor (1981)

29
(54)

Chrousos (1984) (392)

Keech (1989)

78 (128)

Basti (1996)

(192)

Mean
BCVA
Follow-up >6/18

BCVA
>6/60

0-18 yrs
18 mo
(16 weeks)
0-18 yrs
18 mo
(17.4 weeks)
0-20 yr
5.5 yr

0-30 mo
(18 wk)
2-8 yr

44.8 mo
11.3 mo

44.15%

63.64%

Basti (1996)

Basti (1996)

Type of
Surgery
(no. of patients)

Post.
Caps.
Opa.

Other
Complications

Aspiration alone
PC intact (28)
Lensectomy (23)

68.0%

Not
mentioned
Not
mentioned
7.2% (glaucoma)
1.3% (RD)
5.8% (glaucoma)
2.9% (RD)

Aspiration alone 62.1%


(304)
Roto extraction
11.7%
and primary
capsulotomysmall (34)
Ocutome aspira0%
tion-wide post
capsulotomy (54)
Aspiration alone 75.0%
(20)
Lensectomy
0%
anterior vitrectomy
(LAV) (23)
ECCE+IOL (87)
43.7%

ECCE + PPC +
AV + IOL (82)

3.6%

Eckstein (1999) 56 (112)

3 mo10 yrs
(53 mo)

3 yr

57.1%

94.6%

Lens aspiration
66.1%
with primary
posterior
capsulotomy (56)
Lensectomy
1.8%
(vitreophage) (56)

Yorston (2000)

0-11 yr
(3.5 yr)

3 mo

44.0%

91.2%

Lens aspiration
35.7%
and anterior capsulotomy (56)

71 (118)

Anterior capsulo- 1.6%


tomy + primary
posterior capsulectomy + anterior
vitrectomy(62)
Lensectomy (105) 11.0%

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0%
(glaucoma)
1.8% (RD)
5% (RD)
20% (glaucoma)

1.14% (RD)
8.04% (pupillary
capture)
13.8% (uveitis)
0% (IOL
dislocation)
1.22% (RD)
8.53% (pupillary
capture)
15.9% (uveitis)
2.44% (IOL
dislocation)
1.8% (glaucoma)
16% (amblyopia)
1.8% (pupil
decentration)
3.6% (RD)
3.6% (pupil
decentration)
16% (amblyopia)
1.8% (glaucoma)
30.5% (uveitis)
31.4%
(amblyopia)
1.7% (glaucoma)
30.5% (uveitis)
31.4%
(amblyopia)
1.7% (glaucoma)
0.95% (RD)
11.4% (glaucoma)

Chapter 19: Attacking Childhood Cataract Blindness in the Economically Emerging Countries
Recommended Surgical Steps
Under general anesthesia, two limbal incisions are
recommended utilizing a 20 gauge microvitreoretinal
(MVR) knife at the 10 oclock and 2 oclock positions;
one for an irrigation cannula (connected to a balanced
salt solution [BSS]) and the other one for an aspiration/
cutting handpiece. Epinephrine (1:500,000) is usually
added in the BSS to maintain the pupillary mydriasis.
Although Ringers lactate solution works well for
irrigation associated with adult extracapsular surgery,
temporary corneal clouding can occur when it is used in
the high flow pediatric surgery described here.
Several techniques have been described to open the
anterior capsule. Interested readers are referred to the
details about anterior capsule management discussed by
one of the authors (MEW) elsewhere.29 In brief, infants
and young children have a very elastic anterior capsule,
which easily extends toward the periphery. Manual
continuous circular capsulorhexis (CCC) is challenging,
and there is frequently a run-away rhexis. A practical
alternative to manual CCC is to create a small central
opening in the anterior capsule using a vitrector probe.
This initial hole can be enlarged by biting into the
anterior capsule with the vitrector until the desired 5 mm
opening is achieved. This technique is known as
vitrectorhexis. We recommend using a Venturi pump
vitrector set at a cutting rate of 150 to 300 cuts per minute
and an aspiration maximum of 150 to 250. The lens cortex
and nucleus are usually aspirated easily with either an
irrigation-aspiration or vitrectomy handpiece. When
using the vitrector, intermittent cutting-bursts can
facilitate aspiration of the more gummy cortex of
young children. Complete removal of cortical material
is desired. Even if a primary posterior capsulectomy is
planned, removal of all cortical material will result in
less inflammation and potentially less cortical reproliferation later.
Once the capsular bag is empty, a decision has to be
made regarding management of the posterior capsule.
Most authors agree that infants under 2 years-of-age
should receive an elective posterior capsulectomyanterior vitrectomy. Due to poor compliance and the
difficulty in following these pediatric patients in the
economically emerging countries, we suggest a primary
posterior capsulotomy followed by an anterior vitrectomy for at least children up to 8 years-of-age. Posterior
capsulotomy can be carried out easily with the vitrector,
as described for the anterior capsule. The posterior
capsulotomy should be 4-5 mm in diameter and
approximately one-third of the anterior vitreous should
be removed to ensure a permanently clear visual axis.

169

Smaller posterior capsulectomies with shallow anterior


vitrectomies tend to close down, especially in neonates.
A posterior capsulectomy alone does not guarantee a
permanently clear visual axis, because the vitreous face
can serve as a scaffold on which the lens epithelium can
grow. When this happens, opaque membranes form.
Please note, if the available vitrector is not driven by a
Venturi-pump, anterior and posterior capsulotomy
should be performed manually, prior to the mechanized
anterior vitrectomy.
Optic capture, while helpful in IOL centration (especially, when the IOL haptics are in the ciliary sulcus), does
not assure a permanent clear visual axis in children less
than 6 to 8 years-of-age.44-46 An anterior vitrectomy is
recommended whether optic capture is utilized, or not.
While foldable IOLs can be inserted through either a
corneal or a scleral tunnel, the PMMA IOLs manufactured in the developing world should be inserted through
a scleral tunnel which is securely sutured. A superior
approach is favored since the wound is protected beneath
the brow.
Pars Plana Approach to PPC and AV after
Anterior Approach ECCE
The pars plana approach to LAV is not often utilized
today. However, since pars plana surgery in infants has
not lead to an increase in retinal complications, the
approach has now been advocated for use in young
children in order to perform a posterior capsulectomy
and anterior vitrectomy after an anterior approach ECCE
and after an IOL has been placed into the capsular
bag.47,48 It is much easier to insure in-the-bag placement
of the IOL (especially, the PMMA IOLs used in the
developing world) if it can be implanted prior to the
posterior capsulectomy and anterior vitrectomy. The eye
becomes very soft after the vitrectomy, making the IOL
manipulation and insertion very difficult. Although the
vitrector handpiece can be placed beneath the IOL from
an anterior approach, this maneuver is difficult and may
result in a radial tear in the anterior capsule and/or
displacement of the IOL out of the capsular bag.
When utilizing the pars plana approach to PPC+AV,
the IOL is placed securely into the capsular bag from an
anterior approach after the anterior capsulectomy and
lens aspiration have been completed. The irrigation
cannula remains in the anterior chamber, from the
anterior approach. The vitrector handpiece is placed
behind the IOL through an MVR blade opening made 23 mm posterior to the limbus (2 mm if less than 6 monthsof-age, 2.5 mm from 6 months to 4 years-of-age and 3
mm thereafter). The MVR must be aimed toward the

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170 Section I: Cataract


center of the vitreous cavity, to avoid inadvertently
engaging the peripheral lens capsule. The vitrector
cutting-rate for the posterior capsulectomy should be set
higher than previously recommended for anterior
capsulectomy. This recommendation is made since
vitreous may be removed along with the capsule. A
cutting rate of 350 for the posterior capsule, and 500 for
vitreous removal is recommended. A pars plana
vitrectomy and posterior capsulectomy allows the
surgeon to perform a larger capsulectomy and more
generous vitrectomy without fear of making the IOL
insertion more difficult. It also lessens the possibility of
a vitreous wick to an anterior wound.48
PEDIATRIC CATARACT SURGERY IN THE
ECONOMICALLY EMERGING COUNTRIES:
SPECIAL ISSUES
Use of Ophthalmic Viscosurgical Agents in the
Economically Emerging Countries
High-viscosity ophthalmic viscosurgical agents (OVA)
have commonly been used in several surgical steps (e.g.,
to deepen the anterior chamber, to maintain space, and
to open the capsular fornices, facilitating in-the-bag
fixation of the posterior chamber IOL). 49 However,
despite several advantages, widespread use of the highdensity OVAs may not be possible due to their cost.
Inexpensive OVAs, such as hydroxypropyl methylcellulose (HPMC), can be used as an alternative to highlyviscous OVAs. HPMC can be manufactured and made
available to ophthalmologists at affordable prices.
Additionally, an anterior chamber maintainer can be used
when operating on young patients. Without the highestviscosity OVAs, placing an IOL into the capsular bag of
a pediatric eye which has already received a posterior
capsulectomy and anterior vitrectomy, can be very
challenging. There is a higher risk of either inadvertent
bag-sulcus placement or dislocation through the
posterior capsulectomy and into the vitreous cavity.
Consideration should be given to utilizing the pars plana
approach to the posterior capsulectomy and anterior
vitrectomy in this circumstance. A review of the various
types of OVAs for use in pediatric cataract surgery has
recently been completed.49
Use of IOLs for Pediatric Cataract Surgery in the
Economically Emerging Countries
Aphakic glasses, contact lenses, and IOLs have been
proposed as methods of visual rehabilitation after
pediatric cataract surgery. Spectacles are heavy, ill-fitting

and uncomfortable and have a magnification factor of


20 to 30 percent. Lenses scratch easily and frames easily
break. It is difficult to replace spectacles, once broken or
damaged due to the expense and unavailability,
particularly in the economically emerging countries.
They are unsuitable for monocular aphakia and restrict
visual rehabilitation. Contact lenses are impractical for
most patients in the economically emerging countries,
because the majority live in rural areas where suboptimal living standards and scarcity of clean water
makes personal and ocular hygiene difficult. Regular
follow-up visits to eye care clinics are problematic due
to cost and distance of travel. Contact lenses are
expensive and easily lost. Moreover, personnel qualified
to offer contact lens service are scarce.
Implantation of an IOL during cataract surgery in the
economically emerging countries seems to be a practical
option, while other methods of visual rehabilitation
(aphakic glasses and contact lenses) are less suitable in
this settings. An IOL can provide a full-time correction
with optics that closely simulate those of the crystalline
lens. In the industrialized world, IOL implantation at the
time of cataract surgery is rapidly becoming the most
common means of optical correction for children beyond
infancy. In a recent study done in Africa, Yorston and
coworkers43 also recommend IOL implantation as the
treatment of choice for most children with cataract in the
economically emerging countries.
The authors of the above study43 noted a relatively
high incidence of postoperative fibrinous anterior uveitis.
However, minimizing uveal manipulation and using a
no-iris-touch technique with a closed-chamber and tightfit around inserted instruments, helps to decrease the
incidence of postoperative fibrinous uveitis. Poor
postoperative compliance with topically applied
medication, probably also contributed to the fibrinous
uveitis seen in some children. As intraocular slow-release
steriod (such as Surodex by Oculex Pharmaceuticals, Inc.,
Sunnyvale, CA, USA) becomes available for use in
children, prevention and management of postoperative
uveitis will be less dependant on the use of topical drops
given by the parents in the weeks after surgery. Recent
clinical trials suggested that the intraocular placement
of Surodex is a safe and effective treatment method to
reduce intraocular inflammation after adult cataract
surgery, and clearly is superior to eyedrops in reducing
inflammatory symptoms and aqueous flare as measured
with the laser flare meter.50-52 In a randomized clinical
trial of Surodex steroid drug delivery system for adult
cataract surgery, Tan and associates52 compared the
anterior chamber (AC) versus ciliary sulcus placement
of two Surodex pellets in 71 eyes. No difference in efficacy

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Chapter 19: Attacking Childhood Cataract Blindness in the Economically Emerging Countries
between AC placement and ciliary sulcus placement of
Surodex was detected in this study. Future studies are
needed to test the efficacy of Surodex in reducing the
postoperative inflammation after pediatric cataract
surgery. This will be an important advancement for
developing world surgeons.
Intraocular lenses manufactured from various rigid
and foldable biomaterials have been used for pediatric
cataract surgery. Rigid implants manufactured from
polymethyl methacrylate (PMMA) have significant
application in pediatric cataract surgery in the economically emerging countries. Polymethyl methacrylate
was the first material used for the manufacture of IOLs,
which were being implanted as early as 1949.25 An IOL
implanted in a childs eye must stay there for several
decades without biodegrading. Thus, PMMA has the
longest safety record. Ben Ezra,53 addressing the biocompatibility of lens materials, reported positive impressions
after 17 years of using PMMA posterior-chamber IOLs
in children. The tendency toward increased postoperative
inflammation in children is well recognized. Heparin
surface-modified PMMA lenses have successfully been
used in the pediatric population, with less inflammatory
reactions, cellular deposits and synechia formation.
Efforts are in progress to manufacture PMMA IOLs
inexpensively in the economically emerging countries.54
The better visual acuity afforded by an IOL as compared
to correction with aphakic glasses has played a key role
in stimulating market demand for cataract services from
all economic strata. Vision with an IOL attracts adult
cataract patients to accept surgery at an earlier stage,
when they are still able to work and can pay for the
surgery. Financial self-sufficiency can be attained by the
physician, as cataract surgery programs are able to
recover costs from user fees. The IOL-producing facilities
in Madurai, India (Aurolab of Aravind Eye Hospital) and
in Nepal and Eritrea (Fred Hollows foundations facilities), are successful examples. Aurolab in India, is dedicated to providing affordable medical products to programs
serving the poor. It now produces IOLs, ophthalmic
suture and pharmaceuticals. The IOL division of the
Aurolab was started with the mission of manufacturing
high-quality lenses at prices affordable to the developing
countries. Aurolab has so far supplied more than 1.5
million lenses to its customers in India and 85 other
countries worldwide, since its inception in 1992. In 1999,
Aurolab produced and sold over 600,000 IOLs. Aurolab
has CE Mark Certification for its suture and IOL product
lines, fulfilling the same regulatory requirements as any
European medical device company. Aurolab has proven
that sophisticated medical manufacturing can be
financially self-sustaining, and yet be affordably priced

171

to the poor. The companys affordable IOLs have both


improved cataract surgery outcomes and increased
market demand for improved visual acuity, while reducing the need for thick aphakic glasses.
The Fred Hollows Foundation in Australia is a community-based not-for-profit organization working in
several developing countries. Through skills trainingprograms and the development of new technologies, the
Foundation has built sustainable local centers to prevent
and treat avoidable blindness in developing countries.
To date, the Foundation and its supporters have helped
over 700,000 people all over the world to see again. Like
Aurolab, Fred Hollows foundation IOL facilities in Nepal
and Eritrea manufacture IOLs for use in the developing
world which are high quality and yet affordable.
Foldable lenses allow a much smaller incision than
PMMA IOLs, for children. Since children may traumatize
their eyes after surgery, the size of the incision is of great
importance. Smaller incisions are more practical in
children (in the economically emerging countries) than
adults since the lenses are soft and no hard nucleus is
present. Small incisions incite less inflammation and
require less suture closure. The major disadvantage of
foldable IOLs for children is cost. Aurolab has recently
begun manufacturing a hydrophilic acrylic foldable IOL
in its factory in India. These will be sold for approximately US$ 35. Foldable lenses made from hydrophobic
acrylic biomaterials (Alcon, AcrySof) have become the
most commonly implanted IOL for children in the
USA.(Wilson ME, et al. Pediatric cataract surgery:
practice styles and preferences of ASCRS members,
presented at ASCRS Symposium on Cataract, IOL, and
Refractive Surgery, Philadelphia, PA, June 2002). The
AcrySof IOL are prohibiting expensive (more than US$
100) for use in most developing wold set-up. Alcon, however, has indicated its willingness to support childhood
blindness prevention (Tim Sear, CEO, Alcon Inc., Fort
Worth, Texas, USA, personel communication, January
2002). Perhaps this will include donating AcrySof IOLs
for pediatric use in the economically emerging countries
IOL Power Selection
Selecting the best IOL power to implant in a growing
child presents unique challenges. A lack of instrumentation in the economically emerging countries operatingroom setting, such as the handheld keratometer and the
A-scan ultrasound, creates difficulty in selecting the
appropriate IOL power to use for pediatric cataract
surgery. In order to minimize the need to exchange IOLs
later in life when a large myopic shift occurs, it has been
advised to undercorrect children with IOLs so that they
can grow into emmetropia or mild myopia in adult life.

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172 Section I: Cataract


Dahan and coworkers55 evaluated the lens choice and
suggested the following guidelines. For children less than
2 years-of-age, perform biometry and undercorrect by
20 percent. Alternatively, axial-length measurement can
be done and 28 diopters (D), 27 D, 26 D, 24 D, 22 D IOLs
can be implanted for axial lengths of 17, 18, 19, 20 and
21 mm, respectively. For children between 2 and 8 yearsold, these authors suggest doing biometry and undercorrecting by 10 percent. If emmetropia or mild myopia is
selected as the target refraction in operating young
children, high myopia will likely occur later.56
Residual hyperopia (i.e., following IOL implantation)
should be managed with spectacles if possible. In some
developing world settings, obtaining and maintaining
spectacles after surgery is not feasible. Less residual
hyperopia is aimed for in these cases. When operating
bilaterally, however, emmetropia need not always be the
target refraction even when spectacles cannot be
obtained. We have noted much better distance-and-near
functional vision in children than would be predicted
with poor spectacle-compliance for residual hyperopia
in the one to three diopter range.57 Pseudoaccommodation in children with monofocal IOLs can be impressive
even though the reasons for its existence have not been
fully elucidated. For bilateral cataract surgery in the
developing world, an IOL power should be selected for
each eye that is likely to give a postoperative refraction,
after full eye growth, of no more than 4 diopters of
myopia. This strategy will require leaving a moderate
amount of hyperopia in children less than age 3 years
and a mild amount up to age 6 years. If glasses or refractive surgery are readily available to these children when
they reach adulthood, this strategy could be altered.
However, if these refractive aids are not available, it is
preferable to choose moderate hyperopia now to avoid
high myopia (which may affect work performance) later.
Every attempt should be made to obtain an A-scan
ultrasound capability in centers where pediatric cataract
surgery is to be performed. Microphthalmia produces
much lower globe axial-lengths than expected for age.
Form vision deprivation from delays in removal of
cataracts in children can result in much longer globe
axial-lengths than expected. While same-power-for-all
IOL implantation may be preferred over aphakia-for-all,
ultrasound technology is preferred and has little
recurring cost once the equipment is purchased.
EYE-CARE MODEL FOR PEDIATRIC CATARACT
MANAGEMENT IN THE ECONOMICALLY
EMERGING COUNTRIES
How can governments and health planners create the
proper institutional and financial structure to promote

eye care services that are excellent in quality and


accessible to all, not just accessible to the privileged few
who can afford to pay the often out-of-reach market
price? It has been demonstrated that it is possible to
develop eye care programs that are financially selfsufficient, and still able to provide care for the poor.58
Some of these successful models are designed by
ophthalmology leaders in the developing countries
according to the paying capacity and economy of the area
served. Examples of such successes include the Aravind
Eye Hospital, Madurai, TN, India; the L.V. Prasad Eye
Institute, Hyderabad, India; and the Lumbini Eye Care
Project and Tilganga Eye Center, Kathmandu, Nepal.
At the Aravind Eye Hospital (which performed over
200,000 surgeries in 2000), 40 percent of the patients paid
well-above cost, and 60 percent were given service at no
charge. The Hospital is able to develop a substantial
surplus to fuel its growth and expand its services that
include teaching and research. The Lumbini Eye Care
Project in Nepal has achieved financial self-sufficiency.
Since the introduction of cost recovery in late 1993, the
surgical volume at the Project has more-than tripled from
6,000 to 20,000 cases in 1999. The number of patients
receiving an IOL have increased from 50 percent to almost
100 percent. And the program is now able to be fully
self-sustaining from user fees, generating a 40 percent
surplus which it utilizes for institutional growth and freesurgery to the very poor. Lumbini has multitiered pricing
for different income levels: 57 percent of its patients pay
just above cost, 18 percent pay two-thirds cost, and 5
percent pay two or three times cost, while 20 percent
receive free surgery. At the L.V. Prasad Eye Institute,
Hyderabad, India, about 20,000 surgeries are performed
each year: 50 percent pay well above cost, and 50 percent
are provided surgery at no charge. There remains a need
to establish more such centers to focus on pediatric
cataract management in the developing countries.
What do these self-sustaining eye care programs have
in common? Through careful research, they have gained
an understanding of the local capacity to pay and have
priced their services to be affordable to both the rich and
poor alike. Surgical productivity and resource utilization
have been enhanced to significantly decrease per unit
surgical costs. Through training of paramedical
personnel, these programs have liberated their surgeons
sufficiently to increase surgical volume, thus reducing
their per-unit-costs. Each of these models varies
according to the paying capacity of the local population.
All have the characteristic of multitiered pricing to make
eye care affordable to all economic strata, while providing
eye care to the very poor at no charge. These programs
have worked hard to improve quality and increase

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Chapter 19: Attacking Childhood Cataract Blindness in the Economically Emerging Countries
market demand. Emphasis is placed on satisfying the
customer and being accountable to the client. Fee for
service introduces accountability into the patientprovider equation. Providers strive to satisfy the
customer to gain loyalty and reputation within the
market place. Consumer expectation regarding quality
and satisfaction forces providers to improve efficiency,
quality and value in order to remain competitive.
Pediatric cataract surgery will add cost to these regional
centers, since anesthesia and vitrectomy equipment costs
will need to be added. In addition, transportation costs
for children identified by rural health-care workers or
eye-camp teams may need to be provided to assure
prompt referral to centers where pediatric cataract
surgery is performed. Only with cost recovery programs
as described above, will pediatric surgery become
financially feasible.
SIMULTANEOUS BILATERAL PEDIATRIC
CATARACT SURGERY OR IMMEDIATELY
SEQUENTIAL CATARACT SURGERY
Some authors59-62 have proposed simultaneous pediatric
cataract surgery to manage the backlog of cataract
blindness in the economically emerging countries. The
fears of bilateral blinding endophthalmitis or bilateral
postoperative wound rupture have made unilateral
surgery the normal procedure in the industrialized
world. Within the amblyopic years, surgery in the second
eye is usually done within a few days or weeks of the
initial surgery. In the economically emerging countries,
this cautious approach may not be practical. To avoid
the risks and costs of a second anesthesia and to make
maximal use of the vitrector tubing and cutter, bilateral
simultaneous surgery on children should be given strong
consideration.
Published accounts of bilateral simultaneous cataract
surgery have come mostly from well-equipped centers
outside of the economically emerging countries. Zwaan59
studied the results of bilateral surgery in a small group
of patients, and also included a literature review comparing the safety of bilateral simultaneous lensectomies in
children versus the risk of more than one general anesthesia within a short time-frame. Bilateral simultaneous
lensectomies were performed in 9 children (18 eyes), in
whom increased anesthetic risks warranted this approach. The author found no postoperative complications
during the first 6 months post-treatment. This author,
however, recommended that simultaneous removal of
bilateral infantile cataracts should probably be reserved
for selected cases where the anesthetic risk is higher than
average.

173

In another study, Totan and associates60 evaluated the


results of bilateral simultaneous cataract surgery in adult
and pediatric patients under local or general anesthesia.
In this study 12 of 17 pediatric patients with congenital
cataracts had bilateral simultaneous lensectomy,
posterior capsulotomy, and anterior vitrectomy; while 5
patients (ages 10 to 19 years), had bilateral extracapsular
cataract extraction (ECCE) with PC IOL implantation
with an intact posterior capsule. The procedures were
treated as two separate surgeries in the same session,
and care was taken to ensure surgical asepsis. No serious
intraoperative complications occurred (such as posterior
capsule rupture, vitreous loss, endophthalmitis, or
anesthesia-related problems). They concluded that simultaneous bilateral cataract surgery was not associated with
an increased rate of complication, and that vision results
were good. If strict rules of surgical asepsis are followed,
this may be a useful option in a variety of bilateral cases
using general or local anesthesia.
Guo and coworkers61, in a retrospective survey of 32
eyes (16 cases) with simultaneous surgery for bilateral
congenital cataracts, suggested that bilateral simultaneous surgery could be performed to avoid a second
general anesthesia in infants who have bilateral dense
congenital cataracts. Smith and Liu62 compared the benefits and risks to patients, and discussed the new attitude
to simultaneous cataract surgery that has arisen this
millennium. They have given a new term to this procedure; they call it immediately sequential cataract
surgery.
There are many reasons for performing simultaneous
bilateral or immediately sequential cataract surgery in
children in the economically emerging countries. The
benefits to the patients are: a single general anesthesia,
improved visual function, one-step visual rehabilitation,
no anisometropia between operations, bilateral IOL
implantation, and overall fewer hospital visits. The
benefits to the hospital are economic: one pre-assessment
visit, one admission for surgery, and efficient use of the
operating theater and clinic time. To society, the benefits
of simultaneous surgery are: shorter waiting lists for
clinics and surgery, less time off work to accompany the
patient, and less demand on hospital transport services.
Ideally, children would be carefully monitored, and the
family would be assisted with postoperative topical
medication for the first week after surgery, then released
to return to their rural environment.
ROLE OF OPHTHALMOLOGISTS FROM
INDUSTRIALIZED NATIONS
There is a relative oversupply of ophthalmologists in
industrialized nations, and an unacceptable deficiency

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174 Section I: Cataract


of ophthalmologists in many developing countries. The
number of available ophthalmologists varies greatly from
one region of the world to another, from about 1
ophthalmologist per 20,000 persons in North America
and Western Europe to 1 per 35,000 in Latin America or
1 per 100,000 in India. There are even fewer ophthalmologists in some African countries (e.g., 1 per 650,000
persons in Kenya to 1 per 1 million in Ethiopia).63
Expatriate programs to improve ophthalmic
education throughout the world were proposed by Tso
and associates.64 These expatriate programs include:
a. The twinning of institutions of industrialized countries with developing countries. This will be helpful
in initiating liaisons between ophthalmic institutions
that can share their expertise and educational
programs so that these developing institutions can
grow together. Collaborations between such institutions involve areas of education, research,
administration, resource mobilization, exchange of
ideas, skills, and subspecialty development in ophthalmology. A collaboration of the Storm Eye Institute
at the Medical University of South Carolina with
institutes of the developing nations such as Addis
Ababa University in Ethiopia, and the Tilganga Eye
Center in Nepal, are both examples of the application
of this concept for pediatric cataract surgery.
b. Ophthalmology training programs in industrialized
countries can fill some training positions with trainees
from developing countries, who will in-turn make a
commitment to return home after this training.
Program directors and leaders in the field of ophthalmology are mobilizing their efforts. Various
international organizations (e.g., Orbis International,
Seva Foundation, etc.) are now funding fellowships
for international medical graduates, who will return
home following the fellowship to help improve their
countries vision needs. An on-going relationship
between the fellow and the mentor following this
training, is essential. The mentor may even be able to
travel to the practice location of the former fellow for
occasional, short hands-on sessions. Internet consultations should also be established that include digital
image transmission whenever possible.
c. Experienced teachers, following mandatory retirement in industrialized countries, are encouraged to
provide training in developing countries.
PEDIATRIC CATARACT SURGERY IN THE
ECONOMICALLY EMERGING COUNTRIES
Guidelines and Recommendation for
Health Planners and Surgeons
The acceptability, accessibility and affordability of
cataract surgical services must each be carefully

addressed to improve efficiency. In some locations the


facilities are in place but under-utilized because there is
a lack of knowledge, monetary constraints, or a negative
public perception of the surgery due to poor results using
inadequate or poorly-timed treatment. Inadequate
ophthalmic and anesthesiology manpower, the lack of
ophthalmic surgical instruments and poor equipment
maintenance, are also widespread in developing countries. Other problems include the logistic complexities of
identifying the children who will benefit most for surgery
and arranging reliable transportation to the treatment
center.
Emphasis should be placed on the purchase of vitrectomy equipment for pediatric cataract surgery, and
ophthalmic surgeons should be trained in the use of this
equipment. This training should include managing
pediatric cataracts, as well as the secondary membranes
from previous attempts at manual aspiration. Proper
maintenance of surgical standards and monitoring of
outcomes will be very important in pediatric cataract
surgery. This will avoid the increased spending of
resources on additional interventions (for those who have
already had eye surgery), while expanding surgical
access to more people. Efforts should be made to promote
technological advancement, outreach activities and
public awareness, while strengthening service delivery.2
Every attempt must be made to restore vision permanently with one surgical procedure to avoid the negative
public attitudes that follow when children become
functionally blind again for secondary cataract months
to years after surgery.
Children needing cataract surgery should be operated
on by an experienced surgeon who has access to safe
pediatric anesthesia. To accomplish this, several steps are
needed. Health personnel who deal with newborn
babies and young children need to ensure that children
with cataracts are seen by eye specialists. Ophthalmologists must be trained in the assessment, surgery and
long-term management of pediatric cataract patients.
Also, more support personnel, including pediatric
anesthetists, orthoptists, refractionists, low-vision
specialists and special pediatric-educationalists need to
be trained. Lastly, the successful management of childhood cataracts can only improve maximally if referral
systems are adapted to transport these children to
specially-trained surgeons operating in well-equipped
centers.
In conclusion, we recommend the following steps to
improve the long-term visual outcome of children with
cataracts, regardless of the cause of those cataracts. These
recommendations are in addition to the many on-going
efforts aimed at the eradication of childhood cataracts
through such programs as rubella vaccination and

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Chapter 19: Attacking Childhood Cataract Blindness in the Economically Emerging Countries
nutritional improvement. These steps should be funded
by non-government organizations and regional eye
centers through donations and cost-recovery plans. Since
the future of any society is its children, it is time to give
childhood cataract treatment the attention that adult
cataract treatment has received for many years. Figures
19.1A to E, illustrate our preferred surgical techniques
for pediatric cataract surgery in the economically emerging countries. Our recommendations are as follows:
a. Improve the early identification and referral of children with cataract by educating and training
pediatricians, rural health clinic personnel, and eyecamp workers to screen for loss of the eyes red reflex
and poor visual functioning in newborn, toddlers, and
school-aged children (Fig. 19.1A).

175

b. Designate regional centers for the treatment of


pediatric cataracts. Equip these centers with automated venturi-pump-driven vitrectomy machines, Ascan ultrasonography and portable keratometry
equipment for IOL power calculations, a supply of
IOLs in a wide range of powers, and pediatric
anesthesia equipment needed for safe monitoredanesthesia of infants and children. Staff these centers
with well-trained pediatric ophthalmic surgeons and
anesthetists. Training in the industrialized world

Figs 19.1A to E: Illustrates our preferred surgical techniques for pediatric


cataract surgery in the developing world using an automated venturi-pumpdriven vitrectomy machine. (A) Clinical photograph showing densefetal
nuclear cataract. An improvement in the early identification, referral and
successful visual rehabilitation after surgery may be helpful for a positive
public perception and subsequent referral in the developing world. (B and
C) Photograph showing mechanized anterior capsulotomy (vitrectorhexis)
technique and aspiration of the lens substance using an automated venturipump-driven vitrectomy machine. (D and E) Photograph illustrating a
mechanized posterior capsulectomy and anterior vitrectomy. We
recommend this technique for all pediatric cataracts regardless-of-age,
unless long-term follow-up and Nd:YAG laser technology is assured. Even
when this technology and follow-up compliance is assured, in some center
of the developing world, children aged 8 or younger should have a primary
posterior capsulectomy and anterior vitrectomy. Although rigid PMMA IOLs
are commonly used in the developing world, foldable lenses are also being
manufactured in developing world and will be more commonly used in the
future

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176 Section I: Cataract

c.

d.

e.

f.

g.

h.

should be provided for both the surgeon and the


anesthetist together, so they can function as a team.
While ketamine may be utilized in the absence of an
anesthetist, every effort should be made to train both
surgeons and anesthetists, and to equip both for
childhood cataract surgery.
Set-up a twinning relationship between each regional
developing-world pediatric cataract center and an
industrialized-world center that has experience in
pediatric surgery. This will facilitate on-site biomedical-equipment repair training and operatingroom nurse training, as well as continuing medical
education and Internet consultation.
While highly-viscous ophthalmic viscosurgical agents
(Healon-GV and Healon-5) make pediatric IOL
surgery easier and safer, less-expensive agents
(HPMC) are more readily available and can be used
effectively.
When operating on the soft, pliable eyes of children,
a tight-fit incision (20-gauge MVR opening for a 20
gauge vitrectomy handpiece) helps maintain the
anterior chamber.
The vitrectorhexis technique is much easier than
manual CCC for producing a round anterior capsulectomy in young children because of the very elastic
nature of the capsule. Aspiration of the soft lens
substance can be easily performed using an automated venturi-pump-driven vitrectomy machine (Figs
19.1B and C).
Perform mechanized posterior capsulectomy and
anterior vitrectomy (ECCE, PPC, AV, IOL) for all
childhood cataracts regardless-of-age, unless longterm follow-up and Nd:YAG laser technology is
assured. Even when this technology and follow-up
compliance is assured, children aged 8 or younger
should have a primary posterior capsulectomy and
anterior vitrectomy (Figs 19.1D and E).
High quality, yet inexpensive, IOLs should be utilized
for children of all ages. These lenses will most likely
be made of PMMA if manufactured in the
economically emerging countries. Foldable lenses are
some times available through donations and have
recently been manufactured in the economically
emerging countries for the first time. These IOLs, if
donated by manufacturers for the children, must be
utilized for children. Globe axial-length and keratometry measurements should be utilized, whenever
possible, to help select an IOL power. While capsular
fixation is the preferred placement, adult-sized
PMMA IOLs may have to be placed in the ciliary
sulcus of small eyes. If the optic is then prolapsed
through both the anterior and posterior rhexis,

centration can be assured and pupillary capture


avoided (personal communication, D. Yorston, MD,
October, 2001).
i. Secure suturing of the tunnel and paracentesis sites
in children is recommended since leakage is common
and trauma in the early postoperative period is
common. Synthetic absorbable suture is preferred
(Biosorb or Vicryl, 9-0 or 10-0), if available. Donations
of these sutures can usually be arranged.
ACKNOWLEDGEMENT
The authors gratefully acknowledge the partial support
of an unrestricted grant from Research to Prevent
Blindness, Inc, New York, NY, USA; and the editorial
assistance of Luanna R. Bartholomew, Ph.D.
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32. Jensen AA, Basti S, Greenwald MJ, Mets MB. When may the
posterior capsule be preserved in pediatric intraocular lens
surgery? Ophthalmology 2002;109:324-28.
33. Wilson ME. Intraocular lens implantation: Has it become the
standard of care for children? (Editorial). Ophthalmology
1996;103:1719-20.
34. Wilson ME, Apple DJ, Bluestein EC, Wang XH. Intraocular
lenses for pediatric implantation: Biomaterials, designs and
sizing. J Cataract Refract Surg 1994;20:584-91.
35. Wilson ME, Bluestein EC, Wang XH. Current trends in the use
of intraocular lenses in children. J Cataract Refract Surg
1994;20:579-83.
36. Green SM, Clark R, Hostetler MA, et al. Inadvertent ketamine
overdose in children: clinical manifestations and outcome. Ann
Emerg Med 1999;34:492-97.
37. Sudan Pun M, Thakur J, Poudyal G, et al. Ketamine anesthesia
for pediatric ophthalmology surgery in the developing world.
Br J Ophthalmol 2002 (in press).
38. Taylor D. Choice of surgical technique in the management of
congenital cataract. Trans Ophthalmol Soc UK 1981;101:114-17.
39. Chrousos GA, Parks MM, ONeill JF. Incidence of chronic
glaucoma, retinal detachment and secondary membrane

40.

41.

42.

43.
44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.
55.
56.

57.

58.

177

surgery in pediatric aphakic patients. Ophthalmology


1984;91:1238-41.
Keech RV, Tongue AC, Scott WE. Complications after surgery
for congenital and infantile cataracts. Am J Ophthalmol
1989;108:136-41.
Basti S, Ravishankar V, Gupta S. Results of a prospective
evaluation of three methods of management of pediatric
cataracts. Ophthalmology 1996;103:713-20.
Eckstein M, Vijayalakshmi P, Gilbert C, Foster A. Randomized
clinical trial of lensectomy verses lens aspiration and primary
capsultomy for children with bilateral cataract in South India.
Br J Ophthalmol 1999;83:524-29.
Yorston D, Wood M, Foster A. Results of cataract surgery in
young children in east Africa. Br J Ophthalmol 2001;85:267-71.
Koch DD, Kohnen T. A retrospective comparison of techniques
to prevent secondary cataract formation following posterior
chamber intraocular lens implantation in infants and children.
Trans Am Ophthalmol Soc 1997;95:351-65.
Koch DD, Kohnen T. Retrospective comparison of techniques
to prevent secondary cataract formation following posterior
chamber intraocular lens implantation in infants and children.
J Cataract Refract Surg 1997;23(Suppl):657-63.
Vasavada A, Trivedi R. Role of optic capture in congenital
cataract and intraocular lens surgery in children. J Cataract
Refract Surg 2000;26:824-31.
Buckley EG, Klombers LA, Seaber JH, et al: Management of the
posterior capsule during pediatric intraocular lens implantation.
Am J Ophthalmol 1993;115:722-28.
Alexandrakis G, Peterseim MM, Wilson ME. Clinical outcomes
of pars plana capsulotomy with anterior vitrectomy. J AAPOS
2002 (in press).
Pandey SK, Thakur J, Werner L, Izak AM, Apple DJ. Classification, clinical applications and complications of ophthalmic
viscosurgical devices: An update. In: Garg A, Pandey SK.
Textbook of Ocular Therapeutics. Jaypee Brothers Medical
Publisher (P) Ltd, New Delhi, India 2002 (in press).
Tan DT, Chee SP, Lim L, Lim AS. Randomized clinical trial of a
new dexamethasone delivery system (Surodex) for treatment
of post-cataract surgery inflammation. Ophthalmology
1999;106:223-31.
Chang DF, Wong V. Two clinical trials of an intraocular steroid
delivery system for cataract surgery. Trans Am Ophthalmol Soc
1999;97:261-79.
Tan DTH, Chee SP, Lim L, Theng J, Van Ede M. Randomized
clinical trial of Surodex steroid drug delivery system for cataract
surgery: anterior versus posterior placement of two Surodex in
the eye. Ophthalmology 2001;108:2172-81.
BenEzra D: Cataract surgery and intraocular lens implantation
in children, intraocular lens implantation in children. Am J
Ophthalmol 1996;121:224-26.
Venkataswamy G. Intraocular lens implantation in India.
Ophthalmic Surg 1990;21:866-67.
Dahan E. Pediatric cataract surgery. In: Yanoff M, Ducker JS,
eds, Ophthalmology. St Louis, Mosby-Yearbook, 1998; 30.1-30.6
Spierer A, Desantik H. Refractive status in children after longterm follow-up of cataract surgery with intraocular lens
implantation. J Pediatr Ophthalmol Strabismus 1999;36:25-29.
Hutchinson AK, Wilson ME, Saunders RA. Outcomes and ocular
growth rates after intraocular lens implantation in the first 2
years of life. J Cataract Refract Surg 1998;24:846-52.
Rao GN. Ophthalmology in India. Arch Ophthalmol 2000;118:
1431-32.

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178 Section I: Cataract


59. Zwaan J. Simultaneous surgery for bilateral pediatric cataracts.
Ophthalmic Surg Lasers 1996;27:15-20.
60. Totan Y, Bayramlar H, Cekic O, Aydin E, et al.Bilateral cataract
surgery in adult and pediatric patients in a single session. J
Cataract Refract Surg 2000;26:1008-11.
61. Guo S, Nelson LB, Calhoun J, Levin A. Simultaneous surgery
for bilateral congenital cataracts. J Pediatr Ophthalmol
Strabismus 1990;27:23-5; discussion 26-27.

62. Smith GT, Liu CS. Is it time for a new attitude to simultaneous
bilateral cataract surgery? Br J Ophthalmol 2001;85:1489-96.
63. Foster A. Patterns of blindness. In: Duane E, Ed. Clinical
ophthalmology. Vol 5. New York: Harper and Row, 1991.
64. Tso MO, Naumann GO, Zhang SY. Studies of prevalence of
blindness in the Asia-Pacific region and the worldwide initiative
in ophthalmic education. Am J Ophthalmol 1998;126:582-85.

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20

Update on Capsular Dye


Enhanced Cataract Surgery
Suresh K Pandey, Liliana Werner, David J Apple

INTRODUCTION
OPHTHALMIC DYES FOR
ANTERIOR CAPSULORHEXIS
OPHTHALMIC DYES FOR
PHACOEMULSIFICATION
OPHTHALMIC DYES FOR
POSTERIOR CAPSULORHEXIS
OPHTHALMIC DYES FOR
PEDIATRIC CATARACT
SURGERY

INTRODUCTION
Various non-toxic ophthalmic dyes have been extensively used as
diagnostic agents for the detection and management of different ocular
disorders. Table 20.1 summarizes the use of various dyes in ophthalmology.
Dyes such as fluorescein sodium, indocyanine green (ICG), have a long
history of safety in humans.1 There have been an increasing number of
reports of enhanced visualization by staining intraocular tissues during
cataract surgery and vitreoretinal surgery.2-19 Staining of the ocular tissue
by using the ophthalmic dyes makes visual differentiation and
manipulation of tissues easier. Enhanced viewing of the ocular tissues can
promote a surgeons ability to evaluate clinical structural relationships and
may help attain surgical objectives with fewer complications.2-19
Small incision cataract surgery using phacoemulsification has currently
evolved into one of the most successful surgical techniques in ophthalmology and the visual sciences. Many modifications such as continuous
curvilinear capsulorhexis (CCC),20,21 hydrodissection,22-25 hydrodelineation,26 and various maneuvers for nuclear emulsification and cortical cleanup have been added to it, increasing its safety and efficacy. Posterior
capsulorhexis, a technically challenging procedure, has also been recommended for delaying opacification of posterior capsule in pediatric cataracts
and for managing the posterior capsule tears by several surgeons.27-31
We have extensively studied the use of non-toxic ophthalmic dyes
(fluorescein sodium, ICG and trypan blue) to enhance visualization of
various intraocular tissues while performing various critical steps of
modern phacoemulsification procedure7-9,12-14 (Pandey SK, Werner L,
Escobar-Gomez M, Apple DJ. Anterior capsule staining in advanced
cataracts: A laboratory study using post-mortem human eyes; presented
at the joint meeting of American Academy of Ophthalmology, Orlando,
Florida, October 1999; Pandey SK, Werner L, Apple DJ, et al. Dye-enhanced
cataract surgery in human eyes obtained postmortem: A laboratory study
to learn critical steps of phacoemulsification: XVIIth Congress of the
European Society of Cataract and Refractive Surgery, second prize:
Scientific Category, Vienna, Austria, September 1999). In this chapter
we will address the use of non-toxic ophthalmic dyes to successfully stain
the intraocular tissues during various steps of modern phacoemulsification
procedure. For the convenience of readers, we have divided this chapter
in 4 sections, adressing their use in adult and pediatric cataract surgery. To
provide a brief detail to our readers, in Section 1, we will discuss the use of
ophthalmic dyes to stain the anterior capsule while performing CCC in
advanced/white cataracts. In Section 2, we will focus on the use of

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180 Section I: Cataract


Table 20.1: Use of dyes in ophthalmology
Segment

Structure
stained

Anterior segment
Cornea

Iris
Lens

Posterior segment
Retina
Vitreous
Vitreoretinal
surgery

Use

Dye

Epithelial
defects
Contact lens
fitting
Seidels test
Dry eye
Diagnosis of
keratitis
Endothelial cell
count
Neovascularization
Capsulorhexis
(poor or no red
reflex)
Dye-enhanced
cataract surgery

FS*

Angiography
Vitrectomy
IRM*****
peeling

FS
FS
FS, RB**
FS, RB
TB***
FS, ICG****
FS, ICG, TB

Capsulorhexis in Absence of Red Reflex


In todays clinical practice, white, mature and hypermature cataracts are still commonly seen, especially in
the developing world (Figs 20.1A to C).33 It is difficult to
perform a CCC in the presence of mature cataracts
because the red reflex, which is necessary to observe the
actual tearing process, is absent. With poor visibility,
errant capsular tearing is very common and difficult to
control, thus jeopardizing in-the-bag IOL implantation.
The accepted recommendations to aid CCC in such cases
are: dimming the operating room lights, increasing the
operating microscope magnification and coaxial
illumination, and using high-density viscoelastics. The
use of air,34 diathermy,35 endoilluminator,2 vitrectome,
scissors,36 and the two-stage CCC approach33,37 have also
been suggested.
Use of Ophthalmic Dyes in CCC

ICG, TB

FS, ICG
FS, ICG
ICG

*:FS = Fluorescein sodium;**:RB = Rose Bengal;***:TB =


Trypan blue; ****:ICG = Indocyanine green; *****:IRM =
Internal limiting membrane

ophthalmic dyes to help enhance visualization to learn


the critical steps of phacoemulsification surgery, which
include: CCC, hydrodissection/hydrodelineation,
nuclear emulsification, and cortical clean-up. In Section
3, we will address the use of ophthalmic dyes for
posterior capsule staining to learn and perform
technically challenging procedure of posterior
capsulorhexis. Finally, in Section 4, we will focus on the
use of ophthalmic dyes for pediatric cataract surgery.
OPHTHALMIC DYES FOR ANTERIOR
CAPSULORHEXIS
Introduction
Cataract surgeons agree that an anterior CCC should be
the goal of every opening of the anterior capsule. CCC
has gained widespread popularity because it offers
unquestionable advantages over other capsulotomy techniques.20,21 Because of complications such as intraocular
lens (IOL) asymmetrical fixation, decentration, or pea
podding of the IOL haptics associated with the envelope
or the can-opener capsulotomy techniques, CCC is
preferred in PE or planned extracapsular cataract extraction.20,21,32

Ophthalmic dyes such as 2 percent fluorescein sodium,


0.5 percent ICG,5,7,10 and 0.1 percent trypan blue6,7,11,15
have been successfully used for staining the anterior
capsule, for performing CCC. Two main surgical techniques have been used for fluorescein sodium: (a) staining
from above, under an air bubble, and (b) intracameral
subcapsular injection.3,4 Use of 0.001 percent to 0.01 percent and gentian violet solutions and also 0.05 percent
to 0.25 percent crystal violet solution have also been
recently reported for staining the anterior capsule in
animal models (albinos rats and rabbits respectively).16,17
Gentian violet and crystal violet dyes are not preferred
in human eyes due to adverse corneal effects and possible
endothelial cell toxicity.
Study Comparing 3 Ophthalmic Dyes and
2 Surgical Techniques
We have evaluated in an experimental closed-system
surgery, anterior capsule staining for performing CCC
in postmortem human eyes with advanced/white cataracts, using 3 dyes.7 These are fluorescein sodium, ICG,
and trypan blue; and all have been clinically advocated
for use with this procedure. We also compared the two
commonly used methods of staining under an air bubble,
and intracameral subcapsular injection (Pandey SK,
Werner L, Apple DJ. ICG staining reduces your risk,
compare three dyes. In Clinical Update: Cataract. EyeNet
2000; 4:25-26).7
Preparation of the Ophthalmic Dyes
A 2 percent fluorescein sodium solution was prepared
by mixing 1 mL of 10 percent fluorescein for intravenous
use (Alcon Ophthalmic, Fort Worth, TX, USA) with 4 mL

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery

181

of balanced salt solution (BSS). ICG solution (Akorn,


Inc., Buffalo Grove, IL, USA) was prepared by dissolving
25 mg of ICG in 0.5 mL of an aqueous solvent (provided
with the ICG), which was mixed in 4.5 mL of an irrigating
solution (BSS plus, Alcon Ophthalmic, Fort Worth, TX,
USA).5 To obtain 0.1 percent trypan blue, we mixed 1
mL of a 0.4 percent solution (Life Technologies, Grand
Island, NY, USA) in 3 mL of BSS.
Surgical Technique
Randomly accessioned postmortem human eyes (n = 12)
received within 4 days of death in the Center for Research
on Ocular Therapeutics and Biodevices from Eye Banks
nationwide, were used in this study. We only used eyes
presenting advanced/white cataracts (Figs 20.2A and B).
They were immersed in dextran solution for 30 minutes
and prepared according to the technique of Auffarth

Figs 20.1A to C: Slit-lamp photographs showing 3 examples


of advanced/white cataracts. (Courtesy: Abhay R Vasavada,
MD, FRCS, Ahmedabad, India)

Figs 20.2A and B: Gross photographs of human eyes obtained


postmortem showing the presence of a white cataract:
(A) Anterior (surgeons) view, (B) Miyake-Apple posterior view

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182 Section I: Cataract


et al.38 After the eye was fixed in the training head, a selfsealing corneoscleral tunnel incision approximately 3.2
mm wide was made. The iris was pulled out from its
attachment to allow better visualization of the anterior
capsule. Two different techniques were used for the
capsular staining. Initially in 6 globes, air was carefully
injected using a 27 gauge cannula and a 2.0 cc syringe.
Then, the dye was injected over the anterior capsule

D. Visualization of the anterior capsule is


enhanced after staining with ICG

A. Fluorescein sodium

E. Visualization of the anterior capsule is enhanced


after staining with trypan blue
Figs 20.3A to E: Anterior (surgeons) view of a human eye
obtained postmortem with advanced/white cataracts showing
the staining of the anterior capsule under an air bubble

B. ICG

C. Trypan blue

(0.10 ml) within the air bubble (2 globes/dye). After a


few seconds, the air bubble was replaced with sodium
hyaluronate (Healon, Pharmacia Inc., Peapack, NJ,
USA), and CCC was then performed (Figs 20.3A to E).
Alternatively, in the other 6 globes, we used the technique of intracameral subcapsular injection (Figs 20.4A
to D and 20.5A and B). After the aqueous was replaced
with Healon, we carefully injected 0.05-0.10 mL of the
dye beneath the anterior capsule (2 globes/dye) using a
30 gauge needle. A small leakage of dye from the subcapsular space was observed during this step. After the
stained viscoelastic was replaced by clear Healon, the
point of injection was used for beginning the CCC with
Utratas forceps. Blue light enhancement was used
during CCC for fluorescein sodium.
To compare the 2 techniques and the 3 dyes, the
following 2 parameters were evaluated by 2 independent
surgeons (SKP, LW):

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery


a. Ability to perform the staining technique (+ = difficult; ++ = intermediate; +++ = easy),
b. Staining of the anterior capsule (+ = faint; ++ = intermediate; +++ = good).
Photographs were taken using a Topcon camera fitted
to the operating microscope, with and without a blue
filter. The Miyake-Apple posterior video/photographic
technique39,40 was also used in another 3 globes to document any dye leakage into the vitreous cavity (1 globe/
dye). We performed the staining of the anterior capsule
under an air bubble using fluorescein sodium, ICG and
trypan blue in 6 globes (2 globes each). Alternatively, the
same dyes were used for intracameral subcapsular
injection in the other 6 globes (2 globes each).
Results
Table 20.2 shows the results of our evaluation of the 2
staining techniques (under an air bubble, and intracameral subcapsular injection) and the 3 dyes (fluorescein
sodium, ICG and trypan blue). In all globes, CCC was
completed uneventfully. Of these 2 techniques, the intracameral subcapsular injection provided a slightly better
staining of the anterior capsule. The dye remained
trapped in the subcapsular space after the injection, in
contact with the posterior surface of the anterior capsule,
allowing enough time to perform any maneuver. Among
the three dyes used in this study, the staining provided

183

by ICG, at the concentration used, was found to be


slightly superior (Figs 20.4A to D and 20.5A and B). It
was notably easier to localize the ICG stained posterior
surface of the inverse anterior capsular flap while
performing CCC, after the subcapsular injection of the
dye (Figs 20.4C and D). The Miyake-Apple posterior
video/photographic technique demonstrated a leakage
of fluorescein sodium into the vitreous after using both
dye administration methods (under an air bubble and
intracameral subcapsular injection). The intensity of this
leakage increased progressively with time. Figures 20.6A
to C illustrates the progressive leakage of the fluorescein
sodium into the vitreous cavity after intracameral
subcapsular injection. No vitreous leakage was observed
with ICG or trypan blue after using any of the two
aforementioned techniques of anterior capsule staining.
Tables 20.3 and 20.4 summarize the advantages and
disadvantages associated with the use of dyes (fluorescein sodium, ICG and trypan blue) and the techniques
of staining (under an air bubble, and intracameral
subcapsular injection).
Clinical Application and Guidelines for Surgeons
Staining of the anterior capsule with ophthalmic dyes is
a useful alternative for performing CCC in cases of
advanced/white cataract. Fluorescein sodium was the
first dye advocated for this use.2-4 ICG and trypan blue

Table 20.2: Evaluation of the dyes and techniques used for staining the anterior capsule
First surgeon
Eye Technique

1. Under an air
bubble
2. Under an air
bubble
3. Under an air
bubble
4. Subcapsular
injection
5. Subcapsular
injection
6. Subcapsular
injection

Dye

Second surgeon

Ability to
Staining of
perform the anterior capsule**
technique*

FS***

+++

ICG****

+++

++

TB*****

+++

++

FS

+++

++

ICG

+++

+++

TB

+++

++

Eye Technique

7. Under an air
bubble
8. Under an air
bubble
9. Under an air
bubble
10. Subcapsular
injection
11. Subcapsular
injection
12. Subcapsular
injection

*: + = difficult; ++ = intermediate; +++ = easy.


**: + = faint; ++ = intermediate; +++ = good.
***: FS = fluorescein sodium.
****: ICG = indocyanine green.
*****: TB = trypan blue.

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Dye

Ability to
perform the
technique*

Staining
anterior
capsule**

FS

+++

ICG

+++

++

TB

+++

FS

+++

++

ICG

+++

+++

TB

+++

++

184 Section I: Cataract

Figs 20.4A to D: Anterior (surgeons) view of a human eye obtained postmortem with white cataract showing the staining of
the anterior capsule using intracameral subcapsular injection of ICG. Cornea and iris were excised to allow better visualization
of the anterior capsule: (A) Note the entrapment of the dye into the subcapsular space (arrows), (B) The capsulorhexis can be
initiated by grasping the injection hole. (C and D) The visualization of the anterior capsule is enhanced by the staining of its
posterior surface with the dye

Figs 20.5A and B: Anterior (surgeons) view of a human eye obtained postmortem showing the better contrast against the
white cataract provided by the staining of the posterior surface of the anterior capsule with trypan blue

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery

185

Table 20.3: Characteristics of the three dyes used for anterior capsule staining
Dye

Concentration

Advantages

Disadvantages

Fluorescein sodium

2%

Blue light enhancement


can be used

Indocyanine green

0.50%

Trypan blue

0.10%

High molecular weight


No vitreous leakage
High molecular weight
No vitreous leakage

Low molecular weight


Vitreous leakage
Staining of the cornea
Cost may be prohibitive
Not indicated in pregnant/fertile
females and children

Table 20.4: Characteristics of the two techniques used for anterior capsule staining
Staining under an air bubble

Intracameral subcapsular injection

Advantages

Disadvantages

Advantages

Disadvantages

Technically less
invasive
Staining of the peripheral anterior capsular
rim, provides good
visibility while
performing
phacoemulsification
Safer in intumescent
hypermature cataracts

Air-filled anterior chamber


is unsteady
Progressive dilution of
the dye by aqueous

Dye remains trapped in


the subcapsular space
Good staining of the
posterior surface of the
capsular flap

Technically more invasive


Tear of the anterior
capsule, if excessive
injection of dye

Injection hole can be used


for initiating CCC

Anterior capsule tear in


intumescent cataracts

were further recommended for this purpose.5-7,10,11,15,18


ICG and trypan blue selectively stain dead corneal
endothelial cells. Because the endothelial cells are alive
in human cataract surgery, ICG and trypan blue neither
stain these cells nor obstruct the surgeons view. Because
of its smaller molecular weight (376 d), fluorescein
sodium can stain the cornea and also migrate to the
vitreous cavity. We were able to demonstrate the leakage
of fluorescein sodium into the vitreous cavity using the
Miyake-Apple posterior video/photographic technique.
In the study of Horiguchi et al.,5 fluorescein sodium could
not be removed from the vitreous cavity by an irrigationaspiration system. The reconstituted ICG dye is only
good for 10 hours. Because the bottle of ICG is expensive
(approximately US $ 90.00 for 25 mg ICG), it is better to
schedule several patients with absent or poor red reflex
on the same surgery day. Intraocular solutions of trypan
blue have not yet been FDA approved and therefore are
not currently available in the United States; thus, the
solution has to be prepared before surgery. Trypan blue
0.1 percent solution (ready to be used) for capsular
staining is commercialized by DORC International b.v.
(Vn Zuidland, Holland) under the trade name of
VisionBlue, as it was proposed by Melles.6 Recently, a

0.1 percent solution of trypan blue dye became commercially available from Dr Agarwals Pharma Ltd. (Chennai,
India) under the trade name of Blurhex. Trypan blue is
less expensive than ICG, and to the best of our
knowledge, the cost of a 1 mL ampoule of trypan blue
(Blurhex) is approximately US $ 3, compared to the US
$ 90.00 cost of 1 ampoule of 25 mg ICG powder.18
The surgeon should avoid using the trypan blue dye in
fertile women, pregnant women, or children, because,
in some animal studies, when this dye was given intravenously or intraperitoneally (more frequent applications, and at much higher concentrations), it induced
neoplasms (Melles GRJ. Trypan blue dye helps to
visualize capsulorhexis, Cataract and Refractive Surgery
Eurotimes, May-June, 1999).
The surgeon should also be careful when using any
ophthalmic dyes in cataract surgery combined with
implantation of hydrophilic acrylic lenses having a high
water content (73.5%), as this can lead to permanent
staining (discoloration) of the IOL by ophthalmic dyes.
This discoloration may also be associated with a decrease
or alteration in the best-corrected visual acuity,
eventually requiring IOL explantation/exchange. We
have recently analyzed 2 Acqua hydrophilic acrylic

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186 Section I: Cataract

Figs 20.6A to C: Miyake-Apple posterior view of a human eye


obtained postmortem showing the progressive leakage of
fluorescein sodium into the vitreous cavity after intracameral
subcapsular injection. Note that the intensity of the leakage
increases as time progresses: (A) Five minutes after intracameral subcapsular injection, (B) Same globe, 15 minutes
after intracameral subcapsular injection, (C) Same globe, 2
hours after intracameral subcapsular injection

lenses explanted secondary to bluish discoloration after


use of trypan blue dye.41
The techniques originally reported for staining the
anterior capsule using fluorescent sodium are: staining

from above under an air bubble, as proposed by Nahra


and Castilla (Nahra D, Castilla M, Capsulorhexis in no
view cataract: Staining of the anterior capsule with 2
percent fluorescein, presented at the annual meeting of
the American Academy of Ophthalmology, October 1996,
Chicago, Illinois, USA), and intracameral subcapsular
injection of fluorescein sodium (staining from below)
with blue-light enhancement. 3,4 The first technique
(staining under an air bubble) is currently used by most
surgeons. One benefit is the staining of the peripheral
anterior rim, which is otherwise difficult to visualize
during the phacoemulsification procedure.6 However, air
in the anterior chamber makes it unsteady. Any
instrument entering the eye will cause some air to escape,
with a rise of the lens-iris plane. A small amount of highdensity viscoelastic placed near the incision can prevent
the air bubble from escaping the anterior chamber, thus
minimizing the risk of sudden collapse. Also, with this
technique, there is a progressive dilution of the dye by
the aqueous humor. This may be a possible explanation
for the fainter staining observed with this technique in
recent clinical reports, without compromising its
usefulness (Steinert RF, ICG dye aids in visualization of
the anterior capsule, Ophthalmology Times, May 15,
1999). Most of the drawback of this technique can be
avoided by careful use of a viscoelastic solution to seal
the incision site. Akahoshi proposed the soft shell stain
technique for performing a CCC in white cataract cases
(Akahoshi T, Soft shell stain technique fort white cataract,
presented at the ASCRS symposium on Cataract, IOL,
and Refractive Surgery, Boston, MA, May 2000). A small
amount of viscoelastic (Viscoat) was injected into the
anterior chamber followed by high molecular weight
viscoelastic material (Provisc) to fill up the chamber
completely. The author then injected ICG solution on the
lens surface with a bent G27 viso cannula. The anterior
capsule was uniformly stained green and easily visualize
while the cornea remained unstained. According to
author, the soft shell stain technique is extremely useful
for CCC of white cataracts.
Alternatively, the dye solution can be mixed with
viscoelastic agents. Kayikicioglu and coworkers15 proposed a technique for limiting the contact of trypan blue
by mixing the dye with a viscoelastic solution. These
researchers mixed 0.4 percent trypan blue with 1 percent
sodium hyaluronate in a 2 mL syringe. The dye, mixed
in a viscoelastic solution, is injected onto the anterior lens
capsule, which covers the anterior capsule without
coming in contact with the corneal endothelium. Trypan
blue mixed with sodium hyaluronate greatly increase the
visibility of the anterior lens capsule without significantly
touching the adjacent tissues. There is a potential risk of

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery


corneal decompensation after intraocular use of selfmixed solution; however, these authors used this
technique without significant surgical and postoperative
adverse effects.
Intracameral subcapsular injection is another, but less
commonly used, technique of anterior capsule staining.
It has the advantage of trapping the dye in the
subcapsular space, mostly in the center and in the
midperipheral part. It gives sufficient time for the
surgeon to perform any maneuver until the CCC releases
it. Meanwhile, the dye remains in contact with the
posterior surface of the anterior capsule. This may be a
possible explanation for the better staining observed in
our laboratory study on postmortem human eyes.7 The
capsule and cortex are both stained by the dye used, but
they can be clearly distinguished from the feathery
appearance of the cortex and the smooth staining of the
capsule. The CCC is fairly easy to perform by grasping
the injection hole. This technique was originally proposed
for fluorescein with blue-light enhancement, but we also
used it with ICG and trypan blue. When the capsular
flap is inverted, the stained posterior surface of the
anterior capsule enhances visualization and thus
facilitates tearing during CCC. In our study, this was
more obvious with the intracameral subcapsular injection
of ICG.7 Further, this can be performed without the need
for any special type of illumination, such as a cobalt bluefilter. We would like to emphasize that there is the risk
of anterior capsule tear formation after subcapsular
injection of dye. However, we did not observe this
complication (anterior capsule tear) in any postmortem
human eyes used in our laboratory study.7 We would
certainly not recommend the intracameral subcapsular
injection technique for performing CCC in intumescent
and hypermature cataracts owing to the high
intralenticular pressure and fragile anterior lens capsule
that may easily result in radial tear formation.
Horiguchi et al,5 reported the technique of staining
the anterior capsule using a 2 percent solution of ICG in
patients with mature cataracts. They compared the
results of phacoemulsification and IOL implantation in
2 groups of 10 eyes. In the first group, the anterior capsule
was stained with ICG before CCC, and in the second, no
dye was used. There was no statistically significant
difference reported in their study between both groups
concerning specular-microscopy endothelial cell
counting, and laser flare-cell photometry, thus the
staining procedure was considered to be safe.
Clinical experience with ICG and trypan blue for
anterior capsule staining in mature white or brunescent
cataracts was first reported by David Chang42 in two
consecutive, non-randomized series of mature or brune-

187

scents cataracts. The technique of dye injection under an


air bubble, ICG dye was used in the first series, and
trypan blue in the subsequent series. According to author,
both dyes provided consistently excellent visualization
and clinical results without any adverse effects. However,
trypan blue created a more intense and persistent staining
and provided superior visualization when compared
with ICG, according to this first clinical study (Chang
DF, MD. Compare two dyes. EyeNet 2000; 4:22).42
We would like to provide some recommendations and
guidelines for ophthalmic surgeons regarding suitable
ophthalmic dyes and the anterior capsule staining
technique. These are based on our experience in postmortem human eyes, as well as published clinical reports
from several other surgeons. Both ICG and trypan blue
are currently preferred over fluorescein sodium dye, due
to better staining of the anterior capsule and the absence
of vitreous leakage (due to high molecular weight). Both
these dyes provide excellent visualization of the anterior
capsule flap during CCC, without causing any toxic
effects on the corneal endothelium. Trypan blue has the
advantage of being less costly when compared to the cost
of ICG. However, trypan blue should be avoided in
fertile/pregnant females and in children due to the
possible teratogenic and/or mutagenic effects observed
in animal studies when using this dye. Further studies
may be helpful to determine the least available
concentration of the trypan blue dye that can be used to
stain the anterior lens capsule in order to perform the
CCC. ICG remains a valuable alternative for these special
patients (children and pregnant females). Staining under
the air bubble technique is safer and therefore recommended for intumescent and hypermature cataract
patients presenting with high intralenticular pressure and
a fragile anterior lens capsule. Viscoelastic solutions can
be used to visco-seal the incision site in order to avoid
escape of the air bubble, and to minimize any anterior
chamber fluctuations. Alternatively, mixing the dye with
a viscoelastic solution may also be used for better anterior
capsule staining, and for limiting the contact with
adjacent ocular tissues.
OPHTHALMIC DYES FOR PHACOEMULSIFICATION
Introduction
It is important to practice the phacoemulsification (PE)
procedure in a wet laboratory setting in order to reduce
the learning curve and enhance the safety margin before
operating on the real patient.42-46 Human eye bank or
animal eyes are commonly used for this purpose. The
surgeon must be familiar with the critical steps of the PE
procedure. Each step is therefore to be learned indepen-

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188 Section I: Cataract


dently and carefully in order to achieve a successful
outcome and reduce complications. This is even more
important when dealing with advanced/white cataracts
in a clinical setting. The absence of a red reflex in such
cases renders CCC as well as nucleus sculpting maneuvers difficult, if not impossible.47
In the first Section, we have discussed a detailed
evaluation of the staining of the anterior capsule for CCC
in advanced cataracts, comparing 3 dyes (fluorescein
sodium, ICG, and trypan blue dyes), and two injection
techniques, in postmortem human eyes. All dyes
provided satisfactory staining of the anterior capsule for
CCC. However, fluorescein sodium progressively leaked
into the vitreous.7 In this Section we report our experience
with the application of 0.5 percent ICG and 0.1 percent
trypan blue to obtain complete hydrodissection/delineation, to stain the nuclear substance during nuclear
emulsification, and to stain capsular bag during the
cortical clean-up. Application of the ophthalmic dye for
performing phacoemulsification is termed Dye-enhanced
Phacoemulsification and this section will focus on the use
of dye to enhance visualization for learning, and
performing critical steps of the phacoemulsification
procedure.
Study of Dye-enhanced Phacoemulsification
Surgical Technique
Randomly accessioned postmortem human eyes (n = 16)
obtained within 4 days of death from eye banks
nationwide were used in our study.8
They were prepared according to the Miyake-Apple
posterior video technique.39,40 Two independent surgeons
(LW, SKP) evaluated the use of 0.5 percent ICG and 0.1
percent trypan blue to perform the critical steps of PE in
8 eyes (2 eyes/dye/surgeon). Dye solutions were prepared as previously described in this chapter (Section
1). In 8 other eyes used as controls, the PE procedures
were performed without the use of dye. After the cornea
and iris were removed, a CCC (4.5 to 5.5 mm in diameter)
was initiated using a 26 gauge needle cystitome and
completed using Utratas forceps. A complete cortical
cleaning hydrodissection was performed by injecting
2-3 cc of the dye solution (0.5% ICG or 0.1% trypan blue)
between the lens capsule and the cortex with a 27 gauge
cannula. This was followed by hydrodelineation: placement of a 27 gauge cannula deep into the nucleus and
injection of the dye solution created the colored fluidwave marking the separation of the nucleus and the
epinucleus. Balanced salt solution (BSS) was used to
perform hydrodissection/delineation in the control

group. Nuclear emulsification (Alcon Legacy 20,000,


Alcon Surgical, Fort Worth, TX) was performed using
the divide-and-conquer nucleofractis technique.47 One to
two microdrops of the dye solution were instilled into
the capsular bag, and cortical clean-up was performed
using the irrigation and aspiration system.
The enhancement of visualization while performing
each step of the surgery using the dyes was evaluated
by the two independent surgeons. They particularly
noted:
a. If the use of a colored solution helped in visualizing
the fluid waves and the plane of cleavage during
hydrodissection/delineation,
b. If the staining of the nucleus substance helped in
appreciating the depth of the phaco tip and its position in relation to the posterior capsule during the
nuclear emulsification, and
c. If the staining of the inner surface of the capsular bag
helped in identifying residual cortical material during
the cortical clean-up procedure using the irrigationaspiration system.
Results
Our experimental study suggested that both dyes (0.5%
ICG, and 0.1% trypan blue) successfully enhanced
visualization while performing critical steps of the PE
procedure, when compared to the control group.8 During
hydrodissection/hydrodelineation, the use of dye helped
to visualize the formation of a complete cleavage between
the capsule and cortex, as well as between the nucleusepinucleus complex (Figs 20.7A and B). Incomplete
cleavage could be easily identified by using a colored
solution, and promptly completed by reinjection in the
appropriate quadrant.
During the nuclear emulsification procedure, the use
of dye helped in appreciating the position of the phaco
tip and its relation with the posterior capsule, thus increasing the safety of the procedure (Figs 20.8A and B).
For the complete cleaning of the capsular bag, the
use of dye provided better visualization of the residual
cortical material during the irrigation-aspiration
procedure (Figs 20.9A and B). It was easy to differentiate
the feathery, irregular staining of the cortex from the
smooth staining of the capsule.
Learning Critical Steps of Phacoemulsification
It is important to learn the critical steps of the PE procedure, which include CCC, hydrodissection, hydrodelineation, nuclear emulsification maneuvers, and cortical
clean-up. In a series of 7,169 patients undergoing phacoemulsification, Gimbel reported 36 peroperative

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery

189

Figs 20.7A and B: Gross photographs of a human eye obtained postmortem. Cornea and iris were excised to allow better
visualization: (A) Anterior (surgeons) view showing hydrodissection/hydrodelineation enhanced by trypan blue. Notice the
complete (360 degrees) blue-colored fluid wave indicating separation of the nucleus/epinucleus complex, (B) Sagittal section
of the same crystalline lens, showing the demarcation zone between the nucleus/epinucleus complex (arrows)

Figs 20.8A and B: Gross photographs of a human eye obtained postmortem taken from an anterior (surgeons) view while
performing nucleus sculpting. Cornea and iris were excised to allow better visualization: (A and B) Gimbels divide-and-conquer
nucleofractis technique. Notice that trypan blue dye enhances visualization of the groove. This is helpful to judge the position
of the phaco tip and its relation with the posterior capsule

posterior capsule tears.48 Of these, 19 (53%) occurred


during the irrigation/aspiration step and 13 (36%)
occurred during the phacoemulsification itself. Five and
six percent of the posterior capsule tears occurred during
the IOL implantation and the hydrodissection,
respectively. Visualization while performing each step
can be enhanced by the use of different dyes, thus
increasing their safety margin.
CCC
We have addressed the techniques of anterior capsule
staining for anterior capsulorhexis using fluorescein
sodium, ICG, and trypan blue dyes in Section 1 of this
chapter. In Section 2, we used only ICG and trypan blue,

on account of the drawback of vitreous leakage


associated with fluorescein sodium. In addition to the
staining of the anterior capsule when performing CCC,
ICG and trypan blue can also be successfully used to learn
other critical steps of the PE procedure in a laboratory
setting. We believe that the use of dye would not only be
useful during the anterior capsule management in white
cataracts, but also for learning and practicing the other
critical steps of phacoemulsification procedure as
discussed here.
Hydrodissection/Hydrodelineation
Hydrodissection is an important step of small incision
cataract surgery using phacoemulsification. The use of

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190 Section I: Cataract

Figs 20.9A and B: Gross photographs of human eyes obtained postmortem taken from an anterior (surgeons) view after the
completion of irrigation/aspiration. Cornea and iris were excised to allow better visualization. Note the cleaned capsular bags,
stained green and blue after the use of ICG and trypan blue dyes, respectively. The arrows demonstrate in both cases the
staining of the minimal residual cortical material. (A) ICG (B) Trypan blue

this procedure was first reported by Faust.22 Fine24 added


the concept of cortical cleavage hydrodissection to
separate the superficial cortex from the lens capsule. The
use of dye (instead of BSS) helps in the localization of
the complete (360 degree) cortical cleavage plane,
separating the equatorial and posterior capsule from the
cortex. It is much easier to visualize a dye-colored fluid
wave of hydrodissection. Therefore, it helps in achieving
complete separation between capsule and cortex. Hydrodelineation,26 associated with the formation of a golden
ring, is sometimes difficult to notice. With the injection
of a capsular dye solution, however, the surgeon can
successfully visualize the demarcation between the
nucleus and the epinucleus (Fig. 20.7A). In this situation,
an incomplete hydrodissection/delineation can be easily
identified and completed by injecting more stained fluid
in that particular quadrant, if needed. After achieving
complete hydrodissection and hydrodelineation it is
easier to perform nuclear emulsification with less ultrasound power and time, decreasing the need for cortical
clean-up and the risk of posterior capsule tears. Recent
studies from our laboratory suggest that hydrodissectionenhanced cortical clean-up is an unidentified but important factor for delaying the onset of posterior capsule
opacification.49
Nuclear Emulsification
A number of different techniques have been used by
surgeons for nuclear emulsification of hard and soft
cataracts. While performing nuclear emulsification

maneuvers, visualization of the depth at which the phaco


tip is sculpting is crucial. Its significance cannot be
overemphasized for preventing complications like
unnoticed posterior capsular tears, vitreous loss and
dislocation of the nucleus into the vitreous cavity. When
a good red reflex is present, the surgeon can rely on an
increasingly brighter-red reflex to gauge proximity to the
posterior capsule while sculpting the nucleus. However,
the absence of a red reflex (e.g. in advanced, white,
mature or hypermature cataracts) complicates nucleus
emulsification because it is difficult to judge the depth
of the phaco tip during sculpting (Chang D. Solutions
offered for mature white cataracts. Ocular Surg News 1999;
6:8). The staining of the nucleus (lens substance) helps
in visualizing the position of the phaco tip and its relation
with the posterior capsule, thus enhancing the safety
margin of the procedure.
Cortical Clean-up
Studies have shown that at least half of the cases of
capsular tears and vitreous loss occur at the time of
cortical clean-up.48 Staining of the capsular bag enhances
its visualization and the surgeon can distinguish feathery,
irregular staining of residual cortex from smooth staining
of the anterior, equatorial and posterior capsule. Thus,
the staining facilitates the cleaning of residual cortical
matter from the capsular bag. Posterior capsule staining
can also be very useful to learn and perform the PCCC
procedure, details of which will be provided in Section 3
of this chapter .

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery


Possible Clinical Application and Future Trials
Our laboratory study provides evidence that both dyes
(ICG and trypan blue) can be used in the clinical setting
of living human eye operations to achieve a complete
hydrodissection/delineation.8 They can also be used to
visualize the depth of the phaco tip during sculpting and
its relation to the posterior capsule, especially in patients
with a poor or absent red reflex (advanced/white
cataracts). It is easier to differentiate the cortical matter
from the anterior or posterior capsules after the staining
of the capsular bag. This would be helpful in achieving
a complete cortical clean-up during the irrigation/
aspiration steps, with lower incidence of posterior
capsule tear.
In summary, the use of dyes (ICG and trypan blue)
during small-incision adult cataract surgery using PE
facilitated complete hydrodissection and hydrodelineation, nuclear emulsification maneuvers and a complete
cortical clean-up. We believe that, in addition to
practicing an anterior capsulorhexis, these dyes can also
be used to enhance visualization for learning other
important steps of the phacoemulsification procedure in
a wet laboratory setting.8 This study also suggests the
need for future clinical trials using these dyes in a clinical
setting of living human eye operations.
OPHTHALMIC DYES FOR
POSTERIOR CAPSULORHEXIS
Introduction
Posterior continuous curvilinear capsulorhexis (PCCC)
is a posterior continuous central capsulotomy technique
described by Gimbel and Blumenthal and coworkers in
1990. 27,28 PCCC is recommended for converting an
irregular tear of the posterior capsule into a
circumscribed cut not extending to the equator.27,29 It can
also be used for the removal of posterior capsular plaques
in posterior subcapsular or polar cataracts.50
Recently, the use of PCCC combined with optic
capture of an IOL30,31 and/or anterior vitrectomy51-54
successfully evolved for delaying the development of
posterior capsule opacification (PCO) or secondary
membrane formation in pediatric cases. Primary
posterior capsulotomy, in the form of PCCC, is especially
important in younger children for maintaining a longterm clear visual axis in order to prevent the development
of amblyopia.55 Besides children, some surgeons also
recommend to perform PCCC during extracapsular
cataract extraction or during the PE procedure in adults,
because this is a more effective and safer procedure than

191

the Nd: YAG laser capsulotomy for the management of


PCO.56,57
However, to learn and perform PCCC is technically
challenging due to the thin and transparent nature of the
posterior capsule. Further, it should not be attempted if
visibility is mediocre and/or vitreous pressure is assessed
to be high.
Study on Dye-enhanced Posterior Capsulorhexis
Considering the wide clinical implications of PCCC and
keeping the difficulty to learn and perform this important
procedure in mind, we carried out a study in human eyes
obtained postmortem.9 We evaluated if the staining of
the posterior capsule with different dyes could be useful
to facilitate PCCC, similar to the anterior capsule staining
for performing anterior capsulorhexis in cataracts with
poor or no red glow.
Surgical Technique
Randomly accessioned postmortem human eyes (n = 12)
obtained within 4 days of death from eye banks
nationwide were used in this study. The eyes were
prepared according to the Miyake-Apple posterior video
technique.39,40 They were sectioned at the equator and
the anterior segment was mounted on a glass slide to
provide a posterior perspective of this portion of the eye.
After the cornea and iris were removed, a capsulorhexis
5.0 to 5.5 mm in diameter was initiated using a 26 gauge
needle and completed using a Utratas forceps. A complete cortical-cleavage hydrodissection was performed by
injecting balanced salt solution (BSS, Alcon Ophthalmic,
Fort Worth, TX, USA) between the lens capsule and the
cortex with a 27 gauge cannula. This was followed by
careful hydroexpression of the nucleus, avoiding damage
to the posterior capsule. Cortical clean-up was performed
using an irrigation/aspiration system.
Two independent surgeons (SKP, LW) evaluated the
use of dye to enhance visualization of the posterior capsule during PCCC (4 eyes/surgeon). Both surgeons were
inexperienced with the PCCC procedure and performed
it for the first time in their professional career. PCCC was
also performed in 4 other eyes (2 eyes/surgeon) without
the use of dye. The posterior capsule was stained by
instilling 1 microdrop of the dye solution into the capsular
bag. We used 0.5 percent ICG and 0.1 percent trypan blue
solutions (4 eyes/dye). The dye solutions were prepared
as described by us earlier in this chapter (Section 1). After
waiting 1-2 minutes, the excessive dye was washed out.
The capsular bag was filled with a viscoelastic agent
(Healon, Pharmacia Inc., Peapack, NJ, USA) and PCCC

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192 Section I: Cataract


was initiated by using a 26 gauge needle cystotome and
completed using a Utratas forceps. Optic capture of a
posterior chamber intraocular lens (PC-IOL), as well as
an anterior vitrectomy, were also practiced.
Results
Our laboratory study in 8 postmortem human eyes confirmed that the posterior capsule can be successfully
stained using ICG and trypan blue (Figs 20.10A to D and
20.11A to D). For both surgeons, it was much easier to
initiate and complete PCCC successfully after staining
of the posterior capsule, when compared to the control
(non-stained) eyes. PCCC was completed fairly easily in
all globes, due to better visualization of the stained

posterior capsule flap (PCF) against the transparent (nonstained) anterior hyaloid phase (AHP) of the vitreous
(Figs 20.10A to C and 20.11A to C). It was simpler to
perform optic capture of PC-IOLs after staining the
posterior capsule (Figs 20.10D and 20.11D). Both dyes
used in this study provided satisfactory visualization
when performing PCCC.
Clinical Application and Future Trials
PCCC is currently getting more and more attention due
to its clinical implication in the prevention of the PCO
development primarily in children, and to some extent
in adults. Additionally, this procedure is also important
in the management of posterior capsule tears of

Figs 20.10A to D: Gross photographs of a human eye obtained postmortem showing posterior continuous curvilinear
capsulorhexis (PCCC) after the staining of the capsular bag with indocyanine green (ICG). Cornea and iris were excised to
allow better visualization: (A) Anterior (surgeons) view of the cleaned and stained capsular bag showing initiation of the
PCCC. Note that it is easier to visualize the stained posterior capsule flap (PCF) against transparent (non-stained) anterior
hyaloid phase (AHP) of the vitreous, (B) The PCCC is in progress, (C) The PCCC is completed. Note the stained PCCC
margin; PCF: posterior capsule flap, and (D ) Higher magnification of the optic-haptic junctions after intraocular lens (IOL)
optic capture. Both haptics are present in the capsular bag and the IOL optic is captured behind the posterior capsule

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery

193

Figs 20.11A to D: Gross photographs of a human eye obtained postmortem showing posterior continuous
curvilinear capsulorhexis (PCCC) after the staining of the capsular bag with trypan blue. Cornea and iris were
excised to allow better visualization: (A) Anterior (surgeons) view of the cleaned and stained capsular bag
showing initiation of the PCCC. Note that it is easier to visualize the stained posterior capsule flap (PCF) against
transparent (non-stained) anterior hyaloid phase (AHP) of the vitreous, (B) The PCCC is in progress, (C) The
PCCC is completed. Note the stained PCCC margin; PCF: posterior capsule flap, (D ) Higher magnification of
the optic-haptic junctions after intraocular lens (IOL) optic capture. Both haptics are present in the capsular bag
and the IOL optic is captured behind the posterior capsule

congenital, traumatic or surgical origin, and the pealing


of plaques associated with posterior polar and posterior
subcapsular cataracts.50 As mentioned before, learning
PCCC is technically challenging due to the thin,
transparent, and elastic nature of the posterior capsule.
Attempting PCCC in the presence of poor visibility
associated with positive vitreous pressure is difficult, and
may cause an inadvertent radial tear extending toward
the equator. Cauwenberge, Rakic and Galand58 recently
reported the etiology, management and outcome of
complicated posterior capsulorhexis. In a 1-year
retrospective analysis of 650 patients, they identified 32

(5%) cases of complicated PCCC. According to them, the


most frequent problem was the performance of a central
capsulorhexis within the optimum size (<5 mm in
diameter). This was not possible in 14 (44%) cases in their
series. In 12 (37%) cases, a PCCC was carried out with
great difficulty because of either insufficient visibility
during the procedure or an anatomically changed capsule
(floppy or fibrotic in its center). Vitreous loss occurred in
6 (19%) cases during the PCCC procedure. All the
aforementioned complications were reported by these
authors despite their 4-year experience with the PCCC
procedure, performed on more than 1,300 patients.

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194 Section I: Cataract


Posterior capsulorhexis, which is considered technically difficult and challenging, became easier to learn and
perform after staining the posterior capsule with ICG or
trypan blue. Staining enhances visualization of the
posterior capsule flap, which can be easily recognized
against the transparent anterior hyaloid phase of the
vitreous.
OPHTHALMIC DYES FOR
PEDIATRIC CATARACT SURGERY
Beside in adults, ophthalmic dyes can also be used to
facilitate anterior and posterior capsulorhexis during
pediatric cataract surgery. We have evaluated the use of
2 ophthalmic dyes, 0.5 percent ICG, and 0.1 percent
trypan blue for staining the posterior capsule, while
performing PCCC in pediatric eyes obtained postmortem
(Figs 20.12A to C).14 As we have mentioned before, learning the posterior capsulorhexis procedure, and achieving
a consistent size of the posterior capsule opening for
performing the optic capture, can be difficult for the
beginning surgeon due to the thin and transparent nature
of the posterior capsule. This is especially important in
pediatric eyes, which are particularly associated with a
thin sclera and a positive vitreous pressure, thus making
PCCC difficult, if not impossible.52,53,55 Gimbels technique of PCCC with IOL optic capture can be successfully
practiced after staining the posterior capsule.30,31 Vitreous
loss can be easily identified by the formation of colored
localized clumps, depending on the type of dye used.
In brief, results of our laboratory study in postmortem
human eyes revealed that posterior capsule staining
using ICG or trypan blue is very helpful when
performing the PCCC procedure both in adults and
children. The need remains for future clinical trials using
these dyes to stain the posterior capsule when performing
PCCC. This technique can be helpful for the beginning
surgeon, or in the presence of poor visibility.
SUMMARY AND CONCLUSIONS
The use of non-toxic ophthalmic dyes to enhance visualization during the various steps of cataract surgery has
been summarized in Table 20.5. Based on our experience
of ophthalmic dyes for cataract surgery, we confirm that
capsule staining using various dyes in cataractous eyes
with poor or no red reflex, helps create an intact anterior
capsulorhexis.7 Several laboratory and clinical studies
suggested that both ICG and trypan blue are safe and
provide excellent visualization of the anterior capsule
flap during CCC.5-7,10,12,13,59 The trypan blue dye has the
advantage of being less expensive than ICG. However,
trypan blue dye should not be used in fertile/pregnant

Figs 20.12A to C: Photographs of a pediatric eye obtained


postmortem, taken from anterior (surgeons view) illustrating
the use of the capsular dye to enhance visualization during
various steps of the pediatric cataract surgery: (A) Posterior
capsulorhexis after the staining of the capsular bag with trypan
blue, (B) Posterior capsulorhexis and optic capture of a foldable
IOL after the staining of the capsular bag with trypan blue,
(C) Visualization of a posterior capsule tear after staining of
the capsular bag with ICG (arrows)

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery

195

Table 20.5: Summary of ophthalmic dyes in adult and pediatric cataract surgery
Step

Dye

*CCC

2% FS**

Study

Structure stained

Indication

Anterior lens capsule

Patients with
poor or no
red reflex

a. Under an
air bubble
b. Intracameral
subcapsular inj.

Mansour2

(anterior surface)

Hoffer/
McFarland3

(posterior surface)

0.5% ICG***
Under an air bubble

Horiguchi
et al5

(anterior surface)

0.1%TB****
Under an air bubble

Melles
et al6

(anterior surface)

2% FS, 0.5% ICG, and


0.1% TB
a. Under an air bubble
b. Intracameral
subcapsular inj.

Pandey/Werner
et al7,13

Hydrodissection/
delineation

0.5% ICG, 0.1%TB

Pandey/Werner
et al8, 13

Interfaces
capsule-cortex
epinucleus-nucleus

Visualization of the
cortical cleavage planes
and nucleus dimensions

Nucleus
sculpting

0.5% ICG, 0.1% TB

Pandey/Werner
et al8, 13

Nuclear substance

To judge phaco tip


depth and relations
with post. capsule

Capsular bag
cleaning

0.5% ICG, 0.1% TB

Pandey/Werner
et al8, 13

Inner surface of
capsular bag

Complete cleaning of
capsular bag

*****PCCC

0.5% ICG, 0.1%TB

Pandey/Werner
et al9,13

Anterior surface
of posterior capsule

Posterior capsule
staining for PCCC

(anterior surface)
(posterior surface)

*: CCC = Continuous curvilinear capsulorhexis; **: FS = Fluorescein sodium; ***: ICG = Indocyanine green;
****:TB = Trypan blue; *****: PCCC = Posterior continuous circular capsulorhexis

females nor in children due to the possibilty of a teratogenic and/or mutagenic effect. ICG remains a valuable
alternative for these special patients. Anterior capsule
staining under the air bubble technique provides good
visualization without the possibility of an anterior
capsule tear formation, thus suitable in intumescent and
hypermature cataract patients. In addition, our laboratory studies demonstrate that the ophthalmic dyes can
be successfully used to enhance visualization while
learning the other critical steps of phacoemulsification.8
Also the technically more challenging procedure of
posterior capsulorhexis can be performed with more
facility.9
REFERENCES
1. Hogan RN, Zimmerman CF. Sodium fluorescein and other tissue
dyes. In Zimmerman TJ, et al (Eds): Textbook of Ocular Pharmacology. Philadelphia, PN, Lippincott-Raven, 1997; 849-63.
2. Mansour AM. Anterior capsulorhexis in hypermature cataracts
(letter). J Cataract Refract Surg 1993; 19:116-17.

3. Hoffer KJ, McFarland JE. Intracameral subcapsular fluorescein


staining for improved visualization during capsulorhexis in
mature cataracts (letter). J Cataract Refract Surg 1993; 19:566.
4. Fritz WL. Fluorescein blue light assisted capsulorhexis for
mature or hypermature cataract. J Cataract Refract Surg 1998;
24:19-20.
5. Horiguchi M, Miyake K, Ohta I, Ito Y. Staining of the lens
capsule for circular continuous capsulorhexis in eyes with white
cataract. Arch Ophthalmol 1998; 116:535-37.
6. Melles GRJ, Waard PWT, Pameyer JH, Beekhuis WH. Trypan
blue capsule staining in cataract surgery. J Cataract Refract Surg
1999; 24:7-9.
7. Pandey SK, Werner L, Escobar-Gomez M, Roig-Melo EA, Apple
DJ. Dye-enhanced cataract surgery. Part 1: Anterior capsule
staining for capsulorhexis in advanced/white cataract. J
Cataract Refract Surg 2000; 26:1052-59.
8. Werner L, Pandey SK, Escobar-Gomez M, Hoddinott DSM,
Apple DJ. Dye-enhanced cataract surgery. Part 2: Learning
critical steps of phacoemulsification. J Cataract Refract Surg
2000; 26:1060-65.
9. Pandey SK, Werner L, Escobar-Gomez M, Werner LP, Apple DJ.
Dye-enhanced cataract surgery. Part 3: Posterior capsule staining
to learn posterior continuous curvilinear capsulorhexis. J
Cataract Refract Surg 2000; 26:1066-71.

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196 Section I: Cataract


10. Newsom TH, Oetting TN. Indocyanine green staining in
traumatic cataract. J Cataract Refract Surg 2000; 26:1691-93.
11. Nodarian M, Feys J, Sultan G, Salvanet-Bouccara A. Capsulorhexis staining by trypan blue in mature cataract surgery. J Fr
Ophtalmol 2001; 24:274-76.
12. Pandey SK, Werner L, Apple DJ. Staining the anterior capsule
(Letter to the Editor). J Cataract Refract Surg 2001; 27:647-48.
13. Pandey SK, Werner L, Apple DJ, et al. Update on dye-enhanced
cataract surgery. In Chang DF, ed, Hyerguide Online Textbook
of Ophthalmology, Thorofare, NJ, Slack, 2001.
14. Pandey SK, Werner L, Apple DJ, et al. Dye-enhanced pediatric
cataract surgery. J Pediatr Ophthalmol Strabismus 2001
(submitted).
15. Kayikicioglu O, Erakgun T, Guler C. Trypan blue mixed with
sodium hyaluronate for capsulorhexis. J Cataract Refract Surg
2001; 27:970.
16. Unlu K, Askunger A, Soker S, et al. Gentian violet solution for
staining the anterior capsule. J Cataract Refract Surg 2000;
26:1228-32.
17. Gamal Eldin SA, el Mehelmy EM, el Shazli, Mostafa YM.
Experimental staining of the anterior lens capsule in albino
rabbits. J Cataract Refract Surg 1999; 25:1289-94.
18. Agarwal A, Agarwal A, Agarwal S. Trypan blue in the management of mature cataracts. In Agarwal S, Agarwal A, Sachdev
MS, Mehta KR, Fine IH, Agarwal A, (Eds): Phacoemulsification,
Laser Cataract Surgery and Foldable IOLs. New Delhi, India,
Jaypee Brothers 2000; 618-23.
19. Burke SE, DaMata AP, Snyder ME, et al. Indocyanine greenassisted peeling of the internal limiting membrane. Ophthalmology 2000; 107:2010-14.
20. Gimbel HV, Neuhann T. Development, advantage, and methods
of the continuous circular capsulorhexis technique. J Cataract
Refract Surg 1990; 16:31-37.
21. Assia EI, Apple DJ, Barden A, et al. An experimental study
comparing various anterior capsulotomy techniques. Arch
Ophthalmol 1991; 109:642-47.
22. Faust KJ. Hydrodissection of soft nuclei. Am Intraocular Implant
Soc J 1984; 10:75-77.
23. Anis AY. Origin of hydrodissection (reply letter to the editor).
J Cataract Refract Surg 1995; 21:6.
24. Fine IH. Cortical cleaving hydrodissection. J Cataract Refract
Surg 1992; 18:508-12.
25. Koch DD, Liu JF. Multilamellar hydrodissection in phacoemulsification and planned extracapsular surgery. J Cataract
Refract Surg 1990; 16:559-62.
26. Gimbel HV. Hydrodissection and hydrodelineation. Int
Ophthalmol Clin 1994; 34:73-90.
27. Gimbel HV. Posterior capsule tears using phacoemulsification
causes, prevention and management. Eur J Implant Refract Surg
1990; 2:63-69.
28. Blumenthal M, Assia E, Neumann D. The round capsulorhexis
capsulotomy and the rationale for 11.0 mm diameter IOL. Eur J
Implant Refract Surg 1990; 2:15-19.
29. Castaneda VE, Legler UF, Tsai JC, et al. Posterior continuous
capsulorhexis. An experimental study with clinical applications.
Ophthalmology 1992; 2:63-69.
30. Gimbel HV, DeBroff BM. Posterior capsulorhexis with optic
capture: Maintaining a clear visual axis after pediatric cataract
surgery. J Cataract Refract Surg 1994; 20:658-64.
31. Gimbel HV. Posterior capsulorhexis with optic capture in
pediatric cataract and intraocular lens surgery. Ophthalmology
1996; 103:1871-75.
32. Pande M. Continuous curvilinear (circular) capsulorhexis and
planned extracapsular cataract extraction: are they compatible?
Br J Ophthalmol 1993; 77:152-57.

33. Vasavada AR, Singh R, Desai J. Phacoemulsification of white


cataracts. J Cataract Refract Surg 1998; 24:270-77.
34. Brusini P. Capsulorhexis in mature cataracts: Why not? Doc
Ophthalmol 1992; 81:281-84.
35. Hausmann N, Richard G. Investigations on diathermy for
anterior capsulotomy. Invest Ophthalmol Vis Sci 1991; 32:215559.
36. Vajpeyee RB, Angra SK, Honavar SG, et al. Capsulotomy for
phacoemulsification in hypermature cataracts. J Cataracts
Refract Surg 1995; 21:612-15.
37. Gimbel HV. Two stage capsulorhexis for endocapsular
phacoemulsification. J Cataract Refract Surg 1990; 16:246-49.
38. Auffarth GU, Wesendahl TA, Solomon K, et al. A modified
preparation technique for closed system ocular surgery of
human eyes obtained postmortem: An improved research and
teaching tool. Ophthalmology 1996; 103:977-88.
39. Miyake K, Miyake C. Intraoperative posterior chamber lens
haptic fixation in the human cadaver eye. Ophtalmic Surg 1985;
16:230-36.
40. Apple DJ, Lim ES, Morgan RC, et al. Preparation and study of
human eyes obtained postmortem with the Miyake posterior
photographic technique. Ophthalmology 1990; 97:810-16.
41. Werner L, Apple DJ, Crema A, Izak A, Pandey SK, Trivedi RH,
Ma L. Permanent bluish discoloration of a hydrophilic
intraocular lenses caused by intraoperative use of trypan blue.
J Cataract Refract Surg 2001 (in press).
42. Chang DF. Capsule staining and mature cataracts: A comparison
of indocyanine green and trypan blue dyes. Br J Ophthalmol
(video report) July 2000.
43. Pandey SK, Werner L, Escobar-Gomez M, Apple DJ, et al.
Creating cataracts of varying hardness to practice extracapsular
cataract extraction and phacoemulsification. J Cataract Refract
Surg 2000; 26:322-29.
44. Pandey SK, Werner L, Vasavada AR, Apple DJ. Induction of
cataracts of varying degrees of hardness in human eyes obtained
postmortem for cataract surgeon training. Am J Ophthalmol
2000; 129:557-58.
45. Synder RW, Donnenfeld ED. Teaching phacoemulsification to
residents and physicians in transition. Int Ophthalmol Clin 1994;
34:191-99.
46. Synder RW, Allinson RW, Fante RG, et al. Learning phacoemulsification surgery. Ophthalmology 1992; 99:448-53.
47. Gimbel HV. Divide and conquer nucleofractis phacoemulsification and variations. J Cataract Refract Surg 1991; 17:281-91.
48. Gimbel HV. Posterior capsule tears using phacoemulsification
causes, prevention and management. European J Implant
Refract Surg 1990; 2:63-69.
49. Peng Q, Apple DJ, Visessook N, Werner L, Pandey SK, et al.
Surgical prevention of posterior capsule opacification. Part II.
Enhancement of cortical clean up by focusing on hydrodissection. J Cataract Refract Surg 2000; 26:188-97.
50. Vasavada A, Singh R. Phacoemulsification in eyes with posterior
polar cataract. J Cataract Refract Surg 1999; 25:238-45.
51. Basti S, Ravishankar U, Gupta S. Results of a prospective evaluation of management of pediatric cataracts. Ophthalmology
1996; 103:713-20.
52. Pandey SK, Wilson ME, Trivedi RH, Izak AM, Macky TA, Werner
L, Apple DJ. Pediatric cataract surgery and intraocular lens
implantation: Current techniques, complications and management. Int Ophthalmol Clin 2001; 41:175-96.
53. Wilson ME, Pandey SK, Werner L, Ram J, Apple DJ. Pediatric
Cataract Surgery: Current Techniques, Complications and
Management. In Agarwal S, Agarwal A, Sachdev MS, Mehta

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Chapter 20: Update on Capsular Dye Enhanced Cataract Surgery


KR, Fine H, Agarwal A, (Eds): Phacoemulsification, Laser
Cataract Surgery and Foldable IOLs. New Delhi, India, Jaypee
Brothers Medical Publishers (P) Ltd, 2000; 39:369-88.
54. Ram J, Pandey SK, Infantile cataract surgery: Current techniques, complications and their management. In Dutta LC, (Ed):
Modern Ophthalmology. New Delhi, India, Jaypee Brothers
Medical Publishers (P) Ltd, 2000; 378-84.
55. Vasavada A, Desai J. Primary posterior capsulorhexis with and
without anterior vitrectomy in congenital cataracts. J Cataract
Refract Surg 1997; 23.
56. Galand A, Cauwenberge VF, Moosavi J. Posterior capsulorhexis

197

in adult eyes with intact and clear capsules. J Cataract Refract


Surg 1996; 22:458-61.
57. Galand A. Primary posterior capsulorhexis in adults. In Nema
HV, Nema N (Eds) Recent Advances in Ophthalmology 4. New
Delhi, India, Jaypee Brothers Medical Publishers (P) Ltd, 1998,
157-61.
58. Cauwenberge VF, Rakic JM, Galand A. Complicated posterior
capsulorhexis: Aetiology, management, and outcome. Br J
Ophthalmol 1997; 81:195-98.
59. Sharma N, Pangtey MS, Dada VK. Experience with indocyanine
green dye (letter). J Cataract Refract Surg 2001; 27:1342.

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198 Section I: Cataract

21

Update on Ophthalmic
Viscosurgical Devices
Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak, Vidushi Sharma

BACKGROUND
CLASSIFICATION OF
THE OVDs
CLINICAL APPLICATIONS OF
THE OVDs
COMPLICATIONS OF
THE OVDs

BACKGROUND
Viscoelastic substances are solutions with dual properties; they act as
viscous liquids as well as elastic solids or gels. The ideal viscoelastic
substance in ophthalmology should be viscous enough to prevent collapse
of the anterior chamber at rest, yet liquid enough to be injected precisely
through a small cannula. It should be elastic or shock absorbing and should
enhance coating yet has minimal surface activity. It should be cohesive
enough to be removed to be easily removed from the anterior chamber but
not so cohesive that it is aspirated during irrigation and aspiration, which
would provide no protection to endothelial cells during surgical
manipulations. It should be eliminated from the eye in the postoperative
period without an effect on intraocular pressure.6-8,20,22,23
Viscosurgery was a term coined by Balazs10,11 to describe the use of these
solutions that had viscous, elastic and pseudoplastic properties during and
after surgical procedures. During viscosurgery, viscoelastic substances are
used as a fluid or a soft surgical instrument. The viscoelastic sodium
hyaluronate was first used in ophthalmic surgery in 1972, when it was
introduced as a replacement for vitreous and aqueous humor.10,11 Since
then ophthalmic surgical procedures had undergone considerable
advancement. The use of viscoelastic materials has become commonplace
in anterior and posterior segment surgeries. These agents facilitate delicate
and often difficult intraocular manipulations during various ophthalmic
surgical procedures. They are used during cataract surgery and intraocular
lens (IOL) implantation to maintain the anterior chamber depth and
capsular bag distention, thus creating and preserving working space for
the ophthalmic surgeon. These agents are designed to protect the delicate
corneal endothelial cells during the surgery.20
The viscoelastic substances has been termed as ophthalmic viscosurgical devices (OVDs).9 A detailed discussion regarding biocompatibilty,
physical, and rheological properties of the OVDs are beyond the scope of
this chapter. Interested readers may consult the excellent review article(s)
published by Liesegang on this topic.21,22 The viscoelastic substances must
be non-toxic, non-pyrogenic, non-inflammatory, non-immunogenic, and
sterile for use in the human eyes. The substance should not interfere with
the normal metabolism of the cells in contact with it. Substances that are
immunogenic, may cause granulation or capsule formation, stimulate cell
invasion, or interfere with epithelization or blood coagulation cannot be
used in the eyes. 17,22,23 Each viscoelastic substance has unique physicochemical properties which determines its clinical applications.22,23,38,39,44
Figures 21.1A to C is a gross photograph showing physical characteristics

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 199


(viscosity) of 3 different concentration of the sodium
hyaluronate solution (Healon, Healon-GV and Healon5).

In this chapter, we will provide an update of currently


used OVDs and will focus on the newly available
viscoadaptive viscoelastics (e.g. Healon-5), their clinical
applications and complications. Some of the details
related to OVDs had been discussed in the previous
chapter of this textbook.14 The current chapter is based
on the review of the published literature on this topic
and also derived from the information and illustrations
available from the manufacturer. This chapter is divided
in 4 sections:
Section 1: Classification of currently available OVDs;
Section 2: Clinical application of the OVDs;
Section 3: Complications associated with OVDs;
Section 4: Summary and conclusions.
CLASSIFICATION OF THE OVDs
Table 21.1 presents summary of the currently available
OVDs. OVDs can be classified according to their zero
shear viscosity and cohesion. The zero shear viscosity is
directly proportional to the molecular weight. This
classification describes the surgical behavior of the
viscoelastics and is as follows.7
1. High viscosity cohesive OVDs
a. Super viscous-cohesive OVDs (>1,000,000 mPs)
b. Viscouscohesive OVDs (Between 100,000 and
1,000,000 mPs)
2. Lower viscosity dispersive OVDs
3. Viscoadaptive OVDs (e.g. Healon-5)
High Viscouscohesive OVDs
The super viscous-cohesive group includes Healon-GV
and I-visc plus while the viscouscohesive group
includes products like I-visc, Provisc, Healon,
Amvisc, Amvisc plus and others. All these products
contain sodium hyaluronate.
High viscouscohesive OVDs are indicated in many
routine procedures and are used to create space and also
stabilize the surgical microenvironment. Examples of
situations where they are used include deepening the
anterior chamber, to enlarge small pupils, to dissect
adhesions, and during IOL implantation to push back
the iris and vitreous.
Super Viscouscohesive OVDs

Figs 21.1A to C: Gross photograph showing physical characteristics (viscosity) of 3 different concentration of the sodium
hyaluronate solution: (A) Healon, (B) Healon-GV,
(C) Healon-5

Healon-GV (greater viscosity) is a sterile, non-pyrogenic agent produced from rooster coombs. It has a
concentration of 1.4 percent sodium hyaluronate and a
molecular weight of 5 million Daltons.
It is used as a surgical aid in various anterior segment
procedures such as cataract extraction, IOL implantation,

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200 Section I: Cataract


Table 21.1: Classification of ophthalmic viscosurgical devices (OVDs)
Higher viscosity: Cohesive OVDs
Viscosurgical
agents

Manufacturer

Molecular
Wt (D)

Source

Viscoadaptive (fracturable)
Healon-5
Pharmacia Inc.

5.0 M

Super Viscous
Healon-GV

Pharmacia Inc.

I-Visc Plus

Osmlality
Viscosity
(mOsm/liter)

Vo(mPs)

Rooster Coombs Hyaluronic


Acid

322

2.3 Na Ha
(23mg/ml)

7.0M

5.0 M

Rooster Coombs Hyaluronic


Acid

310

1.4 Na Ha
(14 mg/ml)

2.0M

I-Med Pharma

7.9M

Rooster Coombs Hyaluronic


Acid

1.4 Na Ha
(14 mg/ml)

4.8 M

Viscous
I-Visc

I-Med Pharma

6.1 M

Roster Coombs

Hyaluronic
Acid

336

1.0 Na Ha
(10 mg/ml)

1.0 M

Healon

Pharmacia Inc.

4.0M

Rooster Coombs Hyaluronic


Acid

302

1.0Na Ha
(10 mg/ml)

230K

Provisc

Alcon

2.0M

Microbial
fermentation

Hyaluronic
Acid

307

1.0Na Ha
(10 mg/ml)

280K

Amvisc Plus

IO lab (B and L
surgical)

1.0M

Rooster Coombs Hyaluronic


Acid

340

1.6Na Ha
(16 mg/ml)

100K

Amvisc

IO Lab (B and L 1.0M


surgical)

Rooster Coombs Hyaluronic


Acid

318

1.2 Na Ha
(12 mg/ml)

100K

Biolon

Biotech general
corp

Bacterial
Fermentation

279

1.0 Na Ha
(12 mg/ml)

215K

3.0M

Chemical
compound

Hyaluronic
Acid

Low viscosity: Dispersive OVDs


Medium Viscosity
Alcon
Viscoat

500K

Bacterial
Fermentation
Shark Fin

Hyaluronic acid 325


Chondriotin
Sulphate

3.0 NaHa
4.0 CDS
(40 mg/ml)

41K

Vitrax

Allergan

500K

Rooster coombs

Hyaluronic
Acid

310

3.0Na Ha
(30 mg/ml)

25K

Cellugel

Vision biology
(Alcon)

100K

Synthetic

Hydrooxypropyl methylcellulose

305

2.0 Chemically 38K


modified
HPMC

Ocucoat

Storz (B and L
surgical)

86 K

Wood pulp

Hydroxyproply- 285
methylcellulose

2.0 HPMC
(20 mg/ml)

4K

Visilon

Shah and Shah

86 K

2.0 HPMC
(20 mg/ml)

4K

Viscon

Dr. Agarwals
Pharma

86 K

Hydroxyproplymethylcellulose

2.0 HPMC
(20 mg/ml)

4K

Visicrome

Croma Pharma

2.0 HPMC
(20 mg/ml)

Vo (mPs)= Zero shear Viscosity(milli Pascal Seconds); (D) = Daltons; M = Millions; K = Thousand; NaHa = Sodium hyaluronate;
HPMC = Hydroxypropylmethylcellulose; CDS = Chondroitin sulphate

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 201


corneal transplant surgery and glaucoma surgery. In
presence of high positive pressure, Healon-GV has 3
times more resistance to pressure than Healon. I-Visc
was introduced as a Healon-GV clone. It has superior
viscous and cohesive properties at low shear viscosity
when compared to Healon-GV (Table 21.1).
Super viscous-cohesive agents are better in current
day techniques where topical and intracameral
anesthesia are used and the surgeries are entirely inthe-bag phacoemulsification. High cohesiveness of
superviscous and viscous materials result in easy
removal as a single mass at the end of the surgical
procedure, thus preventing the increased intraocular
pressure postoperatively.
Lower ViscosityDispersive OVDs
Dispersive agents have low molecular weight and shorter
molecular chains. Medium viscosity, dispersive OVDs
possess zero shear viscosities between 10,000 and 100,000
mPs. Very low viscosity, dispersive agents include all of the
unmodified hydroxyproplymethycellulose (HPMC)
agents.
These dispersive materials when injected into the eye
have the property of fracturing and breaking into smaller
bits and thus disperse in the anterior chamber. They
include Viscoat, Cellugel, Vitrax, Ocucoat and
others (Table 21.1).
Most of the dispersive OVDs are HPMC-hydroxypropyl methylcellulose, derived from wood pulp.
Cellugel is a chemically modified HPMC. Viscoat is
a combination of sodium hyaluronate and chondroitin
sulphate. Vitrax is a compound of low molecular weight
molecular hyaluronate.
The clinical use of these agents is to hold back vitreous
out of the surgical field especially in cases of zonular
disinsertion. They are helpful in a compromised corneal
endothelium conditions, as they are capable of dividing
the anterior chamber into OVD-occupied space and
surgical zone in which irrigation/aspiration can be
continued without the mixing of the two areasknown
as surgical compartilization.
The disadvantage of lower viscosity dispersive OVDs
is that they do not maintain or stabilize spaces as
compared to higher viscosity cohesive agents. They tend
to be aspirated in smaller fragments during irrigation/
aspiration thus leading to irregular viscoelastic aqueous
interface, thus partially obscurring the surgical view of
the posterior capsule. They also form microbubbles and
can be trapped at the irregular interface thus further
obscurring visibility. Moreover they are difficult to
remove at the end of the surgery because of low cohesion.

Soft Shell Technique


This technique was developed by Arshinoff, in order to
take advantage of the best properties of both lower
viscosity-dispersive agents and high viscosity-cohesive
agents and to minimize the drawbacks of each by using
them together. In this technique first the lower viscosity
dispersive is injected into the anterior chamber, followed
by high viscosity-cohesive agent, which is injected into
the center of the lower viscosity-dispersive viscoelastic
thus pushing it outwards and compressing it into a
smooth, even layer against the corneal endothelium. This
protects the endothelium during lens removal.
Prior to the implantation of the IOL, the reverse is
done. High viscosity cohesive is injected first to partially
fill the anterior chamber and the capsular bag, followed
by injection of lower viscosity dispersive into the center
of high viscosity cohesive agent. This allows the free
movement of the IOL through the dispersive agent, with
better stabilization of the surrounding iris and the
capsular bag by the high viscosity agent.48
Removal of the OVDs is easily accomplished at the
end of the surgery, since low viscosity dispersive OVA
can be aspirated from the central anterior segment first,
followed by higher cohesive agent. DuoVisc-a combination of high viscocitycohesive Provisc and the lower
viscosity dispersive Viscoat.
Viscoadaptive OVDHealon-5
The existing viscoelastic products all have drawbacks. A
cohesive viscous product used to create and maintain
space may not stay in the eye during phacoemulsification.
On the other hand, a less viscous dispersive product stays
during phacoemulsification but often traps fragments or
air bubbles and does not maintain adequate space during
the surgical procedure.
Recently the new viscoadapative viscoelastic Healon5 has been developed to change its behavior at different
flow rates.3 It acts as a viscous cohesive viscoelastic agent
at lower flow rates and as a pseudodispersive viscoelastic
agent at higher flow rates. It is all in one device that
adapts its behavior to the surgeons needs during the
entire course of surgery.
This is a steam sterilized, non-pyrogenic solution. It
is highly purified non-inflammatory, high molecular
weight sodium hyaluronate at a concentration of 23 mg/
ml (2.3%) dissolved in a physiological buffer. It has an
osmolality and a pH similar to those of the aqueous
humor. It has a viscosity at rest about 7 million times
higher than aqueous humor. It is extracted from rooster
coombs.

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202 Section I: Cataract


Hyaluronate is a polysaccharide made up of disaccharide units linked by glycosides bonds. It occurs
naturally on the corneal endothelium bound to specific
receptors. The natural hyaluronate is reduced during
irrigation but can be restored by an exogenous one.
Healon-5 has a high affinity to the receptors. It acts as
a scavenger by neutralizing the free radicals formed
during cataract surgery using ultrasound.
Characteristics and Advantages of
the Viscoadaptive OVDs
1. Viscoadaptive OVD (Healon-5) is specifically developed so that, at different flow rates it has different
functions. At lower flow rates it behaves as a very
cohesive viscoelastic like a Healon-GV. At higher
flow rates, e.g. in chopping techniques, it begins to
fracture and behaves similarly to a dispersive
viscoelastic, such as Viscoat. Hence Healon-5 has
features that can change according to the needs of
the surgeon during various stages of cataract surgery.
2. It is crystal clear as pure water and has somewhat
higher refractive index than the aqueous humor.
Hence it increases the clarity within the surgical field.
3. It also has the ability to protect the delicate corneal
endothelial cells from debris and turbulence during
phacoemulsification, particularly with very low
endothelial cell count. In a recent study by Holzer et
al.,16 the average loss of corneal endothelial cells was
lowest for their surgeries using Healon-5 compared
to other OVDs.
4. Viscoadaptive OVD (Healon-5) is also helpful in
patients with suboptimal pupil size because the
viscomydriasis allows for a larger capsulorhexis and
keeps the pupil larger during phacoemulsification
thus increasing the visibility.
5. It also neutralizes the positive vitreous pressure and
prevents capsulorhexis from extending by temporarily stopping all action, thus allowing the surgeon
to determine what is going on inside the eye, analyze
his or her options and effect the appropriate
management.
6. The high viscosity of Healon-5 creates space and
stabilizes the anterior segment. The elasticity absorbs
shock and protects ocular tissues during IOL unfolding, which is slowed down and is more controlled.
7. Healon-5 is also easy to remove. The Rock and
Roll technique10 with suitable settings for each type
of phacoemulsifications, was found to be a safe
method for complete removal of it. In this technique
there is sufficient turbulence created and this fractures
Healon-5 into small pieces. The other method for
Healon-5 removal is the two compartment techni-

que (TCT).50 Full advantage of the agents viscoadaptive properties is taken in this technique. The superior
space maintaining capacity of Healon-5 in the
anterior chamber is utilized while removing the
substance from the capsular bag. In the second step
the anterior chamber is cleaned.
There is a learning curve for surgeons using Healon5, but as surgeons begin making a number of small
procedural adaptations, the advantages of the viscoadaptive OVD will increasingly become apparent.
CLINICAL APPLICATIONS OF THE OVDs
In recent years the field of viscosurgery has broadened
rapidly. It has been used both intraocularly as well as
extraocularly, which includes cataract, cornea, glaucoma,
viteroretinal, strabismus and oculoplastic surgeries.7,22,23,30
Use of OVDs in Cataract Surgery
OVDs are helpful in each step of modern cataract surgery
using phacoemulsification with IOL implantation.5,13,41,43
Some of these details are shown in the schematic photograph (Figs 21.2A to C and 21.3).
Capsulorhexis
In order to perform an intact and successful
capsulorhexis, the contents of the anterior chamber have
an important role. Till date balanced salt solution (BSS),
air and OVDs have been used. Out of these three the
best is viscoelastic as it is considered the easiest, safest,
and the most reproducible method in both routine and
difficult cases (Figs 21.2A and B). To perform a good
capsulorhexis, the viscoelastic to be used should have
the four basic features:
1. High molecular weight and high viscosity at zero
shear rate, which maintains the anterior chamber.
2. Excellent visibility provided by high transparency.
3. Make surgical maneuvers easy, due to high elasticity
and pseudoplasticity.
4. It should gives a good capsular flap control, providing
the soft and permanent spatula effect.
Cleavage of Lens Structure
It is best performed with the use of OVDs. The ideal viscoelastic material keeps the anterior chamber shape
unchanged during BSS injection and also avoids
increase in pressure, which can be produced with
excessive amount of BSS known as capsular blockade.

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 203

Figs 21.2A to F: Schematic photograph showing use of the OVD (viscoadaptive OVD-Healon-5 in this figure) during the
various steps of the cataract surgery: (A) Injection of the viscoadaptive OVD in the anterior chamber through a 25 G cannula,
(B) Capsulorhexis is in progress, (C) Phacoemulsification in progress, (D) Viscoadaptive OVD is transparent and easy to see
during removal (left). Note the presence of the air bubbles within the anterior chamber after use of dispersive viscoelastic
solution (right), (E) Implantation of a posterior chamber intraocular lens in the capsular bag, (F) Removal of the viscoadaptive
OVD using irrigation-aspiration tip. (Courtesy: Pharmacia Inc. Peapack, NJ, USA)

Nuclear Emulsification
During phacoemulsification, the viscoelastic is likely to
remain in the anterior chamber instead of leaking out of
the eye (Fig. 21.2C). OVDs help in preserving the space

and also because of their low cohesiveness, they remain


in the anterior chamber despite high irrigation flow.
Moreover OVDs adhere to the corneal endothelium, thus
protecting the corneal endothelial cells. Healon and
Healon-GV does not trap the air bubble and provide

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204 Section I: Cataract


rotation maneuvers (Figs 21.2E and F). Beside posterior
chamber IOL implantation, OVD has also been used for
implantation of other IOL designs (e.g. anterior chamber,
iris fixated, artisan lenses, etc.) (Fig. 21.3).52
Cataract Surgery in Pediatric Patient

Fig. 21.3: Besides posterior chamber IOL fixation in the capsular bag, OVDs can also be used for implantation of the various
phakic and aphakic IOL designs in the anterior chamber, ciliary
sulcus, etc. Use of the OVD facilitated the implantation of the
Artisan IOL as shown in this photograph (Courtesy: Camil
Budo, MD)

excellent endothelial protection (Fig. 21.2D). This is


because of:
1. Scavenger effectThis effect captures the free radicals released during phaco with consequent
inactivation.
2. Binding sitesThere are chemical receptors for viscoelastic materials on the corneal endothelium. A
molecular bond seems to occur between the viscoelastic solution and the corneal endothelium.
3. High elasticityThis also smoothes the possible
impacts of the lens material against the endothelium.
The phaco tip being in a closed system, its vibrations
are transmitted to the internal structures of the eye but
viscoelastic provides a smothering shield against them.
Irrigation and Aspiration
The role of viscoelastic during this procedure is the
protection of the endothelium. This is possible due to
high adhesiveness. It remains where it is placed, without
mixing with the cortex because of its low cohesiveness
thus helping in easy removal of cortex.
Capsular Bag Filling and IOL Implantation
During IOL implantation, it is necessary to expand the
capsular bag with a viscoelastic. It allows the surgeon to
keep the bag well opened and formed thus allowing the
easy IOL implantation. OVD is also helpful in correct
positioning, centering and allowing for possible IOL

Pediatric cataract surgery like the adult surgery has


undergone major changes in recent years with the
evolution of techniques including small incision and the
development of modern IOLs. The main principle lies in
the control of the very elastic nature of ocular tissues.42
It is difficult to perform a good capsulorhexis in the
presence of high capsular elasticity. Moreover there is
low scleral rigidity, greater intravitreal pressure that
makes the capsulorhexis even more difficult, as the
pressure tends to curve the capsulorhexis. But with the
use of viscoelastic, e.g. Healon-GV the effective push
is in the opposite direction and hence completion of
capsulorhexis can be done.
In pediatric cases, the capsulorhexis must be started
in the central portion and not towards the equator, in
order to prevent radial extension. The high density
viscoelastic agents stabilizes the posterior chamber and
pushed back the vitreous face during the posterior
capsulorhexis. During IOL implantation, the capsular bag
is kept open and the anterior chamber is well formed
thus ensuring easy and safe implantation of the IOL in
the bag. These agents also help to dilate the pupil thus
maintaining a good intraoperative mydriasis.55-57
OVDs like Healon-GV can easily be removed at the
end of the surgery including the position which is behind
the IOL due to its high cohesiveness thus preventing
capsular blockade.
Use of the OVDs in Glaucoma Surgery
Viscocanalostomy
Viscocanalostomy is a new surgical procedure for
glaucoma therapy.45 Viscoelastics play an important role
in this procedure. Figures 21.4A to F illustrates the
surgical steps of viscocanalosotomy. Viscocanalostomy
literally means opening of the canal by means of viscoelastic substance. This procedure is a non-penetrating
and independent from external filtration. The advantages
are decreased risk of infection, and decreased incidence
of cataract, hypotony and flat anterior chamber as the
anterior chamber is not opened, and moreover, with the
absence of external filtration the bleb formation is
prevented and also the related discomfort with it. It
minimizes the risk of late infections and is independent
from conjuntival and episcleral scarring.

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 205

Figs 21.4A to F: Surgical steps of viscocanalosotomy. (A) Deep block construction incision, (B) Cutting the
deep block in a single plane with a spoon blade, (C) Proximal to Schlemms canal there is a subtle change in
the scleral fibers, from a crossing pattern to a tangential pattern, with an increased opacity, (D) Descemets
window, (E) Cannulating Schlemms canal with three puffs of viscoelastic directed at the osteum, (F) Tight
closure suture of the flap. (Courtesy: Dr. med. Tobias Neuhann, M.D., Munich, Germany)

Viscocanalostomy allows the aqueous to leave the eye,


through Schlemns canal and episcleral veins thus
restoring the natural outflow pathway. This procedure
creates a bypass by which aqueous humor reaches
Schlemns canal, skipping the trabecular meshwork. A
chamber is produced inside the sclera, which is in direct

communication with the Schlemns canal. There is also a


communication through the Descemets membrane with
the anterior chamber.
The OVDs should have high pseudoplasticity to allow
injection into Schlemns canal through a small needle and
should have high viscosity at shear rate of zero to

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206 Section I: Cataract


maintain the spaces as long as possible. Healon-GV and
Healon-5 are viscoelastics of choice for this procedure.
OVDs for Intraocular Delivery of
Dyes or Anesthetic Agents
Researchers and vision scientists have been using OVDs
as a vehicle to deliver capsular dyes for use during
cataract surgery.1,25 Mixing these substances with the
viscoelastic agent was attempted to prolong their effect
and to limit the adverse effect on ocular tissues. Ciba
Vision Corp (Duluth, GA, USA), has recently proposed
mixing an OVD with lidocaine. This was termed viscoanesthesia and was intended to prolong the anesthetic
effect of intracameral lidocaine, as a complement to
topical anesthesia. Also, the steps of intracameral
injection of OVDs and of intracameral injection of lidocaine, as a complement to topical anesthesia, would be
combined in only one step. In this chapter we will briefly
address the use of OVDs for viscostaining and
viscoanesthesia.
Viscostaining of the Anterior Lens Capsule
Various non-toxic ophthalmic dyes have been extensively
used as diagnostic agents for the detection and
management of different ocular disorders. Dyes such as
fluorescein sodium, indocyanine green (ICG), and trypan
blue have been increasingly used for enhancing
visualization by staining intraocular tissues during the
adult and pediatric cataract surgery and vitreoretinal
surgery. Staining of ocular tissues by using ophthalmic
dyes makes visual differentiation and manipulation of
tissues easier. Enhanced viewing of ocular tissues can
assist a surgeons ability to evaluate clinical structural
relationships and may help attain surgical objectives with
fewer complications.
Uses of various capsular dyes for staining the anterior
lens capsule in white, mature cataracts have been
reported.31-37,46,53 The techniques originally reported for
staining the anterior capsule using fluorescein sodium
are: staining from above under an air bubble, as proposed
by Nahra and Castilla27 and intracameral subcapsular
injection of fluorescein sodium (staining from below)
with blue-light enhancement. The first technique
(staining under an air bubble) is currently used by most
surgeons. One benefit is the staining of the peripheral
anterior capsular rim, which is otherwise difficult to
visualize during the phacoemulsification procedure.
However, air in the anterior chamber makes it unsteady.
Any instrument entering the eye will cause some air to
escape, with a rise of the lens-iris plane. A small amount

of high-density viscoelastic placed near the incision can


prevent the air bubble from escaping the anterior
chamber, thus minimizing the risk of sudden collapse.
Also, with this technique, there is a progressive dilution
of the dye by the aqueous humor. This may be a possible
explanation for the fainter staining observed with this
technique in recent clinical reports, without compromising its usefulness. Most of the drawbacks of this
technique can be avoided by careful use of a viscoelastic
solution to seal the incision site. Akahoshi1 proposed the
soft shell stain technique for performing a CCC in
white cataract cases. A small amount of viscoelastic
(Viscoat) was injected into the anterior chamber
followed by high molecular weight viscoelastic material
(Provisc) to fill up the chamber completely. The author
then injected ICG solution on the lens surface with a bent
G27 viso cannula. The anterior capsule was uniformly
stained in green and easily visualized while the cornea
remained unstained. According to the author, the soft
shell stain technique is extremely useful for CCC in white
cataracts.
Alternatively, the dye solution can be mixed with
viscoelastic agents a technique known as viscostaining
of the anterior lens capsule. Kayikicioglu and coworkers19 proposed a technique for limiting the contact of
trypan blue to corneal endothelium by mixing the dye
with a viscoelastic solution. These researchers mixed 0.4
percent trypan blue with 1 percent sodium hyaluronate
in a 2 mL syringe. The dye, mixed in a viscoelastic solution, is injected onto the anterior lens capsule, which
covers the anterior capsule without coming in contact
with the corneal endothelium. Trypan blue mixed with
sodium hyaluronate greatly increases the visibility of the
anterior lens capsule without significantly touching the
adjacent tissues. There is always a potential risk of corneal
decompensation after intraocular use of self-mixed
solutions; however, these authors used this technique
without significant surgical and postoperative adverse
effects.
Use of OVDs in Topical Ophthalmic
Anesthesia (Viscoanesthesia)
Anesthetic techniques for cataract surgery have also
advanced significantly. General anesthesia was preferred
in past years, followed by various techniques of injectable
anesthesia including retrobulbar, peribulbar, sub-Tenon,
and subconjunctival anesthesia. Due to marked improvements in surgical techniques, it is no longer essential to
ensure complete akinesia of the eye and as a consequence,
the technique of topical anesthesia has been popularized
as phaco anesthesia. This includes eyedrops applica-

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 207


tion, sponge anesthesia, eyedrops plus intracameral
injection, and most recently gel application.15,40 Topical
anesthesia is the preferred technique for the members of
the American Society of Cataract and Refractive Surgery
(ASCRS) in the United States (49%; range 37%-63%)
according to a survey conducted by David Leaming in
2000.21 It revealed that as high as 82 percent of the
respondents using topical anesthesia preferred eye drops
in association with intracameral injection of lidocaine.
We have recently completed some studies to evaluate
the use of viscoelastic agents mixed with topical
anesthetic solution (lidocaine). The aim of these studies
was to evaluate the safety of this new solution (termed
as viscoanesthesia) to intraocular structures.24,32,51 Our
animal and experimental studies were divided into 3
parts. In Part I,24 we determined the toxicity of the
viscoanesthetic solution to the corneal endothelium using
a rabbit model. In Part II,51 we evaluated the toxicity of
viscoanesthetic solutions to uveal tissues and retina in a
rabbit model after performing phacoemulsification.
Finally, in Part III,32 using postmortem human eyes, we
evaluated and compared to currently available OVDs in
regard to the surgical aspects such as injection and
aspiration of the viscoanesthetic solutions. In brief, our
experimental study demonstrated that addition of
varying concentrations of lidocaine to sodium hyaluronate (Ophthalin Plus) neither significantly altered its
viscosity or consistency nor changed its removal time
from the capsular bag. Our animal studies on viscoanesthesia (Part I, II) in rabbit eyes had suggested that
viscoanethetic solution with lidocaine concentrations up
to 1.65 percent are not toxic for the corneal endothelium,
uveal or retinal tissues. Future clinical trails are necessary
to address the issue of efficacy of viscoanesthetic
solutions to provide prolonged topical anesthesia.
Removal of the OVDs
Several techniques has been reported in the literature for
removal of the OVDs. These include: Rock and roll technique, two-compartment technique and bimanual irrigation/aspiration technique. 4 Figures 21.5A to H are
photographs from a human eye obtained postmortem
(Miyake-Apple posterior view) showing the sequence of
the experimental surgical technique of the removal of
fluorescein-colored viscoelastic solutions (green color as
viewed with oblique illumination) from the capsular bag
using the rock and roll technique.
An effective technique to remove Healon-5 is to
create maximum turbulence to make it fracture into large
pieces. This can be accomplished using rock and roll
technique with standard I/A tip, 0.3 mm, with high

settings; a flow rate of 25-30 ml/min., and vacuum 350500 mm Hg, depending on the type of pump. If a
peristaltic pump is used the vacuum should be set
towards the lower limit. A bottle height of 60-70 cm above
the eye level. Figures 21.6A to C summarizes the removal
technique of viscoadaptive agent, Healon-5.
An alternative technique has been developed
allowing the use of less turbulence, using a standard I/
A tip, 0.3 mm, with effectual flow at 20-25 ml and vacuum
250-3000 mm Hg. The bottle height should be 60-70 cm
above eye level. Figures 21.7A and B present the steps of
removal technique of the viscoadaptive agent, Healon5, using another technique.
We would like to emphasize that a careful and
thorough removal of the OVDs from the capsular bag
and the anterior chamber of the eye is must after the end
of the surgery. This is important to avoid complications
such as rise in intraocular pressure, crystallization of the
IOL surface (see later).47 Studies have shown that complete removal of viscoelastic material from the capsular
bag can be more difficult when some hydrophobic acrylic
lenses are used because of the IOLs tacky surfaces (Apple
DJ, Auffarth GU, Pandey SK. Miyake posterior view
video analysis of dispersive and cohesive viscoelastics,
video presented at the Symposium on Cataract, IOL, and
Refractive Surgery, Seattle, WA, April 1999).
COMPLICATIONS OF OVDs
OVDs have many positive attributes but their drawbacks
and complications must be given careful considerations.
Some of the important complications are as follows.
Increase in Intraocular Pressure
Increase in intraocular pressure is the most important
postoperative complication of OVDs. It was first noted
with Healon. The increase in pressure can be severe
and prolonged, if the material is not thoroughly removed
at the end of the surgery. The rise in pressure occurs in
the first 6 to 24 hours and resolves spontaneously within
72 hours postoperatively.2,12 The rise in pressure is due
to the mechanical resistance of the trabecular meshwork
to the large molecules of the viscoelastic material, which
decreases the outflow facility. Hence to decrease the
incidence of this complication, many have advocated
removing and aspirating the viscoelastic material from
the eyes at the end of the surgery.16
Crystallization on the IOL Surfaces
Olson et al29 reported a physician survey, laboratory
studies, and clinical observations of intraoperative

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208 Section I: Cataract

Figs 21.5A to H: Gross photographs from a human eye obtained postmortem (Miyake-Apple posterior view) showing the
sequence of the experimental surgical technique of the removal of fluorescein-colored viscoelastic solutions (green color as
viewed with oblique illumination) from the capsular bag was documented by video taping: (A) This figure shows the eye after
capsulorhexis and removal of lens substance (cortex and nucleus) by phacoemulsification. Note the edge of the anterior
capsulectomy (arrows), (B and C) Injection of fluorescein-colored viscoelastic solution (in this example, Ophthalin Plus), with
a 27-gauge Rycroft cannula through the orifice of the anterior capsulectomy, (D) Capsular bag completely filled with viscoelastic
solution, (E) Same eye after insertion of a one-piece, modified C-loop posterior chamber IOL in the capsular bag (arrows),
(F) Viscoelastic solution removal with automated aspiration, set at 250 mm Hg (Alcon Legacy 20,000), (G) Final removal of
viscoelastic substance. The surgeon reached behind the IOL optical edge to remove all the viscoelastic material, (H) Aspect
after complete removal of the viscoelastic solution

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 209

Figs 21.6A to C: Schematic photograph showing the one of


the removal technique of viscoadaptive agent (Healon-5),
as recommended by the manufacturer: (A) The surgeon circle
the I/A hand piece in the anterior segment at iris plane, (B and
C) The surgeon gently rest the I/A hand piece on the anterior
surface of the optic. Press gently on the IOL optic on one side
and rotate the I/A hand piece directing the flow into the bag.
Direct the hand piece port towards the equator of the capsular
bag and stay in this position for a few seconds, and then repeat
on the other side of the IOL optic until Healon-5 is completely
removed. Finally sweep the anterior chamber including the
angles and repeat the step, if necessary. (Courtesy: Pharmacia
Inc. Peapack, NJ, USA)

Figs 21.7A and B: Schematic photograph showing an


alternative removal technique of viscoadaptive agent (Healon5), as recommended by the manufacturer: (A) Start the
removal directly after IOL implantation, while the anterior
chamber is still filled with Healon-5 and before the IOL has
been centered. Go behind the IOL optic without engaging the
flow of the I/A tip (port up) and then start flow. Remove Healon5 from the capsular bag first and ensure that lens has
adequately centered. During removal of Healon-5 from the
capsular bag, the continuous flow of irrigation fluid keeps the
bag inflated and reduces the risk of aspirating the capsular
bag. While maintaining continuous flow remove the tip from
behind the optic and place it on top of optic, (B) Continue the
removal by circling the I/A tip at the iris plane, or on the optic
surface, then make an additional sweep in the anterior chamber
paying particular attention to angles. (Courtesy: Pharmacia
Inc. Peapack, NJ, USA)

crystallization on IOL surfaces. These authors sent a


survey to all ophthalmologists in the states of Wyoming,
Idaho, Montana, Utah, and Colorado (USA) asking
whether crystallization on the IOL surface had occurred
in any of their patients and what viscoelastics, IOLs, and
other solutions were used. All returned surveys were
tabulated and analyzed by standard statistical means. A
sample of crystallization from an IOL submitted by a
physician on a glass slide was analyzed to ascertain the

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210 Section I: Cataract


relative elemental composition. During in vitro laboratory
studies, BSS Plus (Alcon Surgical, Fort Worth, Texas,
USA) and BSS (Alcon Surgical) were analyzed for
precipitation. Healon-GV (Pharmacia/Upjohn,
Kalamazoo, Michigan, USA) and calcium chloride were
combined in various solutions and examined for
precipitate formation. Silicone IOLs were placed in
different BSS and BSS Plus solutions with different
viscoelastics and varying calcium concentrations. In
seven patients, prominent crystallization on IOL surfaces
was examined, photographed, and followed for up to 3
years. Results of this interesting survey showed that 206
surveyed ophthalmologists returned 181 surveys (88%)
and reported 29,609 cataract surgeries with IOL implantation. In 22 eyes (0.07%) (22 patients) intraoperative
crystallization was observed on the IOL surface during
1993. The survey indicated there was a correlation with
BSS Plus (chi-square = 4.9, P = .0268) and silicone IOLs
(chi-square = 6.8, P = .0093). The analyzed sample
submitted by one of the surgeons showed the cation to
be calcium. The authors concluded that crystallization
on the IOL surface during cataract surgery is a rare
occurrence that may be associated with calcium as the
cation. An osmotic gradient around the IOL is observed
with increased calcium concentration. If encountered
surgically, the lens should be exchanged in the operating
theater after irrigating the anterior chamber with BSS
and completely filling the capsular bag with a low
molecular weight viscoelastic.18,29
Since 1993 we received in our Center more than 9,000
IOLs explanted because of different complications.
During gross and microscopic analyses of these lenses,
it was not uncommon to find crystals on their surfaces,
which exhibited some degree of birefringence (Figs 21.8A
and B). Sometimes they had the typical fern-like appearance found after precipitation of viscoelastic or salt
solutions. We believe those crystals correspond to precipitation of viscoelastic solutions used by the surgeons
during the explantation procedure. These may crystallize
on the surfaces of the IOLs sent to our Center in a dry
state.
Many lenses sent to our Center were explanted
because of the presence of crystalline deposits on their
optical surfaces. They caused significant decrease in
visual function requiring lens esplantation/exchange
(Figs 21.8A and B). Our analyses demonstrated that these
deposits were also composed of multiple confluent small
crystals, which sometimes did not assume a fern-like
appearance, but rather an amorphous arrangement.54
Therefore, it could not be confirmed whether they were
related to deposition/crystallization of viscoelastic
material. Further studies are necessary to evaluate

whether they may correspond to the crystallization of


residual viscoelastics in an aqueous environment, late
postoperatively. Most specifically, scanning electron
microscopy coupled with a surface analysis technique
such as energy-dispersive X-ray analysis could determine
the elemental composition of the deposits observed on
the surfaces of our explanted lenses. These observations
highlight the fact that any viscoelastic agent should be
thoroughly removed from the capsular bag and anterior
chamber of the eye during cataract surgery.
Capsular Block Syndrome or Capsular
Bag Distension Syndrome
Miyake and associates26 proposed a new classification
of capsular block syndrome (CBS), a newly described
complication of cataract-IOL surgery, to improve understanding of the etiology and provide effective treatment.
Three groups of eyes with CBS were reviewed by these
authors: eyes originally reported and diagnosed as
having CBS; eyes experiencing CBS after hydrodissection
and luxation of the lens nucleus; and eyes with CBS
accompanying liquefied after-cataract or capsulorhexisrelated lacteocrumenasia. These researchers noted that
in all 3 groups, the CBS occurred in eyes with a
capsulorhexis. It was characterized by accumulation of
a liquefied substance within a closed chamber inside the
capsular bag, formed because the lens nucleus or the
posterior chamber IOL optic occluded the anterior
capsular opening created by the capsulorhexis.
Depending on the time of onset, CBS was classified as
intraoperative (CBS seen at the time of lens luxation
following hydrodissection), early postoperative
(originally described CBS), and late postoperative (CBS
with liquefied after-cataract or lacteocrumenasia). The
etiology of the accumulated substance and the method
of treatment are different in each type according to their
study. These authors concluded that CBS is a complication of cataract/IOL surgery that can occur during and
after surgery. Correctly identifying the type of CBS is
crucial to understand the nature and effective treatment
of this disorder.
Recently use of high-density viscoelastic agents, such
as Healon-GV, has been found to be associated with
complication of late CBS. Sugiura and associates 49
analyzed the transparent liquid between the posterior
lens capsule and the posterior chamber (PC) IOL in early
postoperative capsular block syndrome and discussed
the mechanism of posterior capsule distention. These
authors evaluated 3 cases of capsular block syndrome
presenting with transparent liquid in the distended
capsular bag 1 day after cataract surgery. The transparent

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 211

Figs 21.8A and B: Crystallization on the IOL surfaces secondary to precipitation of the OVDs on the surfaces: (A) Light
photomicrographs taken from the anterior surface of intraocular lenses, which were explanted because of different complications
(including error in power calculation) and sent to our center for analyses. A typical fern-like appearance of the crystals found on
the surface of the lenses can be observed. Birefringence under polarized light is observed in the bottom picture, (B) Gross and
light microscopic photographs taken from the posterior surface of a 3-piece silicone lens explanted because of opacification of
the lens optic caused by a whitish deposit. The crystals found on the surface of the lens do not have a typical fern-like
appearance, but exhibit birefringence under polarized light (bottom picture)

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212 Section I: Cataract


liquid material between the posterior capsule and PC
IOL was aspirated and analyzed using high-performance
liquid chromatography (HPLC). Also, sodium hyaluronate was diluted using a dialyzer to determine whether
the aqueous humor was drawn into the capsular bag by
an osmotic gradient across the capsule. Results of their
study suggested that the elution time of the samples was
almost the same as that of sodium hyaluronate 1.0
percent. The concentration of the samples ranged from
3.29 to 9.01 mg/mL by HPLC analysis. The sodium
hyaluronate absorbed the physiological salt solutions
through the dialyzer and expanded to 1.9 times its
original volume. These results indicate that the main
ingredient of the transparent liquid in capsular bags is
sodium hyaluronate and that the distention is caused by
aqueous humor being drawn into the capsular bag by
an osmotic gradient across the capsule when the
capsulorhexis diameter is smaller than that of the PC IOL
and by viscoelastic material retained and trapped in the
bag intraoperatively.
Pseudo-anterior Uveitis
The pseudo-anterior uveitis occurs because of the OVDs
viscous nature and also the electrostatic charge of the
materials.28 The red blood corpuscles (RBCs) and inflammatory cells remain in the anterior chamber, thus giving
it the appearance of uveitis. It spontaneously resolves
within three days, requiring no treatment. Sometimes an
intraocular hemorrhage gets trapped between the
vitreous space and the OVD in the anterior chamber and
mimics the appearance of vitreous hemorrhage.28
SUMMARY AND CONCLUSIONS
The choice of a viscoelastic substance depends largely
on the intended surgical use. At the present time, no
single viscoelastic agent is ideal under all circumstances.
For any particular surgical task, the surgeon should
consider the multiple physicochemical characteristics of
each viscoelastic material available as well as their
desirable and undesirable clinical effects, then choose the
most appropriate substance. As new materials are
developed and as our knowledge of the physical
properties, clinical effects, and surgical indications are
better defined, the selection process for choosing the best
product should improve.20
Widespread success in clinical situations has been
achieved with pure hyaluronate and combination
sodium hyaluronate chondroitin sulfate material.
Although expensive, viscoadaptive agent-Healon-5,
has some distinct advantages. Methylcellulose posses

special advantages of lower cost, no requirement of


refrigeration, a larger quantity of the material per unit.
REFERENCES
1. Akahoshi T. Soft shell stain technique for the white cataract,
presented at the ASCRS Symposium on Cataract, IOL, and
Refractive Surgery, Boston, MA, May 2000.
2. Anmarkrud N, Begaust B, Bulie T. A comparison of Healon and
Amvisc on the early postoperative pressure after extracapsular
cataract extraction with implantation of posterior chamber lens.
Acta Ophthalmol Scand. 1996; 74:626-28.
3. Anna Densjo. Healon 5, The worlds first Viscoadaptive.
Ophthalmic express 1998; 6:4.
4. Arshinoff S.A. Rock and roll removal of Healon GV (video).
Presented at the American Society of Cataract and Refractive
Surgery Film Festival; Seattle,WA; 1996;1-5.
5. Arshinoff SA, Hofmann I. Prospective, randomized trial
comparing Micro Visc Plus and Healon GV in routine
phacoemulsification. J Cataract Refract Surg 1998;24:814-20.
6. Arshinoff SA, Opalinski YAV, Ma J. The pharmacology of lens
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JS, eds, Ophthalmology. St Louis, Mosby-Yearbook, 1998;4:20.121.6.
7. Arshinoff SA. Dispersive and cohesive viscoelastics materials
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8. Arshinoff SA. Dispersivecohesive viscoelastic soft shell
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10. Balazs EA, Freeman MI, Kloti R, et al. Hyaluronic acid and
replacement of vitreous and aqueous humour. Mod Prob
Ophthalmol 1972;10:3-21.
11. Balazs EA. The development of sodium hyaluronate (healon)
as a viscosurgical material in ophthalmic surgery. In Eisner G,
ed. Ophthalmic Viscosurgery. Bern, Switzerland: Medicopia,
1986:1-19.
12. Barron BA, Busin M, Page C, et al. Comparison of the effects of
Viscoat and Healon on post operative intraocular pressure. Am
J Ophthalmol 1985;100:377-84.
13. Cobo M, Beaty N. VITRAX? (sodium hyaluronate) in anterior
segment surgery: a review and clinical study summary. Adv
Ther 1990; 7:51-60.
14. Garg A. Viscoelastic substances and other surgical adjuncts. In
Garg A, ed., Textbook of Ophthalmology. Jaypee Brothers, New
Delhi, India, 2001, pp 126-38.
15. Pandey SK, Werner L, Apple DJ, Agarwal A, Agarwal A,
Agarwal S. No anesthesia clear corneal phacoemulsification
versus topical and topical plus intracameral anesthesia:
Randomized clinical trial. J Cataract Refract Surg 2001; 27:164350.
16. Holzer MP, Tetz MR, Auffarth GU, Welt R, Volker H. Effects of
Healon 5 and 4 other viscoelastic substances on intraocular
pressure and endothelium after cataract surgery. J Cataract
Refractive Surg 2001;27:213-18.
17. Hyndiuk RA, Schultz RO. Overview of the corneal toxicity of
surgical solutions and drugs and clinical concepts in corneal
edema. Lens Eye Toxic Res 1992; 9:331-50.
18. Jensen MK, Crandall AS, Mamalis N, Olson RJ. Crystallization
on intraocular lens surfaces associated with the use of Healon
GV. Arch Ophthalmol 1994;112:1037-42.

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Chapter 21: Update on Ophthalmic Viscosurgical Devices 213


19. Kayikicioglu O, Erakgun T, Guler C. Trypan blue mixed with
sodium hyaluronate for capsulorhexis. J Cataract Refract Surg
2001; 27:970.
20. Larson RS, Lindstrom RL, Skelnik DL. Viscoelastic agents.
CLAO J 1989; 15:151-60.
21. Leaming DV. Practice styles and preferences of ASCRS members
2000 survey. J Cataract Refract Surg 2001; 27:948-55.
22. Liesegang TJ. Viscoelastics. Surv Ophthalmol 1990; 34:268-93.
23. Liesegang TJ. Viscoelastics. Int Ophthalmol Clin 1993; 33:12747.
24. Macky TA, Werner L, Apple DJ, Izak AM, Pandey SK, Trivedi
RH. Viscoanesthesia Part II: Evaluation of the toxicity to ocular
structures after phacoemulsification in a rabbit model. J Cataract
Refract Surg 2002 (in press).
25. McDermott ML, Edelhauser HF. Drug binding of ophthalmic
viscoelastic agents. Arch Ophthalmol 1989; 107:261-63.
26. Miyake K, Ota I, Ichihashi S, et al. New classification of capsular
block syndrome. J Cataract Refract Surg 1998;24:1230-34.
27. Nahra D, Castilla M, Capsulorhexis in no view cataract: Staining
of the anterior capsule with 2 percent fluorescein, presented at
the annual meeting of the American Academy of Ophthalmology, October 1996, Chicago, Illinois,USA.
28. Nirankari VS, Karesh J, Lakhanpal V. Pseudovitreous hemorrhage: A new introperative complication of sodium hyaluronate.
Ophthalmic Surg 1981;12:503-04.
29. Olson RJ, Caldwell AS, Jensen MK, Huang SC. Intraoperative
crystallization on the intraocular lens surface. Am J Ophthalmol
1998; 126:177-84.
30. Pandey SK, Ram J, Werner L, Gupta A, Apple DJ. Persistent
pupillary membrane. Br J Ophthalmol 2000; 84:554.
31. Pandey SK, Werner L, Apple DJ, et al. Dye-enhanced pediatric
cataract surgery. J Pediatr Ophthalmol Strabismus 2002 (in
press).
32. Pandey SK, Werner L, Apple DJ, Izak AM, Trivedi RH, Macky
TA. Viscoanesthesia Part III: Evaluation of the removal time of
viscoelastic/viscoanesthetic solutions from capsular bag of
human eyes obtained postmortem. J Cataract Refract Surg 2002
(in press).
33. Pandey SK, Werner L, Apple DJ, et al. Update on dye-enhanced
cataract surgery. In Chang DF, ed., Hyperguide Online Textbook
of Ophthalmology, Thorofare, NJ, Slack, 2001, (http://
www.ophthalmic.hyperguide.com).
34. Pandey SK, Werner L, Apple DJ. Capsular dye-enhanced
cataract surgery. In Nema HV, Nema N, eds., Recent Advances
in Ophthalmology, Volume 6, Jaypee Brothers, New Delhi, India,
2002, PP 11-29.
35. Pandey SK, Werner L, Apple DJ. Staining the anterior capsule.
J Cataract Refract Surg 2001; 27:647-48.
36. Pandey SK, Werner L, Escobar-Gomez M, Roig-Melo EA, Apple
DJ. Dye-enhanced cataract surgery. Part I. Anterior capsule
staining for capsulorhexis in advanced/white cataracts. J
Cataract Refract Surg 2000; 26:1052-59.
37. Pandey SK, Werner L, Escobar-Gomez M, Werner LP, Apple DJ.
Dye-enhanced cataract surgery. Part III. Staining of the posterior
capsule to learn and perform posterior continuous curvilinear
capsulorhexis. J Cataract Refract Surg 2000; 26:1066-71.
38. Poyer JF, Chan KY, Arschin SA. New method to measure the
retention of viscoelastic agents on a rabbit corneal endothelial
cell line after irrigation and aspiration. J Cataract Refract Surg
1998; 24:84-90.
39. Poyer JF, Chan KY, Arschin SA. Quantitative method to
determine the cohesion of viscoelastic agents by dynamic
aspiration. J Cataract Refract Surg 1998; 24:1130-35.

40. Ram J, Pandey SK. Anesthesia for cataract surgery. In Dutta


LC, ed, Modern Ophthalmology. Jaypee Brothers, New Delhi,
India, 2000, PP 325-30.
41. Ram J, Pandey SK. Indications and contraindications of
phacoemulsification. In Dutta LC, ed., Modern Ophthalmology.
Jaypee Brothers, New Delhi, India, 2000, pp 437-40.
42. Ram J, Pandey SK. Infantile cataract surgery: Current
techniques, complications and their management. In Dutta LC,
ed., Modern Ophthalmology. Jaypee Brothers, New Delhi, India,
2000, pp 378-84.
43. Saini JS, Pandey SK. Advances in techniques of penetrating
keratoplasty. In Nema HV, Nema N, eds., Recent Advances in
Ophthalmology, Volume IV, Jaypee Brothers, New Delhi, India,
1998, pp 37-51.
44. Silver FH, Librizzi JJ, Benedetto D. Physical properties of model
viscoelastic materials. J Appl Biomater. 1994; 5:227-34.
45. Stegmann R,Pienaar A, Miller D.Viscocanalostomy for open
angle glaucoma in black African patients. J Cataract Refract Surg
1999;25:316-22.
46. Steinert RF. ICG dye aids in visualization of the anterior capsule.
Ophthalmology Times, May 15, 1999.
47. Storr-Paulsen A. Analysis of the short-term effect of two viscoelastic agents on the intraocular pressure after extracapsular
cataract extraction. Sodium hyaluronate 1% vs hydroxypropyl
methylcellulose 2%. Acta Ophthalmol (Copenh) 1993; 71:17376.
48. Strobel J. Comparison of space maintaining capabilities of
Healon and Healon GV during Phacoemulsification. J Cataract
Refract Surg 1997;23:1081-84.
49. Sugiura T, Miyauchi S, Eguchi S, et al. Analysis of liquid accumulated in the distended capsular bag in early postoperative
capsular block syndrome. J Cataract Refract Surg 2000;26:42025.
50. Tetz MR, Holzer MP. Healon 5 clinical performance and special
removal technique (Two Compartment Technique). In
Viscoelastics in ophthalmic surgery, Eds, Buratto L, Giardini P,
Belluci R,. Thorofare, NJ, USA, Slack 2000, PP 401-04.
51. Trivedi RH, Werner L, Apple DJ, Izak AM, Pandey SK, Macky
TA. Viscoanesthesia Part I: Evaluation of the toxicity to corneal
endothelial cells in a rabbit model. J Cataract Refract Surg 2002
(in press).
52. Werner L, Izak AM, Isaacs RT, Pandey SK, Apple DJ. Evolution
and pathology of intraocular lens implantation. In Yanoff M,
Ducker JS, eds, Ophthalmology. St Louis, Mosby-Yearbook, 2002
(in press).
53. Werner L, Pandey SK, Escobar-Gomez M, Hoddinott DSM,
Apple DJ. Dye-enhanced cataract surgery. Part II. An experimental study to learn and perform critical steps of phacoemulsification in human eyes obtained post-mortem. J Cataract
Refract Surg 2000; 26:1060-65.
54. Werner L, Shugar JK, Apple DJ, Pandey SK, Escobar-Gomez M,
Visessook N, Evans BB. Opacification of piggyback IOLs
associated to an amorphous material attached to interlenticular
surfaces. J Cataract Refract Surg 2000;26:1612-19.
55. Wilson ME, Trivedi RH, Apple DJ, Batholomew L, Werner L,
Pandey SK. Ophthalmic viscosurgical agents (OVAs): A guide
for the pediatric cataract surgeons. J Cataract Refract Surg 2002.
56. Wilson ME, Pandey SK, ThakurJ. Pediatric cataract surgery in
the developing world. Br J Ophthalmol 2002.
57. Wilson ME, Pandey SK, Werner L, Ram J, Apple DJ. Pediatric
Cataract Surgery: Current Techniques, Complications and
Management. In Agarwal S, Agarwal A, Sachdev MS, Mehta
KR, Fine H, Agarwal A, eds., Phacoemulsification, Laser
Cataract Surgery and Foldable IOLs. Jaypee Brothers Medical
Publishers, New Delhi, India, 2000, pp 369-88.

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214 Section I: Cataract

22

Update on Twenty First Century


CataractIntraocular Lens Surgery
A Journey from Large Incision/Rigid Lenses to Ultrasmall Incision/Foldable Lenses
Suresh K Pandey, Liliana Werner, David J Apple,
Andrea M Izak, Vidushi Sharma, Amar Agarwal

BACKGROUND
LARGE INCISION CATARACT
SURGERY AND IMPLANTATION
OF RIGID LENSES
SMALL INCISION CATARACT
SURGERY AND IMPLANTATION
OF FOLDABLE LENSES
ULTRASMALL INCISION
CATARACT SURGERY AND
IMPLANTATION OF
ROLLABLE LENSES
THE FUTURE CHALLENGES

BACKGROUND
At the beginning of the 21st century, modern cataract-intraocular lens (IOL)
surgery has become one of the safest, most successful, and most frequently
performed outpatient surgeries in the industrialized world including North
America.1-6 In former times, when anesthesia and fine surgical instrumentation were beyond conception, the cataractous lens was dislocated
into the vitreous (couching) (Fig. 22.1). Thanks to considerable advancement in microsurgical techniques modern cataract surgery can be
performed using sub-1mm incision and history reaches a full circle with
reports of no-anesthesia cataract surgery.7-9 In this chapter, we attempted
to summarize major evolutionary advancements of surgical techniques
and IOL designs/biomaterials for cataract surgery. However, it is almost
impossible to provide details of each and every evolution.

Fig. 22.1: Illustration from a 1966 facsimile of a 1583 German atlas of a renaissance
eye surgery showing the ancient technique of couching. Left: Frontal view. Right:
An example of ornamental couching needles (From: Bartisch, G.: Augendienst,
Dresden, Germany, 1583)

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215

Fig. 22.2: Photographs of Ridleys 8th


implant operation, on May 10, 1951. These
pictures were taken from the original film. The
clips range from the von Graefe incision of
approximately 10-11 mm in length (upper left)
to the lens removal (lower left) and the IOL
insertion (low center and right)

LARGE INCISION CATARACT SURGERY AND


IMPLANTATION OF RIGID LENSES

Foldable Lenses Manufactured from Hydrophobic


and Hydrophilic Acrylic and Silicone Biomaterials

Sir Harold Ridleys cataract extraction and implantation


of an IOL marked the beginning of a major change in the
practice of ophthalmology (Fig. 22.2). The first operation,
done at St. Thomass Hospital, London, was a two-step
procedure. The extracapsular removal of the cataract took
place on November 29, 1949. The insertion of the pseudophakos, manufactured by Rayner, Ltd., United Kingdom,
occurred as a secondary procedure on February 8, 1950.
Ridley selected acrylic as the initial biomaterial based
on the experience of ophthalmologists who dealt with
World War II injuries involving Perspex plastic1,2 (Fig.
22.2).

A variety of foldable IOL designs manufactured from


hydrophobic or hydrophilic acrylics as well as silicone
biomaterials are available to the anterior segment
surgeon (Figs 22.3 to 22.5).5,6 Choice of foldable lens
design varies from surgeon to surgeon. Foldable lenses
with truncated optics manufactured from hydrophobic
acrylic lenses are preferred by the surgeons due to
reduced incidence of posterior capsule opacification
(PCO).
Silicone polymer was the first biomaterial used for
foldable lenses (Figs 22.6A to C).

SMALL INCISION CATARACT SURGERY AND


IMPLANTATION OF FOLDABLE LENSES
Charles D Kelman, MD, believed that cataracts could
theoretically be removed through a 2-or 3-mm incision
by using vibrational energy to fragment the lens inside
the eye. Dr Kelman garnered the idea reportedly after a
visit to the dentist, where he found an ultrasonic device
being used to help remove plaque and debris from teeth.
Phacoemulsification, invented and pioneered by
Dr Kelman, has become the most preferred method
of cataract surgery in USA and the industrialized world.4

ULTRASMALL INCISION CATARACT SURGERY AND


IMPLANTATION OF ROLLABLE LENSES
Bimanual phacoemulsification can now be performed
through an ultrasmall (0.9 mm) incision using the
Phakonit technique. Pioneered by Dr Amar Agarwal,
Phakonit had been performed in more than 500 cases
without use of topical anesthesia.7,8 Ongoing research for
the development of laser probes, cold phaco, microphaco,
and micro-incision cataract surgery (MICS) confirm
the interest of leading ophthalmologists and manufacturers in the direction of ultrasmall incisional cataract
surgery.

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216 Section I: Cataract

Figs 22.3A to C: Illustrate characteristics of the single-piece AcrySof lens (Alcon Labs., Fort Worth, TX, USA). A: Gross
photograph of a human eye obtained postmortem implanted with this lens design, showing optimal centration of the lens and
clear capsular bag. B: Scanning electron photomicrograph showing the velvet finishing of the lens edge. C: Gross photograph
showing the yellow color of the AcrySof Natural lens (under investigation)

Figs 22.4A and B: present features of the Sensar lens with the OptiEdge technology (Allergan Inc., Irvine, CA, USA). This
design is stated to combine the advantage of truncated optics and at the same time eliminate the drawbacks such as glare, etc.
A: Clinical picture of a patient implanted with this lens design (courtesy: Allergan Surgical). B: Scanning electron photomicrograph
showing the 3 components of the OptiEdge

Figs 22.5A to F: Summarize some of the hydrophilic acrylic lenses being used today. A: Gross photograph showing the Rayner
Centerflex lens. B: Clinical picture of a patient implanted with this lens design (courtesy: Dr. Michael Amon, Vienna, Austria).
C: Scanning electron photomicrograph showing the square edge of the Centerflex lens. D: Gross photograph of a human eye
obtained postmortem implanted with the Ciba Vision MemoryLens, showing good centration of the lens and clear capsular
bag, with the exception of the presence of Soemmerings ring formation limited to one quadrant. E: Gross photograph showing
the Bausch and Lomb Hydroview lens. F: Clinical picture of a patient implanted with this lens design (courtesy: Dr. Manfred
Tetz, Berlin, Germany)

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Chapter 22: Update on Twenty First Century CataractIntraocular Lens Surgery

217

Figs 22.6A to C: Illustrate the newly available silicone lenses. A: Clinical picture of a patient implanted with the CeeOn Edge
(Pharmacia Inc., Peapack, NJ, USA) lens (Courtesy: Dr KD Solomon, Charleston, SC, USA). B: Gross photograph showing an
experimental implantation of the same lens design in a human eye obtained postmortem, prepared according to the MiyakeApple posterior video-photographic technique. C: Gross photograph showing the ClariFlex 3-piece silicone lens with the
OptiEdge technology (Allergan Inc., Irvine, CA, USA)

Figs 22.7A to D: Illustrate the Phakonit technique with implantation of the ThinOptX rollable IOL (Abingdon, VA, USA). A:
Photograph showing the ThinOptX rollable IOL. B: The cataract was removed through a 0.9 mm incision using the phakonit
technique. The ThinOptX IOL was gently rolled between the thumb and index fingers of the surgeon and inserted through a
sub-1.5 mm incision. C: The ThinOptX IOL is unfolding inside the capsular bag, upon normal body temperature. D: Note the
well-centered ThinOptX IOL in the capsular bag. Viscoelastic solution is being removed using bimanual irrigation/aspiration
probes. AcrySmart is another IOL design that can be inserted through ultrasmall incision as shown in Figures 8A-D

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218 Section I: Cataract

Figs 22.8A to D: Illustrate the AcrySmart IOL design. The pre-folded dehydrated IOL unfolds
in balanced salt solution (model H44-IC-1). B: Later stage in the unfolding process. C: The prefolded dehydrated IOL was inserted in the capsular bag. D: Gross photograph showing the
AcrySmart model 48 S
Table 22.1: Six factors to eradicate PCO
Three surgery-related factors (capsular surgery)

Three IOL-related factors (Ideal IOL)

1.

Hydrodissection-enhanced cortical clean-up

1.

2.

In-the-bag fixation

2.

3.

Small CCC diameter slightly smaller than


that of IOL optic. This places the CCC edge
on the anterior surface of the optic and helps
sequester the capsular bag. This creates a
shrink wrap of the capsule around the
IOL optic

3.

Biocompatible IOL to reduce


stimulation of cellular proliferation
Maximal IOL optic-posterior
capsule contact, angulated hepatic,
bioadhesive biomaterial to
create a shrink wrap
IOL optic geometry square,
truncated edge

THE FUTURE CHALLENGES

B. Restoration of accommodation

Despite of considerable advancement surgeons need to


overcome two important challenges. These include:
A. Eradication of posterior capsule opacification

Eradication of Posterior Capsule Opacification


We have proposed 6 factors to eradicate PCO (Table
22.1).10 Efforts are in progress to eradicate PCO, a nagging

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Chapter 22: Update on Twenty First Century CataractIntraocular Lens Surgery

219

Fig. 22.9: Illustrate the concept of a sealed capsule irrigation device (SCID)
or perfect capsule being developed by Dr Anthony Maloof

Figs 22.10A to D: A: Gross photograph showing the Morcher BioComFold lens. B: Schematic drawing
representing the HumanOptics Accommodative 1 CU lens implanted in the capsular bag of a human eye.
C: Schematic drawing representing the C and C CrystaLens. D: Gross photograph showing an
experimental implantation of the Visiogen Inc. (Irvine, CA, USA) intraocular accommodating system in a
human eye obtained postmortem, prepared according to the Miyake-Apple posterior video-photographic
technique. The capsular bag of the eye was stained with trypan blue, to enhance visualization of the lens.
The picture was taken from an anterior view with retroillumination

complication of cataract-IOL surgery. Eradication of


PCO is critical for success of multifocal and accommodative lenses.
Restoration of Accommodation
Efforts are in progress to restore accommodation after
cataract-IOL surgery using accommodative lenses as
shown in Figures 22.10A to D.
REFERENCES
1. Apple DJ, Auffarth GU, Peng Q, Visessook N. Foldable
intraocular lenses: Evolution, clinicopathologic correlations,
complications. Thorofare, NJ, Slack, 2000.
2. Apple DJ, Ram J, Foster A, Peng Q. Elimination of cataract
blindness: A global perspective entering the new millennium.
Surv Ophthalmol 2000; 45:S1-S160.
3. Pandey SK, Wilson ME, Trivedi RH, Izak A, Macky TA, Werner
L, Apple DJ. Pediatric cataract surgery and intraocular lens
implantation: Current techniques, complications and management. Int Ophthalmol Clin 2001; 41:175-96.
4. Lineberger EJ, Hardten DR, Shah GK, Lindstrom RL.
Phacoemulsification and modern cataract surgery. Surv
Ophthalmol 1999; 44:123-47.

5. Werner L, Apple DJ, Schmidbauer JM. New intraocular lenses,


new technology. In: Buratto L, Werner L, Zannini M, Apple DJ
(Eds): Phacoemulsification Principles and Techniques.
Thorofare, Slack, NJ, 2002 (In press).
6. Werner L, Izak AM, Isaacs RT, Pandey SK, Apple DJ. Evolution
and pathology of intraocular lens implantation. In: Yanoff M,
Ducker JS (Eds): Ophthalmology. St Louis, Mosby-Yearbook,
2002 (in press).
7. Agarwal A, Agarwal S, Pandey SK, Agarwal A, Bagmar A, Shah
SP. Phakonit: Lens removal through 0.9 mm incision. J Cataract
Refract Surg 2001; 27:1531.
8. Pandey SK, Werner L, Agarwal A, Agarwal S, Agarwal A, Lal
V, Patel N, Hoyos JE, Callahan W, Callahan JS, Callahan JD.
Phakonit: Cataract removal through a sub-1mm incision and
implantation of ThinOptX rollable intraocular lens. J Cataract
Refract Surg 2002 (in press).
9. Pandey SK, Werner L, Apple DJ, Agarwal A, Agarwal A,
Agarwal S. No anesthesia clear corneal phacoemulsification
versus topical and topical plus intracameral anesthesia:
Randomized clinical trial. J Cataract Refract Surg 2001; 27:164350.
10. Werner L, Apple DJ, Pandey SK. Postoperative proliferation of
anterior and equatorial lens epithelial cells. In: Buratto L, Osher
RH, Masket S (Eds): Cataract Surgery in Complicated Cases.
Slack Inc., Thorofare, NJ, 2000, 399-417.

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220 Section I: Cataract

23

Update on Posterior Capsule Opacification:


Etiopathogenesis, Clinical Manifestations,
Pharmacological and Surgical Prevention
Suresh K Pandey, Liliana Werner, David J Apple, Andrea M Izak

INTRODUCTION
POSTERIOR CAPSULE
OPACIFICATION (SECONDARY
CATARACT)
BACKGROUND AND
SIGNIFICANCE
WHY TO ERADICATE PCO?
ETIOPATHOGENESIS
CLINICAL MANIFESTATIONS
PREVENTION OF POSTERIOR
CAPSULE OPACIFICATION
ANALYSIS OF ND: YAG
POSTERIOR CAPSULOTOMY
RATES

INTRODUCTION
Opacification of the posterior capsule caused by postoperative proliferation
of cells in the capsular bag remains the most frequent complication of
cataract surgery. In addition to classic posterior capsule opacification
(PCO), postoperative lens epithelial cell (LEC) proliferation is also involved
in the pathogenesis of other entities. These include anterior capsule
opacification (ACO) and interlenticular opacification (ILO); a more recently
described complication related to piggyback IOLs. Thus, there are three
distinct anatomic locations within the capsular bag where clinically
significant opacification may occur postoperatively (Fig. 23.1). In this chapter
we will discuss the etiopathogenesis, clinical manifestations, pharmacological,
surgical as well implant related factors for prevention of the PCO. Interested
readers may consult the published articles for other modalities of capsular bag
opacification including ACO and ILO.1,10-12,88,89,92,93,95-98,101-104
POSTERIOR CAPSULE OPACIFICATION (SECONDARY CATARACT)
BACKGROUND AND SIGNIFICANCE
Posterior capsule opacification (PCO, secondary cataract) has been
recognized since the origin of extracapsular cataract surgery (ECCE) and
was noted by Sir Harold Ridley in his first intraocular lens (IOL)
implantations.3,8 It was particularly common and severe in the early days
of IOL surgery when the importance of cortical clean-up was less
appreciated. Through the 1980s and early 1990s, the incidence of PCO
ranged between 25-50 percent.7,8
Improvements in cataract surgical technique have led to a gradual,
but steady, decrease in the incidence of this complication. Our data show
that through a combination of modern techniques and IOL designs, the
incidence of Nd: YAG laser posterior capsulotomy is now decreasing into
single digits.4-6,78-80
WHY TO ERADICATE PCO?
Although cataract is the most common cause of blindness in the world,
after-cataract is an extremely common cause as well. Jan GF Worst, MD

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Chapter 23: Update on Posterior Capsule Opacification 221

Fig. 23.1: Schematic illustration of the microscopic anatomy


of the lens and the capsular bag, showing the A cells of the
anterior epithelium and the E cells, the important germinal
epithelial cells of the equatorial lens bow

B. Dense PCO and/secondary membrane formation


particularly common following pediatric IOL implantation.73 A delay in diagnosis can cause irreparable
amblyopia.
C. PCO represents a significant cost to the US healthcare
system. Nd:YAG laser treatments of almost one
million patients per year have cost up to $250 million
annually.
D. A posterior capsulotomy can increase the risk of
posterior segment complications in high myopes and
patients with uveitis, glaucoma, and diabetic retinopathy.
E. PCO of even a mild degree can decrease near acuity
through a multifocal IOL, and may interfere with the
function of accommodating IOL designs.
F. Finally, a significant incidence of PCO means that
cataract surgery, alone, may not restore lasting sight
to the 25 million people worldwide who are blind
from cataract.
ETIOPATHOGENESIS

Fig. 23.2: Gross photograph of an explanted foldable posterior


chamber intraocular lens (STAAR, 1-piece silicone-plate, small
hole) showing multiple Nd: YAG laser lesions on the optical
surface

stated recently the most meaningful development in


intraocular implant research in the next five years will be
effective prevention of secondary cataract formation
(International Intraocular Implant Club Report, Vol. 1,
No. 2, January 1999). Eradication of PCO following ECCE
has major medical and financial implications:
A. Nd:YAG laser secondary posterior capsulotomy, can
be associated with significant complications. Potential
problems including IOL damage, postoperative intraocular pressure elevation, cystoid macular edema,
retinal detachment, and IOL subluxation (Fig.
23.2).36,37,40,41

Postoperative proliferation of lens epithelial cells in the


capsular bag is central to the pathogenesis of PCO.
Proliferation of these cells can also lead to ACO, and
ILO.14,25-29,49,54,70,71 In the normal crystalline lens, the
epithelial cells are confined to the anterior surface at the
equatorial region and the equatorial lens bow. This single
row of cuboidal cells can be divided into two different
biological zones (Fig. 23.1):
A. The anterior-central zone (corresponding to the zone
of the anterior lens capsule) consists of a monolayer
of flat cuboidal, epithelial cells with minimal mitotic
activity. In response to a variety of stimuli, the anterior
epithelial cells (A cells) proliferate and undergo
fibrous metaplasia. This has been called pseudofibrous metaplasia by Font and Brownstein.24
B. The second zone is important in the pathogenesis of
pearl formation. This layer is a continuation of
anterior lens cells around the equator, forming the
equatorial lens bow (E cells). Unlike within the Acell layer, cell mitoses, division, and multiplication
are quite active in this region. New lens fibers are
continuously produced in this zone throughout life.
The majority of clinical PCO is caused by the
proliferation of remnant or regenerated lens epithelial
cells left in the capsular bag following cataract surgery
(Figs 23.3 and 23.4A and B). Although both types of cells
(from the anterior central zone and from the equatorial
lens bow) have the potential to produce visually
significant opacification, most cases of classic PCO are

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222 Section I: Cataract

Fig. 23.3: Gross photograph of a human eye obtained


postmortem (Miyake-Apple posterior photographic technique)
showing Soemmerings ring formation. The equatorial
remnants of a classic Soemmerings ring are composed of
cortical material and proliferating E-cells. Although extensive
cortical remnants remain forming a massive Soemmerings
ring, the central optic region of the visual axis has remained
clear in this case, due to the barrier effect provided by the
intraocular lens

caused by proliferation of the equatorial cells. The term


posterior capsule opacification is actually a misnomer. It
is not the capsule which opacifies. Rather, an opaque
membrane develops as retained cells proliferate and
migrate onto the posterior capsular surface.
The opacification usually takes one of two
morphologic forms. One form consists of capsular pearls,
which can consist of clusters of swollen, opacified
epithelial pearls or clusters of posteriorly migrated
equatorial epithelial (E) cells (bladder or Wedl cells). It
is probable that both lens epithelial cell types can also
contribute to the fibrous form of opacification. Anterior
epithelial (A) cells are probably important in the
pathogenesis of fibrosis PCO, since the primary type of
response of these cells is to undergo fibrous metaplasia.
Although the preferred type of growth of the equatorial
epithelial (E) cells is in the direction of bloated, swollen,
bullous-like bladder (Wedl) cells, these also may
contribute to formation of the fibrous form of PCO by
undergoing a fibrous metaplasia. This is a particularly
common occurrence in cataracts in third world settings
where cataract surgery has been delayed for many years,
and where posterior subcapsular cataracts have turned
into fibrous plaques.
Equatorial cells (E-cells) are also the responsible for
formation of a Soemmerings ring. The Soemmerings
ring, a dumb-bell or donut-shaped lesion that often forms
following any type of rupture of the anterior capsule,

Figs 23.4A and B: Gross photographs of a pseudophakic


human globe obtained postmortem implanted with a 1-piece
all PMMA lens. Note the presence of a Nd: YAG laser posterior
capsulotomy, (A) Posterior view (Miyake-Apple posterior
photographic technique), (B) Anterior (surgeons) view

was first described in connection with ocular trauma. The


pathogenetic basis of a Soemmerings ring is rupture of
the anterior lens capsule with extrusion of nuclear and
some central lens material. The extruded cortical
remnants then transform into Elschnig pearls. It is not
widely appreciated that a Soemmerings ring forms
virtually every time that any form of ECCE is done,
whether manual, automated or with phacoemulsification
(Figs 23.5A to E). This material is derived from proliferation of the epithelial cells (E-cells) of the equatorial lens
bow. We have noted that these cells have the capability
to proliferate and migrate posteriorly across the visual
axis, thereby opacifying the posterior capsular. Because
the Soemmerings ring is a direct precursor to PCO,
surgeons should strive to prevent its formation.
Cells types other than lens epithelial cells may be
involved in PCO. As extracapsular cataract surgery
(ECCE) is always associated with some breakdown of

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Chapter 23: Update on Posterior Capsule Opacification 223

Figs 23.5A to E: Biocompatibility analyses can be obtained by evaluating and scoring peripheral PCO (Soemmerings ring)
and central PCO. Using these techniques we have been able to note apparent differences in materials in terms of inhibiting
both central and peripheral PCO. Gross photographs from behind (Miyake-Apple posterior photographic technique) of human
eyes obtained postmortem showing varying degree of the Soemmerings ring formation: (A) Grade 0 (Alcon AcrySofTM acrylic
IOL), (B) Grade 1 (Allergan SI-40 silicone IOL), (C) Grade 2 (Silicone optic/polyimide haptics), (D) Grade 3 (PMMA optic/
PMMA haptics), (E) Grade 4 (PMMA optic/prolene haptics)

the blood-aqueous barrier, inflammatory cells, erythrocytes, and many other inflammatory mediators may be
released into the aqueous humor. The severity of this
inflammatory response may be exacerbated by the IOL.
This foreign body elicits a three-stage immune response
that involves many different cell types, including
polymorphonuclear leukocytes, giant cells, and fibroblasts. Collagen deposition onto the IOL and onto the
capsule may cause opacities and fine wrinkles to form
in the posterior capsule. In most cases, however, this

inflammatory response is clinically insignificant. Iris


melanocytes also have been shown to adhere to and
migrate over the anterior surface of the posterior capsule.
CLINICAL MANIFESTATIONS
The interval between surgery and PCO varies widely,
ranging anywhere from three months to four years after
the surgery. Although the causes of PCO are multifactorial as reported in the several studies, there is

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224 Section I: Cataract

6 Factors to Reduce PCO


3 Surgery-Related Factors (Capsular Surgery)
1. Hydrodissection-enhanced cortical clean-up.
2. In-the-bag fixation.

3 IOL-Related Factors (Ideal IOL)


1. Biocompatible IOL to reduce
stimulation of cellular proliferation.
2. Maximal IOL optic-posterior capsule
contact, angulated haptic, bioadhesive
biomaterial to create a shrinkwrap.

3. CCC diameter slightly smaller than that


of IOL optic. This places the CCC edge of the
anterior surface of the optic and helps
sequester the capsular bag, creating a
3. IOL optic geometry: square, truncated
shrink wrap of the capsule around the IOL optic
edge.
Fig. 23.6: Factors that significantly influence the formation of PCO. Three factors are related to
the type and quality of surgery and three are related to IOL material/design

an inverse correlation with age.7,18,20,23,35 Young age is a


significant risk factor for PCO, and its occurrence is a
virtual certainty in pediatric patients.105
Visual symptoms do not always correlate to the
observed amount of PCO. Some patients with significant
PCO on slit lamp examination are relatively asymptomatic while others have significant symptoms with mild
apparent haze, which is reversed by capsulotomy.17
PREVENTION OF POSTERIOR CAPSULE
OPACIFICATION
PCO prevention has been an active research interest of
ours since 1982. Based on our work, we would review
the principles of PCO prevention. These measures can
be divided into two categories. One strategy is to
minimize the number of retained/regenerate cells and
cortex (including the Soemmerings ring) through
thorough cortical clean-up. The second strategy is to
prevent the remaining cells from migrating posteriorly.
The edge of the IOL optic is critical in the formation of
such a physical barrier.
We have identified three surgery-related factors and
three IOL-related factors that are particularly important
in the prevention of PCO (Fig. 23.6).
Three Surgery Related Factors to Reduce PCO
Hydrodissection-enhanced Cortical Clean-up
A very important and underrated factor is the
hydrodissection component of the operation (Figs 23.7A
to C). Dr. I. Howard Fine perfected and popularized this
technique and coined the term cortical cleaving

hydrodissection.22 Until fairly recently, many surgeons


had a rather fatalistic attitude regarding removal of lens
cortex and cells during ECCE, either manual or automated, or with phacoemulsification. The common
opinion was that removing all or even most equatorial
cells from the bag is impossible. PCO was therefore
considered an inevitable complication. This conclusion
was partly because PCO occurred in up to 50 percent of
cases. We now know from autopsy and experimental
studies that good cortical and cellular clean-up can be
accomplished in a much more efficient fashion in a
majority of cases than had previously been believed. The
hydrodissection procedure with special focus on freeing
and rotating the lens nucleus facilitates lens substance
removal without zonular-capsular rupture. Recently, we
have shown an important additional long-term
advantage of hydrodissection; namely, a means of more
efficient removal of cortex and cells that in turn is
essential in reducing PCO. With careful, meticulous
hydrodissection, the operation is much easier and faster,
cortex and cell removal is much more thorough and
formation of an unwanted Soemmerings ring is
minimized. A successful performed cortical cleaving
hydrodissection provides an easy way to extract the
entire lens cortex as well as nucleus, often without the
need for cortical aspiration. The necessary tenting up of
the anterior capsule is best achieved by using a cannula
with a bend at the tip allowing a flow of fluid toward
the capsule to efficiently separate capsule from cortex.
In-the-Bag (Capsular) Fixation
The hallmark of modern cataract surgery is the achievement of consistent and secure in-the-bag (capsular)

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Chapter 23: Update on Posterior Capsule Opacification 225

Fig. 23.7A: Control group; Gross photograph obtained from


behind (Miyake-Apple posterior view) showing the obscuration
of the central visual axis

fixation (Fig. 23.6). The most obvious advantage of inthe-bag fixation is the accomplishment of good optic
centration and sequestration of the IOL from adjacent
uveal tissues. The numerous other advantages have been
described in detail elsewhere. However, it is not often
appreciated that this is also extremely important in
reducing the amount of PCO.
The primary function of in-the-bag fixation is enhancing the IOL-optic barrier effect, which is functional and
maximal when the lens optic is fully in-the-bag with
direct contact with the posterior capsule. In case one or
both haptics are not placed in the bag, a potential space
is created, allowing an avenue for cells to grow
posteriorly toward the visual axis. The reader may recall
the barrier ridge IOL design devised by Kenneth Hoffer
in the 1980s, which did not function sufficiently in this
period. The reason was not a problem with the concept
or the IOLs themselves, but in that time only about 30
percent of posterior chamber IOLs were implanted in the
bag.
The growth of incidence of in-the-bag fixation,
although steady and positive, reached what appears to
be a limit with non-phaco ECCE of about 60 percent.
Apparently, the reason is that many cases over the years
had been done with classic large-incision extracapsular
surgery with rigid IOLs, often with can-opener anterior
capsulotomy. We have to be aware of the fact that secure
and permanent in-the-bag fixation only occurred in a
maximum of about 60 percent of cases. This rate appears
to be the best achievable with these early techniques.
However, when considering modern foldable lens
implantation, the number rapidly rises to over 90 percent.
It is not the foldable IOL itself, or even the small incision
in and of itself that provides this positive result, but rather
the fact that successful foldable IOL insertion generally
requires meticulous surgery, with the necessity of
performing a continuous curvilinear capsulorhexis
(CCC) and secure implantation of both IOL loops in the
bag.
Capsulorhexis Edge on IOL Surface

Figs 23.7B and C: Photomicrographs taken from the right and


left sides of the capsular bag, respectively. Note the presence
of exuberant cortical material and lens epithelial cells (H and
E X200, H and E X100 respectively)

A less obvious, but significant addition to precise in-thebag fixation, is creating a CCC diameter slightly smaller
than that of the IOL optic. For example, if the IOL optic
were 6.0 mm, the capsulorhexis diameter would ideally
be slightly smaller, perhaps 5.0-5.5 mm. This places the
cut anterior capsule edge on the anterior surface of the
optic, providing a tight fit (analogous to a shrink wrap)
and helping to sequester the optic in the capsular bag
from the surrounding aqueous humor (Fig. 23.6). This
mechanism may support protecting the milieu within the

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226 Section I: Cataract


capsule from at least some potentially deleterious factors
within the aqueous, especially some macromolecules,
and some inflammatory mediators. The concept of
capsular sequestration based on the CCC size and shape
is subtle, but more and more surgeons appear to be
applying this principle and seeing its advantages.
Three IOL-related Factors to Reduce PCO
In addition to the three above-mentioned surgery-related
factors we will describe briefly the three IOL-related
factors, which in our opinion play an important role in
the eradication of PCO.
Biocompatibility
Lens material biocompatibility (Figs 23.6, and 23.11 to
23.13) is an often misunderstood term. It may be defined
by many criteria, e.g. the ability to inhibit stimulation of
epithelial cellular proliferation: the less the cell
proliferation the less the chance for secondary cataract
formation. The Alcon AcrySof IOL scored well with
these criteria, with respect to Soemmerings ring
formation, PCO and with respect to anterior capsule
opacification. In addition, the amount of cell proliferation
is greatly influenced by surgical factors, such as copious
cortical clean-up. Furthermore, the time factor plays a
role, such as the duration of the implant in the eye. Additional long-term studies are required to assess the overall
role of biocompatibility in the pathogenesis of PCO.
Maximal IOL Optic Posterior Capsule Contact
Other contributing factors in reducing PCO are posterior
angulation of the IOL haptic and posterior convexity of
the optic (Fig. 23.6). This is due to the creation of a shrink
wrap, a tight fit of the posterior capsule against the back
of the IOL optic. The relative stickiness of the IOL optic
biomaterial probably helps producing an adhesion
between the capsule and IOL optic. There is preliminary
evidence that the Alcon AcrySof IOL biomaterial
provides such enhanced adhesion, or bioadhesion.4648,58 This will require further study.
Barrier Effect of the IOL Optic
The IOL optic barrier effect (Fig. 23.6), plays an important
role as a second line of defense against PCO, especially
in cases where retained cortex and cells remain following
ECCE. The concept of the barrier effect goes back to the
original Ridley lens. If accurately implanted in the
capsular bag, it provided an excellent barrier effect, with
almost complete filling of the capsular bag and contact

of the posterior IOL optic to the posterior capsule (no


space, no cells). A lens with one or both haptics outof-the-bag has much less of a chance to produce a barrier
effect. Indeed, the IOL optics barrier function has been
one of the main reasons that PC-IOLs implanted after
ECCE throughout the decades did not produce an
unacceptably high incidence of florid PCO. Actually, the
barrier effect has enabled the success of IOL implantation
after ECCE during the past decades.
A subtle difference between classic optics with a
round tapered edge and optics with a square truncated
edge became evident recently (Fig. 23.6). The effect of a
square-edge optic design as a barrier was first discussed
by Nishi et al in the articles related to PCO.59-69 In a clinicopathological study, our laboratory was the first to confirm
this phenomenon in human eyes.74,75 We reported our
results of a large histopathological analysis covering the
IOL barrier effect, with special reference to the efficacy
of the truncated edge. A truncated, square-edged optic
rim appears to be cause a complete blockade of cells at
the optic edge, preventing epithelial ingrowth over the
posterior capsule.42,43,50,51,55,56,83,86,87 The enhanced barrier
effect provided by this optic geometry probably functions
as an icing on the cake. It seems to provide another
reserve factor, in addition to the five above-mentioned
factors, contributing in diminishing the overall incidence
of visually significant PCO.
Our studies up to date have shown, that the Alcon
AcrySof IOL best achieves the goals of these three IOLrelated factors (Fig. 23.6). Other IOL designers are rapidly
moving to provide comparable features, especially a
conversion to sharp edges. A major disadvantage of the
truncated edge is the possible formation of clinical visual
aberration, e.g. glare, halos and crescents. Subtle changes
in manufacturing are now helping alleviate these
complications. An example of this include introduction
of Optic Edge IOL manufactured by Allergan. This IOL
has squared posterior edge and a round anterior edge.
Therefore, it avoids the glare and other disadvantages
and on the other hand the squared posterior edge is
helpful to prevent/delay development of PCO.
Confirmation of 6 Factors in Clinical Studies
We would like to mention 3 studies that confirm the
advantage of applying one or more surgical/IOL related
factors to prevent or delay PCO formation. In a large
clinical study, Ram, Pandey, Apple, Werner and
associates79 has confirmed previous pathological studies
showing the need for mandatory in-the-bag fixation of
posterior chamber IOLs (both rigid and foldable) to help
reduce the incidence of PCO. This is true for both ECCE
and phacoemulsification. This study was performed in

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Chapter 23: Update on Posterior Capsule Opacification 227


Chandigarh, India, and was a combined effort of the
Postgraduate Institute of Medical Education and
Research (PGIMER), Chandigarh, India, and the Center
for Research on Ocular Therapeutics and Biodevices,
Storm Eye Institute, Charleston, SC, USA. This study
comprised 278 eyes of 263 patients having ECCE and
318 eyes of 297 patients having phacoemulsification with
PC IOL implantation. Posterior capsule opacification
leading to a decrease in Snellen visual acuity of 2 or more
lines was considered visually significant. The presence
of PCO and IOL haptic fixation were evaluated
postoperatively using slit lamp biomicroscopy. Haptic
position was noted as in-the-bag (B-B), 1 haptic in the
bag and 1 in the sulcus (bag-sulcus [B-S]), or both haptics
out of the bag (sulcus-sulcus [S-S]). In addition, the rate
of visually significant PCO was compared among 3 IOL
biomaterials: poly(methyl methacrylate), silicone, and
hydrophobic acrylic. Visually significant PCO occurred
in 42.45 percent of eyes having ECCE and 19.18 percent
of eyes having phacoemulsification (P <.001, chi-square
test) after a mean follow-up of 2.4 years +/- 0.7 (SD). In
both groups, visually significant PCO was significantly
less in eyes with B-B fixation than in those with B-S or SS fixation (P <.001). The rate of visually significant PCO
in all eyes in the phacoemulsification group with B-B
fixation was low (11.90%) and was significantly lower in
eyes with a hydrophobic acrylic IOL (2.22%; P <.05, chisquare test). The results of this study suggested in-thebag PC IOL fixation is required to consistently reduce
the incidence of PCO. Thorough removal of lens
substance, including hydrodissection-assisted cortical
clean-up, and in-the-bag PC IOL fixation seem to be the
most important factors in reducing PCO, regardless of
surgical procedure or IOL type used. Intraocular lens
biomaterial and design also help prevent PCO.
Ravalico and associates81 studied an ideal capsulorhexis size that could able to reduce PCO incidence. These
authors retrospectively evaluated 107 patients who had
extracapsular cataract extraction with capsulorhexis and
capsular bag IOL implantation. The PCO site (central,
paracentral, and peripheral) and degree (mild, moderate,
and severe) were evaluated in relation to the capsulorhexis edge location relative to the IOL optic. Patients
were divided into three groups. Group 1: capsulorhexis
free edge located on the IOL optic for 360 degrees; Group
2: capsulorhexis free edge located asymmetrically on and
peripherally to the IOL optic; Group 3: capsulorhexis free
edge located peripherally to IOL optic for 360 degrees.
Each group was divided into two subgroups; one
received polyHema IOLs and the second, PMMA IOLs.
Results of this study have shown that, in Groups 1 and
2, the capsular transparency was higher than in Group 3
(P < .04). Central opacification percentage was lower in

Group 1 than in Groups 2 and 3 (P < .04). No statistically


significant differences between the polyHema and the
PMMA subgroups were seen. These authors concluded
that capsulorhexis with a slightly smaller diameter than
the IOL optic appears to be better than a large-size
capsulorhexis in reducing the incidence of PCO.
T. Akahoshi, MD, had reported his experience of
AcrySof IOL implantation in more than 17,000 human
eyes in Japan. The incidence of YAG capsulotomy had
been found to be 1.19 percent (207 out of 17,329) after 75
months of the follow-up period. Among the YAG treated
cases, 81.2 percent had an eccentric and incomplete
coverage of the lens optics by the anterior capsulorhexis
margin. In 8.2 percent of the cases, the anterior capsule
margin was on the optics edge and 10.6 percent was
completely outside. Long-term follow-up revealed that
the incidence of after cataract formation in AcrySof is
extremely low. The size and position of the CCC,
however, seems to be one of the most important factors
to reduce the YAG capsulotomy rate. (T. Akahoshi, MD
Clear corneal cataract surgery and AcrySof implantation. Presented in the ASCRS Symposium on Cataract,
IOL and Refractive Surgery, Boston, MA, April 28, 2001).
Pharmacological Prevention of PCO
Several experimental studies using intraocular infusion
of drugs like colchicine, methotrexate, retinoic acid and
5-fluorouracil (5-FU) had also been performed in animal
models to prevent PCO.19,76,77,82,83,91,92,95
We designed an intracapsular ring to prevent capsular
bag contraction and also to inhibit LECs proliferation and
metaplasia by sustained release of 5-FU. We prospectively studied the effects of the intracapsular rings
on the prevention of PCO by analyzing the postmortem
ocular specimens macroscopically and histologically. We
also evaluated the toxic effects of 5-FU on the corneal
endothelium, capsular bag and retina of the rabbits.72
Seventeen rabbits were divided into 3 groups: (i) six
rabbits (6 eyes) had phacoemulsification (PE) only
(control group); (ii) six rabbits (6 eyes) had PE with
implantation of an open loop hydrogel intracapsular ring,
(iii) five rabbits (5 eyes) had PE with implantation of ring
with sustained release of 0.25 g/hour of 5-FU for 9 days.
All eyes in the 3 groups were followed for 8 weeks before
enucleation. Assessment of capsular bag shrinkage,
positioning of the intracapsular ring and evaluation of
central and peripheral PCO for intensity and area were
done by stereomicroscopy from a posterior (MiyakeApple) view.2,53 Residual equatorial lens epithelial cells
were counted by the same observer in histological
sections. Transmission electron microscopy (TEM) of

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228 Section I: Cataract


cornea, capsular bag and retina was done to evaluate
the toxicity of 5-FU.
No significant difference was seen in the degree of
capsular bag shrinkage in the 3 groups. Decentration of
the intracapsular ring was seen in 2 eyes (1 each in group
2 and 3 respectively). A statistically significant difference
(p <0.05, Student T test) was obtained between the
control group and eyes with intracapsular ring, concerning the area and intensity of central PCO. No difference
was seen between the latter and the group with rings
releasing 5-FU. No evidence of toxicity of 5-FU to
intraocular structures (cornea, capsular bag and retina)
was demonstrated with TEM analysis. Our study
revealed that implantation of intracapsular ring may
prevent central PCO after cataract surgery by
mechanically blocking migration of lens epithelial cells
towards the central visual axis. The potential pharmacological effect of 5-FU for PCO prevention was not
demonstrated in this experimental study.72
The use of intracapsular tension rings to prevent PCO
and PCO-related capsular bag shrinkage has recently
been reported by several authors.44,45,52 Kugelberg and
co-workers44 examined after-cataract development and
eye growth in lensectomized newborn rabbits implanted
with open PMMA capsular tension rings of two different
sizes (7 mm and 10 mm). The wet mass of the aftercataract was measured at 3 months after surgery in eyes
with and without ring. A significant reduction in the wet
mass of the after-cataract was seen in the eye with 10
mm rings in comparison to those with the 7 mm rings or
the aphakic eyes.
Nishi and co-workers62,63 investigated the inhibitory
effect of a discontinuous capsular bend created by an
IOL with a band-shaped loop or a capsular tension ring
on migrating lens epithelial cells. The round form of the
open-circular loop of a PMMA IOL was changed to a
band-like shape, 1 mm wide and 0.2 mm thick. A capsular tension ring of the same shape with a diameter of 14
mm was also made. They implanted the IOL or the ring
into the capsular bag in 5 rabbit eyes after cataract
surgery. The same IOL with an unmodified haptic or a
conventional capsular tension ring was implanted in the
contralateral eye as a control. Gross and histopathological
examinations were performed in the enucleated eyes
after 8 weeks. LECs accumulation was seen at the
equatorial corner outside the IOL haptic or the ring, with
inhibition of LEC migration toward the center. In the
control eyes, LECs accumulated inside the haptic or ring,
forming a Soemmerings ring, showing markedly less
inhibition of LECs migration.
Hara and co-workers30,31 determined the efficacy of
an equator ring in maintaining the circular contour of
the capsular bag equator and the transparency of the

posterior capsule after crystalline lens extraction in 12


rabbit eyes. A flexible silicone ring was implanted in the
capsular bag in seven rabbit eyes. A 13.0 mm Sinskeystyle posterior chamber IOL was also implanted inside
the ring. Three other eyes received only equatorial rings
and two eyes received only IOLs. All eyes were followed
up for 3.5 months. The authors reported equatorial
distortion and severe PCO in 2 eyes that received only
the IOL. In nine (90%) of the 10 eyes implanted with the
rings, the circular contour of the equator was preserved,
and seven (70%) of these 10 eyes had transparent
posterior capsules.
Hashizoe et al33 also evaluated the efficacy of a flexible, silicone equator ring in maintaining capsular bag
integrity at the equator and transparency of the posterior
capsule, but using cynomolgus monkeys. The eyes were
followed for an average of 5.9 months. The ring
effectively maintained the circular contour of the capsular
bag and posterior capsule transparency. The authors
concluded that the equator ring is a promising device
for maintaining capsular bag integrity and minimizing
PCO after cataract surgery.
Nagamoto and Bissen-Miyajima 57 designed four
prototypes of rings for supporting and preserving the
postoperative integrity of the capsular bag, independently of IOL implantation following circular curvilinear
capsulorhexis (CCC). An open, PMMA ring, inserted
experimentally in cadaver eyes through a 3.5 mm
incision, adjusted well to various capsular bag sizes and
could be implanted with common IOL types. Although
some capsular shrinkage occurred, in general the
roundness of the capsular bag equator was preserved.
The control specimens with the IOL alone had capsular
shrinkage in areas that were not in contact with the
haptics, thus the capsular bag was deformed. The
untreated controls capsular bag (no ring, no IOL) folded
and lost their roundness.
An open-loop intracapsular ring has the advantage
of being implanted in the eye through a small incision.
We used intracapsular rings manufactured from a
hydrogel biomaterial, i.e. copolymer of hydroxy propyl
methacrylate (HPMA)-methylmethacrylate (MMA).
Recently flexible closed-loop equator rings manufactured
from silicone elastomer have also been investigated by
some authors.30,31 No study compared the efficacy of
open-loop, intracapsular hydrogel rings and silicone
rings in preventing PCO and capsular bag shrinkage.
Intraocular application of pharmacologic agents has
also been investigated by several authors as a means to
prevent PCO. 15,16,32,34,38,38 The idea is to selectively
destroy the LECs and avoid toxic side effects on other
intraocular tissues such as the sensitive corneal
endothelium. Most of the pharmacologic agents being

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Chapter 23: Update on Posterior Capsule Opacification 229


tested are used for cancer therapy (e.g. antimetabolites
as methotraxate, mitomycin, daunomycin, 5-FU,
colchicine, and daunorubicin), anti-inflammatory
substances, hypo-osmolar drugs, and immunological
means have also been investigated.
Published studies concerning the pharmacological
prevention of PCO were mostly cell culture and in vitro
experiments but some animal test results are also available. Hartmann et al32 and Sourdille and Ducournau93
reported the first clinical studies in patients using an
antimetabolite, daunorubicin, for PCO prevention,
nevertheless longer follow-up is necessary to evaluate
the long-term effect of this drug. Pharmacologic agents
in combination with a sustained drug delivery system
(SDDS) have been used by some authors.32,44 The idea is
to extend the intraocular delivery time to a longer period
and thereby avoid toxic intraocular drug levels by release
of a constant therapeutic drug concentration.
Solomon et al92as shown in a rabbit model that slow
release of 5-FU prevents toxic drug levels. The effect of
this antimetabolite on PCO reduction was significant in
comparison to the controls. Legler et al17 performed a
similar study with colchicine. Significant PCO reduction
was observed with no toxic side effects in the group with
the lowest colchicine concentration. In this study,44 the
SDDS had the shape of a wafer and was inserted in the
capsular bag without an IOL.
In our current in vivo study, the drug tested was 5-FU
and we found that the shrinkage of the capsular bag
diameter was less in groups 2 and 3 when compared to
group 1. However, this difference was not statistically
significant. This can probably be correlated with the
degree of peripheral PCO. There was no significant
difference in the intensity and area of peripheral PCO
among the 3 groups. Also, in our study the eyes were
followed-up only for 8 weeks. Due to the small numbers
of specimens in each group, we could not conclude that
the open intracapsular ring was not effective to prevent
the shrinkage of the capsular bag.
Gross evaluation of enucleated eyes using the
Miyake-Apple posterior view revealed that implantation
of an intracapsular ring prevented central PCO when
compared to control group (Figs 23.7 to 23.9). This correlates well with the results of Kugelberg and co-workers 44 concerning after-cataract and eye growth in
lensectomized newborn rabbits, and with the study
by Nishi and co-workers62,63 investigating the inhibitory
effect of a discontinuous capsular bend on migrating lens
epithelial cells.
In our aforementioned rabbit study,72 we also performed the counting of the equatorial LECs in histological
sections as reported by Ruiz et al82 We noticed that LECs

Fig. 23.8A: Intracapsular ring group; Gross photograph


obtained from behind (Miyake-Apple posterior view) showing
the presence of some lens epithelial cells with relatively clear
visual axis

Figs 23.8B and C: Photomicrographs taken from the right and


left sides of the capsular bag respectively. Note the mechanical
blockage due to the presence of the intracapsular ring (H and
E X100)

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230 Section I: Cataract

Fig. 23.9A: Intracapsular ring with 5-FU group; Gross


photograph obtained from behind (Miyake-Apple posterior
view). Note the clear visual axis

Figs 23.9B and C: Photomicrographs taken from the right and


left sides of the capsular bag respectively
Figs 23.7 to 23.9: Assessment of posterior capsule
opacification in the 3 groups in our in vivo rabbit study72

were significantly less in eyes with an intracapsular


ring (groups 2 and 3) when compared to the control
group (Figs 23.7 to 23.9). This could be explained by the
presence of the ring in the capsular bag not allowing the
central migration of the LECs, creating a barrier effect
(no space-no cell theory). Although in our study the
intracapsular ring with a round edge presented a barrier
effect, this was not able to completely prevent the central
migration of the residual regenerative cortex in some
eyes. Figure 23.8 shows an example of migration of
regenerative/retained cortex in one of the eyes in group
2 which underwent implantation of the intracapsular
ring. Future studies may be helpful to precisely address
the effect of squared-edged intracapsular ring on the
hindrance of PCO as several recent studies demonstrated
that square edged IOL optics offer a better barrier effect,
when compared to round edged IOL optics.
The antimetabolite 5-FU specifically acts on mitotic
cells by inhibiting the enzyme thymidylate synthetase.
Therefore, the postmitotic tissues of the anterior and
posterior chambers of the eye should not be affected by
the action of this antimetabolite and only the proliferative
activity of the LECs of the anterior capsule could be
affected by the sustained release of this drug. We could
not find any evidence of toxicity of 5-FU to the corneal
endothelium or retina with TEM analyses. We are aware
that the corneal endothelium in rabbit corneas, in contrast
to human, has a tremendous regenerative capacity. As
reported by Van Horn and co-workers,100 even if 50
percent of the central corneal endothelial cells are
destroyed by transcorneal freezing, within 10 days
sufficient cell division and migration occur to completely
repopulate the area of Descemets membrane denuded
of cells, and the corneal thickness returns to normal. Thus,
results regarding the toxicity of 5-FU to corneal
endothelial cells need to be interpreted with caution. In
human eyes, cells that do not rapidly replicate, such as
those of corneal endothelium, iris, ciliary body, and retina,
are supposed to be less sensitive to the drug. Except for
the lens epithelium, all structures within the anterior and
posterior chambers are post mitotic.
Our experimental study could not demonstrate an
additional effect of 5-FU for prevention of PCO when
compared to the mechanical effect provided by the
presence of the intracapsular ring. The 5-FU drug
delivery properties of the biomaterial were dependent
on the hydration of the polymer.15 The rate of 5-FU release
was calculated by the manufacturer (Corneal
Laboratories) according to a preliminary (in vitro) study15
and the peak (nontoxic) of 5-FU concentration for the
intraocular tissues as studied by Rootman and
associates.82 Based on these studies, 5-FU concentration

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Chapter 23: Update on Posterior Capsule Opacification 231

Fig. 23.10: Tabulation of Nd: YAG laser


capsulotomy rates on 8 different IOL types
between January 1988 up to 2001. These
are listed with the highest capsulotomy
rates below. Note that the 2 rigid optic
designs had the highest rates

Figs 23.11A to D: Hydrophobic acrylic IOLs had the lowest PCO formation and therefore the Nd: YAG laser posterior capsulotomy
rates. The lowest PCO rate was confirmed by gross and histological evaluation: (A) Human eye obtained postmortem, MiyakeApple posterior photographic technique of a single-piece hydrophobic acrylic optic/haptics (Alcon AcrySof) PC-IOL showing
a symmetric fixation and excellent centration. The surgical technique was excellent and there is virtually no retained/regenerative
material (Soemmerings ring). This obviously represents good cortical clean-up, and also suggests good biocompatibility with
minimal proliferation, (B) Histological evaluation shows the posterior capsule totally cell-free. The IOL optic is the empty space
between the capsules on the left (Massons trichrome stain, X200), (C) A 3-piece acrylic optic/PMMA haptics (Alcon AcrySof)
showing a good example of excellent cortical clean-up, and also suggesting good biocompatibility, with minimal cellular
proliferation, (D) Photomicrograph showing evidence of excellent cortical clean-up. The haptic site is the small round empty
space (right) in the equatorial fornix. Note how the regenerative cortical material is blocked at the square/truncated edge of the
IOLs optic (Massons trichrome stain, X100)

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232 Section I: Cataract

Figs 23.12A to D: The silicone optic IOLs showed less PCO scores: (A) Gross photograph from behind (Miyake-Apple posterior
photographic technique) demonstrating a single piece plate-haptic silicone IOL with large positioning holes. There is moderate
cell growth/proliferation (Soemmerings ring), but the posterior capsule behind the IOL optic remains clear, (B) Histological
evaluation shows how the Soemmerings ring grows above and behind the IOLs optic. Also note the extensive anterior capsule
opacification, commonly associated with this IOL design (Massons trichrome stain, X200), (C) Miyake-Apple posterior view of
a 3-piece silicone optic/prolene haptics PC-IOL (Allergan SI 30) with a small amount of Soemmerings ring, and incipient PCO
formation under the IOLs optic, (D) Histological evaluation shows the retained/regenerative cortical material (Soemmerings
ring) forms a membrane that grows into the visual axis (Massons trichrome stain, X100)

in the anterior chamber and capsular bag of the rabbits


was maintained at 1 g/ml during 7 days. According to
the manufacturer, the ring could be modified to contain
larger amounts of 5-FU, with eventually a better effect
on prevention of PCO. Nevertheless, additional studies
would be necessary to determine the effects of this
modification on ocular structures, with regards to 5-FU
toxicity.
In summary, according to our macroscopic and
histological evaluations, the presence of an intracapsular
ring seems to prevent central PCO after cataract surgery
by a mechanical effect. An open-loop intracapsular ring
can be implanted in the eye through a small incision and
offers a barrier effect preventing the central migration of
the LECs towards the posterior capsule. Associated

release of 5-FU might have an additional impact on the


inhibition of PCO, at least on central PCO, although this
could not be demonstrated statistically in our study.
Concerning the toxicity of the 5-FU release to the corneal
endothelium, no definitive conclusion can be drawn from
this study, on account of the proliferation capacity of
rabbit corneal endothelial cells. This fact raises concerns
on the applicability of this concept to the human eye.
ANALYSIS OF ND: YAG POSTERIOR
CAPSULOTOMY RATES
Complete analysis of our large series of eyes obtained
postmortem has helped us develop the above-mentioned
six factors that we believe greatly contributes to the

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Chapter 23: Update on Posterior Capsule Opacification 233

Figs 23.13A to D: A rigid PMMA lenses showed the highest scores, with higher levels of cellular proliferation and PCO
formation: (A) Miyake-Apple posterior view of a pseudophakic human eye obtained postmortem, showing a PMMA optic/
prolene haptics IOL with moderate Soemmerings ring formation. In this case the barrier effect created by the edge of the IOL
optic has retarded a significant growth of cells toward the visual axis, (B) Note the large Soemmerings ring on the right (dark
red stain), meaning extensive cellular proliferation (Massons trichrome stain, X200), (C) This PMMA IOL has extensive
Soemmerings ring formation. Note that the central PCO, seen here as a white membrane growing over the posterior surface
of the IOL optic, is derived from the Soemmerings ring, (D) Photomicrograph showing the enormous migration of cortical
material onto the posterior peripheral surface of the lens optic towards the visual axis (Massons trichrome stain, X200)

reduction of PCO. Furthermore, an analysis of Nd: YAG


laser posterior capsulotomy rates among 8 commonly
used intraocular lens models has led us to the optimistic
conclusion that the incidence of PCO is rapidly diminishing, especially at least in the industrialized world. Figure
23.10 shows the ranking of the Nd: YAG laser posterior
capsulotomy rates (%) for eight lens designs as of
December 2000, starting with the lens showing the lowest
percentage at the top and the highest rate at the bottom
(Fig. 23.10). Note that the four lenses with the lowest rates
ranging between 3.3 percent and 20.7 percent are modern
designs, mostly implanted after 1992 in contrast to the
four lenses with the higher rates ranging between 23.3
percent and 33.7 percent. These were all older designs,
already in the database prior to 1992. The difference in

the Nd: YAG laser rates between the acrylic IOLs and
the other IOL types was found to be statistically
significant (P < 0.05, for all comparisons, Chi square test).
The Nd: YAG laser rate of all 6 foldable IOLs collectively,
15.3 percent (170/1109), was significantly lower than the
rate of the rigid IOLs (Figs 23.11 to 23.13) (32.3%; 1722/
5316; P < 0.05, Chi square test). If one removes the
AcrySof IOL from the group, the rate noted amongst
the other foldable IOLs studied increases to 158/748
(21.1%). In order to evaluate the influence of lens quality
vs the influence of the surgical technique on the PCO/
Nd: YAG laser posterior capsulotomy rates, it is useful
to follow a trend-line over a long-term period. Under
optimal conditions, but not possible in this analysis, the
information should be viewed considering the age and

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234 Section I: Cataract

Fig. 23.14: Trend line of a theoretical intraocular lens showing the 3 possible courses with the
progression of the analysis in our Center

the duration of each implant. However, the dates of


implantation or the time between implantation and death
were difficult to determine, due to ethical considerations.
These variables are going to factor out over time as larger
numbers are obtained and the trend time line is
extended.
Tracking the trend time lines for each lens design
will be necessary to help rule out other factors in addition
to the duration of each implant in the eye (for example,
the quality of surgery) in order to properly assess the
differences among the IOLs (Fig. 23.14). Various
surgeons criteria for Nd: YAG laser capsulotomy (e.g.
aggressive, conservative) also play a role in the rate.

Nevertheless surgeons criteria, surgical technique, and


implant duration will become equalized as the number
of accessions and the duration of the study increases.
SUMMARY AND CONCLUSIONS
A major reduction of Nd:YAG laser capsulotomy rates
towards single digits is now available because of
application of these surgical factors and modern lenses at least in the industrialized world (Fig. 23.15). This will
obviously be of great benefit to patients in achieving
improved long-term results and avoidance of Nd:YAG
laser capsulotomy complications. Eradication of the
Nd:YAG laser procedure will help control what has been

60
50
40

PCO (%)

30
20
10
0
1980

1986

1990

1996

2000

YEAR
Fig. 23.15: Graph showing the decrease of PCO rates from 30-50 percent in the 1980searly 1990s, to approximately 25 percent in the middle 1990s and probably, as is strongly
suggested by our laboratory work, to less than 10 percent in the new millennium

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Chapter 23: Update on Posterior Capsule Opacification 235


the second most expensive cost to the US Medicare
System. This evolutionary process is now ongoing,
having begun in earnest and volume in approximately
1992 as the major shift towards better capsular surgery
and insertion of foldable IOLs through small incisions
occurred.
We believe analyzing human pseudophakic globes
obtained postmortem is helpful in understanding how
these various lenses are performing in relation to PCO.
To date one cannot precisely determine the relative
proportion or contribution of IOL design vs. surgical
techniques to the decrease of Nd:YAG laser rates
observed here, but this could be possible with continuing
analysis including annual updates and increasing
numbers of pseudophakic autopsy eyes. The tools,
surgical procedures, skills, and appropriate IOLs are now
available to eradicate PCO. Continued motivation to
apply the 6 factors noted in this article, the efficacy of
which have been further suggested in a recent study, will
help diminish this final major complication of cataractIOL surgery exactly fifty years after Ridleys first
encounter with this complication.
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delivery system: An experimental animal study and literature
review. J Cataract Refract Surg 1996; 22:1070-78.
96. Toldos JJM, Roig AA, Benabent EC. Total anterior capsule
closure after silicone intraocular lens implantation. J Cataract
Refract Surg 1996; 22:269-71.
97. Trivedi RH, Izak A, Werner L, Macky TA, Pandey SK, Apple
DJ. Interlenticular opacification of piggyback intraocular lenses.
Int Ophthalmol Clin 2001; 41:47-62
98. Tsuboi S, Tsujioka M, Kusube T, Kojima S. Effect of continuous
circular capsulorhexis and intraocular lens fixation on the bloodaqueous barrier. Arch Ophthalmol 1992; 110:1124-27.
99. Ursell PG, Spalton DJ, Pande MV. Anterior capsule stability in
eyes with intraocular lenses made of poly(methyl methacrylate),
silicone, and AcrySof. J Cataract Refract Surg 1997; 23:1532-38.
100. Van Horn DL, Sendele DD, Seideman S, Buco PJ. Regenerative
capacity of the corneal endothelium in rabbit and cat. Invest
Ophthalmol Vis Sci 1977; 16:697-13.
101. Werner L, Apple DJ, Pandey SK, et al. Analysis of elements of
interlenticular opacification. Am J Ophthalmol 2002;133:32026.
102. Werner L, Apple DJ, Pandey SK. Postoperative proliferation of
anterior and equatorial lens epithelial cells: A comparison
between various foldable IOL designs. In Buratto L, Osher R,
Masket S, (Eds): Cataract Surgery in Complicated Cases.
Thorofare, NJ, Slack, 2000; pp 399-417.
103. Werner L, Pandey SK, Apple DJ, Escobar-Gomez M, McLendon
L, Macky T. Anterior capsule opacification: Correlation of
pathological findings with clinical sequelae. Ophthalmology
2001; 108:1675-81.
104. Werner L, Pandey SK, Escobar-Gomez M, et al. Anterior capsule
opacification: A histopathological study comparing different
IOL styles. Ophthalmology 2000; 107:463-67.
105. Wilson ME, Pandey SK, Werner L, et al. Pediatric cataract
surgery: Current techniques, complications and management.
In Agarwal A, Agarwal S, Fine H, Sachdeva M, Agarwal A,
(Eds): Phacoemulsification, laser cataract surgery and foldable
IOLs. Slack Inc., Thorofare, NJ, USA, 2000, pp 369-88.

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238 Section I: Cataract

24

Pediatric CataractIOL Surgery:


Past, Present and Future
Suresh K Pandey, M Edward Wilson, Liliana Werner, David J Apple, Vidushi Sharma

INTRODUCTION
PEDIATRIC CATARACT
INTRAOCULAR LENS SURGERY:
PAST (1951 TO 1989-90S)
PEDIATRIC CATARACT
INTRAOCULAR LENS SURGERY:
PRESENT (1990S TO PRESENT)
PEDIATRIC CATARACT
INTRAOCULAR LENS
SURGERY: FUTURE

INTRODUCTION
Several advances for surgical management of childhood cataracts have
occurred in the last 2 decades owing to advances in microsurgical
techniques, availability of better ophthalmic viscosurgical agents and
appropriately sized and styled implants, suitable for small eyes. However,
surgeons continue to face the unique challenges posed by childrens eyes
(Fig. 24.1). This brief write-up is separated in 3 sections (section A, B and
C) to summarize the major past, present and future advancements in the
field of pediatric cataract surgery and intraocular lens implantation.
Interested readers can also refer to our recent video on this interesting
subject (Wilson ME, Pandey SK, Werner L, Apple DJ. Pediatric cataract
surgery: Past, present and future, Third Prize for Special Cases, Annual
Video Festival, XXth Congress of the European Society of Cataract and
Refractive Surgeons, Nice, France, September 2002).
PEDIATRIC CATARACTINTRAOCULAR LENS SURGERY:
PAST (1951 TO 1989-90S)
It is well-known that Sir Harold Ridley performed the first adult case of
intraocular lens implantation in November 1949 on a 46-year-old female
(Fig. 24.2).

Fig. 24.1: Pediatric cataract IOL surgery: The challenge

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Chapter 24: Pediatric CataractIOL Surgery: Past, Present and Future 239

Fig. 24.2: First cataract IOL surgery


(Sir Harold Ridley 1949-1950)

Fig. 24.3: Pediatric cataract IOL surgery: Past (insertion of a


Ridley lens in a child) Implantation of Ridley IOL in a 9-yearold child by Dr E Epstein, S Africa (June 26, 1952)

Fig. 24.4: Pediatric cataract


IOL surgery past (Insertion of
a Ridley lens in a child)

To the best of our knowledge, Dr Edward Epstein of


Johannesburg, South Africa implanted for the first time a
Ridley IOL in a child. He operated a 9-year-old child for
traumatic cataract in 1951 (Fig. 24.3). In one of his most
recent communications, Dr Epstein commented on the
fixation and centration of his first pediatric IOL (Fig. 24.4).
He metioned at first I thought that in those children with
the implant remaining central, that irrigation and aspiration
had not cleared all the equatorial lens substance which thus
favored a Soemmering ring that made a frame for the implant.
Later it suddenly dawned that the apices of the 4 anterior
capsular flaps created by the cruciate discission, pushed by the

swelling cortex had become adherent to the posterior surface of


the iris Amazing one did not think that was the way to go i.e.
in-the-bag, when implanting lenses. But remember in those
day microscopes were not used, viscous material not available
and the thinnest sutures were 6x0 ropes!!
Subsequently Dr Peter Choyce from England
implanted the Choyce Mark 1 intraocular lenses in the
right eye of an eight-year-old child. In a monograph on
intraocular lenses and implants published in 1964,
Dr Choyce mentioned In June, 1957 - i.e. only three months
after the original injurya 13 mm (thick haptic) anterior
chamber implant was inserted (Fig. 24.5).

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Fig. 24.5: Pediatric cataract


IOL surgery past (Insertion of
a Choyce lens in a child)

240 Section I: Cataract

Fig. 24.6: Pediatric cataractIOL surgery past (Insertion of a Choyce lens in a child)

Fig. 24.7: Pediatric cataractIOL surgery


past (Insertion of Sinskey lens in a child)

Some part of the surgical steps of the cataract surgery


and implantation of Choyce Mark 1 intraocular lens
performed by Dr. Choyce are shown in this Figure 24.6.
Dr Robert Sinskey, Dr David Hiles and others began
to implant posterior chamber lenses routinely in the
1980s. Dr Sinskey implanted the very flexible 3-piece
Sinskey style posterior chamber intraocular lenses after
performing the cataract surgery (Fig. 24.7).
Dr Marshall M Parks, Dr David Taylor and others
pioneered the use of primary posterior capsulectomy and
anterior vitrectomy for management of pediatric
cataracts in the late 70s and early 1980s. This mechanized
approach drastically reduced the need for repeated
surgeries nearly eliminating secondary membranes.
Implantation of intraocular lenses was not common

Fig. 24.8: Pediatric cataractIOL surgery


past (Posterior capsule management)

during this period. Therefore, the use of aphakic contact


lenses was the preferred method for correction of aphakia
in 1980s. Dr Wilson and more than 100 other fellows
over the years have learned this technique from Dr Parks
(Fig. 24.8).
PEDIATRIC CATARACTINTRAOCULAR LENS
SURGERY: PRESENT (1990S: TO PRESENT)
The last decade witnessed the considerable advances in
technology and microsurgical techniques in the field of

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Chapter 24: Pediatric CataractIOL Surgery: Past, Present and Future 241

Fig. 24.9: Pediatric cataractIOL surgery clinical and laboratory research at the Storm Eye Institute

Fig. 24.10: Pediatric cataractIOL surgery clinical and laboratory research


at the Storm Eye Institute

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242 Section I: Cataract

Fig. 24.11: Pediatric CataractIOL surgery clinical and laboratory research at the Storm Eye Institute
(Storm Eye Institutes Drs Suresh K Pandey, Liliana Werner, M Edward Wilson and David J Apple)

Fig. 24.12: Pediatric cataractIOL surgery present: Recommendations and guidelines

pediatric cataract surgery and intraocular lens implantation pioneered by several surgeons. During this time
implantation of an intraocular lens became common
place for correction of aphakia in children beyond their
second birthday.
Clinical and research studies done at the Storm Eye
Institute and elsewhere helped considerably to select the

most suitable technique for capsule management, the


selection of appropriate intraocular lens size, design and
biomaterial for children and infants (Figs 24.9 to 24.11).
Based on extensive clinical and research work done
in this subject at the Storm Eye Institute, our present
preferred cataractIOL surgical technique for infants
and children younger than 6 years - anterior capsule can

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Chapter 24: Pediatric CataractIOL Surgery: Past, Present and Future 243

Fig. 24.13: Pediatric cataractIOL surgery


multifocal IOL implantation

be opened manually, using a vitrector (termed as


Vitrectorhexis) or a bipolar radiofrequency diathermy
or by Fugo plasma blade. Aspiration of the lens substance
and complete cleaning of the capsular bag; performance
of a posterior capsulorhexis using vitrector, which is
termed as posterior vitrectorhexis, capsular bag fixation
of a single-piece hydrophobic lens through a small
incision using the injector. A primary posterior
capsulectomy and anterior vitrectomy may be helpful to

maintain a long-term clear visual axis, especially in


infants and children younger than 6 years of age. For
children older than 6 years with relatively less elastic
anterior capsule, a manual capsulorhexis, which remains
a gold standard, can safely be performed. Additionally,
a cortical cleaving hydrodissection can also be used (Fig.
24.12).
Management of the posterior capsule remains a
challenge due to very high rate of posterior capsule
opacification. Several techniques have been proposed for
posterior capsule management on pediatric cataract
surgery as shown in this slide. Dr Howard Gimbel from
Calgary, Canada proposed a technique of a posterior
capsulorhexis with optic capture for maintaining a clear
visual axis as shown in this video clip. This procedure is
technically challenging and opacification of ocular media
may occur even after the posterior capture of the
intraocular lens optic.
PEDIATRIC CATARACTINTRAOCULAR
LENS SURGERY: FUTURE
Pediatric cataract surgery in the future will be constantly
refined to facilitate visual outcome and to reduce the
postoperative complications. Pacing with adult cataract
surgical procedure, use of intraocular lenses implanted
through an ultrasmall incision, as well as implantation

Fig. 24.14: Pediatric cataractIOL surgery future: Restoration of accommodation

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244 Section I: Cataract

Fig. 24.15: Pediatric cataractIOL surgery future: Elimination of PCO

of the multifocal and accommodative lenses will


increasingly be used for children (Figs 24.13 and 24.14).
More research efforts are needed to understand some of
the crucial issue such as selection of the intraocular lens
power, incidence of postoperative glaucoma and
techniques to reduce the posterior capsule opacification.
Elimination of posterior capsule opacification and
restoration of accommodation are 2 major issues that
need to be addressed in near future. Solutions are being
developed that can potentially eliminate all residual
epithelial cells in the pediatric lens capsule. These substances may be delivered via a sealed capsule irrigation
device such as one pioneered by Dr Anthony Maloof
(Fig. 24.15).

SUMMARY
We attempted to summarize the evolution of pediatric
cataract surgery and the intraocular lens in this slide,
though it is impossible to mention all the advancements
in this field. Most of these advances has been one of the
most important achievements in modern ophthalmology.
The availability of refined and perfected microsurgical
techniques, ophthalmic viscosurgical agents and modern
foldable implants represent a major milestone in this
evolutionary process. With continued improvements in
surgical techniques, availability of multifocal and
accommodative lenses the refractive and visual outcomes
in pediatric cataract surgery will continue to improve in
this century.

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Chapter 25: Update on Delayed Postoperative Opacification of Rigid and Foldable Intraocular Lenses

245

25

Update on Delayed Postoperative


Opacification of Rigid and
Foldable Intraocular Lenses
Suresh K Pandey, Liliana Werner, Andrea M Izak, David J Apple

OVERVIEW
INTRODUCTION
SECTION I: DELAYED
OPACIFICATION OF PMMA IOL
OPTIC BIOMATERIAL:
SNOWFLAKE
OR CRYSTALLINE OPACIFICATION
SECTION II. OPACIFICATION OF
FOLDABLE HYDROPHILIC
ACRYLIC LENSES

OVERVIEW
Postoperative opacification of the foldable hydrophilic acrylic lens designs
is a major concern among surgeons, and manufacturers. The majority of
cases are reported from Asia, Australia, Canada, Europe, Latin America,
and South Africa. However, mostly in North America we have noted cases
of snowflake opacification of the rigid PMMA lenses, a new syndrome
of biodegradation of PMMA biomaterial. Our analysis of all 28 cases
showed that dense snowflake lesions were clustered in the central part of
the lens optic with the peripheral part largely unaffected behind the iris.
We classified the cases of snowflake opacification of the PMMA IOLs into
four grades according to density and the severity of the lesions. This entity
possibly attributed to breakdown of PMMA polymer within the
biomaterial. We have termed these lesions snowflake opacifications on
the basis of morphology. SEMs of the bisected IOL revealed that these
lesions were clustered in the anterior 1/3 of the optic substance and the
posterior 2/3s remained free.
We have also analyzed 3 major hydrophilic acrylic lenses, explanted
due to varying degree of IOL opacification, secondary to different patterns
of dystrophic calcification. These designs include the Bausch and Lomb
Hydroview, Medical Developmental Research- SC60B-OUV and
Ophthalmic Innovations International, Aqua-Sense. During the past 3
years, we have studied a total of 87 of the aforementioned opacified
explanted hydrophilic acrylic designs, which were sent to our laboratory
by surgeons worldwide. Clinicopathological studies done at our Center
confirmed that the opacification of the Hydroview lens appeared to be
due to dystrophic calcification on the anterior and posterior lens optic
surfaces. This was also confirmed by two different histochemical methods
as shown here. In the majority of the SC60B-OUV lenses, the opacification
was also due to precipitation of calcium and was histochemically
demonstrated within the substance of the optic biomaterial. Drs Dick and
Frohn from Germany attributed the opacification to degeneration of the
UV filtration material. Gross microscopic and histochemical examination
of the explanted Aqua-Sense lenses also revealed that opacification was
attributed to external and internal precipitation of calcium. Scanning
electron microscopic analyses of the external surfaces of Hydroviewa lens
designs confirm the presence of cerebriform deposits, as shown in the left

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246 Section I: Cataract


top, and left middle photographs. Deposits were present
within the optic substance or over its surface of an SC60BOUV and an Aqua-Sense lens, as shown in the middle
and right pictures. Spectroscopic analyses of cut sections
of the lens optic showed peaks of calcium and phosphate.
Together with surgeons, manufacturers, and scientists
worldwide, our laboratory is working to explore the etiopathogenesis of the miniepidemic of IOL opacification.
In numerous recent publications, we have discussed this
complication in detail and cautioned surgeons to be
vigilant for timely follow-up of patients implanted with
these lenses. To prevent the occurrence of lens opacification Bausch and Lomb, Medical Developmental
Research and Ophthalmic Innovations International,
modified the IOL packaging and/or changed the source
of IOL polymers. They now believe the problem is
resolved. However, final verification will require further
clinical study. In conclusion, possible guidelines for
prevention and management of IOL opacification are
listed here. The IOL explantation/exchange is currently
the only available treatment. Future clinical studies will
determine the efficacy of modifications performed on
polymers and packaging. Surgeons should remain
vigilant in careful follow-up of patients implanted with
these lenses.
INTRODUCTION
It has been over 50 years since Harold Ridleys first
implant and the cataract-IOL procedure has reached an
extraordinarily high level of quality and performance.
This has no doubt been one of the most satisfying
advances of medicine in the 20th Century. Millions of
individuals with visual disability or frank blindness from
cataracts have and continue to benefit from this

procedure. Modern refractive surgery is a first cousin or


spin-off of the techniques also preferred by anterior
segment surgeons. Continuous high tech innovations
now occurring assure that keratorefractive and phakic
IOL procedures are and will continue to provide a service
to many patients with significant ammetropia.
Since past 3 years, we have extensively studies the
opacified explanted rigid PMMA and foldable hydrogel
IOL (Pandey SK, Werner L, Apple DJ, Kaskaloglu MM,
Izak AM, Cionni RJ. Intraocular Lens Opacification,
Second prize in the category Intraocular Lenses at the
ASCRS/Alcon Annual Video Festival, Congress of the
American Society of Cataract and Refractive Surgeons,
Philadelphia, PA, USA, June 2002; Pandey SK, Werner
L, Apple DJ, Kaskaloglu MM, Izak AM, Cionni RJ.
Intraocular Lens Opacification, Third prize for Scientific
Value at the ESCRS/Alcon Annual Video Festival,
Congress of the European Society of Cataract and Refractive Surgeons, Nice, France, September 2002; Pandey SK,
Werner L, Apple DJ, Kaskaloglu MM, Izak AM, Cionni
RJ. Intraocular Lens Opacification, Opacification, Opacification, Best-of-Show video award, Annual Meeting of
the American Academy of Ophthalmology, Orlando,
Florida, USA, October 2002).
In this write-up we will be discuss striking and often
visually disabling opacifications occurring on IOL optics,
both on some modern foldable IOLs as well as a PMMA
IOL optic degradation occurring with some models a
decade or more after implantation (Fig. 25.1). Many of
the complications we will discuss here are totally
unexpected and unnecessary vision-threatening and
sometimes blinding IOL opacificationscomplications
that we should not have to concern ourselves within our
current advanced stage in the evolution of the cataract-

Fig. 25.1: Opacification of rigid and foldable lenses

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Chapter 25: Update on Delayed Postoperative Opacification of Rigid and Foldable Intraocular Lenses
IOL procedure. Some of these are occurring because
many surgical procedures today are often performed
outside the realm of supervision and oversight of both
non-governmental and governmental authorities such as
the Food and Drug Administration.
This chapter is divided in 2 sections; in section A, we
will address a newly described clinical condition caused
by an unexpected late opacification of PMMA, that we
termed as snowflake opacification or degeneration of
polymethyl methacrylate (PMMA) posterior chamber
IOL optic biomaterial. In section 2, we will discuss the
clinicopathological studies of explanted opacified
foldable lenses manufactured from hydrophilic acrylic
biomaterial.
SECTION I: DELAYED OPACIFICATION OF PMMA
IOL OPTIC BIOMATERIAL: SNOWFLAKE
OR CRYSTALLINE OPACIFICATION
Over the past 50 years PMMA has been rightly considered a safe, tried and true material for IOL manufacturing with good and high quality control. PMMA
biomaterial was used as an optic biomaterial in Sir
Harold Ridleys original IOL, manufactured by Rayner
Intraocular Lenses Ltd, London, UK, and first implanted
in 1949-1950.1 Although surgeons in the industrialized
world and in selected areas in the developing world have
largely transitioned to foldable IOL biomaterials, PMMA
does remain in widespread use in many regions.
Biomaterial studies on PMMA IOL optics were rarely
required. Until now, any untoward complications such
as PMMA-optic material alteration/breakdown have not
been seen with this material and its fabrication.
However, we have recently reported gradual but
progressive late postoperative alteration/destruction of
PMMA optic biomaterial causing significant decrease in

247

visual acuity, sometimes to a severity that requires IOL


explantation (Fig. 25.2). The first clinical case of the type
that we observed was a documentation of photographs
sent to us by David Davis, MD, of Hayward, CA, in 1993.
He noted crystalline formations in 7 IOPTEX Research
(Azuza, CA) 3-piece PMMA IOLs. Over the past 4 years,
25 cases including 9 explanted IOLs were submitted to
Center for Research on Ocular Therapeutics and Biodevices (Fig. 25.2).2,3
All of the explanted IOLs were 3-piece posterior
chamber (PC)-IOLs with rigid PMMA optical components and blue polypropylene or extruded PMMA
haptics. These had been implanted in the early 1980s to
early 1990s in most cases and the clinical symptoms
appeared late postoperatively, ca. 8-15 years after the
implantation. The clinical, gross, light and electron
microscopic profiles of all the cases showed almost
identical findings, differing only in the degree of intensity
of the snowflake lesions that in turn reflected the
severity and probably the duration of the opacification.
In the early stages of many of the cases, the lesions were
first noted clinically by a routine slit lamp examination,
in the absence of visual disturbances. Most examiners
described the white-brown opacities within the IOL
optics as crystalline deposits (Fig. 25.3). They appeared
to progress gradually in most cases. Clinically, the slowly
progressive opacities of the IOL optics usually start as
scattered white-brown spots within the substance of the
IOL optic. These usually do not have an impact on the
patients VA. They gradually increase in intensity and
number, eventually reaching a point where the VA loss
necessitates removal or exchange of the IOL. In addition
to visual loss the symptoms included decrease in contrast
sensitivity and various visual disturbances and aberrations, including glare. Figure 25.3 presents the classification of snowflake lesions as proposed by Apple and
associates.2,3

Fig. 25.2: Opacification of rigid and foldable lenses

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248 Section I: Cataract

Fig. 25.3: Classification of snowflake lesion

Clinicopathological Study of Explanted Lenses


The opacities of the IOL optics may start as scattered
white-brown spots within the substance of the IOL optic
and remain stable or slowly progressive. Some may
gradually increase in intensity and numbers, eventually
reaching a point where a visual acuity loss may
necessitate removal or exchange of the IOL. In addition
to visual loss the reported symptoms included decrease
in contrast sensitivity and various visual disturbances
and aberrations, including glare. In early stages there was
usually no effect on Snellen visual acuity but a gradual
decrease of visual acuity was noted in the late stage of
the process. Associated systemic disorders were not

described. Metabolic imbalances have not been


implicated as pathogenetic factors. Because the lesions
invariably appeared years later in a very late postoperative period there is almost certainly no direct
connection between the opacities and substances used
intraoperatively. In the examinations we performed to
identify the nature of the deposits, including energy
dispersive spectroscopy (EDS) we did not document any
exogenous chemicals apart from elements present in
PMMA itself (carbon, oxygen).
High power three-dimensional light microscopy (Fig.
25.4, top left) and SEM (Fig. 25.4 top middle) of the
surfaces of bisected IOL optics were the most informative
examinations with regard to determining the structure

Fig. 25.4: Snowflake lesions of PMMA IOL: Microscopic, ultrastructural studies

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Chapter 25: Update on Delayed Postoperative Opacification of Rigid and Foldable Intraocular Lenses
of the opacifications. The term snowflake applies best
to the clinical and low power microscopic appearance of
each lesion (Fig. 25.4, top left). High power examination
revealed that the lesions are spherical or stellate, the
shape depending on the contour of the surrounding
pseudocapsule (Fig. 25.4). The interior of the sphere does
not appear to contain fluid.
To date there have not been any clinicopathologic
reports on this complication nor any hypotheses regarding its pathogenesis. We suggest that manufacturing
variations in some lenses fabricated in the 1980searly
1990s may be responsible. It is possible that the late
change in the PMMA material process is facilitated by
long-term ultraviolet (UV, solar) exposure. This is
supported by 2 pathologic observations. First, many
opacities have been indeed clustered in the central zone
of the optic, extending to mid-peripheral portion but
often leaving the distal peripheral rim free of the
opacities. This observations would support the hypothesis that the slow and sometimes progressive lesion
formation noted here might relate to the fact that the IOLs
central optic is exposed to ultraviolet radiation over an
extended period, whereas the peripheral optic may be
protected by the iris. Furthermore, the opacities are
present most commonly and intensely within the anterior
1/3 of the optics substance (Fig. 25.4, bottom). Since the
anterior strata of the optic are the first to encounter the
ultraviolet light, this might explain why the opacities are
seen more frequently in this zone.
Since it is plausible the lesions may be ultravioletinduced, and it is highly unlikely that non-porous PMMA
allows an entrance of aqueous into the optic substance,
we postulate that the lesions are dry and that the
PMMA disruption might be related to a specific manufacturing problem that eaves the optic susceptible to
damage.
PMMA is manufactured by polymerization of the
MMA monomer. This manufacturing process utilizes
many different polymerization techniques, and various
components such as UV absorbers and initiators.
Therefore various impurity profiles are possible. An
initiator substance starts such process. A frequently used
initiator is azo-bis-isobutyryl nitrile (AIBN).4-6 It is
possible that UV radiation is a contributing factor,
however, the exact pathogenesis can as of now only be
hypothesized. Potential causes of a snowflake lesion
include (1) insufficient post-annealing of the cured
PMMA polymer; (2) excessive thermal energy during
the curing process leaving voids in the polymer matrix;
(3) non-homogeneous dispersement of the UV chromophore and/or thermal initiator into the polymer chain;
(4) poor filtration of the pre-cured monomeric compo-

249

nents (MMA, UV blocker, thermal initiator). Another


possible pathogenic factor could be an inadvertent use
of excessive initiator substance during the polymerization process that may facilitate the formation of the
snowflake lesions. The N=N bond of the AIBN initiator
may be disrupted by gradual UV exposure with a release
of nitrogen gas (N2). Such gas formation can be caused
by either heat or UV light exposure. Indeed the normal
polymerization process for PMMA synthesis consists in
part of a heat-induced N2 formation as a byproduct.
During normal polymerization the N2 escapes from the
mixture. However, with a poor manufacturing process,
for example using excessive initiatormore than the
fractional amount requiredunwanted initiator may be
entrapped in the PMMA substance. Slow release of
gaseous N2 within the PMMA substance trigged by longterm UV exposure would explain the formation of the
cavitations within the snowflake lesions. The outer
pseudocapsule might consist of PMMA, whereas the
central space contains the N2 gas admixed with convoluted material also possibly consisting of degenerated
PMMA. There is nothing in the molecular structure of
the PMMA that in and of itself could be compressed to
form such an expansile material that might create the
round circular cavitations of the snowflake lesions.
These hypothetical mechanisms have the potential to
form micro-heterogeneity within the PMMA polymer
that, overtime and potentially with exposure to UV
radiation, could result in a lesion within the polymer.
Additional experimentation is necessary to determine if
any of these proposed mechanisms for the formation of
a snowflake lesion are realized.
Awareness of this delayed complication may be
warranted in developing countries, where PMMA IOLs
are still used in the majority of cases. Virtually all IOLs
manufactured today appear to be satisfactory. However,
one should always be aware that some early IOLs from
American manufacturers, including some described in
this report, have been delivered to the developing world
over the years, sometimes implanted without regard to
expiration dates on the packaging. It would be very
unfortunate to see this complication showing up in
underprivileged areas where patients have almost no
recourse to treat visual loss/blindness of this type.
The emergence of this complication could have
represented a true disaster, except for the fact that many
of the patients implanted with these IOLs are now
deceased. However, there are probably still sufficient
number of patients living with varying stages of this
complication. This necessitates that todays ophthalmologists to be aware of, to diagnose, and to know when
not to explant and/or exchange these lenses. It is

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250 Section I: Cataract


important to know the nature of this syndrome in order
to spare by now elderly patients and their doctors
unwarranted anxiety about the cause of his or her visual
problems/loss and also to obviate request for unwarranted diagnostic testing.
SECTION II. OPACIFICATION OF FOLDABLE
HYDROPHILIC ACRYLIC LENSES
Introduction
Foldable hydrophilic acrylic intraocular lenses (IOLs),
also known as hydrogel lenses are not yet available in
the United States but have been marketed by several
firms for several years in international markets. Most of
the currently available hydrophilic acrylic lenses are
manufactured from different copolymers acrylic with
water contents raging from 18 to 28 percent, and an
incorporated UV absorber.6,7 They are packaged in a vial
containing distilled water or balanced salt solutions, thus
being already implanted in the hydrated state and in their
final dimensions. Hydration renders these lenses flexible,
enabling the surgeons to fold and insert/inject them
through small incisions. Many surgeons have adopted
the use of hydrophilic acrylic IOLs because of their easierhandling properties and biocompatibility.8,9 Although
hydrophilic surfaces have been shown to lower the

inflammatory cytological response to the IOL,9 some


currently available hydrophilic acrylic IOL designs have
been associated to reports on late postoperative opacification caused by calcium precipitation.10-35 Postoperative opacification of the foldable hydrophilic acrylic lens
designs is a major concern among surgeons, and
manufacturers. The majority of cases are reported from
Asia, Australia, Canada, Europe, Latin America, and
South Africa.
We describe in this chapter the analyses performed
in our laboratory on hydrophilic acrylic lenses of 3 major
designs during past 3 years (Fig. 25.5). They were all
explanted because of whitish discoloration of the optic
component, or of the whole lens, related to different
forms and degrees of dystrophic calcification (Werner L,
Apple DJ, Pandey SK. Late postoperative opacification
of hydrophilic intraocular lens designs; presented at the
ASCRS Symposium on Cataract, IOL and Refractive
Surgery, Best Paper of the Session, San Diego, CA, April
28, 2001; Werner L, Apple DJ, Pandey SK, Izak AM, et al.
Ground glass opalescence of hydrophilic acrylic
intraocular lenses; poster presented at the Annual
Meeting of American Academy of Ophthalmology, New
Orleans, LA, November 11-14, 2001; Pandey SK, Werner
L, Apple D, Kaskaloglu MM, Izak AM, Cionni RJ.
Intraocular Lens Opacification, Opacification,
Opacification, Second prize in the category Intraocular

Fig. 25.5: Hydrogel lens designs presented with delayed postoperative opacification

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251

Fig. 25.6: HydroviewTM IOL: microscopic and histochemical evaluation

Lenses at the ASCRS/Alcon Annual Video Festival,


Congress of the American Society of Cataract and
Refractive Surgeons, Philadelphia, PA, USA).
Bausch and Lomb: Hydroview (H60M)
The first group of explanted hydrophilic acrylic lenses
analyzed in our Center because of whitish discoloration
was represented by the Bausch and Lomb Surgical (Rochester, NY) HydroviewTM IOL (Figs 25.5 and
25.6).13-18 The optic material of these IOLs is composed
of a cross-linked copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate, with a bonded
benzotriazole-type UV absorber. The water content of
this material is 18 percent and the refractive index is
1.474. The haptics are modified C loops made of bluecolored PMMA, polymerically cross-linked with the
optics by means of an interpenetrating polymer network,
which provides a one-piece design with a true optic zone
of 6.0 mm. This IOL design has been implanted for several
years in international markets; over 400,000 have been
implanted worldwide. However, although it was cleared
for marketing in November 1999 by the United States
Food and Drug Administration (FDA), it has not yet been
launched for general implantation in this country.
Starting in November 1999, we have received in our
Center 25 explanted HydroviewTM lenses for pathological
analyses.13-18 In each case, the lens has been explanted
due to the presence of a granularity on its optical surfaces
associated with decrease in visual acuity and glare, in
the late postoperative period. At the time of explantation,

the age of the 25 patients ranged from 54 to 92 years (75.65


8.57). Two patients were in treatment for
cardiovascular diseases, 4 were diabetic and the others
were otherwise healthy. The lenses were explanted from
4 to 40 months postoperatively (24.42 10.18) after the
primary procedure due to opacification observed at the
level of the optics, associated with decrease in visual
acuity (from 20/20 after the primary procedure to hand
movements in some cases) and significant glare. In only
two cases, the lens was explanted earlier than one year
after the primary procedure (4 and 10 months). The
surgeons described the findings as a brown granularity
or small red corpuscles present on both external optical
surfaces of the lenses (Fig. 25.5, top left). In some cases,
the optic of the lenses was almost completely covered
by those structures, giving them a frosty and very
reflective appearance. Nd: YAG laser was performed in
many cases in an attempt to clean the optical surfaces,
without success.
Medical Developmental Research: SC60B-OUV
In the second group described here, the hydrophilic IOL
to be recently associated with clinically significant
postoperative optic opacification is the SC60B-OUV
lens (Figs 25.5, middle, and 25.7). The manufacturer and
distributor of this design is Medical Developmental
Research (MDR Inc., Clearwater, FL). The material used
for the manufacture of these IOLs is composed of a crosslinked copolymer of poly 2(hydroxyethyl methacrylate)
(HEMA) and methyl methacrylate (MMA), with an

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252 Section I: Cataract


incorporated UV absorber. The water content of this
material is 28 percent and the refractive index is 1.46.
This is a one-piece design, so the haptics are manufactured from the same material as the optical component.
Since 1999 we analyzed 54 explanted SC60B-OUV
IOLs manufactured by MDR in our Center.26-29 All of the
lenses were explanted because of late postoperative
opacification of the optic associated with decreased
visual function. At the time of explantation, the ages of
the patients ranged from 63 to 82 years (71.00 6.49). Six
patients were diabetic, but the majority of the patients
did not have any known associated systemic or ocular
conditions. The lenses were explanted from 7 to 32
months postoperatively (19.63 7.63). In only two cases,
the lens was explanted earlier than one year after the
primary procedure (7 and 9 months). In general, the
patients returned at around 12 months and later after
the surgery complaining of a significant decrease in
visual acuity (from 20/20 after the primary procedure
to 20/200 in some cases). The clinical characteristics of
these lenses were different from the previously described
granularity covering the optical surfaces of the
Hydroview design. The clinical appearance of the
SC60B-OUVTM lenses was that of a clouding similar to a
nuclear cataract (Fig. 25.5, middle).
Ophthalmic Innovations International,
Inc.: Aqua-Sense
The third recent group of hydrophilic acrylic designs we
analyzed in our Center because of whitish discoloration

were explanted Aqua-Sense lenses, manufactured by


Ophthalmic Innovations International, Inc., (OII),
Ontario, CA, USA (Figs 25.5, right, and 25.8).34,35 This is
also a one-piece lens, all manufactured from the same
material, a hydrophilic acrylic copolymer with incorporated UV absorber. The material has a refractive index
of 1.46 and a water content of 25 percent. Although
whitish discoloration was showed with all of the 3
designs, the intensity of the phenomenon with the AquaSenseTM is different. The opacity of the lenses available
to us for analyses was much more severe than that
associated with most cases of the 2 above-mentioned
designs.
Since the beginning of 2001, we received 8 AquaSense lenses in our laboratory.34,35 At the time of
explantation, the age of the 8 patients from this group
ranged from 25 to 78 years (58.29 16.85). Three patients
were diabetic, the others were otherwise healthy. The
lenses were explanted from 4 to 14 months postoperatively (10.33 5.51) after the primary surgery. In only
one case, the lens was explanted earlier than one year
after the primary procedure (4 months). The visual acuity
of the patients in general decreased from 20/20 to 20/60
after the primary procedure, with significant associated
glare. The clinical appearance of the Aqua-Sense lenses
was also that of a clouding similar to a nuclear cataract
(Fig. 25.5, right). As with the two above-mentioned
designs, Nd: YAG laser was performed in some cases in
an attempt to clean the optical surfaces, without
success.

Fig. 25.7: SC60B-OUV IOL: Microscopic and histochemical evaluation

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253

Fig. 25.8: Aqua-sense IOL: microscopic and histochemical evaluation

Clinicopathological Analyses
The explanted hydrogel IOLs were submitted by several
ophthalmic surgeons from various countries (Australia,
China, Sweden, Egypt, Germany, South Africa, Turkey,
UK, and others) for pathological analysis. Once received
in our Center, the IOLs were immediately placed in 4
percent formaldehyde in 0.1 M phosphate buffer, pH 7.4.
Care was taken to avoid any manipulation of the IOLs
optics with forceps or other grasping instruments. Some
lenses were bisected for explantation, and only one half
of them were available to us.
Gross (macroscopic) analysis of the explanted IOLs
was performed and gross pictures were taken using a
camera (Nikon N905 AF, Nikon Corporation, Tokyo,
Japan) fitted to an operating microscope (Leica/Wild
MZ-8 Zoom Stereomicroscope, Vashaw Scientific, Inc.,
Norcross, GA, USA). The unstained lenses were then
microscopically evaluated and photographed under a
light microscope (Olympus, Optical Co. Ltd., Japan).
They were rinsed in distilled water, immersed in a 1
percent alizarin red solution (a special stain for calcium)
for 2 minutes, rinsed again in distilled water and
reexamined under the light microscope.35-38
We then performed full thickness sections through
the optic of the explanted lenses. Some of the resultant
cylindrical blocks were directly stained with 1 percent
alizarin red. The others were dehydrated and embedded
in paraffin. Sagittal sections were performed and stained
using the von Kossa method for calcium (staining with
nitrate solution for 60 minutes; exposure to a 100-watt

lamp light; rinsing with distilled water; reaction with


sodium thiosulfate solution for 2 minutes; rinsing with
distilled water; counterstaining in nuclear fast red
solution for 5 minutes). Calcium salts stain in dark brown
with this technique.35-38
Some lenses in each group were air-dried at room
temperature for 7 days, sputter-coated with aluminum
and examined under a JEOL JSM 5410LV scanning
electron microscope (SEM). The specimens were then
further analyzed by Dr. D. G. Dunkelberger (Electron
Microscopy Center of the University of South Carolina,
Columbia, SC) under a Hitachi 2500 Delta scanning
electron microscope equipped with a Kevex X-ray
detector with light element capabilities for energy
dispersive X-ray analyses (EDS).
Incisional biopsies of conjunctiva and iris were also
obtained from one patient during removal and exchange
of a HydroviewTM IOL.18 This was done in order to rule
out the presence of dystrophic calcification in those
tissues.
Gross and Light Microscopic Analyses
Figures 25.6 to 25.8, summarized the gross, microscopic
and histochemical findings in 3 different types of opacified explanted foldable hydrophilic lenses manufactured
by the Bausch and Lomb, MDR and OII Inc., respectively.
By gross and microscopic evaluations, the presence of
granular deposits on the optical surfaces of the
Hydroview lenses was noted to cause different degrees
of IOL haze/opacification, directly proportional to the

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254 Section I: Cataract


amount of deposits and the surface of the lenses covered
by them. In some cases, both optical surfaces were almost
completely covered by a confluent granular layer,
whereas in other cases some intervening clear areas were
observed. Also, intervening clear areas, probably corresponding to marks caused by forceps during the folding
process, were observed in all lenses.
The optical surfaces and the haptics of the SC60BOUV lenses were in general free of deposits. However,
there were multiple small structures initially noted to
resemble glistenings within the central 5-mm of the
IOL optical component. These were found to be the cause
of each lens opacification. The edges of the optics and
the haptics appeared clear in the majority of the cases.
However, in one cases, the entire optical component and
the haptics were completely opaque (Pandey SK, Werner
L, Apple DJ, Kaskaloglu MM, Anand N, Izak AM, et al.
Different patterns of calcium precipitation in the optic
and haptics of foldable hydrophilic acrylic lenses;
presented at the ASCRS Symposium on Cataract, IOL
and Refractive Surgery, San Diego, CA, April 28, 2001).29
Light microscopy demonstrated that the opacification
was caused by the presence of multiple granular deposits
within the optic component of the lenses, sometimes
extending to the haptics.
All of the Aqua-Sense lenses were completely
opacified, presenting a bright whitish discoloration.
Multiple, small granular deposits were observed on the
external surfaces of the lenses, and also within their
substance.
Multiple pits related to Nd: YAG laser treatments
were also observed on the posterior surface of some of
the IOLs in each group.
Histochemical Stainings
The deposits on the surfaces of the Hydroview IOLs
stained positive with alizarin red in all cases (Fig. 25.6).
No positive staining was observed on the haptics of the
IOLs. Sagittal histological sections through the optic of
this lens design, stained using von Kossas method
showed a continuous layer of dark brown, irregular
granules on the anterior and posterior optical surfaces,
and the edges of the lenses (Fig. 25.6). Histochemical
evaluations of the conjunctival and iris biopsies obtained
from one of the patients were negative.
Alizarin red staining of the surfaces of the SC60BOUV lenses was in general negative. Analysis of the
cut sections (sagittal view) of the lens optics revealed
multiple granules of variable sizes in a region beneath
the external anterior and posterior surfaces of the IOLs.
The granules were distributed in a line parallel to the
anterior and posterior curvatures of the optics. They
stained positive with alizarin red (Fig. 25.7). Sagittal

histological sections stained with the von Kossa method


also confirmed the presence of multiple dark brown/
black granules mostly concentrated in a region immediately beneath the anterior and posterior optical surfaces
(Fig. 25.7).
Staining with alizarin red revealed spots of granular
deposits on the external surfaces of the Aqua-Sense
lenses (Fig. 25.8). In some cases, a fine granularity was
covering the lenses external surfaces. Analysis of cut
sections (sagittal view) of the lens optic revealed multiple
granules of variable sizes in a region beneath the external
anterior and posterior surfaces of the IOLs. As with the
previous lens design, the granules were distributed in a
line parallel to the anterior and posterior curvatures of
the optics and they stained positive with alizarin red and
the von Kossa method (Fig. 25.8).
Scanning Electron Microscopy
Figure 25.9, summarized the ultrastructural findings in
3 different types of opacified explanted foldable hydrophilic lenses manufactured by the Bausch and Lomb,
MDR and OII Inc., respectively. The aspect of the 3 lens
designs observed under light microscopy was confirmed
by SEM. Analyses of the anterior optical surfaces of some
Hydroview lenses revealed granular deposits composed of multiple spherical-ovoid globules, scattered in
some areas, and confluent in others (Fig. 25.9). SEM
analysis of cut sections (sagittal view) of the optic of some
SC60B-OUV lenses confirmed that the region immediately subjacent to the IOLs outer surfaces as well as
the central area of the optical cut sections were free of
deposits. This also revealed the presence of the granules
in the intermediate region beneath the anterior and
posterior surfaces (Fig. 25.9). With the Aqua-Sense
lenses, SEM of the anterior surface revealed the presence
of small granular deposits (Fig. 25.9). Analyses of cut
sections of this lens design demonstrated features similar
to those described with the SC60B-OUV lens (Fig. 25.9).
Energy Dispersive X-Ray Spectroscopy
With the 3 lens designs, EDS performed precisely on the
deposits revealed the presence of calcium and phosphate
peaks (Fig. 25.9). EDS was also performed on areas free
of deposits to serve as controls, showing only peaks of
carbon and oxygen (Fig. 25.9).
Possible Factors Involved in the
Pathological Mechanism
We can divide the phenomenon of crystalline deposition
on IOL optics into 2 general time frames: intra or shortly
postoperative versus late postoperative (circa 12 months).

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255

Fig. 25.9: Opacified hydrogel lenses:


ultrastructural evaluation

Jensen et al39 in 1994 first described the formation of


crystalline deposits on the surface of IOLs during cataract
surgery in a series of 11 patients. The deposits would
last a long time (at least 6 months) if sequestered by the
posterior capsule, and they had a significant effect on
the visual acuity (20/40 or worse). The common features
in all cases were the use of Healon GV (PharmaciaUpjohn Ophthalmics, Kalamazoo, MI, USA), a high
molecular-weight hyaluronate sodium, and BSS or BSS
Plus (Alcon Surgical Inc, Forth Worth, TX, USA). The
authors hypothesized that the phosphate components
used in the viscoelastic preparations to buffer the solution could have reacted with calcium from irrigating
solutions or the aqueous humor of the patients, and
precipitated. Nevertheless, no analysis of the deposits
was performed. Although they were also noted on
PMMA IOLs, the severe cases were all associated with
silicone lenses, suggesting that silicone is a better
substrate for this phenomenon. The same group described later 22 other cases of intraoperative crystallization
on IOL surfaces.39,40 Again, all the severe cases were
associated with silicone lenses, but viscoelastics other
than Healon GV have also been used. In these studies,
a sample of the material was submitted to scanning
electron microscopic analysis and X-ray photoelectron
spectroscopy, for elemental identification. The cation of
concern was found to be calcium.
Crystalline precipitation on the surface of hydrogel
lenses with water content higher than Hydroview

lenses (Iogel 1103, Alcon Laboratories, Fort Worth, TX,


USA) was first described by Amon and Menapace in
1991.42,43 They evaluated in vivo the surfaces of 200
consecutive IOLs over a 1.5-year postoperative period.
In their study, the presence of few, dust-like white precipitates of unknown origin on the surface of 7 percent of
the lenses were described. Nevertheless, no comment was
made on the time of presentation and the evolution of
the deposits.
Bucher et al44 in 1995 reported a case of dystrophic
calcification of the same hydrogel IOL, in an 80-year-old
woman with chronic lymphatic leukemia. On the first
postoperative day, a brown-white material was observed
behind the IOL. During the second postoperative month,
the material turned white and changed its shape. Two
months after the surgery, granular whitish spots appeared on the anterior surface of the IOL. Their confluence
with time formed a band-shaped white layer on the
anterior optic surface. White granules also developed in
the corneal stroma at the site of a paracentesis, but not at
the incision. The lens was explanted due to decreased
visual acuity. Special staining and surface analyses
revealed the material to contain calcium hydroxyapatite.
Intraocular solutions used during the surgery in this case
were Ringers lactate with epinephrine, sodium hyaluronate as viscoelastic and thymoxamine, which is a
phosphate-buffered solution used to achieve miosis.
Although the patient had chronic lymphatic leukemia,
no disturbance of calcium metabolism was detected and

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256 Section I: Cataract


the electrolyte levels were normal on several occasions
before and after the development of calcification. The
authors hypothesized that an oversupply of calcium,
from residual lens material, and of phosphates, from the
thymoxamine solution, reacted originating the deposits.
All the previous reports concerning crystalline
deposit formation on IOL surfaces, mostly in the early
postoperative period, seem to be related to calciumphosphate reaction with formation of calcium salts.39-44
Indeed, hydroxyapatite is the thermodynamically stable
phase of calcium phosphate in biological systems.
Calcium and phosphate are present in blood and interstitial fluids at levels that nearly exceed their solubility
product. Although the calcium content of the normal
aqueous humor is low, about half that of the serum, any
cause of a localized increase in calcium or phosphate,
such as intraocular inflammation or administration of
intraocular drugs rich in these elements might result in
dystrophic calcification. 45-47 Some studies reported
corneal calcium-phosphate precipitates related to the
phosphate buffer concentration in Viscoat (Alcon
Laboratories, Fort Worth, TX, USA).45-46 Viscoat is a
specific formulation of chondroitin sulfate and sodium
hyaluronate dissolved in isotonic physiological
phosphate-buffered solution.48 The phosphate buffer
concentration was reduced since these reports, in order
to prevent the precipitation phenomenon. The crystalline
lens itself (or residual cortical material) is a potential
source of phosphates. Sources of calcium in cataract
surgery scenario could be represented by aqueous humor,
intraocular irrigating solutions and also by crystalline
lens. Indeed, the concentration of calcium adsorbed to
lens proteins is high.
We decided to start the tests by using the alizarin red
staining technique. This method is very simple to perform
and it is one of the most specific. Demonstration of
calcium with this anthraquinone-derivative dye depends
on a chelation process with the dye.36,37 The von Kossa
silver test demonstrates the presence of calcium through
a metal substitution technique.38 This method confirmed
our findings with alizarin red. Later, scanning electron
microscopic (SEM) and energy dispersive X-ray spectroscopic (EDS) analyses revealed the deposits to be
composed of calcium and phosphates.
Calcium deposition observed in our cases occurred
in the late postoperative period. In the cases of surface
deposition, one might speculate that it is similar to the
calcium deposition associated with spoilation of soft
contact lenses. The term spoilation is used to describe
physical and chemical changes in the nature of the
hydrophilic soft contact lenses and various deposits that
may impair their optical properties and produce

discomfort and intolerance. Contact lens spoilage may


occur in some cases as early as in 48 hours of wear, but
in the majority of cases it occurs after 3-6 months of daily
or extended wear. Filmy deposits on the surface of soft
contact lenses are in general represented by protein,
calcium, lipid and/or bacterial components. Factors that
may predispose the formation of calcium deposits on soft
contact lenses include dry-eye syndrome, increased levels
of calcium and phosphate in the tears and inflammation.
In addition to producing a film, calcium can form chalky
white granules that may take the shape of barnacles with
concentric rings or lamellae. They resemble rock
formations and exhibit birefringence under polarized
light.49-54
Heavy inorganic films often cause damage to the soft
contact lens surface, since the material may penetrate
into the lens matrix. Thus, after chemical removal of
the deposits, pits and other irregularities usually
remain.52-53 In the case of Hydroview IOLs, chemical
removal of calcium phosphate revealed the presence of
few small pits and fissures at SEM, that were found to
be artifactual, rather than permanent damage caused by
the deposits on the IOLs surfaces (George Green, PhD at
Bausch and Lomb, personal communication, February
2000). Yu et al19,20 and Groh et al21 in transmission electron
analyses of this same lens design, found calcium precipitates within the lens substance, in a region immediately
subjacent to the external surfaces.
Chang and associates10 published the first clinical
report on late postoperative opacification of the second
group of lenses (SC60B-OUVTM IOL), when they noted a
central clouding associated with a decrease in visual
acuity. No inflammatory reaction was observed. They
speculated whether the IOL opacity could be caused by
a process similar to the glistenings associated with a
hydrophobic acrylic lens, the Alcon AcrySof.55-57 We
had a similar impression after our initial gross and light
microscopic examinations of these lenses. However, the
clinical profile noted with the AcrySof IOL is different.
The occurrence of Alcon AcrySof-related glistenings
has been described as early as 1 week after cataract
surgery, and the time frame is highly variable, as opposed
to at around 24 months with the SC60B-OUVTM IOLs.
Clinical studies on the AcrySof IOL have demonstrated
that contrast sensitivity has been decreased in some
patients, but clinically significant decrease on visual
acuity has been rare.55 In vitro studies have suggested
that the occurrence of glistenings in AcrySof IOLs may
be related to variations in the temperature (t), with
formation of vacuoles within the submersed acrylic
polymer when there is a transient increase in temperature
above the glass transition temperature, approximately

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Chapter 25: Update on Delayed Postoperative Opacification of Rigid and Foldable Intraocular Lenses
18.5 C for AcrySof (Apple DJ, Clinicopathological
correlation of vacuoles in an acrylic IOL Best Paper of
the Sessionpresented at the ASCRS Symposium on
Cataract, IOL and Refractive Surgery, April 1998, San
Diego, CA, USA). Glistenings may then subsequently
form from anterior chamber fluid. It has been reported
that the IOL packaging, the AcryPak, and the sterilization technique used with that system may have made
the IOL susceptible to the micro-vacuole formation. In
vitro studies have also demonstrated that the temperature at which the IOLs were stored and shipped in the
dry state had no influence on the glistenings and was
thus unrelated to this phenomenon.56
In contrast to the findings of what morphologically
resembled glistenings noted in these clinical and in
vitro analyses, light microscopic analyses of the cut
sections of the optics (sagittal views) revealed that the
structures causing the opacification with the SC60BOUVTM lenses are not fluid-filled vacuoles, but rather
are granules of variable sizes. Frohn A., Dick H.B., and
coworkers have evaluated 41 of these lenses by light
microscopy, high performance liquid chromatography,
sodium dodecyl sulfate polyacrylamide gel electrophoresis, spectrometric analysis, and autoclaving. Neither
fatty acids nor proteins could be identified within the
IOLs. Spectrometric analysis yielded absorption peaks
in the ultraviolet spectral range. According to the same
authors, these findings indicate premature aging of the
ultraviolet blocking agent within the lenses, the source
of the opacification being a change in the IOL material
itself. Indeed, the material of these IOLs does contain an
incorporated UV absorber which functions to protect the
retina from ultraviolet radiation in the 300-400 nm range,
protection normally provided by the crystalline lens. We
have not yet done studies to verify Frohns and Dicks
findings that unbound UV-absorber monomers or any
impurity causes opacification within the IOL optic. Their
findings and the calcification process demonstrated by
us may be correlated, although our data does not allow
us to make definitive conclusions.
There have been reports on brownish discoloration
and central haze of silicone lenses, both in the early 1990s,
as well as recently (Schulze RR, Apple DJ, Progressive
pigmentation of Staar silicone IOLs: Case report,
presented at the ASCRS Symposium on Cataract, IOL
and Refractive Surgery, May 20-24, 2000, Boston, MA,
USA).58-60 This complication has been generally observed
in the early postoperative period, e.g. around 6 weeks
after cataract surgery and IOL implantation. In general,
it is clinically insignificant; IOL explantation has rarely
been performed. These reports have suggested that the
brown haze was due to light scatter from water vapor

257

that may diffuse into the silicone when immersed in an


aqueous medium. This may be caused by some anomaly
of the curing process during the manufacture of those
lenses or by incomplete extraction of large polymers. UV
blocking agents did not seem to be in issue with lens
discoloration since the phenomenon was also observed
with silicone IOL models not containing these agents.
Additional filtration steps in the manufacturing process
of silicone lenses seemed to solve the problem. Chromatographic detection and characterization of unbound
constituents of the SC60B-OUVTM lenses should be
performed to address this issue with this IOL.
Dr. Mahmut Kaskaloglu (Turkey) has implanted 361
of these lenses between November 1997 and October
1999. He observed 18 cases of late postoperative opacification of the SC60B-OUVTM lens, 9 of which had associated visual symptoms sufficient to justify explantation
and submit for pathological analysis. Of the 18 cases of
opacification, 5 patients were diabetic (2 explantations).
(Kaskaloglu M, Werner L. Visual outcomes of the
patients with an opacified hydrophilic acrylic IOL;
presented at the ASCRS Symposium on Cataract, IOL
and Refractive Surgery, Best Paper of the Session, San
Diego, CA, April 29, 2001). 29 To date there is no means
to establish a definitive relationship between diabetes
and this complication. Again, three separate tests strongly
suggested that the granules are at least in part composed
of calcium, the alizarin red stain, the von Kossa stain and
SEM analyses with EDS. EDS demonstrated the presence
of calcium peaks only at the level of the deposits, not in
the center of the optic and not in the region immediately
subjacent to the surface. Interestingly, although the
SC60B-OUVTM design is a single piece lens entirely
manufactured from a single acrylic material, the opacifying granules were present only in a specific region of
the IOLs optic. The reasons for this pattern are still
unknown to us. It may represent a diffusion-type pattern
or absorption of material from aqueous humor.
The Aqua-SenseTM IOL design represents the third
group of such cases. Calcium deposition on the external
surface of the lens as well as within the substance of the
optic and haptic components has been observed with all
Aqua-SenseTM lenses analyzed in our Center.34,35
Dr. Wynand Troskie (South Africa) has implanted 187
of these lenses between August 1999 and October 2000.
Thus far as of the time of this writing, he has observed
23 cases of postoperative opacification of the AquaSense lens, 16 of which had associated visual symptoms sufficient to justify explantation and submit the
explants for pathological analysis. Of the 23 cases of
opacification, 4 patients were diabetic (3 explantations).
The Aqua-SenseTM lenses analyzed by us revealed a total

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258 Section I: Cataract


opacification occurring to an extent that we have never
seen since we began examining IOLs in 1983.
At the time of this writing, the number of reported
cases with the HydroviewTM lens is relatively small; 309
of approximately 400,000 lenses implanted worldwide.
In 96 cases, the IOL changes were clinically significant,
decreasing patient vision enough to result in lens
explantation. The clinical reports have not been randomly
distributed. Although this IOL model has been implanted
in 3,500 centers worldwide, reports have appeared in
clusters. The vast majority has come from 31 ophthalmic
practices in 11 countries. We have studied cases from
several of these centers, including practices in Australia,
Canada, and Sweden.
In a February 2001 letter to surgeons who have
implanted the HydroviewTM IOL, Bausch and Lomb
described their investigation into the phenomenon.
Surface chemistry studies identified the lens deposits as
a layered mixture of octacalcium phosphate, fatty acids,
salts, and small amounts of silicone (Guttman C, Hydroview calcification resolved. Ophthalmology Times, 2001;
26:No. 4). An in vitro model was then constructed to find
out how the material deposited onto the lens. This model,
according to the manufacturer, revealed a migration of
silicone from a gasket in the lens packaging onto the
surface of the IOL. The models also showed that in
addition to silicone, fatty acids had to be present to attract
calcium ions to the lens surface. A separate retrospective
clinical case/control study was also conducted by the
manufacturer at the sites where the highest incidences
of calcification were reported. A compromised bloodretinal barrier seemed to be associated with the appearance of calcified deposits.
No reports of presumed calcification were received
prior to introduction of the SureFold system. According
to Bausch and Lomb studies, part of the components of
this packaging contains silicone, which may come off the
packaging onto the lens optic. It then appears to be a
catalyst for calcium precipitation. Fatty acids and silicone,
perhaps in association with a metabolic disease in the
affected patient, could result in the calcification.
As of May 2000, MDR had announced 56 cases of late
postoperative lens opacification out of over 75,000
SC60B-OUVTM lenses implanted worldwide. They were
aware of at least 20 other cases that required explantation
because of significant visual loss, in addition to these
described here. The manufacturer has withdrawn all
SC60B-OUVTM IOLs that have been fabricated from
material obtained from their previous polymer supplier
and have sent in June of 2000 an informational letter to
all lens users. All of these IOLs are now being
manufactured from polymer material obtained from a
new source.

The manufacturer of the Aqua-Sense TM lens has


reported 12 similar cases, besides the cases described here
(Mr. Rick Aguilera, President OII, personal communication, Amsterdam, The Netherlands, September 2001).
The manufacturer also stated that researchers have found
silicone particles on the surface of the lenses. The silicone
contaminants appeared to come from some components
of the IOL packaging. Those silicone components have
been removed and changed to Teflon. Also, the
manufacturer stated that they have implemented new
manufacturing processes involving proprietary
technology to minimize exposure of in-process lenses to
chemical agents and remove any residual of these
substances during the final stages of manufacture.
Residual water-soluble process compounds are now
extracted before packaging and sterilization by a process
OII named the P.U.R.ETM system (Precision Unresolvedmaterials Extraction). The Aqua-SenseTM IOL was then
re-released in January 2001.
Prevention and Treatment
The opacification described in our reports have an
entirely different appearance than classic posterior
capsule opacification or anterior lens epithelial cell
proliferation.
It is important for the surgeons who implanted lenses
from these three groups to recognize this condition.
Excessive Nd: YAG laser treatment, in an attempt to clean
the optical surfaces of the lenses may jeopardize implantation of a new lens in the capsular bag after explantation
of the opacified lens. The adherence of the deposits to
the optical surfaces of the lenses seems to be extremely
strong and Nd: YAG laser treatment was proven to be
ineffective in the cleaning of the lenses surfaces. The
cause of this condition seems to be multifactorial, and
until the pathogenic mechanism is not fully clarified,
explantation and exchange of the IOL is the only available
treatment.
Surgeons usually face two important challenges
during explantation of these opacified lenses. Firstly,
fibrosis along the capsulothexis edge and secondly the
capsular adhesions around the lens haptics. A few radial
incisions may be helpful to increase the rhexis diameter
and to remove the capsular flap. It is very important to
well viscodissect the lens from the capsular bag, in order
to liberate any adherence to this structure. The lens is
removed after being folded inside the eye, bisected, or
intact through a larger incision. The status of the capsular
bag should then be carefully inspected, which will
influence the decision about the site for fixation of the

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Chapter 25: Update on Delayed Postoperative Opacification of Rigid and Foldable Intraocular Lenses
new lens. Methods for the prevention of this condition
are also not completely defined to date. Long-term
clinical studies will determine the efficacy of modifications performed on IOL polymers and packaging for
prevention of lens calcification.
SUMMARY
Each hydrophilic acrylic IOL design available in the
market is manufactured from a different copolymer
acrylic. To the best of our knowledge, the calcification
problem described in this text cannot be generalized to
all of the lenses in this category. The incidence of IOL
explantation because of calcification remains low, much
less than 1 percent in each of the 3 groups described here.
The mechanism is not fully understood, but it does not
seem to be directed related to substances used during
the surgery as it occurred in the late postoperative period.
Also, the substances used during the surgery were not
the same in all cases. The majority of the patients involved
had an associated systemic disease; therefore, the
possibility of a patient-related factor, such as a metabolic
imbalance cannot be ruled out.
Lot history, component history, process changes,
surgical setting and techniques, environmental factors,
preexisting patients conditions, and packaging have been
examined. It is now important to carefully follow clinical
outcomes of these lens designs in order to assure if this
phenomenon will disappear following the changes in
polymer source or packaging.
ACKNOWLEDGEMENT
The authors would like to thank all the ophthalmic
surgeons around the world for submitting the explanted
rigid PMMA and hydrogel intraocular lenses for
pathological analysis at our Center.
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27. Macky TA, Trivedi RH, Werner L, et al. Degeneration of UV
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Research). In: Werner L, Apple DJ, (Eds). Complications of
Aphakic and Refractive Intraocular Lenses. Int Ophthalmol
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28. Apple DJ, Werner L, Pandey SK. Opalescence of hydrophilic
acrylic lenses (letter). Eye 2001;15:97-98.
29. Izak AM Werner L, Pandey SK, Apple DJ. Opacification of
modern foldable hydrogel intraocular lens designs. Eye. 2002,
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30. Sharma TK, Chawdhary S. The opalescence of hydrogel
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31. Sharma A, Ram J, Gupta A. Late clouding of an acrylic
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33. Pavlovic S, Magdowski G, Brueckel B, Pavlovic S.
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35. Werner L, Izak AM, Apple DJ, Pandey SK, et al. Complete
calcification of a hydrogel lens design: Case reports and
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36. McGee Russell SM. Histochemical methods for calcium. J
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37. Carr LB, Rambo ON, Feichtmeir TV. A method of demonstrating
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39. Jensen MK, Crandall AS, Mamalis N, Olson RJ. Crystallization
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41. Olson RJ, Caldwell KD, Crandall AS, et al. Intraoperative
crystallization on the intraocular lens surface. Am J Ophthalmol
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42. Amon M, Menapace R. Cellular invasion on hydrogel and


polymethyl methacrylate implants: An in vivo study. J Cataract
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43. Amon M, Menapace R. In vivo observation of surface
precipitaces of 200 consecutive hydrogel intraocular lenses.
Ophthalmologica 1992;204:13-18.
44. Bucher PJM, Buchi ER, Daicker BC. Dystrophic calcification of
an implanted hydroxyethylmethacrylate intraocular lens. Arch
Ophthalmol 1995; 113:1431-35.
45. Ullman S, Lichtenstein SB, Heerlein K. Corneal opacities
secondary to Viscoat. J Cataract Refract Surg 1986;12:489-92.
46. Binder PS, Deg JK, Kohl FS. Calcific band keratopathy after
intraocular chondroitin sulfate. Arch Ophthalmol 1987;105:
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47. Jensen OA. Ocular calcifications in primary hyperparathyroidism. Histochemical and ultrastructural study of a case.
Comparison with ocular calcifications in idiopathic hypercalcemia of infancy and in renal failure. Acta Ophthalmol
1975;53:173-86.
48. Liesegang TJ. Viscoelastics. Int Ophthalmol Clin 1993;33:12747.
49. Gasset AR, Lobo L, Houde W. Permanent wear of soft contact
lenses in aphakic eyes. Am J Ophthalmol 1977;83:115-20.
50. Winder AF, Ruben M, Sheraidah Ga. Tear calcium levels and
contact lens wear. Br J Ophthalmol 1977; 61:539-43.
51. Levy B. Calcium deposits on glyceryl methyl methacrylate and
hydroxyethyl methacrylate contact lenses. Am J Optomet
Physiol Opt 1984;61:605-07.
52. Bowers RWJ, Tighe BJ. Studies in the ocular compatibility of
hydrogels: A review of the clinical manifestations of spoilation.
Biomaterial 1987;8:83-88.
53. Bowers RWJ, Tighe BJ. Studies of the ocular compatibility of
hydrogels: white spot deposits: chemical composition and
geological arrangement of components. Biomaterial 1987;8:17276.
54. Tripathi RC, Tripathi BJ, Silverman RA, Rao GN. Contact lens
deposits and spoilage: Identification and management. Int
Ophthalmol Clin 1991;3:91-120.
55. Dhaliwal DK, Mamamlis N, Olson RJ, et al. Visual significance
of glistenings seen in the AcrySof intraocular lens. J Cataract
Refract Surg 1996;22:452-57.
56. Omar O, Pirayesh A, Mamalis N, Olson RJ. In vitro analysis of
AcrySof intraocular lens glistenings in AcryPak and Wagon
Wheel Packaging. J Cataract Refract Surg 1998;24:107-13.
57. Anderson C, Koch DD, Green G, et al. Alcon AcrySofTM acrylic
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Foldable Intraocular Lenses. Thorofare, NJ, Slack, 1993;161-77.
58. Milauskas AT. Silicone intraocular lens implant discoloration
in humans (letter). Arch Ophthalmol 1991;109:913.
59. Watt RH. Discoloration of a silicone intraocular lens 6 weeks
after surgery (letter). Arch Ophthalmol 1991;109:1494.
60. Koch DD, Heit Le. Discoloration of silicone intraocular lenses
(letter). Arch Ophthalmol 1992;110:319-20.

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Chapter 26: Corneal Topography in Cataract Surgery 261

26

Corneal Topography in
Cataract Surgery
Athiya Agarwal, Sunita Agarwal, Amar Agarwal, Nilesh Kanjani

INTRODUCTION
CORNEA
KERATOMETRY
KERATOSCOPY
COMPUTERIZED
VIDEOKERATOGRAPHY

INTRODUCTION
Topography is defined as the science of describing or representing the
features of a particular place in detail. In corneal topography, the place is
the cornea, i.e. we describe the features of the cornea in detail.
The word Topography is derived1,2 from two Greek words:
TOPOS- meaning place
and
GRAPHIEN- meaning to write.

ORBSCAN
NORMAL CORNEA
CATARACT SURGERY
EXTRACAPSULAR CATARACT
EXTRACTION
NON-FOLDABLE IOL
FOLDABLE IOL
ASTIGMATISM INCREASED
BASIC RULE
UNIQUE CASE
PHAKONIT

CORNEA
There are basically three refractive elements of the eye, namely: axial length,
lens and cornea. The cornea is the most important plane or tissue for
refraction. This is because it has the highest refractive power (which is
about + 45 D) and it is easily accessible to the surgeon without going inside
the eye.
To understand the cornea, one should realize that the cornea is a
parabolic curve its radius of curvature differs from center to periphery.
It is steepest in the center and flatter in the periphery. For all practical
purposes the central cornea, that is the optical zone is taken into
consideration, when you are doing a refractive surgery. A flatter cornea
has less refraction power and a steeper cornea has a higher refraction
power. If we want to change the refraction we must make the steeper
diameter flatter and the flatter diameter steeper.
KERATOMETRY
The keratometer was invented by Hermann Von Helmholtz and modified
by Javal, Schiotz, etc. If we place an object in front of a convex mirror we
get a virtual, erect and minified image (Fig. 26.1). A keratometer in relation
to the cornea is just like an object in front of a convex reflecting mirror.
Like in a convex reflecting surface, the image is located posterior to the
cornea. The cornea behaves as a convex reflecting mirror and the mires of
the keratometer are the objects. The radius of curvature of the corneas
anterior surface determines the size of the image.
The keratometer projects a single mire on the cornea and the separation
of the two points on the mire is used to determine corneal curvature. The
zone measured depends upon corneal curvature -the steeper the cornea,
the smaller the zone. For example, for a 36-D cornea, the keratometer

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262 Section I: Cataract


The objects used in the keratometer are referred to as
mires. Separation of two points on the mire are used to
determine corneal curvature. The object in the keratometer can be rotated with respect to the axis. The
disadvantages of the keratometer are that they measure
only a small region of the cornea. The peripheral regions
are ignored. They also lose accuracy when measuring
very steep or flat corneas. As the keratometer assumes
the cornea to be symmetrical it becomes at a disadvantage
if the cornea is asymmetrical as after refractive surgery.
Fig. 26.1: Physics of a convex mirror. Note the image is virtual,
erect and minified. The cornea acts like the convex mirror and
the mire of the keratometer is the object

KERATOSCOPY
To solve the problem of keratometers, scientists worked
on a system called Keratoscopy. In this, they projected a
beam of concentric rings and observed them over a wide
expanse of the corneal surface. But this was not enough
and the next step was to move into computerized
videokeratography.
COMPUTERIZED VIDEOKERATOGRAPHY

Fig. 26.2: Keratometers measure the central 3 mm of the


cornea, which generally behaves like a sphere or a
spherocylinder. This is the reason why keratometers are
generally accurate. But in complex situations like in keratoconus or refractive surgery they become inaccurate

measures a 4 mm zone and for a 50-D cornea, the size of


the cone is 2.88 mm.
Keratometers are accurate only when the corneal
surface is a sphere or a spherocylinder. Actually, the shape
of the anterior surface of the cornea is more than a sphere
or a spherocylinder. But keratometers measure the central
3 mm of the cornea, which behaves like a sphere or a
spherocylinder. This is the reason why Helmholtz could
manage with the keratometer (Fig. 26.2). This is also the
reason why most ophthalmologists can manage
management of cataract surgery with the keratometer.
But today, with refractive surgery, the ball game has
changed. This is because when the cornea has complex
central curves like in keratoconus or after refractive
surgery, the keratometer cannot give good results and
becomes inaccurate. Thus, the advantages of the
keratometer like speed, ease of use, low cost and minimum maintenance is obscured.

In this some form of light like a placido disk is projected


onto the cornea. The cornea modifies this light and this
modification is captured by a video camera. This
information is analyzed by computer software and the
data is then displayed in a variety of formats. To simplify
the results to an ophthalmologist, Klyce in 1988 started
the corneal color maps. The corneal color maps display
the estimate of corneal shape in a fashion that is
understandable to the ophthalmologist. Each color on
the map is assigned a defined range of measurement.
The placido type topographic machines (Fig. 26.3) do not
assess the posterior surface of the cornea. The details of
the corneal assessment can be done only with the Orbscan
(Bausch and Lomb) as both anterior and posterior surface
of the cornea are assessed.

Fig. 26.3: Placido type corneal topography machine

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Chapter 26: Corneal Topography in Cataract Surgery 263

Fig. 26.4: Orbscan

Fig. 26.6: Topography showing an astigmatic cornea

ORBSCAN
The orbscan (Bausch and Lomb) corneal topography
system (Fig. 26.4) uses a scanning optical slit scan that is
fundamentally different than the corneal topography that
analyses the reflected images from the anterior corneal
surface. The high-resolution video camera captures 40
light slits at 45 degrees angle projected through the cornea
similarly as seen during slit lamp examination. The slits
are projected on to the anterior segment of the eye: the
anterior cornea, the posterior cornea, the anterior iris and
anterior lens. The data collected from these four surfaces
are used to create a topographic map.
NORMAL CORNEA
In a normal cornea (Fig. 26.5), the nasal cornea is flatter
than the temporal cornea. This is similar to the curvature
of the long end of an ellipse. If we see Figure 26.5 then
we will notice the values written on the right end of the

pictures. These indicate the astigmatic values. In that is


written Max K is 45 @ 84 degrees and Min K is 44 @ 174
degrees. This means the astigmatism is + 1.0 D at 84
degrees. This is with the rule astigmatism as the
astigmatism is Plus at 90 degrees axis. If the astigmatism
was Plus at 180 degrees then it is against the rule
astigmatism. The normal corneal topography can be
round, oval, irregular, symmetric bow tie or asymmetric
bow tie in appearance. If we see Figure 26.6 we will see
a case of astigmatism in which the astigmatism is + 4.9
D at 146 degrees. These figures show the curvature of the
anterior surface of the cornea. It is important to remember
that these are not the keratometric maps. So the blue/green
color denote steepening and the red colors denote flattening. If
we want the red to denote steepening then we can invert
the colors.
CATARACT SURGERY
Corneal topography is extremely important in cataract
surgery. The smaller the size of the incision lesser the
astigmatism and earlier stability of the astigmatism will occur.
One can reduce the astigmatism or increase the astigmatism of a patient after cataract surgery. The simple
rule to follow is that- wherever you make an incision that
area will flatten and wherever you apply sutures that area will
steepen.
EXTRACAPSULAR CATARACT EXTRACTION

Fig. 26.5: Topography of a normal cornea

One of the problems in Extracapsular cataract extraction


is the astigmatism which is created as the incision size is
about 10-12 mm. In Figure 26.7, you can see the
topographic picture of a patient after extracapsular
cataract extraction (ECCE). You can see the picture on
the left is the preoperative photo and the picture on the

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264 Section I: Cataract

Fig. 26.7: Topography after extracapsular cataract extraction (ECCE). The figure on the left
shows astigmatism of + 1.1 D at 12 degrees preoperatively. The astigmatism has increased to +
4.8 D as seen in the figure on the right

right is a postoperative day 1 photo. Pre-operatively one


will notice the astigmatism is + 1.0 D at 12 degrees and
postoperatively it is + 4.8 D at 93 degrees. This is the
problem in ECCE. In the immediate postoperative period
the astigmatism is high which would reduce with time.
But the predictability of astigmatism is not there which
is why smaller incision cataract surgery is more
successful.
NON-FOLDABLE IOL
Some surgeons perform phaco and implant a nonfoldable IOL in which the incision is increased to 5.5 to
6 mm. In such cases the astigmatism is better than in an
ECCE. In Figure 26.8, the pictures are of a patient who
has had a non-foldable IOL. Notice in this the preoperative astigmatism is + 0.8 D @ 166 degrees. This is
the left eye of the patient. If we had done a phaco with a
foldable IOL the astigmatism would have been nearly
the same or reduced as our incision would have come in
the area of the astigmatism. But in this case after a phaco
a non-foldable IOL was implanted. The postoperative
astigmatism one week postoperative is + 1.8 D @ 115
degrees. You can notice from the two pictures the
astigmatism has increased.

FOLDABLE IOL
In phaco with a foldable IOL the amount of astigmatism
created is much less than in a non-foldable IOL. Let us
look now at Figure 26.9. The patient as you can see has
negligible astigmatism in the left eye. The picture on the
left shows a preoperative astigmatism of + 0.8 D at 166
degrees axis. Now, we operate generally with a temporal
clear corneal approach, so in the left eye, the incision will
be generally at the area of the steepend axis. This will
reduce the astigmatism. If we see the postoperative photo
of day one we will see the astigmatism is only + 0.6 D
@ 126 degrees. This means that after a day, the astigmatism has not changed much and this shows a good
result. This patient had a foldable IOL implanted under
the no anesthesia cataract surgical technique after a Phaco
cataract surgery with the size of the incision being
2.8 mm.
ASTIGMATISM INCREASED
If we are not careful in selecting the incision depending
upon the corneal topography we can burn our hands.
Figure 26.10, illustrates a case in which astigmatism has
increased due to the incision being made in the wrong

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Chapter 26: Corneal Topography in Cataract Surgery 265

Fig. 26.8: Topography of a non-foldable IOL implantation

Fig. 26.9: Topography of phaco cataract surgery with a foldable IOL implantation

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266 Section I: Cataract

Fig. 26.10: Increase in astigmatism after cataract surgery due to incision being made in the
wrong meridian. Topography of a phaco with foldable IOL implantation

meridian. The patient had a 2.8 mm incision with a


foldable IOL implanted after a phaco cataract surgery
under the no anesthesia cataract surgical technique. Both
the pictures are of the right eye. In Figure 26.10, look at
the picture on the left. In the picture on the left, you can
see the patient has an astigmatism of + 1.1 D at axis 107
degrees. As this is the right eye with this astigmatism we
should have made a superior incision to reduce the preoperative astigmatism. But by mistake we made a
temporal clear corneal incision. This has increased the
astigmatism. Now if we wanted to flatten this case, we
should have made the incision where the steeper
meridian was. That was at the 105 degrees axis. But
because we were doing routinely temporal clear corneal
incisions, we made the incision in the opposite axis. Now
look at the picture on the right. The astigmatism has
increased from + 1.1 D to + 1.7 D. This shows a bad result.
If we had made the incision superiorly at the 107 degrees
axis, we would have flattened that axis and the
astigmatism would have been reduced.
BASIC RULE
The basic rule to follow is to look at the number written
in red. The red numbers indicate the plus axis. If the
difference in astigmatism is say 3 D at 180 degrees, it

means the patient has + 3 D astigmatism at axis 180


degrees. This is against the rule astigmatism. In such
cases, make your clear corneal incision at 180 degrees so
that you can flatten this steepness. This will reduce the
astigmatism.
UNIQUE CASE
In Figure 26.11, the patient had a temporal clear corneal
incision for Phaco cataract surgery under no anesthesia
with a non-foldable IOL. Both the pictures are of the left
eye. The figure on the left shows the postoperative
topographic picture. The postoperative astigmatism was
+ 1.8 D at axis 115 degrees. This patient had three sutures
in the site of the incision. These sutures were put as a
nonfoldable IOL had been implanted in the eye with a
clear corneal incision. When this patient came for a follow
up we removed the sutures. The next day the patient
came to us with loss of vision. On examination, we found
the astigmatism had increased. We then took another
topography. The picture on the right is of the topography
after removing the sutures. The astigmatism increased
to + 5.7 D. So, one should be very careful in analyzing
the corneal topography when one does suture removal
also. To solve this problem one can do an astigmatic
keratotomy.

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Chapter 26: Corneal Topography in Cataract Surgery 267

Fig. 26.11: Unique case- Topographic changes after suture removal

Fig. 26.12: Topography of a Phakonit with a rollable IOL

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268 Section I: Cataract

Fig. 26.13: Topography of a Phakonit with an Acritec IOL

PHAKONIT
Phakonit is a technique devised by Dr Amar Agarwal in
which the cataract is removed through a 0.9 mm incision.
The advantage of this is obvious. The astigmatism created
by a 0.9 mm incision is very little compared to a 2.6 mm
phaco incision. Today with the rollable IOL and the
Acritec IOLs which are ultra-small incision IOLs one
can pass IOLs through sub 1.4 mm incisions. This is seen
clearly in Figures 26.12 and 26.13. Figure 26.12 shows
the comparison after Phakonit with a rollable IOL and
Figure 26.13 with an Acritec IOL. If you will see the
preoperative and the postoperative photographs in
comparison you will see there is not much difference
between the two. In this case a rollable IOL was implanted. The point which we will notice in this picture is that
the difference between the preoperative photo and the
one day postoperative photo is not much.

who should utilize this instrument but also the cataract


surgeon. The most important refractive surgery done in
the world is cataract surgery and not Lasik (Laser-insitu keratomileusis) or PRK (Photorefractive keratectomy). With more advancements in corneal topography,
Topographic-Assisted Lasik will become available to
everyone with an Excimer Laser. One might also have
the corneal topographic machine fixed onto the operating
microscope so that one can easily reduce the astigmatism
of the patient.
REFERENCES
1. Gills JP et al: Corneal topography: The Stateof-the Art. New
Delhi: Jaypee Brothers, 1996.
2. Sunita Agarwal, Athiya Agarwal, Mahipal S Sachdev, Keiki R
Mehta, I Howard Fine, Amar Agarwal: Phacoemulsification,
Laser Cataract Surgery and Foldable IOLs (2nd edn). New
Delhi: Jaypee Brothers, 2000.

SUMMARY
Corneal topography is an extremely important tool for
the ophthalmologist. It is not only the refractive surgeon

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Section II

Refractive Surgery
27. AberropiaA New Refractive Entity
Soosan Jacob, Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Tahira Agarwal
28. Presbyopic Lasik
Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Guillermo Avalos
29. Zyoptix
Amar Agarwal, Nilesh Kanjani, Ashish Doshi, Sonika Doshi, Sunita Agarwal,
Athiya Agarwal, J Agarwal, T Agarwal
30. Ocular Pharmacokinetics in Refractive Surgery
Ashok Garg
31. Phakic Refractive Lens (PRL) Indications and Techniques
Dimitrii D Dementiev, Kenneth J Hoffer
32. Visual Acuity with Contact Lenses vs LASIK in Myopia
Melania Cigales, Fernando Rodriquez Mier, Marta Marsan, Jairo E Hoyos
33. Contact Lens Fitting in Refractive Surgery
Ashok Garg
34. Primary Posterior Corneal Elevation
Amar Agarwal, Nilesh Kanjani, Ashish Doshi, Sonika Doshi,
Sunita Agarwal, Athiya Agarwal, J Agarwal, T Agarwal

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27

AberropiaA New Refractive Entity

Soosan Jacob, Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Tahira Agarwal

INTRODUCTION
WAVEFRONT ANALYSIS
ABERROPIA
ABERROPIA PATIENTS
ZYOPTIX

INTRODUCTION
We propose the existence of a hitherto unidentified entity which we label
as aberropia wherein patients with best corrected visual acuity (BCVA)
of < 6/12 (0.50) improved by > two Snellen lines after refractive correction
of their wavefront aberration. Preoperatively, corneal topography did not
account for the lack of improvement in BCVA and they had no other known
cause for the decreased vision.

RESULTS
DISCUSSION

WAVEFRONT ANALYSIS
The next evolution to come on to the visual science scene in refractive
ocular imaging is the aberrometer, the Orbscan and wavefront analysis.
This technology is based on astrophysical principles, which astronomers
use to perfect the images impinging on their telescopes. Dr. Bille, the
Director of the Institute of Applied Physics at the University of Heidelberg
first began work in this field while developing this specific technology for
astronomy applications in the mid-1970s. For perfect imaging, astrophysicists have to be able to measure and correct the imperfect higherorder aberrations or wavefront distortions that enter their telescopic lens
system from the galaxy. To achieve this purpose, adaptive optics are used
wherein deformable mirrors reform the distorted wavefront to allow clear
visualization of celestial objects. Extrapolating these same principles to
the human eye, it was thought that removal of the wavefront aberrations
of the eye might finally yield the long awaited and much desired ultimate
goal of supervision.
ABERROPIA
So far, the only parameters that could be modified to obtain the optical
correction for a given patients refractive error were the sphere, cylinder
and axis even though this does not give the ideal optical correction many
a times. This is because the current modes for correcting the optical
aberrations of the eye do not reduce the higher order aberrations. The ideal
optical system should be able to correct the optical aberrations in such a
way that the spatial resolving ability of the eye is limited only by the limits
imposed by the neural retina, i.e. receptor diameter and receptor packing.
Thus, there may be a large group of patients whose best corrected visual
acuity (BCVA) may actually improve significantly on removal of the optical
aberrations. These optical aberrations are contributed to by the eyes entire
optical system, i.e. the cornea, the lens, the vitreous and the retina. We
conducted a study to determine the existence of a hitherto unidentified

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272 Section II: Refractive Surgery


entity which we label as aberropia wherein patients
with best corrected visual acuity of < 6/12 (0.50), corneal
topography not accounting for the lack of improvement
in BCVA and with no other known cause for decreased
vision improved by > two Snellen lines after refractive
correction of their wavefront aberration.
ABERROPIA PATIENTS
Ten eyes of 7 patients were included in a retrospective
study carried out at the Dr. Agarwals Eye Institute, India
between May to June 2002. Only patients who had visual
acuity less than 6/12 (0.50) prior to the procedure and
whose visual acuity improved by more than or equal to
two lines after the procedure were included in the study.
None of these patients had any other known cause for
decreased vision and their corneal topography did not
account for the lack of improvement in BCVA. The
routine patient evaluation including uncorrected (UCVA)
and best corrected (BCVA), slit lamp examination,
applanation tonometry, manifest and cycloplegic
refractions, Orbscan, aberrometry, corneal pachymetry,
corneal diameter, Schirmer test and indirect ophthalmoscopy had been performed for all the patients. Patients
wearing contact lenses had been asked to discontinue
soft lenses for a minimum of 1 week and rigid gas
permeable lenses for a minimum of 2 weeks before the
preoperative examination and surgery. Informed consent
was obtained from all patients after a thorough
explanation of the procedure and its potential benefits
and risks.
ZYOPTIX
The Zyoptix procedure was then performed using the
Bausch and Lomb Technolas 217 Z machine. The
parameters used were: wavelength 193 nm, fluence 130
mJ/cm2 and ablation zone diameters between 4.8 mm
and 6 mm. The Hansatome (Bausch and Lomb) was used
in all the eyes. Either the 180 m or the 160 m plate was
used in all the eyes. The aberrometer and the Orbscan,
which checks the corneal topography, are linked and a
zylink created. An appropriate software file is created
which is then used to generate the laser treatment file.
Postoperatively, the patients underwent complete
examination including UCVA, BCVA, slit lamp examination, Orbscan and aberrometry. The mean follow up
was 37.5 days.
For statistical analysis, the Snellen acuity was converted to the decimal notation. Continuous variables were
described with mean, standard deviation, minimum and
maximum values.

Fig. 27.1: Desired versus achieved correction of


spherical equivalent at 1 month

RESULTS
Ten eyes of 7 patients satisfied the inclusion criteria. The
mean age of the patients was 29.43 years 5.8 (SD) (range
22 to 35 years). 4 patients were females and 3 were males.
The mean preoperative spherical equivalent was
11.28 D 2.60 D (range 15.00 to -5.4 D). The mean
spherical equivalent at 1 month postoperative period
was 0.16 0.68 D (range 1.0 to 1.5). Mean preoperative
sphere was 10.85 2.56 (range 14.5 to 5.00D) and the
mean postoperative sphere was 0.13 0.68 D (range-1
to 1.5) at 1 month. The mean preoperative cylinder was
0.85 0.50 (range 0 to 1.75). The postoperative mean
cylinder was 0.08 0.24 D (range 0 to 0.75 D) at one
month.
Postoperatively, at the end of first month, 70 percent
of the patients were within 0.5 D and 90 percent were
within 1D of emmetropia. The predictability of the
spherical equivalent is shown in Figures 27.1 and 27.2
and of the cylinder is shown in Figure 27.3. All patients
achieved a BCVA of > 6/9 (0.67), 80 percent achieved
> 6/6 (1.00) and 10 percent achieved a BCVA of 6/5 (1.25)
(Fig. 27.4). One patient had a postoperative UCVA of
6/18 (0.33) but the BCVA improved to 6/9 (0.67).
DISCUSSION
Zyoptix is the new generation of excimer laser used for
the treatment of refractive disorders. Until recently,
refractive disorders were treated with standard techniques, which took into consideration only the subjective
refraction. Zyoptix technique on the other hand, takes
into account the patients subjective refraction, ocular

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Chapter 27: AberropiaA New Refractive Entity 273

Fig. 27.2: Predictability of postoperative spherical


equivalent

Fig. 27.3: Desired versus achieved correction


of cylinder at 1 month

Fig. 27.4: Preoperative versus 1 month postoperative BCVA

optical aberrations and corneal topography, with the


latter not only for the diagnosis, but also for the
therapeutic treatment, in order to design a personalized

treatment based on the total structure of the eye. The


wavefront technology in Zyoptix uses the Hartmann
Shack aberrometer based on the Hartmann-Shack
principle1 demonstrated by Liang et al2 to measure the
eyes wave aberration. This wavefront sensor has been
improved by increasing the density of samples taken of
the wavefront slope in the pupil.3 All Hartmann-Shack
devices are outgoing testing devices in that they evaluate
the light being bounced back out through the optical
system. A narrow laser beam is focused onto the retina
to generate a point source. The out coming light rays
which experience all the aberrations of the eye pass
through an array of lenses which detects their deviation.
The wavefront deformation is calculated by analyzing
the direction of the light rays using this lenslet array.
Parallel light beams indicate a good wavefront and nonparallel light beams indicate a wavefront with aberrations, which does not give equidistant focal points. This
image is then captured onto a ccd camera and the
wavefront is reconstructed. The data is explained mathematically in three dimensions with polynomial functions.
Most investigators have chosen the Zernike method for
this analysis although Taylor series can also be used for
the same purpose.4 Data from the wavefront map is
presented as a sum of Zernike polynomials each describing a certain deformation. At any point in the pupil, the
wavefront aberration is the optical path difference
between the actual image wavefront and the ideal
spherical wavefront centered at the image point.5
Any refractive error which cannot be corrected by
sphero-cylindrical lens combinations is referred to by
physicists as higher order aberrations, i.e. comma,
spherical aberration, chromatic aberration. The Zernike
Polynomials, which describe ray points, are used to
obtain a best fit toric to correct for the refractive error of
the eye. The points are described in the x and y coordinates and the third dimension, height, is described in
the z-axis. The local refractive correction of each area of
the entrance pupil can be determined by calculating from
the wavefront polynomial the corresponding local radii
of curvature and hence the required spherocylindrical
correction.6 Thus each small region of the entrance pupil
has its own three parameters that characterize the local
refractive correction: sphere, cylinder and axis.6 The
global aberrations of the entire optical system including
the cornea, lens, vitreous and the retina are thus
measured. The great advantage of wavefront analysis is
that it can describe these other aberrations.
The first order polynomial describes the spherical
error or power of the eye. The second order polynomial
describes the regular astigmatic component and its
orientation or axis. Third order aberrations are consi-

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274 Section II: Refractive Surgery


dered to be coma and fourth order aberrations are considered to be spherical aberration. Zernike polynomial
descriptions for wavefront analysis typically go up to
the tenth order of expression. The first and second orders
describe the morphology of a normal straight curve. More
local maximum and minimum points require higher
orders of the polynomial series to describe the surface.
Normal eyes exhibit spherical7,8 and coma9,10 aberrations
in addition to exhibiting defocus and astigmatism.
Ideally, the difference in the magnitude of the local
refractive correction of each area of the entrance pupil
should not exceed 0.25 D. Lower spherocylindrical
corrections are generally associated with lower wavefront
aberrations.6 These observations regarding variation in
local ocular refraction along different meridians are also
confirmed by Ivanoff11 and Jenkins.12 Van den Brink13
also commented on the change in refraction across the
pupil. Clinically significant changes of at least 0.25 D in
one or both components of the spherocylindrical correction might normally be expected for decentrations of
about 1 mm. Rayleighs quarter wavelength rule states
that if the wavefront aberration exceeds a quarter of a
wavelength, the quality of the retinal image will be
impaired significantly.14 Thus the aberration in eyes starts
to become significant when the pupil diameter exceeds
1-2 mm.6 Thus it is not possible to correct the entire
wavefront aberration with a single spherocylindrical lens.
As conventional refractive procedures such as LASIK also
reduce only the second order aberrations, the visual
acuity will still be limited by aberrations of third and
higher order aberrations. These patients are likely to
undergo tremendous improvement in their BCVA after
correction of their aberrations by Zyoptix.
In the Zyoptix system, the aberrometer and the
orbscan, which checks the corneal topography, are linked
and a zylink created. An appropriate software file is
created which is then used to generate the laser treatment
file. The truncated gaussian beam shape used in Zyoptix
combines the advantages of the common beam shapes,
i.e. flat top beam and the gaussian beam, creating a
maximized smoothness and minimized thermal effect.
Thus Zyoptix gives a smoother corneal surface, reducing
glare and increasing visual acuity. The larger optical
zones reduce haloes. Zyoptix also causes a reduction of
the ablation depth by 15-20 percent and a reduced
enhancement rate.
In a patient with higher order aberrations, LASIK
does not remove the higher order aberrations and the
point-spread function is a large blur. Zyoptix on the other
hand, performs customized ablation and removes the
higher order aberrations thus minimizing the wavefront
deformation. The point-spread function is therefore a
small spot of light.

In our study, the mean preoperative spherical


equivalent improved from 11.28 D 2.60 to 0.16 D
0.68 and the mean preoperative cylinder improved from
0.85 D 0.50 to 0.08 D 0.24. Ninety percent of the
patients were within 1 D and 70 percent were within
0.5 D of emmetropia. The orbscans were normal in all
the eyes (Figs 27.5 and 27.6). The aberrations were
reduced drastically in all the eyes (Figs 27.7 and 27.8)
and the BCVA improved in all cases by > two lines.
Reduction of the aberrations of the eye can thus result in
an improved BCVA postoperatively.
Improving the optics of the eye by removing aberrations increases the contrast and spatial detail of the retinal
image. Reduction of higher order aberrations may not
improve high contrast acuity much more in eyes where
spherocylindrical lenses alone improve the BCVA to 6/3
(2.00) or better. In contrast, in otherwise normal eyes
where the BCVA is limited to 6/12 (0.50) or 6/6 (1.00)
due to optical aberrations, reduction of higher order
aberrations should improve visual acuity.
Realization of the best possible unaided visual acuity
may be limited at the cortical, retinal and the spectacle,
corneal, or implant level. All maculae may not be able to
support 6/3 (2.00) vision. Insufficient cone density or suboptimal orientation of cone receptors or a sub-optimal
Stiles-Crawford profile of the macula may make 6/3
(2.00) vision impossible. Clinical or sub-clinical amblyopia may make achievement of supervision impossible.
But, in spite of this, there may be a certain patient
population who have the potential for an improved
BCVA on removal of their wavefront aberrations. The
corneal topography does not account for the decreased
preoperative visual acuity in these patients, neither do
they have any other identifiable cause for the decrease
in acuity except for an abnormal wavefront. It is
important that this subgroup of patients are identified
and their optical aberrations neutralized so that they are
not deprived of the opportunity to gain in their BCVA.
Wavefront sensing technology, at present, does not
in most cases define the exact locale of the pathology
causing the aberration. Hence, clinical examination and
other refractive tools, such as corneal topographic mapping, along with sound clinical judgment is required for
proper understanding of the eye and its individual
refractive status. Also, wavefront aberrations may not
remain static. Numerous authors,15-18 have shown that
ocular optical aberrations probably remain constant
between 20 and 40 years of age but increase after that.
Aberrations also change during accommodation19,20 and
may be affected by mydriatics.21 Thus, the patient should
be informed about these possibilities while taking the
consent for the procedure. Long-term studies are required

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Chapter 27: AberropiaA New Refractive Entity 275

Fig. 27.5: Preoperative orbscan of the right eye of a patient showing no abnormality

Fig. 27.6: Preoperative orbscan of the left eye of a patient showing no abnormality

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276 Section II: Refractive Surgery

Fig. 27.7: Pre- and postoperative aberrometry of the right eye


of the same patient showing removal of higher order
aberrations. The figure on the top is the preoperartive
aberrometer reading and the one below is the postoperative
reading. Note the figures on the left end which show the higher
order aberrations. One will notice in the preoperative picture
higher order aberrations present whereas in the postoperative
picture these have disappeared

Fig. 27.8: Pre- and postoperative aberrometry of the left eye


of the same patient showing removal of higher order aberrations. The figure on the top is the preoperartive aberrometer
reading and the one below is the postoperative reading. Note
the figures on the left end which show the higherorder
aberrations. One will notice in the preoperative picture higher
order aberrations present whereas in the postoperative picture
these have disappeared

to determine the stability of the postoperative refraction,


residual aberrations and changes in BCVA if any.

these individual patients, aimed at neutralizing the


wavefront aberrations of the eye is safer, more predictable, provides better visual acuities and reduces the
incidence of unsatisfactory outcomes. Further studies are
required to assess the long-term outcomes.

CONCLUSION
In conclusion, removal of the wavefront aberration may
extend the benefit of an improved BCVA to patients with
an abnormal wavefront. The subgroup of patients with
higher order aberrations, normal corneal topography and
no other known cause for decreased vision may thus
benefit immensely with wavefront guided refractive
surgery. Customized refractive surgery tailor-made for

REFERENCES
1. B Platt, RV Shack. Lenticular Hartmann screen,Opt Sci Center
News (University of Arizona) 1971;5:15-16.
2. J Liang, B Grimm, S Goelz, J Bille. Objective measurement of
the wave aberrations of the human eye with the use of a
Hartmann-Shack wavefront sensor. J Opt Soc Am 1994;11:194957.

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Chapter 27: AberropiaA New Refractive Entity 277


3. Liang J, Williams DR et al. Aberrations and retinal image quality
of the normal human eye, J Opt Soc Am A, 1997; 14(11):
2873-83.
4. Oshika T, Klyce SD, Applegate RA et al. Comparison of corneal
wavefront aberrations after photorefractive keratectomy and
laser in situ keratomileusis, Am J Ophthalmol, 1999; 127:1-7.
5. Fincham WHA, Freeman MH. Optics 9th ed. London:
Butterworths, 1980, Born M, Wolf E. Principles of Optics (2nd
ed), New York: Macmillan, 1964;203-32.
6. Charman WN, Walsh G. Variations in the local refractive
correction of the eye across its entrance pupil. Optometry and
Vision Science 1989;66(1):34-40.
7. Rosenblum WM, Christensen JL. Objective and subjective
spherical aberration measurement of the human eye. In Wolf E
(Ed): Progress in Optics, North-Holland, Amsterdam, 1976;
13:69-91.
8. Campbell MC, Harrison EM, Simonet P. Psychophysical
measurement of the blur on the retina due to optical aberrations
of the eye. Vision Res 1990;30:1587-1602.
9. Howland HC, Howland B. A subjective method for the
measurement of monochromatic aberrations of the eye. J Opt
Soc Am 1977;67: 1508-18.
10. Walsh G, Charman WN, Howland HC. Objective technique for
the determination of monochromatic aberrations of the human
eye. J Opt Soc Am A1 1984;987-92.

11. Ivanoff A. About the spherical aberration of the eye. J Opt Soc
Am 1956; 46: 901-03.
12. Jenkins TCA. Aberrations of the eye and their effects on vision.
Part 1. Br J Physiol Opt 1963; 20: 59-91.
13. Van den Brink G. Measurements of the geometric aberrations
of the eye. Vision Res 1962; 2: 233-44.
14. Born M, Wolf E. Principles of Optics (2nd ed). New York:
Macmillan, 1964;203-32.
15. Kaemmerer M, Mrochen M, Mierdel P et al. Optical aberrations
of the human eye. Nature Medicine (in press).
16. Oshika T, Klyce SD, Applegate RA et al. Changes in corneal
wavefront aberration with aging. Invest Ophthalmol Vis Sci
1999; 40:1351-55.
17. Calver RI, Cox MJ, Elliot DB. Effect of aging on the monochromatic aberrations of the human eye. J Opt Soc Am A 1999;16:
2069-78.
18. Guirao A, Gonzalez C, Redondo M et al. Average optical performance of the human eye as a function of age in a normal
population. Invest Ophthalmol Vis Sci 1999; 40: 203-13.
19. Krueger R, Kaemerrer M, Mrochen M et al. Understanding
refraction and accommodation through ingoing optics aberrometry: a case report. Ophthalmology (in press).
20. He JC, Burns SA, Marcos S. Monochromatic aberrations in the
accommodated human eye. Vis Res 2000; 40:41-48.
21. Fankhauser F, Kaemerrer M, Mrochen M et al. The effect of
accommodation, mydriasis, and cycloplegia on aberrometry.
ARVO abstract 2248. Invest Ophthalmol Vis Sci 2000; 41: S461.

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278 Section II: Refractive Surgery

28

Presbyopic LASIK
Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Guillermo Avalos

INTRODUCTION
PREVIOUS EXCIMER LASER
TECHNIQUES
HISTORY
PRINCIPLE
PROLATE AND OBLATE CORNEA
TECHNIQUE
KERATOMETRY AND
PACHYMETRY
ASTIGMATISM
PLANO EXAMPLE
HYPEROPIC EXAMPLES
MYOPIC EXAMPLE

INTRODUCTION
Presbyopia, is the final frontier for an ophthalmologist. In the 21st century
the latest developments, which are taking place, are in the field of
presbyopia. In presbyopia, the nearest point that can be focused gradually
recedes, leading to the need for optical prosthesis for close work such as
reading and eventually even for focus in the middle distance.
PREVIOUS EXCIMER LASER TECHNIQUES
Presbyopic photorefractive keratectomy (PRK) has been tried. In this using
the excimer laser, a mask consisting of a mobile diaphragm formed by
two blunt blades was used to ablate a 10-17 micron deep semilunar-shaped
zone immediately below the papillary center, steepening the corneal
curvature in that area.
Monofocal vision with LASIK has also been tried to solve the problem
of presbyopia. The goal in such cases is to make the patient anisometropic.
In this one eye is used for distance vision and the other for near vision.
This is obviously not indicated in all subjects. The residual consequences
are partial loss of stereopsis, asthenopia, headache, aneisokonia and
decreased binocularity.
HISTORY
Guillermo Avalos1,2 started the idea of Presbyopic LASIK. This is called
the PARM technique. He held a live surgical conference in Mexico where
he had invited the Agarwals to perform Phakonit and the no-anesthesia
cataract surgery technique. There he discussed with them the idea of
presbyopic LASIK and when they came back they started the technique.
PRINCIPLE
The objective is to allow the patient to focus on near objects while retaining
his ability to focus on far objects, taking into account the refractive error of
the eye when the treatment is performed. With this LASIK technique the
corneal curvature is modified, creating a bilateral multifocal cornea in the
treated optical zone. A combination of hyperopic and myopic LASIK is
done aiming to make a multifocal cornea. We determine if the eye is
presbyopic plano, presbyopic with spherical hyperopia or presbyopia with
spherical myopia. These may also have astigmatism in which case the
astigmatism is treated at the same time.

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Chapter 28: Presbyopic LASIK 279


PROLATE AND OBLATE CORNEA
It is important for us to understand a prolate and oblate
cornea before we progress further on the technique of
presbyopic LASIK. The shape of spheroid (a conoidal
surface of revolution) is qualitatively prolate or oblate,
depending on whether it is stretched or flattened in its
axial dimension. In a prolate cornea the meridional
curvature decreases from pole to equator and in an oblate
cornea the meridional curvature continually increases.
The optical surfaces of the normal human eye both cornea
and lens is prolate. This shape has an optical advantage
in that spherical aberration can be avoided. Following
LASIK the prolateness of the anterior cornea reduces but
is insufficient to eliminate its spherical aberration. Thus
one should remember the normal cornea is prolate. When
myopic LASIK is done the cornea becomes oblate. When
hyperopic LASIK is done the cornea becomes prolate.
Every patient treated with an excimer laser is left with
an oblate or prolate-shaped cornea depending upon the
myopia or hyperopia of the patient. The approach to
improve visual quality after LASIK is to apply geometric
optics and use the patients refraction, precise preoperative corneal height data and optimal postoperative
anterior corneal shape in order to have a customized
prolate shape treatment.

Fig. 28.1: Hyperopic LASIK done on the cornea. Myopic


prolate cornea produced

TECHNIQUE
First of all a superficial corneal flap is created with the
microkeratome. The corneal flap performed with the
microkeratome must be between 8.5 to 9.5 mm in order
to have an available corneal surface for treatment of at
least 8 mm. In this way, the laser beam does not touch the
hinge of the flap. In India the Bausch and Lomb LASIK
machine is used and in Mexico the Apollo machine is
used. Once the flap has been created a hyperopic ablation
in an optical zone of 5 mm is done (Fig. 28.1). The treated
cornea now has a steepness section. The cornea is thus
myopic, prolate. This allows the eye to focus in a range
that includes near vision but excludes far vision.
With this myopic-shaped cornea, one now selects a
smaller area of the central cornea that is concentric with
the previous worked area. The size of the area is a 4 mm
optical zone. A myopic LASIK is now done with the 4
mm optical zone (Fig. 28.2). The resulting cornea now
has a central area (oblate) that is configured for the eye
to focus on far objects and a ring shaped area that allows
the eye to focus on near objects (Fig. 28.3). The flap is
now cleaned and replaced back in position.

Fig. 28.2: Myopic LASIK done. Myopic ablation of 4 mm


optical zone performed to create a central oblate cornea

exceed 48 D. The keratometer reading should be taken


from topography and not from a manual keratometer
machine. For each hypermetropic dioptre corrected, the
corneal curvature increases in 0.89 keratometric dioptres
as an average. It is recommended to treat patients with
keratometry in the range between 41 to 43 D to obtain
postoperative curves under 48 D. If the cornea is more
than 48 D, it produces undesired optical alterations like
glare, halos, decreased visual acuity and decreased
contrast sensitivity. The preoperative and postoperative
keratometer readings should be nearly the same for the
patient to be comfortable.

KERATOMETRY AND PACHYMETRY


Pachymetry is not important for this procedure. The preoperative keratometry reading is extremely important.
The postoperative keratometer reading should not

ASTIGMATISM
If astigmatism is present, it is recommended to use as a
limit 2.5 D. One should also remember there is an induced

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280 Section II: Refractive Surgery


HYPEROPIC EXAMPLES
Now let us look at presbyopic LASIK being performed
in a hyperopic eye.
Example 2

Fig. 28.3: Schematic diagram of a presbyopic cornea in which


hyperopic and myopic LASIK has been done. The patient can
thus focus for near and distance

astigmatism of 0.5 to 0.75 D created by the corneal shape


after the surgery and this can decrease one or two lines
of uncorrected visual acuity.
PLANO EXAMPLE
Now let us look at treating presbyopic patients who are
basically plano for distance.
Example 1
Let us take a patient who is plano for distance and is 20/
20. For near on addition of + 2 D the patient is J1. The
preoperative keratometer let us say is 41 D.
There are three steps in the presbyopic LASIK
treatment.
Step 1 For distanceNo treatment is required as the
patient is plano 20/20
Step 2 For nearHyperopic LASIK is done of + 2 D. A
5 mm optical zone is taken. We have already
mentioned that each dioptre of hyperopia
corrected changes the corneal curvature by 0.89
D, which is approximately 1 D. So the keratometer changes from 41 to 43 D (approximately)
Step 3 Myopic LASIK of minus 1 D with a 4 mm optical
zone. So keratometer now becomes 42 D.
Regression occurs for hyperopia treatment to about
1 D, so we have done myopic ablation of minus 1 and
not minus 2 D. The preoperative keratometer reading
was 41 D and postoperative keratometer reading is
42 D, which is nearly the same.

Let us take a patient who is hyperopic for distance and


is 20/20 with + 1 D. For near on addition of + 3 D the
patient is J1. The preoperative keratometer let us say is
42 D.
There are three steps in the presbyopic LASIK
treatment.
Step 1 For distanceHyperopic LASIK is done of + 1
D with a 5 mm optical zone. So keratometer
changes from 42 D to 43 D.
Step 2 For near- Hyperopic LASIK is done of + 3 D. A 5
mm optical zone is taken. We have already
mentioned that each dioptre of hyperopia
corrected changes the corneal curvature by 0.89
D, which is approximately 1 D. So the keratometer changes from 43 to 46 D (approximately)
Step 3 Myopic LASIK of minus 2 D with a 4 mm optical
zone. So keratometer now becomes 44 D.
Regression occurs for hyperopia treatment to about
1 D, so we have done myopic ablation of minus 2 and
not minus 3 D. The preoperative keratometer reading
was 42 D but after making the patient plano it is 43 D.
The postoperative keratometer reading is 44 D, which is
nearly the same.
Though we have to correct totally 4 D for hypermetropia we take it in two steps. One should not do it in
one step as that much hyperopia corrected in one step
makes the central cornea too steep to perform the myopic
ablation.
Example 3
Let us take a patient who is hyperopic for distance and
is 20/20 with + 3 D. For near on addition of + 3 D the
patient is J1. The preoperative keratometer let us say is
44 D.
The pre-operative keratometer reading is 44 D and
we have to correct 3 D for distance and 3 d for near. So if
we do presbyopic LASIK we will make the keratometer
reading 50 D. So, one should not treat such patients with
presbyopia LASIK.
MYOPIC EXAMPLE
Now let us look at myopic patients.

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Chapter 28: Presbyopic LASIK 281


Example 4
Let us take a patient who is myopic for distance and is
20/20 with minus 2 D. For near on addition of + 2 D the
patient is J1. This means the patient is plano for near.
The preoperative keratometer let us say is 43 D.
There are three steps in the presbyopic LASIK
treatment.
Step 1 For distancePatient is myopic so no treatment
is required.
Step 2 For nearHyperopic LASIK is done of + 2 D. A
5 mm optical zone is taken. We have already
mentioned that each dioptre of hyperopia
corrected changes the corneal curvature by
0.89 D, which is approximately 1 D. So the
keratometer changes from 43 to 45 D (approximately)
Step 3 Myopic LASIK of minus 3 D with a 4 mm optical
zone. So keratometer now becomes 42 D.
Regression occurs for hyperopia treatment to about
1 D, so we have done myopic ablation of minus 3 and

not minus 4 D. The preoperative keratometer reading


was 43 D but patient was myopic by 2 D, so actually the
keratometer reading should be 41 D. D. The postoperative keratometer reading is 42 D, which is nearly the
same.
We did myopic ablation of 3 D, as patient is myopic
of 2 D and presbyopic of 2 D. Regression factor taken is
1 D.
SUMMARY
This idea of presbyopic LASIK is not the end of it all.
This technique needs further improvisations to become
the technique of choice for one and all.
REFERENCES
1. Guillermo Avalos. Presbyopic LASIKThe PARM technique.
In Amar Agarwals Presbyopia: A Surgical Textbook. Slack Inc,
USA, 2002.
2. Agarwal T et al. Presbyopic LASIKThe Agarwal technique.
In Amar Agarwals Presbyopia: A Surgical Textbook. Slack Inc,
USA, 2002

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282 Section II: Refractive Surgery

29

Zyoptix
Amar Agarwal, Nilesh Kanjani, Ashish Doshi, Sonika Doshi,
Sunita Agarwal, Athiya Agarwal, J Agarwal, T Agarwal

INTRODUCTION

INTRODUCTION

ABERRATIONS

Since as early as middle of 19th century it has been known that the optical
quality of human eye suffers from ocular errors (aberrations) besides the
commonly known image errors such as myopia, hyperopia and
astigmatism.1 In early 1970s Fyodorov introduced the anterior radial
incisions to flatten the central cornea to correct myopia.2 Astigmatic
keratotomy,3 Keratomileusis and Keratophakia, Epikeratophakia4 and
currently Excimer Laser5 have been used to manage the various refractive
errors. These refractive procedures correct lower order aberrations such
as spherical and cylindrical refractive errors however higher order aberrations persist, which affect the quality of vision but may not significantly
affect the Snellen visual acuity. Refractive corrective procedures are known
to induce aberrations.6 It is the subtle deviations from the ideal optical
system, which can be corrected by wavefront and topography guided
(customized ablation) LASIK procedures.7

ZYOPTIX LASER
ORBSCAN
ABERROMETER
ZYLINK
RESULTS
DISCUSSION

ABERRATIONS
Optical aberration customization can be corneal topography guided which
measures the ocular aberrations detected by corneal topography and treats
the irregularities as an integrated part of the laser treatment plan. The
second method of optical aberration customization measures the wavefront
errors of the entire eye and treats based on these measurements.7 Wavefront
analysis can be done either using Howlands aberroscope8 or a Hartmann
Shack wavefront sensor.9 These techniques measure all the eyes aberrations
including second-order (sphere and cylindrical), third-order (coma-like),
fourth-order (spherical), and higher order wavefront aberrations. Based
on this information an ideal ablation plan can be formulated which treats
lower order as well as higher order aberrations.
ZYOPTIX LASER
ZyoptixTM (Bausch and Lomb) is a system for Personalized Vision Solutions,
which incorporates ZywaveTM Hartmann Shack aberrometer coupled with
OrbscanTM II z multi-dimensional device, which generates the individual
ablation profiles to be used with the Technolas 217 Excimer Laser system.
Thus this system utilizes combination of wavefront analysis and corneal
topography for optical aberration customization.

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Chapter 29: Zyoptix

Fig. 29.1: Orbscan

283

Fig. 29.2: Hartmann-Shack aberrometer

ORBSCAN
The Orbscan (Bausch and Lomb) corneal topography
system (Fig. 29.1) uses a scanning optical slit scan that is
fundamentally different than the corneal topography that
analyses the reflected images from the anterior corneal
surface. The high-resolution video camera captures 40
light slits at 45 degrees angle projected through the cornea
similarly as seen during slit lamp examination. The slits
are projected on to the anterior segment of the eye: the
anterior cornea, the posterior cornea, the anterior iris and
anterior lens. The data collected from these four surfaces
are used to create a topographic map. This technique
provides more information about anterior segment of the
eye, such as anterior and posterior corneal curvature and
corneal thickness.10 It improves the diagnostic accuracy
and it has passive eye-tracker from frame to frame, 43
frames are taken to ensure accuracy. It is easy to interpret
and has good repeatability. Three different maps are
taken, and the one featuring the least eye movements is
used. The maximum movements considered acceptable
are 200.
ABERROMETER
ZywaveTM is based on HartmannShack aberrometry
(Fig. 29.2) in which a laser diode (780 nm) generates a
laser beam that is focused on the retina of the patients
eye. An adjustable collimation system compensates for
the spherical portion of the refractive error of the eye.
Laser diode is turned on for approximately 100 milliseconds. The light reflected from the focal point on the
retina (source of wavefront) is directed through an array
of small lenses (lenslet) generating a grid like pattern
(array) of focal points. The position of the focal points
are detected by ZywaveTM. Due to deviation of the points

from their ideal position, the wavefront can be


reconstructed. Wavefront display shows (a) higher order
aberrations (b) predicted phoropter refraction (PPR)
calculated for a back vertex correction of 15 mm.
(c) Simulated point spread function (PSF). ZywaveTM
examinations are done with (a) single examination with
undilated pupil (b) five examinations with dilated pupil
(mydriasis) non-cycloplegic, using 5 percent Phenylephrine drops. One of these five measurements, which
matched best with the manifest refraction of the
undilated pupil, is chosen for the treatment.
ZYLINK
Information gathered from Orbscan and Zywave are then
translated into treatment plan using ZylinkTM software
and copied to a floppy disc. The floppy disc is then
inserted into the Technolas 217 system (Fig. 29.3), fluence
test carried out and a Zyoptix treatment card was
inserted. A standard LASIK procedure is then performed
with a superiorly hinged flap. A HansatomeTM microkeratome is used to create a flap. Flap thickness varied
from 160m to 200m. A residual stromal bed of 250m
or more is left in all eyes. Optical zone varied from 6 mm
to 7 mm depending upon the pupil size and ablation
required. Eye tracker is kept on during laser ablation.
Postoperatively all patients are followed up for at least 6
months.
RESULTS
We did a study comprising 150 eyes with myopia and
compound myopic astigmatism. Preoperatively, the
patients underwent corneal topography with Orbscan
II zTM and wavefront analysis with ZywaveTM in addition
to the routine pre-LASIK work up. The results were

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284 Section II: Refractive Surgery

Fig. 29.5: Compares preoperative and postoperative


UCVA (Efficacy)
Fig. 29.3: Technolas 217 z Excimer laser system

assimilated using ZylinkTM and a customized treatment


plan was formulated. LASIK was then performed with
Technolas 217 system. All the patients were followed
up for at least six months.
Mean preoperative BCVA (in decimal) was 0.83 0.18
(Range 0.33- 1.00). Mean postoperative (6 months) BCVA
was 1.00 0.23 (Range 0.33-1.50). Difference was
statistically significant (p=0.0003). Out of 150 eyes that
underwent customized ablation, 3 eyes (2%) lost two or
more lines of best spectacle corrected visual acuity
(BSCVA).
Safety index = Mean postoperative BSCVA/mean
preoperative BSCVA = 1.20 (Fig. 29.4). Mean preoperative UCVA was 0.06 0.02 (Range 0.01-0.50). Mean
postoperative UCVA was 0.88 0.36 (Range 0.08 1.50).
Difference was statistically significant (p =0.0001).
Efficacy index = Mean postoperative UCVA/mean
preoperative UCVA = 14.66 (Fig. 29.5). Preoperatively,

Fig. 29.4: Shows changes in BSCVA 6 months postoperatively (Safety)

Fig. 29.6: Shows the refractive results


postoperatively after 6 months

none of the eyes had UCVA of 6/6 or more and one eye
(0.66%) had UCVA of 6/12 or more. At 6 months postoperatively, 105 eyes (69.93%) had UCVA of 6/6 or more
and 126 eyes (83.91%) had UCVA of 6/12 or more.
Mean preoperative spherical equivalent was -5.25 D
1.68 D (Range -0.87 D to 15 D). Mean postoperative
spherical equivalent (6 months) was 0.36 D 0.931 D
(Range 4.25 D to +1.25). Difference between the two was
statistically significant (p<0.05) (Fig. 29.6). 132 eyes
(87.91%) were within 1.00 D of emmetropia while 120
eyes (79.92%) were within 0.05 D of emmetropia. 1 eye
(0.66%) was overcorrected by > 0.5 D and 1 eye (0.66%)
was overcorrected by >1D. The mean pupil diameter was
5.1mm 0.62mm. Preoperatively, 95 eyes (63.27%) had
third order aberrations.42 eyes (28%) had second order
aberration alone, while 13 eyes (8.65%) had fourth and
fifth order aberrations. Postoperatively, 60 eyes (40%)
had third order aberration.75 eyes (50%) had second
order alone while 15 eyes (10%) had higher order
aberrations.

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Chapter 29: Zyoptix


DISCUSSION
HartmannShack wavefront sensor was first used by
Liang and colleagues to detect ocular aberrations.11 They
applied an adaptive optics deformable mirror to correct
the lower and higher order aberrations of the eye. They
reported a 6 times increase in contrast sensitivity to high
spatial frequency when the pupil was large. This study
demonstrated that correction of higher order aberrations
could lead to supernormal vision in normal eyes.
In our series, using Zyoptix and Technolas 217 system,
which is wavefront and corneal topography guided, we
yielded results that are comparable to standard LASIK
procedure12. In a series of 347 eyes, McDonald et al 12
reported a postoperative refraction of 0.29 0.45 D
(-0.36 0.93 D in our series) with standard LASIK. Fifty
seven percent of the eyes in their series had postoperative
UCVA of =6/6. In our study, 70% of the eyes had UCVA
of =6/6, six months postoperatively.
Higher order aberrations were reduced postoperatively in our study. Third-order aberration (coma)
was most common in our series, followed by secondorder (defocus and astigmatism) and fourth-order
(spherical aberration). Postoperatively, after 6 months,
there was considerable decrease in third-order and
fourth-order aberrations. While most of the eyes had only
defocus and astigmatism (i.e. second -order aberration).
A slight increase in fourth-order aberration (spherical)
was noted. Spherical aberration is known to increase after
LASIK13-15. Roberts has reported that cornea changes its
shape in response to ablation and this change, along with
wound healing effects have to be taken into account
before customized correction can nullify higher-order
aberrations. Roberts and coworkers suggest that increase
in spherical aberrations following LASIK may be caused
by a biomechanically induced steepening and thickening
that may occur in mid periphery of the cornea13. MacRae
and coworkers have reported that simply creating a
LASIK flap increases higher-order aberrations in
unpredictable manner14. They suggest that improved
results can be obtained using a surface ablation such as
PRK or LASEK, or by doing a two-stage LASIK, with the
second stage adjusting for the aberration created by the
flap and initial ablation.
Scotopic visual complaints have been the bugbear of
LASIK procedures, ranging from mild annoyance to
severe optical disability.16,17 Night time starbursts, reduced contrast sensitivity and haloes are the most common
complaints.16,17 Spherical aberration that is induced
during LASIK may account for this scotopic complaints.14
Pupil diameter is another factor that is important. When
pupil diameter is large, as in young patients, dim light

285

vision is improved after customized correction.18,19 In our


series, 11 percent of the patients complained of haloes
around light at night and difficult night driving. In dim
light, the mean pupil diameter in these patients was
4.2 mm while it was 5.9 mm in other patients. Smaller
pupil diameter and induced higher-order aberration may
account for these scotopic visual complaints.
Twenty-five percent of the patients in our series
reported improvement in bright light vision, while 40
percent showed improvement in dim light vision. A
similar improvement was noted by Cox and co-workers
(presentation by Cox IG at Zyoptix Alliance meeting, 2002
reported in Ocular Surgery News, July 2002 volume 13,
number 7). In our series, treatment optical zone ranged
from 6mm to 7mm. Treatment with larger optical zones
and transition zones as compared to conventional LASIK
may be possible since entire corneal topography and not
just the central cornea overlying pupil along with
wavefront ablation in dilated pupil are considered during
treatment. This may induce lesser spherical aberration
post-LASIK and account for improved scotopic vision.
Though we did not measure contrast sensitivity and
glare acuity postoperatively, our results suggest
improved quality of vision and fewer glare problems
with Zyoptix treatment. A more temporal appraisal of
the procedure has to be carried out with comparison to
standard LASIK. Short-term results suggest wavefront
and topography guided LASIK may be a safe and
effective procedure which improves the visual
performance.
CONCLUSION
Wavefront and topography guided LASIK procedure
leads to better visual performance by decreasing higher
order aberration. Scotopic visual complaints may be
reduced with this method.
REFERENCES
1. Helmholtz H: Handbuch der physiologischen optik. Leipzig:
Leopold Voss.1867; 137-47.
2. Fyodorov S N, Durnev V V: Operation of dosaged dissection of
corneal circular ligament
3. Binder PS, Waring GO III: Keratotomy for astigmatism. In
Waring GO III (Ed.): Refractive keratotomy for myopia and
astigmatism. Mosby Year Book 10851198, 1992. in cases of
myopia of mild degree. Ann Ophthalmol II: 1979;1885-90.
4. Kaufmann HE: Correction of aphakia Am J Ophthalmol 1980;
89:1.
5. McGhee CNJ, Taylor HR, Garty DS et al: Excimer Lasers in
Ophthalmology: Principles and Practice Martin Duntz: London,
1997.

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286 Section II: Refractive Surgery


6. MacRae S, Porter J, Cox IG, et al. Higher-order aberrations after
conventional LASIK. ISRS: Dallas, Texas, 2000.
7. MacRae SM: Supernormal vision, hypervision, and customized
corneal ablation. Guest Editorial J Cat Refract Surg 2000; 26(2).
8. Howland HC, Howland B: A subjective method for the
measurement of monochromatic aberrations of the eye, J Opt
Soc Am 1977; 67:1508-18.
9. Liang J, Williams DR, Miller DT. Supernormal vision and highresolution retinal imaging through adaptive optics. J Opt Soc
Am 1997; 2884-92.
10. Fedor P, Kaufman S. Corneal topography and imaging.
eMedicine Journal, 2001;2(6).
11. Liang J, Williams D. Aberrations and retinal image quality of
the normal human eye. J Opt Soc AM A 1997;14:2884-92.
12. McDonald MB, Carr JD, Frantz JM, et al. Laser in situ
keratomilieusis for myopia up to 11 diopters with up to 5
diopters of astigmatism with summit autonomous LADAR
Vision excimer laser system. Ophthalmology2001; 108: 309-16.
13. Roberts C. The cornea is not a piece of plastic. J Refract Surg
2000;16:407-13.

14. MacRae SM, Roberts C, Porter J, et al. The biomechanics of a


LASIK flap. ISRS Mid Summer Meeting: Orlando, Florida,
2001.
15. Applegate RA, Howland HC, Klyce SD. Corneal aberration and
refractive surgery. In: MacRae S (Editor). Customized Corneal
Ablation. Thorofare NJ: Slack, Inc., 2001.
16. Holladay JT, Dudeja DR, Chang J. Functional vision and corneal
changes after laser in situ keratomileusis determined by contrast
sensitivity, glare testing, and corneal topography. J Cataract
Refract Surg 1999; 25: 663-69.
17. Perez-Santonja JJ, Sakla HF, Alio JL. Contrast sensitivity after
laser in situ keratomileusis. J Cataract Refract Surg 1998; 24:
183-89.
18. Applegate R, Howland H, Sharp R, et al. Corneal aberrations
and visual performance after refractive keratectomy. J Refract
Surg 1998;14: 397-407.
19. Oshika T, Klyce S, Applegate R, et al. Comparison of corneal
wavefront aberrations after photorefractive keratectomy and
laser in situ keratomileusis. Am J Ophthal 1999; 127:1-7.

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Chapter 30: Ocular Pharmacokinetics in Refractive Surgery 287

30

Ocular Pharmacokinetics
in Refractive Surgery
Ashok Garg

INTRODUCTION
PRK (PHOTOREFRACTIVE
KERATECTOMY)
LASIK SURGERY

INTRODUCTION
Ever since Theo Seiler in 1987 and Marguerite Mcdonald in 1988 did the
first corneal ablation in normal sighted eye, Excimer laser refractive surgery
has produced revolutionary changes in the field of ophthalmology. Refractive surgery is certainly a high tech advancement in the field of ophthalmic
surgery of the last decade of this millennium which has come as a great
boon to spectacle weary patients all around the world.
Two most common excimer laser refractive surgeries being performed
today are PRK (Photorefractive Keratectomy for low to moderate myopia
up to 6 Diopters) and LASIK (Laser in situ Keratomileusis for low to high
Myopia upto 20 Diopters and Hypermetropia upto + 8 Diopters). Ocular
therapeutics have certain role to play in postoperative (Postprocedure)
phase specially in PRK surgery.
In this chapter I will discuss the preprocedure and postprocedure
considerations of ocular therapeutics in detail in PRK as well as in LASIK
surgery. Every refractive surgeon should have clear concept of ocular
therapeutics in his mind before starting the procedure to ensure better
clinical results to the patients.
PRK (PHOTOREFRACTIVE KERATECTOMY)
PRK is most commonly performed refractive surgery for low to moderate
myopia worldwide. It is now gradually becoming a safe procedure due to
newer technologies and the availability of better anti-inflammatory drugs
both steroidal and non-steroidal to reduce corneal scarring and haze. As
patient selection criteria and other technical modes have been discussed
in other chapters of this book, I am discussing ocular therapeutics section
here.
Preoperative Ocular Therapeutics
Preoperatively patient is given combination of topical antibiotic
(Lomefloxacillin 0.3%) and NSAID diclofenac (1%) sodium drops. Twentyfour hours prior to procedure, this combination is started at 4 hourly
interval. A mild oral sedation with valium (diazepam 5-15 mg) helps the
patient to overcome the anxiety to the procedure.
Topical Anesthesia
For PRK surgery, topical anesthesia is the best anesthesia selected worldwide.

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288 Section II: Refractive Surgery


2-5 minutes before operation patient is given any of
the following topical anesthetic agents.
Proparacaine HCl
0.5 percent
Benoxinate HCl
0.4 percent
Tetracaine HCl
0.5 percent
Proparacaine is used most commonly followed by
benoxinate and tetracaine. Other topically applied
anesthetics (Xylocaine 4%) are used far less commonly
due to problems with irritation, allergy etc. Both proparacaine and benoxinate have a rapid onset of action and
cause little discomfort making them excellent choices.
Onset of anesthetic action starts within 15-20 seconds
with proparacaine, benoxinate and tetracaine and effects
last for 15-20 minutes enough for completion of PRK
surgery.

gradual and regular. Type VII collagen is produced and


large number of fibroblasts populate the anterior stroma.
This phase corresponds to a clinical phase of subepithelial
haze and loss of initial refractive effect.
In the long-term phase development of fibrous metaplasia is complete. Subepithelial stroma remodels itself.
Clinically this corresponds to a phase of decreasing
corneal haze and increasing refractive stability.
Standard modality for the management of patients
undergoing PRK, the major considerations are:a. Closure of epithelial defect
b. Post PRK pain management.
c. Modulation of refractive and visual results.

Dosage

It is recommended that the size of epithelium to be removed to be kept to the minimum. The best possible
methods to facilitate healing of corneal epithelium are: Patching
Bandage contact lens
Collagen shield.

Topic proparacaine, benoxinate or tetracaine are given


in the dosage of 2 drops in each eye 2-3 times repeated at
the interval of one minute.
After topical anesthesia patient is carefully centered
and local preparation with iodine solution (Betadine) is
done and the operative eye is given a sterile plastic
ophthalmic drape that covered the eyelid margins and
the cilia.
Postoperative (Postprocedure)
Therapeutic Management
Corneal wound healing and its modulations after excimer
laser PRK surgery are complex phenomenon. In PRK the
corneal epithelium is debrided after which stromal
ablation is performed. A 7-10 day epithelial healing phase
follows with the final stromal effects being observed
weeks to months later.
Ocular therapeutics are given post PRK according to
phases and time course of corneal wound healing. The
temporal response of cornea to PRK can be divided into
three phases.
1. Acute (1 to 3 weeks)
2. Intermediate (3 weeks to 6 months), and
3. Long-term ( 6 months or more).
During the acute phase cornea mounts its initial
response to epithelial removal and photoablation. The
earliest phase involves the healing of epithelial injury
and is characterised by migration of epithelium which
occurs 12-24 hours after injury 2-3 days after the insult,
epithelial cell proliferation is evident. Endothelial
migration and possibly epithelial cell proliferation also
begins this time. The acute phase corresponds to a clinical
appearance of general corneal clarity.
In the intermediate phase the epithelium remodels
itself to normal thickness if the surface contours are

Epithelial Defect Closure

Patching The common practice among ophthalmologists is to patch the eye for 24 to 48 hours following
laser procedure. Operated eye is padded putting topical
antibiotic and mydriatic eyedrops and an antibiotic
ointment. The next day padding is changed. Some
refractive surgeons prefer to give oral antibiotic
(Ciprofloxacillin 500 mg bd for 5 days). After 48 hours
patching is removed and eye is kept open.
Bandage contact lens Contact lens fitting is dependant
on the
Standard of care
Better patient compliance
Better comfort
Earlier return to normal activities
Despite the advantage one needs to be cautious of
the following complications due to contact lens fitting
which are
Infectious keratitis
Tight lens syndrome
Problems with patient compliance
Contraindicated with the use of topical NSAIDs
Collagen shield Some refractive surgeons advocate the
use of collagen shield instead of patching or contact lens
but this modality is not very popular.
Post PRK Management
One of drawbacks of the PRK procedure is problem of
pain caused by the exposure of nerve endings due to the
loss of epithelium.

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Chapter 30: Ocular Pharmacokinetics in Refractive Surgery 289


The causes of pain are
Mechanical
Epithelial defect
Thermal
Acoustic
Course of post PRK pain is most intense during the
first 24-36 hours followed by dramatic reduction but
foreign body sensation may persist epithelial closure.
Once the exposed nerves are covered by healing
epithelium patient experience no more pain.
Following PRK corneal sensation returns to baseline
within 12 weeks. The various modalities for managing
the pain are
Oral analgesic (Preferably oral diclofenac or nimesulide for 5 days. Tab diclofenac sustained released
75 mg bd or tab. Nimesulide 100 mg bd for 5 days
continuously relieve the patient of PRK pain to great
extent.
Topical non-steroidal anti-inflammatory drugs like.
Topical diclofenac 1 percent 4 times a day or
Topical ketorolac 0.5 percent 4 times a day helps in
reducing the pain
Topical lubricant eye drops 4-5 times a day gives the
patient a soothing sensation. Polyvinyl alcohol liquifilm tear drops helps in post PRK pain.
In excessive pain, topical anesthetics like proparacaine 0.5 percent drops 3-4 times a day helps the
patients to overcome the pain.
Modulation of Refractive and Visual Results
A. Corneal wound healing following excimer laser
ablation.
i. The refractive outcome is dependant upon the
balance between initial ablation depth and the
healing and remodelling of the epithelium and the
stroma.
ii. Molecular and cellular inflammatory response
iii. Activation, proliferation and migration of corneal
cells to wound.
B. Corneal haze (Post PRK)
i. Incidence depends on
Time post-treatment
Size of ablation
Depth of ablation
Excimer laser used
Individual wound healing variability.
ii. Haze occurs in 2 phases
Early (within 2 weeks of procedure)
Decreased transparency associated with
reduced optical performance due to epithelial
and surface irregularities

Late (2-6 months postprocedure)


Subepithelial deposit on the layer at epithelial
and stromal junction.
May peak at 3 months and then decrease.
iii. Therapeutic considerations should work towards.
Reducing haze or scarring
Improving predictability of refractive outcome
To prevent regression.
For this refractive surgeon prefer to give a combination of topical NSAIDs and topical steroids. Combination is preferred because topical NSAIDs reduce
corneal haze while topical steroids have a certain role to
prevent regression.
The regimes of choice are
i. Topical dexamethasone eyedrops (0.1%) starting
from 3rd post PRK procedure day 3-4 times a day
up to 2 weeks followed by switching to topical
FML (0.1%) (Fluorometholone drops) or topical
rimexolone (1%) drops from 15th day to 6 months
with the same dosage. It is gradually tapered off.
ii. Topical NSAIDs like ketorolac 0.5 percent solution
or diclofenac 1 percent solution 4 times a day for
6 months and gradually tailed off. Topical NSAIDs
and topical steroids is an ideal combination and
have maximum effect on corneal haze and visual
outcome. Some refractive surgeons prefer to give
topical FML or topical rimexolone eyedrops
straight from 3rd post PRK day instead of topical
dexamethasone for initial 15 days (because of
greater side effects of topical dexamethasone
drops). Topical FML (0.1%) or topical rimexolone
(1%) have greater effectiveness in controlling
corneal inflammation and have better ability to
inhibit leukocyte accumulation in the cornea.
Their potency as an powerful anti-inflammatory
agent is similar to dexamethasone.
Combination of topical non-steroidal and steroidal
therapy is given for 6 months post PRK and then
gradually tapered off. When topical steroids are given
for an extended period of time after PRK an important
consideration is possibility of steroid induced rise in
intraocular pressure. Because all wound healing activity
after wide area ablation occurs within the superficial
cornea, it is probably preferable to minimise the amount
of corticosteroid within the aqueous humour.
It is essential for the regular check-up of the operated
patient.
PRK patient is usually called for follow-up by
refractive surgeon on
2nd post PRK day
10th day

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290 Section II: Refractive Surgery

20th day
4th week
8th week
12th week
18th week
24th week

On each follow-up following examination is done


Visual check-up
IOP with non-contact tonometer
Slit lamp examination for haze
Topography to see central island and corneal profile.
Recent Update in Post PRK Medications
Several topical agents have been used in an attempt to
modify the stromal wound healing following PRK
surgery.
i. Topical NSAIDs like diclofenac sodium (1%) or
ketorolac (0.5%) reduces the accumulation of
prostaglandin E and inflammatory cells in the
corneal stroma but on the other hand has been
associated with the development of sterile
infiltrates following PRK.
ii. The combination of mitomycin C with topical
steroids like FML (0.1%) or rimexolone (1%) decreases the sub-epithelial fibrosis associated with
healing after PRK surgery.
iii. Application of cytokines to reduce corneal haze and
scarring has been demonstrated recently. Cytokines
are proteins secreted by cells that regulate important biological properties of target cells. Cytokines
act by an exocrine pathway to influence corneal
wound healing.
iv. Topical interferon eyedrops given four times daily
for 5 weeks reduces the corneal haze remarkably
in eyes following a 6.00D excimer laser PRK.
v. Topical dexamethasone (0.1%) in combination with
interferon 2 produce less haze .
vi. Topical FGF treatment applied four times daily
until complete epithelial wound healing occurred
significantly reduces corneal haze 5-13 weeks
following deep stromal laser ablations.
vii. Application of topical anti TGF-1 antibody reduces
corneal fibrosis remarkably.
viii. Treatment of corneas following excimer PRK with
a synthetic MMP inhibitor reduces intrastromal
epithelial migration after laser ablations.
The above mentioned topical agents are in advanced
stage of research and some time more will be needed to
be available as commercially.
So the present option for PRK medication is combined
therapy of topical NSAIDs and steroids. Refractive

surgeon has to keep strict watch on the potential adverse


effect of topical steroids. Inspite of the use of topical FML
of rimexolone which have less propensity to raise IOP
than comparable dose dexamethosone practically
patients with IOP rise are seen by every refractive
surgeons in their practice.
It is worthwhile to mention here complications of
topical steroids in details following post PRK phase.
It has been commonly observed even in educated
peoples that even after the stoppage of topical steroid
therapy by the ophthalmologists after a specific time,
patients continue to put these drops for indefinite time
without the consultation of doctor. It is essential to inform
the patient well in advance about the potential adverse
effects of topical steroids so that patient may not go for
self-medication in future.
Complications of Topical Steroids
a.
b.
c.
d.
e.

Elevated IOP (steroid induced glaucoma)


Cataract
Delayed wound healing
Infection and ulceration
Periocular dermatitis.

Steroid induced glaucoma Prolonged use of topical


steroids may cause an elevation of intraocular pressure
leading to optic nerve damage and visual field changes
which are synonymous with chronic open angle glaucoma. Steroid-induced glaucoma is most common
complication seen by refractive surgeons following PRK
surgery. The elevation of IOP can occur within days of
starting therapy or it can occur months later. Raised IOP
by steroids is related to the cytoplasmic and nuclear
receptors for steroids that have been shown in the
trabecular meshwork.
Steroid-induced elevations in IOP appear to be secondary to decreased facility of aqueous outflow. The
mechanisms include accumulation of glycosaminoglycans or an increase in debris in the trabecular meshwork due to inhibition or phagocytosis.
Clinical Symptoms
The patient is usually asymptomatic unless the intraocular pressure increases enough to cause corneal edema
(Decreased vision, halos, photophobia) or pain.
Clinical signs of prolonged elevation of IOP include
optic nerve cupping and visual field defects (Figs 30.1
and 30.2).
Treatment
Steroid-induced IOP elevations almost always respond
within days to weeks of stopping the steroids. It is not

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Chapter 30: Ocular Pharmacokinetics in Refractive Surgery 291

Fig. 30.1: Steroid induced glaucoma-pallor and cupping of the optic disk

Fig. 30.2: Progression of steroid induced glaucoma


(large glaucomatous cup and optic atrophy)

always possible to abruptly stop steroids because of


underlying ocular condition being treated then option
for treatment include.
a. Decreasing the effects of steroids by
Stopping of particular steroid
Decreasing the frequency of strength of the steroid
being used
Using a different type of steroid/FML, rimexolone or medrysone are less prone to pressure
elevation than dexamethasone.
Using non-steroidal anti-inflammatory eyedrops
(diclofenac 0.1%, ketorolac 0.5%) instead of
streoids.

Medications to decrease in IOP may be needed if


the intraocular pressure is very high or IOP rise
persists after changing, reducing or stopping the
steroids.
-blockers (timolol 0.5% twice a day, levobunolol
0.5% once or twice a day or betaxolol 0.25-0.5%
twice a day).
Apraclonidine 0.5 percent 2-3 times a day or
brimonidine 0.2 percent twice a day.
Carbonic anhydrase inhibitors (Dorzolamide 2%
drops three times a day).
Acetazolamide drops (5%) thrice a day or methazolamide 25-50 mg 1-2 tablets three times a day.
Sometime glaucoma surgery is necessary if IOP
rise does not respond to discontinuing the steroid/
or medical therapy. Argon laser trabeculoplasty
and glaucoma filtering surgery are necessary
treatment modalities.
Cataract formation Cataract development specially
posterior subcapsular type has been seen to occur after
prolonged treatment with topical steroids. With the
stoppage of the steroids, some of these changes are either
partially or totally reversible. However, visual impairment is variable. Once visual impairment has taken place,
complete resolution of the lenticular opacification cannot
be expected (Figs 30.3 and 30.4).
The pathophysiology of steroid-induced cataract
formation is by mechanism affecting water transport by
increasing cation influx. This leads to excess water in cells
causing intumescence of the cell and a disparity of the
refractive index from the surrounding medium. The
steroids also binds to specific amino acid groups within

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292 Section II: Refractive Surgery

Fig. 30.3: Steroid induced cataract (mature type)

Fig. 30.5: Interstitial herpetic keratitis with a recurrent dendritic ulcer due to topical steroids (rose bengal staining of
degenerated cells in corneal epithelium around the ulcer
margin)

the lens cell fibers. These combined factors are


responsible for the loss of transparency.
Delayed wound healing Corneal wound healing may
be inhibited by proliferation of fibroblasts and new
vessels on prolonged use of topical steroids.

Infection and ulceration Prolonged use of topical


steroids lead to infectious keratitis specially herpetic
keratitis (Fig. 30.5). Reactivation of herpes simplex virus

Fig. 30.4: Progression of steroid-induced cataract (Posterior subcapsular type)

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Chapter 30: Ocular Pharmacokinetics in Refractive Surgery 293


of novice refractive surgeon. Indeed the LASIK surgery
has come of age.
Here, now I shall discuss the ocular therapeutics used
in LASIK surgery before and after the procedure.
Preprocedure Therapeutic Medications
Preoperatively patient is given broad range topical
antibiotic eyedrops (Preferable lomefloxacillin (0.3%) or
ofloxacillin (0.3%) at 4 hourly interval starting 24 hours
prior to surgery.
A mild oral sedation (diazepam 3-10 mg) is given in
all cases. Bilateral simultaneous surgery is done in all
cases.
Topical Anesthesia
Fig. 30.6: Steroid-induced mycotic keratitis
(Courtesy: Kanski Clinical Ophthalmology,
Butterworth International Edition)

is seen in certain patients. Fungal ulcers are also more


common in topical steroid treated patients (Fig. 30.6).
Periocular dermatitis Periocular dermatitis resulting
from long-term use of fluorinated steroid drops have
been seen. This dermatitis is similar to perioral dermatitis
and should not be confused with allergic contact
dermatitis.
LASIK SURGERY
LASIK (Laser assisted in situ keratomileusis) offers a
unique opportunity to provide ametropia to patients with
refractive error ranging from 20.00 D of myopia to +8.00
D of hyperopia. The rapid visual recovery and decreased
incidence of complications associated with LASIK make
it far superior to both excimer photoablation (PRK) and
automated lamellar keratoplasty (ALK).
LASIK provides an extra-ordinary accurate method
of tissue removal (0.20-0.25 um tissue per pulse). The
extreme pain, haze, regression and slow visual rehabilitation of PRK are absent thus the minimum use of postprocedure medications specially topical steroids and its
potential adverse effects.
Although pre-procedure medications are same in
LASIK as those in PRK surgery while post-procedure
medications are drastically reduced in LASIK surgery
leading to quick visual rehabilitation of patient postoperatively.
Development of automated microkeratome Hansatome has make LASIK surgery more safe even in the hand

For LASIK surgery, refractive surgeon prefers to give


topical anesthesia because of rapid onset of action and
lesser irritation to the patient.
2-5 minutes prior to the surgery any of the following
topical anesthetic agent can be safely used.
0.5 percent
Proparacaine HCl
Benoxinate HCl
0.4 percent
Tetracaine HCl
0.5 percent
Proparacaine is most commonly used anesthetic agent
followed by benoxinate and tetracaine. Other topical
agent like xylocaine (4%) is less commonly used due to
problems of irritation, allergy etc.
Proparacaine, benoxinate and tetracaine have rapid
onset of action and cause little tingling sensation and
irritation to the patient.
Onset of anesthetic action starts within 15-20 seconds
with these agents and effects last for 15-20 minutes sufficient for the completion of LASIK surgery. Proparacaine
or benoxinate are given topically in the dosage of 2 drops
in each eye 2-3 times repeated at the interval of one
minute.
After topical anesthesia some refractive surgeons
prefer to instill pilocarpine 1 percent in the eye to aid in
marking the optical axis.
Pachymetry is performed and patient is carefully
centred and eyelids are cleaned with betadine solution
(Iodine solution) and operative eye is given a sterile
plastic ophthalmic drape to cover the eyelid margins and
the cilia.
Post-Procedure Therapeutic Medications
The biggest advantage of LASIK over PRK is the minimum use of ocular therapeutic in postoperative phase.

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294 Section II: Refractive Surgery


The visual recovery in LASIK is virtually immediate
owing to the preservation of the epithelium of the cornea.
Typically recovery is painless and post-procedure
refractions and vision are remarkably stable during the
postoperative period. During the initial active postoperative phase. Refractive surgeons prefer to give
a. Oral antibiotic (Ciprofloxacillin 500 mg bd for 5 days).
b. FML (0.1%) eyedrops four times a day for two weeks.
c. Topical lubricant like polyvinyl alcohol liquifilm tear
drops 4 times a day for two weeks.
d. Topical antibiotic (Lomefloxacillin 0.3%). QID for a
week. Immediately after LASIK procedure some
surgeons prefer to give patch for 2-3 hours. While
other view is to ask the patient to wear a clear eye
shield nightly for a week.
e. Oral analgesic (Tab. Diclofenac 75 mg SR BD for three
days if needed but not in routine).
Patient operated for LASIK surgery is called for
follow-up on
Second day post-procedure
First week
Second week
Third week
One each follow-up following examinations are done
Vision check-up
IOP with non-contact tonometer
Slit lamp examination for Haze
Topography to see corneal profile.
Corneal wound healing and its modulations after
LASIK surgery have multiple components. LASIK is a
refractive surgical procedure that is performed in several
steps and each step involved a different structure of
cornea.
Phases of Healing
Following LASIK injury healing occurs in several phases.
The earliest phase involves the healing of epithelial injury
and is characterised by the migration of epithelium which
occurs 12-24 hours after procedure 2-3 days after the
insult, epithelial cell proliferation is evident. Six months
after the surgical insult the development of fibrous
metaplasia is complete. Throughout these phases of
healing the types of cytokine communication are
operating to create an integrated repair of injured corneal
areas.
Although LASIK is safe and reliable procedure yet it
is susceptible to all the complications noted in PRK
procedure which includes over correction, under

correction, decentration, infection, loss and displacement


of flap, central islands and epithelial in growth.
Cornea healing following LASIK should be
considered as a combination of events involving the
response to injury of the epithelium and stroma.
Understanding these events and the molecules that
regulate the wound healing response should enable the
refractive surgeon to induce fewer complications and aid
in developing therapeutic modalities to alter wound
healing precisely.
Close follow-up and attention to postoperative
medications and surface lubrication will enable the
surgeon to achieve better results.
FURTHER READING
1. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.
2. Bartlett JD, Clinical Ocular Pharmacology, ed.4, Boston:
Butterworth-Heinemann,2001.
3. Bartlett JD, Ophthalmic Drug Facts, Lippincott William and
Wilkins, 2001.
4. Crick RP, Trimble RB, Textbook of Clinical Ophthalmology,
Hodder and Stoughton, 1986.
5. Duane TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
6. Duvall, Ophthalmic Medications and Pharmacology, Slack Inc,
1998.
7. Ellis PP, Ocular Therapeutics and Pharmacology, ed. 7 : C.V.
Mosby, 1985.
8. Fechner, Ocular Therapeutics, Slack Inc., 1998.
9. Fraunfelder, Current Ocular Therapy, ed. 5 : W.B. Saunders,
2000.
10. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
11. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
12. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
13. Goodman LS, Gilman A, Pharmacological Basis of Therapeutics,
ed.7, New York: Macmillan, 1985.
14. Haveners, Ocular Pharmacology, ed. 6 : C.V. Mosby, 1994.
15. Kanski, Clinical Ophthalmology, ed. 4 : Butterworth
Heineman, 1999.
16. Kershner, Ophthalmic Medications and Pharmacology, Slack.
Inc., 1994.
17. Olin BR et al, Drugs Facts and Comparisons, Facts and Comparisons, St. Louis, 1997.
18. Onofrey, The Ocular Therapeutics, Lippincott-William and
Wilkins, 1997.
19. Rhee, The Wills Eye Drug Guide, Lippincott William and
Wilkins, 1998.
20. Steven Podos, Textbook of Ophthalmology, New Delhi: Jaypee
Brothers Medical Publishers, 2001.
21. Zimmerman, Textbook of Ocular Pharmacology: Lippincott and
William and Wilkins, 1997.

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Chapter 31: Phakic Refractive Lens (PRL) Indications and Techniques 295

31

Phakic Refractive Lens (PRL)


Indications and Techniques
Dimitrii D Dementiev, Kenneth J Hoffer

INTRODUCTION
PATIENT SELECTION
PREOPERATIVE
PREPARATION
PREPARATION OF THE PATIENT
ANESTHESIA
INSTRUMENTATION
HANDLING THE IMPLANT

INTRODUCTION
The history of the phakic refractive lens for the posterior chamber started
for me in 1985 after the author started to work in the Moscow Research
Eye Micro-surgery Institute headed by Dr. Fyodorov. There the idea was
born to find and study a phakic IOL, made of soft and elastic material
(silicone) to implant for the correction of high myopia.
The article by Dr. Benedetto Strampelli of Italy, in 1954, regarding his
experience with anterior chamber lenses (Fig. 31.1) led us to consider new
surgical techniques and new phakic IOL models. Strampellis ideas failed
because of poor materials, absence of modern surgical equipment and the
lack of modern modalities such as viscoelastic. The first prototype of the
phakic myopic implant was the Mushroom IOL, made from silicone (Figs
31.2 and 31.3).

SURGICAL STEPS
OPERATIVE MEDICATIONS
POSTOPERATIVE CARE
CONCLUSION
PEDIATRIC USAGE
FUTURE APPLICATIONS

Fig. 31.1: Anterior chamber phakic IOL

The implant was fixated by the pupil, its haptic was placed in the
posterior chamber and optic part was placed in the anterior chamber (Fig.
31.2).
From 1986 to 1990, more than 400 implantations of this design were
performed by Dr. Zuev and myself. We were impressed with the refractive
results we obtained, but because of pupil fixation and small optic zone
diameter, we saw complications such as pupillary block, anterior capsule
opacification, cataract, endothelial cell loss, night glare, and inflammatory
reactions.

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296 Section II: Refractive Surgery


This new model permitted us to use less traumatic
surgical techniques than before, and to avoid many of
the complications caused by the previous Mushroom
model.
Since 1992, the development of the posterior chamber
implants was divided in 3 paths, the difference being in
the PRL fabrication from different materials:
1. Silicone Posterior Chamber Phakic IOLlater to be
known as PRLTM
2. Collamer Posterior Chamber Phakic IOLlater to be
known as ICLTM
3. Silicone-elastomer PC Phakic IOL by CHIRONADATOMED.
These different implants have been under experimental study by different investigators. Today only two
Posterior Chamber Phakic Implants are under US FDA
study:
1. ICLTM by STAAR Surgical AG, Switzerland
2. PRLTM by IVI-Medennium, Irvine, CA, USA
In this chapter our experience with Phakic Refractive
Lenses (PRL) or the silicone posterior chamber implant,
will be described.
PATIENT SELECTION
Myopic Range

Fig. 31.3: Pupil fixated phakic IOL

These experiences forced us to interrupt our study


with this model. We looked for new silicone formulas
and worked on changes to the implant configuration that
would permit us to implant it in the posterior chamber.
We began working with Igor Valunine, PhD and he
managed to create a high refractive index silicone, from
which he made the new model of the Posterior Chamber
Phakic IOL. Based on the work with the Mushroom lens,
the concept of a purely posterior chamber PRL was
proposed and was made from a completely new silicone
material which was not toxic and had a higher refractive
index. The configuration, parameters and the mechanism
of fixation of this PRL was completely different from the
previous Mushroom model. It was intended for
implantation entirely in the posterior chamber with
fixation on the zonular fibers. The optical zone diameter
was 4.5 mm and the total length was 10.0 mm. The lens
was created for surgical high myopia correction starting
from 10.0 D. This lens was the first prototype of all
other posterior chamber PRLs available on the market
today.

From 6.00 D to 22.00 D for the present.


In the future it will be possible to start implanting
them for myopia range from 4.00 D to 25.00 D (Fig.
31.4).
Hyperopic Range
From +3.00 to +16.00 D.

Fig. 31.4: Posterior chamber myopic PRL

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Chapter 31: Phakic Refractive Lens (PRL) Indications and Techniques 297
Keratoconus Correction and Correction of the
Refractive Error after Previous Surgery
PRL implantations can be performed for keratoconus
correction with a high myopia component and for
overcorrection of a previous refractive procedure such
as RK, PRK, or LASIK. We have also had to exchange a
previous model of PRL with a new one.
Poor Candidates
1.
2.
3.
4.
5.
6.

Clouded or non-transparent cornea


Cataract
Lens subluxation
Glaucoma or ocular hypertension
Shallow anterior chamber (less then 3.0 mm)
Vitreoretinal problems that would preclude good
vision or require posterior segment intervention
7. Previous ocular surgery: vitreoretinal surgery, glaucoma filtration, etc.
8. Patients age more than 55.

Fig. 31.5: Hyperopic implant

PREOPERATIVE PREPARATION
PRL Power Calculation
It is important to obtain a precise refraction of the eye
(with accurate vertex distance measurement) as well as
an accurate axial length and corneal power readings to
use the various methods.
Russian Method: Vertex Chart
Fig. 31.6: Hyperopic PRL

A +16.0 D hyperope is the maximum we have


corrected (Figs 31.5 and 31.6).
Because the anterior chamber of the hyperopic eye is
usually shallow, it is safer to limit the hyperopic
correction for PRL implantation to a maximum of +11.00
D unless there is a deep AC greater than 3.0 mm.
Unilateral High Myopia with Amblyopia in Children
So far we have performed seven implantations for correction of unilateral high myopia in children with
amblyopia. In cases of progressive myopia, scleral
reinforcement surgery is recommended.53-57
Combined Astigmatism
In cases with astigmatism greater than 1.0 D we have
performed PRL implantation with additional AK surgery
waiting at least one month after the PRL procedure.

The spherical equivalent of the most accurate refraction


of the eye is used to interpolate the power of the posterior chamber PRL. These powers are based on a simple
vertex correction from 12 mm to the corneal plane. This
does not seem to make sense optically, but so far has
resulted in excellent accuracy in our experience.
Holladay Refraction Formula
Holladay published a formula in the AJO in 1993 to calculate the power of an IOL for an aphakic eye or ametropic pseudophakic eye (piggyback IOL) or a refractive
lens (PRL) for a phakic eye. It does not need the axial
length but requires the corneal power, preoperative
refractive error and desired postoperative refractive error
as well as the vertex distance of both.
a. For Emmetropia the formula is as follows:
PRL=1336/((1336/((103/((103/RPRE)-V))+K))ELP-1336/((1336/K)-ELP),
where RPRE = Preop Rx; V = vertex of RPRE;
K = Average K; and ELP = estimated ACD of PRL
b. For Ametropia, it is more complex:

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298 Section II: Refractive Surgery


PRL=1336/((1336/((103/((103/RPRE)-V))+K))-ELP-1336/
((1336/((103/((103/RPO)-V))+K))-ELP)
where RPO = Desired PO Rx; V = vertex of RPO
Iridectomy
Surgical
Usually we recommend performing a surgical iridectomy
at the time of PRL implantation. We feel it should be a
basal iridectomy made at 12:00 and we prefer to perform
it after the PRL is inserted. It is of the utmost importance
to make sure that it is a complete iridectomy by checking
whether the pigment layer has been cut through. This
must be done carefully so as not to damage the crystalline
lens.
Laser
Those surgeons who prefer not to make it surgically must
do it by YAG-Laser. It is recommended that two YAG
iridectomies always be performed at around two weeks
before the surgery and that they be made at 11:00 and
1:00. To avoid light and additional images passing
through the iridectomies, it is very important not to make
them too large and to make them as peripheral as
possible. We had one patient with severe complaints of
night glare. The iridectomy was found to be too large
and located nearer to the pupil. We decided to suture it
and after it became smaller, the patients complain
decreased. We have concluded that the iridectomys size
and placement is very important.
Medications
Medications can be divided into preoperative, during
surgery and postoperative:
1. Preoperative: Remove any contact lenses 36-48 hours
before the surgery and start the installation of antibiotics drops [Tobrall (Alcon)].
2. Surgery:
a. Hypotensive: Diamox is given 250 mg 30 minutes
before surgery.
b. Mydriatics: Maximum pupil dilatation is needed
during the surgery. We never use Atropine as
we need rapid pupil constriction at the end of
surgery.
c. Miotics: Acetylcholine is used in the AC for pupil
constriction.
d. Steroids: Subconjunctival injection of corticosteroid at the end of the procedure as well as a 4.0 mg
cortisone injection intramuscular (IM).

3. Postoperative:
a. Steroid-antibiotic drops (Tobradex, Alcon) 5-6
times a day for 7-10 days
b. Mydriatic drops for 3 days (no Atropine)
c. Diamox 250 mg for 2-3 days.
4. Other: The first day postoperative, transitory IOP
increase can be noticed (viscoelastic was not
completely removed from the AC or the PC). If the
IOP is more than 20 mm/Hg, it is necessary to
increase the dose Diamox to 250 mg, 3-4 times a day
till the IOP becomes normal.
PREPARATION OF THE PATIENT
To reduce the risk of infection and postsurgical
inflammation the surgeon has to pay attention to the
patient preparation. All the patients must be subjected
to routine blood and urine test and ECG.
We ask all our patients who wear contact lenses to
take them off prior to surgery and start using
antibiotic drops (TOBRAL) 3 days before the surgery
in the eye which will be operated.
The patients are asked to come to our Day-Hospital
in the morning of the surgery NPO. Everyone receives
an informed consent to read and are asked to sign it.
The pupil is dilated by mydriatic drops (Visumidriatic + phenynephrin) until the pupil reaches a
minimum of 5.0 mm diameter.
ANESTHESIA
Local
Retrobulbar or peribulbar anesthesia has always been
used. Topical can be used also, but it is very important
that the eye does not move at all during the sensitive
period where the haptics are placed behind the iris using
the spatula. A sudden unexpected movement could cause
you to damage the crystalline lens and cause a cataract.
INSTRUMENTATION
Incision
Incision clear cornea incision blade (diamond trapezoid
Dementiev blade 3.5 mm by Rumex International, USA)
(Fig. 31.7).
Insertion
Wide Dementiev Forceps for PRL implantation (Janac
Co., Italy) (Fig. 31.8).

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Chapter 31: Phakic Refractive Lens (PRL) Indications and Techniques 299

Fig. 31.9: Iridectomy forceps

Fig. 31.7: Trapezoid clear cornea 3.5 mm


dementiev diamond PRL blade

picked up using the special forceps. It is important to be


careful to be sure that the lens does not come into contact
with the skin, conjunctiva, lids, lashes or epithelium of
the cornea because some microelements can be attracted
to and become deposited on the lens surface. It is necessary to be sure that the implant is grasped with the
forceps in the correct position. The anterior surface of
the lens should be up and posterior surface should be
down. This can be seen by observing the fact that the
PRL has a similar convexity (curvature) paralleling that
of the natural lens. While grasping the lens with the
forceps, dont squeeze it too hard since it can be easy
damaged. We dont fold the lens; it is self-folding during
its insertion. After the implant has been grasped in the
correct manner and orientated in the forceps, we irrigate
it profusely using BSS from a syringe. It is important to
inspect it carefully and with fine forceps gently remove
any foreign particulate matter or fibers that may have
become attached to its surface. The lens is now ready for
insertion.

Fig. 31.8: Dementiev PRL forceps

SURGICAL STEPS
Manipulation
Dementiev PRO Spatula-Manipulator (Janac Co., Italy).

DO NOT START THE SURGERY IF THE PUPIL IS NOT


WIDER THAN 5.0 MM.

Iridectomy

Incision

Standard set for manual iridectomy: Iris scissors + iris


forceps (Rumex Int., USA) (Fig. 31.9).
Other
Standard lid speculum and eye fixation forceps (Rumex
Int., USA)
HANDLING THE IMPLANT
The PRL implant is supplied in a plastic sterile container.
After the container is opened, the implant has to be

Usually the incision is placed at the temporal cornea. Our


experience recommends performing a clear corneal, selfsealing incision of 3.0-3.2 mm in width. The incision can
be made with either a diamond or stainless steel blade
(Fig. 31.10).
Any method of fixation may be used to ensure that
there is no possibility of the blade contacting the anterior
lens capsule since the pupil is widely dilated. The incision
architecture should be one the surgeon is familiar with
for self-sealing cataract surgery. Non-suture closure is
the intended aim.

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300 Section II: Refractive Surgery

Fig. 31.10: Clear cornea self sealing incision


Fig. 31.11: Implant insertion

Viscoelastic Insertion
Next the anterior chamber should be filled with viscoelastic to achieve a chamber of not less than 3.0 mm in
depth. It is also helpful to place some viscoelastic under
the iris to make more room to facilitate lens insertion in
the posterior chamber.
Paracentesis
This incision is needed to perform the iridectomy and to
create an additional entry point for the lens manipulator
that will be needed in the next step to position the PRL
in the posterior chamber.
We make it no larger than 0.5 mm and it should be
placed at the 12:00 position. It can be made with a
stainless steel or diamond knife. The position of the knife
has to be perpendicular to the cornea surface and the cut
has to be made at the limbus so that the iridectomy will
be more basal. This will avoid:
1. Light passing through the iridectomy and the upper
lid will cover it (less halos),
2. The possibility of the iridectomy being blocked by
the edge of the PRL (pupillary block).
Lens Insertion
THIS IS THE MOST IMPORTANT AND DELICATE
STEP OF THE PROCEDURE;
The surgeon has to be extremely careful:
1. Not to damage the implant (very soft, thin and rather
expensive),
2. Not to damage the anterior capsule with the forceps,
3. Not to touch the endothelium with the implant or the
forceps.

Fig. 31.12: PRL insertion

The implant is grasped by the special forceps that is


designed to prevent damage to the PRL (protection of
the optical zone of the PRL). Only the haptic area of the
implant is in contact with the forceps. Since the lens is
very thin, we can insert it through a 3.0-3.2 mm incision
without any additional folding (Figs 31.11 and 31.12).
After the implant has been inserted into the anterior
chamber, the forceps must be opened gently to allow for
the release of the lens. Care must be taken that there are
no unexpected sudden movements of the eye during this
crucial maneuver.
If, after the lens is inserted, it is discovered that it is
upside down, it is necessary to correct this.
Retroiris Placement and Centration
Next, we must manipulate the peripheral edges of the
implant under the iris. Using the spatula-PRL Manipu-

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Chapter 31: Phakic Refractive Lens (PRL) Indications and Techniques 301
lator (entered through the paracentesis at 12:00), we move
the two lateral edges of the lens under the pupil margin
and under the iris. In this step, it is very important to
pay maximum attention so as not to put pressure on the
crystalline lens capsule. It is important to avoid anterior
capsule and cortical damage. It is very important not to
push too hard to get it under, but rather try to fold it
with the spatula and then release it under the iris to avoid
damage to the zonular fibers. When all four feet are
under the iris satisfactorily, the PRL optic zone is then
gently centered using the same manipulator.
Iridectomy
I prefer to perform the iridectomy at 12:00 through the
paracentesis site. The iridectomy has to be as peripheral
as possible. This decreases the risk of the PRL blocking
it. During this step, bleeding is possible. If this should
happen, I prefer to reinject viscoelastic in the area of
bleeding to act as a tamponade. After an appropriate
waiting period (and clotting has occurred), the
viscoelastic must again be removed.

Fig. 31.13: PRL in situ after pupil constriction

Patch
Placing a patch on the eye is not obligatory
OPERATIVE MEDICATIONS

Viscoelastic Removal

General

We now must try to remove all the viscoelastic by irrigation. It is extremely important to remove as much as
possible and not to leave any in the anterior or posterior
chamber. If this is not accomplished it may create:
1. Postoperative IOP increase,
2. Viscoelastic crystallization between the anterior
capsule and the posterior surface of the implant.
If it is not possible to remove all the viscoelastic by
irrigation, irrigation-aspiration may be used, but be
thoughtful of damaging the endothelial cells.

Pupil Constriction
It is important to constrict the pupil as much as possible
before the iridectomy is performed. We recommend
injecting acetylcholine solution into the AC to accomplish
this (Fig. 31.13).
Incision Closure
It is not necessary unless security of wound closure is in
doubt.

The use of BSS is recommended.


Viscoelastic of low density is recommended.
Acetylcholine is used in the AC for miosis.
Corticosteroid subconjunctival injection.
Pilocarpine drops are used at the end of the surgery.
Antibiotic drops are used at the end of surgery.

POSTOPERATIVE CARE
The Routine Postoperative Treatment is
1. Steroid plus antibiotic drops 5-6 times a day for
10-12 days (tobradex, alcon).
2. Mydriatic drops (no atropine) with 3-4 hours action
(not complete pupil dilatation), 2-3 times a day for
4-5 days.
3. Diamox 250 mg tablets
a. the first day PO: 250 mg + 250 mg a day.
b. from the second day PO: 125 mg +125 mg a day
for 2- 3 days.
4. Systemic steroids: We use them for the first/second
day PO.
5. Non-steroid drops: From 10-12 days (after the Tobradex is finished). We use Voltaren for 7 days.

Cortisone Subconjunctival Injection


At the conclusion of the procedure, it is preferred to inject
cortisone solution subconjunctivally at 12:00. I feel it
helps to close the paracentesis by the conjunctiva.

CONCLUSION
PRL implantation is :
1. Safe

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302 Section II: Refractive Surgery

Fig. 31.14: PRL in situ (UBM picture)

2.
3.
4.
5.
6.

Predictable
Reversible
Inexpensive for the doctor or the patient.
Able to achieve immediate and stable refractive effect.
Able to increase BUCVA and BCVA.
The technique is relatively safe and easy to perform
for any skilled cataract surgeon. The complications we
have seen are not serious and have been treatable. The
two main problems we need to look for in longer follow
up are subcapsular opacity (till now we have only one)
and pigment dispersion that may lead to glaucoma. Our
study shows that there is not pigment dispersion in
negative-powered silicon PRLs but some slow dispersion
in the positive-powered PRLs. The UBM ultrasound
study showed us that the implant does not touch the
anterior capsule, but we need to know more about contact
between the PRL and the capsule and iris (Fig. 31.14).
The goal of any refractive procedure is emmetropia,
and the predictability of the PRL implantation is very
promising in providing stable long-term emmetropia.
The most important point concerning PRL implantation is its reversibility. There are no refractive procedures
which can be reversed. With the promising results, and
more modern materials, surgical and diagnostic
equipment, it will be one of the most exciting areas of
ocular surgery.
PEDIATRIC USAGE
In cases of high unilateral myopia in children, PRL
implantation can be used instead of amblyopia treatment
with aniseikonic spectacles or forcing a contact lens.
The youngest patient in which we have implanted a
myopic PRL was 14.00 D at the age of seven. Twenty

months PO, 20/40 vision without correction was obtained


in this amblyopic eye which was 20/100 best corrected
preoperative. There are not many reasonable alternatives
today to help these young patients. Spectacle correction
is practically impossible and it is not easy to make them
wear contact lenses. These eyes are destined to become
strabismic with deep amblyopia for life. With PRL
implantation, we can not only correct myopia but treat
amblyopia and prevent strabismus. We prefer and recommend performing scleral reinforcing surgery one to two
months prior to implantation for the purpose of slowing
the growth of the eyeball. Even if the refractive error
changes when the child grows to adulthood, the PRL
implant can be easily exchanged and the procedure can
be repeated.
We are planning to start correcting hyperopia in the
near future, but till now, we don't have any clinical
experience in hyperopic correction with PRL
implantation in children. The surgical technique is the
same that we use for our adult patients. The only
difference is that general anesthesia is recommended, and
manual iridectomy at the time of surgery is preferable.
FUTURE APPLICATIONS
Piggyback Over IOLs
When two IOLs are necessary, it is certainly conceivable
that the second lens could be a posterior chamber PRL
that could be easily inserted in the capsular bag or in the
ciliary sulcus. In such special eyes that require piggyback
lenses the calculations of IOL power are often not as
accurate and it may be necessary to exchange anterior
lens the more. A PRL is much easier to remove and replace
than an IOL.
Pseudophakic Ametropia Correction
Every patient who is unhappy with the refractive results
of their cataract/IOL surgery could be offered a rather
simple procedure of posterior chamber PRL implantation
over the top of the IOL. This would open a whole new
market for the anterior segment surgeon and replace the
dangers inherent in removing and replacing a wellplaced IOL in the bag. Patients could be almost assured
of obtaining the refractive result they desire.
Those patients who wish to try monovision could
have the non-dominant eye implanted with an additional
appropriate plus power PRL over the emmetropic IOL.
If they could not tolerate the monovision, the PRL could
be easily and atraumatically slipped out.

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Chapter 31: Phakic Refractive Lens (PRL) Indications and Techniques 303
Multifocal Correction
The posterior chamber PRL could open two fronts in the
use of multifocal IOLs.
1. Any and all patients could try the concept by having
an emmetropic IOL implanted with a multifocal PRL
placed on top of it during their cataract removal. After
the patient has had sufficient time to become
accustomed to it, they could decide whether they wish
to keep it or have it easily slipped out.
2. All patients who have missed the chance for getting
a multifocal IOL could now have a multifocal PRL
placed on top of their IOL to try it out. Again, if they
didnt like it, it could be easily removed. Perhaps any
over or under-correction in the original IOL could also
be taken into account in the PRL distance power.

16.

17.

18.

19.

20.
21.

BIBLIOGRAPHY
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12. Brauweiler P, Busin M, Wehler T: High incidence of cataract
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13. Brown D: Use of the STAAR surgical implantable contact lens
for high myopia. ASCRS annual meeting, Boston, USA, 1997.
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Dementiev D: Silicone phakic posterior chamber intraocular lens
(P-PCIOL) and the management of pediatric Anisometropia.
ASCRS annual meeting, San Diego, USA, 1998.
Dementiev D, Rozakis G, Hatsis A et al: The 5 years experience
in the phakic refractive posterior chamber IOL. Implantation
for the correction of high ametropia. Binkhorst Symposium
during XXVIII International Congress of Ophtalmology,
Amsterdam, Holland, 1998.
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Corneal Surgery 1990;6: 242-44.
Fechner PU: Phakic IOLs is promising for high myopia by
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Fyodorov, Zuev, Aznabaev: Intraocular correction of high
myopia with negative posterior chamber lens. Ophthalmosurgery 1991;3: 57-58.
Fyodorov, Zuev, Tumanian et al: Clinical and functional followup of minus IOL implantation in high grade myopia. Ophthalmosurgery 1993;2:12-17.
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edema, and iris-suported intraocular lenses. Ophthalmology
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Guell JL: Cataract formation after phakic IOL implantation,
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Hatsis A: Phakic posterior IOLs for the correction of high
hyperopia and high myopia. ASCRS, Boston, USA, 1997.
Hatsis A: Silicone posterior chamber intraocular lens (P-PCIOL),
American Blind Eye Study. ASCRS annual meeting, San Diego,
USA, 1998.
Hodkin M, Lemos MM, McDonald MB et al: Near vision
sensitivity after photorefractive keratectomy. J of Cataract
Refractive Surgery 1997;23(Suppl 2).
Hoffer KJ: Predicting silicone phakic posterior chamber IOL
power in the management of high hyperopia. ASCRS annual
meeting, San Diego, USA, 1998.
Holladay JT: Refractive power calculation for intraocular lenses
in the phakic eye. Amer J Ophthalmol 1993;116: 63-66(24).
Izak M: Worst myopia iris claw IOL implantation. ASCRS
annual meeting, Boston, USA, 1997.
J Worst: Phakic high myopia correction. ASCRS meeting, Boston,
1997.
Kanski J: Clinical ophthalmology. In Woo GC, Wilson MA (Eds):
Current Methods of Treating and Preventing Myopia,
Butterworth Ltd., 1989. Optometry and Vision Science 1990;
67(9): 719-27.
Kariger U: Refractive Baikoff anterior chamber lenses
implantation. ASCRS, 1997.
Landesz M, Worst JGF, Siertsema JV et al: Correction of high
myopia with the Worst myopia claw intraocular lens, XXVIII
International Congress Ophthalmology, Amsterdam, Holland,
1998.
Lavery F: Laser in situ Keratomileusis for Myopia. Journal of
Refractive Surgery 14(Suppl 2): 1998.

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37. Luger MHA: The Staar collamer phakic posterior chamber IOL
to correct myopia and hyperopia, XXVIIIth ICO, Amsterdam
1998.
38. Marinho A et al: Phakic IOLs: The state of the art. ASCRS annual
meeting, San Diego, USA, 1998.
39. Marinho A, Neves MC, Pinto MC et al: Posterior chamber silicone phakic intraocular lens. Journ Refrac Surg 1997;13(Suppl
3).
40. Pallicaris I: Barraquer lecture. AAO annual meeting, San
Francisco, USA, 1997.
41. Rozakis G, Dementiev D, Avalos G et al: Complications of
silicone phakic posterior chamber intraocular lens (P-PCIOL)
for the correction of high ametropia. ASCRS annual meeting,
San Diego, USA, 1998.
42. Rozakis G, Dementiev D, Hatsis A et al: Complications of silicon
phakic posterior chamber lenses for the correction of high
ametropia. ASCRS, San Diego, USA, 1998.
43. Saragoussi JJ et al: Damage to the corneal endothelium by minus
power anterior chamber intraocular lenses. Refract Corneal Surg
1991;7.
44. Saragoussi JJ, Puech M, Assouline M et al: Ultrasound biomicroscopy of Baikoff anterior chamber phakic intraocular
lenses. Journal of Refractive Surgery 1997;13(Suppl 2).
45. Sosnier Z: Evaluation of the effect of Synder-Thompson
scleroplasty based on the behavior of the axial dimension of
the eye ball. Klin Oczna 1989;91: 19-20.
46. Strampelli B: Supportalita di lenti acriliche in camera anteriore
nella afachia e nai vizi di r refrazione. Ann Ottalmol Clin Oculist
1954;80: 70-82.
47. Tarutta E, Saksanova E: Peripheral segments of the fundus oculi
in highly myopic patients after scleroplasty. Vestn Opht 1991;
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48. Tereschenko A: Complications of minus silicone posterior


chamber phakic lenses. ASCRS annual meeting, Boston, USA,
1997.
49. Tratta E, Shamlokova E: An analysis of the late results of
scleroplasty in progressive myopia. Ophthal Zh 1989;4: 204-07.
50. Tumanian E: Surgical correction of high myopia by the method
of implantation of negative phakic IOL. Diss Kand Medic
(Russian) 1989;158-64.
51. Tumanian E, Zuev VK, Koslova TV: Hydrodynamics before and
after implantation of negative IOL in highly myopic phakic eye.
Ophthalmosurgery 1997;4:50-56.
52. Vorotnikova EK, Kurenkov VV, Polunin GS: Retreatment of
regression after photorefractive keratectomy for myopia. Journal
of Refractive Surgery 1998;14(Suppl 2).
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healing after PRK in rabbit eyes. Journal of Refractive Surgery
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Orleans, USA, 1998.
55. Worst JGF: Iris anatomy and its surgical implications, XXVIII
International Congress of Ophthalmology, Amsterdam,
Holland, 1998.
56. Worst JGF: Recent improvements in phakic refractive correction
with iris claw lens. ASCRS annual meeting, San Diego, USA,
1998.
57. Zaikova M, Molokova N: Scleroplasty results in progressive
myopia with use of allogenic. Vestn Opht 1990;106(3): 16-19.
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32

Visual Acuity with


Contact Lenses Vs LASIK in Myopia
Melania Cigales, Fernando Rodriguez-Mier, Marta Marsan, Jairo E Hoyos

INTRODUCTION
OPTICAL PHYSIOLOGY
MATERIALS AND METHODS
RESULTS

INTRODUCTION
There are several options to consider for correcting refractive errors
spectacles, contact lenses or refractive surgery. All of these options, starting
with spectacles which were already recommended by Daza de Valds1 in
1623, through contact lenses2,3 and finally surgical correction by means of
refractive surgery,4,5 are all valid for the correction of refractive errors but
should always be considered bearing in mind the knowledge, practice and
experience of the ophthalmologist and the best optical and visual benefit
for the patient. Many medical and surgical factors influence the selection
of one therapeutic option over another, including complications from the
use and abuse of contact lenses, the potential complications of the refractive
surgery, the difficulty of wearing spectacles in certain jobs or leisure
activities, or the psychological rejection to their use.
In this study we will only present the results of our comparisons of
visual outcomes with contact lenses and refractive surgery, in reference to
myopic patients who underwent LASIK surgery. Visual differences between
contact lenses and refractive surgery with LASIK will be explained on the
basis of the optical analysis of image size, visual field and the chromatic
quality of the images obtained with corrective spectacles. The analysis was
performed using charts based on the principles of optics, thickness factors,
distance from the eye and lens powers.
OPTICAL PHYSIOLOGY
Visual acuity is the ability of the eye to perceive the details of a shape or
form. The minimum separable is the minimum distance at which two points
may be perceived as separate.
The majority of myopic patients report better visual quality and acuity
with contact lenses than with glasses. Let us consider some aspects related
to vision which change depending on whether the refractive error is
corrected with spectacles or with contact lenses.
Ocular Accommodation
With spectacles, the vergence of the object changes as it passes through the
glasses, which is not the case with contact lenses because of their close
contact with the cornea. The range of accommodation of a myopic patient
using contact lenses will be much larger than with spectacles, and the higher

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306 Section II: Refractive Surgery


the myopia, the larger the range of accommodation.6
Patients with high myopia complain of problems with
near vision during the first few days of contact lens wear.
Ocular Convergence
When spectacles are used for correcting myopia, the optic
centers on the spectacles are centered for distant vision
giving rise to a nasal prism effect in near vision which,
in turn, creates a smaller convergence than would exist
with the naked eye.7 Convergence in the patient corrected
with contact lenses will be greater than in the patient
corrected with spectacles, since correction will move
together with the movement of the eye without creating
the prism effect.
Visual Field
The visual field for the contact lens wearer is the same as
would exist with the naked eye. The field shrinks with
the use of spectacles depending on the vertex distance,
the diameter of the glasses, the frame, etc.8
Optical Aberrations
Chromatic aberrations (induced by the nature of the
material) as well as geometric aberrations (due to lens

geometry) occur with spectacles because the curvature


and power of the glasses cannot be the same throughout
the entire surface; for this reason, when the eye is not
looking through the optical center of the spectacles, visual
quality diminishes. For one material, the distortion effect
of the lens is greater the longer the passage through it
and the greater the angle at which light hits and leaves
the surface. Therefore, lens aberration will be greater the
higher its power and the farther away it is from the
cornea.9 Contact lenses, because of their smaller size and
their ability to rotate with the eye, give rise to much
smaller aberrations.
Magnification of the Retinal Image
The retinal image is the image of an object formed on the
retina and may be focussed or unfocussed depending
on whether it coincides with the optical image or not (Fig.
32.1).
Optical correction of a refractive error is achieved
when the image focus of the corrective lens is made to
coincide with the focal point of the ametropic eye, in this
case the myopic eye. Therefore, the power of the
corrective lens will vary depending on the distance at
which it is placed from the eye. In myopic patients, the
farther away from the eye, the greater the lens power

Fig. 32.1: Myopes image with and without correction. Image formation of an object O located to the left. No
use of optical correction is depicted below. When the minus lens is used, the object forms a smaller image
(I2) which is located further back

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Fig. 32.2: Lens power and magnification. Lenses of lower and greater power, respectively, are depicted
above and below. Both are located at the same distance from the eye. The image (I) formed by the higher
power lens is formed farther away and it is smaller than the other image (I2)

required for correcting the same refractive defect and vice


versa and, in each case, the lens-induced vertex
magnification will be different.
Vertex magnification is the relationship between the
retinal image of the compensated eye and the retinal
image of the non-compensated eye.10
Vertex magnification = 1/(1Vd Sp) = Y/Y
Where
Vd = Vertex distance of the spectacles
Sp = Spectacle power
Y = Retinal image through the glasses (sharp image)
Y = Uncorrected retinal image (blurred image)
The formula implies that the greater the power of the
spectacles in a myopic patient (Sp), or the greater the
vertex distance (Vd), the smaller the retinal image seen
through the spectacles (Y) (Figs 32.2 and 32.3).
The same formula can be used to compare the size of
the retinal image which would be theoretically obtained
in an emmetropic patient and in a myopic patient
wearing 5.00 D spectacles, both of them with a visual
acuity of 0.8 (using the letter E on the Snellen chart at
3 meters).

The following formula is used to calculate the size of


the letter (Y):
Y = d u (rad) = d u 2.9 104 = (d 2.9 104 )/VA

Where
Y = Object size in meters
d = Distance between the object and the eye in
meters
u = Angle in radians formed by object height and
distance in relation to the eye
u = 1 rad
VA = Visual acuity on the Snellen decimal scale
Thus, the size of the object (Y) seen by a patient with
0.8 visual acuity from a 3 meter distance (d) will be: Y =
(3 2.9 104 )/0.8 = 1.09 103 meters (Fig. 32.4).
Retinal Image for an Emmetrope
Let us now calculate the size of the retinal image in an
emmetropic patient capable of distinguishing an object
1.09 103 meters in size.
Our theoretical eye has only one 60 diopter lens, and
the formula is then applied as follows:

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308 Section II: Refractive Surgery

Fig. 32.3: Vertex distance and magnification. Considering two lenses of equal power but placed at a
different distance from the eye, the closer the lens is to the eye, the greater the corrective effect and the
larger the images size

Fig. 32.4: Objects size and visual acuity. The minimun separable is the minimum value at which two close points are seen
as separate

Y = u [(1+ Vd R)/(R + Ep)]


u = Y/X

Where
Y = Retinal image in meters
u = Angle in radians formed by the height and
distance of the object in relation to the eye
Vd = Spectacle vertex distance = 12 mm
R = Spectacle power at the cornea = 0 D (emmetropic patient)
Ep = Eye power (theoretical eye = 60 D)
Y = Object size in meters
X = Distance in meters between the object and the
eye.
Thus, the retinal image (Y) for the emmetrope will
be:
Y= 3.63 104 [(1 + 12 103 0)/
(0 + 60)] = 6.05 106 meters
Retinal Image for a Myope
The following is the calculation of the retinal image (Y)
in a myopic patient wearing 5.00 D spectacles who is
capable of seeing the same object.
Considering that it is an axial myopia, Ep = 60 D, the
refraction value is calculated on the corneal plane (r):

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Chapter 32: Visual Acuity with Contact Lenses Vs LASIK in Myopia


R = Sp/(1 Vd Sp)
Sp = Spectacle power = 5.00 D
Vd = Vertex distance = 12 mm.
If the patient has a 5.00 D myopia, then R = 4.72 D
and the retinal image will be: Y = 3.63 104 [(1 + 12
103 4.72)/( 4.72 + 60)] = 6.19 106 meters.
The image will be blurred because the object is farther
away from the remote point for the myopic eye and larger
in size than the one obtained on the retina of the
emmetropic eye (6.05 106 m.). Now let us consider the
vertex magnification of the retinal image when the
patient looks at the same object through spectacles.
Vertex amplification = Y/Y = 1/(1 Vd Sp)
Where
Vd = Vertex distance = 12 mm
Sp = Spectacle power = 5.00 D
Y = Myopic retinal image without spectacles
Y = Myopic retinal image with spectacles
Y = 0.94 Y = 5.82 106 meters
Therefore, for the same visual acuity (0.8), the size of
the retinal image through the spectacles of a myopic
patient (Y= 5.82 106) will be significantly smaller than
the one in the emmetropic eye (Y= 6.05 106). This

309

means that the discrimination ability in this patient is


greater because he or she is able to see a much smaller
image.
Now let us calculate the visual acuity of an emmetropic eye which is capable of discriminating the size of the
retinal image of the 5.00 D myope through his or her
spectacles (Y = 5.82 106):
Y = u [(1 + Vd R)/R + Sp] = u (1/Sp)
u = Y Sp = 5.82 106 60 = 3.49 104 meters
u = Y/X;Y = u X = 3.49 104 3 = 1.05 103
meters
VA*= (d 2.9 104)/Y = (3 2.9 104 )/
(1.05 103) = 0.83
Therefore, a 5.00 D myopic patient wearing
spectacles, with a visual acuity of 0.8, when fitted with
contact lenses would achieve a theoretical visual acuity
(VA*) of 0.83.
We will use the same procedure described above to
calculate image amplification in other myopic patients,
all of them with a visual acuity of 0.8 (measured with
the letter E of the Snellen chart at 3 meters), wearing
10.00 D, 15.00 D and 20.00 D spectacles, respectively
(Fig. 32.5).
These results show why high myopes improve their
visual acuity with contact lenses, since the magnification

Fig. 32.5: Magnification and visual quality. The table shows the magnification calculations for different
myopic ametropias. VA* is the theoretical visual acuity that would achieve the patient wearing contact lenses

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310 Section II: Refractive Surgery

Fig. 32.6: Contact lens and magnification. A lens of 8.87 D placed on the cornea (vertex distance = 0 mm)
produces a larger image at the same focal distance as a lens with the equivalent power (10.00 D) placed at
a vertex distance of 12 mm

effect of the retinal image disappears. When comparing


a common spectacle lens with a contact lens of equivalent
power, in the myopic patient the image size obtained with
the spectacle lens is smaller than the one obtained
through the contact lens (Fig. 32.6). The higher the
myopia, the greater this difference will be.
The purpose of the following study is to determine
what happens to the visual acuity of this myopic patient
who is a contact lens wearer and decides to undergo
refractive surgery. We will also assess whether the vision
achieved after LASIK is the same as the one achieved
with contact lenses, considering that surgery also
eliminates the magnification effect produced by the
spectacles, or whether there are other factors which might
prevent this from happening.
MATERIALS AND METHODS
A total of 100 myopic eyes wearing contact lenses to
correct myopia or myopic astigmatism were studied: 55
eyes soft contact lens wearers, 34 eyes rigid gaspermeable (RGP) contact lens wearers, and 11 eyes toricsoft contact lens wearers.
The eyes were divided into four groups on the basis
of the spherical equivalent (Fig. 32.7):
Group A: Up to 5.00 diopters (23 eyes)
Group B: From 5.25 to 10.00 diopters (39 eyes)

Group C: From 10.25 to 15.00 diopters (22 eyes)


Group D: More than 15 diopters (16 eyes).
All patients underwent a thorough ophthalmological
examination. Corrected visual acuitys for distance and
near were measured. Visual acuity data were collected
and analyzed in decimal fraction units. Visual acuity was
assessed in all cases with the contact lenses worn by the
patients before surgery, and it was compared with the
visual acuity obtained after LASIK surgery, using the
Snellen decimal scale.
Refraction was performed under cycloplegia and
surgery was planned for cycloplegic refraction. A
computerized corneal topography was performed (TMS1, Computed Anatomy Inc., software release 1.61, New
York, NY) and the Simulated Keratoscope reading (Sim
K) was used to analyze the pre- and postoperative corneal
curvature.
Contact lens wear was discontinued before surgery,
for a period of 2 weeks for soft lens wearers and 4 weeks
for RGP lens wearers. All of the patients signed an
informed consent before surgery.
All of the interventions were performed by the same
surgeon (JH) at the Instituto Oftalmolgico de Sabadell
(Barcelona, Spain). The intervention was myopic LASIK
using the Automated Corneal Shaper microkeratome
(Chiron Vision, Claremont, CA) to create a flap 8.5 mm in
diameter and 160 m in thickness. The myopic ablation

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Chapter 32: Visual Acuity with Contact Lenses Vs LASIK in Myopia

311

Fig. 32.7: Types of contact lenses. The table shows the relationship between
refraction, contact lenses and patients

was performed with the broad beam excimer Apollo laser


(Apollo Vision Inc, California, CA), using a 193 nm wavelength, a 260 to 290 mJ/cm2 fluency energy, a 10 Hz
repetition frequency and a cut rate of 0.25 microns per
pulse. The patient was asked to fix the eye on a heliumneon light and the ablation was centered on the visual
axis. The surgery was planned to the cycloplegic refraction correction expressed in terms of a negative cylinder,
and the astigmatism was treated by flattening the steepest
meridian.
RESULTS
The following was observed when comparing visual
acuity with contact lenses in the 100 eyes studied with
the visual acuity without optical correction achieved after
LASIK (Fig. 32.8):
Visual acuity diminished (from 1 to 5 lines of vision)
in 41 percent of eyes
Visual acuity improved (from 1 to 6 lines of vision) in
34 percent of eyes
Visual acuity maintained the same in 25 percent of
eyes.
Visual acuity remained the same or improved in the
majority of eyes (59%) after LASIK. The analysis of the
reasons for improved visual acuity after LASIK revealed
that 70 percent were using undercorrected contact lenses

Fig. 32.8: Visual acuity without correction. The graph shows


the visual results obtained in the 100 eyes studied comparing
the visual acuity with contact lenses before LASIK and the
uncorrected visual acuity (UCVA) achieved after LASIK

and 12 percent had contact lenses in bad condition. The


main cause for diminished visual acuity after LASIK was
undercorrection after surgery (55%), but undercorrection
was intentional in 30 percent of these cases because their
presbyopic age.

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312 Section II: Refractive Surgery

Fig. 32.9: Visual acuity without correction. The table shows the visual results obtained in each group comparing the
visual acuity with contact lenses before LASIK and the uncorrected visual acuity (UCVA) achieved after LASIK

When analyzing these visual results for the different


groups of myopia (Fig. 32.9) we find that myopias up to
10.00 D (groups A and B) showed the best improvement
after LASIK surgery, whereas myopias greater than
10.00 D (groups C and D) showed the greatest reduction
of visual acuity after surgery. This is explained by the
poor predictability of LASIK in high myopias.
Overrefraction was performed with contact lenses in
order to determine the best preoperative visual acuity,
which was then compared with the best-corrected visual
acuity (BCVA) after LASIK. The results were as follows
(Fig. 32.10):
52 percent maintained the same visual acuity.
30 percent gained visual acuity after LASIK (from 1
to 5 lines of vision).
18 percent lost visual acuity after LASIK (15 eyes lost
one line of vision and 3 eyes lost two lines).
The majority of eyes (82%) maintained or gained
visual acuity after LASIK. The analysis of these results
according to myopia groups (Fig. 32.11) showed that the
group which gained most visual acuity after LASIK was
group A with less than 5.00 D (52%), while the group
with the greatest loss was group D with more than
15.00 D (44%).
The expected theoretical result would have been that
in the majority of eyes, the BCVA after LASIK should

Fig. 32.10: Visual acuity with correction. The graph shows


the visual results obtained in the 100 eyes studied comparing
the preoperative best corrected visual with contact lenses
with the best-corrected visual acuity (BCVA) after LASIK

have been the same as with contact lenses before surgery


and would have been even better, considering that in
some cases the lenses were soiled and did not allow for
good visual quality. This theoretical outcome was
obtained for the groups with less than 15.00 D myopia

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Chapter 32: Visual Acuity with Contact Lenses Vs LASIK in Myopia

313

Fig. 32.11: Visual acuity with correction. The table shows the visual results obtained in each group comparing the preoperative best corrected visual with contact lenses with the best-corrected visual acuity (BCVA) after LASIK

(groups A, B and C), where 87 percent of the eyes maintained or improved the visual acuity obtained with contact lenses, and where the eyes that showed loss of vision
(13%) lost only one line.
The group with myopia greater than 15.00 D (group
D) showed the greatest loss of visual acuity after LASIK
as compared with the preoperative visual acuity with
contact lenses (44%). However, this was not associated
with a surgical complication, considering that the cases
selected for this visual assessment had no complications
during or after LASIK. It was found that 71 percent of
the patients with more than 15.00 D who lost vision were
rigid gas-permeable (RGP) contact lens wearers with a
preoperative visual acuity with contact lenses ranging
between 0.6 and 0.8, which is higher than expected in
these high myopias.
No association was found between loss of visual
acuity and post-LASIK keratotomy studied with
topography (Sim K). Similar Sim K values were found
both in eyes that lost vision as well as in eyes which
maintained the same vision after LASIK.
We believe that the loss of visual acuity found in the
group with more than 15.00 D myopia could be
associated with the small optical zones used for LASIK
correction in these high myopes. Optical zones greater
than 5 mm were used in groups A, B and C, but in group

D (> 15.00 D) 5 mm optical zone was used and these


patients reported splitting of the image edges which
prevented clear vision. This might be the cause for visual
acuity loss in these eyes which were able to see very small
images before surgery and which saw split images
difficult to decipher after surgery as a result of the
interference with the edge of the optical zone.
CONCLUSION
Refractive surgery has a number of ophthalmological and
psychological connotations. LASIK is a refractive
technique used to solve a refractive error which, in many
cases, had been solved totally or partially by contact lens
wear. Therefore, it is mandatory to assess patients
expectations regarding this form of surgery.
We have observed that the higher the myopia, the
greater the degree of patient satisfaction after LASIK,
since there is no longer a need to depend on the optical
correction. However, there is also a greater possibility of
undercorrection and of inducing glare and halos in night
vision as a result of the optical zone diameter and corneal
shaping used for correcting the refractive error.
REFERENCES
1. Daza de Valds. Uso de los anteojos. Sevilla. Ed. Garsi, Madrid
1982;1623.

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314 Section II: Refractive Surgery


2. Mann IC: History of contact lenses. Trans Soc UK 1938;58:109.
3. Ridley F: Clinical significance of contact lenses. Br Ortho J
1954;10: 10.
4. Trokel S, Srinivasan R, Braren B: Excimer laser surgery of the
cornea. Am J Ophthalmol 1983;94:125.
5. Buratto L, Ferrari M, Rama P: Excimer laser intraestromal
keratomileusis. Am J Ophthalmol 1992;113:291-95.
6. Optics, refraction and contact lenses. Basic and Clinical Science
Course Section 3. American Academy of Ophthalmology: San
Francisco 1997.

7. Belmonte N: Refraccin Ocular. Ediciones Doyma, S.A.


Barcelona 1989.
8. Duke-Elder S, Abrams D: Ophthalmic optics and refraction. In
Duke-Elder S (Ed): System of Ophthalmology Kimpton: London
1970;5.
9. Welford WT: Aberrations of the Symmetrical Optical Systems
Academic Press, 1974.
10. Yves Le Grand: Optique physiologique. Ed. Revue dOptique,
Paris, 1964.

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Chapter 33: Contact Lens Fitting in Refractive Surgery 315

33

Contact Lens Fitting in


Refractive Surgery

Ashok Garg

CONTACT LENS FITTING AFTER


RADIAL KERATOTOMY
CONTACT LENS FITTING AFTER
PHOTOREFRACTIVE
KERATECTOMY (PRK)
CONTACT LENS FITTING IN
LASIK SURGERY

Contact lenses have significant role to play in the modern refractive surgery,
whether it is Radial Keratotomy, Photo refractive Keratectomy (PRK) and
latest lasik surgery, no system is yet so perfect to achieve 100 percent
uncorrected emmetropia. In such situations patients are weary of putting
spectacles again for overcorrected/undercorrected visual acuity and
astigmatism. Contact lenses are the only viable effective way to achieve
20/20 visual acuity.
Let me discuss here the significance and usefulness of contact lens fitting
in various refractive procedures being practiced by ophthalmologists
worldwide.
CONTACT LENS FITTING AFTER RADIAL KERATOTOMY
Till the last decade Radial keratotomy was the treatment of choice for curing
myopia and to certain degree of hypermetropia. Although this technique
is now out of favour in developed countries but still in developing countries
RK surgery is treatment of choice for more than 50 percent of patients.
This may be due to high cost factor in modern LASIK surgery.
Despite advancements in diamond knife and techniques of radial
keratotomy about 15-20 percent of patients remain under corrected or over
corrected (1 D or greater). Such patients are ideally suited for contact lens
fitting to achieve 20/20 vision.
Indications for Contact Lens Fitting in RK Surgery

Over correction
Under correction
Irregular astigmatism
Regular astigmatism
Anisometropia
Fluctuating vision
Contact lens fitting following RK surgery poses difficulty to both patient
and ophthalmologist because of post RK corneal topography. Patient is
emotionally down due to unfulfilled expectations of free of spectacles and
contact lenses.
Computerized corneal topography shows the central corneal flattening
which reduces the myopia power of eye along with relative steepening of
peripheral cornea (Figs 33.1 and 33.2). Epithelium may show dystrophic
changes, hypoesthesia and punctate lesions.

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316 Section II: Refractive Surgery

Fig. 33.1: Corneal topography before and after RK


surgery (picture in left showing cornea before RK
while one on the right after RK. Note blue coloration in the areas of keratotomy lines. (Courtesy: Dr
Agarwals Eye Hospital, Chennai, India)

In intersecting incisions there may be marked surface


irregularity which may lead to decentration, central pool,
intermediate touch and marked ocular irritation due to
lifting of edges. Tear pool stagnation may result in
hypoxic damage.
In such corneas contact lenses tend to slip themselves
over the steeper part of the cornea which leads to
decentration and improper vision.

Lens should not move excessively


Lens weight should be uniform over a large part of
cornea
Proper centration to achieve optimal vision.

Fitting Procedure
It is generally recommended to wait at least for 3-6
months after radial keratotomy before contact lens fitting.
Generally large rigid gas permeable lenses (RGP lenses)
are lenses of choice in post RK condition because these
lenses provide excellent oxygen transmission, move
perfectly on the cornea and provides good tear exchange
and good visual acuity (Figs 33.3 and 33.4). These lenses
are fitted by hit and trial method on the basis of following
primary requisites:
Good Tear Exchange

Fig. 33.2: Corneal topography in post RK cornea (Note flat


central cornea and peripheral steepening)

Fig. 33.3: Contact lens fitting in post RK period

Fig. 33.4: Ideal fluorescein pattern in post RK phase with


RGP contact lenses

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Chapter 33: Contact Lens Fitting in Refractive Surgery 317


Choice of RGP Trial Lenses
If post RK corneal flattening is not excessive (about 38 D
or greater) than regular RGP lens (Spherical or aspheric)
and of high oxygen transmissibility can be fitted usually
a large lens of 9.5 mm diameter is selected on the basis
of choosing a trial lens 2.5 D steeper than the post operative Keratometry. Final fitting is done on the basis of
Fluorescein pattern. Preferably select a large diameter
RGP lens and achieve optimal fitting by changing the
base curve. Trapped air bubbles may be dealt with
fenestration.
For extreme central corneal flattening a number of
special lenses are commercially available. Menicons
Plateau lens is an ideal one in which the lens periphery
is steeper than the base curve. This configure suits the
post RK corneas profile.
The following steps may be used when fitting RGP
lenses following RK surgery.
Large lens diameter (9.511 mm) is generally
recommended.
Optic zone should be small relatively in relation to
over all lens diameter (7 mm optic zone is recommended for a 9.5 mm over all lens diameter).
Thin lenses should be used for optimum oxygen
transmission. If a problem of lens flexure arises,
switch to thicker lens design.
Base curve of RGP lens after RK = 6.5 + 0.9 post
operative K/where K is average postoperative
Keratometry). Usually the contact lens should align
with superior midperipheral cornea. Some times postoperative K readings may result in excessive lens
movement and centration problems.
RGP lenses generally have flatter peripheral curves
than the base curve.
Generally lens power is calculated equal to preoperative spherical equivalent or over refraction is done.
Minus power must be added in final contact lens
fitting as in Post RK there is gap between the flat
central cornea and the contact lens which is filled with
tears thus creating a plus power.
Decentration is a common problem in post RK contact
lens fitting. If the lens slips too high than prism may
be added or lens diameter can be increased. If the
lens rides low a lenticular lens can be used or lens
diameter can be decreased.
Toric lenses may be given to correct the residual
astigmatism.
Therapeutic lens can be fitted in high myopia cases
showing postoperative under correction. These
lenses may be used to mould the cornea (orthokeratology).

If air bubble become trapped. Under the lens in the


gap of central flattened cornea and contact lens and
tears may pool due to poor tear exchange than corneal
edema may develop leading to poor visual acuity. In
such situation lens diameter may be decreased, base
curve is flattened or the lens is fenestrated.
Reverse curve lens is available commercially for
reshaping the flattened apical cornea with steeper
peripheral curves. These lenses may be used in post
RK fitting.
Fitting Technique
First fit the flattened central area. Choose the trial lens
1 D steeper than the flattest curve. Assess the fit using
Fluorescein staining for centration and alignment.
Generally 7.5-8 mm of optic zone is standardized but
can be altered depending on lateral lag.
If lag is less than smaller optical zone is preferred.
The reverse curve should be 3 D steeper than the base
curve with a variation between 2-4 D.
Fit the peripheral curve zone so that there is touch in
the transition zones and a minimal edge stand off of
0.1mm.
Soft contact lenses should be reserved for sensitive
cases and should be prescribed with a great caution
because of potential risk of infection and vascularisation. If soft lenses are to be fitted than select
lenses with high oxygen transmission. Lens care
compliance should be monitored and lenses should
be replaced frequently.
Post Fitting Complications and Failures
Besides the general problems associated with contact
lens fitting, sometime corneal vascularization may
develop which ascends into the incisions from the
limbus. The reported incidence of neovascularisation
is as high as 32-58 percent.
There is reporting of contact lens failure which may
be due to irritation, fluctuating vision, neovascularisation and changes in refractive error.
CONTACT LENS FITTING AFTER
PHOTOREFRACTIVE KERATECTOMY (PRK)
In last decade photo therapeutic keratectomy (PRK) was
procedure of choice for refractive surgery. Since the
inception of sophisticated LASIK surgery and PRK
procedure shortcomings, it has also gone out of favour
among ophthalmologists.
In PRK surgery contact lens fitting has a significant
role specially postoperatively.

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318 Section II: Refractive Surgery

Fig. 33.5: Corneal topography in post PRK cornea (Note central


corneal flattening and unchanged mid peripheral cornea)

In excimer laser PRK it involves an average 50100 um deep ablation over a 5-6 mm wide area of central
cornea which results in central flattening and reduced
myopia. However midperipheral corneal topography
remains unchanged (Figs 33.5 and 33.6).
Indications for Post PRK Contact Lens Fitting
Bandage contact lens to reduce pain in immediate
postsurgical period. Following PRK patient experiences marked ocular pain for 48-72 hours which can
be sharply reduced by giving bandage contact lens.
To restore binocular vision by fitting the lens in the
fellow eye in conditions when one eye is only
operated or patient himself is reluctant for second eye
PRK surgery in the same sitting.
To correct over or under correction to achieve 20/20
vision.
As compared to RK surgery, lesser PRK surgery
patients need postsurgical refractive correction due to
regression, irregular astigmation or under correction.
Generaly PRK patients have predictable postsurgical
corneal topography.
Usually post PRK refractions are stable at 6 months
interval. RGP contact lenses should be fitted ideally 1824 weeks after surgery. RGP lenses are generally fitted
in post PRK stage because of their high oxygen transmissibility. The lens parameters in preoperative phase
are the best predictors of the lens parameters in post
PRK stage. If the patient has not worn any lens prior to
PRK procedure the nonoperated eye or pre-operative
Keratometric (K) reading can be safely used for the initial
lens selection. Rigid gas permeable lenses can be fitted
with either lid attachment or inter palpebral fit. Lens
movement shall vary with the fitting approacha lid
attachment fit may move <1mm with each blink while
an interpalpebral central fit may move more.

Fig. 33.6: Fluorescein pattern of RGP contact lenses in post


PRK phase cornea (Showing peripheral and apical clearance
and mid peripheral alignment)

Fitting technique of contact lens in Post PRK phase is


mentioned as below:
Evaluate pre-surgical cornea by K reading or
corneoscopic mapping.
Trial RGP lens fit should be assessed by an alignment
Fluorescein pattern analysis with marked pooling
over the 6 mm laser area.
Do over refraction to determine optimal visual acuity.
By computerized corneal topography select flattest
reading of topography at the 5 mm zone for initial
base curve.
As the midperipheral corneal topography remains
unchanged after PRK procedure so it is relatively easier
to fit contact lenses after PRK as compare to post RK
surgery. Care should be taken to ensure proper tear
exchange under the lens (Avoid tear pooling) to allow
for venting of debris.
Apart from RGP lenses, hydrogel contact lenses with
high oxygen transmission can also be fitted following
PRK procedure as the post PRK cornea is least susceptible
to neovascularization.
CONTACT LENS FITTING IN LASIK SURGERY
Contact lenses have significant role to play specially postoperatively in modern refractive surgery like lasik
surgery.
Despite a lot of technological advancements being
made in the field of lasik surgery and other refractive
surgeries like new wave front technology, custom
ablation technology, laser microkeratomes, aberrometers,
LASIK and conductive Keratoplasty (CK). No system
is yet not completely perfect to achieve 100 percent
uncorrected 20/20 visual acuity. Contact lenses provides
an excellent alternative to achieve post LASIK emmetropia. Here I shall describe the role of contact lenses preoperatively and postoperatively in LASIK surgery.

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Chapter 33: Contact Lens Fitting in Refractive Surgery 319

Fig. 33.7: Corneal topography showing


RGP contact lens induced corneal
warpage. (Courtesy: Dr Agarwals Eye
Hospital, Chennai, India)

Contact Lens Fitting before LASIK Surgery


There are certain indications preoperatively where we
can fit contact lenses to the patients.
Fellow Eye
Usually LASIK surgery is performed Bilaterally.
Sometime patient is anxious and wishes to have only one
eye performed in single sitting followed by second eye
few weeks later. In such cases contact lenses are fitted in
the fellow (unoperated) eye to achieve binocular vision
and emmetropia. This is temporary arrangement of lens
fitting in non-lasered eye till the patient is operated upon
for the second eye. This arrangement restores binocular
vision and confidence and safety in patient while driving
and in out door movements.
Corneal Warpage
In day to day practice we have seen patients wearing
rigid or semi-rigid gas permeable lenses (RGP) showing

Fig. 33.8: Corneal topography changes showing in corneal


warpage due to PMMA contact lenses

symptoms of corneal warpage leading to Induced


Irregular astigmatism (Figs 33.7 to 33.9). In such cases
RGP lenses are replaced by soft contact lenses. Patients
have to wait for 18-24 weeks before any LASIK surgery
is performed in such eyes to provide time to the cornea
to recover from the warpage effects and returns to its
normal anatomical shape. As the cornea reshaping takes
place. It is preferable to change the soft contact lenses
every two months. After achieving healthy cornea switch
the patient to spectacles till the three consistent and stable
topography and refraction readings are obtained before
performing LASIK surgery.
Contact Lens Fitting in Post-LASIK Phase
Immediate Post LASIK Surgery Period
Following Lasik surgery patient experiences considerable amount of pain which may persist for 48-72 hours.
Bandage contact lenses are advised in immediate Post
LASIK period in conjunction with topical non-steroidal

Fig. 33.9: Corneal topography after 1 week of removing contact


lens in the same patient (note relative corneal flattening
superiorly)

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320 Section II: Refractive Surgery

Fig. 33.10: Corneal topography after LASIK (Note


the blue color in the centre showing central corneal
flattening after LASIK) (Courtesy: Dr Agarwals Eye
Hospital, Chennai, India)

Medication (Diclofenac sodium, Ketorolac tromathamine


or suprofen) to reduce pain discomfort appreciately.
Bandage contact lenses are currently being prescribed
routinely in immediate post LASIK period for 48-72 hours
with excellent results.
Early Post LASIK Surgery Period
In early post LASIK period contact lenses are given for:
i. Over correction, under correction and astigmatism
(Regular and irregular) to achieve optimal vision.
ii. For epithelial defects to provide healing of the
cornea.
iii. For high myopia if residual number remains.
Usually soft contact lenses are prescribed which acts
as a conformer. Inspite of Modern LASIK Surgery

a number of patients are still confronted with over


correction, under correction or astigmatism.
For post LASIK contact lens fitting integrity
of the flap after 12 weeks of surgery is considered
sufficient to withstand the minor trauma and
movement of an RGP lens. By 12 weeks refraction
and corneal thickness changes get stabilized (Figs
33.10 to 33.12).
Epithelial defect develop as a result of epithelial basement dystrophy or excessive instillation of
topical anesthetic drops prior to the use of microkeratome. This may result in epithelial sloughing.
The microkeratome blade slides across the
epithelium and denudes a portion of the epithelium. In epithelial defect cases contact lens is
prescribed to hold the flap firmly in place when

Fig. 33.11: Corneal topography showing


regression after a myopic LASIK. (Courtesy:
Dr Agarwals Eye Hospital, Chennai, India)

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Chapter 33: Contact Lens Fitting in Refractive Surgery 321

Fig. 33.12: Corneal topography showing


central islands after LASIK (Courtesy: Dr
Agarwals Eye Hospital, Chennai, India)

there is Myopia of more than 6 Diopters. This


prevents wrinkles and leads to good conformity of
corneal flap to the underlying corneal stroma.
iv. For proper molding: Soft contact lenses are fitted
as conforming shall have a smoothing effect
specially in irregular cornea and reduces the risk
of wrinkles and folds to the minimum.
v. Unilateral LASIK procedure : When one eye is
treated by LASIK for more than one specific reasons
including patient unwillingness, contact lens in the
fellow eye is fitted to obtain binocular vision and
emmetropia.
vi. Pre-enhancement fitting: In certain situations one
eye remains undercorrected and needs enhance-

ment after a duration of 8-24 weeks. In such cases


contact lens is fitted to achieve emmetropia so that
patients may lead normal life specially in relation
to driving, Reading and TV viewing, etc. Contact
lenses are specially useful when there are central
islands that require sometime to disappear.
vii. Induced Keratoconus: Keractesia or induced
Keratoconus develops as a result of too little stroma
left after LASIK surgery. This condition is although
rare and develops specially in high myopia, contact
lenses specially tailored for Keratoconus are often
fitted in such cases (Figs 33.13 and 33.14).
viii. In LASIK surgery contraindicated cases when
patients are unfit for LASIK surgery due to physio-

Fig. 33.13: Corneal topography of patient


with keratoconus (Note red area which is
steep cornea). (Courtesy: Dr Agarwals Eye
Hospital, Chennai, India)

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322 Section II: Refractive Surgery

Fig. 33.14: Fluorescein pattern (R/E) showing RGP contact


lens fitting in mild keratoconus with excellent superior and
apical aligment

logical and pathological conditions, their refractive


error can be corrected by contact lenses which is
an excellent option to achieve optimal vision
without spectacles.
Usually low pachymetry readings, slit lamp
abnormalities and abnormal corneal topography
observations are main causes of LASIK surgery
contraindications. Developing cataract, corneal
pathology and associated retinal pathologies are
other factors for contraindication of LASIK surgery.
In following clinical conditions contact lenses are
treatment of choice and are preferred to refractive
surgery.

Healed Keloids which may be adversely affected by


Lasik surgery.
Patients with thin and irregular corneas leading to
Keratoconus.
Patients having systemic collagen diseases.
Highly anxious and nuisance patients who expect
only 20/20 vision after Lasik surgery.
High myopes (15-20 Diopters) when LASIK surgery
is contraindicated and patient is not willing to
undergo alternate surgical procedures.
When corneas are extremely thinned for second laser
enhancement.
For achieving emmetropia prospects of contact lenses
in refractive surgery are quite bright. Custom designed
contact lenses, Bifocal contact lenses of disposable type,
extended wear and non-disposable type shall help the
patient to maintain optimal vision.
FURTHER READING
1. Agarwal Amar et al. Text Book of Ophthalmology. New Delhi:
Jaypee Brothers Medical Publishers (P) Ltd. 2002;4.
2. Agarwal Amar et al. Refractive Surgery. New Delhi: Jaypee
Brothers Medical Publishers (P) Ltd. 2000.
3. Agarwal Amar et al. Lasik and beyond Lasik. Highlights of
ophthalmology, Panama, 2001.
4. Harold stein. Contact lenses in refractive durgery. Highlights
of ophthalmology, 2002;1:10-13.
5. Harold Stein et al. Contact Lenses, New Delhi: Jaypee Brothers
Medical Publishers (P) Ltd, 1997.
6. Dada VK et al. Textbook of contact lenses, New Delhi: Jaypee
Brothers Medical Publishers (P) Ltd, 1996.

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Chapter 34: Primary Posterior Corneal Elevation 323

34

Primary Posterior
Corneal Elevation
Amar Agarwal, Nilesh Kanjani, Ashish Doshi, Sonika Doshi,
Sunita Agarwal, Athiya Agarwal, J Agarwal, T Agarwal

INTRODUCTION
ORBSCAN
PRIMARY POSTERIOR CORNEAL
ELEVATION
DISCUSSION

INTRODUCTION
Keratoconus is characterized by non-inflammatory stromal thinning and
anterior protrusion of the cornea. Patients with this disorder are poor
candidates for refractive surgery because of the possibility of exacerbating
keratectasia. The development of the corneal ectasia is a well-recognized
complication of the LASIK and attributed to unrecognized preoperative
forme fruste keratoconus. It is known that posterior corneal elevation is
an early presenting sign in keratoconus and hence it is imperative to
evaluate posterior corneal curvature (PCC) in every LASIK candidate.
ORBSCAN
The Orbscan (Bausch and Lomb) corneal topography system uses a
scanning optical slit scan that is fundamentally different than the corneal
topography that analyses the reflected images from the anterior corneal
surface. The high-resolution video camera captures 40 light slits at 45
degrees angle projected through the cornea similarly as seen during slit
lamp examination. The slits are projected on to the anterior segment of the
eye: the anterior cornea, the posterior cornea, the anterior iris and anterior
lens. The data collected from these four surfaces are used to create a
topographic map. This technique provides more information about anterior
segment of the eye, such as anterior and posterior corneal curvature and
corneal thickness. It has an acquisition time of 4 seconds.1 It improves the
diagnostic accuracy and it has passive eye-tracker from frame to frame, 43
frames are taken to ensure accuracy. It is easy to interpret and has good
repeatability. The diagnosis of keratoconus is a clinical one and early
diagnosis can be difficult on clinical examination alone. Orbscan has
become a useful tool for evaluating the disease, and with the advent of its
use, abnormalities in posterior corneal surface topography have been
identified with keratoconus. Posterior corneal surface data is problematic
because it is not a direct measure and there is little published information
on normal values for each age group. In the patient with increased posterior
corneal elevation in the absence of other changes, it is unknown whether
this finding represents a manifestation of early keratoconus. The decision
to proceed with refractive surgery is therefore more difficult. We always
use the Orbscan system to evaluate our potential LASIK candidates
preoperatively to rule out primary posterior corneal elevations.

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324 Section II: Refractive Surgery


PRIMARY POSTERIOR CORNEAL ELEVATION
All eyes undergoing LASIK are examined by Orbscan.
Eyes are screened using quad maps with the normal band
(NB) filter turned on. Four maps include: (a) anterior
corneal elevation: NB = 25 of best-fit sphere, (b)
posterior corneal elevation : NB = 25 of best fit sphere,
(c) Keratometric mean curvature: NB = 40 to 48 D, K, (d)
Corneal thickness (pachymetry): NB = 500 to 600 . Map
features within normal band are colored green. This
effectively filters out variation falling within normal
band. When abnormalities were seen on normal band
quad map screening, a standard scale quad map was
examined. For those cases with posterior corneal
elevation, we also generated three-dimensional views of
posterior corneal elevation. In all eyes with posterior
corneal elevation, the following parameters were generated: (a) radii of anterior and posterior curvature of the
cornea, (b) posterior best fit sphere, (c) difference between
the corneal pachymetry value in 7 mm zone and thinnest
pachymetry value of the cornea.
Figures 34.1 to 34.6 show the various topographic
features of an eye with primary posterior corneal
elevation detected during our pre-LASIK assessment. In
Figure 34.1 (general quad map) upper left corner map is
the anterior float, upper right corner map is posterior
float, lower left corner is keratometric map while the

lower right is the pachymetry map showing a difference


of 100 m between the thickest pachymetry value in
7 mm zone of cornea (613 m) and thinnest pachymetry
value (513 m). In Figure 34.2, normal band scale map
of anterior surface shows with the rule astigmatism in
an otherwise normal anterior surface (shown in green),
the posterior float shows significant elevation inferotemporally. In Figure 34.2 only the abnormal areas are
shown in red so it is easy to make out. Figure 34.3 is threedimensional representation of the maps in Figure 34.2.
Figure 34.4 shows three-dimensional representation of
anterior corneal surface with reference sphere. Figure 34.5
shows three-dimensional representation of posterior
corneal surface showing a significant posterior corneal
elevation. Figure 34.6 shows amount of elevation
(color coded) of the posterior corneal surface in microns
(50 m).
DISCUSSION
Topography is valuable for preoperative ophthalmic
examination of LASIK candidates, which includes a
thorough history, an external slit lamp and fundus
examination, and a good refraction. Three-dimensional
imaging allows surgeons to look at corneal thickness, as
well as the corneal anterior and posterior surface and
can predict the shape of cornea after LASIK surgery.

Fig. 34.1: General quad map of an eye with primary posterior corneal elevation

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Chapter 34: Primary Posterior Corneal Elevation 325

Fig. 34.2: Quad map with normal band scale filter on in the same eye as in Figure 34.1

Fig. 34.3: Three-dimensional normal band scale map

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326 Section II: Refractive Surgery

Fig. 34.4: Three-dimensional anterior float

Fig. 34.5: Three-dimensional posterior float

Topographic analysis using three dimensional slit


scan system allows us to predict which candidates would
do well with LASIK and also confers the ability to screen
for subtle configurations which may be a contraindication
to LASIK. In our study 3 percent (12 out of 400 eyes) of
the eyes screened for myopic LASIK were found to have
primary posterior corneal elevation ranging from 49 m
to 60 m on posterior float analysis. In a presentation
(Incidence and severity of posterior corneal of 100 consecutive LASIK candidates evaluated with Orbscan,
January 1999) by Dr. Vukich J, MD and Dr. Sanders D,
MD, the incidence of posterior corneal elevation in LASIK
candidates was reported as 9 percent. In our series as
well as in above-mentioned study, all the eyes with
primary posterior corneal elevation had otherwise
normal anterior curvature and no evidence of anterior
segment pathology. All these patients were asymptomatic. The exact incidence of asymptomatic posterior
corneal elevation has not been established but our results
suggest that a significant proportion of LASIK candidates
may harbor this posterior surface anomaly. What
amounts to a significant primary posterior corneal
elevation is still unknown and is under investigation.
It is known that corneal ectasias and keratoconus have
posterior corneal elevation as the earliest manifestation.2
The precise course of progression of posterior corneal
elevation to frank keratoconus is not known. Hence it is
necessary to study the posterior corneal surface
preoperatively in all LASIK candidates. Elevation is not
measured directly by Placido based topographers, but

Fig. 34.6: Three-dimensional posterior


corneal elevation measured in microns

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Chapter 34: Primary Posterior Corneal Elevation 327


certain assumptions allow the construction of elevation
maps. Elevation of a point on the corneal surface displays
the height of the point on the corneal surface relative to
a spherical reference surface. Reference surface is chosen
to be a sphere. Best mathematical approximation of the
actual corneal surface called best-fit sphere is calculated.
One of the criteria for defining forme fruste keratoconus
as given by Dr. Potgieter is a posterior best fit sphere of
> 55.0 D, while Dr. E. Charlembos has included posterior
best fit sphere of >51.0 D as a criterion for defining forme
fruste keratoconus. Average posterior best fit sphere in
our series was 52.53 D (range 50.2 to 55.3). This showed
that all the eyes in our study were near the range of
keratoconus for posterior best-fit sphere.
Ratio of radii of anterior to posterior curvature of
cornea > 1.21 and < 1.27 has been considered as a
keratoconus suspect (Definition of Dr. Charolembos).
Edmund C has reported a ratio of 1.20 in a study of
keratoconic eyes. Our series had an average ratio of 1.24
(range from 1.21 to 1.31) which fell in the keratoconic
range in light of the above mentioned definitions in spite
of a normal anterior corneal surface. Average pachymetry
difference between 7 mm zone on the cornea and the
thinnest point on the cornea was 127 m (96 to 206 m)
which was more than the reference value of 100 m as
suggested by Dr. Potgieter in his definition of forme fruste
keratoconus. Posterior corneal surface data is
problematic because it is not a direct measure and there
is little published information on normal values for
various age groups. Increased posterior corneal elevation
in the absence of other changes may be a manifestation
of early keratoconus. The decision to proceed with LASIK
in such eyes is difficult.
Posterior corneal surface topographic changes after
LASIK are known. Increased negative keratometric
diopters and oblate asphericity of the PCC are common
after LASIK leading to mild keratectasia.3,4 Lamellar
refractive surgery reduces the biomechanical strength of
cornea which may lead to mechanical instability and
keratectasia. Iatrogenic keratectasia represents a
complication after LASIK that may limit the range of
myopic correction.5 Corneal ectasia has also been reported after LASIK in cases of forme fruste keratoconus.6
Posterior corneal bulge may be correlated with residual
corneal bed thickness. The risk of keratectasia may
be increased if the residual corneal bed is thinner than
250 m.7 Age, attempted correction and the optical zone
diameter are other parameters that have to be considered to avoid post LASIK ectasia.8,9 In the light of the fact
thact keratoconus may have posterior corneal elevation

as the earliest manifestation, preoperative analysis of


PCC to detect a posterior corneal bulge is important to
avoid post LASIK keratectasia. The rate of progression
of posterior corneal elevation of frank keratoconus is
unknown. It is also difficult to specify that exact amount
of posterior corneal elevation beyond which it may be
unsafe to carry out LASIK. Atypical elevation in the
posterior corneal map more than 45 m should alert us
against a post LASIK surprise. Orbscan provides reliable,
reproducible data of the posterior corneal surface and
all LASIK candidates must be evaluated by this method
preoperatively to detect an early keratoconus.
SUMMARY
We suggest that primary posterior corneal elevation
should be considered a contraindication to performing
LASIK. The following parameters must be analysed in
all LASIK candidates to rule out primary posterior
corneal elevation: (a) ratio of radii of anterior to posterior
curvature of cornea: > 1.21 and < 1.27, (b) posterior bestfit sphere: > -50.0 Dsph, (c) difference between thickest
corneal pachymetry value at 7mm zone and thinnest
pachymetry value: > 90 m, (d) posterior corneal
elevation > 50 m. Further studies are required to
quantify the significance of primary posterior corneal
elevation and their role in post LASIK keratectasia.
REFERENCES
1. Fedor P, Kaufman S. Corneal topography and imaging.
Medicine Journal, 2001;vol 2, no 6.
2. McDermott GK. Topographys benefits for LASIK. Review of
Ophthalmology. Editorial, vol no:9:03 issue.
3. Seitz B, Torres F, Langenbucher A, et al. Posterior corneal
curvature changes after myopic laser in situ keratomileusis.
Ophthalmology 2001;108(4): 666-72.
4. Geggel HS, Talley AR. Delayed onset keratectasia following laser
in situ keratomileusis. J Cataract Refract Surg 1999;25(4):
582-86.
5. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser
in situ keratomileusis. J Refract Surg 1998;14(3):312-17.
6. Seiler T, Quurke AW. Iatrogenic keratectasia after laser in situ
keratomileusis in a case of Forme Fruste keratoconus. J Refract
Surg 1998;24(7):1007-09.
7. Wang Z, Chen J, Yang B. Posterior corneal surface topographic
changes after laser in situ keratomileusis are related to residual
corneal bed thickness. Ophthalmology 1999;106(2):406-09.
8. Pallikaris IG, Kymionis GD. Astyrakakis NI. Corneal ectasia
induced by laser in situ keratomileusis. J Cataract Refract Surg
2001;27(11):1796-02.
9. Argento C, Cosentino MJ, Tytium A et al. Corneal ectasia after
laser in situ keratomileusis. J Cataract Refract Surg 2001;
27(9):1440-48.

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Section III

Glaucoma
35. Modern Glaucoma Surgery
Jes Mortensen
36. Laser Sclerotomy, Laser Phakonit and IOL Implantation
Sunita Agarwal, Sundaram, Asha B
37. Viscocanalostomy
Norbert Krber, Robert Stegmann, Clive O Peckar, GL Simn-Castellvi
38. Update on Antiglaucoma Therapy
Ashok Garg
39. Triple Procedure Trabeculectomy with Phaco and IOL Implantation
Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Anand A Bagmar, R Rajalakshmi

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35

Modern Glaucoma Surgery


Jes Mortensen

INTRODUCTION
GLAUCOMA SURGERY
METHODS
RESULTS

INTRODUCTION
In spite of more than 100 years of treatment by pressure lowering
medication in glaucoma it is still not brought to evidence that decreasing
the intraocular pressure (IOP) is beneficial.
Glaucoma is now considered a optic neuropathy not a disease of the
chamber angle (Fig. 35.1).

COMPLICATIONS
CONCLUSION

Fig. 35.1: Schematic illustration of the two outflow routes: the


conventional one through the trabecular meshwork and the
uveoscleral outflow routes (with permission from PharmaciaUpjohn)

Many different drugs have been developed to lower the IOP:


pilocarpine, beta-blockers, adrenaline drugs and recently, prostaglandin
analogs. The older drugs facilitate the escape of aqueous humor through
the trabecular meshwork. During the last 20 years drugs that diminish the
aqueous production have been introduced and now recently drugs that
facilitate the uveoscleral outflow have been put to the weapon to fight
high IOP in glaucoma (Fig. 35.2).
GLAUCOMA SURGERY
Surgery for the management of glaucoma is much older than medication.
Graefe in Germany operated open-angle glaucoma back in the 19th century
with an iridectomy. Open-angle glaucoma was operated to increase the
outflow of the aqueous. Many different operations have been tried. Lately

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332 Section III: Glaucoma

Fig. 35.2: Three-dimensional structure of the trabecular meshwork in the human eye. The inner uveal meshwork extends
towards the iris root and forms the so-called ciliary meshwork
separating the intermuscular spaces from the anterior chamber (with permission from the Pharmacia-Upjohn)

trabeculectomy has been seen as the golden standard.


Trabeculectomy is a well tested operation to lower the
IOP, but has quite a few postoperative complications:
Hyphema, shallow or flat anterior chamber (AC),
hypotony; choroidal detachment, hypotony maculopathy
all due to excessive filtration, later follows cataract in 50
percent of the operated eyes.
A new approach to trabecular surgery has deve
loped to minimize the complications just mentioned.
Three main groups can be seen today: Mermoud in
Switzerland, Sourdille in France and Stegmann in
South Africa.
The name of the new procedure is not quite given,
but all agree upon one item that the procedure shall be
non-penetrating trabecular surgery. Mermoud advocates
a deep sclerectomy and makes a Descemets window to
facilitate percolation of the aqueous humor through this
window from the AC. To further facilitate the aqueous
humor to flow under the scleral flap to the subconjunctival space a collagen implant is placed in the bed of the
deep sclerectomy.
Sourdille makes a deep sclerectomy and deroofing
of the Schlemms canal and a Descemets window to
facilitate the flow of aqueous from AC to the scleral bed.
To further facilitate the outflow he puts a cross-linked
sodium hyaluronate implant in the bed.
Stegmann has another approach named, viscocanalostomy by the inventor. He uses a deep sclerectomy,
deroofing of the Schlemms canal and the generation of
a Descemets window. To facilitate the flow of aqueous
high-viscosity sodium hyaluronate is injected into the

Schlemms canal to open the canal and after the superficial flap has been securely sutured the same is injected
under the flap to prevent fibrinogen production that
could prevent the free flow into the lake as the
functional space is named by Stegmann.
Sourdille and Stegmann agree that subconjunctival
filtration is not wanted. In more than 80 percent no
filtration can be seen postoperatively. Stegmann thinks
that the outflow happens through collector channels and
aqueous veins. Stegmann has intraoperatively shown
that outflow through these routes happens by injecting
sodium hyaluronate into the canal of Schlemm.
Increase of the uveoscleral outflow might also be an
explanation to the pressure lowering effect the nonpenetrating procedures give in the operated eye.
The most important aspect is that these procedures
have very few and modest complications. The latest
studies done by the mentioned investigators have also
shown at least same good ability to lower the IOP is found
after trabeculectomy.
Stegmann has even shown that his success rate in
trabeculectomy of less than 20 percent in the black
African patients operated for open-angle glaucoma,
increases to more than 80 percent with viscocanalostomy
in the same population.
METHODS
First time I heard about viscocanalostomy was at
the ECCRSs meeting in Gothenburg, autumn 1996.
Professor Stegmann gave a lecture about his method and
results.
I was thrilled and started up spring 1997 doing
viscocanalostomy, that is I tried hard to learn. Later that
year I had the opportunity to have Stegmann as my
teacher. That was really a hard learning curve still going
on. First we did the operations according to Stegmanns
concept, but as we learnt more from the other groups we
have modified the operation.
We do the operations mostly in local anesthesia and
use the subtendonal anesthesia. Sutures are placed at the
cornea-scleral border (if the operation is at 12 Oclock
placed at 10 and 2 Oclock, if the operation is at 6 Oclock,
sutures are placed at 4 and 8 Oclock) (Fig. 35.3) Due to
the anatomy of Schlemms canal you cannot operate
nasally or temporally.
A fornix-based conjunctival flap extending from half
past one to half past ten is dissected. Bipolar cautery is
done very carefully. A scleral flap is dissected 5 5 mm
(Fig. 35.4) I start with my guarded knife set at 200-250
microns cutting a curved incision parallel to the limbus
in a distance of 5 mm. A crescent knife is then used to
undermine the scleral-flap exactly the same way I do my

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Chapter 35: Modern Glaucoma Surgery

Fig. 35.3: Sutures are placed and conjunctiva cut

Fig. 35.4: A crescent knife used to undermine


the scleral flap

phaco-flaps, but of course bigger. It is a time-saving


procedure. The flap is cut free and folded over the cornea
(Fig. 35.5). Before surgery I always place a thick cover of
Healon 5 to protect the cornea, that helps me even to
fixate the scleral flap.The flap is extended half a mm to
one mm into clear cornea.
A second flap is dissected 0.5 mm inside the border
of the superficial flap (Fig. 35.6A). This flap is dissected
down to Descemets membrane through the Schlemms
canal (Fig. 35.6B). That is the difficult part of the operation
to tell if you are dissecting deep enough. If you go too
deep you will see the choroid free in the bottom of the
wound (Fig. 35.6C). That is no catastrophe, it may even
give you a landmark, but that is only in the beginning of
the dissection. If you go too deep at the end you will
perforate into the AC.

333

Fig. 35.5: The flap is cut free and folded over the cornea

In the modest pigmented eyes of the Swedish patients,


you have to look very carefully. Your landmark should
be a thin layer of sclera covering the choroid shining
through the almost translucent scleral layer, giving a
gray-blue color.
As the inner flap is dissected forward the next stop
will be approximately posterior to limbus: Schlemms
canal. The structure that should warn you is a cottonlike fiber running parallel to the limbus (Fig. 35.7), when
you pass through this layer a smooth interior surface of
Schlemms canal reveals itself (Fig. 35.8). Now stop!
Now is the time for lowering the IOP by a paracentesis
(Fig. 35.9). Do lower the pressure so you get hypotony of
the eye. Should you accidentally cut the Descemets
window you will not end up with the iris in the knee.
Dissect first with the same round knife you just used to
dissect the flap to free the first part of the window, you
can then just put a gentle pressure on Schwalbes line
with a spear sponge to separate Descemets membrane
from the corneoscleral junction (Fig. 35.10). If you are
right you will now see aqueous percolating through the
window (Fig. 35.11).
Viscocanalostomy is done both left and right with a
150-micron cannula introduced through the ostia of
Schlemms canal (Fig. 35.12). Be careful not to inject to
forcefully as you might fill the AC with Healon 5 and
that could give a very high pressure next day. To see that
the viscocanalostomy is done right, I always look if the
bloodstream in the collecting venules is broken by the
absorbed Healon 5, that is clearly seen especially if you
put a drop of Healon 5 as a magnifying glass over the
venules (Fig. 35.13).
The deeper flap is excised with Vannas scissors and
now I place an implant (Fig. 35.14). If the eye had no
operation before, I use Corneals Sk Gel 3,5,if the eye

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334 Section III: Glaucoma

Fig. 35.6A: A second flap is dissected 0.5 mm inside the


border of the superficial flap

Fig. 35.6B: Your landmark should be a thin layer of sclera


covering the choroid shining through the almost translucent
scleral layer, giving a gray-blue color

Fig. 35.6C: If you go too deep you will see the choroid free
in the bottom of the wound

Fig. 35.7: Cotton-like fiber running parallel to limbus

had earlier surgery I use the Staars collagen implant, as


I then want to get a filtration.
The superficial scleral flap is tightly sutured (Fig.
35.15) in most cases to omit filtration, peroperative a
subtendonal corticosteroid and antibiotics are injected.
Local steroid is given as eyedrops for 4 to 6 weeks 3 times
a day.

cation, the mean follow-up was 35 months. That is quite


remarkable results.
Personal communication gives that the results
achieved operating the white population are even better.

RESULTS
Stegmanns results are from his operation in black
Africans which is due to Stegmann the most difficult
population to get success with filtering procedures for
glaucoma. He presents an IOP reduction of 64 percent in
160 cases. The success rate is 82.7 percent without medi-

COMPLICATIONS
Choroidal detachment seen in 2 cases, high IOP first day
22 cases, and cataract 1 case.
CONCLUSION
The riddle of glaucoma has not yet been solved. The
disease is today seen as a neuropathy of the visual nerve.

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Chapter 35: Modern Glaucoma Surgery

335

Fig. 35.8: Smooth interior surface of Schlemms


canal reveals itself

Fig. 35.10: Put a gentle pressure on Schwalbes line


with a spear sponge

Fig. 35.9: Time for lowering the IOP by a paracentesis

Fig. 35.11: Aqueous percolating through the window

The treatment is still focused on lowering the IOP. Firstly


by drugs, when that is not sufficient operation. The
golden standard for many years has been trabeculectomy,
known for effective lowering the pressure, but plagued
with quite severe complications not seldom seen, that
has led to a search for new operations. The nonperforating trabecular surgery, which has few and not often
severe complications can be the answer. Time will show
if the lowering of the IOP is as good as the trabeculectomy
at the long run. Stegmann in South Africa has shown
results that is even better than ordinary trabeculectomy
in the most difficult population to operate: black Africans.
Mermoud in Switzerland and Sourdille in France have
shown similar results in a white population. Stegmann
uses non-implant but high-viscosity sodium hyaluronate

(Healon GV), Mermoud uses collagen implant (Staar)


and Sourdille use reticulated hyaluronic acid implant (Sk
Gel, Corneal).
I will end my chapter quoting professor Stegmann:
Over the last eight years, I have ensured myself a
great deal more sleep since I no longer go to work in the
morning expecting a plethora of complications associated
with filtering operations, such as trabeculectomy, which
I used to perform. In fact, I have not done a single trabeculectomy as an elective procedure in the last 10 years.
REFERENCES
1. Sommer A, Tielsch JM, Katz J et al: Relationship between
intraocular pressure and primary open-angle glaucoma among
white and black Americans. Arch Ophthalmol 1991;109:1090.

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336 Section III: Glaucoma

Fig. 35.12: Viscocanalostomy is done both left and right


with a 150 micron cannula

Fig. 35.13: The bloodstream in the collecting venules is


broken by the absorbed Healon 5
2. Gupta N, Weinreb R: New definitions of glaucoma. Current
Opinion in Ophthalmology 1997;8:38-41.
3. Bengtsson B: Characteristics of manifest glaucoma at early
stages. Graefes Arch Clin Exp Ophthalmol 1989;277:241-43.
4. Caprioli J, Bergstrom T, Harbin T et al: Primary open angle
glaucoma. Preferred practice pattern. San Francisco: American
Academy of Ophthalmology, 1992.
5. Fechtner RD, Weinreb R: Mechanisms of optic nerve damage in
primary open angle glaucoma. Surv Ophthalmol 1994;39:2342.
6. Anderson DR: Glaucoma: The damage caused by pressure. XL
VI Edward Jackson memorial lecture. Am J Ophthalmol 1989;
108: 485-95.
7. Leske MC, Connell AMS, Wu SY et al: Risk factors for openangle glaucoma. The Barbados eye study. Arch Ophthalmol
1995;113: 918-24.

Fig. 35.14: An implant, corneals Sk Gel 3,5 is placed

Fig. 35.15: The superficial scleral flap is tightly sutured

9. Rossetti L, Marchctti I, Orzalesi N et al: Randomized clinical


trials on medical treatment of glaucoma. Are they appropriate
to guide clinical practice? Arch Ophthalmol 1993;111:96-103.
10. Collaborative Normal-Tension Glaucoma Study Group. The
effectiveness of intraocular pressure reduction in the treatment
of normal-tension glaucoma. Am J Ophthalmol 1998;126:48797.
11. Anders Heijl: New concept of glaucoma. Lkartid 1999;96:168891.
12. Stegmann R, Pienaar A, Miller D: Viscocanalostomy for openangle glaucoma in black African patients. J Cataract Refract
Surgery 1999;25:316-22.
13. Gianoli F, Schnyder CC, Bovey E et al: Combined surgery for
cataract and glaucoma:Phacoemulsification and deep sclerectomy compared with phacoemulsification and trabeculectomy.
J Cataract Refract Surgery 1999;25:340-46.

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Chapter 35: Modern Glaucoma Surgery


14. Mermoud A, Schnyder CC, Sickenberg M et al: Comparison of
deep sclerectomy with collagen implant and trabeculectomy in
open-angle glaucoma. J Cataract Refract Surgery 199925:32331.
15. Sourdille P, Santiago P, Villain F et al: Reticulated hyaluronic
acid implant in non-perforating trabecular surgery. J Cataract
Refract Surgery 1999;25:332-39.
16. Drake M: Complications of glaucoma filtration surgery. Int
Ophthalmol Clin 1992;32(4):115-30.
17. Clarke MP, Vernon SA, Sheldrick JH: The development of
cataract following trabeculectomy. Eye 1990;4:577-83.
18. Costa VP, Spaeth GL, Eiferman RA et al: Wound healing
modulation in glaucoma filtration surgery. Ophthalmic Surg
1993;24:152-70.
19. Khaw P: New surgical treatments for glaucoma. Br J Ophthalmol 1999;83:1-3.
20. Kozlov VI, Bagrov SN, Anisimova SY et al: Non-penetrating
deep sclerectomy with collagen. Ophthalmosurgery 1990;3:
44-46.
21. Chiou AGY, Mermoud A, Hdiguer SE: Glacome malin par
blocage ciliaire apres sclerectomie profondeimagerie par biomicroscope a ultrasons. Klin Monatsbl Augen-heilkd 1996;
208:279-81.
22. Chiou AGY, Mermoud A, Jewelewicz DA: Post-operative
inflammation following deep sclerectomy with collagen implant

23.
24.
25.
26.
27.

28.
29.
30.
31.

337

versus standard trabeculectomy. Graefes Arch Clin Exp


Ophthalmol 1998;236:593-96.
Stegmann RC: Visco-canalostomya new surgical technique
for open angle glaucoma. Ann Inst Barraquer 1995;25:229-32.
Sanchez E, Schnyder CC, Sickenberg M et al: Deep sclerectomy:
results with and without collagen implant. Int Ophthalmol 1997;
20:157-62.
Fyodorov SN, Kozlov VI, Timoshkina NT et al: Nonpenetrating
deep sclerectomy in open angle glaucoma. Opthalmosurgery
1990;3:52-55.
The Fluorouracil Filtering Surgery Study Group. Fluorouracil
filtering surgery study one-year follow-up. Am J Ophthalmol
1989;108:625-35.
Sickenberg M, Chiou AGY, Bigar F et al: Deep sclerectomy with
collagen implant: a new non-penetrating filtering surgery.
Scientific poster 55. American Academy of Ophthalmology
Annual Meeting, Atlanta, Georgia, USA, 1995; program, 134.
Stewart WC, Shields MB: Management of anterior chamber
depth after trabeculectomy. Am J Ophthalmol 1988;106:41-44.
Freedman J, Gupca M, Bunke A: Endophthalmitis after
trabeculecromy. Arch Ophthalmol 1978;96:1017-18.
Arenas E: Trabeculectomy ab externo. Highlights Ophthalmol
1991;19(9): 59, 62-64.
Chiou AGY, Mermoud A, Hdiguer SEA et al: Ultra-sound
biomicroscopy of eyes undergoing deep sclerotomy with
collagen implant. Br J Ophthalmol 1996;80:541-44.

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338 Section III: Glaucoma

36

Laser Sclerotomy, Laser


Phakonit and IOL Implantation
Sunita Agarwal, Sundaram, Asha B

INTRODUCTION
HISTORY
ND: YAG LASER
LASER SCLEROTOMY WITH
ND: YAGINSTRUMENTATION
SURGICAL TECHNIQUES

INTRODUCTION
Lasers have been in use for the treatment of glaucoma for the last few
decades. A bloodless sutureless technique of using the Nd:YAG laser has
been started by the authors (SA) to treat glaucoma. This is called Laser
Sclerotomy. If the patient has a cataract then one can do the cataract removal
with the Laser Phakonit technique followed by either a Rollable or Foldable
IOL implantation.
HISTORY
The author first performed this technique on a diabetic patient who was
already undergoing hemodialysis as a result of renal failure. His renal
failure made the use of acetazolamide an absolute contraindication. Using
the Nd:YAG laser of the Paradigm machine which is also used for cataract
surgeries by the author, the author performed the laser sclerotomy. In this,
the idea was to create a hole via the clear corneal incision in the trabecular
meshwork. The hole passes through and through to exit the sclera forming
a filtering channel into the subconjunctival space.
ND:YAG LASER
It is a solid state laser having an ionizing effect causing photodisruption,
thermal effect causing photovaporization, photocoagulation and
photocarbonization. The laser fibreoptic (Fig. 36.1) has a Helium Neon
aiming beam with the diameter of the optic end being 380 . This fibreoptic
is encased within a silicon sleeve. The male socket connects the fibreoptic
to the laser machine. The laser machine the author advocates is the
Paradigm Photon machine which works at 3 Watts.
LASER SCLEROTOMY WITH ND:YAG INSTRUMENTATION
0.9 mm Diamond Blade: custom made diamond blade similar to the
one used in laser Phakonit (0.9 mm incision cataract surgery).
Viscoelastic: Hydroxy Methylcellulose used for maintenance of anterior
chamber with protection of corneal endothelium.
Nd:YAG Laser Fibreoptic.
Paradigm Laser Machine

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Chapter 36: Laser Sclerotomy, Laser Phakonit and IOL Implantation

Fig. 36.1: Nd:YAG laser fibreoptic: (1) laser fibreoptic, (2) male
socket, (3) diameter of ocular end of laser fibreoptic is 380,
(4) helium neon aiming beam

339

Fig. 36.3: 0.9 mm diamond blade for clear corneal incision

Fig. 36.4: Anterior chamber filled with viscoelastic


Fig. 36.2: Paracentesis with viscoelastic injection

SURGICAL TECHNIQUE
Paracentesis

parallel but about 2 mm away from the limbus and the


tunnel directed towards the limbus. The sclerotomy is
then performed in the same area.
Laser Sclerotomy

The anterior chamber is filled initially with viscoelastics


to facilitate a smooth incision (Fig. 36.2). Hydroxy methyl
propyl cellulose (viscon) is the preferred viscoelastic. The
site of paracentesis is preferably 45 degrees away from
the main incision so that a repository may be used later
on for control of the eyeball during the procedure.

After the corneal incision is made the anterior chamber


is filled with more viscoelastic (Fig. 36.4) and then the
laser fibreoptic (Fig. 36.5) is introduced through the clear
corneal incision. A short burst of laser is given directly
opposite the intended site of sclerotomy (Fig. 36.6). The
procedure is performed without the need of an operative

Clear Corneal Incision


A keratome/diamond blade of 0.9 mm size (Fig. 36.3) is
used to make a clear corneal incision superiorly
depending on the site planned for sclerotomy. The entry
point may be directly opposite the planned site of sclerotomy or juxtaposed to the planned site of sclerotomy.
Depending on the surgeons preferences the director of
the blade may be adjusted accordingly with the initial
entry point parallel to the limbus and the tunnel incision
varying according to the planned site of sclerotomy.
Recently the author has opted for a variation in the
conventional corneal tunnel with the initial entry point

Fig. 36.5: Laser fibreoptic introduced through main incision


and repositor is used to support the laser fibreoptic

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340 Section III: Glaucoma

Fig. 36.8: BSS is injected into the anterior


chamber to form bleb
Fig. 36.6: Laser ablation through the
trabecular meshwork

Fig. 36.9: PBI is made in the area of sclerotomy


using Nd:YAG laser or iris scissors
Fig. 36.7: Laser ablation carried through the
sclera 1.5 mm from corneal limbus

goniolens using just the aiming beam as a guide. When


the aiming beam is seen about 1.5 mm (Fig. 36.7) from
the limbus a short burst of laser brings the laser fibreoptic
out of the scleral bed and under the conjunctiva. Following this the fibreoptic is removed and the anterior chamber washed with BSS to remove traces of viscoelastic.
BSS is injected near the sclerotomy site and subconjunctival bleb formation (Fig. 36.8) is looked for to
assess the patency of the sclerotomy.

Fig. 36.10: Anterior chamber is reformed and


incision sealed with stromal hydration

Laser Phakonit and IOL Implantation


Peripheral Iridectomy
Depending on whether a PBI was done before or not a
peripheral iridotomy (Fig. 36.9) may be done near the
area of sclerotomy using the laser itself but preferably
only in pseudophakic or aphakic patients lest the
crystalline lens gets damaged inadvertently.

If the patient has a cataract then one can perform the


cataract extraction with the Laser Phakonit technique
followed by an IOL implantation. This concludes a triple
procedure which is less traumatic than performing a
triple procedure with trabeculectomy.
Phakic Laser Sclerotomy

Closure of Incision
The clear corneal incision is closed by stromal hydration
(Fig. 36.10).

Laser sclerotomy has been performed safely in phakic


individuals. Care has to be exercised when the laser is
used, to prevent inadvertent damage of the crystalline

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Chapter 36: Laser Sclerotomy, Laser Phakonit and IOL Implantation


lens with the laser energy. Iris pigmentation of the lens
is the only complication seen in 20 percent of the phakic
patients treated.
Laser Sclerotomy in Pseudophakia and Aphakia
About 55 percent of the patients who underwent laser
sclerotomy were already operated for cataract. Results

341

varied according to the degree of preoperative IOP


and the type of glaucoma. A case of keratoplasty with
pseudophakos was treated with this procedure. When
impending ciliary staphyloma formation conventional
trabeculectomy could not be performed. Also long-term
use of anti-glaucoma medication has resulted in
subconjunctival fibrosis. The laser sclerostomy in this case
was useful.

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342 Section III: Glaucoma

37

Viscocanalostomy
Norbert Krber, Robert Stegmann, Clive O Peckar, GL Simn-Castellv

INTRODUCTION
OPERATIVE TECHNIQUE
COMPLICATIONS
RESULTS IN TWO GROUPS OF
PATIENTS
DISCUSSION

INTRODUCTION
About 10 years ago the development of viscocanalostomy as a new
technique of filtering, but not fistulating surgery was started by Robert
Stegmann in Pretoria (South Africa). The idea was to create a route for the
aqueous to diffuse through an intact window in Descemets membrane
above Schwalbes line into a subscleral lake and into surgically created
and dilated ostia of Schlemms canal. The development of Healon GV
by Balazs et al1-4 was a major contribution as this substance has antiinflammatory effects in combination with the property to stay in place for
some days in the dilated Schlemms canal and the scleral lake.
The need for such a technique arose because of the very hard outcomes
of filtration surgery in black patients.5 In white patients complications are
reported in 30 percent6 in the early phase. Later on, intraocular pressure
(IOP) is normalized in 40 percent of the whites without local therapy, and
in 80 percent with some medication. Thus, the development of a different
technique with less complications and a better outcome especially in black
patients was a logical consequence.
OPERATIVE TECHNIQUE
The original technique is described as follows: topical flurbiprofen sodium
(Ocufen, Ocuflur) is applied preoperatively, and a subconjunctival
injection of dexamethasone sodium phosphate (Decadron-Decadran)
is given approximately 20 minutes before the start of surgery in black
patients.
The technique is performed under general anesthesia. A lid speculum
is inserted, and a superior rectus muscle bridle suture placed (3/0 black
braided silk). A fornix-based conjunctival flap extending from 2 to 10
oclock is retracted to expose the sclera. Bipolar coagulator is not used.
Adequate hemostasis is achieved using topically administered POR-8. A
parabolic-shaped scleral flap, 5.0 4.0 mm, of one-third scleral thickness
(+250 microns) is dissected to create a lamellar flap extending 0.5 mm into
clear cornea (Fig. 37.1).
A second parabolic flap is dissected 0.5 mm inside the border of the
initial flap extending into clear cornea for 0.5 mm. This second flap is
approximately two- third of the scleral thickness to leave a thin translucent
layer of sclera overlying the choroid (Fig. 37.2).
As this flap is dissected forward in the correct plane, Schlemms canal
is readily visualized approximately 1.0 mm posterior to the limbus (Fig.
37.3) Exposure of Schlemms canal shows the important landmark of
smooth gray-white tissue, which constitutes the roof of the canal (Fig. 37.4).

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Chapter 37: Viscocanalostomy 343

Fig. 37.1: Under general anesthesia, once the eye is ready


and the conjunctival flap has been done, a parabolic-shaped
scleral flap, 5.0 x 4.0 mm, of one-third scleral thickness (+250
microns) is dissected to create a lamellar flap extending 0.5
mm into clear cornea

Fig. 37.3

Fig. 37.4

Fig. 37.2

With Schlemms canal unroofed, a finely polished


cannula (outer diameter 150 microns) is inserted into the
lumen of Schlemms canal, both left and right, to inject
high-density sodium hyaluronate (Healon GV) for 4.0
to 6.0 mm on each side (Fig. 37.5). The diameter of
Schlemms canal is enlarged to about 230 microns from
its usual diameter of 25 to 30 microns (Fig. 37.6).
A paracentesis is made with a minidiamond blade,
and aqueous is removed from anterior and posterior
chambers. Gentle pressure on Schwalbes line using a

cellulose sponge separates Descemets membrane from


the corneoscleral junction (Fig. 37.7). This maneuver
creates an intact window in Descemets membrane
through which aqueous diffuses from the anterior
chamber into the subscleral lake.
The deep scleral flap is then excised at its base using
a Vannas scissors (Fig. 37.8). Five 11/0 polyester fiber
(Mersilene) sutures are used to close the superficial
flap in a watertight manner. Healon GV is then injected
into the subscleral lake (Fig. 37.9) The conjunctival flap
is sutured using 11/0 Mersilene sutures.
Subconjunctival steroid and an antibiotic (ciprofloxacin hydrochloride or gentamicin) are injected in the
inferior fornix.7

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344 Section III: Glaucoma

Fig. 37.5
Fig. 37.7: Using cellular sponge, gentle pressure is applied at
Schwalbes line to separate Descemets membrane

Fig. 37.6

COMPLICATIONS

Fig. 37.8: Excision of deep scleral flap with Vannas scissors

Early complications including operative problems may


be
Exposure of the ciliary body
Rupture of Descemets membrane
Hyphema
Astigmatism.
During the preparation of the inner flap an
inadverted exposure of small portions of the ciliary
body may happen. This will not change the outcome of
surgery. No special correcting measures are necessary.
A rupture of Descemets membrane while creating
the window may happen, if enough mechanical force
is applied, or if the pressure in the anterior chamber has
not been lowered properly by a previous paracentesis.

In case of a complete ruptureparallel to Schwalbes


linewith a deep anterior chamber, together with a wide
open chamber angle glaucoma, the procedure can be
completed as usual. If the angle is shallow, a peripheral
iridectomy should be performed (a small corneal incision
is then needed). The rest of the viscocanalostomy can be
brought to the end as usual.
A small hyphema is not rare, specially in eyes with a
very high pressure before surgeryit spontaneously
resolves in a short period of time. In 1 case of Robert
Stegmanns series, a drainage was necessary.
Suturing the outer flap too tight may create a high
astigmatism. This can be managed by cutting the suture

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Chapter 37: Viscocanalostomy 345

Fig. 37.9

responsible for the astigmatism 6 to 8 weeks after surgery.


As late complications, can be noted:
Iris adhesion to the Descemets window
Bleb formation
Fibrotic closure of the ostia of Schlemms canal or
of the Descemets window
Early exercising with raised intrathoracic pressure (or
other Valsalva maneuvers) may lead to iris adhesions
covering the Descemets window. These adhesions may
be cut with a YAG laser. If unable to do so, a surgical
synechiolysis may be helpful.
If bleb formation occurs, the bleb is shallow and
localizedit has the appearance of the blebs we dislike
to see after a fistulating procedure. Traditional problems
associated with filtering blebs like encysted blebs,
dellen formation, rupture of the bleb (leakage) or excessive filtration do not occur. In most cases a revision of
the bleb will be unnecessary.
Fibrin formation and fibrotic closure of the ostiae lead
to a pressure rise a few days after surgery. A strong antiinflammatory treatment and a very clean cut preparation
of the edges of the inner flap reduce the number of the
incidents, which cannot always be avoided.
Fibroblastic proliferation on the anterior and/or
posterior surface of Descemets window may result in a
reduced aqueous outflow. In some patients, a revision of
the operation performing a mechanical cleaning of the
inner lake and the ostiae and a refilling with Healon GV
may be of help. If unsuccessful, a new viscocanalostomy
procedure in a different site is indicated.
RESULTS IN TWO GROUPS OF PATIENTS

ocular pressure, measured in millimeters of mercury) was


47.4 + 13 (SD). None of the patients was on medical
therapy at the time of surgery. All patients were operated
by the same surgeon (R Stegmann).
Postoperative mean IOP was 16.85 + 8.0 mmHg
without any medical therapy, which represented an IOP
reduction of 64 percent. The mean follow-up was 35
months and the longest follow-up, 64 months. One
hundred seventy-six cases achieved an lOP of 22 mm
Hg or less without medical therapy, representing a
success rate of 82.7 percent. Among these patients, several
had an IOP decrease of more than 80 percent.
Addition of a topical beta-blocking agent in cases
considered as a statistical failure, increased the success
rate to 89 percent. Of the 38 cases considered to have
failed (i.e. IOP over 22 mmHg and not yet on medical
therapy), the mean IOP decrease was 48 percent.
There were few complications associated with the
procedure. Hyphema occurred in 7 patientsin 1 patient,
drainage was necessary and in the other 6 patients,
hyphemas spontaneously cleared in 48 to 72 hours. One
intraoperative vitreous hemorrhage occurred which was
attributed to the rapid reduction in IOP due to the paracentesis. Only 5 percent of the surgeries resulted in bleb
formation. In all cases the bleb was shallow and localized
and did not cause problems related with blebs, like
dellen formation, encapsulated or ruptured blebs.
There were no flat chambers or choroidal detachments
common with traditional filtration procedures There was
no cataract development in the 48 patients under 40 years
of age. The incidence of cataract in patients over years of
age, compared with that in the control group was not
investigated.7
Group 2. Cologne-Group (N Krber)
57 eyes of 49 white patients with a variety of glaucomatous problems (Table 37.1):
Table 37.1: Results in Cologne-group (N Krber)
POAG (chronic open-angle galucoma)
PEX-Glaucoma (exfoliative glaucoma)
POAG with previous glaucoma surgery
Aniridia/cataract/glaucoma
Nan-ophthalmos, Iridectomy
Angle closure in neovascular glaucoma with
resolved neovascularization
Silicone-glaucoma
Traumatic angle closure-recession

42
3
4
2
2
2
1
1

Group 1. Pretoria-Group (R Stegmann)


214 eyes of 157 black African patients with uncontrolled
open-angle glaucoma. Mean preoperative IOP (intra-

All patients in this group were operated by one


surgeon (N Krber) the same way described above.

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346 Section III: Glaucoma


Mean preoperative IOP was 35 + 7.1 mm Hg
Mean number of 3 topical medications.
3 cases also treated with oral 250 mg of acetazolamide
(Diamox-Edemox) three times a day.
One month after surgery mean IOP was 15.5 + 9.4
mmHg in 40 eyes and after 6 months 17-6 + 6.8 mmHg
in 43 eyes.
One year after surgery mean IOP was 15.9 + 4.3 in 29
eyes, 6 of them requiring a topical therapy. Two of them
needed two topical drugs..
In this group, 1 eye was uncontrolled after surgery
and needed revision surgery because of excessive
scarring in the subscleral lake (fibrosis). 2 eyes did well
after reopening the lake and the lumen, and 1 eye achieve
normal pressures after a second viscocanalostomy in a
different site (previously failed trabeculectomy, 360
angle closure before the first viscocanalostomy; failure
of the first viscocanalostomy by iris attachment to the
Descemets window).
Two years after surgery we could follow 8 eyes. The
mean IOP was 15.0 + 5.0 mmHg.
As complication, we noticed small hyphemas in 3
eyes, which resolved spontaneously. Bleb formation
occurred in 20 percent with no further problems elsewhere described like dellen formation, ptosis,
epiphora, photophobia or hypotony-related side effects.
DISCUSSION
The multiple complications of filtrating and fistulating
surgical procedures to treat glaucoma have lead to
attempts with new techniques that avoid entering the
anterior chamber.8-10 During the last years this idea has

been taken up again.11-16 The results are promising, with


good pressure reduction over a period of about 12 to 14
months. Viscocanalostomy has shown to be a method
employing the idea of not entering the anterior chamber
and excluding the problems of fistulating procedures,
though having its own minor problems.
The high success rate even in a black African population and in other populations17,18 as well as in our
Cologne-group over longer periods of time without
the dependence on a functioning filtering bleb and
without any need for antimetabolites 7,19 make this
technique very promising.
Viscocanalostomy may have different mechanisms
of action to reduce IOP .
Aqueous humor outflow from the anterior chamber
through the window in Descemets membrane into
the scleral lake may use the new pathways in
Schlemms canal, apart from the normal physiologic
way. This proposed mechanism of action is supported
by the observation that the injection of high-viscosity
sodium hyaluronate into Schlemms canal during
viscocanalostomy produces a presence of viscoelastic
substances in the aqueous veins as blood is displaced
(Figs 37.10 and 37.11).
Another possible reason for the procedures success
is that it increased uveoscleral outflow. Aqueous
passing through Descemets membrane into the
scleral lake can diffuse into the uveoscleral outflow
system that is adjacent to the lake.
Finally, a combination of both increased egress of
aqueous through Schlemms canal and increased
uveoscleral outflow may be the reason for the
pressure reduction.7

Figs 37.10 and 37.11: Notice that high-viscosity sodium hyaluronate into Schlemms canal during viscocanalostomy
produces a presence of transparent viscoelastic substances in the aqueous veins, as blood is displaced, the vein looks empty
(arrows)

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Chapter 37: Viscocanalostomy 347


The Spanish Experience

REFERENCES

The idea of good IOP reduction without the hypotonyrelated risks and complications (specially hypotony
macular damage and choroidal detachment), made
viscocanalostomy very attractive to us, despite the fact
that the black population is non-significant in our
country.
We were definitely attracted by the excellent results
reported (personal communication) by the German
group in Cologne (Germany). Although our experience
is limited to a very small number of patients (19 patients)
and that all the patients were chronic open-angle
glaucomas, the facts are that the technique worked well
in the short term (less than two years). Close follow-up
demonstrated that IOP was quite unstable the first weeks
after surgery. No differences were clearly appreciated
between men and women.
It is not an easy surgical techniqueit should be
reserved to experienced surgeons. No major complications were noticed, but two unwanted openings of the
anterior chamber. To perform this technique, the instruments have to be diamond-sharp (we learned from our
experience in glaucoma surgery and only use diamond
knifes)keeping the right dissection plane with nonsharp instruments is not easy and may be dangerous. A
big advantage of this surgical technique is that you can
easily reconvert to a classical trabeculectomy or to a
Scheies technique at any stage.
Anterior chamber hemorrhagesmost non-significant have been almost a constant in our series, but
resolved spontaneously within the first week. The
formation of a small bleb has also been frequent (more
than 50% of the patients), despite the fact that viscocanalostomy is intended to be non-fistulating: Healon
GV, while absorbed, together with eye movements
keep the edges of superficial scleral flap open enough
for a bleb to form.
Examining these patients about two years after
viscocanalostomy has shown that IOP reduction is not
stable in time in the Spanish population we operated.
There was an IOP rise with time. About 50 percent of the
patients are now (almost two years after surgery) under
topical aqueous suppressants: before analyzing this
percentage, we want to make it clear that we consider
that only less than 15 mmHg is a successful IOP after a
surgical procedure for glaucoma.
We are now experiencing a modification of the technique described by Robert Stegmann, by placing under
the superficial scleral flap a piece of solid sodium
hyaluronate. Too early to talk on it.

1. Denlinger JL, Eisner G, Balazs EA: Age related changes in the


vitreous and lens of rhesus monkeys (Macaca mulatta).
IInitial biomicroscopic and biochemical survey of reeranging animals. Exp Eye Res 1980;31:67.
2. Denlinger JL, Balazs EA: Replacement of the liquid vitreous
with sodium hyaluronate in monkeys. I. Short-term evaluation.
Exp Eye Res 1980;3l:8l.
3. Balazs EA: Physiology of the vitreous body. In Schepens CL
(Ed): Importance of the Vitreous Body in Retina Surgery with
Special Emphasis on Reoperations, CV Mosby: St. Louis, 1960;
144.
4. Denlinger JL, El-Mofty Alam, Balazs EA: Replacement of the
liquid vitreous with sodium hyaluronate in monkeys. IIlongterm evaluation. Exp Eye Res 1980;30:101.
5. Broadway D, Frierson I, Hitchings R: Racial differences in the
results of glaucoma filtration surgeryare racial differences in
the conjunctiva cell profile important ? Br J Ophthalmol 1994;
78:466-75.
6. Spaeth GL, Katz RJ, Terebuh A: Glaucoma surgery. Duanes
Ophthalmol 1999.
7. Stegmann R, Pienaar A, Miller D: Viscocanalostomy for openangle glaucoma in black African patients. J Cataract Refract Surg
1999;25:316-22.
8. Krasnov MM: Sinusotomyfoundation, results, prospects.
Trans Am Ophthalmol Otolarygol 1972;76:369-74.
9. Zimmermarnn r3, Kooner KS, Ford VJ et al: Trabeculectomy vs
non-penetrating trabeculectomya retrospective study of two
procedures in phakic patients with glaucoma. Ophthalmic Surg
1984;15:734-40.
10. Kozlov VI, Bargov SN, Asisimova SY et al: Non-penetrating
deep sclerotomy with collagen. Ophthalmo-Surgery 1990;3:
44-46.
11. Sanchez E, Selnyder CC, Sickenberg M et al: Deep sclerotomy
results with and without collagen implant. Int Ophthalmol 1997;
20:157-62.
12. Chiou AGY, Mermoud A, Hdiguer SEA et al: Ultrasound
biomicroscopy of eyes undergoing deep sclerotomy with
collagen implant. Br J Ophthalmol 1996;80:541-44.
13. Sourdille P, Santiago PY, Villain F et al: Reticulated hyaluronic
acid implant in non-perforating trabecular surgery. J Cataract
Refract Surg 1999;25:332-39.
14. Mermoud AE, Schnyder CC, Sickenberg M et al: Comparison
of deep sclerectomy with collagen implant and trabeculectomy
in open-angle glaucoma. J Cataract Refract Surg 1999;25:
323-31.
15. Demailly P, Lavat P, Kret O et al: Non-penetrating deep sclerectomy (NPDS) with or without collagen device (CD) in primary
open-angle glaucomamiddle-term retrospective study. Int
Ophthalmol 1997;20:131-40.
16. The deroofing of Schlemms canal in patients with open-angle
glaucoma through placement of a collagen drainage device.
Ophthalmic Surgery and Lasers 1998;29:216-26.
17. Carassa RG, Bettin P, Fiori M et al: Viscocanalostomya pilot
study. Europ J Ophthalmol 1998;8:57-61.
18. Tretz MR, Vlcker HE, Nimsger C et al: Erste Erfahrungen mit
der Viscocanalostomie mit tiefer Skleraresektion 12 Kongress
der DGll 1998; Springer-Verlag: Berlin 1999.
19. Drake M: Complications of glaucoma filtration surgery. Int
Ophthalmol Clin 1992;32(4):115-30.

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348 Section III: Glaucoma

38

Update on Antiglaucoma Therapy


Ashok Garg

MIOTICS
ALPHA-ADRENERGIC AGONISTS
SYMPATHOMIMETICS
ADRENERGIC BLOCKING AGENTS
(BETA-BLOCKERS)
CARBONIC ANHYDRASE
INHIBITORS
ETHOXAZOLAMIDE
PROSTAGLANDINS
CALCIUM CHANNEL BLOCKERS
ANTIMETABOLITES
(ANTI-FIBROPROLIFERATIVE
AGENTS)
RECENT ADVANCES IN
GLAUCOMA THERAPY
FUTURE DIRECTIONS

In the last decade antiglaucoma therapy has undergone revolution. A


number of new potent ocular hypotensive agents are now available
commercially for the effective and better medical management of all type
of glaucomas. These new ocular hypotensive drugs have excellent efficacy
with least side effects. They are highly effective in lower doses and lower
concentration making the compliance of patients more treatment oriented
and practical. For the purpose of antiglaucoma therapy glaucoma may be
grouped as
Primary open angle glaucoma
Primary angle closure glaucoma
Primary congenital glaucoma
Secondary glaucoma of diverse etiology.
Various antiglaucoma agents used in ophthalmology are as follows.
The mechanism of action of various antiglaucoma drug in IOP reduction
is given in Figure 38.1.
Miotics
Cholinergic agents
Acetylcholine chloride
Pilocarpine hydrochloride and nitrate
Pilocarpine combinations
Carbachol

THE ROLE OF
NEUROREGENERATION

Fig. 38.1: Pathways to IOP reduction: a comparison of the sites and


mechanism of action of various antiglaucoma drugs
(Courtesy: Allergan India Ltd)

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Chapter 38: Update on Antiglaucoma Therapy

349

Hyperosmotic agents
Glycerin
Isosorbide
Mannitol
Urea powder or solution
Calcium channel blockers
Antimetabolites (Anti-fibroproliferative agents)
Recent advances (Ocular hypotensive lipids, neuroprotective and neuroregenerative agents)

Anticholinesterase agents
Physostigmine salicylate and sulfate
Demecarium bromide
Echothiophate iodide
Isoflurophate
Alpha-adrenergic agonists
Apraclonidine
Brimonidine tartrate
Dapiprazole HCl
Clonidine
Sympathomimetics
Dipivalyl epinephrine (Dipivefrin hydrochloride)
Epinephrine borate, bitartrate or HCl
Adrenergic Blocking Agents (Beta-blockers)
Betaxolol hydrochloride
Carteolol hydrochloride
Levobunolol hydrochloride
Metipranalol hydrochloride
Timolol maleate and hemi-hydrate.

MIOTICS
Cholinergic Agents
The direct acting miotics are cholinergic agents which
have effect on muscarinic (parasympathomimetic)
receptors in the eye. Pharmacological effects include
miosis, constriction of the pupil and accommodation
(contraction of the ciliary muscle). Various antiglaucoma
agents of this group are (Fig. 38.2):

Carbonic anhydrase inhibitors


Acetazolamide
Dichlorphenamide
Methazolamide
Dorzolamide hydrochloride
Brinzolamide
Ethoxazolamide

Acetylcholine Chloride
It is used only for intraocular (intracameral route)
administration to induce miosis during ocular surgery.
It produces complete miosis in seconds by irrigating the
iris after delivery of lens in cataract surgery, in
penetrating keratoplasty, iridectomy and other anterior,
segment surgery where rapid, complete miosis may be
required.

Prostaglandins
Latanoprost
Bimatoprost
Unoprostone
Travoprost

Dosage It is available as powder and fresh ophthalmic


solution (1:100 acetyl choline chloride) is prepared before

+ CH3
O
|
CH3C O CH2 CH2 N CH3 Cl
|
CH 3

Carbachol
(carcholin, doryl,
Carbamyl chloride)

Pilocarpine
(Hydrochloride or
nitrate)

+ CH3
O
|
NH2C O CH2 CH2 N CH3 Cl
|
CH 3
=

Acetylcholine

C
CH2
CH CH
|
|
|
||
C2H5 CH CH CH2 C N CH3

Fig. 38.2: Chemical structures of cholinergic agents

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350 Section III: Glaucoma

Fig. 38.3: Antiglaucoma drug which acts by


draining out more fluid
(Courtesy: Allergan India Limited)

use. Usually 0.5-2 ml of this solution is required to


produce satisfactory miosis. Solution need not to be
flushed from the chamber after miosis occurs. Since
acetylcholine has short duration of action (10-20 minutes)
pilocarpine may be applied topically before dressing to
maintain miosis. As the aqueous solution of acetylcholine
is unstable, so fresh solution is prepared before use.
Adverse reactions On ophthalmic use it may cause
transient lenticular opacities. Systemically it may cause
bradycardia, hypotension, flushing and sweating.
Pilocarpine
Pilocarpine is most commonly and widely used oculohypotensive drug of miotic group (Direct acting parasympathomimetic cholinergic drug).
It is used as first drug of choice either alone or in
combination with other antiglaucoma drugs. Principal
mode of action of pilocarpine to reduce IOP is by
enhanced aqueous outflow of stimulating ciliary muscle
contraction and pull on the scleral spur and trabecular
meshwork (Fig. 38.3). Pilocarpine is indicated in chronic
open angle glaucoma (chronic simple glaucoma), acute
angle closure glaucoma, chronic synechial angle closure
glaucoma (following peripheral iridectomy) and
following cyclodialysis surgery.
It is primarily contraindicated in inflammatory
glaucoma, malignant glaucoma or known allergic cases.
Dosage It is available in topical ophthalmic solution
form, ocuserts and in gel form.
In topical ophthalmic solution forms two salts of
pilocarpine are available for use.

1. Pilocarpine hydrochloride in the strengths of 0.25


percent, 0.50 percent, 1 percent, 2 percent, 3 percent,
4 percent, 6 percent, 8 percent and 10 percent eyedrops.
2. Pilocarpine nitrate (Allergan) in strengh of 1 percent,
2 percent and 4 percent eyedrops.
Patient is advised to instill 1-2 drops topically in the
affected eye upto 3 to 4 times daily. The frequency of
instillation and the concentration are determined by the
response of the patient. The normal concentration range
used is 0.5 percent to 4 percent. Concentration greater
than 4 percent are more effective specially in patients
with dark pigmented eyes because pilocarpine is
absorbed by melanin pigment.
Gel doses (4%): Apply 15 mm ribbon in the conjunctival sac of the affected eye once a day preferably at
bed time.
During acute phase, the miotic must be instilled into
the unaffected eye to prevent an attack of angle closure
glaucoma.
In milder open angle glaucoma therapy is usually
initiated with 1-2 percent concentration. Onset of miotic
effect starts in 10-30 minutes and duration of effect is 46 hours. It is usually prescribed for every 6 hours.
Pilocarpine Ocular Therapeutic System (Ocusert)
Pilocarpine can also be given by (Pilocarpine ocular
therapeutic system) ocusert P-20 or ocusert P-40, or by
soft contact lenses. Pilocarpine when given with polymer
vehicle (1.6% polyvinyl pyrrolidine) have a prolong
duration of action and improved pressure control.
Ocuserts are changed weekly. P-20 ocuserts are generally
used in patients controlled with 2 percent drops or less
and P-40 in those requiring higher doses (Fig. 38.4).
Ocusert reduces the amount of drug necessary to
achieve adequate medical control. Ocusert initially
releases the drugs at 3 times the rated value in first hour
and declines to the rated value in approximately 6 hours.
A total of 0.3-0.7 mg pilocarpine is released during the
initial 6-hour period (one drop of 2 percent pilocarpine
solution contains 1 mg pilocarpine). During the
remainder of the 7 days period the release rate is within
20 percent of the rated value.
During the first several hours after insertion, induced
myopia may occur but it decreases to low baseline level
(approx 0.5 diopters or less) with ocusert after several
hours. So it is advised to place the ocusert into conjunctival cul-de-sac at bed time. By morning induced myopia
is at stable level.
Ocuserts have to be kept in refrigerator at 2-8oC.
Ocusert Pilo-20 (ocular therapeutic system)
releases 20 mcg pilocarpine per hour for 1 week

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biosoluble matrix provides drug release upto 24 hours


when placed in cul-de-sac.
Adverse reactions
Ocular side effects include fluctuating myopia. Pupillary miosis (it may lead to diminished night vision,
contraction in peripheral visual fields or diminished
visual acuity.
Shallowing of anterior chamber which may convert
open angle glaucoma with narrow angles into partial
angle closure glaucoma systemic side effects include
sweating, gastrointestinal over activity, salivation,
nausea, tremor, headache, brow pain, bradycardia
and hypotension.
Pilocarpine (Topical) is used in combination with
other antiglaucoma agents. Various pilocarpine
combinations used in ophthalmology are:Pilocarpine and Epinephrine Combinations
The combination of pilocarpine and epinephrine
provides additive effects in lowering intraocular
pressure.
Pilocarpine lower IOP by a direct cholinergic action
which improves outflow facility on chronic use. Epinephrine also reduces IOP by increasing outflow facility.
Fig. 38.4: Ocusert in place in lower conjunctival cul-de-sac

Ocusert Pilo-40 (Releases 40 mcg pilocarpine per


hour for 1 week).
It has been clinically shown that ocusert 20 mcg is
roughly equal to 0.5 percent or 1 percent pilocarpine
drops and 40 mcg is roughly equal to 2 percent and
4 percent drops. Ocusert reduces the amount of drug
necessary to achieve adequate IOP control therefore
therapy may be started with 20 mcg ocusert system
inspite of topical pilocarpine solution strength the patient
previously used. Therapy may be started with 40 mcg
ocusert system depending upon the patient age, family
history, disease progression.
If IOP is reduced to desired level with the 20 mcg
system, the patient should continue its use replacing each
unit every week. If IOP reduction is not reached upto
desired level with 20 mcg system, then transfer the
patient to the 40 mcg system. If situation demands,
concurrent use of epinephrine, -blocker or carbonic
anhydrase inhibitor is indicated. Ocusert drug release
rate is not altered by other ophthalmic preparations.
Another polymer (Piloplex) when given twice a day
has more effect than plain pilocarpine. Recent data have
shown that pilocarpine when given in a synthetic

Dosage Pilocarpine hydrochloride concentration


varied from 1-6 percent and epinephrine bitartrate 1
percent solution (E-Pilo1E-Pilo6). Patient is advised to
instill 1-2 drops of this combination in the affected eyes
1-4 times daily. Individual with heavily pigmented irides
may require larger doses.
Pilocarpine and Physostigmine Combination
Pilocarpine and physostigmine combination is used on
the basis that improved response may be obtained.
Pilocarpine reduces IOP by direct cholinergic action with
improved outflow facility while physostigmine is a
reversible inhibitor of cholinesterase and has indirect
cholinergic effect.
Dosage It is available as pilocarpine 2 percent and 0.25
percent physostigmine salicylate combination
ophthalmic drops.
Patients is advised to instill 1-2 drops in the affected
eyes up to 4 times daily.
In addition to these combinations, pilocarpine 2-4
percent is given to instill alongwith 0.5 percent. Timolol
(or another beta-blocker) which yields notable lower IOP
than either agent used along.
Pilocarpine broate or nitrate 1 percent with clonidine
0.125 percent (These combinations have been shown to

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352 Section III: Glaucoma


have in 1.4 percent PVA potential IOP lowering effect
and excellent tolerance.
Carbachol
Carbachol is dual action parasympathomimetic which
produces direct motor end plate stimulation.
It mechanism of action and physiological effects are
similar to pilocarpine.
Carbachol eyedrops are longer acting than pilocarpine, thus having a great stabilising effect on diurnal
pressure and myopia fluctuation. It may also be used in
patients allergic to pilocarpine, otherwise the indications
are similar to that in pilocarpine.
An intracameral preparation for intraoperative use
induces miosis and inhibits postoperative pressure rise.
Carbachol is also not given in inflammatory glaucoma,
malignant glaucoma or known allergic cases.
Dosage Topically in ophthalmic eyedrops it is available
in concentrations of 0.75 percent, 1.5 percent, 2.25 percent
and 3 percent.
Patient is advised to instill 1-2 drops topically in the
eyes upto 3 times daily. Carbachol effect starts within
10-20 minutes and effect last upto 8 hours. Carbachol 3
percent is approximately equivalent to 4 percent pilocarpine and 15 percent roughly equivalent to 2 percent
pilocarpine.
For intracameral administration it is available in the
concentration of 0.01 percent in 1.5 ml ampoules. Gently
Instill not more than 0.5 ml into the anterior chamber
during ocular surgery. Miosis is achieved within 2-5
minutes after application.
Adverse reactions On topical use it can lead to corneal
clouding, persistent bullous keratopathy, postoperative
iritis following cataract extraction with intra ocular use,
transient ciliary and conjunctival injection, ciliary spasm
and retinal detachment. Systemic adverse effects include
sweating, salivation, GI cramps, vomiting, diarrhea,
flushing, epigastric distress, asthma, syncope.
Anticholinesterase Agents
Physostigmine
It is reversible cholinesterase inhibitor and thus enhances
the effects of endogenous acetylcholine. Increase in cholinergic activity leads to intense miosis and contraction of
the ciliary muscle (Fig. 38.5). Decrease in IOP results
primarily from increased facility of outflow of the
aqueous humor. Physostigmine is indicated mainly for
reduction of IOP in primary glaucoma. Other indications
include chronic open angle glaucoma (specially with

aphakia), chronic synechial angle closure glaucoma


(following peripheral iridectomy) and following
cyclodialysis surgery. In glaucoma cholinesterase
inhibitors are used for those patients who fail to respond
to direct acting cholinergic alone or in combination with
epinephrine, -blockers or a carbonic anhydrase inhibitor.
Contraindications Anticholinesterase agents should not
be used in narrow angle glaucoma without an iridotomy
because of the extreme miosis they produce as well as
possible forward lens movement which may actually
increase pupillary block, inflammatory glaucoma,
glaucoma associated with iridocyclitis, hypersensitivity
to cholinesterase inhibitors.
Dosage
Physostigmine salicylate is available as ophthalmic
solution in concentration of 0.25 percent and 0.5
percent. Patient is advised to instill 2 drops into the
affected eyes upto 4 times a day.
Physostigmine sulfate is available as 0.25 percent
ophthalmic ointment.
Apply a small quantity of ophthalmic ointment to
lower fornix upto three times a day.
Demecarium Bromide
The mechanism of action of demecarium is similar to that
of physostigmine. In addition to indications already
mentioned demecarium is also used in accommodative
esotropia (Convergent strabismus).
Dosage Demecarium bromide is available as ophthalmic solution in conc of 0.125 and 0.25 percent.
Because of prolonged duration of action of demercarium administration of drug is required only twice a
day, some patients may achieve adequate IOP control
with once a day administration.
Because of its tendancy to produce severe adverse
effects including systemic reactions, use the lowest dose
consistent with adequate control. The 0.125 percent
strength used twice daily results in smooth control of
physiological diurnal variation in IOP. This is the
preferred dosage for most open angle glaucoma patients.
For initial therapy place 1-2 drops into the eye. Usual
dose is 1-2 drops twice a week to 1-2 drops twice a day.
Closely observe the patient during the initial period
of therapy. Keep frequency of use to a minimum in all
patients to reduce chances of iris cyst development.
Accommodation esotropia treatment Essentially equal
visual acuity of both eyes is a prerequisite to successful
treatment. In esotropia uncomplicated by amblyopia or

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Chapter 38: Update on Antiglaucoma Therapy

Echothiophate
(Phospholine)
Iodide

C2H5
|
O
+
|
(CH3)3 N CH2 CH2 S P = O . I
|
O
|
C2H5
CH3+
|
CH3 N CH3
|

Demecarium
bromide
(Humorsol,
Tosmilen)

CH3+
|
CH3 N CH3
|
O

O CH 3

CH3
|
OC N (CH2)10 N C O

CH3 CH 3
|
|
N
N
Physostigmine
(eserine)

CH3 NHCOO
CH 3
CH 3 +
|
CH3 N CH3
|

Neostigmine
bromide
(Prostigmine)

Br

CH3

OC N
CH3

Isoflurophate
(Floropryl)

H
|
CH3 C CH3
|
O
|
FP=O
|
O
|
CH3 C CH3
|
H
Fig. 38.5: Chemical structures of anticholinesterase agents

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353

354 Section III: Glaucoma


anisometropia. Instill demecarium 0.125 percent
ophthalmic drops not more than 1 drop at a time in both
eyes every day for 2-3 weeks too severe a degree of miosis
may interfere with vision. Then reduce dosage to 1 drop
every other day for 3-4 weeks and review the patient
status. Continue with a dosage of 1 drop every 2 days to
1 drop twice a week. The latter dosage may be
maintained for months. Do not use more than directed
and caution is necessary to avoid overdosage.
Echothiophate Iodine
Echothiophate is most frequently used agent. It depresses
both plasma and erythrocyte cholinesterase.
Echothiophate irreversibly inactivate Cholinesterase
and have prolonged effect. It is indicated in subacute or
chronic angle closure glaucoma after iridectomy or where
surgery is refused or contraindicated and in certain nonuveitic secondary type of glaucoma specially glaucoma
after cataract surgery.
Dosage Echothiophate iodide is available as powder
and topical ophthalmic solution is reconstituted in the
concentrations of 0.03 percent, 0.06 percent, 0.125 percent
and 0.25 percent.
Two doses per day preferred (Morning and bed time
dose) to maintain a smooth diurnal tension curve as
possible. It is unnecessary and undesirable to exceed a
schedule of twice a day. Instill the daily dose or one of
the two daily doses just before retiring to avoid inconvenlence due to miosis.
For early chronic simple glaucoma instill a 0.03
percent solution just before retiring and in the morning
in cases not controlled by pilocarpine. Change therapy
if IOP fails to remain at acceptable level.
Tolerance may develop after prolonged use, a rest
period restores response to the drug. Echothiophate may
be coadministered with epinephrine, -blockers and
Carbonic anhydrase inhibitors.
For accommodation esotropia instill one drop of 0.125
percent solution once a day into both eyes at retiring for
2-3 weeks, if the esotropia is accommodative, a favorable
response may begin within few hours, use lowest
concentration and frequency to achieve satisfactory
results.
Isoflurophate
Isoflurophate like echothiophate depresses both plasma
and erythrocyte chrolinesterase. It is indicated in early
chronic simple glaucoma, advanced chronic simple
glaucoma, Aphakic glaucoma and for accommodative
esotropia.

Dosage Isoflurophate is available as topical ophthalmic ointment in conc of 0.025 percent in a polyethylene
mineral oil gel. Because of its prolonged duration of
action administration of drug is required twice a day.
Preferably apply one dose before retiring to lessen
blurring of vision. Wash hands immediately after
administration. Isofluorophate hydrolyzes in the
presence of water to form hydrofluoric acid. To prevent
absorption of moisture and loss of potency, keep ointment
tube tightly closed.
For glaucomain initial therapy place 0.25 inch strip
of ointment into the eye every 8-72 hours. A decrease in
IOP should occur within few hours. During this period
keep the patient under supervision and perform tonometry at hourly for 3-4 hours to be sure that no immediate
rise in pressure occurs.
For accommodative esotropia not complicated by
amblyopia or anisometropia use not more than 0.25 inch
strip oint at a time in both eyes every night for 2 weeks.
Dosage is then reduced from 0.25 inch strip once a week
for 2 months after which re-evaluate the patient status.
Precautions While Using Anticholinesterase Agents
Miosis usually cause difficulty in dark adaptation.
Use caution while driving at night or performing
hazardous tasks in poor light.
Ophthalmic ointment may retard corneal healing.
Use in glaucoma only when shorter acting miotics
have proven indequate except in aphakic patients.
Sulfite sensitivitysome of these ophthalmic
preparations contains sulfites which may cause
allergy type reactions.
Use caution in patients with bronchial asthma,
vagotonia, peptic ulcer, pronounced bradycardia and
hypotension.
Adverse Reactions of Anticholinesterase Agents
Ocular Side Effects
Stinging, burning sensation, lacrimation, allergic follicular conjunctivitis, accommodative spasm, shallowing
of anterior chamber, diminished night vision and
peripheral field, lid muscle twitching, conjunctival and
ciliary redness, browache, activation of latent iritis or
uveitis, induced myopia, iris cyst formation, lacrimal
punctal stenosis, tear abnormalities.
Retinal detachment and vitreous hemorrhage.
Prolonged use may casue conjunctival thickening,
posterior synechiae to the lens, cataractous lens changes.
Paradoxical increase in IOP by pupillary block may
follow instillation.

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355

Indications Apraclonidine is instilled to control increase


in IOP after anterior segment laser surgery, acute shortterm pressure spikes and more recently as concomitant
therapy with other antiglaucoma drugs at least upto
3 months in chronic primary or secondary glaucoma.
As we know that optic nerve head damage and visual
field loss may result from acute elevation in IOP that can
occur after argon laser surgical procedures.
The onset of action of apraclonidine is usually within
one hour and maximum IOP reduction occurs 3-5 hours
after application of single dose.
Contraindications It includes hypersensitivity to the
drug and cardiac disease with untreated arteriovenous
block or bradycardia.

Fig. 38.6: Antiglaucoma drugs which act by decreasing


aqueous production (Courtesy: Allergan India Limited)

Systemic Side Effects


Anticholinesterase agents may cause
Diarrhea, nausea and abdominal cramps if excessively absorbed.
Urinary incontinance, salivation.
Difficulty in breathing, cardiac irregularities.
Succinylcholine anesthesia should be avoided if
possible in such patients recently on these agents.
Overdosage Due to overdosage, if systemic effects
occur, give parenteral atropine sulphate IV if necessary.
Adults > 0.4 0.6 mg
Children0.05 mg/kg IV initially followed by
maintenance with 0.02 0.05 mg/kg titrated. Pralidoxime
chloride has been useful in treating systemic effects due
to cholinesterase inhibitors. Use in addition not as
substitute to atropine.
ALPHA-ADRENERGIC AGONISTS
Apraclonidine
Apraclonidine is relatively selective -adrenergic agonist.
When instilled into the eye, apraclonidine reduces IOP
and has minimal effect on cardiovascular parameters. It
is a clonidine derivative. The mechanism of action of
apraclonidine is not completely established but it appears
to be beta-2 receptor stimulation that results in decreased
aqueous humor production (Fig. 38.6).

Dosage It is available as topical 0.5 percent ophthalmic


solution (5 ml vial) and 1 percent solution in a single
dose 0.25 ml container. Usual dosage is one drop 1 hour
before laser surgery and 1 drop immediately after the
procedure or one drop just immediately postlaser
appears equally effective and superior to any other
glaucoma drug. This dose decreases the incidence of
postlaser pressure spikes of 10 mmHg or more to less
than 2 percent and lasts 12 hours. Adjunctive treatment
for short-term pressure increase is 1 drop of 0.25 percent
apraclonidine three times a day. There is a 30 percent
allergic response to the 0.50 percent drops.
Adverse reactions On topical use in laser surgery
adverse effects reported are upper lid elevation (1.3%)
conjunctival blanching (0.4%) burning or itching sensation and subconjunctival hemorrhage. Systemic side
effects are gastrointestinal reaction, bradycardia,
vasovagal attack, palpitation, orthostatic hypotension
CNS disturbances include insomnia, irritability and
decreased libido all of which are transient.
Caution should be taken regarding close monitor of
patients who develop exaggerated reductions in IOP as
apraclonidine is a potent depressor of IOP.
Brimonidine Tartrate (Alphagan)
It is recently introduced second generation alphaadrenergic receptor agonist with high degree of
selectivity to alpha-2 receptors. It delivers the efficacy of
a2 agonists along with systemic and ocular safety (Figs
38.7 to 38.9).
Fluorophotomeric studies in human beings have
shown that brimonidine tartrate has a dual mechanism
of action as (Fig. 38.10)
It decreases aqueous humor production like beta
blockers.
It increases uveoscleral outflow like prostaglandins.

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356 Section III: Glaucoma

Brimonidine (ALPHAGANTM
Eyedrops) binding sites were
found in the iris epithelium,
ciliary epithelium, ciliary
muscle, retina, retinal pigment
epithelium and/or choroid

Fig. 38.7: Receptor binding sites for brimonidine in human eyes (Courtesy: Allergan India Limited)

Fig. 38.8: Specific brimonidine stimulating 2 adrenoreceptors (Courtesy: Allergan India Limited)

Due to this decisive mode of action it has a peak


hypotensive effect occurring at 2 hours postdosing.
After ocular administration of 0.2 percent solution
plasma concentrations peak within 1-4 hours and
declined with a systemic half life of approximately 3
hours.

Brimonidine has binding sites in the iris epithelium,


ciliary epithelium, ciliary muscle, retina, retinal pigment,
epithelium and choroid.
Indications Brimonidine is indicated for lowering IOP
in patients with open angle glaucoma or ocular hyper-

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Chapter 38: Update on Antiglaucoma Therapy

357

Brimonidine has a quinoxaline ring that gives it greater selectivity


Fig. 38.9: Chemical structure of alpha2-adrenergic agonists (Courtesy: Allergan India Limited)

field loss. Brimonidine has a unique action of lowering


intraocular pressure with minimal effect on cardiovascular (heart rate, blood pressure) and pulmonary
parameters.
As brimonidine is a new generation alpha-2 agonists
it is more potent than previous first generation agents of
this group (clonidine and apraclonidine). Specific higher
alpha-2 selectivity provides sustained lowering of IOP,
systemic safety and ocular tolerability. Brimonidine is
also an oxidatively stable agents which may account for
its lower ocular allergy rate than apraclonidine.
It provides sustained IOP lowering over at least 12
months period with no evidence of tachyphylaxis. It can
safely be used as monotherapy in newly diagnosed
glaucoma patients or treated previously with other antiglaucoma drugs. It can also be prescribed as adjunctive
therapy with beta blocks or in patients who cannot take
beta blockers due to pulmonary or cardiovascular
diseases.

Fig. 38.10: Brimonidine dual mode of action (decreased inflow and increased uveoscleral outflow) (Courtesy: Allergan
India Limited)

tension. The IOP lowering effect of it diminishes over


time in some patients.
Elevated IOP presents a major risk factor in
glaucomatous field loss. The higher the level of IOP, the
greater the chances of optic nerve damage and visual

Contraindications It is contraindicated in patients with


hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in
patients receiving monoamine oxidase (MAO) inhibitor
therapy.
It should be used with caution in patients with depression, cerebral and coronary insufficiency, orthostatic
hypotension, thromboangitis olbiterans or Raynauds
phenomenon. It should be used in pregnant and lactating
mothers only if potential benefit to the mother justifies
the potential risk to fetus.
Dosage It is available as 0.2 percent ophthalmic
solution (in 5, 10 and 15 ml vials). The recommended

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358 Section III: Glaucoma


dose is one drop in the affected eyes two times daily. For
those patients whose IOP peaks in the afternoon or who
need additional IOP control an additional drop of
brimonidine in the afternoon can be instilled.
Patients wearing soft contact lenses should be instructed to wait atleast 15 minutes after instilling brimonidine
to insert soft contact lenses (as the preservative in topical
solution benzalkonium chloride may be absorbed by soft
contact lenses).
Adverse reactions Adverse reaction are reported in less
than 3 percent of patients. It includes lid crusting, burning
and stinging sensation, ocular hyperemia, headache, oral
dryness, blurring, fatigue, drowsiness, ocular allergic
reactions, ocular pruritus.
Other side effects reported are adbnormal taste
depression, hypertension, anxiety, palpitation and
syncope.
No information is available on overdosage in humans
on topical use. In humans, systemic metabolism of
brimonidine is extensive. It is metabolised primarily by
the liver. Urinary excretion is the major route of
elimination of drug and its metabolites.
Brimonidine tartrate is one of the safest drugs for
long-term use in glaucoma patients.
It is 1000 times more selective for the alpha-2
adrenoceptor that lower IOP, significantly.
Had little effect on the alpha-1 receptors that produce
unwanted ocular side effects such as mydriasis, lid
retraction and intraocular vasoconstriction. Brimonidine
safety and efficacy fits it into new paradigm of glaucoma
management.
Recently another topical preparation Alphagan P
(containing 0.15% Brimonidine purite) is also commercially available. Clinically its safety and tolerability
profile has been shown better than 0.2% Brimonidine
tartrate. The recommended dosage is to instill one drop
in the affected eye twice a day.
Alphagan is also commercially available in combination with topical timolol (0.2% Brimonidine tartrate with
0.5% timolol maleate).
Dosage To instill one drop in the affected eye twice a
day. This combi pack has an additional IOP lowering
effect and safety with better compliance.
Dapiprazole
Dapiprazole hydrochloride is an alpha-adrenergic
blocker. It blocks the alpha-adrenergic receptors in
smooth muscle and produces miosis through an effect
on the dilator muscle of the iris.
This drug does not have any significant effect on
ciliary muscle contraction therefore it does not induces a

significant change in the anterior chamber depth of the


lens thickness.
Dapiprazole has shown safe and rapid reversal of
mydriasis produced by phenylephrine and to lesser
extent by tropicamide. Dapiprazole may induce partial
increase in accommodative amplitude in patients who
had decreased accommodative amplitude due to
tropicamide treatment.
Dapiprazole does not significantly alter IOP in
normotensive eyes or in patients with elevated IOP.
Indications For treatment of iatrogenically induced
mydrisis produced by phenylephrine (adrenergic) or
tropicamide (parasympatholytic) agents.
Contraindication Dapiprazole is contraindicated in
conditions when constriction is undesirable like in acute
iritis or hypersensitivity to any component of this
preparation.
Dosage and administration It is available as lyophilized
powder 25 mg (0.5% solution when reconstituted) in vial
with 5 ml diluent.
Shake container for several minutes to ensure mixing
before use.
Dosage The recommended dosage is to instill 2 drops
into the conjunctiva of each eye followed by additional
2 drops after 5 minutes. Instill the medicine after the
ocular examination to reverse the diagnostic mydriasis.
Precautions Patient should be informed in advance that
dapiprazole use may cause difficulty in dark adaptation
and may also reduce field of vision. Care should be taken
when driving at night or doing other activities in diffuse
illumination.
Adverse reactions Conjunctival injection in more than
75 percent of patients for 15-20 minutes, burning and
stinging sensation (50%), headache (30-40%). Other
adverse effects reported are lid erythema, ptosis, lid
edema, chemosis, punctate keratitis, corneal edema,
photophobia and dryness of the eye.
Clonidine
Topically it is available as 0.125 percent, 0.25 percent and
0.50 percent ophthalmic solutions clonidine is an effective
ocular hypotensive agent but in therapeutic doses when
applied to the eye is partially absorbed systemically and
produce marked hypotension. Clonidine alone is now
not used in ophthalmology.
SYMPATHOMIMETICS
Sympathomimetic agents (Adrenergic agonists) effect on
the eye include pupil dilatation, increased outflow of
aqueous humor and vasoconstriction. Systemic effects

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Chapter 38: Update on Antiglaucoma Therapy

HO

Epinephrine

OH
|
CH CH2 N

359

H
CH3

HO

HO

Norepinephrine

OH
|
CH CH2 N

H
H

HO
CH3 O
|
||
CH3 C C O
|
CH3
CH3
|
CH3 C C O
|
||
CH3 O

Dipivefrin
(Propine)

Phenylephrine
(Neosynephrine)

HO

OH
H
|
CH CH2 N
CH3

OH
|
CH CH2 N

H
CH3

Cl
Clonidine
(Catapres)

HN C
Cl

N CH2
|
N CH2
H

Fig. 38.11: Chemical structures of sympathomimetic agents

from ophthalmic instillation of these products are usually


mild. The various agents used from this group in ophthalmology are (Fig. 38.11).
Epinephrine
Epinephrine has direct stimulant effects on and
adrenergic receptors. Epinephrine increases both
aqueous outflow ( and stimulation) and decreases
aqueous humor formation (Alpha stimulation in the
ciliary body). It is additive to the cholinergics,
anticholinesterases and carbonic anhydrase inhibitors in
pressure lowering effects.
Indications It is primarily used in the open angle
glaucoma/chronic simple glaucoma) or in conjunction
with miotics with mildly shallow chambers.

Contraindications Hypersensitivity to epinephrine,


narrow angle glaucoma and in aphakic and pseudophakic glaucomas.
Dosage Epinephrine is available as the hydrochloride,
borate and bitartrate salts.
These preparations are therapeutically equal when
given in equivalent doses of epinephrine base. It is
available in strengths of 0.5 percent-2 percent. There is
no significant difference in the clinical efficacy of the
preparations. The bitartrate has only 50 percent drug
available as free base.
Usual dosage of epinephrine prescribed is 1 percent
two-three times a day. In patients with dark irides
epinephrine 2 percent may be more potent than 1 percent.
Epinephrine produces a significant decrease in IOP and
duration of decrease is 12-24 hours.

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360 Section III: Glaucoma


Epinephrine is also available in combination with
pilocarpine 1-6 percent. Pilocarpine with 1 percent
epinephrine to be used two-four times a day. When used
in conjunction with miotics, instill the miotic first.
Adverse reactions Ocular effects include topical allergy.
Approx 10-15 percent patients are unable to tolerate longterm epinephrine and usually in such cases epinephrine
must be discontinued.
In 20-30 percent of aphakic patients epinephrine cause
cystoid macular edema after 1 week to months of therapy.
This is almost reversible on cessation of epinephrine
therapy. Other ocular side effects include dark pigmented
conjunctival deposits, canalicular obstruction.
Systemic effects reported are palpitation, tachycardia,
cardiac arrhythmia, hypertension, faintness, trembling,
sweating and pallor.
Discontinue the use of topical epinephrine prior to
general anesthesia with anesthetics which sensitize the
myocardium to sympathomimetics (e.g. cyclopropane or
halothane).
Patients should immediate report for any decrease
in visual acuity during the course of therapy.
Dipivalyl Epinephrine (Dipivefrin Hydrochloride, DPE)
DPE is prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid enhancing its
lipophilic character and as a consequence its better
penetration into the anterior chamber. Penetration is 17
times more than that of epinephrine.
It was synthesized for use on epinephrine allerges as
well as for non-sensitized glaucoma patients. Prodrugs
are usually not active in themselves and require biotransformation to the parent compound before therapeutic
activity is seen. These modifications are undertaken to
enhance absorption, decrease side effects and enhance
stability and comfort thus making the parent compound
more useful.
Propine is converted to epinephrine inside the eye
by enzyme hydrolysis. The liberated epinephrine an
adrenergic agonist appears to exert its action by
decreasing aqueous production and by enhancing outflow facility.
Dipivefrin hydrochloride is a more efficient way of
delivering the therapeutic effects of epinephrine with
fewer side effects than are associated with conventional
epinephrine therapy.
Pharmacokinetics The onset of action with one drop
of dipivefrin occurs about 30 minutes after treatment with
maximum effect seen at about an hour.
Dipivefrin does not produce miosis or accommodative spasm which cholinergic agents are known to
produce. The blurred vision and night blindness often

associated with miotic agents are not present with


dipivefrin therapy.
Indications Dipivefrin is indicated as initial therapy for
the control of IOP in chronic open angle glaucoma and
ocular hypertension patients. Patients not responding
adequately with other antiglaucoma therapy may
respond to replacement or addition of dipivefrin.
Contraindications DPE should not be given in patients
with narrow angle since any dilation of pupil may
predispose the patient to an attack of angle closure
glaucoma. DPE is also contraindicated in patients who
are hypersensitive to this drug.
Dosage It is available as 0.1 percent topical ophthalmic
solution (in 5, 10 and 15 ml packs). The usual dosage of
DPE is to put one drop in the affected eye every 12 hours.
Replacement with DPE When patients are transferred
to DPE from other antiglaucoma agents other than
epinephrine, on the first day continue the previous
medication and add one drop of DPE in each eye every
12 hours, on the following day discontinue the previously
used antiglaucoma agent and continue with DPE only.
When patients are transferred from conventional
epinephrine therapy to DPE, simply discontinue the
epinephrine medication and put the patient on DPE
alone. Using prodrug means less drug is needed for
therapeutic effect since absorption is enhanced with DPE.
At 0.1 percent DPE is less irritating than 1 percent
solution of epinephrine hydrochloride or bitartrate. 0.1
percent DPE used bid is roughly equivalent to that of 2
percent epinephrine. DPE should not be prescribed with
anticholinesterases as they may inhibit the esterases.
Adverse reactions On topical use adverse reactions are
less than that of epinephrine. However, it may cause
burning and stinging sensation, conjunctival injections,
follicular conjunctivitis and allergic reactions. It may lead
to adrenochrome deposits in conjunctiva and cornea
although in a very low percentage of cases.
Aphakic patients should be treated cautiously on DPE
also as it may cause cystoid macular edema although
frequency is very less. Systemic side effects are also very
few.
ADRENERGIC BLOCKING AGENTS
(BETA BLOCKERS)
Beta blockers are commonly used as antiglaucoma
therapy worldwide. Betaxolol, carteolol, levobunalol,
metipranolol and timolol are beta-blockers used in
ophthalmology.
Out of these timolol, levobunolol, carteolol and metipranolol are nonselective beta-1 (Cardiac) and beta-2

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Chapter 38: Update on Antiglaucoma Therapy

361

H 3C
Betaxolol hydrochloride
(Betoptic)

HCCHNHCH2CHCH2O
|
OH

H 3C

CH2CH2OCH2

O
||
Levobunolol hydrochloride
(Betagan)

CH3
|
OCH2CHCH2NHC CH3 HCl
|
|
OH
CH3
S

Timolol maleate
(Timoptic)

N
O

CH 3
|
CHCOOH
OCH2CHCH2NHC CH3 ||
|
|
CHCOOH
OH
CH3

Fig. 38.12: Chemical structures of beta-blockers (adrenergic blocking agents)

(smooth muscle, pulmonary) receptors blocking agents


while betaxolol is cardioselective. Betaxolol has 100 times
more affinity for beta-1 than beta-2 receptors.
Topical beta blockers do not have significant membrane stabilizing (Local anesthetic) or intrinsic sympathomimetic activity. They reduce elevated or normal IOP
with or without glaucoma.
Beta blockers mechanism of action is by reduction of
aqueous production. These agents reduce IOP with little
or no effect on pupil size or accommodation. Blurred
vision and night blindness often associated with miotics
are not associated with these agents. In addition in
cataract patients, the inability to see around the lenticular
opacities when the pupil is constricted is avoided. These
agents may be absorbed systemically.
The non-selective drugs lower IOP by blockade of
beta-2 receptors in the ciliary processes resulting in
decreased aqueous production. The details of various
beta-blockers used in ophthalmology is as follows (Fig.
38.12):
Betaxolol
As already mentioned betaxolol is cardioselective having
greater affinity for beta-1 receptors than beta-2 receptors.
Mechanism of action The mechanism by which betaxolol causes decreased aqueous production is little
unknown as there are few beta-1 receptors in the eye but

there may be spill over to bind beta-2 receptors as well.


The drug molecule betaxolol releases from beta-1
receptor site as early as 3 hours after topical administration yet clinical effect may last upto 2 weeks. This
prolonged effect may result from release of beta-blockers
from depots in iris pigment epithelial melanin.
Indications In treatment of ocular hypertension and
chronic open angle glaucoma. Betaxolol may be used
alone or in combination with other antiglaucoma drugs.
Contraindications It includes known drug allergy. While
betaxolol is the blocker of choice in patients at risk for
pulmonary reaction because of its greater beta-1 (cardiac)
selectivity, the drug may induce bronchospasm in some
patients.
Dosage Betaxolol hydrochloride is available as topical
ophthalmic solution in conc of 0.25 percent and 0.5
percent (in 2.5, 5, 10 and 15 ml packs). Usual dosage is 12 drops in the affected eyes twice daily.
Adverse reactions On ophthalmic (Topical) use ocular
irritation, discomfort and occasional tearing are reported.
Other lesser side effects reported are decreased corneal
sensitivity, erythema, itching, corneal punctate staining,
keratitis and photophobia. Systemic side effects are few
except for insomnia, depressive neurosis.
The IOP lowering response to betaxolol may require
a few weeks to stablise. Determine the IOP during the
first month of treatment.

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362 Section III: Glaucoma


Carteolol
Carteolol hydrochloride is nonselective beta blocker. Its
mechanism of action is by decreasing aqueous production. Carteolol unlike other beta blockers, has intrinsic
sympathomimetic activity possibly resulting in fewer
side effects. It also lacks timolol tendency to raise serum
cholesterol and lower high density lipoproteins, a factor
to consider in cardiovascular patients.
Indications In primary and secondary open angle
glaucoma including inflammatory glaucomas, acute and
chronic primary and secondary angle closure glaucoma,
ocular hypertension.
Precautions and contraindications include known
drugs allergy and use with caution in patients with
asthma, emphysema, bronchitis, heart block, congestive
heart failure, cardiovascular diseases and cardiomyopathy.
Dosage Carteolol hydrochloride is available as topical
ophthalmic solution in conc. of 1 percent (in 5 and 10 ml
packs). Usual dosage is one drop in the affected eye twice
a day.
Adverse reactions Ocular effects include allergy,
punctate keratitis, diplopia, corneal anesthesia and ocular
irritation.
Systemic effects include bradycardia, cardiac arrest,
acute asthma, pulmonary edema, lacrimal canalicular

compression should be advised to patients at any risk.


Other systemic side effects reported are lethargy, depression, impotence, hallucinations and GIT disturbances.
Levobunolol
Levobunolol is non-cardioselective beta adrenoceptor
blocking agent equipotent at both beta-1 and beta-2
receptors. Levobunolol is 60 times more potent than its
dextro-isomer in its beta-blocking activity. It is longacting hypotensive action due to its active metabolite,
dihydrolevobunolol that has significantly longer half
life than timolol. Levobunolol does not have significant local anesthetic or intrinsic sympathomimetic
activity. It has been shown to be as effective as timolol
in lowering IOP. Levobunolol when instilled in the eye
will lower elevated IOP as well as normal intraocular
pressure whether or not accompanied by glaucoma.
The primary mechanism of ocular hypotensive action
of levobunolol HCl in reducing IOP is most likely a
decrease in aqueous humor production. It reduces IOP
with little or no effect on pupil size in contrast to miosis
which cholinergic agents are known to produce. Only
levobunolol increases ocular pulse while achieving better
IOP control (Figs 38.13 and 38.14).
The onset of action with one drop of levobunolol can
be seen within one hour after treatment with maximum
effect seen between 2-6 hours. A significant decrease can
be maintained for upto 24 hours following a single dose.

Fig. 38.13: Change in pulsatile flow (Levobunolol causes greatest percentage increase in pulsatile flow)
(Courtesy: Allergan India Limited)

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Chapter 38: Update on Antiglaucoma Therapy

363

Fig. 38.14: Levobunolol increased ocular pulse (Courtesy: Allergan India Limited)

Indications Levobunolol is indicated for control of intraocular pressure in chronic open angle glaucoma and
ocular hypertension. Contraindications are same as with
other non-selective beta-blockers.
Dosage Levobunolol hydrochloride is available as
topical ophthalmic solution in conc of 0.25 percent and
0.5 percent (in 2, 5, 10 ml packs) usual dosage is 1-2 drops
in the affected eyes once a day.
Adverse reactions On ophthalmic use it may cause
transient ocular burning, blepharoconjunctivitis, stinging
and decrease corneal sensitivity. Systemic side effects
include bradycardia, arrhythmia, browache, syncope,
heart block palpitation, cardiac arrest, congestive heart
failure, dizziness, lethargy and urticaria.

solution. Depending on the patients response, the dosage


strength may be changed or the patient may be stabilized
on a single day application.
Adverse reactions On topical use occasional mild and
transient stinging sensation, corneal hyposensitivity,
decrease in lacrimal secretion may occur. Headache may
occur at the beginning of treatment which will disappear
within few days. Reversible uveitis has also been
reported.
Systemic side effects include bronchial asthma,
dyspnea, bradycardia and can inhibit insulin secretion
in diabetic patients who require treatment. These patients
should be closely monitored.

Metipranolol

Timolol Maleate

Metipranolol hydrochloride is a nonselective beta-blocker. It lowers IOP by blocking beta-2 receptors in the ciliary
processes resulting in decrease aqueous production.

Timolol is one of the most common and most old betablocker being used worldwide till today. It is non-selective beta-blocker which has pressure lowering effect
primarily due to reduced aqueous production by blocking beta-2 receptors in the ciliary processes. Timolol may
act directly on the ciliary epithelium to block active
transport or ultrafiltration.

Indication It is indicated in chronic open angle


glaucoma, aphakic glaucoma and to decrease IOP after
cataract extraction, capsular glaucoma, pigmentary
glaucoma, Juvenile and hemorrhagic glaucoma.
It is contraindicated in patients who are hypersensitive to any of its component, bronchial asthma, obstructive pulmonary diseases and bronchial hyperactivity.
Dosage It is available as topical ophthalmic solution
in conc of 0.1 percent, 0.3 percent and 0.6 percent [in 5
ml pack and single dose unit (0.3%)]. Usual dosage is to
instill one drop in the affected eye twice daily.
If the intraocular pressure decrease is insufficient
treatment should be continued with a higher strength

Indications In primary and secondary open angle


glaucoma as initial therapy either alone or in combination
with miotics. Other indications are inflammatory
glaucoma, acute and chronic primary and secondary
angle closure glaucomas, ocular hypertension and
childhood glaucoma.
Contraindications include known drug allergy and
all other conditions as already explained in other betablockers therapy.

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364 Section III: Glaucoma


Dosage Timolol maleate is available as topical ophthalmic solution in strengths of 0.25 percent and 0.5
percent (in 2, 5,10, 15ml packs). It is also available as
ophthalmic gel in conc of 0.25 percent and 0.5 percent.
For initial therapy usual dosage is 1 drop of 0.25
percent ophthalmic solution to be instilled in the affected
eye twice a day. If clinical response is not adequate change
the dosage to 1drop of 0.5 percent solution twice a day.
If the IOP is maintained as satisfactory level, change the
dosage to 1 drop once a day. Timolol is also available as
hemi-hydrate in the conc of 0.25 percent and 0.5 percent
with the same dosage schedule.
Recently timolol (0.5%) is also available in unique gel
forming solution (GFS). It has unique mechanism of gel
formation and has been reported with 24-hour IOP
control with once-a-day therapy.
It is available as 0.5 percent gel forming solution in
2.5 and 5 ml packs (Instill one drop once daily preferably
at bed time). For GFS use invert the closed container and
shake once before each use. Administer other ophthalmic
drugs at least 10 minutes before the gel use. When
patients are switched from timolol solution twice daily
to the gel once daily, the ocular hypotensive effect should
remain constant.
Adverse reactions On topical use adverse effects
reported are ocular irritation, conjunctivitis, blepharitis,
keratitis, decreased corneal sensitivity, visual disturbances including refractive changes, diplopia and ptosis.
Systemic effects include bradycardia, arrhythmia, hypotension, syncope, heart block, cerebral ischemia,
congestive heart failure, palpitation, cardiac arrest,
bronchospasm, dyspnea, respiratory failure, headache,
dizziness, fatigue, lethargy, hallucinations, confusion,
hypersensitivity reactions, sexual dysfunctions, hypokalemia, cystoid macular edema, dry mouth and
behavioral changes.

Acetazolamide
(Diamox)

N N
||
|| O
C
C ||
CH3CNH
S
SN
||
||
O
O
CH3 N N
||
|| O
C
C ||
S
SN
CH3CN
||
||
O
O

Methazolamide
(Neptazane)

Cl
Dichlorphenamide
(Daranide)

Ethoxzolamide
(Cardrose)

Cl

C 2H 3O

H
H

H
H

O
||
H
SN
||
H
O
O
||
H
SN
||
H
O
S O
|
||
H
CSN
||
H
N
O

Fig. 38.15: Chemical structures of carbonic


anhydrase inhibitors

This action is independent of systemic acid-base


balance. By inhibiting the hydrogen ion secretion by the
renal tubule, these agents cause increased excretion of
sodium, potassium, bicarbonate and water, thus producing an alkaline diuresis.
Indications CAIs are used as additive therapy in the
management of various acute glaucomas, but also in
chronic management of primary and secondary open
angle and angle closure glaucomas not adequately
controlled on topical medication. Various agents of this
group used in ophthalmology are (Fig. 38.15):

CARBONIC ANHYDRASE INHIBITORS

Acetazolamide

Carbonic anhydrase inhibitors (CAIs) were first shown


to lower intraocular pressure in glaucoma in 1954. Since
then CAIs are commmonly prescribed by ophthalmologists in glaucoma cases as monotherapy or adjunctive
therapy with other antiglaucoma agents. But the clinical
utility of oral CAIs has been limited as a result of increase
in incidence of systemic side effects.
These agents are non-bacteriostatic sulphonamides
that non-competitively inhibit the enzyme carbonic anhydrase. This ciliary body enzyme (carbonic anhydrase) is
related to aqueous humor formation most likely via
active secretion of bicarbonate. CAIs decrease the rate
of aqueous humor formation resulting in decreased intraocular pressure.

Acetazolamide is one of the most commonly used


antiglaucoma agent worldwide. As already mentioned
its mechanism of action is by inhibiting enzyme carbonic
anhydrase resulting in decrease in intraocular pressure.
Indications As a monotherapy or adjunctive treatment
of chronic simple (open angle) glaucoma, secondary
glaucomas, preoperatively in intraocular surgery and in
acute angle closure glaucoma where delay in surgery is
desired to lower IOP.
Contraindications Hypersensitivity to these compound,
cross-sensitivity between antibacterial sulphonamides
and sulphonamide derivative diuretics. Patients with
significant respiratory disease should be given cautiously

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Chapter 38: Update on Antiglaucoma Therapy


because of metabolic and possible respiratory acidosis
effects (on systemic use).
Depressed sodium and potassium serum levels,
marked kidney and liver diseases or dysfunction,
adrenocortical insufficiency, etc.
Dosage and administration Acetazolamide is available
as 125 mg, 250 mg tablets and 500 mg capsules (sustained
release) sequels. It is also available as powder for IV injection 500 mg (as sodium) per vial. Recently it has been
commercially available as 5 percent topical ophthalmic
drops. Established dosages for near maximum effects are:
Oral acetazolamide tablets 250 mg 6 hourly (adults)
Dosage in excess of 1g daily does not usually increase
the effect. In children oral dose is 10-15 mg/kg/day
in divided doses every 6-8 hours.
Acetazolamide sustained release capsule dosage is
500 mg every 12 hourly.
Parenteral IV therapy may be used for rapid relief of
increased IOP. A complementary effect occurs when
acetazolamide is used with miotics. IV route is
preferred because IM administration is painful due
to alkaline pH of the solution.
For IV administration reconstitute each 500 mg vial
powder with atleast 5 ml of sterile water for injection.
Reconstituted solutions retain potency for a week if
refrigerated. However since their products contains no
preservative, preferably use within 24 hours of reconstitution.
If oral liquid dosage form may be required (specially
in children), acetazolamide tablet may be crushed and
suspended in honey or syrup.
Dosage of recently introduced 5 percent topical
acetazolamide ophthalmic drops (Actamid eyedrops) is
one drop to be instilled in the affected eye twice a day.
Topical acetazolamide drops have marked IOP reducing
effect with the advantage of least systemic adverse effects
as seen with systemic forms of acetazolamide. Topically
it can be used either alone or in combination of other
antiglaucoma agents.
Recently clinical data have shown that IOP lowering
effect of 5 percent acetazolamide eyedrops is certainly
better than oral acetazolamide (250 mg QID). The
significant difference in adverse experience, prevalence
and discontinuation rate between topical and oral
acetazolamide indicate that topical acetazolamide
therapy possesses significantly better tolerability and
excellent clinical IOP lowering response.
Adverse reactions On topical preparation use, least side
effects have been reported except for transient burning
and stinging sensation and ocular irritation. On systemic
use unfortunately 40-50 percent of glaucoma patients are
unable to tolerate CAIs for long-term because of various
disabling side effects.

365

A symptom complex of malaise, metallic taste,


fatigue, depression, anorexia and weight loss is the most
frequent side effect. Loss of libido specially in young
males may also occur. Other adverse effects reported are
anorexia, nausea, vomiting, hematuria, glycosuria,
urinary frequency renal colic, hepatic insufficiency,
nervousness, drowsiness, depression, confusion,
headache paresthesia of extremities, numbness, transient
myopia (reversible on drug discontinuation), urticaria,
pruritus, rashes and blood dyscrasias, etc.
Dichlorphenamide
This is another carbonic anhydrase inhibitor used in
glaucoma treatment. It is most effective when given with
miotics. In acute angle closure glaucoma dichlorphenamide may be used with miotics and osmotic agents to
repidly reduce intraocular pressure.
Dosage Dichlorphenamide is available as oral tablets
in strength of 50 mg.
The usual dosage is 100-200 mg initially followed by
100 mg every 12 hourly until the desired response is
obtained.
The maintenance dosage is 25-50 mg 1 to 3 times daily.
Adverse reactions are same as mentioned earlier in
acetazolamide section.
Methazolamide
Methazolamide is used in the treatment of various types
of acute and chronic glaucomas as an adjunctive
treatment with other antiglaucoma agents.
Dosage Methazolamide is available as 25 mg and 50
mg tablets. The standard dosage is 50-100 mg two to three
times a day until the desired response is obtained. It may
also be used with miotics and osmotic agents in acute
glaucoma cases.
Adverse reactions are similar to as reported with
acetazolamide.
Dorzolamide
Dorzolamide hydrochloride a carbonic anhydrase inhibitor specially formulated to allow topical ophthalmic
administration resulting in local inhibition of carbonic
anhydrase in the ciliary body effectively minimising
systemic side effects. The side effects frequently reported
with oral actazolamide have been least reported with
dorzolamide.
It is effective as a beta-blocker in initial or combined
therapy for open angle glaucoma.
Dorzolamide was first made commercially available
in topical form in 1995. Dorzolamide is a topical carbonic
anhydrase inhibitor whose hydrophilic properties are

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366 Section III: Glaucoma


such that it can penetrate the cornea and reach the ciliary
body in sufficient concentrations to suppress aqueous
production effectively.
Indications Topical dorzolamide is used as therapy in
the management of various acute primary and secondary
open angle and angle closure glaucomas.
It is used as monotherapy or in combination with
other antiglaucoma agents specially beta-blockers.
Dosage It is available commercially as
Topical 2 percent ophthalmic solution (in 5 ml pack).
A combination of topical dorzolamide hydrochloride
(2%) with timolol maleate (0.5%).
Usual dosage with 2 percent dorzolamide drops is to
instill one drop in the affected eye three times a day until
desired response is obtained. It decreases IOP by about
20 percent dosage for combination of topical dorzolamide (2%) and timolol maleate (0.5%) is to instill one
drop in the conjunctival sac in the affected eyes two times
a day. If another topical antiglaucoma agent is being used,
administer the two atleast ten minutes apart.
This combination of topical dorzolamide and timolol has been shown to decrease IOP by 43 percent more
than either timolol or dorzolamide alone.
Adverse reactions Topical dorzolamide therapy has
least side effects. Ocular adverse effects seen are ocular
burning and stinging sensation, ocular irritation. Taste
abnormalities although reported low with dorzolamide
as compare to acetazolamide are generally characterised
as a transient bitter taste occurring upon instillation while
metallic taste of longer duration is associated with
acetazolamide. However, dorzolamide possesses significantly better tolerability.
Carbonic anhydrase inhibitor and beta-adrenergic
blocking agent combination (Dorzolamide hydrochloride and timolol maleate):

glaucoma or ocular hypertension who are insufficiently


responsive to beta-blockers.
Contraindications Hypersensitivity to any of its component, H/O bronchial asthma, severe chronic obstructive
pulmonary disease, sinus bradycardia or overt cardiac
failure.
Dosage and administration It is available as topical
ophthalmic solution (containing 20 mg dorzolamide and
5 mg timolol per ml) in 5 and 10 ml dispenser with
controlled drop tip.
Precautions Although administered topically dorzolamide hydrochloride and timolol maleate is absorbed
systemically. Therefore, severe systemic reactions may
occur due to sulfonamide, dorzolamide. Besides it, severe
respiratory reactions and cardiac reactions including
death due to bronchospasm in patients with asthma have
been reported;
Patients with cardiac failure, obstructive pulmonary
disease, diabetes mellitus, myasthenia gravis, major
surgery or acid-base and electrolyte disturbances should
use this combination with great care and under strict
ophthalmologist supervision.
For pregnant, lactating mothers and children below
12 years, this combination use is generally not recommended.
Adverse reactions The most frequently reported
adverse effects are taste perversion (bitter, sour or
unusual taste). Ocular burning or stinging, conjunctival
hyperemia, blurred vision, superficial punctate keratitis
and itching. The systemic advers effects reported are
dizziness, headache, insomnia, behavioral changes,
vertigo, nervousness, abdominal pain, nausea, anorexia,
urinary tract infection, contact dermatitis, angioedema,
urticaria, hypersensitivity reactions, arthralgia, etc.

Pharmacokinetics Dorzolamide hydrochloride and


timolol maleate topical combination decreases elevated
IOP whether or not associated with glaucoma by
reducing aqueous humor secretion.
As we know that elevated IOP is a potential risk factor
in the pathology of optic nerve damage and glaucomatous visual field loss. Dorzolamide hydrochloride is
the inhibitor of human carbonic anhydrase II while
timolol maleate is non-selective (-1 and -2) adrenergic
receptor blocking agent that does not have significant
intrinsic sympathomimetic activity. The combined effect
of these two agents results in additional IOP reduction
as compare to either component administered alone.
Dorzolamide and timolol reach the systemic circulation
when applied topically.

Brinzolamide

Indications This combination is specially prescribed for


reduction of elevated IOP in patients with open angle

Dosage It is available as 1 percent ophthalmic suspension in 2.5, 5, 10 and 15 ml plastic bottles with controlled

It is recently introduced antiglaucoma drug of carbonic


anhydrase inhibitor group. It is reported to have significant IOP lowering effect and IOP reduction is equivalent
to 2 percent dorzolamide. But it is significantly more
comfortable than topical dorzolamide. It is safe and well
tolerated.
Indications It is indicated in the treatment of elevated
intraocular pressure in patients with open angle
glaucoma or ocular hypertension. It can be given as
monotherapy or as adjunctive therapy in combination
with other antiglaucoma drugs.
Contraindications It is contraindicated in patients who
are hypersensitive to any componant of this product.

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Chapter 38: Update on Antiglaucoma Therapy

367

dispensing tip. Recommended dosage is to instill one


drop in the affected eye three times a day, when it is used
concomitantly with topical antiglaucoma drugs than the
drugs should be administered 10 minutes apart.
Adverse reactions Ocular side effects reported are
blurred vision and bitter, sour or unusual taste, blepharitis, dermatitis, foreign body sensation, ocular discharge,
headache, hyperemia, ocular discomfort, pain, keratitis.
The other adverse effects although with very low
incidence are conjunctivitis, alopecia chest pain, diarrhea,
diplopia, dizziness, keratoconjunctivitis, keratopathy,
lid margin crusting or sticky sensation, tearing and
urticaria.
Precautions
Carbonic anhydrase activity has been observed in
both the cytoplasm and around the plasma membrane
of corneal endothelium.
Brinzolamide, is sulphonamide, although administered topically, it is absorbed systemically therefore
same type of adverse reactions attributable to suphonamide may occur with topical administration.
The concomitant administration of topical brinzolamide and systemic carbonic anhydrase inhibitors is
not recommended due to potential for an additive
effect on the known systemic effects of CAIs.

Fig. 38.16A: Latanoprost chemical structure (PGF2


analogue) [Courtesy: Pharmacia India (Pvt.) Limited]

Precautions Vision may be temporarily blurred following oral ethoxazolamide administration. Care should be
advised in operating machinery or driving a motor
vehicle.
Adverse reactions The most common adverse effects
reported with oral ethoxazolamide are blurred vision and
bitter, sour or unusual taste. Other symptoms include
dry eye, foreign body sensation, ocular discharge, pain
and ocular pruritus.
The systemic effects include dryness of mouth,
dyspepsia, diarrheas and dizziness.
PROSTAGLANDINS

ETHOXAZOLAMIDE
Ethoxazolamide is a sulfonamide which is carbonic
anhydrase inhibitor II and is administered orally.
Indications For the treatment of elevated IOP in patients
with ocular hypertension or open angle glaucoma.
Dosage and administration It is available in 125 mg
tablet form. The recommended dosage is 125 mg tablet
four times a day.

Latanoprost (Xalantan)
Latanoprost is recently introduced new third generation
antiglaucoma agent.
It is new phyenyl substituted prostaglandin analogue.
Chemically, it is 13,14, dihydro-17 phenyl-18, 19, 20
trinorprostaglandin F2-iso-propyl ester (Figs 38.16A to
C). Latanoprost is a prostanoid selective FP receptor

Fig. 38.16B: Latanoprost as a prodrug [Courtesy: Pharmacia India (P) Limited]

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368 Section III: Glaucoma

Fig. 38.16C: Latanoprost hypothesised mechanism of action [Courtesy: Pharmacia India (P) Limited]

Fig. 38.17: Mechanism of action of latanoprost (pre- and post-treatment increased uveoscleral outflow around the
obstructed trabecular meshwork) (Courtesy: Pharmacia and Upjohn India (Pvt) Ltd)

(Prostaglandin F2 receptor and PGF2 agonist) which


has an improved therapeutic index in the eye.
It is believed to significantly reduce intraocular
pressure through a unique outflow mechanism by
covering the outflow of aqueous humor. It can be used
as monotherapy or in combination with other
antiglaucoma agents.
Mechanism of action It has an interesting mode of
action. Latanoprost is believed to increase uveoscleral
outflow around the obstructed trabecular meshwork (a
unique mechanism of action proven effective as a stand
alone treatment or in conjunction with other glaucoma
therapies (Timolol maleate, pilocarpine, dipivefrin and
acetazolamide). In this uveoscleral outflow pathway, the

aqueous humor percolates through the ciliary muscle,


suprachoroidal space and the sclera instead of existing
the eye through the trabecular meshwork and schlemm
canal. Latanoprost has not been found to exert any
significant effect on aqueous humor production (Figs
38.17 to 38.19).
Latanoprost regulate uveosclearal outflow by MMP
(Matrix Metallo Proteinases) mediated alterations in
ciliary muscle ECM (Extracellular Matrix Metabolism).
Additional mechanisms include relaxation of the ciliary
muscle, compaction of the ECM and cytoskeletal
alterations. Exposure of ciliary smooth muscle cells to
latanoprost include expression of matrix metallo
proteinase-I (MMP-I) reflecting increased transcription
of the MMP-I gene. When the drug passes into the

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Chapter 38: Update on Antiglaucoma Therapy

Fig. 38.18: Latanoprost image gallery (mechanisms of action/uveoscleral outflow = G_082)


[Courtesy: Pharmacia and Upjohn India (Pvt) Ltd]

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369

370 Section III: Glaucoma


Indications It is indicated for reduction of elevated IOP
in patients with open angle glaucoma and ocular
hypertension who are intolerant to other antiglaucoma
drugs.
Contraindications Known hypersensitivity to latanoprost or any other ingradient in this product.

Fig. 38.19: Latanoprost image gallery (mechanisms of action/uveoscleral out-flow = G_082) [Courtesy: Pharmacia and
Upjohn India (Pvt) Ltd]

anterior chamber it interacts with the receptor and then


receptor complex interacts with nuclear genetic material
which leads to transcription of mRNA and the production
of proteins that ultimately cause the biosynthesis of
MMPs which alter the collagens within the uveoscleral
pathway. Gene transcription offers the potential of more
specific regulation of the uveoscleral outflow pathway.

Dosage It is available as 0.005 percent topical ophthalmic solution (in 2.5 ml pack) to be stored in refrigerator
at 2-8oC when unopened. Once opened it may be stored
at room temperature upto 25oC for 6 weeks. Usual dosage
is to instill one drop (15 g) in the affected eyes once
daily preferably in the evening.
The dosage of latanoprost should not be exceeded
once daily since it has been shown that more frequent
administration may decrease in IOP lowering effect.
Reduction of intraocular pressure starts approximately
3-4 hours after administration and maximum effect is
reached after 8-12 hours.
Latanoprost may be used concomitantly with other
antiglaucoma drugs to lower IOP. Such drugs should be
administered 5 minutes apart.
Recently topical latanoprost (0.005%) and timolol
(0.5%) combined ophthalmic solution (Xalacom) has been
launched commercially. The salient feature for this new
combination reported are that. It bolster treatment compliance, reduces the washout associated with the use of
sequential eyedrops and improve the better long-term
IOP control in patients (17-34%) who proved inadequately controlled on either loose or fixed dose multiple
drop regimes.
The salient features of latanoprost ophthalmic
solutions are as follows:
Once daily dosage increases the patient compliance.
IOP reduction ranging from 27-35 percent after 6
months.
No cardiopulmonary contraindications, hence does
not get in way of everyday living.
Diurnal intraocular pressure measurements at
baseline and after 6 and 12 months of treatment with
latanoprost have statistically significant clinical
impact.
Uniform diurnal and circadian IOP reduction with
once a day dosage.
Latanoprost has been shown to maintain significant
IOP reduction in over 12 months while no other
antiglaucoma agent has such sustained effect.
Had no statistically significant adverse effect on heart
rate, systolic or diastolic blood pressure and on
respiratory functions.
Proven effective as stand alone treatment.
Potential for different mechanisms of action when
used in conjunction with other topical glaucoma
therapies.

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Chapter 38: Update on Antiglaucoma Therapy

371

Fig. 38.20: Iris color change (6 months after treatment with topical latanoprost. Left hand side photographs (pretreated) and
right hand side photograph (post-treated). Note the change in color pattern of iris [Courtesy: Pharmacia and Upjohn India
(Pvt) Ltd]

Precautions should be taken and patients should


be informed in advance about.
Possibility of iris color changes as latanoprost may
gradually change eye color (iris color) increasing
the amount of brown pigment in the iris by
increasing the number of melanosomes (pigment

granules). The change occurs slowly for several


months to years and resultant color change may
be permanent. Iris pigmentation changes may be
more noticeable in patients with green brown/
blue-gray-brown or yellow brown irides (Fig.
38.20).

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372 Section III: Glaucoma


Adverse reactions The ocular adverse events reported
on long-term use are blurred vision, burning and stinging
sensation, conjunctival hyperemia, itching, increased iris
pigmentation and punctate epithelial keratopathy.
Less than 1 percent of patients treated with latanoprost require discontinuation of therapy due to conjunctival hyperemia.
Other ocular side effects reported are excessive
tearing, eye pain, lid crusting, lid edema, lid erythema,
diplopia and photophobia. The most common systemic
adverse effects seen are upper respiratory tract infection,
cold, flu, pain in the muscles, joint, back, chest pain,
angina pectoris, rashes and allergic reaction. However,
the incidence of adverse effects is very low.

Fig. 38.21A: Chemical structure of bimatoprost


(Courtesy: Allergan India Ltd)

Overdosage Apart from ocular irritation, conjunctival


and episcleral hyperemia the ocular effects of latanoprost
administered at high doses are not known.
Bimatoprost (Lumigan)
Bimatoprost is pharmacologically unique compound of
prostaglandin group which appears to mimic the
prostamides. Prostamides are the newest members of the
fatty acid amide family which are potent ocular
hypotensive agents (Figs 38.21A and B).
Bimatoprost has been reported not only highly
efficacious but also long acting drug. It represents a new
generation of IOP lowering drugs.
Pharmacokinetics Bimatoprost is pharmacologically
unique according to functional and binding studies at
recombinant and natural receptors. Bimatoprost does not
require conversion to an active metabolites to exert potent
pharmacological activity. It is also stable in solution and
does not undergo facile hydrolytic conversioin.
Chemically bimatoprost is related to prostamide-F a
newly discovered, naturally occurring substance that is
biosythesized from anandamide in a pathway that
includes the enzyme cyclooxygenase-2 (COX-2).
Mechanism of action Bimatoprost mildly stimulates the
aqueous humor flow both during day and night.
Enhancement of uveoscleral outflow the primary
mechanism of action of latanoprost is partly responsible
for the ocular hypotensive effect of bimatoprost.
However, its primary ocular hypotensive action is due
to reduction in tonographic resistance to outflow. Thus
bimatoprost enhances the pressure sensitive outflow
pathway. Additional IOP lowering effect may include
increase in the rate of flow via the pressure-insensitive

Fig. 38.21B: Diagrammatic prostamide biosynthetic pathway


in the anterior ocular segment and its effect on IOP (Courtesy:
Allergan India Ltd)

outflow pathway and a lowering of the extra ocular


recipient pressue (Episcleral venous pressure).
Reduction of tonographic resistance to aqueous
humor outflow reduces steady state IOP an effect that is
beneficial for the treatment of glaucoma.
In addition reduction of resistance allows the eye to
recover more quickly from transient IOP elevations.
Indications To lower intraocular pressure in patients
with open angle glaucoma and ocular hypertension

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Chapter 38: Update on Antiglaucoma Therapy


who are intolerant of other IOP lowering medications or
who inadequately responded to other IOP lowering
drugs.
Contraindications Hypersensitive to prostamides or any
other ingradient in the product
Dosage and administrations Bimatoprost is available
as 0.03 percent topical ophthalmic solution in 3 ml plastic
dispenser bottle with controlled dropper tip. Recommended dosage is to instill one drop in the affect eye once a
day preferable at bed time.
Adverse reactions Adverse effects include iris pigmentation (Bimatoprost may gradually change eye color by
increasing the amount of brown pigmentation of the iris
due to increase in pigment granules in melanocytes),
Conjunctival hyperemia, hypertrichosis, burning and
stinging sensation, ocular pruritus, ocular pain, eyelid
edema and foreign body sensation. Systemic side effects
include nausea, abdominal pain, dizziness, sinusitis, etc.
Precautions Before starting the treatment with bimatoprost patients should be told about eye color changes on
prolong use.
In pregnant, lactating mother and children bimatoprost is generally not recommended.
Unoprostone (Rescula)
It is recently launched PGF2 analogue of prostaglandin
group unoprostone isopropylate is the first docosanoid
derivative for glaucoma treatment. This compound was
first developed in Japan for use in open angle glaucoma
or ocular hypertension. Soon it became commercially
available.
Like latanoprost unoprostone lower intraocular
pressure by increasing uveoscleral outflow and without
affecting aqueous humor production. Unoprostone a
docosanoid derivative therapy is a new glaucoma drug
which enhances blood supply to the delicate sensory
tissues at the back of the eye.
Indications Unoprostone is indicated for the treatment
of primary open angle glaucoma or ocular hypertension not responding adequately to other IOP lower
medications.
Dosage and administration Unoprostone is available as
0.15 percent topical ophthalmic solution in 5 ml plastic
bottle. Recommended dosage is to instill one drop in
the affected eye twice a day. It can be given continuously
for a long period and it maintains lower intraocular
pressure even over a longer period of 12 months.
Recently unoprostone (0.15%) is also available with
timolol (0.5%) as topical ophthalmic solution (Combination therapy).

373

Recommended dosage with this topical solution is to


instill one drop in the affected eye twice a day. Due to
synergistic effect and better compliance this solution has
been shown to lower intraocular pressure in a effective
way.
Adverse reactions Ocular adverse effects include iris
pigmentation (Eye color changes), conjunctival hyperemia, ocular irritation, burning and stinging sensation
and ocular pruritus.
Travoprost (Travatan)
It is also recently launched antiglaucoma drug of
prostaglandin group. It has highly selective affinity for
FP receptors and is equally effective to latanoprost and
bimatoprost in lowering intraocular pressure in cases of
primary open angle glaucoma or ocular hypertension.
Commercially it is available as 0.004 percent topical
ophthalmic solution in 5 ml plastic bottle.
Recommended dosage is to instill one drop in the
affected eye once or twice a day.
Adverse reactions Ocular adverse effects reported are
ocular hyperemia, iris pigmentation, decreased visual
acuity, eye discomfort, foreign body sensation, ocular
pain and ocular pruritus.
Hyperosmotic Agents
Systemic hyperosmotic agents glycerin, isosorbide and
mannitol are used in immediate control of intraocular
pressure in acute glaucoma cases.
Mechanism of action These agents lower intraocular
pressure by increasing plasma tonicity sufficiently to
draw water out of the eye.
Indications Used as adjunctive therapy for rapid
lowering of IOP in acute attacks of glaucoma or prior to
ocular surgery when preoperative reduction of IOP is
indicated. Onset of action is 30 minutes and last for 4-6
hours.
Contraindications Well established anuria, severe
dehydration, acute pulmonary edema, severe cardiac
decompensation.
Preparations and dosage
1. Glycerin: It is available as 50 percent and 75 percent
lime flavored oral solution (in 120 and 220 ml pack).
Standards dosage is 1.0 1.5 g/kg body weight given
1-1.5 hours before surgery. In other indications of
glaucomas except surgery usual dosage is 2-3 ml/kg
(4-6 ounces/patient). It is better tolerated and may
be given three-four times a day.

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374 Section III: Glaucoma


Topical glycerin is a viscous solution listed to clear
corneal edema for a better view of intraocular
structures.
2. Isosorbide: It is available as 45 percent mint flavored
solution (in 220 ml pack) with dosage of 1-2 g/kg
(1.5-3.0 ml/pound body weight) given 2-4 times a day.
3. Mannitol: It is available as 5-25 percent hyperosmotic
agent (in 50, 100, 150, 500 and 1000 ml packs). Standard adult dosage is 0.5-2.0 g/kg body weight given
as usual 15-20 percent solution over a period as short
as 30 minutes. Most common is 25-100 ml of mannitol
solution be given by slow IV push. When used preoperatively administer it 1-1 hours before surgery
to achieve maximal effect. Mannitol solution when
exposed to low temperature may crystalize. Concentrations greater than 15 percent have a tendency to
crystalize. If crystals are observed, warm the bottle
in hot water or autoclave then cool it to body temperature before administrating.
Adverse reactions It may include severe systemic
hypertension aggravation, nausea, vomiting, marked
diuresis, urinary retention.
Confusion congestive heart failure, fluid and electrolyte imbalance, acidosis, drymouth, chills urticaria, fever,
pulmonary edema, diabetic hyperglycemia. These drugs
are contraindicated in oliguria or anuria.
CALCIUM CHANNEL BLOCKERS
Calcium channel blockers such as diltiazem, nifedipine
and verapamil which inhibit calcium influx in vascular
smooth muscle, decrease vascular tone and increase
blood flow.
Recent studies indicate that these oral calcium
channel blockers are useful in low tension glaucoma by
increasing optic nerve blood flow.

ing the production of thymin. It is toxic drug and should


be used carefully.
Indication and dosage It is used as adjuvant in glaucoma filtering surgery (Intraoperative and postoperatively) to control IOP.
It can be used in glaucoma filtering surgery in juvenile
open angle glaucoma, aphakic glaucoma, neovascular
glaucoma, failed glaucoma surgery, buphthalmos, ICE
syndrome, steroid induced glaucoma and chronic angle
closure glaucoma.
Intraoperative use 5 FU is increasingly used as a single
intraoperative application. A 3 2 mm piece of cellulose
sponge soaked with 50 mg/ml 5 FU is placed under the
conjunctival flap for the duration of 60 seconds taking
care to avoid the cut edge of conjunctiva. The sponge is
than removed and the area is irrigated with 5-10 ml of
Ringer lactate solution (Figs 38.22 and 38.23).
5 FU can also be given by subconjunctival route
during filtering surgery. A freshly prepared 0.5 cc of
solution containing 5 mgm of 5 FU (prepared from
commercially available 50 mg/ml to 10 mgm/ml in
physiological saline) is injected subconjunctivally with
27G needle 180 o away from the filtering site. On
subsequent postoperative days (day +1) 5 mg of 5 FU
injection is given subconjunctivally administered 90-180o
degree away from the bleb over a 2-week period. It
should not be given if corneal grafting was also done.
Clinical datas have shown that intra- operative 5 FU is
as effective as postoperative injections in glaucoma
filtering surgery. The results of surgery indicate that 5
FU is safe and effective adjuvant in glaucoma filtering

ANTIMETABOLITES
(ANTI-FIBROPROLIFERATIVE AGENTS)
Today there is increased frequency of use of adjunctive
mitomycin or 5-fluorouracil (5FU) both cidal to fibroblasts and usually yields intraocular pressure lower than
trabeculectomy alone and comparable to full thickness
procedures.
5-Fluorouracil (5FU)
It is a fluorinated analogue of pyrimidine. It has been
shown to block mitosis or retinal pigment epithelial cells
and more significantly fibroblasts. This drug acts by
binding the enzyme thymidilate synthetase thus prevent-

Fig. 38.22: The conjunctiva is then reposed on to the sponge.


It is left for five minutes after which the area is rinsed with
BSS

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Chapter 38: Update on Antiglaucoma Therapy

375

Daunorubicin
Intraoperative daunorubicin has been found more
effective and less toxic than 5 FU and mitomycin C. It is
obtained from Streptomyces coeruleorubidus and is also
cytotoxic.

Fig. 38.23: Application of sponge soaked 5-fluorouracil to


sclera before the scleral flap is cut

surgery in controlling IOP. Limbal based flap is preferable


to fornix based flap with the use of 5 FU in glaucoma
filtering surgery.
Mitomycin C
Mitomycin C is anti-fibroproliferative agent. It is
obtained from Streptomyces caespitosus and has cytotoxic
properties similar to those of polyfunctional alkylating
agents.
Indications It is usually applied once at the time of
surgery (intraoperatively). A 3 2 mm cellular sponge
moistened with a 0.2-0.4 mg/ml (0.02-0.04%) mitomycin C is applied to the bed of trabeculectomy flap for
4-5 minutes followed by profuse saline irrigation.
Mitomycin C is specially useful for glaucoma filtering
surgery in children, because subconjunctival 5 FU
therapy in children requires use of multiple general
anesthesia and thereby not a suitable option in children
with congenital glaucoma.
Similarly for encapsulated filtering bleb revision
mitomycin C is quite effective patients undergoing
surgery for encapsulated. Filtering bleb revision receive
intraoperative mitomycin C. Mitomycin C has marked
IOP lowering effect and decreased dependance on postoperative antiglaucoma medications and decreased
corneal toxicity.

Indication It is used as an adjuvant treatment in glaucoma filtering surgery on any type of glaucoma.
Intraoperatively it is given on 4 4 mm cellulose
sponge soaked in daunorubicin (0.2mg/ml) 0.25 ml is
applied below the conjunctival flap over the proposed
site for trabeculectomy for 3 minutes.
After that cellulose sponge is removed and ocular
tissue is gently rinsed with 10 ml Ringer lactate solution.
With intraoperative use of daunorubicin there was
appreciable control of IOP after glaucoma filtering
surgery and there was no localised thin or a vascular
bleb reported (postoperatively).
Other antimetabolites being tested clinically for intraoperative use during glaucoma filtering surgery are:
Doxorubicin
Bleomycin
Mithramycin
Adverse side effects Adverse side effects of 5 FU, mitomycin C and daunorubicin are frequent at full doses and
lesser at lower doses.
Ocular adverse effects reported with the use of these
antimetabolies are leaks, epithelial defects, corneal haze,
conjunctival congestion and discomfort. A therapeutic
contact lens will decrease 5 FU induced discomfort but
the more serious side effects indicate treatment with
antimetabolites be stopped immediately.
RECENT ADVANCES IN GLAUCOMA THERAPY
Continuous and extensive research is going on for a
typical antiglaucoma drug that can normalise elevated
IOP, has long-term efficacy, does not produce serious
systemic and ocular side effects or long-term sequelae
after discontinuing the drug therapy to enhance
compliance and it should be simple for the patient to
administer preferably with once daily dosage.
Lot of clinical work being done to produce an ideal
drug which can prevent optic nerve damage and further
loss of vision or can reverse the disease process by repairing the optic nerve and restoring lost vision. The efficacy
of future compound must be balanced against its safety
profile when used as mono or adjunctive therapy. New
antiglaucoma agents which have been launched
commercially or to be launched in very near future are:

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376 Section III: Glaucoma


a. Unoprostone (Prostaglandin (PGF2 analogue)
b. Ocular hypotensive lipids
c Neuroprotective agents.

angle glaucoma and will be important alternative for


managing the IOP component in a vision sparing
therapeutic paradigm.

Unoprostone

Neuroprotective Agents

It is recently launched PGF2 analogue. Unoprostone


isopropylate is the first docosanoid derivative for
glaucoma treatment. This compound was first developed
in Japan for use in open angle glaucoma or ocular
hypertension. It became commercially available in 1994.
Like latanoprost, unoprostone lowers intraocular
pressure by increasing uveoscleral outflow and without
affecting aqueous humor production. Unoprostone a
docosanoid derivative therapy is a new glaucoma
treatment which enhances blood supply to the delicate
sensory tissues at the back of the eye.

This is an exciting line of research for the treatment of


glaucoma. Unravelling the mechanism of neuroprotective action and retinal ganglion cell apoptosis may also
open new therapeutic avenues for treatment of glaucoma.
As we know that elevated intraocular pressure is
indisputably a key factor in glaucoma, an emerging
concept suggests that other factors specially retinal
ganglion cell death which also underlie this optic nerve
disorder.
A growing evidence points to the potential for
neuroprotection of the optic nerve and indicates that
therapeutic strategies may be most successful if they aim
at vision sparing through the promotion of cell survival.
Retinal ganglion cell death is initiated when
pathological events like ischemia, axonal injury, changes
in lamina cribrosa blocks the transport of growth factors
from the brain to retinal ganglion cells. The blockage of
these neurotrophins initiates a damaging cascade and
the cell is unable to maintain its normal furnctions. When
retinal ganglion cells undergo apoptosis and release
oxygen-free radicals, gene expression changes unfavorably, mitochondria alter, and excitatory toxins are
released during optic nerve injury.
Apoptosis is a two-hit mechanism. Apoptosis cells
are triggered by a stimulus to activate the death gene
and a second stimulus produces the chain of events.
Triggered cells respond to the noxious insult more easily
than untriggered cells. The potential exists for cell rescue
and therefore for therapeutic protection of the optic nerve
and ganglion cell fibres but it may involve more than
lowering of IOP. Lowering of IOP in patients with high
pressure and no physical findings will likely protect
against visual field loss but in patients who have already
suffered visual loss, the effect of pressure lowering is
unclear. Reverse of cupping may occur but not much
improvement in vision. Latest research work show that
lowering of IOP is not the answer. There is role of
molecular and cellular biology level involvement.
There has been tremendous advances in the treatment
of acute and chronic neural damage and glaucoma
involves a chronic optic neuropathy. High IOP is primary
factor for injury leading to retinal ganglion cell death
but additional factors may sensitize or kill retinal
ganglion cells beyond this initial injury. This cell death
pathway can constitute a focus for neuroprotection. The
aim is to increase the resistance of the neurons to stresses
that might trigger apoptosis and influences the signalling
pathway towards cell survival rather than cell death.

Dosage It is available as topical ophthalmic solution


in the strength of 0.12 percent. Usual dosage is to instill
one drop in the affected eye twice a day. It can be given
continuously for a long period and it maintains lower
intraocular pressures over a long period of 12 months.
Unoprostone 0.12 percent has IOP lowering effect similar
to timolol with few ocular or systemic side effects.
Ocular Hypotensive Lipids (OHL)
Two new antiglaucoma agents belonging to class of
compounds termed ocular hypotensive lipids (OHL) are
on clinical trials (AGN191129, AGN192024). These
compounds contain a neutral substituent for the carboxylic acid group of PGF2 and are not fatty acids. These
are relatively metabolically stable unlike the prodrug
latanoprost and esterified PGF2 analogue that is readily
metabolised into active PGF2. As these compounds do
not significantly interact with the FP or other known
prostanoid receptors.
These compounds have different pharmacological
profiles yet are potent ocular hypotensive agents. Clinical
trials were conducted on these OHL in cases of open
angle glaucoma and ocular hypertension cases. Twice
daily dosing at concentration of 0.01 percent produced
significant IOP lowering (26% decrease from baseline and
is certainly superior to that of timolol (0.5% BD).
These new OHL compounds continue to produce a
significant IOP lowering effect upto 24 hours after the
last drug instillation. These compounds are well tolerated
and have a very favorable ocular and systemic safety
profile with no patients drop out due to adverse events.
These OHL compounds have novel receptor selectivity
and unique pharmacology and they shall provide an
excellent alternative IOP lowering agent for the first line
and second line therapy of ocular hypertension and open

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Chapter 38: Update on Antiglaucoma Therapy


Drugs which can affects this cell death pathway
through differing mechanisms and provide effective
neuroprotection are:
1. alpha-2 agonists.
2. N-methyl-D-aspartate (NMDA) antagonists
3. NMDA channel blockers
4. Calcium channel blockers
5. Glutamate antagonists
6. Nitric oxide inhibitors
7. Neurotrophic factors
8. Free radical scavengers
9. Naftidrofuryl
Alpha-2 Agonists
Selective alpha-2 agonist already commercially available
for the treatment of glaucoma is brimonidine tartrate
(Alphagan). It binds to cell receptors and signal cells to
carry out neuroprotective functions. It has been shown
that brimonidine preserves retinal ganglion cell survival
and photo-receptor functionality.
Brimonidine is a good candidate because it does
decrease the IOP and activates alpha-2 pathways that
enhance neuronal survival. Brimonidine mechanisms of
action for providing neuroprotection is to be
upregulation of the expression of the antiapoptotic genes
bcl-2 and bcl-xl while having no impact on the expression
of the pro-apoptotic bax gene. This tilts the balance
toward the survival of the neuron even after ischemic
insult.
Research studies have shown that brimonidine rescue
photoreceptors from degeneration after light damage and
upregulated basic fibroblast growth factor (bfGF) in the
retina which promotes neuronal survival. The more the
expression of bfGF, the more likely the survival of the
neuron. The topical application of brimonidine 0.5
percent-1.0 percent conc BID for 15 days raise the expression of bfGF 3-4 folds. This show that topical application
of brimonidine can deliver enough drug to the back of
the eye to give neuroprotection.

377

Research studies have also shown the elevated glutamate


levels with in vitreous body of glaucoma patients. These
observations led to the investigation of compounds that
may block this potential neuropathological componant
of glaucoma.
Of these compounds, memantine a non-compettive
NMDA receptor antagonists derived from amantadine
with proven neuroprotective properties shows
considerable promise for neuroprotective efficacy in
glaucoma. Memantines non-competitive interaction
with the NMDA receptor results in blockade of toxic
effects of glutamate without significant effects on normal
cellular function. This is based on the finding that
memantine only binds to the NMDA channel when open.
In addition memantines rapid kinetics of blocking and
unblocking the open channel may allow for near normal
levels of NMDA receptor function in areas of low
glutamate and provides effective blockade in the face of
pathologically high concentration of glutamate. This is
in contrast to non-competitive NMDA antagonists that
bind in both the open and closed states and may block
NMDA receptor function altogether.
Clinical studies have shown that memantine provide
protection of retinal ganglin cells from glutamate induced
neurotoxicity and from acute retinal ischemic/reperfusion injuries.
Memantine is just entering into commercial development (Allergan) for neuroprotection in glaucoma, the
clinical profile shows great promise for memantine as
an effective agent for the prevention of glaucomatous
optic neuropathological progression even in those
patients who had IOP controlled with conventional
therapy or in glaucomatous patients who do not overty
present an IOP componant (Normotensive or low tension
glaucoma) in their disease.
In addition to memantine, a number of other potential
non-IOP lowering direct acting neuroprotective agents
are shown to have an application is glaucoma. Many of
these agents focus on other routes of overcoming
glutamate cytotoxicity.
Compounds on clinical trails are:

NMDA Antagonists
The N-methyl D-aspartate (NMDA) antagonists memantine provides neuroprotection by blocking pathological
increases in glutamate which drives cell death by
facilitating calcium entry into the cell.
It is direct acting non-IOP lowering neuroprotective
agent.
As we know that glutamate is an important neurotransmitter in the retina. Under pathological conditions
elevated glutamate is linked to neuronal cell death.

Eliprodil
It is a non-competitive NMDA antagonist, provide
protection from glutamate medicated cytotoxicity to
retinal ganglion cells.
Riluzole
It is presynaptic glutamate release inhibitor which has
been shown to have potential neuroprotective utility.

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378 Section III: Glaucoma


L-deprenyl
It is monoamine oxidase -inhibitor which provide
neuro- protection to RGCs from retinal injury with
promising results. L-deprenyl inhibit apoptosis of serum
deprived retrovirusimmortalised retinal ganglion cells
in vivo and decrease the apoptosis index of primary mix
retinal cells when deprived of specific neurotrophic
factors. Extensive clinical trials are going on the efficacy
of these compounds in a neuroprotective paradigm for
glaucoma management.
Other useful compounds to battle against progressive
glaucomatous optic neuropathy may evolve from
extensive research work being conducted on the mechanisms of secondary neuronal damage.
Nitrous oxide inhibitors, antioxidants, free radical
scavangers and other agent mentioned in general
monograph of neuroprotective agents that potentially
inhibit secondary retinal ganglion damage elicited by
release of noxious compounds from dying cells may
prove useful.
Nitrous oxide synthase inhibitors have shown neuroprotective potential. Similarly antioxidants and free
radical scavengers superoxide dismutase, catalase and
vitamin E have been found to have potential neuroprotective utility. Research studies have shown that
essential factors promote retinal ganglion cell survival
and resistance to damage may explore new angle of
neuroprotective agents. Growth factors such as bfGF,
brain derived neurotrophic factors (BDNF) and neurotrophin-4 have the ability to promote retinal ganglion
cell survival.
Through molecular genetic technology, we shall be
able in near future to directly modulate the expression
of genes such as bcl-2 which plays a major role in
controlling the intracellular apoptotic program. Further
caspase inhibitors may also prove useful in the
preservation of retinal ganglion cells.
FUTURE DIRECTIONS
A new futuristic glaucoma therapeutic management
paradigm whereby clinical success is no longer simply
measured by achieved level of intraocular pressure
control but also by the long-term preservation of visual
function and patient quality of life is expected to dramatically improve upon current treatment alorithms for
ocular hypertension and glaucoma.
To meet this new challenge, a therapeutic cocktail
approach with new and available antiglaucoma agents
will be most likely choice. Ideal drug candidates for this
new combination therapy will offer better IOP lowering

efficacy with fewer side effects and to provide additional


means of vision sparing through direct protection of optic
nerve of the currently available antiglaucoma drugs.
Latanoprost represents a promising approach to IOP
lowering while brimonidine is candidate for both ocular
hypotensive efficacy and the potential for enhancing
retinal ganglion cell survival. In addition RGC death
elicited by the high levels of glutamate may be overcome
by memantine or other compounds that effectively block
this common secondary neuropathological pathway.
Ideally neuroprotection in glaucoma shall be achieved
by combining agents that effectively reduce IOP and
directly protect the optic nerve through the promotion
of cellular survival or inhibition of cell death signals.
The relationship of ocular hemodynamics with the
glaucomatous optic neuropathological progression is
under investigation. While direct protection of optic
nerve seems to offer the certain hope for preventing
disease progression regardless of etiology, new clinical
information shall reveal and role for agents with positive
hemodynamics effects in optimising the therapeutic
regime.
While monotherapy with effective, ocular hypotensive agents may be sufficient for the preservation of visual
function is most of patients, a therapeutic cocktail
approach suited to each individual to preserve visual
function with available medicines will most likely
represent the new paradigm for glaucoma management
in 21st century.
A new drug combinations that employ agents which
complement each other through district mechanism of
action shall be of future choice.
New and more sensitive procedures that are able to
detect ganglion cell damage in humans before visual field
defects occur are developed and we shall be able to
expedite evaluation of the neuroprotective efficacy of
available and new drugs and new drug combinations in
development.
Research into the basic pathophysiological mechanisms of glaucomatous optic neuropathy will eventually
open new therapeutic pathways. Better understanding
of the underlying genetic basis of heritable forms of
glaucoma should provide new diagnostic tools and
potential for new therapeutic avenues.
There are reports of an autoimmune component in
certain types of glaucoma. Our understanding of these
complex immune disorders improves and we may be able
to tailor therapies to address this potential confounding
issue. Promising new focus on vision sparing, greater
patient safety and tolerability will provide improved
treatment options and long-term preservation of vision
and quality of life.

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Chapter 38: Update on Antiglaucoma Therapy


THE ROLE OF NEUROREGENERATION
Death of retinal ganglion cells as already mentioned is
the final common pathway not only of glaucomatous
optic neuropathy but all optic neuropathies.
A broad range of new drugs are being clinically tried
for the possible future use to prevent retinal ganglion
cell death in glaucoma. The aims include preventing the
initiation of the apoptosis program, protection of
undamaged but at risk axons and ganglion cells, rescue
of marginally damaged axons and ganglion cells.
A great deal of research is being directed toward
applying new molecular and cellular techniques to
induced regeneration of mammalian central nervous
axons. This shall be an important step in therapy for
glaucomatous optic nerve atrophy (which can lead to
least partial recovery of optic nerve function following
atrophy from the glaucoma).
Synthesis of cytokines and growth factors for reactive
astrocytes and altered expression of cell surface adhesion
molecules including neural cell adhesion molecule (NCAM) hold promise.
The search for pharmacological neuroprotectant and
neuroregenerative agents for the treatment of glaucoma
promises to be most exciting pathways for the future
treatment of glaucoma.
FURTHER READING
1. AAO, Clinical Science Course on Glaucoma, 2000.
2. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.
3. Bartlett. JD, Clinical Ocular Pharmacology, ed.4, Boston:
Butterworth-Heinemann,2001
4. Bartlett. JD, Ophthalmic Drug Facts, Lippincott William and
Wilkins, 2001.
5. Becker - Shaffers, Diagnosis and Therapy of Glaucoma, ed. 7:
C.V. Mosby, 1999.
6. Bucci, Glaucoma: Springer-Verlag, 1996.
7. Chandler and Grant, Glaucoma, ed. 4: Lippincott William and
Wilkins, 1997.

379

8. Crick. RP, Trimble RB, Textbook of Clinical Ophthalmology:


Hodder and Stoughton, 1986.
9. Dreyer, Neuroprotection in Glaucoma: AAO, 2000.
10. Duane. TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
11. Duvall, Ophthalmic Medications and Pharmacology, Slack Inc,
1998.
12. Ellis. PP, Ocular Therapeutics and Pharmacology, ed. 7: C.V.
Mosby, 1985.
13. Fechner, Ocular Therapeutics: Slack Inc., 1998.
14. Fraunfelder, Current Ocular Therapy, ed. 5: W.B. Saunders, 2000.
15. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
16. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
17. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
18. Goodman. LS, Gilman. A, Pharmacological Basis of Therapeutics, ed.7, New York: Macmillan, 1985.
19. Gross, Clinical Glaucoma Management, Lippincott William
and Wilkins, 2001.
20. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.
21. Higginbotham, Clinical Guide to Glaucoma Management:
Butterworth Heinemann, 1996.
22. Kanski, Clinical Ophthalmology, ed. 4: ButterworthHeineman,
1999.
23. Kanski, Glaucoma: Butterworth Heinemann, 1996.
24. Kershner, Ophthalmic Medications and Pharmacology, Slack.
Inc., 1994.
25. Krieglstein, Glaucoma Update VI: Springer Verlag, 2000.
26. Olin BR et.al., Drugs Facts and Comparisons: Facts and
Comparisons, St. Louis, 1997.
27. Onofrey, The Ocular Therapeutics; Lippincott-William and
Wilkins, 1997.
28. Rhee, The Wills Eyedrug Guide, Lippincott William and
Wilkins, 1998.
29. Shields, Textbook of Glaucoma, ed. 4, Lippincott William and
Wilkins, 1997.
30. Shields, Color Atlas of Glaucoma, Lippincott William and
Wilkins, 1997.
31. Speath, The Glaucoma: Lippincott William and Wilkins, 1999.
32. Steven Podos, Textbook of Ophthalmology, New Delhi: Jaypee
Brothers Medical Publishers, 2001.
33. Zimmerman, Textbook of Ocular Pharmacology, Lippincott and
William and Wilkins, 1997.

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380 Section III: Glaucoma

39

Triple ProcedureTrabeculectomy
with Phaco and IOL Implantation
Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Anand A Bagmar, R Rajalakshmi

INTRODUCTION
TWO-STEP SURGICAL
TECHNIQUE
PREPARATION OF
THE SCLERAL FLAP
PHACO
COMPLETING THE
TRABECULECTOMY
POSTOPERATIVE CARE
DISCUSSION

INTRODUCTION
Trabeculectomy has been done as a surgical option to control intraocular
pressure (IOP) in patients with uncontrolled primary open-angle glaucoma
(POAG). In many elderly patients, treatment of coexisting cataract during
a trabeculectomy assumes importance. Reports indicate that combined
trabeculectomy and cataract surgery is effective in treating such cases.1
We discuss in this chapter the technique of combined trabeculectomy
and phacoemulsification with an intraocular lens (IOL) implantation for
patients with POAG and coexistent visually significant cataract.
The patients are tried on maximum medications, and trabeculectomy
is offered as an option only when the IOP does not get controlled with
maximum medications. Trabeculectomy combined with phacoemulsification and IOL implantation is advised if an associated cataract was visually
significant.
TWO-STEP SURGICAL TECHNIQUE
All patients are operated under peribulbar anesthesia. A two-site procedure
is performed rather than a single site technique.
PREPARATION OF THE SCLERAL FLAP
Trabeculectomy was always done at the 12 o clock position. First of all a
superior rectus bridle suture is fixed so that good exposure is present
superiorly (Fig. 39.1). A fornix-based superior conjunctival flap is then
created. Wet field bipolar cautery is applied when necessary (Fig. 39.2). A
quadrilateral partial thickness 5 4 mm scleral flap is then taken. The
flap is dissected anteriorly upto the sclerocorneal junction using the same
scleral tunnel knife that one would use to create a scleral tunnel for phaco
(Figs 39.3 and 39.4). Once the flap has been created, the flap is lifted up
with a forceps to see that it is complete (Fig. 39.5).
PHACO
The anterior chamber is then entered with a 26-gauge needle and
viscoelastic substance injected (Fig. 39.6). This incision is made temporally.
The needle with viscoelastic is injected inside the eye in the area where
the second site is made. This will distend the eye so that when you make
a clear corneal incision, the eye will be tense and one can create a good

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Chapter 39: Triple ProcedureTrabeculectomy with Phaco and IOL Implantation 381

Fig. 39.1: Eye with cataract and glaucoma. Superior rectus


secured to give good exposure superiorly

Fig. 39.4: 5 by 4 mm scleral flap being made with a scleral


dissector upto the corneoscleral junction

Fig. 39.2: Fornix based conjunctival flap made. Wet field


cautery being done

Fig. 39.5: Scleral flap lifted

Fig. 39.3: 5 by 4 mm scleral flap being made


with a scleral dissector

Fig. 39.6: 26 gauge needle with viscoelastic injecting viscoelastic inside the eye. Note the trabeculectomy flap is
superior and this incision is temporal

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382 Section III: Glaucoma

Fig. 39.7: Clear corneal incision. Note the straight road inside the eye in the left hand. The right hand is performing the
clear corneal incision. This is a temporal incision and the
surgeon is sitting temporally

valve. Now use a straight rod to stabilize the eye with


the left hand (Fig. 39.7). With the right hand make the
clear corneal incision. A temporal 2.8-mm clear corneal
incision is made with a diamond knife.
When we started making temporal incisions, we
positioned ourselves temporally. The problem by this
method is that, every time the microscope has to be
turned which in turn would affect the cables connected
to the video camera. Further the theater staff would get
disturbed between right eye and left eye. To solve this
problem, we then decided on a different strategy. We
have operating trolleys on wheels. The patient is wheeled
inside the operation theater and for the right eye the
trolley is placed slightly obliquely so that the surgeon
does not change his or her position. The surgeon stays
at the 12 oclock position. For the left eye the trolley with
the patient is rotated horizontally so that the temporal
portion of the left eye comes at 12 oclock. This way the
patient is moved and not the surgeon.
Capsulorhexis with a bent 26-gauge needle under
viscoelastics is then done (Fig. 39.8). Hydrodissection is
subsequently done. Phacoemulsification is then started
using the karate chop technique (Fig. 39.9). The nucleus
is first chopped (Figs 39.10 and 39.11) into four quadrants by a karate chop technique before being phacoemulsified (Fig 39.12). Irrigation and aspiration is done
to remove any residual cortex. (Fig 39.13). A PC IOL is
then implanted in the capsular bag (Fig. 39.14).

Fig. 39.8: Rhexis being done with a needle. Rhexis started


from the centre, moved to the right and then down. Rhexis
should not be started from the centre moved to the left and
then downwards

Fig. 39.9: Phaco probe placed at the superior


end of the rhexis

COMPLETING THE TRABECULECTOMY


Shifting back to trabeculectomy, the partial thickness
scleral flap is then lifted. A deeper full thickness scleral

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Fig. 39.10: Karate chopping done

Chapter 39: Triple ProcedureTrabeculectomy with Phaco and IOL Implantation 383

Fig. 39.11: Final bits of nucleus removed

Fig. 39.14: PC-IOL being implanted

Fig. 39.12: Nucleus fully removed

Fig. 39.15: Agarwal punch starting to create a


trabeculectomy opening

Fig. 39.13: Cortical aspiration completed. Note the straight


rod in the left hand, which helps control the movements of the
eye

Fig. 39.16: Trabeculectomy opening completed

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384 Section III: Glaucoma

Fig. 39.17: Peripheral iridectomy being done

Fig. 39.19: Conjunctiva and clear corneal wound sutured

Fig. 39.18: Peripheral iridectomy completed

Fig. 39.20: Completion of the case. Note the


peripheral iridectomy

flap 2 2 mm is excised using an Agarwal punch


(Figs 39.15 and 39.16). Then a peripheral iridectomy is
performed (Figs 39.17 and 39.18). The external scleral
flap is reposited back and closed by two radial 10-0 nylon
sutures applied at both the corners. Tenons membrane
and conjunctiva were repositioned back to the limbus
using one or two 10-0 nylon sutures (Figs 39.19 and
39.20). The clear corneal incision is closed with a 10-0
suture to prevent shallowing of the anterior chamber. The
sutures are removed after a week.

tapered over a period of two weeks. The patients were


examined on the first postoperative day, once weekly for
one month, and once monthly for the first 3 months.
Additional follow-ups are provided whenever indicated.

POSTOPERATIVE CARE
All patients are treated with tobramycin (0.3%)
dexamethasone (0.1%) eyedrops four times a day for one
month postoperatively and then the dosage gradually

DISCUSSION
Trabeculectomy combined cataract extraction is now
gaining popularity in treating patients with coexisting
POAG and cataract because of its encouraging results.
Trabeculectomy combined extracapsular cataract extraction (ECCE) corrected both the above problems in one
sitting. But, there is a high incidence of postoperative
hypotony, choroidal detachment and hyphema.1
The later advancement in small incision cataract
surgery, phacoemulsification, is found to give good results

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Chapter 39: Triple ProcedureTrabeculectomy with Phaco and IOL Implantation 385
and has a lower incidence of the above complications.1, 6
The combined procedure has been shown to improve both
visual acuity and lower IOP in many patients.1-15
Performing both procedures at the same sitting is more
convenient for patients, decreases the frequency of postoperative pressure spikes and decreases the number of
glaucoma medications required to control IOP in many
patients.2 Other advantages of combined surgery include
more rapid visual recovery and lower cost compared to
a two-stage surgery. This can be either done by a single
site or a two-site approach.2
A leaking wound will be effective for a trabeculectomy whereas a watertight closure is required for a
cataract. This two-site procedure helps to achieve both.
Temporal clear corneal phacoemulsification combined
with a separate superior trabeculectomy involves fewer
manipulations of conjunctiva and sclera in the region of
trabeculectomy. The possible induced inflammation from
the phacoemulsification tip is in a separate quadrant
from that of the trabeculectomy flap. In addition the
separate site facilitates the use of a fornix-based conjunctival flap for the trabeculectomy. The two-site procedure
also has decreased pooling of fluid and facilitates surgery on patients who have prominent brows. Two-site
trabeculectomy combined phacoemulsification has been
found to give a better pressure lowering effect and lesser
need for postoperative medications.2
We used Staar plate haptic silicone foldable IOLs
because it has been shown that acrylic lenses are associated with higher mean IOP than silicone lenses.4 We
have not used mitomycin in our study group as it has
been shown that mitomycin is not helpful in modifying
the surgical outcome.6 No statistical difference has been
found between control and mitomycin groups of nonselected patients with POAG in the overall success rate
of trabeculectomy procedure.9 Also mitomycin C supplemented with combined surgical procedure also has been
shown to have potential for complications like hypotony,
filtering bleb leaks and fibrin in anterior chamber,6 and
chronic hypotony induced maculopathy and endophthalmitis.8
Our study confirms the earlier reports that combined
procedures have lower IOP1-3 and have a lesser need to
continue postoperative medications.3, 5 Our study shows
that combined trabeculectomy and phacoemulsification
leads to low astigmatism and early stabilization of
refraction and visual rehabilitation because of its small
incision. The minimal tissue manipulation at the

trabeculectomy site in this two-site approach may be the


reason for its improved long-term filtration.
A separate two-site combined trabeculectomy with
phacoemulsification appears to be a safe and effective
surgical approach for visual rehabilitation and IOP
control in patients with concurrent cataract and
glaucoma.
REFERENCES
1. Alan S Kosmin, Wishart, Ridges: Long term intraocular control
after cataract extraction with trabeculectomy, phacoemulsification versus extracapsular technique. J Cat Ref Surgery
1998;24: 249-55.
2. Tomara Wyse, Meyer, Ruderman, Krupin et al: Combined
trabeculectomy and phacoemulsification. a one site vs a twosite approach. Am J Ophthal 1998;125:334-39.
3. Hidenobu Tanihara, Honjo, Inatani, Honda et al: Trabeculectomy combined with phacoemulsification and an intraocular
lens for the treatment of primary open-angle glaucoma and
coexisting cataract. Ophthalmic Surgery and Lasers 1997;28(10).
4. Lemon, Shin, Song, Lee et al: Comparative study of silicone
versus acrylic foldable lens implantation in primary glaucoma
triple procedure. Ophthalmology 1997;104:1708.
5. Dong H Shin, Kim, Sheth, Ren et al: The role of adjunctive
mitomycin C in secondary glaucoma triple procedure as compared to primary glaucoma triple procedure. Ophthalmology
1997.
6. John S Conen, Greft, et al: A phaco-controlled double masked
evaluation of mitomycin C in combined glaucoma and cataract
extraction. Ophthalmology 1996;103-1942.
7. Lemon, Dong Shin, Kim, Bsee et al: Limbus based vs fornix
based conjunctival flap in combined glaucoma and cataract
surgery with adjunctive Mitomycin. Am J Ophthalmol 1998;125:
340-45.
8. Dong Shin, Ren, Juzych, Hughesh et al: Primary glaucoma triple
procedure in-patients with primary open angle glaucomathe
effect of mitomycin C in-patients with and without prognostic
factors for filtration failure. Am J Ophth 1998;125:346-52.
9. Dong Shin, Hughes, Man Song et al: Primary glaucoma triple
procedure with or without adjunctive Mitomycinprognostic
factors for filtration failure. Ophthalmology 1996;103:1935-33.
10. Allan Kosmin, Wishart, Redges: Silicone versus polymethyl
acrylate lenses in combined phacoemulsification and trabeculectomy. J Cat Refract Surg Jan/Feb 1997.
11. Ashok Vyas, Bacon, Percival: Phacotrabeculectomycomparison of results from 3.5 and 5.2-mm incisions. Ophthalmic
Surgery and Lasers 1998;29(3).
12. Kunjin Yang, Monstor, Blanco, Wilson et al: Mitomycin C
supplemented trabeculectomy, phacoemulsification and
foldable lens implantation. J Cat Refract Surgery May 1997.
13. Gulgun Tazel, Kolker, Kass et al: Comparative results of
combined procedures for glaucoma of cataract. Ophthalmic
surgery and lasers 1997;28(7).
14. J Jill Hopkins, Apel, Graham E, Rootman et al: Early intraocular
pressure after phacoemulsification combined with trabeculectomy. Ophthalmic Surgery and Lasers 1998;29(4).
15. DCR Jayamanne: The outcome of 2.3-mm incision combined
phacoemulsification, trabeculectomy and implantation of nonfoldable intraocular lens. Eye 1997;11:91-94.

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Section IV

Retina
40. Update on Photodynamic Therapy (Verteporfin) in Age-related Macular Degeneration
S Natrajan, Anand Bagmar, Nazimul Hussain, Anjli Hussain, Shahana Mazumdar
41. Indocyanine Green Angiography
S Natrajan, Shahana Mazumdar, Nazimul Hussain, Anjli Hussain, Anand Bagmar
42. Perfluorocarbon Liquids in Vitreoretinal Surgery
Amar Agarwal
43. Trypan Blue Assisted Epiretinal Membrane Removal
Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Saurabh Choudhry, Reena M Choudhry
44. Diabetic RetinopathyCurrent Concepts and Recent Advances
Ashish Mahobia, Manish Nagpal, PN Nagpal, Kamal Nagpal, Sandeep Arora
45. Advances in the Management of Age-related Macular Degeneration
Sandeep Arora, Manish Nagpal, PN Nagpal, Kamal Nagpal, Ashish Mahobia

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40

Update on Photodynamic Therapy


(Verteporfin) in Age-related
Macular Degeneration
S Natrajan, Anand Bagmar, Nazimul Hussain, Anjli Hussain, Shahana Mazumdar

INTRODUCTION
TECHNIQUE
VERTEPORFIN
POST-TREATMENT REGIME

INTRODUCTION
Age-related macular degeneration (ARMD) is the major cause of blindness
in elderly people.1 Ten percent those affected patients retain usable vision.2
Out of these, 25 percent are caused by retinal pigment epithelium (RPE),
choriocapillaris and neurosensory retina atrophy also called Dry ARMD.3
Currently there is no treatment available for these patients. Remaining 75
percent of patients have wet or exudative ARMD. They experience severe
visual loss. The disease process includes choroidal neovascularization
(CNV), disciform scarring, vitreous hemorrhage, pigment epithelial
detachment and tears.3
There are various modalities of treatments like laser treatment, radiation
therapy, vitamin supplements, surgical excision of neovascular membranes,
macular translocation, and transpupillary thermotherapy and photodynamic therapy.4-9
Macular photocoagulation study (MPS) showed 50 percent recurrence
of treated vessels and scotoma following the treatment. Submacular surgery
and fovea translocation did not show magnificent visual benefit due to
RPE atrophy.4-9 Photodynamic therapy (PDT) is an emerging technology
for the treatment of neovascular process affecting eye and other parts of
the body especially treatment of CNV in wet ARMD.10
The basic principle of PDT is the activation of a dye by low power laser
light to induce coagulation of the neovascular vessels. The dye particles
absorb the photons and move to a higher energy state which results in the
creation of an excited oxygen which damages cell membranes,
mitochondria and vascular endothelial cells.11-12 This can be performed
with safety with regard to the surrounding normal neurosensory retina. In
photocoagulation therapy, pigments present in a neovascular as well as
surrounding normal tissue absorb thermal energy, which results in
unintended but unavoidable bystander effect on the normal tissue. This
lack of specificity limits the usefulness of photocoagulation for CNV
especially in subfoveal and juxtafoveal region.
In contrast to photocoagulation, in PDT due to nonthermal and
photodynamic properties of verteporfin where drug is activated by laser
to induce regression of CNV, we achieve its therapeutic effect. Although a
large area of retina is exposed to energy, there is no thermal effect exerted
on the neurosensory tissue. Instead a laser light acts as a catalyst to activate
the photo-active dye within the neurosensory vessels, inducing occlusion

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390

Section IV: Retina

Figs 40.1A and B: Fundus photograph and FFA of right eye shows subfoveal CNV.
Visual acuity 6/60. Patient underwent PDT

Figs 40.2A and B: At 3 months follow-up after 1st treatment, FFA showed leakage.
Visual acuity - 6/24. Patient underwent 1st re-treatment

of the vessel and sparing the normal surrounding


tissue.
TECHNIQUE
PDT is done by an IV infusion of (1-2 mg/kg) of the
verteporfin into the antecubital vein.
After administration for IV infusion of a drug for
10 minutes, laser energy is then applied 15 minutes
from the time of infusion to the area of interest with

the help of fundus contact lens. The patient is advised


to sit in a light restricted room for 1 hour after treatment to minimize the possibility of photo toxicity from
the dye.
VERTEPORFIN
Visudyne is administered in liposomal form as an IV
infusion over 10 min. It binds to circulating low-density
lipoprotein (LDL) in the bloodstream. Prolioferative

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Chapter 40: Update on Photodynamic Therapy (Verteporfin) in Age-related Macular Degeneration 391
endothelial cells in CNV have higher levels of LDL
receptors than normal vascular tissue. Verteporfin-LDL
complexes are rapidly absorbed by CNV. Nonthermal
red laser light at 689 nm, 50 J/cm2, 600 mW/cm2) for
83 seconds. 13 Fifteen minutes after the start of the
visudyne infusion. Activation causes release of oxygen
free redials. Endothelial damage and throbs formation
occurs due to it. It leads to an occlusion of abnormal
vessels.

The treatment effect of PDT is not immediately visible


to examine but the lesion develops over a period of hours
after the appreciation of laser energy to the fundus.
Various drugs available for PDT like Ethyl etiopurpurin,
Leutin texaphyrin, Verteporfin. Verteporfin (VisudyneTM)
is most widely used.
POST-TREATMENT REGIME
Completely avoid exposure to sunlight for 48 hours
Avoid halogen light
To wear ANSI approved 100 percent UV protecting
glasses
To wear clothes that completely cover the body
Preparation of the Patient for PDT

Fig. 40.3A

For the correct diagnosis of CNV, eligible for treatment


with visudyne, FFA and ICG angiography associated
with stereoscopic color fundus photography have to be
performed.
The angiogram should not be taken more than 7 days
before treatment with visudyne.
Define eligibility of the patient based on the lesion,
componentsclassic and occult CNV, their proportions,
size and closeness to the optic disc.

Figs 40.3A to C: At 6 months follow-up, FFA and ICG showed healed CNV. Visual acuity stabilized to 6/9

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392

Section IV: Retina


CONCLUSION

Calculation of the Treatment Spot Size


Required Covering the CNV
a. Determine the GLD (greatest linear dimension) on
the photographic image (It should include additional
1000 m to allow margin of 500 m to ensure the
coverage of the lesion)
b. Divide GLD/ magnification of the image (2.5)
Actual GLD on the retina
c. Treatment spot sizeGLD on the retina +1000 mm.
Procedure
Dilution15 mg/7.5 ml vials reconstituted by dilution
with 5 percent D to make 30 ml of 6 mg/m2. Syringe is
loaded into infusion pump. Time is set to 15 minutes to
begin laser. Start infusion pump for 10 minutes. Start laser
15 minutes after start of infusion for 83 sec.
Results
Results of TAP (Treatment of ARMD with PDT study) -13
246 (61%) of 402 eyes lost < 15 letters of visual acuity
from baseline, compared to 96 (47 %) of 207 placebo eye.
(P< 0.001).
Subgroup analysis Sixty-seven percent classic (>50%
classic lesion) vs 39% occult eyes lost < 15 letters of visual
acuity.
Results of VIP Study14
VIP Study Group
High Myopia Group
1 year Follow-up
Control
PDT
VA gain 1 line or more
VA no gain or loss
VA loss 3 lines or more

15%
28%
33%

32%
30%
14%

PDT is a promising treatment modality for the treatment


of SRNV in ARMD. Though there is a high rate of
recurrence of CNV following treatment with PDT,
retreatment is possible.
REFERENCES
1. Abdelsalam A, Del Priorel, Zarbin MA. Drusens in ARMD,
Pathogenesis, natural courses and laser photocoagulation
induced regresion. Surv Ophthalmol. 1999; 44:1-29.
2. Elman NJ, Fine SZ. Exudative ARMD. Retina, Ryan SJ, Mosby,
1994; 1103-41.
3. Klein R. Klein BE, Jensen SC, Meuer SM, The 5 yr. incidence
and progression of age related maculopathy: The Beaver-Dam
eye Study. Ophthalmology 1997;104:7-12.
4. Macular photocoagulation study group: 5-year. follow-up of
fellow eyes of patients with ARMD and unilateral extrafoveal
choroidal neovascularization, Arch Ophthalmol. 1993;111:118999.
5. Devis H, Kaiser PK, Lewis S, and Estafanous M. Macular
Translocation for subfoveal CNV in ARMD. A prospective study.
Am J Ophthalmol. 1999;128:135-46.
6. Mauget Faysee M, Chiquet C, Mileu D et al. Long term results
of radiotherapy for subfoveal NV in ARMD. Br J Ophthalmol.
1999; 83: 923-28.
7. Smith W, Mitchell P, Webb K, Leader SR. Dietary antioxidants
and age related maculopathy. The blue mountains eye study.
Ophthalmology 1999;106:761-67.
8. Meril Pt. Loruso FJ, Lomeo MD et al. Surgical removal of
subfoveal SRNV in ARMD. Ophthalmology 1999;106:782-89.
9. Chong TA, Bird AC. Alternative therapies in exudative ARMD.
Br J Ophthalmol. 1998;82:1441-43.
10. Bressler NM. TAP study group. PDT with vertiporfin of
subfoveal SRNV in ARMD.
11. Henderson BW, Dougherty TJ. How does PDT work - Photochem photobiol 1992;55: 145-57.
12. Moshfeghi Dm, Peyman Ga, Moshfeghi AA et al. Ocular
vascular Thrombosis following Tinethyl etiopurpurin (SnET2)
PDT: Time dependencies. Oph Surg Lasers 1998; 29; 663-68.
13. Treatment of ARMD with PDT (TAP) study group. PDT of
subfoveal CNV in ARMD with Verteporfin: One year results of
2 randomized clinical trials: TAP report. Arch Ophthalmol.
1999;117:1329-45.
14. Mones J. VIP Study Group. PDT with verteporfin of subfoveal
CNV in ARMD study design and baseline VIP randomized
clinical trial. Invest Ophthalmol Vis Sci. 1999;40:S321.

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41

Indocyanine Green Angiography


S Natrajan, Shahana Mazumdar, Nazimul Hussain, Anjli Hussain, Anand Bagmar

INTRODUCTION
ADVANTAGES OF ICG
HISTORY
PHARMACOLOGY
TOXICITY
TECHNIQUE
VARIOUS PHASES OF ICG
ANGIOGRAPHY
ICG IN AGE-RELATED
MACULAR DEGENERATION

INTRODUCTION
In the last few decades there have been major advancements in procedures
for retinal evaluation. Fluorescein angiography revolutionized the
diagnosis of retinal disorders but had some inherent limitations which
could be overcome to a large extent by indocyanine green (ICG)
angiography.
ADVANTAGES OF ICG
ICG dye is a large molecule, highly protein bound and does not escape
from the choroidal vasculature. The dye remains largely within the
choriocapillaris. Its activity is in the infrared range, absorbing at 790-805n
and emitting maximally at 835nm. The retinal pigment epithelium and
choroid absorb only 21 to 38 percent of near infrared light as compared to
55 to 75 percent of blue green light used in fluorescein angiography (FA).1
These properties allow enhanced visualization of the deeper lying choroid
and its associated abnormalities. Overlying hemorrhages, serous fluid, lipid
and pigment that block view of fluorescein angiography, however, allow
visualization of ICG.
HISTORY
Kogure and associates 2 performed the first choroidal absorption
angiography in monkeys in 1970. David performed the first ICG
angiograms in humans during carotid angiography.3 In 1971 Hochheimer4
described choroidal absorption angiography in cats using ICG injections.
One year later, Flower and Hochheimer 5,6 performed intravenous
absorption ICG angiography for the first-time in humans. The same group
then described the superior technique of ICG fluorescein angiography.7,8
However, since the fluorescence efficacy of ICG is only 4 percent of that of
sodium fluorescein, it was difficult to produce high resolution images of
clinical relevance. This was achieved with the advent of digital imaging
systems coupled to infrared cameras9,10 as well as scanning laser ophthalmoscopes (SLO) for ICG videoangiography. The use of 1024 line digital
imaging system produces high resolution and enhanced ICG images.10
Realtime ICG Angiography
Realtime ICG angiography uses a fundus camera with a diode laser
illumination system that has an output at 805nm which can produce images
at 30 frames per second acquired either as a videotape or as a single image
at a frequency of 30 images per second.

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Wide Angle Image


Wide angle image can be obtained with the aid of wide
angle contact lenses with the fundus camera set on
positions for aphakia (A) or hypermetrophia (+).
Digital Subtraction
Digital subtraction uses digital subtraction techniques
and allows imaging in greater detail and in a shorter
period of time.
PHARMACOLOGY
ICG is tricarbocyanine dye which has been used to
measure cardiac output since 1957.12 It is water soluble
with an empiric formula of C43 H47Na O6S2. The dye is
an anhydro-3, 3, 3, 3-tetramethyl 1-1,1-di(4sulfobutyl)4, 5, 4, 5, dibenzoindo tricarbocyanine hydroxide sodium
salt. It has a molecular weight of 775 daltons. It is highly
protein bound to globulins such as a1 lipoproteins. It is
excreted by the liver via bile. It is not detected in cerebrospinal fluid13,14 and does not cross the placenta.15
TOXICITY

Fig. 41.1: Photograph of the indocyanine green dye


(25 mg vial) in the dark bottle and its solvent

Early phase B Seen between 2 to 5 seconds. There is a


complete filling of the large choroidal veins and an early
filling of the retinal arterioles.
Early phase C Seen between 5 seconds to 3 minutes.
There is a gradual filling of the choroidal arterioles. The
large choroidal veins are still seen and the water shed
zone is filled.

The dye is relatively safe and appears to be safer than


fluorescein. Nausea and vomiting are extremely uncommon. However, it should not be performed on patients
allergic to iodine since it contains approximately 5
percent iodide by weight. Also it should not be performed
on patients who are uremic or who have liver disease.
Appropriate emergency equipment should be readily
available.

Late phase Seen between 15 to 60 minutes. There is a


background hyperfluorescence resulting from the
staining of extrachoroidal tissue. The hypofluorescent
choroidal vasculature is silhouetted against the background. The retinal vasculature is not visible.

TECHNIQUE

ICG IN AGE-RELATED MACULAR DEGENERATION

ICG can be performed before or after fluorescein angiography. Usually 25 ml of ICG dissolved in 2 ml solvent is
used (Fig. 41.1). Alternatively 50 mg dissolved in 3 ml of
aqueous solvent is used in poorly dilated or darkly
pigmented patients. Images are taken up to 30 minutes.

By fluorescein angiography about 13 percent of patients


with wet ARMD are found to have a well-defined or
classic neovascular membrane that are amenable to treatment.16 ICG angiography improves the visualization of
the neovascular complex and thus allows potential
treatment of more patients. Yanuzzi and associates
reported that in 39 percent of choroidal neovascular
membranes, seen as occult by fluorescein angiography,
they were able to differentiate into well-defined CNVMs
using ICG angiography. Conducting a study on 1000
consecutive eyes with occult neovascular membranes,
they were able to identify 3 morphological types using
ICG angiography.17 These lesions include focal spots
(29%), plaques (61%) and combination lesions (8%) with

VARIOUS PHASES OF ICG ANGIOGRAPHY


Early phase A Seen in the first two seconds. There is
rapid filling of choroidal arteries and choriocapillaris and
an early filling of choroidal veins. Major retinal blood
vessels are not filled and are silhouetted as dark
structures. A water shed zone is seen running vertically
adjacent to the optic nerve head.

Middle phase Seen between 3 to 15 minutes. There is a


fading of the choroidal and retinal vasculature.

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Chapter 41: Indocyanine Green Angiography 395


both focal spots and plaques. There are three subtypes
of combination lesions based on the location of the hot
spot relative to the plaque, i.e marginal spot (focal spot
at edge of plaque) (3%); overlying spot (hot spot
overlying the plaque) (4%) and remote spot (hot spot
remote from the plaque) (1%). In some, however a
mixture of these lesions were noted whereas in a few no
hyperfluorescence was noted. The authors found that
patients tended to develop the same morphologic type
of CNVM in the fellow eye.
Focal spots Appear as hyperfluorescent lesions less
than 1 disc area in size. They are often seen outside the
foveal avascular zone and thus potentially treatable by
ICG guided/enhanced laser photocoagulation.
Plaque is the most common pattern of neovascularization seen. It is seen as a hyperfluorescent area greater
than 1 disc area in size. These lesions are usually
subfoveal. Hayashi and coworkers showed that leakage
of ICG from CNV was slow compared to fluorescein.18
Chang et al 19 reported on the clinicopathologic
correlation of ARMD with CNV detected by ICG
angiography. Histopathologic examination of the lesion
revealed a thick subretinal pigment epithelium CNVM
corresponding to the plaque like lesion seen with ICG
angiography. Yanuzzi and coworkers10 also reported the
contribution of videoangiography in converting cases of
serous and vascularized pigment epithelial detachments
with occult CNVM into well-defined classic CNVMs.
ICG Dye Enhanced Diode Laser Photocoagulation
The peak absorption of ICG is at a similar wavelength as
the peak emission of the diode laser. Thus dye enhanced
laser photocoagulation may allow selective ablation of
the ICG containing CNVM with relative sparing of the
normal neighboring retina. This is specially useful in
subfoveal CNVMs.

Fig. 41.2A: Fundus photograph of a patient with a pigment


epithelial detachment and exudative age related macular
degeneration

Idiopathic Polypoidal Choroidal


Vasculopathy (IPCV)
IPCV is an anomaly of the choroidal vasculature wherein
some vessels of the inner choroidal vascular network of
vessels end in an aneurysmal bulge or polyp like
structure. These appear as reddish orange, spheroidal
structures and are associated with multiple, recurrent
serosanguinous detachments of the RPE and neurosensory retina following bleeding from these polyps.20
During ICG the larger vessels of the network start to
fill before the retinal vessels. Shortly afterwards, small
hyperfluorescent polyps become visible. They appear
to leak slowly and the surrounding hypofluorescent. In
late phases there is a washout or disappearance of the
dye and the characteristic late staining of an occult
CNVMs absent (Figs 41.3A to D).
Central Serous Chorioretinopathy

Feeder Vessel Treatment


Figures 41.2A to C is a new modality of treatment where
high speed ICG angiography is used to detect extrafoveal
feeder vessels supplying any choroidal neovascular
membranes, specially in cases of subfoveal CNVM. They
are seen in early phase of ICG angiography. The two
patterns noted are the racquet and umbrella. Racquet
patterns are favorable for treatment.
ICG angiography has enhanced the understanding
of several pathologies occurring primarily at the
choroidal level.

The early phase of ICG may show diffuse or multifocal


areas of choroidal hyperpermeability. In the late phases
there is dispersion of the fluorescence and a silhouetting
of the larger choroidal vessels.
Intraocular Tumors
Certain tumours have characteristic ICG patterns.21
Pigmented choroidal melanomas block ICG fluorescence and
are differentiated from hemangiomas and osteomas.
Choroidal hemangiomas show a marked progressive

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Section IV: Retina

Figs 41.2B and C: Early (B) and middle phase (C) ICG angiograms showing a pigment
epithelial detachment and a feeder vessel supplying the occult plaque

Figs 41.3A and B: Fundus photographs of a patient with idiopathic polypoidal choroidal vasculopathy

hyperfluorescence due to the vascularity, which can be


visualized even through overlying hemorrhages.
Choroidal osteomas show characteristic small vessels and
variable blockage in bony areas.
Choroiditis

Bird Shot Retinochoroidopathy


The clinical creamy lesions are seen as multiple hypofluorescent lesions resembling holes in the fluorescence
of the choriocapillaris. They are seen along larger
choroidal vessels.22
Serpiginous Choroiditis23

ICG is useful in the diagnosis and monitoring of patients


with posterior uveitis.

The acute lesions show blockage of fluorescence on ICG,


which reappears after resolution (Figs 41.4A to D).

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Chapter 41: Indocyanine Green Angiography 397

Figs 41.3C and D: Early (C) and middle phase (D) ICG angiograms of the patient in figure showing filling of the polypoidal
lesions with surrounding hypofluorescence due to subretinal hemorrhage and exudation

Fig. 41.4A: Fundus photograph of a patient with healed


serpiginous choroiditis

Multifocal Choroiditis
Multifocal choroiditis patches block fluorescence on ICG
angiography. Some hyperfluorescent spots seen appear
to be subclinical foci of choroiditis.

Fig. 41.4B: Photograph early phase indocyanine green


angiogram of the patient showing areas of hypofluorescence
with larger choroidal vessels seen

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Section IV: Retina

Figs 41.4C to D: Photograph middle (C) and late (D) phase indocyanine green angiogram of the patient
showing areas of hypofluorescence with larger choroidal vessels seen

AMPPE24
24

AMPPE lesions are hypofluorescent in both the early


and late phases and suggest the pathogenesis of choroidal
vascular occlusion secondary to occlusive vasculitis.
MEWDS25
MEWDS25 has a characteristic pattern of hypofluorescent
spots throughout the posterior pole and peripheral retina,
which appear 10 minutes after dye injection and then
persists.
Vogt Koyanagi Harada Disease
The ICG shows signs of choroidal inflammatory vasculopathy such as delayed choriocapillaris perfusion,
perivascular leakage and diffuse choroidal hyperfluorescence. Hypofluorescent dark dots seen in intermediate
stages, represent granulomas. Areas of exudative retinal
detachment may show hyperfluorescent pinpoint areas.
In cases of severe papillitis disc hyperfluorescence is
seen.26
SUMMARY
ICG is an investigational tool to study the choroidal
anatomy and pathology. Used as an adjunct to fluorescein
angiography it has greatly enhanced our understanding
of hitherto ill-understood lesions. It is specially useful in

cases of occult and recurrent choroidal neovascular


membranes. It has been used to detect and characterize
the IPCV abnormality. Various types of choroiditis and
choroidal tumors can be differentiated. ICG videoangiography is being used to study the choroidal blood flow.
The clinical usefulness of this relatively new technique
will become apparent with greater experience.
REFERENCES
1. Geerates WJ, Berry ER, Ocular spectral characteristics as related
to hazards from lasers and other light sources. Am J Ophthalmol.
1968, 66: 15-20.
2. Kogure K, David NJ, Yamanouchi U, Choromokos E, Arch
Ophthalmol. 1970, 83: 209-14.
3. David NJ, Infrared absorption fundus angiography. In Proceedings of International Symposium on Fluorescein Angiography,
Albi, France, 1969, Basel, 1971, Karger.
4. Hochheimer BF, Angiography of the retina with indocyanine
green. Arch Ophthalmol. 1971, 86:564-65.
5. Flower RW, Infrared absorption angiography of the choroid and
some observations on the effects of high intraocular pressures.
Am J Ophthalmol 1972, 74:600-14.
6. Flower RW, Hochheimer BF, Clinical infrared absorption
angiography of the choroid. Am J Ophthalmol 1972 ,73:458-59
(letter).
7. Flower RW, Hochheimer BF, A Clinical technique and choroidal
circulation. Invest Ophthalmol. 1973,12:248-61.
8. Flower RW, Hochheimer BF, Indocyanine green dye fluorescence
and infrared absorption choroidal. Johns Hopkins Med J 1976,
138:3-42.
9. Guyer DR, Puliafito CA, Mones JM, Friedman E, Chang W,
Verdooner SR, Digital indocyanine green angiography in
chorioretinal disorders. Ophthalmology 1992,99:287-90.

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Chapter 41: Indocyanine Green Angiography 399


10. Yannuzzi LA, Slakter JS, Sorenson, JS, Guyer, DR, Orlock DA,
Digital indocyanine green videoangiography and choroidal
neovascularization. Retina 1992,12:191223.
11. Guyer DR, Yannuzzi LA, Slakter JS, Sorenson JA, Hope-Ross
M, Orlock DR, Digital indocyanine green videoangiography of
occult choroidal neovascularization. Ophthalmology 1994,
101:1727-37.
12. Fox IJ, Wodd EH, Applications of dilution curves recorded from
the right side of the heart or venous circulation with the aid of
a new indicator dye. Mayo Clin Proc 1957, 32:541.
13. Ketterer SG, Wiengand BD, The excretion of indocyanine green
its use in the estimation of hepatic blood flow. Clin Res 1959,
7:71.
14. Ketterer SG, Wiengand BD, Hepatic clearance of indocyanine
green. Clin Res 1959, 7: 289.
15. Probst P, Paumgartner G, Caucig H, Fruohlich H, Grabner G,
Studies on clearance and placental transfer of indocyanine green
during labor. Clin Chim Acta 1970, 29:157.
16. Freund KB, Yanuzzi LA, Sorenson JA, et al, Age related macular
degeneration and choroidal neovascularization. Am J
Ophthalmol. 1993, 115:786-91.
17. Guyer DR, Yannuzi LA, Slakter JS et al, Classification of choroidal neovascularization by digital indocyanine angiography.
Ophthalmology 1996, 103:2054-60.
18. Hayashi K, DeLaey JJ, Indocyanine green angiography of
neovascular membranes. Ophthamologica 1985, 190:30-39.

19. Chang TS, Freund KB, de la Cruz, Z, et al, Clinicopathologic


correlation of choroidal neovascularization demonstrated by
indocyanine green angiography in a patient with retention of
good vision for almost four years, Retina 1994, 14:114-24.
20. Kleiner RC, Brucker, AJ, Johnston, RL, The posterior uveal
bleeding syndrome, Retina 1990, 10:9-17.
21. Guyer DR, Yanuzzi LA, Krupsky S, Slakter JS et al, Digital
indocyanine green angiography of intraocular tumours, Semin.
Ophthalmol 1993, 8:224-29.
22. Krupsky S, Foster S, Guyer DR, Gragoudas ES, Friedman E,
Digital indocyanine green angiography of choroidal inflammatory disorders, Invest Ophthalmology (suppl) 1999, 33.
23. Giovannini A, Ripa E, Scasellati-Sforzolini B et al, Indocyanine
green angiography in serpiginous choroidopathy. Eur J
Ophthalmol 1996, 6:299-306.
24. Howe LJ, Woon H, Graham EM, et al, Choroidal hypoperfusion
in acute multifocal posterior placoid pigment epitheliopathy:
an indocyanine green angiography study. Ophthamology 1995,
102:790-98.
25. Ie D, Glaser BM, Murphy RP, et al, Indocyanine green angiography in multiple evanescent white-dot syndrome. Am J
Ophthalmol. 1994, 117:7-12.
26. Bouchenaki N, Herbert CP, The contribution to the appraisal
and management of Vogt Koyanagi Harada disease. Ophthalmology 2001, 108(1) 54-64.

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Section IV: Retina

42

Perfluorocarbon Liquids in
Vitreoretinal Surgery
Amar Agarwal

INTRODUCTION
TYPES
PHYSICAL PROPERTIES
INDICATIONS
OTHER MEDICAL APPLICATIONS

INTRODUCTION
Since long vitreoretinal surgeons have been using lighter-than-water
liquids for tamponading the retina. It was Dr. Stanley Chang from USA
who introduced a heavier-than-water liquid. This was used to flatten
the retina and was an N-perfluorocarbon amine. The basic idea of these
liquids is that as they are heavier than water liquids, they would flatten
the retina or unfold a giant tear.

COMPLICATIONS
TYPES
There are four types of perfluorocarbon liquids used at present.
They are:
i. Perfluoro-N-octane,
ii. Perfluoro-tributylamine,
iii. Perfluoro-decaline, and
iv. Perfluoro-phenanthrene.
The differences in the physical properties between the four is shown in
Table 42.1.
PHYSICAL PROPERTIES
The question which we should ask ourselves iswhy perfluorocarbons?
In other words, what is so good about perfluorocarbons that they can unfold
giant tears or make an IOL float on it.2-5 To answer2-5 this question we
should understand some basics on physics and also understand the physical
properties of these liquids.
Density
Liquids and gases have no definite shape of their own and are capable of
flowing freely around places. Hence, liquids and gases are called fluids.
The study of fluids at rest is called hydrostatics. Now, we say that
perfluorocarbons are heavier than water liquids. This means that their
density is more than water. The density of a substance is calculated by
dividing its mass by its volume.
Density = Mass/Volume

(The difference between mass and weight is that mass is the same
everywhere, whereas weight depends on the gravitational force.) If you

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Chapter 42: Perfluorocarbon Liquids in Vitreoretinal Surgery 401


Table 42.1: Properties of perfluorocarbon liquids
Characteristics

Perfluoro-Noctane

Perfluorotributylamine

Perfluorodecaline

Perfluorophenanthrene

Chemical formula
Molecular weight
Specific gravity
Refractive index
Surface tension
(Dyne/cm at 25C)
Viscosity
(Centistokes at 25C)
Vapor pressure
(mm Hg at 37C)

C3F18
438
1.76
1.27

C12F27N
671
1.89
1.29

C10F18
462
1.94
1.31

C14F24
624
2.03
1.33

14

16

16

16

0.8

2.6

2.7

8.03

50

1.14

13.5

<1

take your weight on the earth and also take your weight
on the moon, the values will be different as the
gravitational force in both the places is different, whereas
your mass will be the same in both the places.
So, when we say density = mass/volume, and we take
water as an example, it means the density of water is 1
gm/cc because 1 cc of water weighs 1gm. In other words,
when we say that perfluorocarbons are heavier than
water liquids, it means that their density is more than
water, i.e. if we take 1 cc of perfluorocarbon, it weighs
1.76 to 2.03 gm.
Fig. 42.1: Refraction of light

Relative Density or Specific Gravity


As water has a density of 1 gm/cc, it is taken as a
standard. If you would compare the density of any other
substance, you should compare it with water and that
gives us the relative density of that substance or the
specific gravity of that substance.
Relative Density = Density of the Substance/
Density of water

As relative density or specific gravity is only a mere


number, it has no units. When we say that perfluorocarbons have a specific gravity from 1.76 to 2.03
depending on the type of perfluorocarbon, it means its
density is 1.76 gm/cc to 2.03 gm/cc and as the density
of water is 1gm/cc, the relative density of perfluorocarbon is 1.76/1 or 2.03/1 which is 1.76 or 2.03. For
example, let us take the example of perfluoro-octane.
Density of perfluoro-octane = 1.76 gm/cc
Density of water
= 1 gm/cc
Relative density or specific
gravity of perfluoro-octane = 1.76/1
= 1.76
The application of this specific gravity is that as the
perfluorocarbons are heavy and have a higher specific
gravity compared to water, when they are injected into

the vitreous cavity, the liquid flattens the retina, displacing subretinal fluid anteriorly through the peripheral
retinal breaks. The flattening force exerted by perfluorocarbon is approximately 3 times greater than an
equivalent volume of fluorosilicone oil and more than
100 times greater than that exerted by sodium
hyaluronate 1 percent.
Refractive Index
To understand refractive index, we should first understand refraction. In a homogenous transparent medium,
light travels in straight lines. But, if a ray of light travels
from one homogenous medium to another, a change in
direction of the ray takes place at the surface of separation
between the two media. This bending of the rays of light
is called refraction (Fig. 42.1).
Laws of Refraction
Law I The incident ray, refracted ray and the normal to
the surface at the point of incidence lie in the same plane.
Law II For a given color of light passing from one
medium to another, the ratio of the sine of the angle of
incidence to the sine of the angle of refraction is a

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constant. This is called the refractive index of the second


medium and is denoted by the letter .
Refractive Index = Sine angle of incidence/
Sine angle of refraction

The refractive index of water for instance is 1.33. The


refractive index of the perfluorocarbons varies from 1.27
to 1.33 depending on the type of perfluorocarbon. From
this, we realize that the index of refraction of the perfluorocarbons is slightly dissimilar to saline. Optically, the
liquids are clear, and as the index of refraction of the
perfluorocarbons is different from that of saline, the
perfluorocarbon bubble interface with saline is visible
when it is injected into the vitreous cavity. As the
difference in refraction between saline is most with
perfluoro-N-octane (1.27), it has the most visible interface when compared to perfluoro-phenanthrene (1.33)
which has the least visible interface.
Another point about the refractive index is that
though the refractive index between perfluorocarbons
and saline is dissimilar it is only slightly dissimilar, so
optical aberrations during membrane dissection are not
induced. If there was a lot of difference in the refractive
index between saline and perfluorocarbons, all the
instruments which are passed into the vitreous cavity
when perfluorocarbons are in the vitreous cavity, will
appear distorted. This can be understood if we pass a
stick in a swimming pool. The stick appears to be broken
and bent at the water surface. This is because in this case
there is a lot of difference between the refractive index
of air and water (Fig. 42.2).
The perfluorocarbons are also immiscible with
silicone oil, and the optical interface is well seen during
perfluorocarbon-silicone oil exchange as the refractive
index between the two is different.
Surface Tension
When water is in a liquid form, its water molecules are
connected to each other by hydrogen bonds (Fig. 42.3).

Fig. 42.2: Refractiona stick in water


appears broken and bent

Fig. 42.3: Surface tension water


molecule in a liquid state

Fig. 42.4: Surface tensionround object


sinks in water

One water molecule connects with four other immediate


neighboring water molecules by the hydrogen bonds. An
exception is at the level of the water surface, where the
water molecule connects with the other water molecules
below and at the sides but not above as there is no water
above. It is these bonds that pull water surface into a
taut sheet, and this phenomenon is known as surface
tension. When water is in the form of ice, these bonds
hold the molecules in a more or less rigid pattern. When
water is heated, the molecules break off from each other
and vaporize as gas.
The surface of water can support amazing weight due
to surface tension if the object is flat enough to take
advantage of surface tension. Imagine a round object of
1 gm. It will sink in water, but if the same object of 1 gm
is made flat as much as possible and placed on the surface
of water it will float, because it has taken advantage of
surface tension of water (Figs 42.4 and 42.5).
If a needle is floating on the surface of the water, the
surface film behaves like an elastic membrane. As soon
as any deformation is produced in the film by the weight
of the object, it is opposed by the surface tension. This is
measured by force per unit length and is expressed in
dynes per cm (Fig. 42.6).

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Chapter 42: Perfluorocarbon Liquids in Vitreoretinal Surgery 403

Fig. 42.7: Surface tensionperfluorocarbon molecules


Fig. 42.5: Surface tensionsame object
made flat floats in water

Fig. 42.8: Viscosity

Fig. 42.6: Surface tensionexpressed


as force per unit length

The application of surface tension in regard to perfluorocarbons is that perfluorocarbons have a surface
tension ranging from 14 to 16 dynes/cm at 25 degree
centigrade. It is because of this surface tension that an
IOL can float on the surface of the perfluorocarbon.
Similarly, a lens can also float on the surface of the
perfluorocarbon. This property of the surface tension
of the perfluorocarbon is used when removing a lens
or IOL from the retinal surface by the vitreoretinal
surgeon.
It is because of surface tension that a water drop is
formed. What happens is that the cohesive force between
the water molecules keeps the water molecules together
and so a drop is formed. Once again this has a clinical
application with perfluorocarbons. As they have a high
surface tension, the molecules between the perfluorocarbons have a strong bond and keep the molecules of
perfluorocarbons together. This helps the perfluorocarbons to remain in one large bubble (Fig. 42.7). This helps
the vitreoretinal surgeon while operating and also while
removing the perfluorocarbon.

Viscosity
There is a certain amount of attraction between molecules of a liquid. The more the molecules are drawn
together the greater the internal friction in the liquid
in other words the greater the resistance to the flow of
the liquid. This resistance is called viscosity or fluid
friction (Fig. 42.8). So, if we want the fluid to flow fast,
then its molecules should not be firmly attracted to each
other or in other words the fluid should be less viscous
like water. If the fluid is more viscous like silicone oil,
then it flows less smoothly.
The perfluorocarbon liquids used are of low viscosity ranging from 0.8 to 8.0 centistokes at 25 degree
centigrade. These are useful to use intraoperatively
because they can be easily injected and aspirated while
using small gauge microsurgical instruments. The low
viscosity also allows perfluorocarbon liquids to be
injected for diagnostic determination of areas of residual
traction and can be easily removed if further membrane
dissection is required. Perfluoro-N-octane is the least
viscous, and the problem is that if there is a posterior
break it can go through the break into the subretinal
space. As perfluoro-phenanthrene has a higher viscosity
it has the advantage of not flowing through a posterior

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Section IV: Retina

Fig. 42.9: Vapor pressure

Fig. 42.11: Vitreon (perfluorophenanthrene)

Boiling Point

Fig. 42.10: Boiling

retinal break or through the zonules into the anterior


chamber.
Vapor Pressure
When a liquid is lying on the surface, part of the liquid
turns into vapor, i.e. gas. This is due to evaporation. The
vapor formed above a liquid has its own kind of pressure
known as vapor pressure which is measured in mm of
Hg at 37 degree centigrade (Fig. 42.9) . The vapor
pressure of the perfluorocarbons varies from 50 to less
than 1 mm of Hg at 37 degree centigrade. Perfluoro-Noctane has the highest vapor pressure. This is
advantageous because a thin layer of liquid will always
remain on the surface of the retina during fluid-air
exchange and with perfluoro-N-octane, this layer will
evaporate quickly as the infusion system flushes air
through the eye.

As the temperature of the liquid is raised, its vapor pressure rises. When it equals the prevailing atmospheric
pressure, the liquid reaches its boiling point. In evaporation, only the surface of the liquid turns to gas, whereas
in boiling all the liquid turns to gas. Thus, boiling is an
extreme case of evaporation. When the liquid reaches
its boiling point, bubbles of vapor form in its interior,
growing larger and larger and violently agitate the entire
liquid causing it to boil away (Fig. 42.10). For instance,
water boils at 100 degree centigrade.
Perfluorophenanthrene has a boiling point of 215
degree centigrade. Thus, we realize that perfluorocarbons
has a boiling point which exceeds that of saline so that
endophotocoagulation can be applied through the fluid
without intraocular vaporization.
INDICATIONS
There are various indications in which perfluorocarbons
are6-13 used (Fig. 42.11).
Giant Tears
Perfluorocarbon liquids offer the greatest advantages
in the management of giant retinal tears. First of all a
vitrectomy is done and the epiretinal membranes are
removed. When the tear is inverted, the perfluorocar-

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Chapter 42: Perfluorocarbon Liquids in Vitreoretinal Surgery 405

Fig. 42.12: Surgery for giant retinal tearsperfluorocarbon


liquids injected to unfold the giant retinal tear

Fig. 42.14: Precautions when injecting


perfluorocarbon liquids

Fig. 42.13: Surgery for giant retinal teargiant retinal tear


unfolded followed by endolaser photocoagulation

bon is injected over the disk to stabilize the posterior


flap (Fig. 42.12). Additional membranes causing
the edge of the tear to curl are then removed. Finally,
more perfluorocarbon liquid is injected till the edge
of the tear, flattening the retina to the periphery (Fig.
42.13). Endophotocoagulation is applied through
the perfluorocarbon along the edge of the tear.
Care should be taken to see that the perfluorocarbon
does not cross the edge of the tear as it can seep into the
subretinal space. Further, one should avoid letting the
anterior meniscus of perfluorocarbon being disturbed by
a forceful stream of balanced salt solution (BSS) otherwise
the result is the creation of numerous small bubbles of
perfluorocarbon that are difficult to remove (Fig. 42.14).
One should also be careful that the anterior meniscus of
perfluorocarbon must not come in direct contact with
the tip of the infusion cannula where the concentrated
stream of BSS will stir up numerous small bubbles of
perfluorocarbons that are difficult to remove later (Fig.
42.15).
Once the endophotocoagulation is completed, a slow
and deliberate fluid-air exchange is done, stopping

Fig. 42.15: Precautions when injected


perfluorocarbon liquids

frequently to allow the edges of torn retina to dry as much


as possible. This should be done to prevent the posterior
flap of the giant retinal tear from slipping posteriorly.
When the edge of the posterior flap of the giant retinal
tear is within the air-bubble, and relatively dry, it does
not slip posteriorly due to the capillary attraction
generated by having only a microscopic layer of fluid
remaining between the retina and the pigment
epithelium. Once the edges of the giant retinal tear are
within the air-bubble, the fluid-air exchange is continued
replacing all the perfluorocarbon and saline with the airbubble.
For long-term tamponade, one can use perfluoropropane gas or silicone oil. Sometimes, the case might
redetach postoperatively and so another alternative is
to use perfluorophenanthrene which can be left in the
eye for 5 to 30 days. Then at that time, the endolaser
reactions would have set in and the perfluorophenanthrene can be removed and replaced once again by some
long-term tamponade.

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Section IV: Retina

Fig. 42.18: Perfluorocarbon liquids injected to settle


proliferative vitreoretinopathy. Part of retina settled
Fig. 42.16: Proliferative vitreoretinopathy

Fig. 42.17: Perfluorocarbon liquids injected to settle


proliferative vitreoretinopathy

Fig. 42.19: Perfluorocarbon liquids injected to settle proliferative vitreoretinopathy. Endolaser now done once the retina
is flat

Proliferative Diabetic Retinopathy


Proliferative Vitreoretinopathy
In these cases, perfluorocarbons are used to assist with
membrane dissection. If the case is a bad case where the
tunnel is closed (Fig. 42.16) and the disk is not seen, a
little bit of perfluorocarbon is injected over the disk after
a vitrectomy (Fig. 42.17). When the tunnel of retina opens
and the disk becomes visible, membrane dissection is
continued using either delamination, segmentation or
peeling. Then some more perfluorocarbon is injected (Fig.
42.18) flattening the retina more. The subretinal fluid will
flow out through the anterior break in the retina. The
peripheral retina can be flattened by a partial fluid-air
exchange. Once the retina is flattened, endolaser
photocoagulation is done over the retinal breaks (Fig.
42.19). The perfluorocarbon can then be replaced by some
long-term tamponade. This technique avoids creating a
posterior retinotomy to drain the subretinal fluid and also
assist in membrane dissection.

Perfluorocarbons can be used for managing proliferative


diabetic retinopathies with tractional retinal detachments
by stabilizing the retina and assisting in membrane
dissection. Further it also helps like a traction test to tell
the surgeon where the traction is.
Dislocated Crystalline Lenses or
Intraocular Lenses
Due to the quality of surface tension, crystalline lenses
or IOL float on the surface of the perfluorocarbons. When
there is a crystalline lens or IOL on the surface of the
retina, a vitrectomy is done and the perfluorocarbon
injected under the crystalline lens or IOL. Gradually the
crystalline lens or IOL (Fig. 42.20) floats up to the pupil
as the perfluorocarbons are continuously injected. Once
in the anterior chamber, the crystalline lens can be removed or the IOL if necessary be sutured onto the sclera.

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Chapter 42: Perfluorocarbon Liquids in Vitreoretinal Surgery 407


bubble. However if a peripheral retinal break is also
present, the retinal detachment will be less elevated
around the perfluorocarbon bubble, and the schlieren
of subretinal fluid will be seen in the vitreous.
8. Removal of subretinal gas
9. When the retinal breaks are not found in a rhegmatogenous retinal detachment, vitrectomy with
perfluorocarbons can be helpful in flattening the
retina and localizing the retinal break. After vitrectomy, the perfluorocarbon liquid is injected to flatten
the retina. The subretinal fluid will be pushed
through the retinal break, exhibiting schlieren, seen
when two liquids of differing refractive indices are
mixed. The retinal breaks can be located by observing
the direction of schlieren flow.
OTHER MEDICAL APPLICATIONS
Fig. 42.20: Dislocated IOL floating on
perfluorocarbon liquids

Miscellaneous
Other indications in which perfluorocarbons are used are
as follows.
1. Management of choroidal or expulsive hemorrhage to
assist with drainage of serous or hemorrhagic fluid.
2. Removal of subretinal macular hemorrhage in patients
with subretinal neovascularization. In these cases, a
retinotomy is made temporal to the hemorrhage and
the perfluorocarbon injected. Due to their heaviness,
they push out the hemorrhage through the retinotomy.
3. Rhegmatogenous retinal detachment with a peripheral break to avoid a posterior retinotomy.
4. Retinal incarceration to the pars plana sclerotomy to
reposition the retina.
5. Traumatic vitreous hemorrhage associated with retinal detachment, to assist in mechanical separation of
the posterior hyaloid and stabilization of the retina
during the vitrectomy.
6. Retinal detachment in patients with a permanent
keratoprosthesis to reattach the posterior retina.
7. Retinal detachment resulting from a macular hole can
be assisted by injection of a small amount of
perfluorocarbon liquid over the posterior pole. The
macular hole will flatten against the pigment epithelium so that endophotocoagulation can be applied.
The liquid is then removed, and a fluid-air exchange
done. Diagnostically, also the perfluorocarbons can
be used to rule out any coexistent peripheral retinal
breaks. When only the macular hole is present, the
subretinal fluid will be displaced peripherally,
resulting in a more bullous configuration around the

Perfluorocarbon liquids have been used as:


i. Artificial blood replacements
ii. Sensitizers during radiotherapy for malignant
tumors.
COMPLICATIONS
One should be careful that the perfluorocarbon is
not left so that it touches the corneal endothelium.
Perfluorophenanthrene can be left in the eye up to 30
days. Sometimes the residual perfluorocarbon is encountered as small gas bubbles might inadvertently be left
behind. Increased intraocular pressure has also been
encountered. Due to the mechanical effects of the perfluorocarbon, there can be narrowing of the outer plexiform
layer and degenerative thinning of the outer nuclear layer
of the retina.
REFERENCES
1. Chang S: Perfluorocarbon liquids in vitreoretinal surgery.
International Ophthalmology Clinics: New Approaches to
Vitreoretinal Surgery: 1992;32(2):153-63.
2. Lakshminarayanan K, Venkataraman M: Physics. KCS Desikan
and Co. Chennai: 1992.
3. Leopold LB, Davis KS: Life Science Library Matter. Time Life
International BV, USA 1974.
4. Lapp RE: Life Science Library Matter. Time Life International
BV, USA, 1974.
5. Subramanyam N, Lal B: A Textbook of BSc Physics. S Chand
and Co: New Delhi, 1985.
6. Glasser BM, Carter JB, Kuppermann BD et al: Perfluoroctane in
the treatment of giant retinal tears with proliferative vitreoretinopathy. International Ophthalmology Clinics: New
Approaches to Vitreo-retinal Surgery 1992;32(2):1-14.
7. Nabin M, Peyman GA, Clark Jr LC et al: Experimental evaluation of perfluorophenanthrene as a high specific gravity vitreous
substitutea preliminary report. Ophthalmic Surgery 1989;
20:286-93.

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Section IV: Retina

8. Blinder KJ, Peyman GA, Paris CL et al: Vitreona new perfluorocarbon. Br J Ophthalmol 1991;75:240-44.
9. Liu Kwan-Rong, Peyman GA, Chen Muh-Shy et al: Use of high
density vitreous substitutes in the removal of posteriorly dislocated lenses or intraocular lenses. Ophthalmic Surgery
1991;22:503-07.
10. Paris CL, Peyman GA, Blinder KJ et al: Surgical technique for
managing rhegmatogenous retinal detachment following
prosthokeratoplasty. Retina 1991;11:301-04.

11. Peyman GA, Conway MD, Soike KF et al: Long-term vitreous


replacement in primates with intravitreal vitreon or vitreon plus
silicone. Ophthalmic Surgery 1991;22:657-64.
12. Peyman GA, Blinder KJ, Paris CL et al: Vitreona new perfluorocarbon vitreous substitute. Afro-Asian J Ophthalmol
1991;10:48-57.
13. Blinder KJ, Peyman GA, Desai UR et al: Vitreona short-term
vitreoretinal tamponade. Br J Ophthalmol 1992;76:525-28.

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Chapter 43: Trypan Blue Assisted Epiretinal Membrane Removal

409

43

Trypan Blue Assisted


Epiretinal Membrane Removal
Amar Agarwal, Athiya Agarwal, Sunita Agarwal, Saurabh Choudhry, Reena M Choudhry

INTRODUCTION
PATIENTS AND TECHNIQUE
RESULTS

INTRODUCTION
Epiretinal membranes can form in various proliferative retinopathies and
cause complications like decreased visual acuity directly by involving the
macula itself or indirectly by causing tractional retinal detachments,
combined retinal detachments or macular detachments. It can also occur
in cases of epimacular proliferation. Epiretinal membrane removal has
been a challenging procedure in posterior segment surgery. Various
methods like peeling, segmentation, delaminating and en bloc removal have
been described in the literature. Identifying the translucent epiretinal
membranes can be a major challenge and differentiating them from retinal
tissue can prevent iatrogenic retinal tears.
We have successfully used Blurhex (trypan blue manufactured by
Dr. Agarwals Pharma, Chennai, India) to stain epiretinal membranes thus
making their removal easier. Blurhex solution is being widely used in the
anterior segment surgery for staining anterior capsule in white cataracts1
to perform capsulorhexis (Fig. 43.1). It has been proved to be safe and
nontoxic to the ocular tissue at low concentration.
PATIENTS AND TECHNIQUE
Ten cases who had proliferative retinopathies with vitreous hemorrhage
underwent conventional three port pars plana vitrectomy (PPV) and
epiretinal membrane removal under peribulbar anesthesia by the same
surgeon at Agarwals Eye Hospital, Chennai. All the patients included in
this study underwent detailed preoperative investigations including
indirect ophthalmoscopy, B scan and IOP measurement. All cases with
increased IOP, signs of rubeosis iridis and fresh vitreous hemorrhage were
excluded from the study.
Patients with significant amount of cataract were taken up for combined
phacoemulsification with IOL and pars plana vitrectomy (PPV). Phacoemulsification was performed prior to PPV but the IOL was implanted at
the end of the surgery. The removal of vitreous in the meridians of the
instrument sclerotomy sites and in the vitreous cavity was first performed.
In cases where the posterior hyaloid was not detached completely it was
carefully removed with the vitrectomy probe. About 0.2 ml of Blurhex
(trypan blue) was slowly injected into the vitreous cavity over the optic
nerve head and epiretinal membranes. All epiretinal membranes stain
light blue in color (Fig. 43.2). The internal limiting membrane does not
stain hence increasing the contrast between the underlining retina and

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Section IV: Retina

Fig. 43.1: Capsulorhexis in a white cataract using


Blurhex to stain the anterior capsule

Fig. 43.2: Epiretinal membrane stained with Blurhex. 0.2 ml


of Blurhex was injected inside the vitreous cavity over the
epiretinal membranes and the excess Blurhex removed with
the vitrectomy probe

epiretinal membranes facilitating precise removal of the


tissue.
The membranes were either peeled, segmented or
delaminated depending on the nature of the membranes.
Using the Sutherland scissors (Fig. 43.3) the attachments
between the epiretinal membranes and the retina were
cut (Fig. 43.4). Gradually, the membrane is lifted off the
retina (Fig. 43.5) till the entire traction has been released
(Fig. 43.6) and the membrane is then removed with the
vitrectomy probe (Fig. 43.7). In all the cases successful

Fig. 43.3: Segmentation of the epiretinal membrane started


using the Sutherland scissors

Fig. 43.4: The membrane which is colored blue is lifted using


the Sutherland scissors after the attachments between the
membrane and the retina have been cut. Note the blue coloration of the epiretinal membrane and the normal color of
the retina behind it

epiretinal membrane removal could be achieved without


any iatrogenic retinal breaks.
Eyes with preexisting retinal breaks underwent fluidair exchange (FAE) and focal endolaser photocoagulation. The IOL was implanted after the completion of
vitrectomy in cases which underwent a combined
cataract surgery.
RESULTS
None of the 10 cases had intraoperative or postoperative
complications. Marked improvement in the visual acuity

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Chapter 43: Trypan Blue Assisted Epiretinal Membrane Removal

Fig. 43.5: Stained epiretinal membranes being removed

411

Fig. 43.7: The retina is seen without any epiretinal membranes. Note the blue colored epiretinal membrane is not
present as it has been removed

compared to the preoperative levels was observed in all


the eyes. The patients were followed up on the first,
seventh, fourteenth days and one month postoperative.
There was no evidence of residual stain in all the cases
postoperatively.
CONCLUSION
In conclusion, Blurhex (trypan blue) assisted pars plana
vitrectomy is a safe and effective adjunct for epiretinal
membrane removal and can minimize intra- and postoperative complications.
Fig. 43.6: The epiretinal membrane has been removed from
its attachment to the retina and is now lying free in the
vitreous cavity near the peripheral retina. It can be removed
easily now with the vitrectomy probe without a risk of a
retinotomy

REFERENCE
1. Agarwal et al, Trypan blue in management of mature cataracts.
In Agarwal A, Agarwal S, Agarwal A et al (Eds): Phacoemulsification, Laser Cataract Surgery and Foldable IOLs (2nd edn).
Jaypee Brothers: New Delhi, 2000;618-23.

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Section IV: Retina

44

Diabetic Retinopathy
Current Concepts and Recent Advances
Ashish Mahobia, Manish Nagpal, PN Nagpal, Kamal Nagpal, Sandeep Arora

INTRODUCTION

INTRODUCTION

PATHOGENESIS

Diabetes mellitus (DM) is a major medical problem throughout the world.


WHO estimates 135 million diabetics worldwide, which by year 2025 will
increase to 300 million. Diabetic retinopathy is one of the major community
health problems after cataract in India. There are some 18 million diabetics
in India. Around 60 percent of them will develop retinopathy.
1. Type I diabetes (insulin-dependent diabetes mellitus, IDDM)This type of
diabetes is usually diagnosed before the age of 40, 10- 15 percent of the
diabetic population have type I diabetes. Between 3-6 percent of siblings
of patients with type I diabetes will also develop diabetes. These patients
experience a high incidence of severe ocular complications and are more
likely to develop systemic problems during their lifetime. It has an
abrupt onset and is due to insulinopenia, thus the patient needs external
insulin.They are more prone to ketosis.
2. Type II diabetes (non-insulin-dependent diabetes mellitus NIDDM)
Majority of diabetic patients, however, have type II diabetes (85-90
percent). Usually it is diagnosed after the age of 40. These patients may
or may not be treated with insulin. Patients with type II diabetes make
up the majority of clinical cases with diabetic eye disease because of
their overall larger numbers.
Ophthalmic complications of diabetes include diabetic retinopathy,
corneal abnormalities, glaucoma, iris neovascularisation, cataracts, and
neuropathies. However, the most common and potentially most blinding
of these is diabetic retinopathy, which is a leading cause of blindness in
people aged 24-75 years.
Blindness usually results from non-resolving vitreous hemorrhage,
traction retinal detachment, or diabetic macular edema.The advent of
panretinal laser photocoagulation for the treatment of proliferative diabetic
retinopathy, and the findings of the Diabetic Retinopathy Study (DRS),1-14
the Early Treatment Diabetic Retinopathy Study (ETDRS),15-18 the Diabetic
Retinopathy Vitrectomy Study (DRVS),19-23 and the Diabetes Control and
Complications Trial (DCCT),24-26 has provided valuable insights into the
understanding and management of diabetic retinopathy and thus helped
tremendously in preventing and treating this disease. However, despite
all these recent advances, we are still unable to prevent its onset, and have
no cure for it. There is still much to learn about diabetic retinopathy.

CLASSIFICATIONS OF DIABETIC
RETINOPATHY
EPIDEMIOLOGY
RISK FACTORS FOR DIABETIC
RETINOPATHY
DIFFERENTIAL DIAGNOSIS
MANAGEMENT
PROGNOSIS
RECENT ADVANCES IN DIABETIC
RETINOPATHY MANAGEMENT

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 413


Table 44.1: Commonly used abbreviations
Abbreviation

Terms

DR

Diabetic retinopathy

FA

Fluorescein angiography

NPDR

Non-proliferative diabetic retinopathy

PDR

Proliferative diabetic retinopathy

H/Ma

Hemorrhages and/or micro aneurysms

HE

Hard exudates

SE or CWS

Soft exudates (cotton-wool spots)

VB

Venous beading

IRMA

Intraretinal microvascular abnormalities

NVD

New vessels on or within 1 disc diameter (DD) of disc margin

NVE

New vessels elsewhere in the retina outside of disc and 1DD from disc margin

SVL

Severe visual loss: visual acuity <5 /200 at two consecutive completed 4-month
follow up visits

MVL

Moderate visual loss: a doubling of visual angle (e.g. 20/40 to 20/80) at two
consecutive completed 4 months follow ups

CSME

Clinically significant macular edema

DM

Diabetes mellitus

IDDM

Insulin-dependent diabetes mellitus

NIDDM

Non-insulin-dependent diabetes mellitus

DRS

Diabetic retinopathy study

ETDRS

Early treatment diabetic retinopathy study

DRVS

Diabetic retinopathy vitrectomy study

DCCT

Diabetes control and complications trial

NADH

Reduced nicotinamide adenine dinucleotide

NAD

Nicotinamide adenine dinucleotide

PVD

Posterior vitreous detachments

PATHOGENESIS
The exact mechanism by which diabetes causes retinopathy is still not clear, but many theories have been put
forward to get a some understanding of the pathogenesis
and the course of disease. It has been postulated that
hyperglycemia in diabetes may cause deleterious effects
through mainly these mechanisms.
1. Aldose reductase pathway: With elevated levels of
glucose in the cells, some of the glucose is shifted from
glycolyitc pathway to polyol pathway. Glucose is
converted to sorbitol by aldose reductase.27 Sorbitol
can be metabolized by sorbitol dehydrogenase into
fructose with the production of NADH, but the rate
of conversion of sorbitol is relatively slow, resulting
in a cellular accumulation of sorbitol, as sorbitol does
not diffuse across cells membranes.27,28 Thus cellular

damage can occur as a result of an increased osmotic


stress. Such is the case in the lens of the eye where
accumulation of sorbitol has been implicated in the
development of cataracts in diabetes.29 In addition
aldose reductase requires NADPH for its functioning.
Hence reduction of NADPH reduces its amount for
the use of nitric oxide synthesis, so the level of nitric
oxide decreases, leading to deceased blood flow and
ischemia.
2. Decreased 2, 3 DPG level: Hypoxia is a very important
factor in the development and progression of diabetic
retinopathy. On molecular level it is explained by
the decreased levels of 2, 3 di-phosphoglycerate (2, 3
DPG) in the erythrocytes. This leads to decreased
oxygen supply to the tissues leading to hypoxia.
3. Vasoproliferative factors: Michaelson in 1948 had first
given the hypothesis of an X-factor which is

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Section IV: Retina

secreted from human retina in response to ischemia,


and which stimulated neovascularization. His
hypothesis turned out to be true and at present several
growth factors have been discovered which stimulate
neovascularization. Most important of these are FGF2 (Fibroblastic growth factor 2 or basic FGF) and
VEGF (Vascular endothelial growth factor). Both of
these have also reported to be synergetic in angiogenesis.29 Also there is up regulation of these factors
by hypoxia,30 evidenced by a higher level, of these
growth factors in the vitrectomised samples in cases
of PDR.31
4. Growth hormone: Growth hormone appears to play a
causative role in the development and progression
of diabetic retinopathy. Impaired glucose metabolism
promotes the release of growth hormone, which in
turn increases fibrinogen and alpha-2 globin level.
This causes hyperaggregation of erythrocytes and
platelets, leading to slugging and resistance of flow
of blood. It was noted that diabetic retinopathy was
reversed in women who had postpartum hemorrhagic necrosis of the pituitary gland (Sheehan
syndrome). This led to the controversial practice of
pituitary ablation to treat or prevent diabetic retinopathy in the 1950s.
5. Prostaglandins: PGI-2 (prostacyclin ) is a potent platelet
aggregation inhibitor and TXA-2 (thromboxane) is a
platelet degranulation and aggregation promoter and
vasoconstrictor. Loss of the normal balance between
these two substance is likely to play a role in the
pathogenesis of diabetic retinopathy.
6. Other possible mechanisms can be:
a. Alteration of the expression of one or many genes
due to hyperglycemia, leading to increased
amounts of certain gene products that can adversely affect cellular functioning.
b. Binding of sugar, non-enzymatically to proteins,
leading to formation of AGE (advanced glycation
end products, e.g. Total glycated hemoglobin),
these products then cause harm to the cellular
metabolism.32
c. Elevated levels of DAG (Di-acyl glycerol) and
protein kinase C (PKC). Elevated levels of these
were associated with decreased retinal flow as
measured by fluorescein angiography.33
d. Increased oxidative stress due to chronic hyperglycemia may lead to formation of an excess of
toxic end products of oxidation, including
peroxides, super-oxides, and oxygen free radicals.
The importance of this hypothesis lies in the fact
that these effects, if proved, can be altered with
the use of anti-oxidants.34

Microscopic Changes
The variety of hematologic abnormalities are seen in
diabetes, such as
a. Increased erythrocyte aggregation.
b. Decreased RBC deformability
c. Increased platelet aggregation, adhesion and life span
d. Abnormal serum lipids
e. Abnormalities in serum and whole blood viscosity,
defective fibrinolysis.
All these predispose to sluggish circulation, endothelial damage and thickening (up to as much as 5 times),
and focal capillary occlusion. This leads to retinal
ischemia, which in turn contributes to the development
of diabetic retinopathy.35-37
CLASSIFICATIONS OF DIABETIC RETINOPATHY
Although there are more than 13 classifications till date
on Diabetic retinopathy.The most accepted are being
mentioned.
.Clinical classification of diabetic retinopathy
1. Non-proliferative diabetic retinopathy (also known
as Background DR)
2. Pre-proliferative diabetic retinopathy
3. Proliferative diabetic retinopathy
4. Maculopathy
a. Focal
b. Diffuse
c. Ischemic
d. Mixed
5. Advanced diabetic disease:
a. Persistent new vessels,
b. Tractional retinal detachment,
c. Neovascular glaucoma.
6. End stage diabetic retinopathy/Burnt out stage.
Clinical (ophthalmologist oriented) classification of diabetic
retinopathy:
Patient may present to the ophthalmologist in the following four ways of visual loss. And depending on the
presentation the management is required.
1. Diabetic maculopathy.
2. Vitreous hemorrhage.
3. Tractional retinal detachment.
4. Involuted diabetic retinopathy.
But the recent studies has given the following classification, which not only helps in understanding the
disease but also has prognostic importance and helps in
deciding the timing and modalities of treatment.
The current most accepted classification (given by ETDRS):
1. Non-proliferative diabetic retinopathy (NPDR)
A. Mild NPDR

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 415


2. Hard exudates with thickening of the adjacent retina
located < 500 m from the center of the macula or
3. A zone of retinal thickening, 1 DD or larger in size
located < 1 DD from the center of the macula.
EPIDEMIOLOGY

Fig. 44.1: CSME with extensive hard exudates

At least one microaneurysm


Definition not met for B, C, D, E or F
B. Moderate NPDR
Hemorrhages and/or MA, > standard photo 2A
Soft exudates, venous beading, and IRMA definitely present
Definition not met for C, D, E or F
C. Severe NPDR (The 4-2-1 rule)
H/Ma > standard photo 2 A in all 4 quadrants
VB (venous beading) in two or more quadrants
IRMA > standard photo 8A in at least one
quadrant
D. Very severe NPDR
Any two or more of C above
Definition not met for E or F
2. Proliferative diabetic retinopathy (PDR)
Composed of:
1. NVD or NVE
2. Preretinal or vitreous hemorrhage
3. Fibrous tissue proliferation
E. Early PDR
New vessels
Definition not met for F
F. High-risk PDR
1. NVD > 1/3-1/2 DA or
2. NVD and vitreous or preretinal hemorrhage
or
3. NVE > 1/2 DA and preretinal or vitreous
hemorrhage
Clinically significant diabetic macular edema
1. Thickening of the retina located < 500 m from the
center of the macula or

In the US approximately 16 million Americans have


diabetes, with 50 percent of them not even aware that
they have it. Of those that know, only one half receive
appropriate eye care. Thus, it is not surprising that
diabetic retinopathy is the leading cause of new blindness
in persons aged 25-74 years in the US, responsible for
more than 8000 cases of new blindness each year. In UK,
the incidence of type II diabetes is 1 percent and that of
type I is 1 per 1000. This means that diabetes is responsible for 12 percent of blindness; the rate is even higher
among certain ethnic groups. True statistics are now
available in our country but it is believed that it is soon
likely to become a major public health menance.
Sex Predilection
There is a greater risk of development of PDR in males
suffering from type I diabetes than females. The incidence
of type II diabetes is higher in females, though the rates
of development of retinopathy do not differ. Patients with
type I diabetes (specially males) have a high risk of
developing PDR, maculopathy being less common as
opposed to those with type II diabetes who have a higher
incidence.
Non-proliferative Diabetic Retinopathy
This is the earliest manifestation of diabetic retinopathy.
It is characterized by:
Microaneurysms
These are the earliest detectable signs of diabetic retinopathy which appear as red dots scattered all over the
fundus. Size varies from 20-100 microns. May appear
yellowish in time as endothelial cells proliferate and
produce basement membrane and also as fibrin and RBC
accumulates in the microaneurysm lumen. Mechanisms
of microaneurysm formation is unknown. Possible
etiologies are weakness of capillary wall (loss of pericytes), release of vasoproliferative factor with endothelial
cells proliferations, abnormalities of adjacent retina and
increased intraluminal pressure.38-40 But we strongly feel
that microaneurysms in majority of the situations are new
vessels in their budding stage and their formation is an

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active phenomena and not a passive phemomenon (as


believed by many). But studies have shown that the
earliest change of DM, even before the development of
early microscopic changes in diabetic retinopathy, is the
decrease in retinal blood flow.41-44 The auto-regulation
of retinal blood flow is significantly impaired even in
diabetic patients with no diabetic retinopathy.45,46 This
impairment in retinal auto-regulation may be linked to
diabetes-associated loss in pericyte function.47,48 Normal
ratio between retinal capillary pericytes and endothelial
cells is 1:1, which is altered in diabetic retinopathy.
Although the exact changes in retinal physiology during
early stages of diabetes remain controversial, it is generally accepted that the measurements of retinal function,
such as retinal blood flow or retinal autoregulation, can
provide a quantitative assessment of retinal status and
subsequent risk for developing retinopathy.
Retinal Hemorrhages
Ruptured microaneurysms (MA) result in retinal hemorrhages either superficially (flame-shaped hemorrhages)
or in deeper layers of the retina (blot and dot hemorrhages). Dot-blot hemorrhages appear similar to microaneurysms if they are small; fluorescein angiography
may be needed to distinguish between the two.
Hard Exudates and Retinal Edema
Increased permeability of vessels results in leakage of
fluid and proteinaceous material, which clinically
appears as retinal thickening and hard exudates. While
the damaged vessels are leaking plasma and oxygen for
the ischemic tissues, the adhesion of posterior hyaloid
to internal limiting membrane (ILM), specially around
macula, comes in the way of the supply of nutrients to
the ischemic zones. The plasma tries to spread itself by
cleavaging the posterior hyaloid from ILM (by chemical
and mechanical means).This happens easily around the
arcades and equator where the adhesion is not so strong.
It does not happen easily and completely within the
arcades and around macula because the vitreous is
relatively firmly adherent (for various reasons). The
plasma permeating out of new vessels finds it difficult
to reach the ischemic region and tries to travel around
the cellular structure of retina in the extracellular
(intercellular) space.
Diabetic Maculopathy
Diabetic macular disease may be present at any level of
retinopathy and alters the structure of the macula in any

of the following manners, significantly affecting its


function. Clinically, macular edema is retinal thickening
within 2 disc diameters of the center of the macula (not
fluorescein leakage without thickening). Retinal thickening or hard exudates with adjacent retinal thickening that
threaten or involve the center of the macula is considered
to be clinically significant.
Diabetic maculopathy can also be of one following types:
1. Diffuse: Characterized by wide spread leakage from
the capillaries, IRMAs, and microaneurysms.
Clinically, there is retinal thickening, loss of foveal
reflex and at a later stage development of cystoid
macular edema.
2. Focal: Localized leaks occur from a microaneurysm,
and hence hard exudates get deposited at the junction
of ischemic and non-ischemic retina. Laser photocoagulation leads to visual improvement.
3. Ischemic: Occurs as a result of non-perfusion of prefoveal capillaries with or without intraretinal fluid
accumulation.This type of maculopathy may exist
with any other type, but its recognition is very
important. Macula appears dull clinically. FA confirms the diagnosis which shows a large foveal
avascular zone (FAZ) or a large area of non-perfusion.
This condition is essentially untreatable.
4. Mixed: Two or more of the above mentioned types
may co-exist.
Other mechanism of maculopathy in diabetic retinopathy is:
1. Traction in the macula by fibrous tissue proliferation
causing dragging of the retinal tissue, surface wrinkling, or detachment of the macula.
2. Retinoschisis (secondary/tractional), involving the
fovea.
3. Intraretinal or preretinal hemorrhage at the macula.
4. Lamellar or full-thickness retinal hole formation.
5. Combination of the above.
Cotton-Wool Spots (CWS)
As the disease progresses, eventual closure of retinal
capillaries occur, leading to hypoxia. Infarction of the
nerve fiber layer leads to the formation of cotton-wool
spots (erroneously called as soft exudates) with
associated stasis in axoplasmic flow. Cotton-wool spots
occur more commonly where the nerve fiber layer is
thickest-around the optic nerve and along temporal
arcades. Once the cotton-wool spots resolve it leads to
atrophy of the nerve fibers and ganglion cells known as
the depression sign. FA shows no capillary perfusion.
CWS are frequently bordered by microaneurysms and
vascular hyperpermeability.

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 417


Venous Caliber Abnormalities
More extensive retinal hypoxia triggers compensatory
mechanisms within the eye to provide enough oxygen
to tissues. Venous caliber abnormalities, such as venous
beading, loops, and dilation signify increasing hypoxia
and almost always are seen bordering the areas of
capillary non-perfusion.
Intraretinal Microvascular Abnormalities (IRMA)
These represent either new vessel growth or remodeling
of preexisting vessels through endothelial cell proliferation within the retinal tissues to act as shunts through
areas of non-perfusion. Extensive IRMA appear like
NVEs, but unlike NVE they dont show, wheel like
networks, extension across major vessels of underlying
retina, and associated fibrous growth. Also on biomicroscopy it appears flat as compared to NVEs which are
mostly elevated. Because of their timely association with
retinal neovascularisation, they are considered an
important indicator of impending PDR.
Proliferative Diabetic Retinopathy
Further increase in retinal ischemia49-50 triggers the production of vasoproliferative factors that stimulate new
vessel formation. Normally there is equilibrium between
the vasoinhibitory and vasoproliferative factors. The
important growth factors that have been discovered are
Insulin like growth factor, Fibroblastic growth factors,
Platelet derived growth factors, Nerve growth factors and
recently discovered VEGF(Vascular endothelial growth
factor). The extracellular matrix is broken down first by
proteases, and new vessels arising mainly from the retinal
venules penetrate the internal limiting membrane and
form capillary networks between the inner surface of the
retina and the posterior hyaloid face.. Neovascularisation
most commonly is observed at the borders of perfused
and non-perfused retina and most commonly occur along
the vascular arcades (temporal arcade more common),
and at the optic nerve head. Eventually most diabetic
persons will develop at least some degree of PDR, with
an incidence approaching 100 percent after 15 years of
disease.51The new vessels break through and grow along
the surface of the retina and into the scaffold of the
posterior hyaloid face. By themselves, these vessels rarely
cause visual compromise. However, they are fragile and
highly permeable. The hemorrhage into subhyaloid
space and seepage into vitreous occurs for two reasons.
It is firstly due to the remarkable congestion on the
venous side of circulation and giving way of venules

under the pressure of stagnating circulation. It is usually


dark red blood, suggestive of venous origin. The vein
tries to accommodate more blood by dilatation, by
looping and by sausage like formations. Treatment with
scatter (pan retinal) photocoagulation may cause these
abnormal veins to become less dilated and more regular.
The reason for venous congestion is quite understandable, extensive areas of microvascular occlusions do not
allow the pulse pressure to push the blood in veins. The
pressure from arterial side to venous side gets dissipated
and remarkably reduced due to loss of connection
between arterial and venous side in the capillary drop
out areas. Another way the hemorrhage can occur is due
to vitreoneovascular adhesions, which come under strain
and stretch (these new vessels are ill-developed and
fragile), with the movement of posterior hyaloid {especially if partial posterior vitreous detachment (PVD) is
present} during the normal movements of eyes (and more
so if they are jerky or forceful). Other factors, i.e. postural
changes, blood pressure fluctuations (including Valsalva
maneuver and certain exercises) and the sudden occurrence of PVD can also cause bleeding into vitreous. If a
PVD is already present, small raspberry like vascular
complexes develop called as Abortive Neovascular Out
Growths (ANVOs).
These new blood vessels initially are associated with
a small amount of fibroglial tissue formation. However,
as the density of the neovascular frond increases, the
degree of fibrous tissue formation also increases. As the
vitreous contracts, it may exert tractional forces on the
retina via these fibroglial connections. Traction may cause
retinal edema, retinal heterotropia, retinal tractional
detachment and tractional retinoschisis. The traction can
also cause retinal tears or holes resulting in TRRD
(Tractional Rhegmatongeous Retinal Detachments). If a
retinal hole is discovered prior to significant retinal
detachment, and there is relatively little tractional or
subretinal fluid, then it is sometimes possible to seal such
a hole with surrounding laser photocoagulation or
cryotherapy. However, if the hole is large, and significant
traction still persists, then relief of traction, re-approximation of the retina is required surgically. But one should
not forget that a retinal detachment or a vitreous
hemorrhage can also be because of only a retinal hole,
and may not be associated with diabetic pathology.
In later stages, the vessels may regress leaving only
networks of avascular fibrous tissue adherent to both the
retina and the posterior hyaloid face, this is known as
the burnt out or involutional stage.52-54
In severe cases, proliferation of new blood vessels
may also occur in the iris and in the anterior chamber

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Section IV: Retina

angle. If the vessels obstruct the aqueous fluid outflow


facilities of the eye, they can lead to neovascular
glaucoma, a severe sight threatening disorder.
RISK FACTORS FOR DIABETIC RETINOPATHY
1. Duration of the diabetes: In patients with type I
diabetes, no clinically significant retinopathy can
be seen in the first 5 years after the initial diagnosis
of diabetes is made. After 10-15 years, 25-50 percent
of patients show some signs of retinopathy. This
prevalence increases to 75-95 percent after 15 years
and approaches 100 percent after 30 years of
diabetes. In patients with type II diabetes, incidence
of diabetic retinopathy increases with the duration
of the disease, 23 percent after 11-13 years, 41
percent after 14-16 years, and 60 percent after 16
years, have NPDR.
2. Glucose control: With the development of home
blood glucose monitoring and with the availability
of glycosylated hemoglobin testing (which shows
average blood glucose level over the last 3-4 wks),
it is now possible of closely and correctly monitor
blood glucose level in patients. Some retrospective
studies and mainly the DCCT study, has demonstrated that intensive glucose control reduced the
incidence and the progression of diabetic retinopathy in patients with insulin-dependent diabetes
mellitus (IDDM). Although no similar trials for noninsulin dependent diabetes mellitus (NIDDM)
patients have been completed, it has been suggested
by the American Diabetes Association (ADA) that
glycosylated hemoglobin levels less than 7 percent
should be the goal in all patients to prevent or slow
down the onset of diabetes-related complications.
Some interesting studies have confirmed that
there is a short term worsening of Diabetic retinopathy55-56 if intensive glucose level control is done,
probably related to increase levels of insulin like
growth factors and other growth factors secretion.57
This is of little clinical importance if the retinopathy
is mild, but can be troublesome if the retinopathy
is moderate to severe.
3. Puberty: Diabetic retinopathy is known to worsen
at the onset of puberty. Exact cause of such a
phenomenon is not known, but a hormonal change
is though to be responsible. This is probably linked
to the increased serum level of IGF-I (Insulin like
growth factor-I), seen in such florid cases of diabetic
retinopathy during puberty.
4. Renal disease: Renal disease, as evidenced by proteinuria, and elevated BUN/creatinine levels, is an

5.

6.

7.

8.

9.

excellent predictor of the presence of retinopathy.58


This probably is due to the fact that both conditions
are caused by DM related micro angiopathies, such
that the presence and severity of one reflects that
of the other. Aggressive management of renal
disease is indicated to avoid nephropathy, which
may increase risk of progression of diabetic
retinopathy and of neovascular glaucoma
Systemic hypertension: Among factors that may cause
a worsening of diabetic retinopathy, hypertension
most commonly has been a subject of investigation.59,60 But it is important to know whether the
association of hypertension with diabetes is
primary or secondary (due to diabetic nephropathy). Independently, hypertension also may
complicate diabetes in that it may result in hypertensive retinal vascular changes superimposed on
the preexisting diabetic retinopathy further compromising retinal blood flow, UK prospective
diabetes study group (UKPDS)61-63 has shown that
a tight control of blood pressure causes a significant
decrease in the risk of deterioration of diabetic
retinopathy.
Elevated serum lipids: It has been suggested that the
proper management of hyperlipidemia may result
in less retinal vessel leakage and hard exudate
formation.64-65 The exact mechanism behind this is
not very clear.
Pregnancy: Pregnancy is known to cause worsening
of Diabetic retinopathy, although there are controversies and some believe that it has no effect in the
progression of diabetic retinopathy. Pregnant
women without any diabetic retinopathy run a 10
percent risk of developing NPDR during their
pregnancy. Of those with preexisting NPDR, 4
percent progress to the proliferative type.
Joint contractures: Association of retinopathy and
contractures has been established. Routine eye
examination is advised in patients with joint
contractures, also proper care of joint contractures
is important.
Cardiovascular disease: Increased risk of peripheral
vascular disease, particularly coronary vascular
disease, is often associated with an increase in the
attenuation and arteriosclerotic closure of the
arterial system of the retina. A decreased risk of
hemorrhage into the vitreous may result. Aggressive management of cardiovascular risk factors
could theoretically remove some of the ischemic
response from retina. Also systemic morbidity and
mortality might decrease.

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 419


10. Ocular factors: Becker had first noted that glaucoma
reduces the severity of diabetic retinopathy. This,
probably is related to the loss of retinal vascular
perfusion and less vascular demand of thinned out
atrophic retina. Myopia also reduces the severity
of diabetic retinopathy.66 Also it was noted that
Diabetic retinopathy is less pronounced in cases
with optic atrophy and chorio-retinal scarring.67 It
was this interesting finding led to the concept of
pan retinal photocoagulation treatment started by
Meyer-schwickerath.68
Ocular surgery seems to aggravate diabetic
retinopathy. A routine extra capsular cataract
surgery (and intra capsular too) is known to worsen
the macular edema in diabetics. Hence a focal/grid
laser should be considered in diabetics with CSME
planning to undergo cataract surgery. Also the
diabetic macular edema may be super added with
cystoid macular edema following cataract surgery,
hence such patients can be treated pre-operatively
with topical and oral non-steroidal anti inflammatory agents and steroids if required, also prolonged dose should be given postoperatively.
Intracapsular or an extracapsular surgery
with a posterior capsular dehiscence, allows diffusion of neovascular growth factors (in a case of
PDR) into anterior chamber, hence more risk of
neovascularisation of anterior chamber. It has been
found that following the occurrence of endophthalmitis which was well treated, the maculopathy
worsened, this is probably related to an additional
stress on macula (due to various inflammatory
modulators and mechanical vitreomacular relationships). These situations create an additional
demand from the retinal (especially macular) tissue
and thereby create an element of active ischemia.
Here the demand of tissue increases and surpasses
the normal supply. In the normal circumstances, the
ischemia is passive in diabetic retinopathy. There
is only reduction in supply due to microvascular
occlusions.
11. Genetic factors: Several studies have explored the
possibility of a HLA association with diabetes. In
particular HLA-D3 and HLA-D4 have been
extensively studied. Although some studies have
reported positive association with HLA-DR3 and
DR4,69 others have failed to find any such relation.70
Results till now are dubious, and there is a considerable scope in further investigation of genetic
factors related to the pathogenesis of Diabetic
retinopathy.

Fig. 44.2: CSME as seen on fluorescein angiography

DIFFERENTIAL DIAGNOSIS

Branch Retinal Vein Occlusion


Central Retinal Vein Occlusion
Ocular Ischemic Syndrome
Radiation Retinopathy
Hemoglobinopathies
Sickle Cell Disease.

Fluorescein Angiography
Fluorescein angiography (FA) is an invaluable adjunct
in the diagnosis and management of diabetic retinopathy.
1. In Preproliferative diabetic retinopathy:
As a baseline investigation for follow up
Maculopathy- to know cause of unexplained
visual loss.
In CSME - to know extent of edema, ischemia, and
its location
To know other areas of capillary non-perfusion
(ischemia) in the fundus.
To detect IRMAs
2. Proliferative diabetic retinopathy:
To detect NVE, NVD which are not clinically
evident.
To know associated maculopathy/unexplained
visual loss.
To confirm clinical findings.
To detect residual or recurrent proliferations after
laser treatment.
Angiographic Risk Factors for
Progression of NPDR to PDR
Analysis of data from the untreated (deferred) eyes in
the ETDRS indicates that the following lesions are

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Section IV: Retina

independently related to outcome: (1) fluorescein leakage, (2) capillary loss on FA, (3) capillary dilatation on
FA, and (4) the color fundus photographic risk factors
(a) IRMA, (b) VB and (c) H/Ma.
Although FA abnormalities provide additional information, the color fundus photographic grading also
gives the same prognostic results.The color fundus
photograph risk factors are IRMAs, venous caliber
changes, hemorrhages and microaneurysms. Hard and
soft exudates have an inverse relationship to the progression of diabetic retinopathy. Therefore, the increase
in power to predict progression from NPDR to PDR by
FA is not of significant clinical importance to warrant a
routine FA.
MANAGEMENT
Clinical Trials of Diabetic Retinopathy
Three nationwide randomized clinical trials have largely
determined the strategies for appropriate clinical
management of patients with diabetic retinopathy.
The DRS (Table 44.2) conclusively demonstrated that
scatter (panretinal) photocoagulation significantly
reduces the risk of SVL from proliferative diabetic retinopathy, particularly when high-risk PDR is present.
Although DRS demonstrated the value of panretinal laser
photocoagulation for eyes with high-risk PDR, guidelines
for the timing of panretinal laser photocoagulation prior
to the development of high-risk proliferative diabetic
retinopathy were not clearly delineated.
The ETDRS (Table 44.3) provided valuable information concerning the timing of scatter (panretinal) laser
surgery for advancing diabetic retinopathy and conclusively demonstrated that focal/grid photocoagulation for
CSME reduces the risk of MVL by 50 percent or more.
Furthermore, the ETDRS demonstrated that both early
scatter (panretinal) laser surgery (before high-risk PDR)
and deferral of treatment until and as soon as high-risk
PDR developed, are effective in reducing the risk of SVL.
Scatter laser surgery, therefore, should be considered as
an eye approaches the high-risk stage and usually
should not be delayed if the eye has reached the highrisk proliferative stage. But in patients who cannot
follow up on a regular basis, PRP at the time of development of severe NPDR is reasonable.It also showed that a
partial scatter treatment (400-650 burns) is not an
alternative to full scatter treatment and was not helpful
in reducing the progression and aspirin did not affect
the progression of Diabetic retinopathy or cataract
formation. The ETDRS also found that 650 mg of aspirin
daily did not offer any benefit in preventing the

Table 44.2: Diabetic retinopathy study (DRS)


Major Eligibility Criteria
Visual acuity >20/100 in each eye.
PDR in at least one eye or severe NPDR in both eye.
Both eyes suitable for photocoagulation.
Major Design Features
One eye of each patient was assigned randomly to photocoagulation (scatter [panretinal], local [direct confluent
treatment of surface new vessels], and focal [for macular
edema] as appropriate). The other eye was assigned to
follow-up without photocoagulation.
The eye assigned to treatment was then randomly
assigned to argon laser or xenon arc photocoagulation.
Major Conclusions
Photocoagulation reduced risk of severe visual loss by
50 percent or more (SVL = VA <5/200 at two consecutively
completed 4-month follow-up visits).
Modest risks of decrease in visual acuity (usually only
one line) and constriction of visual field (risks greater
than xenon than argon).
Treatment benefit outweighs risks for eyes with highrisk PDR (50% 5-year rate of SVL in such eyes without
treatment was reduced to 20 percent by treatment).

Table 44.3: Early treatment diabetic


retinopathy study (ETDRS)*
Major Eligibility Criteria
Visual acuity > 20 / 40 (> 20/400, if reduction caused by
macular edema).
Mild NPDR to non-high risk PDR, with or without
macular edema.
Both eyes suitable for photocoagulation.
Major Design Features
One eye of each patient assigned randomly to early
photocoagulation and other to deferral (careful followup and photocoagulation if high-risk PDR develops).
Patients assigned randomly to aspirin or placebo.
Major Conclusions
Focal photocoagulation (direct laser for focal leaks and
grid laser for diffuse leaks) leads to reduced risk of
moderate visual loss (doubling of the visual angle) by
50 percent or more, and increased the chance of small
improvement in visual acuity.
Both early scatter with or without focal photocoagulation and deferral were followed by low rates of severe
visual loss (5-year rates in deferral subgroups were 2 to
10%, in early photocoagulation groups 2 to 6%).
Focal photocoagulation should be considered for eyes
with CSME.
Scatter photocoagulation is not indicated for mild to
moderate NPDR, but should be considered as retinopathy approaches the high risk stage, and usually should
not be delayed when the high-risk stage is present.

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Table 44.4: Diabetic retinopathy vitrectomy study (DRVS)
A. Recent Severe Vitreous Hemorrhage (Group H)
Major Eligibility Criteria
Visual acuity (VA) < 5 / 200.
Vitreous hemorrhage (VH) consistent with VA,
duration 1-6 months.Macula attached by ultrasound.
Major Design Features
In most patients, only one eye is eligible. Eligible
eye(s) assigned randomly to early vitrectomy or
conventional management (vitrectomy if center of
macula detaches or if VH persists for 1 year, photocoagulation as needed and as possible).
Major Conclusions
Chance of recovery of VA >10/20 increased by early
vitrectomy, at least in patients with type 1 diabetes,
who were younger and had more severe PDR (in most
severe PDR group, >10/20 at 4 years in 50 percent of
early vitrectomy group vs. 12 percent in conventional
management group).
B. Very Severe PDR with Useful Vision (Group NR)
Major Eligibility Criteria
Visual acuity >100/200
Center of macula attached.
Extensive active neovascular or fibrovascular proliferation.
Major Design Features
Same as group H (except conventional management
included vitrectomy after a 6-month waiting period
in eyes that developed severe VH).
Major Conclusions
Chance of VA >10/20 increased by early vitrectomy,
at least for eyes with very severe new vessels.

progression of diabetic retinopathy. Additionally, aspirin


was not observed to influence the incidence of vitreous
hemorrhage in patients who required it for cardiovascular disease (CVD) or other conditions.
The DRVS (Table 44.4) provided guidelines for the
most opportune time to consider vitrectomy surgery for
type I and type II DM patients who suffered from vitreous
hemorrhage or from severe PDR in eyes with useful
vision.Early vitrectomy for eyes with recent severe
vitreous hemorrhage and visual acuity less than 5/200
was beneficial, especially for patients with type I DM.
Furthermore, the chance of achieving visual acuity 10/
20 or better was increased by early vitrectomy in eyes
with severe proliferating neovascular retinopathy, again
specially for patients with type I DM.But the present
modern techniques of microsurgery probably have
improved results over the results from DRVS, although
no randomized trial has been performed. DRVS was

performed before the present advanced vitreoretinal


techniques were developed (including delamination),
also endo laser and indirect laser delivery system was
not available.With these advances the surgical results and
prognosis have certainly improved in PDR.
The DCCT enrolled 1441 patients nationwide with
insulin-dependent diabetes mellitus and minimal or no
diabetic retinopathy. Two study questions were investigated:
1. Primary prevention: Does intensive insulin therapy
prevent development of diabetic retinopathy and
other diabetic complications compared with conventional therapy?
2. Secondary intervention: Does intensive therapy affect
the progression of diabetic retinopathy and other
diabetic complications compared with conventional
therapy?
Patients assigned to intensive therapy used an insulin
pump or took three or more injections of insulin each
day. Frequent self-monitoring of blood glucose levels,
Table 44.5: Diabetes control and
complications trial (DCCT)
Major Eligibility Criteria
Age: 13 39 Years
Primary Prevention:
Duration - insulin-dependent diabetes mellitus;
1-5 years.
No diabetic retinopathy
Secondary intervention:
Duration - insulin-dependent diabetes mellitus;
1-15 years.
Minimal non-proliferative diabetic retinopathy.
Major Design Features
Patients were randomly assigned to conventional
insulin therapy or intensive therapy.
Study questions:
Primary Prevention: Does intensive therapy prevent
the development of retinopathy and other complications compared with conventional therapy?
Secondary intervention: Will intensive therapy affect
the progression of retinopathy and other complications compared with conventional therapy?
Major Conclusions
Intensive therapy reduced clinically meaningful DR
by 35-74 percent; severe NPDR, PDR, and laser
treatment by 45 percent; and the first appearance of
any retinopathy by 27 percent.
Intensive therapy reduced the development of microalbuminuria by 35 percent, clinical proteinuria by 56
percent and clinical neuropathy by 60 percent.
Risk of intensive therapy included hypoglycemia,
catheter complications, weight gain, and ketoacidosis.

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hospitalization for the induction of therapy, strict adherence to meal plans, and frequent follow-up evaluations
were provided.The DCCT demonstrated that intensive
therapy reduced clinically meaningful DR by 35 to 74
percent; reduced the risk of severe non-proliferative
diabetic retinopathy (NPDR), PDR, and laser treatment
by 45 percent; and reduced the development of any DR
by 27 percent. Additionally, intensive therapy reduced
with development of microalbuminuria by 35 percent,
clinical proteinuria by 56 percent and clinical neuropathy
by 60 percent.
UKPDS (United Kingdom prospective diabetes study
group) Study:71 As DCCT studied the role of intensive
blood glucose control in type I diabetics, UKPDS studied
the same in type II diabetics. Results show that there was
a 21 percent reduction in the two step progression of
diabetic retinopathy and 25 percent reduction of the
need for laser photocoagulation.It also showed that tight
blood pressure control in diabetic patients with hypertension led to a 34 percent reduction in the progression
of diabetic retinopathy.
Medical Care
Non-Proliferative Diabetic Retinopathy
Glucose control The DCCT has found that intensive
glucose control in patients with IDDM has decreased the
incidence and progression of diabetic retinopathy.
Although no similar clinical trials for NIDDM exist, it
may be logical to assume that the same principles also
apply here. In fact, the American Diabetic Academy has
suggested that all diabetics (NIDDM and IDDM) should
strive to maintain glycosylated hemoglobin levels of less
than 7 percent to prevent or at the very least minimize
long-term complications of DM including diabetic
retinopathy.
Laser photocoagulation Pioneer of retinal photocoagulation therapy is Meyer-schwickerath, who developed
photocoagulation. In 1955 he treated his first 5 patients
of diabetic retinopathy with photocoagulation. This
involves directing a focused beam of high energy light
to create a coagulative response in the target tissue. The
advent of laser photocoagulation, provided a noninvasive treatment modality that has a relatively low
complication rate and a significant degree of success. The
following are the treatment guidelines.
Patients with mild or moderate NPDR generally are
not candidates for scatter (panretinal) laser surgery and
can be followed safety at 6 to 12 months intervals as
determined by the examiner.

The presence of macular edema, even with mild or


moderate degrees of NPDR, requires follow up in a
shorter period, and if CSME is present, focal/grid laser
treatment is advisable. Coincident medical problems or
pregnancy will influence the period of reevaluation. The
strategy for treating macular edema depends on the type
and extent of vessel leakage.
1. Focal treatment: If the edema is due to leakage of
specific microaneurysms, the leaking vessels are
treated directly with focal laser photocoagulation. A
spot size of 50-200 microns of 0.1 sec duration can be
used. The end point is whitening or darkening of the
micro aneurysm.
2. Grid treatment: In cases where the foci of leakage are
nonspecific or diffuse, a grid pattern of laser burns is
applied. Light to medium intensity burns (50-200
microns of 0.1 sec 0.5 sec) are placed 1 burn size apart
covering the affected area. Grid is not placed within
500 microns of the fovea or within 500 microns of the
optic disc. The main aim is to tickle the RPE cells and
stimulate the retinochoroidal pump to hasten absorption of fluid, and not to destroy the area.
3. Modified grid treatment: In this light intensity burns
(same as that in grid) are given only to focal areas of
leakages (red spots), and whole of the macular area
is not treated.
PROGNOSIS
The ETDRS has found that laser surgery for macular
edema reduces the incidence of moderate visual loss
(doubling of visual angle or roughly a 2-line visual loss)
from 30 percent to 15 percent over a 3-year period.
Favorable prognostic factors are:
Circinate exudates of recent onset
Well-defined leakage
Good perifoveal perfusion
Unfavorable prognostic factors are:
Diffuse edema/multiple leaks
Lipid deposition in the fovea
Macular ischemia
Cystoid macular edema
Preoperative vision of less than 20/200
Hypertension.
Further outpatient care: The frequency of follow-up care
is dictated primarily on the baseline stage of the
retinopathy and its rate of progression to PDR. Patients
are followed up after about 4 weeks and reviewed if any
obvious treatable area remains which was missed, or for
any recurrence. It is treated 4 months after the initial
treatment, confirming the lesions on an FA.

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 423

Fig. 44.3: Laser photocoaulation marks

Only 5 percent of patients with mild NPDR would


progress to PDR in 1 year and a 15 percent risk of
developing high-risk PDR, thus could be monitored
every 6-12 months.
12-27 percent of patients with moderated NPDR
would progress to PDR in 1 year; therefore, they
should be seen every 4-8 months.
52 percent of patients with severe NPDR (preproliferative stage) would progress to PDR in a year
and 60 percent develop high-risk PDR, thus followup care as frequent as 2-4 months is mandatory to
ensure prompt recognition and treatment.
Proliferative Diabetic Retinopathy
Panretinal photocoagulation This is the preferred form
of treatment for PDR.
Technique: This involves applying laser burns over the
entire retina sparing the central macular area. This may
be performed using a variety of delivery systems including the slit lamp, indirect ophthalmoscope, and Endo
Probe. Application starts in a circumference 500 microns
from the disc and 2 disc diameters from the fovea to wall
off the central retina. Moderate intensity burns of 200500 microns (gray-white burns) of 0.1 sec and 250270 mW power, are placed 1 spot size apart, except in
areas of neovascularization where the entire frond is
treated. This procedure is continued peripherally to
achieve approximately 1200-1600 applications over 2-3
sessions, about a week apart. Multiple episodes make it
easier to avoid retrobulbar anesthesia and, occasional
occurrence of choroidal effusion and consequent angle

closure glaucoma. There are chances that occurrence of


PVD during or more commonly after PRP, may lead to
hemorrhage into subhyaloid space or into vitreous, and
that is what we see in some cases following PRP. That is
why we recommend that lower half PRP should be done
first, whenever splitting the PRP treatment into stages.
An argon blue green or green laser (especially for macular
area), diode laser or double frequency YAG is also used.
No differences were found in the effectiveness of argon
versus krypton in the KARNS (Krypton Argon retinal
neovascularization) study.72 Also two small randomized
trials comparing Diode and Double frequency YAG lasers
gave similar results.73,74 Burns along the long ciliary
nerve might be painful under topical anesthesia. Alternatively one can use less power or less duration spots in
that area. Finally if patient is uncooperative, retrobulbar/
peribulbar anesthesia is the option.
On the basis of various studies including DRS and ETDRS
the following are the guidelines for photocoagulation therapy
in PDR:
Treatment should be promptly carried out in eyes
with PDR that have well established NVD and/or
vitreous or preretinal hemorrhage. Treatment is
particularly urgent in case of localized fresh hemorrhage, due to the risk of its dispersion, making any
further laser treatment impossible.
Whenever high risk characteristics are definitely
present, PRP should be carried out in spite of presence
of fibrous proliferation or tractional detachment
(TRD). Areas of fibrous proliferation and TRD should
be avoided, and treatment should be mild to moderate as there is a risk of extension of the localized TRD
into the macula. A combination of vitrectomy and
photocoagulation may be required in some patients.
Whenever neovascularization is seen in the anterior
chamber angle or in the iris, prompt PRP should be
done, irrespective of the presence of or absence of
high risk characteristics.
Eyes with changes of severe ischemia, i.e. extensive
retinal hemorrhages, capillary non-perfusion, severe
beading of veins prominent and multiple cotton-wool
spots also need early photocoagulation as there is a
risk of anterior segment neovascularization.
The criteria for treating severe PPDR or eyes with
NVE only without vitreous or preretinal hemorrhages
is less clearly defined. In cases NVE if active networks
are growing along upper temporal arcade or there is
extensive areas of PPDR, probably these eyes should
also receive treatment.
Eyes with burnt out retinopathy or showing regression of PDR should not be treated with photocoagulation. Small areas of NVE without associated

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Section IV: Retina

hemorrhages also need not be treated and can be kept


under observation only.
In eyes with PDR and macular edema, either focal or
grid treatment of macular edema, can be done first
followed about 4-6 weeks later by PRP.
If delay in treatment is undesirable, the ETDRS
protocol can be used combining focal treatment for
macular edema with PRP in the nasal quadrant at the
first sitting and adding PRP in other quadrants in the
subsequent sittings.
Consideration of systemic factors may influence the
decision to initiate treatment in patients with severe
PPDR or PDR without high risk characteristics. For
example, since PPDR/PDR is known to worsen in
pregnancy or after renal transplant it would be better
to initiate photocoagulation.
Local treatment is done for NVE in conjunction with
scatter laser, carried out by applying overlapping
moderate strong burns to produce a confluent area
of intense whitening of the retina between all the new
vessels. Following this strong burns can be given
directly to the NVE to cause total destruction.But
ETDRS study suggests that scatter treatment alone
should be done as an alternative to local treatment if
NVE is within 2DD of the centre of fovea, and
whenever a local treatment is expected to cause a
scarring larger than 2DD.
One should take care not treat over - hemorrhages,
fibroglial/ tractional bands (or else mild to moderate
burns is used, or anchoring photocoagulation is
done), collateral vessels and areas of retinal detachment.

High-risk PDR is characterized by any one or more of the


following lesions:
1. NVD approximately 1/4 to 1/3 disc area, or more in
size (i.e. greater than or equal to NVD in standard
photo 10A).
2. NVD less than disc area in size if fresh vitreous or
preretinal hemorrhage is present.
3. NVE greater than or equals to disc area in size if
fresh vitreous or preretinal hemorrhage is present.
Patients with macular edema and severe NPDR or
worse should be considered for focal treatment of
macular edema regardless of whether the macular edema
is clinically significant or not, since future need of scatter
laser photocoagulation is imminent. Subsequent scatter
photocoagulation may exacerbate macular edema, and
focal treatment 6-8 weeks prior to scatter photocoagulation may reduce this risk. If it is necessary to complete
both procedures at the same time, the PRP is applied
initially to the nasal third of the retina.

Fig. 44.4: PDR with FV proliferations, laser marks


and hemorrhages

Additional laser (augmentation) In about 25 percent of eyes


who undergo complete PRP for PDR, new vessels persist
or recur to justify additional treatment with laser. In this,
burns are placed between treatment scars, anterior to
them or posteriorly (sparing an area within 500 microns
of the centre of macula) or in the area of new vessel
formation or skip areas of treatment. If scars are very
closely situated, clear indications are necessary before
additional treatment is done, as it might lead to extensive
visual field loss.
The ETDRS guidelines for follow-up treatment after initial
PRP includes consideration of the following factors:
1. Change in new vessels since the last treatment.
2. Appearance of the new vessels (caliber, degree of
network formation, extent of accompanying fibrous
tissue).
3. Frequency and extent of vitreous hemorrhage.
4. Status of vitreous detachment.
5. Extent of photocoagulation scars.
6. Extent of tractional retinal detachment and fibrous
proliferation.
Additional photocoagulation is considered.
a. If new vessels appear active as suggested by presence
of tight networks of fibrous tissue and increase in size
since the last visit.
b. If the extent of new vessels is substantially greater
than it was at the time of initial treatment.
c. If recurrent vitreous or preretinal hemorrhages occur,
especially without any coincidental posterior vitreous
detachment.

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 425


d. If the previous photocoagulation scars are widely
spaced or there are skip areas.
Additional photocoagulation may be less urgent if,
a. The caliber of new vessels has decreased and fibrous
proliferations are developing.
b. There is a single episode of vitreous hemorrhage
coincident with a posterior vitreous detachment and
no recurrent hemorrhage thereafter.
c. There is extensive or almost complete posterior
vitreous detachment.
Mechanism of action of PRP The exact mechanism by
which PRP works is not entirely understood. We have
the following explanations as to how the Laser Photocoagulation alters the basic pathogenesis of diabetic
retinopathy and achieve the alleviating and regressive
effects.
1. Reduces demand and improves circulation.
2. Converts hypoxic areas to anoxic, hence reduces
forming of Neovascular Growth Factor (NVGF), and
helps formation of Neovascular Inhibitor Factor
(NVIF), thus reducing chances of bleeding.
3. Removes custom barrier of Pigment Epithelium (PE),
and hence increased diffusion of choroidal blood into
retina.
4. Causes posterior vitreous detachmentPhotocoagulation causes inflammatory edema in retinal tissue,
swell it up and push the posterior hyaloid off that
region. But the regression of inflammation and the
reduction of swelling of retina in the next 7-15 days
is not accompanied with posterior hyaloid returning
to the retina, hence a localized PVD results. This PVD
helps the movement of plasma proteins over the
surface of retina, and thereby regressing the CSMO.
5. Terrorization (Stress) like effect- It is hypothesised that
laser photocoagulation creates stress like condition
of cells, hence leads to more efficient working of
cellular metabolism, even in deprivated conditions.
Complications and side effects of scatter (panretinal) laser
photocoagulation
1. Field constriction and night blindness- Depends upon
extent of scatter treatment.
2. Foveal burn - Landmarks may be difficult to identify.
3. Macular edema- About 10 percent risk of mild visual
loss.
4. Foveal traction-Occurs with remission of PDR also
occurs with burns applied over blood.
5. Serous and/or choroidal detachment - Acute angle
closure glaucoma is possible.
6. Anterior segment- Posterior synechiae.
Cornea and lens burns, Internal ophthalmoplegia, It
is uncommon with multiple sessions, light to

moderately intense burns, and use of laser instead of


xenon.
7. PainYounger diabeticmore painful, Peripheral
retinamore painful, reassurance required, retrobulbar anesthesia rarely needed .
8. Retrobulbar hemorrhage due to retrobulbar anesthesia injection -Laser surgery can continue, but one
should watch the central retinal artery.
Surgical CareVitrectomy for Diabetic Retinopathy
Vitrectomy may be necessary in cases of:
1. Long-standing (non-resolving) vitreous hemorrhage
(where visualization of the status of the posterior pole
and laser treatment is too difficult).
> 3 months in type I diabetes
> 6 months in type II diabetes
2. Tractional retinal detachment, and combined
tractional and rhegmatogenous retinal detachment.
3. Severe progressive neovascularization.
4. Anterior segment neovascularization with posterior
segment opacity.
5. Ghost cell glaucoma.
6. Severe non-resolving macular edema.
7. Macular edema due to premacular traction.
8. Dense premacular hemorrhage.
9. More uncommon indications include epiretinal
membrane formation.
The Diabetic Retinopathy Vitrectomy Study (DRVS)
has recommended that vitrectomy be advised for eyes
with vitreous hemorrhage, which fails to resolve
spontaneously within 6 months. Early vitrectomy (<6
months, mean of 4 months), may result in a slightly
greater recovery of vision in type I diabetics. When
treatment is delayed, it is mandatory to monitor the status
of the posterior segment by ultrasound to watch out for
signs of macular detachment.
Aims of surgery are:
1. To remove the blood/vitreous opacities to permit
evaluation and possible laser treatment of the posterior pole. Laser photocoagulation can be done
through indirect delivery systems or through the
EndoProbe.
2. To release tractional forces that pull on the retina, to
repair a retinal detachment, and to remove the
scaffolding where the neovascular complexes may
grow into.
3. Division of elevated vessels, sheets bands and separation of epiretinal membrane, and segmentation of
those remaining into separate islands.

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Reported benefits include accelerated resorption of
long standing vitreous hemorrhage and regression of
neovascularization. The inflammation created is known
to hasten the absorption process of vitreous hemorrhage.
The main complication is development of accelerated
tractional retinal detachment, reported in 25 percent to
33 percent of treated eyes. This treatment can be considered before vitrectomy but should be avoided in patient
with tractional retinal detachment or areas of strong
vitreoretinal adhesions.
Technique: The cryo application is usually done transconjunctivally or after a limbal peritomy. In transconjunctival treatment, two rows of three to four applications
are placed in each quadrant at 12 mm and 16 mm from
the limbus. In case of limbal peritomy, about 20 spots in
four rows are placed in each quadrant, usually in two
treatment sessions one week apart. The applications are
generally monitored with indirect ophthalmoscope to see
for area of whitening. At least the superior half should
be done under direct visualization and then same can be
carried out for the inferior half which is usually covered
with vitreous hemorrhage. Otherwise, the application
can be -60C for 10-15 seconds. A careful B-scan ultrasonography should be done in such cases to avoid
treating eyes with tractional retinal detachment.
At all levels of treatment retinopathy, it is important
to be certain that the patients overall diabetes status is
under optimal control.
Practical Conclusions

Figs 44.5A and B: Extensive fibro vascular


proliferations in PDR

Peripheral Cryotherapy
When laser photocoagulation is precluded in the presence of an opaque media, such as in cases of cataracts
and vitreous hemorrhage, cryotherapy may be applied
instead. With the advent of diode laser the role of
peripheral cryoablation has decreased as the infrared
wavelength is able to bypass moderate media opacities.
The principles behind the treatment is basically the same,
i.e. to ablate retinal tissue for oxygen demand to be
decreased and to induce a chorioretinal adhesion, which
could increase oxygen supply to the retina in the hope of
preventing or down-regulating the vasoproliferative
response. It should also be done in cases where PRP has
failed to regress the NVD.

There are four major modes by which visual loss can


occur in diabetic retinopathy, bringing the patient to the
ophthalmologist. Brief management of these clinical
presentations at a glance is as under:
1. Maculopathy
Fluorescein Angiography
Control Diabetes
Grid/Focal laser
Vitrectomy (not totally accepted)
2. Vitreous hemorrhage
PRP after spontaneous clearing of hemorrhage or
after vitrectomy
3. PDR with TRD involving or threatening macula
Vitrectomy with PRP
4. Involuted diabetic retinopathy
Leave it alone.
Patient Education
One of the most important aspects in the management
of diabetic retinopathy is patient education. Inform the

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 427


patient that they play an integral role in their own eye
care. Emphasize the following facts:
1. Time of first eye examination It is recommended that
patients with type I diabetes mellitus should get their
first fundus examination done after 5 years of onset
of diabetes and then should follow up on an yearly
basis. Type II diabetes patients should get an immediate eye examination done on the diagnosis of
diabetes. All pregnant patients with diabetes should
have a pre conception eye examination done and then
should follow up 3 monthly or as advised till 3 months
post partum (Table 44.6).

Table 44.7: Time table based on retinopathy findings


Retinal abnormality

Suggested follow-up

Normal or rare microaneurysms


Mild NPDR
Moderate NPDR
Severe NPDR
CSME

Annually
Every 9 months
Every 6 months
Every 4 months
Every 2-4 months
(careful follow-up)
Every 2-3 months
(careful follow-up)

PDR

Table 44.6
Type of diabetes
mellitus

Recommendation
time of first exam

Routine minimum
follow-up

Type I, IDDM

5 years after onset


or during puberty

Yearly

Type II, NIDDM

At time of diagnosis Yearly

During pregnancy Prior to pregnancy


for counseling
or early in
first trimester

3 monthly or
more frequently
as indicated.
Till 3-6 months
post partum

2. Follow up in patients with diabetic retinopathy: A patient


with very early diabetic changes in the fundus (few
micro aneurysms), is usually advised to see the ophthalmologist yearly. With Mild NPDR, one should
consult an ophthalmologist every 9 months. Patients
with moderate NPDR should be seen every 6 months,
and those with severe NPDR are seen 4 monthly. If
PDR stage is present a 3 monthly follow up is recommended. CSME in any category (even Mild NPDR )
should have a 3-4monthly follow-up.
3. Excellent glucose control is beneficial in any stage of
diabetic retinopathy. It delays the onset and slows
down the progression of the diabetic complications
in the eye.
4. Other systemic problems, such as hypertension, renal
disease, and hyperlipidemia, may contribute to the
progression of the retinopathy and should be
addressed promptly.
5. Smoking, although not directly proven to affect the
course of the retinopathy, also may play a role in
further compromising oxygen delivery to the retina.
Therefore, all efforts should be made in the reduction,
if not outright cessation, of smoking.
6. Visual symptoms (e.g. changes in vision, redness, and
pain) could be manifestations of disease progression
and should be reported immediately.

Figs 44.6A and B: Stabilised PDR with regressed


proliferations and pigmented laser marks. Photocoagulation

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Section IV: Retina


Table 44.8: Recommendations for the management of diabetes in pregnancy

1. Previously diagnosed diabetic

2. Women with insulin-dependent diabetes


of <5 years, no retinopathy, nephropathy,
or hypertension
3. Women with insulin-dependent diabetes
of >5 years, no retinopathy, nephropathy,
or hypertension
4. Women with mild non-proliferative
retinopathy, nephropathy, or hypertension
5. Women with moderate or severe nonproliferative retinopathy, significant nephropathy,
and proteinuria
6. Women with active proliferative retinopathy,
especially with high risk characteristics as
defined by the Diabetic Retinopathy study
7. Women who develop severe optic disc
neovascularization in the first trimester that
responds very poorly to aggressive laser
photocoagulation
8. Women who develop gestational diabetes
mellitus

Baseline dilated fundus examination within 12 months


of a planned pregnancy; comprehensive eye examination in the first trimester; frequency of follow-up
examinations based on severity of retinopathy; patients
should be counseled on the risk of development or
progression of diabetic retinopathy
Perform ophthalmoscopy at least once between
weeks 20 and 30 of gestation
Dilated fundus examination at least once per trimester
Dilated fundus examination at least once
per month
Patient to be educated before or early in pregnancy
regarding the potential risk to the eyes; dilated fundus
examination at least monthly.
Panretinal scatter photocoagulation
Therapeutic abortion may be recommended

No increased risk of the development of diabetic


retinopathy; previous guidelines for monitoring do
not apply in such cases

7. DM in general and diabetic retinopathy in particular


are progressive conditions such that regular followup care with their physician is crucial to detect any
changes that may benefit from treatment.
8. Diabetes and Pregnancy- Recommendations for the
management of diabetes in pregnancy as laid down
by the American Diabetes Association are in Table
44.8:
RECENT ADVANCES IN DIABETIC
RETINOPATHY MANAGEMENT
This can be broadly classified as medical and surgical
advances.
Medical Advances
Gene Therapy
It has been observed that some diabetes mellitus patients
develop diabetic retinopathy despite good control and
others escape retinopathy despite poor control. Also there

have been reports of diabetic retinopathy in patients not


having systemic diabetes. This suggests the role of genetic
factors in the susceptibility to develop diabetic retinopathy. Also evidences like familial clustering of diabetic
cases and occurrence of diabetes in twins, are all proving
the importance of inherited factors in the etiology of
diabetes and its complication.75 The possible candidate
genes for genetic engineering as a treatment modality
for diabetic retinopathy are:76
a. Aldose reductase (ALR) gene
b. Nitric oxide synthetase (NOS) gene
c. Receptor for advanced glycation end products
(RAGE) gene
d. Human leucocyte antigen (HLA) gene
e. VEGF gene
f. Tumor necrosis factor (TNF-) gene.
VEGF (Vascular Endothelial Growth Factor)/
Growth Factor Inhibitors
For nearly last 50 years research has proven that proliferation component of diabetic retinopathy must be the

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 429


result of growth factors released by the retina,77,78 in
response to retinal ischemia. A number of growth factors,
some of which induce capillary growth, have been
isolated within the eye, including basic fibrovascular
growth factor and insulin-like growth factor. 77,79
Although sometimes these growth factors levels are
elevated in eyes with proliferative diabetic retinopathy,
many studies have not found it to be consistently high.
Vascular endothelial growth factor (VEGF) also
known as Vascular premeability factor, is an angiogenic
peptide with molecular weight of 45, 000-dalton protein.
It is known to induce angiogenesis in numerous highly
vascularized and rapidly proliferating tumors,80,81 and
it is 10, 000 times more potent than histamine to causing
vascular permeability. Studies have shown that
numerous retinal cells types including retinal pericytes,
retinal endothelial cells, muller cells, and retinal pigment
epithelium can both produce VEGF and increase its
production under hypoxic conditions.82, 83 Its effect is
endothelial cells-selective with receptors for the molecule
primarily found on endothelial cells. Interestingly, its
production is dramatically elevated under hypoxic
conditions.84 Recently, retinal endothelial cells have been
shown to possess more high-affinity VEGF receptors than
any other cell type reported to date. Studies also show
that VEGF levels are dramatically elevated in the aqueous
and vitreous of patients with actively proliferating
neovascularization (in diabetic retinopathy, central
retinal vein occlusion, rubeosis iridis, and other conditions).85 Interestingly, VEGF is not elevated under these
same conditions when neovascularization is quiescent,
specifically in diabetic retinopathy, during non-proliferative stages and during quiescent proliferative disease,
low levels of VEGF are noted. Also the concentration of
VEGF in vitreous is found to be higher than in aqueous,
suggesting that it is a retina produced factor. Following
laser (panretinal) photocoagulation, the VGF levels were
found to be reduced. Thus it suggests that inhibition of
VEGF (with intravitreal injection of VEGF inhibitors/
anti-VEGF antibodies) or by use of genetic engineering
(anti-sense DNA technology), may result in suppression of neovascularization in vivo.86,87 And if a noninvasive delivery is possible of similar growth factor
inhibitors, it might prove to be an ideal treatment modality for prevention of proliferative diabetic retinopathy,
thus avoiding (the destructive treatment of) panretinal
photocoagulation.
Hence VEGF may have a major role to play in future
in the management of ischemia induced neovascularization of the retina and anterior chamber seen in diabetic
retinopathy.

Role of Aldose Reductase Inhibitors (ARIs)


Studies in animal models of diabetes using aldose reductase inhibitors provided promising results in normalizing
neurologic dysfunction and increased renal glomerular
filtration rate in diabetic rates.88,89 Subsequent clinical
trials did not, however, demonstrate that aldose reductase inhibitors were effective in ameliorating human
neuropathy or retinopathy and had significant side
effects.90, 91 The Sorbinil Retinopathy Trial (SRT), multicenter clinical trial, tested whether a daily dose of
sorbinil, an aldose reductase inhibitor (ARI), reduces the
complications of diabetic retinopathy. But after 3-years
period the drug had no clinically beneficial effect on the
course of diabetic retinopathy in adults with IDDM of
moderate duration.90 Although a slightly slower progression rate in microaneurysm count was noticed. The major
drawback of the study was the complications of the use
of the drug in the study population. About 7 percent
including initial 202 participants had adverse reactions
including toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome. Hence chances
that sorbinil will achieve prophylactic usage, because of
the hypersensitivity reactions and no significant clinical
benefit from the study, are rare. Tolrestat, and other ARIs,
which has a different chemical structure than sorbinil,
are presently under investigation in the United States
and Canada. But discouraging results of the previous
studies suggest that human trials must be undertaken
only after its safety, complications and efficacy is properly
studied and known.
Aminoguanidine
This is an agent inhibiting the formation of Advanced
glycosylated end products (AGE). Studies have shown
that treatment with aminoguanidine may reduce the
vascular changes and basement membrane thickening
in diabetic rats. An important mechanism associated with
the development of abnormal vascular cell function in
diabetes is the Non-enzymatic glycation, which refers
to the ability of glucose to form covalent products by
nucleophilic addition to protein amino groups and
possibly DNA, to form intermediate glycosylation
products.92,93 Further reactions of these intermediates
lead to the formation of advanced glycosylation end
products (AGE) in an irreversible chemical reaction.
Recent studies have shown that infusion of AGE can
cause the some of the vascular abnormalities noted in
diabetes such as increased basement membrane thickening and alterations in vascular contractility. AGE is also
thought to increase the VEGF levels.

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Section IV: Retina

Pyruvate

Prevention of Generation of Vasoactive Agents

Increased glucose metabolism via glycolysis or the polyol


pathway results in an increase in the ratio of NADH to
NAD94,95 leading to changes in the redox potential. This
increased NADH / NAD ratio can cause changes in other
metabolic pathways such as the synthesis of diacylglycerol, DNA repair, and fatty acid oxidation. Pyruvate by
causing normalization of the NADH/NAD ratio,
prevents the adverse effects.

Many studies are focusing now on Endothelin, Angiotensin II, Histamine, Oxygen, modulators of retinal blood
flow. Inhibition of this process with insulin therapy or
islet cell transplants may normalize retinal blood flow
in diabetes.
Vitamin E
Is one of the different factors contributing to vascular
abnormalities in diabetes. Vitamin E is studied as a
therapeutic agent, to inhibit these abnormalities.

Protein Kinase C (PKC)/Di Acyl


Glycerol (DAG) Inhibitors
These enzymes and lipids affect a various vascular
functions such as permeability, contractility, coagulation,
flow, hormone action, growth factors effects, and ultimately basement membrane synthesis and turnover.96,97
All of these variables have been found to be abnormal in
diabetes. DAG activates PKC, causing its translocation
from the cytosol to the cell membrane. Studies in diabetic
rats have shown a causal relationship between elevation
of DAG, activation of PKC, and the development of
abnormal retinal blood flow. Few clinical studies have
also shown a relationship between retinal blood flow
changes and elevations in DAG in diabetic patients with
no diabetic retinopathy.98 Another interesting study has
shown that normalization of PKC activities in diabetes
through the use of specific inhibitors has resulted in
retinal blood flow normalization in diabetic rats.99 PKC
is also an important intermediate involved in the action
of VEGF hence specific inhibition of this PKC may help
to devise a medical therapy to stop neovascularisation).
Inhibitors oh Intracellular Signaling
These are substances which help VEGF like growth
factors to go into a cell and cause bio-chemical reactions
leading ultimately to neovascular growth. Increased level
of free Ca++ has been seen after VEGF binds with cell
surface receptors. Hence an inhibitors of such intra
cellular signalling agents can prove to be helpful in
preventing neovascularisation. Clinical trails are already
going on in patients with cancer for their possible anti
angiogenic effect.
Inhibitors of Toxic Effects of Macular Edema
Substances like lysophosphatidic acid, a component of
serum has been found to cause deleterious effects on
retinal glial cells.100 More research should be done to
directly antagonise such harmful agents which cause
damage to retina due to persistent macular edema.

Anticoagulants
Although Aspirin has not been found to be effective in
preventing the microvacular damage in diabetic
retinopathy. We feel that there is still some hope of
developing a drug which can prevent the vessel occlusion
related changes, which is the basic pathology in diabetic
retinopathy (like increased platelet adhesion, excessive
white cell aggregation, and damage to capillary cell
endothelium) and thus preventing ischemia.
Angiotensin Converting Ezyme (ACE) Inhibitors
and Diabetic Retinopathy
Role of angiotensin converting enzyme inhibitors in
type I diabetes with hypertension has been studied in
the EURODIAB study.101ACE inhibitors have a renoprotective effect and hence probably a retino protective
effect too.
Measurement of Retinal Blood Flow
Retinal blood flow measurement if correlated with the
development of clinically observable pathologies, can
pick up very early diabetic vascular changes and hence
an early intervention can be done. Also it can act as a
means to assess the effectiveness of therapeutic interventions. Generally, fluorescein angiography techniques and
laser doppler velocimetry (LDV) have been the methods
of choice for non-invasive quantitation of retinal blood
flow.
Surgical Advances
1. Surgical management of macular edema. It has been
observed that many eyes of patients with diabetic

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Chapter 44: Diabetic RetinopathyCurrent Concepts and Recent Advances 431

2.

3.

4.

5.

macular edema (with or without superimposed


cystoid macular oedema) improve after spontaneous
posterior vitreous detachment or PVD following
vitrectomy for diabetic maculopathy.102 Also there
was a regression of the maculopathy. Although PVD
can be induced with the help of laser in a non invasive
manner, sometimes the cortical vitreous in the region
of macula is so much thickened and adherent that it
may not allow the occurrence of PVD by focal and or
grid photocoagulation. Such cases may be considered
for surgical induction of PVD, instead of repeat
coagulation.103
Pharmacologic vitreolysis: This can be an excellent way
to induce PVD, and hence cause resolution of diabetic
maculopathy with minimum intervention. A lot of
agents have been studied, which on injection into
vitreous cavity cause a PVD for eg. Plasmin, Chondroitinase, Dispase, tPA. Out of all these chondroitinase
is considered to be the most ideal one.104
Advances in micro-surgical techniques: The surgical
outcome of vitrectomy for diabetic retinopathy has
tremendously improved with the present advances
in micro surgical techniques like
a. Use of wide angle system of visualization for
vitrectomy.
b. Illuminated instruments allowing bimanual
surgery.
c. 4 port vitrectomy (with the assistant holding the
illumination giving the operating surgeon true bi
manuality)
d. ILM peeling for non resolving diabetic maculopathy.105
e. Staining of membranes (with dyes like ICG) can
be helpful in better visualization and surgical
results.
Surgical removal of hard exudates: This has been
reported by some to be an effective means to treat a
non resolving sever maculopathy with severe
exudation persisting for more than 3 months in the
macular area causing profound visual loss. This
involved a pars plana vitrectomy, the massive hard
exudates were removed from the subretinal space
with subretinal forceps.106, 107
Surgical treatment of serous detachments of macula in
diabetic maculopathy: A new method of surgical
treatment for macular serous detachment in diabetic
maculopathy has been reported. This consisted of
vitrectomy, aspiration of subretinal liquid through a
temporal retinotomy, fragmentation and extraction
of the sub and intra retinal exudates through one or
several retinotomies, macular massaging with
fluorodecaline (PFCL), endophotocoagulations (focal

on vascular anomalies and macular grid) and fluidgas exchange (C3F8). The surgical procedure gave
good functional and anatomical results but perhaps
more studies are randomized studies are required to
clearly justify its use in cases of non resolving maculopathies.108
Triamcinolone
There are many studies reporting that Triamcinolone
injection leads to a faster resolution of maculopathy. It is
thought that some amount of inflammation plays a role
in the causation of diabetic maculopathy, specially
exudation. Although it is still not clear whether it is the
causation of PVD, following injection of Triamcinolone
or the drug it self, which helps in the resolution of
maculopathy.109
Injection of Triamcinolone in the vitreous cavity per
operatively has been found give a better visualization of
vitreous gel, thus helping in surgical procedures like
induction of PVD etc.110 This also helps to prevent
breakdown of blood ocular barrier.110.
Use of tPA (Tissue Plasminogen Activator)
tPA is a serine protease that catalyzes the conversion from
plasminogen to plasmin, plays an important role in the
fibrinolytic system and has therefore in recent years
attracted attention in the field of ophthalmology. tPA can
be extremely helpful in dealing with special situations
in diabetic retinopathy like
a. Fibrin blood clots (hyphemas/vitreous clots ) removal
after vitrectomy surgery (111). Intravitreal injection
of tPA can convert.plasminogen to plasmin and
remove the clot.
b. Release adherence of the vitreous body to the retina
(pre operatively) and its related complications like
iatrogenic retinal tears(by injecting tPA, at the beginning of surgery (dose of 25 micro gms) to aid separation
of the vitreous from the retina (causing PVD). Results
till date are inconclusive and more need to be studied
about this.112
c. It is also helpful in managing conditions postoperative fibrinous reaction in vitreous cavity or anterior
chamber, which can be non surgically dealt with tPA.
d. Can be used for non surgical removal of pre macular
hemorrhage.113
Pancreatic and Islet Transplants
Successful pancreatic implant in animal studies have
been associated with decrease or complete cessation of

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432

Section IV: Retina

insulin injections requirements, but an improvement in


diabetic retinopathy has not been reported. This
treatment option holds a lot of scope as it might deal
directly with the cause of basic pathology (Diabetes)
rather than treating its harmful side effects.

9.

10.

CONCLUSIONS
Although studies have proven that prevention and early
medical and surgical intervention can prevent, improve
or stabilize diabetic retinopathy, there is still an
abundance of new cases in our out patient departments
every day who either present late in the course of disease
or present with complications which have a grim
prognosis. Since it is known that diabetic retinopathy
usually causes no symptoms in its earliest stages, an early
diagnosis and intervention cannot be overemphasized.
Techniques and success rates of never advances in
treatment of diabetic retinopathy will continue to improve, and we hope to see surgery for diabetic retinopathy
improve in leaps and bounds in the time to come. But
the most dramatic change and advance in the
management of diabetic retinopathy is expected from the
pharmacologic methods, not only to treat and prevent
vascular occlusion, macular edema, and angiogenesis,
but also as a newer non invasive way to treat diabetic
maculopathy and PDR. Lastly patients with non functional vision efforts should be made to give them social,
psychological, vocational and visual rehabilitation (with
help of low visual aids).

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

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Section IV: Retina

45

Advances in the Management of


Age-related Macular Degeneration
Sandeep Arora, Manish Nagpal, PN Nagpal, Kamal Nagpal, Ashish Mahobia

INTRODUCTION
ALTERNATE LASER TECHNIQUES
FEEDER VESSEL THERAPY
PHOTODYNAMIC THERAPY
TRANSPUPILLARY
THERMOTHERAPY
RADIATION THERAPY
ANTIANGIOGENIC AGENTS
SURGICAL CARE
PREVENTION STUDIES
PATIENT EDUCATION
IMPLANTABLE MINIATURISED
TELESCOPE (IMT)

INTRODUCTION
Age-related macular degeneration (ARMD) is the leading cause of irreversible visual loss in the industrialized world.1-2 Two types of macular
degeneration exist, the dry form and the wet form. The dry, or nonexudative, form involves atrophic and hypertrophic changes in the retinal
pigment epithelium underlying the macula as well as deposits (drusen)
on the RPE. The wet, or exudative,is the form of ARMD, in which abnormal
blood vessels,choroidal neovascular membranes (CNVMs) develop under
the retina, leak fluid and blood, and ultimately cause a blinding disciform
scar in and under the retina. Nonexudative ARMD, which is usually a
precursor of exudative ARMD, is more common. The presentation of
nonexudative ARMD varies; hard drusen, soft drusen, RPE geographic
atrophy, and pigment clumping can be present.It is estimated that for
patients with CNV in the fellow eye,18 percent develop CNV in the study
eye by 2 years and 34 percent by 4 years.In contrast ,for patients with
bilateral geographic atrophy, the risk of developing CNV was relatively
low,being 2 percent at 2 years and 11 percent by 4 years.3,4 The risk is also

Fig. 45.1: Wet ARMD: Central scar from old bleed with surrounding
area of recent bleed from the CNV

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Chapter 45: Advances in the Management of Age-related Macular Degeneration 437


proximately 10 percent for fellow eyes with small drusen,
about 30 percent for fellow eyes with either large drusen
or RPE clumping, and as high as 60 percent for fellow
eyes with both large drusen and RPE clumping.
Severe visual loss though more typically associated
with exudative ARMD, can also occur from nonexudative
ARMD, particularly when geographic atrophy of the RPE
develops in the fovea and causes a central scotoma.
Investigators categorize both geographic atrophy and
exudative ARMD as late ARMD, while less severe forms
of nonexudative ARMD are categorized as early ARMD.
Early ARMD, which comprises 85-90 percent of ARMD
cases, presents with drusen and RPE mottling and is
typically only minimally symptomatic.
Treatment exists for the exudative form,however, its
efficacy is low. Laser photocoagulation of the CNVM is
the gold standard treatment. However, few patients show
well-demarcated classic CNVM that is amenable to laser
treatment, and at least one half of these patients
experience persistent or recurrent CNVM formation
within 2 years.The biggest problem with treatment is a
blinding central scotoma when the CNVM is located
subfoveally, hence many clinicians do not treat subfoveal
CNVM. With these treatment limitations, there has been
much interest in alternate therapies for exudative ARMD,
including photodynamic therapy, transpupillary
thermotherapy, antiangiogenic therapy, surgical therapy,
and radiation therapy.
Laser photocoagulation of the CNVM represents the
best-studied and standard treatment for this disorder.
Several well-designed clinical trials, including the
macular photocoagulation studies (MPS), 5-17
demonstrated that photocoagulation of the CNVM
prevented large decreases in visual acuity compared
to observation for extrafoveal, juxtafoveal, and
subfoveal CNVM (200-2500 m, 1-199 m, and
directly under the geometric center of the foveal
avascular zone [FAZ], respectively). Patients were
eligible for laser photocoagulation, if they manifested
well-defined CNVM with some classic morphology.
Poorly defined or occult-only CNVM were not eligible
for photocoagulation.
In the extrafoveal CNVM studies by the Macular
Photocoagulation Study Group, the proportion of
eyes with severe visual loss (SVL), 6 or more lines of
vision loss, in control versus treated eyes was (1) 41
percent versus 24 percent at 1 year, (2) 63 percent
versus 45 percent at 3 years, and (3) 64 percent versus
46 percent at 5 years.5
The juxtafoveal CNVM studies by the Macular Photocoagulation Study Group showed similar benefits; the
proportion of eyes that experienced SVL in control

eyes versus treated eyes was 45 percent versus 31


percent at 1 year,61 percent versus 50 percent at 3
years, and 57 percent versus 54 percent at 5 years
respectively.6 To avoid iatrogenic laser injury to the
foveal center, in juxtafoveal CNVM, the CNVM was
overlapped by 100 m at all borders in the extrafoveal
studies; however, the CNVM was not treated beyond
its border at the foveal edge if an overlapping laser
burn would coincide with the foveal center in the
juxtafoveal studies.
In the extrafoveal studies, argon blue-green was used,
since it was most readily available in the late 1970s
when these studies were initiated. In the later
juxtafoveal studies, krypton red was used because it
penetrates hemorrhage better than argon blue-green
and it potentially avoids thermal injury to the yellow
macular xanthophyll, which absorbs in the blue range
of the argon blue-green laser wavelengths.9
No significant advantage of one wavelength over the
other wavelength was demonstrated in the later
subfoveal studies by the Macular Photocoagulation
Study Group, which randomized patients into argon
green and krypton red laser photocoagulation.
It is of importance to note that subgroup analysis of
the juxtafoveal studies showed no treatment benefit in
patients with hypertension (i.e., elevated systolic or
diastolic blood pressure, history of antihypertensive use).
Although hypertension may represent a poor prognosticator for laser photocoagulation, the discrepancy in study
findings suggests that hypertension should not exclude
a patient from laser photocoagulation.
The subfoveal studies by the Macular Photocoagulation Study Group included only classic and welldemarcated CNVMs that were less than 3.5 disc areas.
Laser photocoagulation, which included the foveal
center, was associated with SVL in the short-term but
proved beneficial in the long-term compared to observation. At 3 months, the proportion experiencing SVL in
control eyes versus treated eyes was 11 percent versus
20 percent. At 2 years, the proportion of eyes that experienced SVL was 37 percent versus 20 percent (control vs
laser-treated eyes, respectively). Laser-treated eyes in the
subfoveal studies also experienced treatment benefit with
respect to reading speed and contrast sensitivity.
Subgroup analysis demonstrated diminishing treatment
benefit with larger lesions.
Persistence and recurrence after laser photocoagulation are common. According to the MPS definition,
persistence denotes leakage from the peripheral edge of
the laser scar within 6 weeks of treatment; recurrence
denotes new leakage after 6 weeks from treatment.
Persistence was observed in 10 percent and 32 percent

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Section IV: Retina

of treated eyes in the extrafoveal and juxtafoveal studies,


respectively. Possible explanations for this difference
include different biologic behaviors of extrafoveal and
juxtafoveal CNVM, differences in laser wavelengths
(argon green vs krypton red) or the failure to completely
cover the foveal edge of the juxtafoveal CNVM.13-15
To address treatment efficacy of laser photocoagulation for extrafoveal or juxtafoveal CNVM that had
recurred through the foveal center, the subfoveal
recurrent studies included patients with classic, welldemarcated CNVM that had recurred through the foveal
center. The entire lesion, including the prior laser scar,
measured less than 6 disc areas with sparing of some
retina within 1500 m of the foveal center. These studies
showed similar results to recent subfoveal CNVM
studies. Specifically, laser photocoagulation, which
included the foveal center, was associated with SVL in
the short-term but proved beneficial in the long-term
compared to observation.13-15
Laser-treated eyes in the subfoveal recurrent studies
also experienced treatment benefit with respect to
reading speed and contrast sensitivity.
MPS guidelines usually are followed. Only welldefined lesions are eligible for laser photocoagulation;
poorly defined lesions (e.g., almost entirely obscured by
subretinal hemorrhage or purely occult lesions) are not
eligible for laser photocoagulation.
The endpoint of laser photocoagulation is to create a
uniform, white treatment lesion. As aforementioned, the
MPS showed no significant advantage of krypton red
over argon green laser photocoagulation. However, red
may theoretically cause less thermal injury to the macular
xanthophyll in the juxtafoveal region. Red also theoretically penetrates subretinal hemorrhage better than green,
sparing the overlying retina from thermal injury, while
facilitating photocoagulation of any underlying CNVM.
Subfoveal CNVMs are eligible for laser photocoagulation, based on MPS criteria. The subfoveal studies
included only classic, well-demarcated CNVMs that were
less than 3.5 disc areas; subgroup analysis demonstrated
increasing treatment benefit with smaller lesions, particularly those less than 2 disc areas. The best candidates
are those with small lesions and poor vision, while the
worse candidates are those patients with large lesions
and good vision.
According to MPS criteria, patients with subfoveal
recurrent CNVM also are eligible for laser photocoagulation, if the entire lesion, including the prior laser scar,
measures less than 6 disc areas with sparing of some
retina within 1500 m of the foveal center. For these
subfoveal recurrent CNVM, treatment is extended 300
m into the prior laser scar. Since laser photocoagulation
of the fovea in these cases leads to an immediate decrease

in vision, many clinicians refrain from treating patients


with subfoveal CNVM or subfoveal recurrent CNVM;
however, alternate treatments for these patients will soon
be available. To ensure complete treatment of the lesion,
post-treatment photographs can be compared to the
pretreatment angiogram. Areas that harbor CNVM that
have not been covered completely by photocoagulation
burns can be treated. After all sessions of laser photocoagulation, patients are asked to return in 2-3 weeks
for best-corrected visual acuity, slit lamp biomicroscopy,
and FA.
Persistence generally manifests as leakage at the
margin of the laser scar. Patients who show areas of
persistence undergo repeat laser photocoagulation and
are reassessed in 2-3 weeks. Those who show no angiographic evidence of persistence also return in 2-3 weeks
for reassessment; the treating physician may perform FA,
because the risk of persistence is high in the initial
6 weeks after laser photocoagulation. Patients are
reassessed periodically, several times within the first
3 months after treatment and then at 3-4 month intervals.
They are instructed to present immediately if any
changes in central vision, particularly new metamorphopsia or scotomas on Amsler grid testing, are noted.
They also are followed closely for CNVM development
in the fellow eye, as the risk varies, as follows: Approximately 10 percent for fellow eyes with small drusen,
about 30 percent for fellow eyes with either large drusen
or RPE clumping, and as high as 60 percent for fellow
eyes with both large drusen and RPE clumping.
ALTERNATE LASER TECHNIQUES
Based on MPS criteria, only 13-26 percent of patients with
exudative ARMD show well-demarcated classic CNVM,
which is eligible for laser treatment; at least one half of
these patients experience persistent or recurrent CNVM
formation within 2 years. Patients with poorly demarcated or occult-only CNVM comprise the majority of
patients with exudative ARMD; it is unclear whether
laser photocoagulation is beneficial, as these patients
were ineligible for laser therapy in the MPS. Laser
treatment itself irreversibly damages the RPE and retina,
causing an absolute scotoma, which correlates with the
site of the laser photocoagulation scar. Since the treatment causes a blinding central scotoma when the CNVM
is located subfoveally, many clinicians do not treat
subfoveal CNVM.
FEEDER VESSEL THERAPY
To avoid photocoagulating the foveal center, Shiraga 18
and others have attempted to photocoagulate feeder

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Chapter 45: Advances in the Management of Age-related Macular Degeneration 439


vessels to subfoveal CNVM. ICG by digital video
cameras or SLO has proven invaluable in this therapy.
Feeder vessels can be detected in the 20 degee field
images with SLO. Use of SLO makes the images of early
transit phase more distinct compared to IR camera.
Furthermore, the subtraction procedure of images may
show direction of dye filling. However the identification
of feeder vessels is currently limited because of such
factors as the blockage of their fluorescence by exudates,
blood or fibrous tissue and a difficulty in distinguishing
them from choroidal vessels nearby. To attain complete
occlusion of feeder vessels, burns at RPE and choroids
have to be applied with yellow and red dye lasers.
Others have evaluated grid or scatter laser treatment,
avoiding photocoagulation of the fovea when the CNVM
is located subfoveally. The results have been disappointing. In a recent study by Bressler, 51 patients with occult
subfoveal were randomized to macular scatter laser
photocoagulation with confluent laser photocoagulation
of classic CNVM in 8 of these patients. 20 These patients
showed a larger visual acuity decrease from baseline than
that of the control group (52 patients observed for up to
24 months). This difference was greatest within the first
year after randomization; at 24 months, approximately
40 percent of eyes in each group lost at least 6 lines of
visual acuity. Consequently, it is unlikely that a large
randomized prospective study will be conducted to
further evaluate this modality.
PHOTODYNAMIC THERAPY
Laser photocoagulation causes severe collateral thermal
injury to the nonvascular tissues. However use of
intravascular dyes which cause vascular occlusion by a
photochemical reaction , isolated vessel occlusion may
be achieved. Photodynamic compounds, which usually
react with water to create oxygen and hydroxyl free
radicals, are stimulated with a specific light wavelength;
the intensity of this wavelength is low enough to spare
the irradiated tissues from thermal damage. The free
radicals, in turn, react with cell membranes of the
endothelium and blood cells to induce massive platelet
activation and thrombosis. Variables in this reaction
include the intravascular concentration of dye; the
photochemical behavior of the dye; the interval from the
injection to the onset of irradiation; and the intensity,
specificity, and duration of the irradiation.
Photodynamic therapy may involve one of the following mechanisms: (1) occlusion of vessels through a purely
photodynamic mechanism, or (2) enhancement of laser
photocoagulation ablation of CNVM to decrease rates
of persistence and recurrence, while improving the safety

margin by decreasing the thermal energy that is necessary


to achieve occlusion.
Fluorescein and ICG dyes, which are structurally related
and commonly used in ophthalmology, are capable of
photochemical reactions; but the reactions are too weak
at acceptable doses and illumination levels, so no useful
treatment benefit exists. Attempts to use ICG (which
absorbs at 795-810 nm) as a photosensitizer for diode
laser (which emits at 805 nm) photocoagulation have
been made. However, there has been a paucity of reports
showing long-term effectiveness. One primate study
demonstrated little difference between ICG-enhanced
and nonenhanced mild burns. ICG-enhanced moderate
and severe burns showed larger retinochoroidal lesions
and more complete obstruction of the choriocapillaris
than did burns without ICG enhancement.19
Researchers are developing several photosensitizers
in animal models, such as phthalocyanines, rose bengal,
chlorine, lutetium texaphyrin, tin ethyl etiopurpurin, and
benzoporphyrin derivative. BPD (verteporfin) is a
modified porphyrin with an absorption maximum near
689 nm. BPD is cleared rapidly from the body, resulting
in minimal skin sensitivity after 1-3 days. It is complexed
with low-density lipoprotein (LDL) to enhance delivery
to neovascular tissue via LDL receptors on proliferating
endothelium; it also is liposome-encapsulated to enhance
solubility for IV administration. Very low laser energies
are employed to release the dye from the liposomes and
to stimulate the photodynamic action.
Treatment of age-related macular degeneration with
photodynamic therapy study group(TAPS study)
showed that 61 percent of 402 eyes assigned to verteporfin lost fewer than 15 letters of visual acuity at 12
months compared to 46 percent of 207 eyes that received
placebo (P <0.001). In the subgroup analysis, this visual
acuity benefit (67% vs 39%) persisted (P <0.001) when
the CNVM was predominantly classic (50% or more of
the area of the entire complex). No significant differences
in visual acuity were demonstrated when the area of
classic CNVM was less than 50 percent of the entire
complex. Visudyne. Dosage :Administered intravenously
with a dose based on body mass.The drug is prepared
and infused intravenously over ten minutes.The surgeon
waits ten minutes for the drug to accumulate.Fifteen
minutes after beginning infusion,he irradiates the area
of neovascularization with the tailored spot size for 83
seconds.Special precautions: The patient is instructed to
avoid direct light for 2-3 days because this may result in
skin hypersensitivity and burns.
Contraindications
Predominantly occult CNVM and liver dysfunction.

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Section IV: Retina

Fig. 45.4: FA os same patient: premacular translocation

Fig. 45.2: Macular translocation (presurgery)

Fig. 45.5: FA post macular translocation: shift of fovea seen


clearly in relation to temporal arcades. Inferior leak in due to
the retinotomy made for creating the detachment

Fig. 45.3: Post macular translocation

Another dye has been recently approved ,tin ethyl


etiopurpurin (snET2).20 This purpurin dye is structurally
similar to chlorophyll and absorbs maximally at 664
nm,infusion time is 10-20 minutes and the duration of
light swnstivity is 2-4 weeks. Another photosensitizer,
monotexafin lutetium (Lu-tex), which absorbs maximally
at 732 nm and can be utilized as both an imaging and
photosensitizing agent, has shown promise in preclinical
studies.

The advantages of PDT are that it can be done as an


office procedure,has minimal side effects and
complications with proven benefit in clinical trials.
However the downside is the high recurrence rate with
the need for multiple retreatments,making it a very costly
proposition.
TRANSPUPILLARY THERMOTHERAPY
Transpupillary thermotherapy (TTT) involves slowly
heating the subfoveal choroidal neovascular complex
with infrared (810 nm) diode laser light to occlude the
CNVM. The infrared wavelength is thought to penetrate
the retina and RPE to maximally affect the CNVM, while
minimizing thermal injury to the outer retina. Treatment
is performed with a large single spot, which covers the
entire complex.

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Chapter 45: Advances in the Management of Age-related Macular Degeneration 441


Proponents suggest that this technique may play a
role in occult subfoveal CNVM, whereas PDT may have
only a limited role in occult subfoveal CNVM. In an
uncontrolled retrospective series of 16 eyes of 15 patients
who were undergoing TTT for occult subfoveal CNVM,
Reichel found that 94 percent of the eyes showed
decreased exudation on FA; no eyes showed any deleterious effects.22 Advantages offered are a potential benefit
in vision, with minimal retinal damage. It is an office
procedure and no dedicated laser unlike PDT is required.
ICG enhanced TTT is also another proposed modality
showing good promise .
RADIATION THERAPY
CNVMs, which are composed of endothelial cells and
proliferate more rapidly than the endothelial cells of the
retina, may be more sensitive than the retinal vasculature.
Consequently, radiation therapy has been suggested as
a treatment for subfoveal CNVMs. Chakravarthy studied
40 eyes that were afflicted with ARMD-related subfoveal
CNVM (2 classic and 17 occult CNVM). They found that
radiation caused inhibition of CNVM growth but not
regression of the CNVM. This early pilot also suggested
that higher doses of radiation may have a more beneficial
effect in maintaining a stable visual acuity and CNVM
on FA.23
Given this apparent dose-response effect, other
groups have delivered ionizing radiation to the macula
with modalities that may limit the exposure of ionizing
radiation to normal, radiosensitive structures of the eye
(e.g., optic nerve, lens). These modalities include stereotactic external photon beam irradiation of the posterior
pole; brachytherapy, during which radioactive plaques
are sutured to the posterior pole of the eye and explanted
several days later; and proton beam irradiation, which
deposits most of its energy with little scattering at the
desired depth in the eye at a point called the Bragg peak.
Although some of the early pilot studies were optimistic,
there have been conflicting reports about the radiation
therapys efficacy for exudative ARMD. Recent studies
by Spaide and Roesen, which used nonrandomized or
historic controls, suggested no beneficial effect of lowdose radiation therapy for exudative ARMD. 24 Other
small randomized and nonrandomized trials suggested
that radiotherapy was beneficial. Some of these trials
suggested a possible beneficial effect, particularly with
classic CNVM compared to occult CNVM as noted by
Tholen.25
ANTIANGIOGENIC AGENTS
Angiogenesis involves a complex cascade of inhibitory
and stimulatory factors. Soluble growth factors have

been the best-known cell-modulating agents.Surgically


excised and postmortem CNVM tissue and RPE cells
have been shown to be immunoreactive for various
growth factors (e.g., VEGF, TGF-b, PDGF, bFGF), which
are thought to be angiogenic.
The role of VEGF in ocular angiogenesis is established. Peymans group showed up-regulation of VEGF
expression in experimentally induced CNV in pigmented
rats.26 A phase I trial of an intravitreally administered
antiVEGF antibody in exudative AMD subjects has been
recently completed and there are plans to proceed with
additional clinical trials. It is likely that a whole cascade
of soluble factors plays a role in ocular angiogenesis and
CNVM formation. Recent studies suggest that other
growth factors besides VEGF, such as growth hormone
(GH) and insulin-like growth factor (IGF), may play an
important role in ocular angiogenesis.27 Another study
by Danis showed that inhibiting the key regulatory
isoenzyme protein kinase-C beta, which is involved in
signal transduction downstream from angiogenic growth
factors, effectively inhibited preretinal and optic nerve
head neovascularization in a porcine model of branch
retinal vein occlusion and this agent may ultimately be
studied in exudative AMD.28
Nonsoluble modulators include extracellular matrix
elements and intercellular adhesion molecules (ICAMs),
which are both critical to cell behavior and the development of angiogenesis. TIMP-3 has been found to inhibit
the following: chemotaxis of vascular endothelial cells
toward VEGF and bFGF, capillary morphogenesis in
vitro, and bFGF-induced angiogenesis in chorioallantoic
membrane assays. MMPs and TIMPs may play a role in
CNVM formation; MMPs have been found in surgically
excised CNVM, and TIMPs have been localized in the
Bruch membrane.
An orally selective matrix metalloproteinase inhibitor,
currently known as AG3340, has recently undergone
phase II trial in over 100 subjects with exudative AMD
in the United States.The integrins alpha v beta 3 and
alpha v beta 5 represent other examples of nonsoluble
modulators, which have been implicated in ocular
angiogenesis; integrin alpha v beta 3 has been localized
in surgically excised CNVM.
Interferon-alpha was known to inhibit vascular
endothelial proliferation and migration in the laboratory;
it caused regression of hemangioma in humans. Interferons are peptides that influence gene expression and
protein synthesis. A subsequent series described by Fung,
Engler, and Chan suggested that interferon also was
beneficial for ARMD-related subfoveal CNVM that was
not amenable to laser therapy.29 In vitro and animal model
work has demonstrated some angiostatic efficacy.

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Section IV: Retina

However, human studies have shown disappointing


clinical performance and a high incidence of side effects.
Steroid compounds, which are known to possess angiostatic properties, alter extracellular matrix degradation
and inhibit inflammatory cells, which participate in a
neovascular response. Intravitreal steroid injections have
demonstrated effectiveness in experimental subretinal
and preretinal neovascularization. Intravitreal triamcinolone acetonide has been employed in Penfolds
uncontrolled pilot study of CNVM treatment in ARMD.30
Thirty eyes of 28 patients were injected once, and toxicity
was not noted. Eleven eyes experienced improved or
stabilized acuity within 1-3 months of treatment; the
CNVM regressed to inactive fibrosis. Fifteen eyes
experienced a similar outcome, except for slow extension
and exudation from a recurrent CNVM. Four eyes
experienced no obvious treatment benefit.
Challa, reported a favorable effect on the diseases
course over an 18-month period. The authors speculate
that intravitreal triamcinolone has a beneficial effect on
ARMD-related CNVM by inhibiting leukocytes, including macrophages, which normally release angiogenic
factors.31
Another antiangiogenic steroid is anecortave acetate
(Alcon Laboratories). A recent murine model study by
Clark showed that topical administration of this compound inhibited growth of a highly vascularized
intraocular tumor.32 A sustained antiangiogenic steroid
delivery device, similar to a ganciclovir implant, for
exudative AMD is in the offing.
Other agents under investigation include thalidomide, the antiemetic agent that was responsible for tragic
limb deformities in offspring of mothers who took the
drug during the second trimester of pregnancy. This
agent, which is safe in nonpregnant humans, inhibits
postreceptor signal transduction for growth factor
stimulation of endothelial cells. A prospective clinical trial
in exudative ARMD patients is in Cleveland and at the
Scheie Eye Institute. A single case report by Ip et al exists,
in which thalidomide failed to prevent recurrent
neovascularization in a patient who underwent laser
photocoagulation for CNVM that was related to punctate
inner choroidopathy. 33
SURGICAL CARE
Direct surgical excision of subfoveal CNVM has become
possible.
To compare surgery to observation for subfoveal
classic CNVM or hemorrhagic CNVM, the National Eye
Institute is recruiting patients for a submacular surgery
trial (SST). Patients will be followed and assessed for

Fig. 45.6: SRNVM with surround fresh bleeds

Fig. 45.7: Post removal of SRNVM

stabilization or deterioration of visual acuity, change in


contrast sensitivity, cataract development, surgical
complications, and quality of life.Although results in
histoplasmosis and multifocal choroiditis are impressive,
they have been disappointing in ARMD because the
CNVM interdigitates with the RPE, growing both
anterior and posterior to it. This possibly leads to diffuse
dysfunction of the RPE, which remains after the
procedure. Surgical removal of the RPE appears to cause
prompt atrophy of the underlying choriocapillaris with
subsequent outer retinal disorganization.
Macular translocation is one novel treatment of
subfoveal CNVM in which the retina is shifted away from
the underlying subfoveal CNVM. In the original techni-

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Chapter 45: Advances in the Management of Age-related Macular Degeneration 443


Another technique more recently described by de
Juan and Lewis involves limited macular translocation.
In this procedure, pars plana vitrectomy is followed by
detachment of the temporal retina through one or more
retinotomies and BSS is infused into the subretinal space
using a 39 gauge flexible needle.36 The retina is reattached
after the sclera has been surgically foreshortened by
means of preplaced mattress sutures (de Juan) or by
special clips (Lewis).
Tissue Plasminogen Activator (tPA)
Assisted Submacular Surgery

Fig. 45.8: Subfoveal and juxtafoveal lesions

Large submacular hemorrhage is one of the dreaded


complications of AMD with a resultant large scotoma
and poor vision. Early attempts to use tPA to lyse the
clot during surgery assisted aspiration but it took almost
45 minutes for the clot to lyse.37-38
Pneumatic displacement of the liquid subretinal
blood seems a better approach.Intravitreal tPA injection
is given and then a gas bubble displaces the blood away
from the macula. A total dose of 25-33 micrograms is
injected.39-40 Use of PFCL is also useful to displace the
liquefied subretinal blood and can be used in place of
gas.
RPE Transplantation

Fig. 45.9: Same patient: Post TTT shows marked


regression of the lesion with decreased exudates

que by Machemer, the entire retina is rotated 360 during


pars plana vitrectomy.34 A peripheral retinotomy/retinal
detachment/retinal rotation around the optic nerve, and
retinal reattachment in order to rotate the foveal region
away from the diseased underlying choroid and RPE is
carried out. Then, the CNVM can be photocoagulated to
prevent progression to the new foveal location. Eckardt
et al supplement macular translocation with counter
rotation of the whole eye by extraocular muscle surgery.35
This consists of partial transposition of the four rectialong
with folding and retropositioning of the obliques. These
procedure, involves significant and severe risks;
refinement is needed before the technique is adopted in
larger studies.

Several groups are investigating the possibility of


transplanting RPE after surgically excising CNVM in
ARMD. RPE transplantation could theoretically facilitate repair of RPE defects, which occur after CNVM
excision; it is unclear whether functional repair occurs,
since few humans have undergone this procedure in pilot
studies. In ARMD, photoreceptors ultimately are affected, causing severe vision loss because of the loss or
dysfunction of RPE cells rather than any abnormality of
the photoreceptors themselves.
In the past 15 years, a tremendous amount of research
has been conducted in the area of transplantation of RPE
cells. Two techniques have been used, the external (anterior transvitreal) approach and the internal (posterior
trans-scleral) approach. In either technique, RPE cells are
introduced into the subretinal space as cell suspension
or sheets of RPE cells.
The following types of cells currently are being used
for transplanting: human fetal RPE, immortalized RPE,
porcine fetal RPE, and autologous RPE (obtained from
the same eye that is being transplanted, from a remote
location). RPE cells can be harvested from cadaver eyes
within 24 hours of death and can be preserved at 4C for
up to 48 hours. Cryoprecipitate obtained from human

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Section IV: Retina

blood donors can be used for adhesion cultivation and


transfer of human fetal RPE cells.
Transplanted RPE Cells: Survival
Survival of the grafted transplanted RPE cells can be
monitored by labeling them with carbone particles,
fluorescent dye, radioactive level (3-H thymidine), and
lac-2. Fetal RPE cells do not survive and repopulate
because of the unavailability of extracellular matrix
receptors required for attachment and spreading.
However, cleaning and resurfacing the inner collagenous
layer increased the RPE attachment, decreased apoptosis,
and allowed cells to repopulate. Rejection has been
shown to occur early in patients with wet ARMD than in
patients with dry ARMD, most likely because of
compromised blood-retinal barrier in wet ARMD. Rejection seems to be worse in patients with both major
histocompatibility complex (MHC) I and II incompatibility. It seems to be delayed if patients have only MHC
II incompatibility alone.
Prednisone has been shown to play a significant role
in delaying the rejection process by the way of suppressing the humoral immune responses. Cyclosporine, when
given intravitreally, is shown to prolong the survival of
transplanted RPE cells by inhibiting the first phase of
T-cell activation. Azathioprine has been shown to delay
rejection of the transplanted cells by inhibiting the
delayed hypersensitivity reaction and cellular cytotoxic
activity. Autotransplantation of the RPE cells has shown
to significantly reduce degeneration of photoreceptors
and atrophy of choriocapillaris in the rabbits.
Retinal Prosthesis Implantation
Retinal prosthesis implantation is an experimental
procedure that is yet to be approved by the Food and
Drug Administration (FDA). Human implantation is
performed strictly for research purposes. An exception
is Optobionics Inc, which has implanted 6 subretinal
chips, and although promising, appropriate precautions
need to be taken.
On human volunteers (13 end-stage retinitis pigmentosa, 2 age-related macular degeneration [ARMD]),
Liu and Humayun showed the following:41-42
Electric stimulation led to phosphenes.
Fourteen of 15 localized the position of the
electrodes and tracked the stimulus.
Pattern electric stimulation elicited crude shape
recognition. One patient perceived H as U.
Another patient correctly identified a square
electrode pattern as a matchbox.
Macula had a lower threshold for activation.

Currently, 2 approaches are being investigated for


retinal prosthesis, epiretinal and subretinal. The
epiretinal approach does not disrupt the relationship
between the RPE and retina. However, it must remain
stationary on the inner aspect of the retina and withstand
the rapid ocular movement velocity. The intraocular fluid
may produce electric interference. The subretinal
approach accesses the visual signal integration system
at the earliest possible point, thereby allowing the signals
to be processed by the maximal amount of the processing
system.
Biocompatibility Silicone elastomer provides an effective
encapsulation at the silicone-polymide interface.
Humayun showed that an implant can be placed on the
retinal surface with no significant damage to the retinal
architecture beneath the array and no significant decline
in visual function and measured electroretinogram (ERG)
and visual-evoked potential. 42 Humayun placed an
electrical array on a dog retina for up to 11 months.
Epiretinal Approach
Humayun (JHU), Liu (NCST), and Greenberg (Second
Sight) have developed the Multiple Artificial Retina Chip
(MARC) set.
Image input from a personal computer (PC) or camera
Fine-grained reconfigurable architectures (FPGA)
technology for image processing
Class-E amplifier for power and wireless data
transfer (radiofrequency)
Retina 3.55 provides 60 outputs (8 8 resolution)
Rizzo uses 2 computer chips, a tiny solar panel and a
logic circuit.43
This circuit receives the visual scene that enters the
eye and converts this into a pattern of electrical
pulses. This electrical signal is decoded by an electrode array that rests on the surface of the retina. The
logic circuit measures 2 2 mm and contains 10,000
transistors. Rizzos group also has fabricated a chip
that is 4 m in thickness containing 25 electrodes
placed in a 5 5 array.
After the visual information has been decoded, an
820-nm laser is transmitted to the receiver, which is
in contact with the retinal ganglion cell layer. The
decoder is able to output 60 independent channels of
current.
Subretinal Approach
Chow first proposed the subretinal concept in 1994. Each
chip is fabricated from a silicon wafer using complementary metal-oxide semiconductor (CMOS) technology to

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Chapter 45: Advances in the Management of Age-related Macular Degeneration 445


a 30- to 70-m thickness and 1.0- to 3.0-mm diameter.
Microphotodiodes convert light into electricity, which is
delivered to adjacent tissue using microelectrodes.
Microphotodiodes envisioned by both Zrenner and
Chow are similar.
The artificial silicone retina (ASR) is a subretinal chip
developed by Optobionics. It measures 50 m in thickness and 2.0- to 2.5-mm in diameter. Each microphotodiode array consists of individual photodiode subunits
measuring 20 20 m separated by 10-m channel
stops. Each unit is powered by incident light. Each chip
contains 3500 microphotodiodes designed to convert
visual image into electrical impulses to stimulate the
remaining functional cells of the retina. This chip
currently is undergoing human implantation phase. Six
patients have been implanted with the ASR chip. Results
are pending.
A hybrid retinal implant placed in subretinal space is
being investigated by Yagi in Nagoya. This approach
consists of a microelectromechanical system (MEMS) and
transplanted neural cells placed on the unit serving as
living wires. These neural cells are guided to the central
nervous system using axon-guiding substrates. This
method does not require ganglion cells or an optic nerve.
Therefore, this is a better approach for patients with
vision loss due to glaucoma. A photosensor is placed in
the anterior chamber and connected to the signal decoder
placed subretinally. No results are available in the
literature.
Visual Cortex Prosthesis
A group in Illinois Institute of Technology is developing
a 1024-electrode intracortical visual prosthesis array for
implantation into area V1. This array will be connected
to a fully implanted electronic module that will drive
the microelectrodes with biphasic stimulation, in response to commands sent to the implant over a transcutaneous link. Metal microelectrodes will penetrate to layer
4 of the primary visual cortex and a combination of 16electrode arrays, and single hat-pin electrodes will be
distributed over the accessible portion of V1. Wires will
connect the electrodes to four 256-channel stimulator
modules that will be implanted in an extradural space.
The 256-channel stimulator module will be comprised
of custom-fabricated integrated circuits within a custom
hermetic ceramic package. Each module will be
comprised of four 64-channel submodules. Implantable
stimulator circuitry has been fabricated. Safety and
efficacy testing of the system is being performed. Iezzi
at Kresge is working on a chemical neurotransmission
interface rather than electric stimulation used by other

groups.44 All these techniques are in the experimental


stages and we have to wait for results to come before
reach any definite conclusions regarding their benefits.
Gene Therapy
The future horizon shows promise of a gene transfer
treatment for ARMD. The investigational agent, Ad(GV)
PEDF. 11D, is replication-deficient, adenovirus, gene
transfer vector. The transgene in this vector is the cDNA
for human pigment epithelium-derived factor (PEDF).
PEDF is one of the most potent known antiangiogenic
proteins found in human eye. The intravitreal administration of Ad (GV) PEDF. 11D provides a convenient
means of delivering PEDF to the relevant cells within
the eye. In three murine disease models (the laserinduced choroidal neovascularization model, the VEGF
transgenic model, and the retinopathy of prematurity
model) significant inhibition of neovascularization (up
to 85%) was demonstrated.45
It is also known that VEGF plays a crucial role in the
formation of SRN and VEGF soluble receptor gene transfection can inhibit subretinal neovascularisation. This will
contribute to future gene therapy for age-related macular
degeneration.46
Primary Prevention of ARMD
Prevention is the best treatment in this case because no
satisfactory method exists to treat dry AMD. Accumulated evidence suggests that AMD is a genetic disease.
Therefore, children of patients who have lost vision to
AMD are the best candidates for a primary prevention
trial. Such a trial has yet to be conducted. The age relate
eye disease study (AREDS ) evaluated the role of nutrition in AMD.47 It showed that the combination of zinc
and antioxidants had a modest benefit in delaying
progression of ARMD in intermediate(non central
geographic atrophy or atleast one large drusen or atleast
20 intermediate drusen 63 to 125 microns in diameter)
and high risk eyes.It was estimated that after 5 years,the
risk of progression to advanced ARMD was 28 percent
in the placebo group,23 percent in the antioxidant group,
22 percent in zinc group and 20 percent in the
combination group.
Clear evidence shows that smoking accelerates the
disease process. It is recommended that patients who
have a family history of AMD, and specifically those
patients whose first-degree relative has lost vision due
to AMD, should take a multivitamin with lutein each
day. It is advised that patients stop smoking and consider
supplemental oral antioxidants if they are unable to stop
smoking.

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Section IV: Retina

PREVENTION STUDIES
Depending on the type of drusen,particularly the
presence of soft drusen or in numbrs greater than 5,an
eye is at high risk of developing CNV.MPS group felt
that the risk of 60 percent exsisted in the fellow eye after
5 years.
Laser treatment for the prevention of developing
ARMD was thought because of the strong link between
drusens and formation of ARMD. Various studies were
undertaken like.
Prophylactic Treatment of AMD (PTAMD)
Choroidal neovascularization prevention trial(CNVPT)
and Complications of AMD prevention trial(CAPT).
CNVPT used visible argon green laser burns and
diode subthreshold burns were used in PTAMD. Subthrehold burns were created by a test burn in nasal
quadrant.Endpoint was a mild gray lesion with 0.2
Silicone oil removal duration. In the CNVPT, enrollment
was stopped before recruitment was completed as a
higher incidence of CNV (24% vs 2%) was seen in the
laser treated eyes of the fellow eye at the end of first year.
It was thought that these eyes harboured an
occult CNV. Laser treatment may spark off activity in a
dormant CNV.On the other hand, PTAMD, CNV
incidence was not increased in the laser treated eyes.
PATIENT EDUCATION
Patients with GA may have a variety of visual dysfunction. The location of atrophy often suggests the type of
visual dysfunction that will be experienced by the
patient. Many patients with macular degeneration
complain of difficulty in adjusting to changing light
conditions; specifically, they take a significantly longer
time to adjust to indoor lighting after being outside in
bright sunlight. Wrap around outdoor sunglasses that
have an orange tint work for some patients.
Patients who primarily have central atrophy often
note trouble with reading and performing fine motor
tasks. Magnification and increased contrast (via a
monitor or increased illumination) are the best solutions
for such visual dysfunction.
In contrast, other patients have GA that spares the
foveal center but affects the entire perifoveal region.
These patients often can see 20/20, but they are unable
to navigate due to the small area of good visual acuity.
In fact, some of these patients have to scan the screen to
be able to see the 20/400 character. In these patients,
excess magnification would be detrimental, as it would

effectively decease their limited visual field. Increased


contrast and minification, by way of increased illumination and reverse telescopes respectively, may be
beneficial for these patients.
IMPLANTABLE MINIATURISED TELESCOPE (IMT)
This is a new approach to aid vision in patients with
atrophic ARM .It was developed by Dr. Isaac Lipshutz
of Israel-1997, and he has done 7 implants so far .
A small clinical trial is being conducted in the U.S. to
test the safety and efficacy of the device.91 percent of
patients tried with this device reported improvement in
viewing TV and 66 percent reported improved reading
vision.The device is a miniatured 3X telescope contained
in a PMMA carrying device.It contains a number of
microlenses which magnify objects in the patients central
field of vision hey work with the natural optics of the
patients cornea to basically reproduce a classic Galilean
Telescope.It is surgically implanted replacing the eyes
natural lens.
Advantages

Wider visual field than telescopic glasses.


More convenient focal distance [50 cm.]
Better magnification possibilities [8x].
Good resolution and contrast vision.
No excessive light required.
No previous analysis with SLO required.
No need to hold the device with hand.
Most useful in patients with physical disabilities.
Decreased aberrations created by external devices.
Glasses can be used if condition detoriates.
More comfortable and much better aesthetically
accepted.

Diasadvantages

Anisiekonia
Diplopia
Large incision required during surgery
Transient postoperative difficulty in orientation
Analysis of patients psychological profile preoperatively
Special visual rehabilitation training programme
required
IMT resembles an IOL: a central optic cylinder,a
support system and 2 haptics.
Weighs 45 mg.
Consists of a tiny galilean telescope embedded in a
6 mm PMMA implant.

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Chapter 45: Advances in the Management of Age-related Macular Degeneration 447


The telescopic lens is 4.2mm in length and has a 3.2
mm diameter.
Central Optical Cylinder
Resembles a galileo-type telescope.It consists of an anterior positive lens and a posterior negative lens giving a
power of -120D in air.It is biocompatible and is made of
pure glass.
Support System
Contains an antireflex coating.It gives 3X magnification
at 50 cm and is made of PMMA .
Surgical Technique

A 6.5 mm CCC through 3.1 mm limbal incision.


Standard phacoemulsification performed.
Initial 3.1 incision extended to about 12mm.
Surround the system with viscoelastic.
IMT implanted in the capsular bag and haptics
positioned at 12 and 6 hours.
Implantation in the bag provides better stabilization
and avoids decentration.
The pupil is pharmacologically constricted.
Upper peripheral iridectomy performed.
Incision closed with 10/0 nylon interrupted sutures.

Interior Decorator Approach


As a low vision aid it is suggested that the environment
of the patient can be suitably modified so as to help his
disability. The door knobs at home for example can be
large in size, the telephone dial also large.The colour
schemes in the house should be such to give a good
contrast.The staircase easy to maneuver.These and
similar simple modifications can make life much easier
for the patient suffering from ARMD.
REFERENCES
1. National Advisory Eye council (US): Vision research:a national
plan 1994-1998,Bethesda,Md1993,Us department of health and
human services,NIH Pub no 93-3186.
2. National centre for health statistics:plan and operation for the
NHANES III:United states 1988-1994,Vital health stat vol I,1994.
3. Sarks JP, Sarks SH, KillingworthM: Evolution of geographic
atrophy of the pigment epithelium, Eye 1988;2:552-77.
4. Suneness JS, Bressler NM et al: The development of choroidal
neovascularisation in eyes with geographic atrophy form of
age-related macular degeneration,Ophthalmology 1999;106:
910-19.

5. Macular Photocoagulation Study Group: Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year
results from randomized clinical trials. Arch Ophthalmol 1994
112(4): 500-09.
6. Macular pPhototocoagulation Study Group: Five-year followup of fellow eyes of patients with age-related macular degeneration and unilateral extrafoveal choroidal neovascularization .
Arch Ophthalmol 1993;111:1189-99.
7. Macular Photocoagulation Study Group: Argon laser photocoagulation for senile macular degeneration. Results of a
randomized clinical trial. Arch Ophthalmol 1982;100:91223[Medline].
8. Macular Photocoagulation Study Group: Krypton laser photocoagulation for neovascular lesions of age-related macular
degeneration: Results of a randomized clinical trial. Arch
Ophthalmol 1990;108: 816-24.
9. Macular Photocoagulation Study Group: Evaluation of argon
green vs krypton red laser for photocoagulation of subfoveal
choroidal neovascularization in the macular photocoagulation
study. Arch Ophthalmol 1994;112:1176-84.
10. Macular Photocoagulation Study Group: Subfoveal neovascular
lesions in age-related macular degeneration; Guidelines for
evaluation and treatment in the macular photocoagulation
study. Arch Ophthalmol 1991;109:1242-57.
11. Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal neovascular lesions in age-related macular
degeneration. Arch Ophthalmol 1991;109:1220-31.
12. Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal neovascular lesions of age-related macular
degeneration. Arch Ophthalmol 1993;111:1200-09.
13. Macular Photocoagulation Study Group: Recurrent choroidal
neovascularization after argon laser photocoagulation for
neovascular maculopathy. Arch Ophthalmol 1986;104:503-12.
14. Macular Photocoagulation Study Group: Persistent and
recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular
degeneration. Arch Ophthalmol 1990;108:825-31.
15. Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal recurrent neovascular lesions in age-related
macular degeneration. Results of a randomized clinical trial.
Macular Photocoagulation Study Group. Arch Ophthalmol
1991; 109(9):1232-41.
16. Macular Photocoagulation Study Group: Visual outcome after
laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. The
influence of initial lesion size and initial visual acuity. Arch
Ophthalmol 1994;112: 480-88.
17. Macular Photocoagulation Study Group: Argon laser photocoagulation for neovascular maculopathy; Three-year results
from randomized clinical trials. Arch Ophthalmol 1986;104: 694701.
18. Shiraga F, Ojima Y, Matsuo T, et al: Feeder Vessel Photocoagulation of Subfoveal Choroidal Neovascularization Secondary
to Age-related Macular Degeneration. Ophthalmology 1998;
105(4): 662-69.
19. Bressler NM, Maguire MG, Murphy PL: Macular scatter (grid)
laser treatment of poorly demarcated subfoveal choroidal
neovascularization in age-related macular degeneration. Results
of a randomized pilot trial. Arch Ophthalmol 1996;114(12): 145664.
20. Robert W Fowler: Experimental studies if ICG dye enhanced
photocoagulation of choroidal neovascularization feeder
vessels.Am J Ohthalmol 2000:501-12.

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448

Section IV: Retina

21. Peyman GA, Moshfeghi DM, Moshfeghi A, et al: Photodynamic


therapy for choriocapillaris using tin ethyl etiopurpurin (SnET2).
Ophthalmic Surg Lasers 1997; 28(5): 409-17.
22. Reichel E, Berrocal AM, IpM: Transpupillary thermotherapy of
occult subfoveal choroidal neovascularization in patients with
age-related macular degeneration. Ophthalmology 1999;
106(10):1908-14.
23. Chakravarthy U, Houston RF, Archer DB: Treatment of agerelated subfoveal neovascular membranes by teletherapy: a pilot
study. Br J Ophthalmol 1993;77(5):265-73.
24. Spaide RF, Guyer DR, McCormick B, et al: External beam radiation therapy for choroidal neovascularization. Ophthalmology
1998;105(1):24-30.
25. Tholen AM, Meister A, Bernasconi PP: [Radiotherapy for
choroidal neovascularization in age-related macular degeneration. A pilot study using low- versus high-dose photon bean
radiation]. Ophthalmologe 1998; 95(10): 691-98.
26. Okamoto N, Tobe T, Hackett SF, et al: Transgenic mice with
increased expression of vascular endothelial growth factor in
the retina: a new model of intraretinal and subretinal.
27. Smith LE, Kopchick JJ, Chen W, et al: Essential role of growth
hormone in ischemia-induced retinal neovascularization.
Science 1997;13; 276(5319):1706-09.
28. Danis RP, Bingaman DP, Yang Y, et al: Inhibition of preretinal
and optic nerve head neovascularization in pigs by intravitreal
triamcinolone acetonide. Ophthalmology 1996;103(12):2099104.
29. Fung WE: Interferon alpha 2a for treatment of age-related
macular degeneration [letter]. Am J Ophthalmol 1991;112(3):
349-50.
30. Penfold P, et al: Exudative macular degeneration and intravitreal
triamcinolone. A pilot study. Aust N Zeal J Ophthalmol 1995;
23: 293-98.
31. Challa JK, Gillies MC, Penfold PL: Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up. Aust
N Z J Ophthalmol 1998; 26(4): 277-81.
32. Clark AF, Mellon J, Li XY, et al: Inhibition of intraocular tumor
growth by topical application of the angiostatic steroid
anecortave acetate. Invest Ophthalmol Vis Sci 1999; 40(9): 215862.
33. Ip M, Gorin MB: Recurrence of a choroidal neovascular
membrane in a patient with punctate inner choroidopathy
treated with daily doses of thalidomide. Am J Ophthalmol 1996;
122(4): 594-95.

34. Machemer R, Steinhorst UH: Retinal separation, retinotomy, and


macular relocation: II. A surgical approach for age-related
macular degeneration? Graefes Arch Clin Exp Ophthalmol 1993;
231(11):635-41.
36. de Juan E Jr, Loewenstein A, Bressler NM, et al: Translocation
of the retina for management of subfoveal choroidal
neovascularization II: a preliminary report in humans. Am J
Ophthalmol 1998;125(5): 635-46.
37. Lim JI. Subretinal haemorrhage. In Sternberg P, Lim JI (Eds):
Macular disease. Int Ophthalmol Clin 1995;35:95-104.
38. Peyman GA,Nelson et al. Tissue plasminogen activating factor
assisted removal of subretinal hemorrhage. Ophthalmic surg
1991;22:575-82.
39. Ohji M,et al. Pnuematic displacement of subretinal blood
without tissue plasminogen activator.Arch ophthalmol
1998;116:1326-32.
40. Daneshwar H, et al. Management of submacular haemorrhage
with intravitreal sulphur hexafluoride: a pilot study.Can j
ophthalmol 1999;34:385-88.
41. Humayun M, Propst R, deJuan JE: Bipolar surface electrical
stimulation of the vertebrate retina. Arch Ophthalmol 1994;
112(1):110-16.
42. Humayun MS, de Juan JE, Weiland JD: Pattern electrical
stimulation of the human retina. Vision Research 1999; 39: 256976.
43. Wyatt JL, Rizzo JF, Grumet AE: Development of a silicon retinal
implant: epiretinal stimulation of retinal ganglion cells in the
rabbit. Invest Ophthalmol Vis Sci 1994;35(4):1380.
44. Iezzi R: Artificial vision 2000: cortical stimulation. Presented at
Retina 2000 at the American Academy of Ophthalmology
Subspecialty Meeting.
45. Rasmussen H, Chu KW, Campochiaro P, Gehlbach PL, Haller
JA, Handa JT, Nguyen QD, Sung JU. Clinical Research and
Regulatory Affairs, USA.
46. Adenovirus-mediated soluble VEGF/flt-1 receptor gene
transfection: a role of VEGF and possible treatment for SRN in
age-related macular degeneration. Honda M, Sakamoto T,
Ishibashi T, Inomata H, Ueno H. Department of Ophthalmology,
Faculty of Medicine, Kyushu University, Fukuoka, Japan.
47. Age Related Eye disease study Research Group.A randomized,placebo-controlled,clinical trial of high dose
supplementation with vitamins C and E ,and zinc for age related
macular degeneration and vision loss.Arch Ophthalmol
2001;119:1417-36.

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Section V

Ocular Therapeutics
46. Update on Routes of Administration and Drug Delivery Systems in Ophthalmology
Ashok Garg
47. Update on Antibacterial Therapy
Ashok Garg
48. Update on Anti-inflammatory Therapy
Ashok Garg
49. Update on Ophthalmic Dyes
Ashok Garg
50. Quick Look Ocular TherapeuticsAn Update
Ashok Garg
51. Future Drugs in Ophthalmology
Ashok Garg

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46

Update on Routes of
Administration and Drug
Delivery Systems in Ophthalmology
Ashok Garg

LOCAL APPLICATION
SYSTEMIC ADMINISTRATION
MEDICATIONS FORMS USED IN
OPHTHALMOLOGY
PRACTICAL TIPS FOR USE OF
VARIOUS OPHTHALMIC
MEDICATIONS

For ocular drugs to be effective an ideal drug delivery system (DDS) should
deliver the drug at the receptor site in ocular tissues in relatively high
concentration to elicit the desired pharmacological response. Most of the
ophthalmic drugs are applied topically in the form of eyedrops. The time
course of drug deliver from an eyedrop follows a first order kinetics. It is
well-known that about 1 percent or less of an applied dose is absorbed
across the cornea topically to reach the anterior segment of eye.
The major problem in the drug treatment (topical) of ocular diseases is
the difficulty of achieving a sufficient quantity of drug at the desired site
of action. The tight junctions of iris capillaries and retina act as a barrier to
the diffusion of drugs from the blood into the aqueous and vitreous and
the cornea acts as a barrier to drugs applied locally. Another factor quite
important is the rate of removal from the eye of any drug that does actually
penetrate into the aqueous or vitreous because although inflammation may
reduce the barrier to penetration of the drug into the eye, the associated
hyperemia will also speed the removal of the drug from the eye.
During the last decade research is going on in ophthalmic field for a
suitable mode of ocular therapy to provide higher and sustained
penetration of the drugs into the ocular tissues and anterior chamber
promptly and effectively.
Most important factor which modify drug penetration is slow release
of the drug thereby increasing the contact time of the drug to the ocular
structures. The duration of drug action in the eye can be extended by:
a. Reducing drainage through the use of viscosity enhancing agents.
b. Improving corneal drug penetration. An ideal drug delivery system
should have
i. Spatial placement
ii. Controlled drug delivery.
The routes of administration are local and systemic for ocular diseases.
LOCAL APPLICATION
Local application of drugs for the treatment of superficial eye diseases is a
very satisfactory route. When the desired site of action of the drug is inside
the eye then the problem of ocular barrier arises.

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452 Section V: Ocular Therapeutics


Corneal Barrier
For practical purposes cornea can be considered to consist
of three layers. The outer and inner layers (The epithelium and the endothelium) prevent water soluble agents,
e.g. ionised molecules passing into the eye, but permit
the passage of lipid soluble agents whereas the corneal
stroma resists the passage of lipid soluble agents but
freely allows the passage of water soluble agents. Drugs
with dual capability are usually capable of changing from
lipid solubility to water solubility of ionisation. The
effectiveness of corneal barrier may be considerably
reduced by damage to the corneal epithelium.
Scleral Barrier
The sclera unlike cornea does not act as a differential
solubility barrier and is relatively porous. However, there
is unidirectional flow across the sclera from the inside to
the outside of the eye. The intraocular pressure may be
partially responsible for this.

Application to the corneal surface may be in form of


topical drops, ointments, gels, viscous preparations,
constant release membranes and soft lenses. Topical
drops route is commonly used to treat various ocular
infections, inflammation and as topical anesthesia in
modern cataract surgery, phacoemulsification and
LASIK surgery.
The passage of the drug is aided by damage to the
corneal epithelium and on the amount of drug in contact
with cornea and duration of contact.
When topical drops are used, much is lost because it
is washed away by the tears.
Viscous and ointment preparations of drugs including oil suspensions and methyl cellulose solutions
prolong contact time. This reduces the total quantity of
drug given to the patients as well as reducing the
unwanted frequency of medication giving better patient
compliance.
Membrane Bound Devices
Ocusert System

Methods of Local Application of Drugs


a.
b.
c.
d.

Application to corneal surface.


Subconjunctival route.
Retrobulbar route.
Direct injection into the aqueous or vitreous.

Application to the Corneal Surface


The drug through this route must fulfil the necessary
criteria for passing the corneal barrier to penetrate into
the eye.
Formally, the drug delivery kinetics passing through
this route can be divided in two parts.
First order kinetics In this conc of drug available for
penetration falls off exponentially as the medication is
diluted and washed away by the tear film and drug conc
achieved in posterior segment of the eye is very less. This
type of drug delivery is provided by aqueous or high
viscosity solutions, ointments or hydrogel drug delivery
system.
Zero order kinetics In this system drug is held in
reservoir and is released into the tear film at the constant
rate to provide constant drug conc in the cornea or
aqueous.
This drug delivery system is provided by ocuserts,
soluble ophthalmic drug inserts (SODI) and the osmotic
pumps, and liposomal drug delivery system, cotton
pledgets and filter paper strips.

This system was the first ophthalmic drug delivery


system approved by US FDA for use in human beings.
Ocuserts provide zero order kinetics drug release.
The ocuserts is a device with a two membrane sandwich with a pilocarpine reservoir in the center. The
copolymeric membrane is ethyline vinylacetate also
encased between the membranes is a white titanium
dioxide ring that aids in visualizing and handling the
inserts.
Ocuserts not only provides zero order delivery of the
drug but the total amount of drug needed for therapeutic
effect is much less than what used as drops or suspension.
Ocuserts are soft and extremely flexible and can be
placed either under the upper or lower lid.
The problems with ocuserts can be cost factor, foreign
body sensation or incidental loss of ocusert from the culde-sac. Other type of ocuserts are diffusible units osmotic
units and erodible units. Drugs that can be delivered
through ocuserts are pilocarpine, antibiotics, steroids,
carbachol or a combination.
Drug Impregnated Inserts
Soluble ophthalmic drug inserts (SODI) were first
introduced in seventies and are made of polymers of
acrylamide, ethylacrylate and vinyl pyrolidone. SODI
dissolve in the cul-de-sac and is capable to provide
detectable drugs levels in the cornea upto 48 hours.
Wafers were introduced in eighties. Warfers are
soluble ophthalmic inserts made of succinylated collagen.

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Chapter 46: Update on Routes of Administration and Drug Delivery Systems in Ophthalmology

453

These wafers are 6 mm x 12 mm in size and are inserted


into the inferior cul-de-sac. Antibiotics can be delivered
through this route.
Hydrogel Contact Lens Delivery
The hydrogel contact lenses (soft lenses) by virtue of their
high water content and large intermolecular pore size,
absorb water soluble drugs and release them initially in
a high pulse and then release gradually. Hydrogel lenses
can be used to deliver water soluble drugs like dexamethasone, antibiotics and pilocarpine. These lenses can
be an excellent route of administration. The lens is
inserted into the eye after being presoaked in the drug
solution. This device is often used in the management of
dry eye disorders.
Osmotic Pumps

Fig. 46.1: Sub-Tenons plane relationship (cross-section view)

Osmotic pump recently introduced is the drug delivery


system of future to treat various ocular diseases
commonly. Osmotic pumps, contain salt enclosed in one
compartment and drug enclosed in an adjacent
compartment. Both compartments have flexible walls.
This type of device can deliver any type of medication
into the eye regardless of its solubility or molecular
weight. The development of new polymeric membranes
for use as drug inserts envelops, has recently begun.
Research work is going on suitable new site specific
drugs delivery system, one side coated hydroxy propyl
cellulose inserts, sub-Tenon administration of drug
through collagen sponges connected with silicon tube
work is going on Margan Therapeutic Lens as continuous
corneal perfusion system and on colloidal suspension
capsules with an oily core in which drugs is dissolved
(nano capsules).
Periocular Administration
When higher concentrations of drugs are required they
can be injected locally into the periocular tissues. Periocular drug administration include injection under
bulbar conjunctiva, under Tenon capsule (sub-Tenons)
(Fig. 46.1) and behind globe itself and peribulbar route.
Drugs most often delivered in this manner include
steroids and antibiotics. Local anesthetics are commonly
injected through peribulbar route prior to cataract
extraction and other intraocular surgical procedures.
Subconjunctival Route
This route including injection under the bulbar conjunctiva used to achieve high concentrations of drug in the

anterior chamber. Antibiotics, steroids, mydriatics can


be given by this route.
Subconjunctival injections are painful so this route is
used only in severe cases of ocular inflammation or
infection of the anterior segment.
Retrobulbar Route
Drugs can be delivered to the back of the orbit by retrobulbar injections. This is the route for local anesthesia in
ocular surgery. Steroids may also be injected by this route
to reduce optic nerve or posterior segment inflammation
(Fig. 46.2).
Intracameral Administration
Intracameral administration involves placing drug
directly into the anterior chamber of the eye. This is most
commonly associated with cataract extraction, IOL
implantation and phacoemulsification during which a
viscoelastic substance is injected into the anterior
chamber to protect the corneal endothelium. Antibiotics
are not routinely injected into the anterior chamber as
there is significant risk of complications as well as drug
toxicity.
Intravitreal Administration
The intravitreal injection is primarily reserved as a last
effort to save eye with severe acute infection or intraocular inflammation. Intravitreal antibiotics is the
treatment of choice for endophthalmitis. Intravitreal
liquid silicone is used for the treatment of complicated

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454 Section V: Ocular Therapeutics

Fig. 46.2: Retrobulbar and peribulbar anesthesia (needle positions)

retinal detachment. Recently intravitreal ganciclovir has


been used with success in treating cytomegaloretinitis
in patient with AIDS.

This is new administration route for local anesthesia

which is highly useful, safe, effective and technically


easier. In this method consisting of a limbal sub-Tenon
administration of retrobulbar anesthesia using a blunt
irrigating cannula. This technique can be used involving
anterior and posterior segment surgery (Figs 46.3 and
46.4).

Fig. 46.3: Parabulbar (flush) local anesthesia


(surgeons view)

Fig. 46.4: Parabulbar (flush) local anesthesia


(cross-section view)

Parabulbar (Flush) Administration

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Chapter 46: Update on Routes of Administration and Drug Delivery Systems in Ophthalmology
Peribulbar Administration
Peribulbar administration is mainly used for giving local
anesthesia for modern intraocular surgery. Since the exit
of retrobulbar route peribulbar is safe and effective route
of administrating local anesthesia. Peribulbar route is safe
because here local injection is given out of muscle cone
and complications like intraconal hemorrhage or
damage to optic nerve are ruled out.
In this method a cocktail of lignocaine and bupivacaine is injected at the junction of lateral 1/3rd and
medial 2/3rd of inferior orbital rim by 26 gauge 1 long
needle which is directed backward and medially to its
whole length. At present after topical anesthesia,
peribulbar anesthesia is most commonly used method
of giving local anesthesia worldwide (Fig. 46.5).
Direct Injection into the Globe
Drugs are often introduced into the eye during ocular
surgery. Care is taken that the conc of drug the vehicle
and the type of preservative is suitable. Antibiotics may
be injected directly into the aqueous and vitreous in cases
of Endophthalmitis.
SYSTEMIC ADMINISTRATION
General rules for systemic drug administration apply but
there is an effective blood aqueous and blood vitreous

455

barrier so that intraocular levels of systemically


administered drugs are usually lower than the serum.
Most drugs will cross the aqueous and vitreous in
cases of ocular inflammatory diseases which increases
permeability. In systemic administration drugs can be
given orally or by intramuscular intravenous injections.
Although most ocular diseases respond to topical therapy
but certain ocular disorders require systemic drug
administration. Oral administration of certain drugs may
be most effective route of drug delivery. Carbonic
anhydrase inhibitors for treatment of glaucoma, steroids
for optic neuritis, uveitis, analgesics for the management
of pain associated with ocular trauma, antibiotic therapy
for ocular infections and antihistaminic therapy for acute
ocular allergy are few examples of oral administration.
Parental administration includes intramuscular (IM)
and intravenous (IV) injections. Hydroxy cobalamin
(Vitamin B12) and certain antibiotics are given through
IM route. Continuous IV infusion of various antibiotics
may be required for treatment of endophthalmitis and
other severe ocular infections.
The futuristic considerations in ocular drug delivery
system is to make drug delivery in therapeutic conc in
the posterior segment of the globe. The new modifications
in ocular DDS design must not only work on the corneal
route for drug absorption but also of other routes like
scleral route. There is also need of sophisticated technology to monitor the pharmacokinetics.
MEDICATIONS FORMS USED IN OPHTHALMOLOGY
Solutions and Suspensions
This is one of the most common forms of drug delivery
system being used in ophthalmology today. Most of the
topical ocular preparations are commercially available
as solutions or suspensions which are applied directly
to the eye from the bottle via sterile eye dropper provided
along with.
Patient should be cautioned about touching the
dropper tip to the eye as it can lead to contamination of
the medication beside causing ocular injury. Patient
should not also touch tip of the dropper with hand to
avoid contamination of preparation. Suspension forms
should be shaken before use to provide an accurate
dosage of drug.
Ointments

Fig. 46.5: Needle positions for retrobulbar or peribulbar


anesthesia (frontal view)

This is second most common form of drug delivery


system used in ophthalmology. The main purpose for an

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456 Section V: Ocular Therapeutics


ophthalmic ointment vehicle is to prolong drug contact
time with the eye. Ointments are specially useful for
treating children who may not cooperate for topically
applied solutions. Ointments are specially useful for
medicating ocular injuries such as corneal abrasions
where the eye needs to be patched. Always administer
solutions before ointments as ointments preclude entry
of subsequent drops. In general put 0.25-0.50 inch ribbon
of ointment with a sweeping motion inside the lower lid
by squeezing the tube gently and slowly release the
eyelid. Ask the patient to close the eye for 1-2 minutes
and remove excessive ointment around the eye. Patients
should be cautioned about temporary blurring of vision
due to ointment. Patients should avoid activities requiring visual acuity until blurring clears.
Gels
In modern ophthalmic drug delivery systems gels are
fast gaining importance. Ophthalmic gels are similar in
viscosity and clinical usage to ophthalmic ointments. Gels
provide prolonged contact time for medication within
the precorneal tear film.
Sprays
Some ophthalmic medications like mydriatics and
cycloplegics alone or in combination can be administered
as spray to the eye to dilate pupil or cycloplegic examination. This form is specially used for pediatric patients
and solution is administered using a sterile perfume
atomizer or plastic spray bottle.
Lid Scrubs
Certain commercial ophthalmic preparations (eyelid
cleansers, antibiotic solutions or ointments) can be
applied directly to eyelid margin for the treatment of noninfectious blepharitis. This is ideally achieved by applying the medication to the end of the special cotton tipped
applicator and then scrubbing the eyelid margins several
times daily. Gauze pads supplied with commercially
available eyelid cleansers are also suitable.
Medication Devices Used in Ophthalmology
Contact Lenses
Therapeutic soft contact lenses with high water content
are of great benefit in treating several ophthalmic
diseases. Soft contact lenses can absorb water soluble
drugs and release them into the eye over a prolonged

duration. These lenses are specially useful in promoting


sustained release of solutions or suspensions that
normally would be removed quickly from the external
ocular tissues. Therapeutic soft contact lenses are used
commonly as drug delivery devices in the management
of dry eye disorders. Sometimes these lenses are also used
for the treatment of ocular infections specially bacterial
corneal ulcers.
Corneal Shields
Porcine or bovine scleral collagen shields are commercially available which are usually non-cross linked and
homogenized. Corneal shields are generally placed as a
bandage on the cornea following surgery or injury to
protect and lubricate the cornea. For treating bacterial
corneal ulcers corneal shields are used in conjunction
with topical antibiotics with good results.
Cotton Pledgets
Small cotton pieces can be soaked with topical ophthalmic solutions and placed in conjunctival sac. Such devices
certainly allow a prolonged ocular contact time with
solutions that are normally instilled topically into the eye.
Generally cotton pledgets are used for the administration
of mydriatic solutions. This drug delivery device promotes maximum mydriasis in an effort to break posterior
synechiae or to dilate sluggish pupils.
Filter Paper Strips
Fluorescein strips are commercially available as drug
impregnated filter paper strips (Sodium fluorescein,
Rose bengal or Flurexon). These filter strips help to
ensure sterility of sodium fluorescein which can be
easily contaminated with Pseudomonas aeruginosa when
prepared in solution. These test strips are used diagnostically to identify corneal injuries and infections.
Schirmer tear test strips are also available commercially
for diagnosing dry eye disorders.
Artificial Tear Inserts
A specially designed rod-shaped pellet of hydroxy
propyl cellulose without preservative is commercially
available to be inserted into the inferior conjunctival sac
with a special applicator. Following insertion, these
devices absorbs fluid, swells and then releases the nonmedicated polymer to the eye for a duration of 24 hours.
Ocuserts are specially used in the treatment of dry eye
disorders.

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Chapter 46: Update on Routes of Administration and Drug Delivery Systems in Ophthalmology
Membrane Bound Inserts
Ocuserts are membrane controlled drug delivery system
which deliver a constant quantity of medication to the
eye for a week continuously. Pilocarpine ocuserts are
commonly used in the treatment of glaucoma. These
ocuserts are placed on to bulbar conjunctiva under the
upper or lower eyelid. Pilocarpine ocusert is a useful
substitute for pilocarpine drops or gel in glaucoma
patients who have poor compliance with more frequent
drug instillation.
PRACTICAL TIPS FOR USE OF VARIOUS
OPHTHALMIC MEDICATIONS
Proper administration of ophthalmic drugs is absolutely
essential to achieve optimal therapeutic results. Here I
shall describe several common practical points which
should be informed to the patients before starting any
ophthalmic formulation.
a. Never instill more than one properly placed drop of
ophthalmic solution or suspension into the affected
eye. Normal eye retains 10mcl of fluid on an average.
Generally eyedropper delivers 25-50 mcl/drop of
fluid.
For proper placement of drop into the eye ask the
patient to tilt head backward or lie down in supine
position with gaze upward. Gently grasp lower eyelid
below eyelashes and pull the eyelid away from the
eye to form a pouch. Put dropper directly over eye.
Avoid contact of dropper with the eye. Keep the
dropper tip about one inch away from the eye. Look
upward before instilling the drop. Release the lid
slowly and close eye gently for 2-3 minutes.
b. Systemic absorption of ophthalmic solution or suspension can be minimized by compressing the
canaliculus and lacrimal sac for 3-5 minutes after
instillation. This compressing certainly retards the
passage of drops via nasolacrimal duct into the areas
of potential absorption like nasal and pharyngeal
mucosa.
c. When multisolution therapy is indicated ideally instill
the drops separately at 5 minutes interval. This
ensures that first solution drop is not flushed away
by the second or second is not diluted by first one.
d. Certain ophthalmic factors may increase absorption
from ophthalmic dose forms like lax eyelids specially
in elderly patients and diseased eyes which forms a
great pool for retention of topical solution or
suspension.
e. Discourage the use of eye cup in cases of eye lotions
due to risk of contamination and spreading disease.

457

f. Ophthalmic suspensions generally mix with tears


poorly and remain in the lower cul-de-sac longer than
solutions.
g. Ophthalmic ointments are helpful in maintaining
contact between ocular tissues and drug by decreasing the rate as slow as 0.5 percent per minute.
Ophthalmic ointments provide maximum contact
between drug and ocular tissues.
h. Ophthalmic ointments should be instilled preferably
at bedtime as it may impede delivery of other
ophthalmic drugs to the affected eye by acting as a
barrier to contact.
i. Ointments may blur vision during waking hours so
bed time use is generally recommended.
j. Monitor expiration dates of ophthalmic medications.
Do not use outdated drugs.
k. Ophthalmic solutions and ointments are generally
misused. Patient use these medications on their own
without counseling ophthalmologists. Appropriate
patient education and counseling with prescribing
and dispensing of ophthalmic medicines is essential.
FURTHER READING
1. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.
2. Bartlett. JD, Clinical Ocular Pharmacology, ed.4, Boston:
Butterworth-Heinemann,2001.
3. Bartlett. JD, Ophthalmic Drug Facts: Lippincott William and
Wilkins, 2001.
4. Crick. RP, Trimble RB, Textbook of Clinical Ophthalmology:
Hodder and Stoughton, 1986.
5. Duane. TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
6. Duvall, Ophthalmic Medications and Pharmacology: Slack Inc,
1998.
7. Ellis. PP, Ocular Therapeutics and Pharmacology, ed. 7: C.V.
Mosby, 1985.
8. Fechner, Ocular Therapeutics: Slack Inc., 1998.
9. Feibel RM, Current Concepts in Retrobulbar Anaesthesia: Surv.
Ophthalmol, 1985; 30: 102.
10. Fraunfelder, Current Ocular Therapy, ed. 5: W.B. Saunders, 2000.
11. Fraunfelder FT, Ophthalmic Drug Delivery Systems: Surv.
Ophthalmol, 1974; 18: 292.
12. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
13. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
14. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
15. Goodman. LS, Gilman. A, Pharmacological Basis of Therapeutics, ed.7, New York: Macmillan, 1985.
16. Halberg GP, Drug Delivery Systems for Topical Ophthalmic
Medication, Ann. Ophthalmol, 1975; 7: 1199.
17. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.
18. Kanski, Clinical Ophthalmology, ed. 4: Butterworth
Heineman, 1999.

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458 Section V: Ocular Therapeutics


19. Kershner, Ophthalmic Medications and Pharmacology: Slack.
Inc., 1994.
20. Olin BR et.al., Drugs Facts and Comparisons: Facts and
Comparisons, St. Louis, 1997.
21. Onofrey, The Ocular Therapeutics; Lippincott-William and
Wilkins, 1997.
22. Rhee, The Wills Eye drug Guide: Lippincott William and
Wilkins, 1998.

23. Robin JS, ophthalmic ointments; Surv. Ophthalmol, 1978; 22:


335.
24. Steven Podos, Textbook of Ophthalmology, New Delhi: Jaypee
Brothers Medical Publishers, 2001.
25. Zimmerman TJ, Therapeutic Index of Topically Applied Ocular
Drugs, Arch. Ophthalmol, 1984; 102: 551.
26. Zimmerman, Text book of Ocular Pharmacology: Lippincott and
William and Wilkins, 1997.

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47

Update on Antibacterial Therapy


Ashok Garg

INDICATIONS FOR
ANTIMICROBIAL THERAPY
MECHANISMS OF RESISTANCE
OF ANTIBIOTICS
INDICATIONS
DISADVANTAGES
CLASSIFICATION OF
ANTIBACTERIAL DRUGS
LEVOFLOXACIN
MISCELLANEOUS

Principles in antibiotic therapy remains the same in all medical specialities.


The rational selection of antimicrobial drugs depends upon the diagnosis,
sensitivity and assay of bactericidal activity. Diagnosis can be made on
the basis of clinical impression. In most infections the relationship between
causative agent and clinical picture is not constant. It is, therefore, important
to obtain proper specimens for bacteriological identification of causative
agent. Then antimicrobial therapy can be started on the basis of Suitable
drug. The suitable drug of a causative organism is based on the following:
1. The site of infection.
2. The age of the patient.
3. The place where the infection was acquired.
4. Mechanical predisposing factors.
5. Predisposing host factors.
The eye is particularly suitable for local application of antibiotics. The
use of systemic antibiotics is limited by relatively poor penetration of
antibiotics into the eye through the blood-eye barrier is reduced when the
eye is inflamed.
The general principles to the management of infection elsewhere in
the body also apply to the ocular antibiotic therapy. An accurate diagnosis
confirmed by the culture and sensitivity from the samples (corneal scraping
in corneal ulcers, conjunctival swab in conjunctivitis and vitreous tap in
endophthalmitis, etc.) is necessary before selecting the most effective
antibiotic.
External ocular infections have the advantage of being treatable with
more toxic antibiotics that cannot be safely used systematically. Such topical
use of toxic antibiotic has the advantage of slowing down the development
of bacterial resistance to the safer antibiotics and the individual advantage
of prescribing a less commonly used antibiotic to which fewer organisms
are already resistant. Inspite of relative delicacy of ocular surface, toxic
effects like epithelial healing defect are not clinically significant with the
use of commercially available ophthalmic antibiotics.
Unique to the eye is lipoidal barrier that resists penetration by the most
antibiotics. The blood-eye barrier is a significant obstacle to the treatment
of the vitreous and aqueous cavities. The sclera and uveal tract are external
to the blood-eye barrier. When large protein molecules leak freely into the
eye, so do antibiotic molecules. The clinically significant problems arise
when minimal damage has been done by the organism entered into the
eye via trauma, surgery or metastatic entry. At this early stage microorganism is relatively safe from systemic or topical antibiotics yet this is
critical time for effective therapy. The routes of administration of antibiotics
to achieve intraocular penetration are subconjunctival, sub-Tenon and
intravitreal injections.

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460 Section V: Ocular Therapeutics


Subconjunctival antibiotic injection produces a
constant and prolonged depot of medication supplying
effective conc in the anterior segment. The main route
for subconjunctival antibiotic injection is through the tear
film and the cornea. The vitreous cavity is the most
difficult area to be penetrated by topical and sub-conjunctival routes. Therefore, direct intravitreal injection of
antibiotic is recommended in desperate situation like
endophthalmitis.
The goal of achieving high antibiotic conc in anterior
segment can be achieved by frequent instillation of
antibiotic drops into the conjunctival sac.
The rational for prophylactic topical antibiotic before
surgery is debatable. Organisms that may otherwise be
considered normal flora such as Staph epidermidis are
potential pathogens to the eye. The use of preoperative
topical antibiotic may decrease or eliminate bacterial
flora from the conjunctiva that their use will not prevent
intraoperative contamination of wound or anterior
chamber.
Antibiotics are chemical substances produced by
microorganisms that have the capacity to inhibit growth
of or even destroy bacteria and other microorganisms in
dilute solution. The chemical structures of most
therapeutic antibiotics have been identified.
The best prerequisite for the correct choice of an
antimicrobial which at the same time will be fully active,
safe and well-tolerated is an exact clinical and bacteriological diagnosis.
The choice of an antimicrobial is not only influenced
by the type and susceptibility of the infecting organisms
but also by mode of action and pharmacokinetics of the
antibiotics, the severity and localisation of infection, liver
and kidney functions and age of the patient.
When more than one antibiotics are used, apart from
the spectrum of the individual antibiotic, synergism and
antagonism must be kept in mind, mechanism of action
of antibiotics is some what variable. Generally, they
achieve their effects by disturbing the metabolic activities
of the bacteria.
Most antibiotics disturb cell wall synthesis of the
bacteria, some interfere with protein synthesis, other
produce alterations in bacterial membrane permeability.
Antibacterial drugs that cause cell wall dysfunction by
inhibiting peptidoglycan synthesis or by alteration of the
osmotic barrier drugs while the other drugs cause
inhibition of nucleic acid synthesis.
Antibiotics may be either bactericidal (those which
kill organisms) or bacteriostatic (which inhibit bacterial
multiplication). Certain antibacterial drugs are designated as bacteriostatic or bactericidal dependent on the
concentration of drug. Many bacteriostatic drugs become

bactericidal when used in higher concentration as may


occur with ophthalmic topical applications.
In preparation of therapy plan, the pharmacokinetics
of the antibiotics must be taken into consideration.
Absorption and blood levels, tissue diffusion and distribution, intraocular penetration, protein binding, metabolism and excretion differ from each antimicrobial
agent.
Because of tear flow, topically instilled antibiotics
have a limited life span in the conjunctival sac and only
a fraction of their volume penetrates the eyeball across
the cornea. Drug penetration may be improved by
frequent instillation, increasing the viscosity of the drug,
by employing the vehicle or by altering the pH of the
drug or by the use of fortified drops.
Topical antibiotics should be selected depending
upon the severity of infection and the suspected ocular
pathogen. Preferably use less potent antibiotics in common ocular infection and reverse megaspectrum and
high conc antibiotics for more severe infections or
fulminant infections.
INDICATIONS FOR ANTIMICROBIAL THERAPY
1. Significant infection of the eye proven bacteriologically and clinically. Topically instilled drugs are
mostly useful in external ocular infections, namely
conjunctivitis, keratitis, keratoconjunctivitis, dacroycystitis, stye, chlazion and to a varying extent in
anterior segment infections.
2. Prophylaxis to
a. Prevent secondary bacterial infection in patients
who are ill with other diseases.
b. To protect healthy persons from the acquisition
or invasion by specific infection to which they are
exposed.
3. Confirmation of suspected diagnosis of significant
bacterial infection by observing clinical response.
The commercially available antibiotics drops and
ointment are marketed in strength from 0.3 to 1 percent.
However, in severe infections of the eye in addition to
systemic therapy, high potency fortified drops are freshly
prepared and used. However, these fortified eyedrops
have a very short life span.
However, indiscriminate use of antibiotics should be
checked as it leads to:
a. Widespread sensitization resulting in hypersensitivity
anaphylaxis.
b. Changes in the normal flora of tear resulting in superinfection due to overgrowth of resistant organisms.
c. Direct drug toxicity due to prolong use.
d. Masking serious infections without eradicating it.
e. Development of drug resistances.

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Chapter 47: Update on Antibacterial Therapy 461


MECHANISMS OF RESISTANCE OF ANTIBIOTICS
a. Production of enzymes that cause inactivation of the
drug, e.g.-lactamase which inactivate penicillin,
acetyltransferases which inactivate chloramphenicol, kinases and other enzymes which inactivate
aminoglycosides.
b. Alteration of drug binding sites. It occurs specially
with aminoglycosides, erythromycin and penicillin.
c. Reduction of drug uptake by the bacteria, e.g. tetracycline.
d. Alteration of enzymes, e.g. dihydrofolate reductase
becomes insensitive to trimethoprim.
e. Some strains of staphylococci have multiple resistance
to practically almost all current antibiotics involving
the above mechanisms, resistance being transferred
by transposons or plasmids.
In order to avoid resistance to topical antibiotics
frequently try to follow following principles to limit the
resistance development.
1. Limit antibiotic use to diagnosed infections caused
by susceptible organisms. It is unnecessary to use
broad spectrum antibiotics in condition like viral
conjunctivitis.
2. Avoid chronic use of antibiotics. Ask the patient to
follow strictly the ophthalmologist advice regarding
the duration of antibiotics use.
3. Use newer antibiotics only when necessary for treatment of infections resistant to traditional therapy.
4. Completly treat all clinical infections and consider
using a second therapeutic agent to prevent emergence of resistant organisms.
In ophthalmic infections there is tendency to use
combination of antimicrobial agents by ophthalmologists.
INDICATIONS
1. To give prompt treatment to the patient.
2. To delay the emergence of microbial mutants resistant
to one drug on chronic use.
3. To treat mixed infections.
4. To achieve bactericidal synergism.
DISADVANTAGES
1. The more drugs are used, the greater the chances for
drug reaction to occur.
2. The cost is unnecessarily high.
3. The relax in attitude of clinician in the effort to establish a specific diagnosis.
4. Antimicrobial combinations may accomplish no more
than an effective single drug.

5. Increased incidence and variety of adverse effect.


6. Superinfection chances are high.
Most common pathogens seen in ocular infective
conditions are:
a. Gram-positive cocci:
Staphylococcus aureus
Staphylococcs epidermidis
Streptococcus pneumoniae
Streptococcus faecalis
and hemolytic streptococci.
b. Gram-negative cocci:
Neisseria gonorrhoea
Neisseria meningitidis
Branhamella and N.sicca, mucosa and flavescens.
c. Gram-negative rods:
Acinetobacter
Enterobacter
Escherichia coli
Haemophillus species (influenzae and aegyptius)
Klebsiella species (pneumoniae and oxytoca)
Moraxella species (lacunata, bovis and nonliquefaciens)
Proteus (merabilis and vulgaris species)
Pseudomonas aeuroginosa and cepacia
Serratia species (marcescens and flexneri)
Brucella species (abortus, suis and melitensis)
Shigella species (sonnei and flexneri)
d. Gram-positive rods:
Cl tetani
Cl welchi
C diphtherial
C Anthracis, cereus and subtilis
Corynebacteria species (diphtheria, xerosis and
haemolyticus)
Listeria monocytogenes.
The broad spectrum antibiotics are variable effective
against both rods and cocci.
CLASSIFICATION OF ANTIBACTERIAL DRUGS
I. Beta-lactams:
Penicillin (Natural and semisynthetic)
Cephalosporins (First, second and third generations).
Cephamycins.
II. Aminoglycosides (Group of antibiotics and semisynthetic antibiotic derivatives)
III. Tetracyclines
IV. Sulphonamides
V. Chloramphenicol
VI. Macrolides including erythromycin, clindamycin,
roxithromycin and spiramycin, vancomycin.

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462 Section V: Ocular Therapeutics


VII. Polypeptides including polymixin B, bacitracin
VIII. Antimicrobial peptides
IX. Fluoroquinolones including
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
Lomefloxacin
Sparfloxacin
Levofloxacin
X. Imidazoles derivatives
XI. Cotrimoxazole
XII. Miscellaneous
Beta-lactams
These are so called because they contain -lactam ring
in their structure. It includes:
a. Penicillins
b. Cephalosporins
c. Cephamycins
Penicillins
Penicillin G is the first antibiotic produced by a fungus
Penicillin chrysogenum.
It acts by interference with synthesis of peptidoglycan
layer of cell wall. Penicillins are bactericidal and only
effective against multiplying organisms.
Penicillins are classified into following groups:
Natural Penicillins
Benzyl Penicillin (Penicillin G) is active against gram +ve
organisms, gram -ve cocci, spirochaetes. It can be given
orally, as drops, S/conjunctivally, parenteral IV or IM. It
is one of the most effective bactericidal antibiotic
although many staphylococci have developed resistance
to it.
Dosage Parenteral IM/IV adults 4-30 million units/24
divides doses 4-6 hourly.
Topically it is given in fortified drops form with conc
of 100000 units/ml (Shelf life - 24 hours). Subconjunctival
injection dose is 0.5-100000 units/ml.
It is drug of choice for streptococcal, pneumococcal
and gonococcal infections.
Semisynthetic Penicillin
Phenoxy methyl Penicillin It is semisynthetic acid resistant
penicillin alternative to Penicillin G.
It acts by inhibition of cell wall synthesis.

Dosage It is given orally 250-500 mgm 6 hourly. It is


equally effective like penicillin G against microorganisms.
Penicillinase resistant penicillins have been developed. There
are:
Methicillin: It is a penicillinase resistant penicillin
speciallly reserved for staphylococcal infections. It is
suitable for subconjunctival
injection in cases of endophthalmitis.
Dosage Parenteral IM/IV: 1-2 G 4 hourly, subconjunctival injection conc is 150-200 mg/ml.
Cloxacillin: It is given orally in dose of 250-500 mgm
6 hrly.
Highly effective against staphylococcal, Penumoccus
and Streptococcus.
Flucloxacillin, Oxacillin and Dicloxacillin are effective
against gram +ve organisms.
Carboxy penicillin include carbenicillin and ticarcillin
are specially effective against Pseudomonas, Proteus
Enterobacter, Klebsiella and E.coli.
Dosage Parenteral 400 mg - 500 mg/kg/day 4 hourly
topically in conc of 4 mg/ml/(fortified drops).
Amino penicillins are bactericidal for both gram +ve
and gram -ve bacteria. Amino penicillins are susceptible
to penicillinase and so ineffective against staphylococcus.
Ampicillin given orally 250-500 mg 4-6 hourly or by
parenteral route.
For S/C conc in inj. 100-200/ml.
Intravitreal inj. conc 500 mg/ml, 10 mg/ml (fortified
drops).
Amoxycillin It is given orally in dose of 250-500 mgm
4-6 hourly:
Broad spectrum penicillin derivatives, e.g. ampicillin
and amoxycillin are effective against a wide range of
organisms but are inactivated by penicillinase.
Adverse reactions of penicillins Hypersensitivity reactions (Minor rash to Anaphylaxis)
Rash, itching, urticaria, fever, asthma, serum sickness
Exfoliative dermatitis
Anaphylaxis
Cross-sensitivity with the cephalosporins.
Cephalosporins
Cephalosporins are obtained from a fungus Cephalosporium. These are derivatives of cephalosporin C produced
by fungus Cephalosporium acromonium. Molecular
structure is closely related to that of penicillins. Mode of
action is similar to penicillins since both group possess B
lactam ring. Cephalosphorins bind to the bacterial

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Chapter 47: Update on Antibacterial Therapy 463


enzymes that are necessary for the formation of the cell
wall and cause inhibition of mucopeptide synthesis hence
bactericidal. Classification by generation is based on
general features of antimicrobial activity and pharmacological properties.
First Generation Cephalosphorins They have good activity
against gram +ve bacteria and relatively modest activity
against Gram -ve microorganisms. Most gram +ve cocci
except enterococci are susceptible.
These are:
Cefazolin
Parenteral dose
:
1-6 gm/day 6-8 hourly
S/C dose
:
100 mg/ml
I/V dose
(Intravitreal dose) :
2000 g/ml
Fortified eyedrops :
50 mg/ml (Shelf life - 1
week)
Cephalothin
Parenteral dose
:
2-12 gm/day 6-8 hourly
S/C dose
:
50-100 mg/ml
Cephapirin
Parenteral
:
1-2 gm every 4 hours
Cephaloridine
Parenteral
:
2-4 gm/day 6 hourly
S/C dose
:
100 mg/ml
Intravitreal dose
:
250 mg/ml
Cephadrine
Oral, IM or IV
:
0.5-1 gm every 6 hours
Cephalexin
Oral
:
0.5 gm-1 gm every 6 hours
Cefadroxyl
Oral
:
1 gm every 12 hours
Cefaclor
Oral
:
0.5-1 gm every 8 hours
Second Generation Cephalosporins These have excellent
activity against gram +ve organism Staphylococcus and
Streptococcus except St faecalis, more active than Ist
generation against gram -ve microorganisms, e.g. E. coli,
Klebsiella, H. influenzae but not active against Bacteroides
and Pseudomonas.
1. Cefamandole:
Parenteral
:
1 gm every 4 hours

Fortified drops

50 gm/ml (Shelf life 7


days)

2. Cefoxitin:
It is more active against anaerobes sp. B. fragilis 1-2
gm every 4 hourly.
3. Cefuroxime
750 mgm-1.5 gm every 8 hours
4. Cefonicid
1-2 gm every 24 hours
5. Cefaranide
1 gm every 12 hours.
6. Cefotiam
1 gm every 12 hours.
7. Cefotetan
1 gm every 12 hours.
Third Generation Cephalosporins: These agents are mainly
effective against gram -ve organisms but not against
staphylococci.These are:
1. Cefotaxime:
Parenteral
:
1-2 gm every 4-6 hours
Fortified eyedrops :
50 mg/ml (shelf life 7
days)
2. Cefoparazone:
1-4 gm every 4-8 hours.
3. Cefixime:
200-400 mg/day
4. Cefsulodin:
0.5-1 gm 6-12 hourly.
5. Ceftazidime:
1-2 gm every 8-12 hours.
The other third generation cephalosporins used are:
Moxalactam
Ceftizoxime (1-2 gm every 8-12 hours)
Ceftriaxone (1-2 gm once a day)
Cefpiramide
Cephalosporins should not ordinarily be used for
infections proven be due to Staph. aureus.
Intraocular cephalosporin levels with systemic
administration are shown in the Table 47.1.
Certazidime, moxalactam, cefotaxime and cefuroxime attain aqueous levels in the bactericidal range for
most enterobacteriaceae except P. aeruginosa. Only

Table 47.1: Cephalosporin dosage and conc in aqueous and vitreous


Drug

Dose

Aqueous(g/ml)

Dose

Vitreous (g/ml)

Cephalothin
Cephalexin
Cefoxitin
Ceftazidime
Cefuroxime
Moxalactam

1 gm (IV)
2 gm (Oral)
2 gm (IV)
2 gm (IV)
1.5 gm
2 gm (IV)

0.55
1.2
3.1
3.39
2.7-6.2
2.4-9.6

2 gm IV
2 gm (IV)

0.83
1.19

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464 Section V: Ocular Therapeutics


ceftazidime levels are in a range that inhibit a high
percentage of P. aeruginosa.
Vitreous penetration of Cephalosporins Vitreous levels
of ceftriaxone after IV administration achieve levels that
exceed the MIC for 90 percent of S aureus as well as many
gram-negative rods excluding P aeuroginosa and
S. epidermidis. Rest of other cephalosporins do not achieve
vitreous levels in the bactericidal range. Therefore,
systemic cephalosporins play a limited role in the
treatment of endophthalmitis.
Subconjunctival cephalosporins may be useful in
enhancing surgical prophylaxis as an adjunct to subconjunctival aminoglycosides.
Intravitreal cephalosporins provide excellent adjunct
to aminoglycosides in the treatment of infectious endophthalmitis. Ceftazidime with vancomycin or cefazolin
with amikacin provide broad spectrum coverage on
intravitreal administration.
Topical cephalosporins are an excellent adjunct to
topical aminoglycosides in the treatment of severe
infectious keratitis. Cefazolin in a dosage of 50 mg/ml
alternating with aminoglycosides every half an hour
round the clock for severe bacterial corneal ulcer is a most
commonly used formulation.
Adverse reactions of Cephalosporins
Pain after IM injection specially cephalothin and
cephapirin
Disulfiram like reactions
Hypersensitivity reactions similar to penicillin
Nephrotoxicity
Pseudomembranous colitis and vitamin K deficiency
False-positive test results for elevated creatinine (by
systemic cephalosporins by killing intestinal flora).
Aminoglycosides
These are produced by soil-actinomycetes. These are
bactericidal agents which act inside the cell by binding
irreversibly to the 30 S ribosome subunits in such a way
that incorrect amino acid sequences are entered into
peptide chains. The abnormal proteins are fatal to microbes. Aminoglycosides are one of the most commonly
used group of antibiotic drugs in ophthalmic practice.
They contain one or two aminosugars glycosidally linked
to an aminocyclitol.
Spectrum They are bactericidal against a broad range
of gram-negative bacilli and Staphylococcus aureus. They
are not effective against streptococci, pneumococci,
anaerobes and spirochaetes. They are given either
topically or systemically only parenterally due to poor
absorption from GI tract.

Adverse reactions
Ototoxicity
Nephrotoxicity
Neurotoxicityvague feelings of lips, headache,
lassitude, dizziness.
Drug fever with eosinophilia
Hematological abnormalities.
They comprise a group of antibiotics and semisynthetic antibiotic derivatives. The various aminoglycosides used in ophthalmology are as follows.
Gentamicin
It is one of the most commonly used aminoglycosides
for acute infections. It is obtained from cultures of micromonospora purpura. It is effective against aerobic gramnegative bacilli including E. coli, Enterobacter, K. pneumoniae, Proteus and P aeuroginosa. Moderately active against
streptococci and inactive against anaerobes.
Dosage
Parenteral3.5 mg/kg/day 8 hours (IM or I/V)
Vials40 mg/ml
Ophthalmic eyedrops in concentration of 0.3 percent
Fortified drops20 mg/ml/(Shelf life 30 days)
Ophthalmic ointment0.3 percent
S/C dose20-80 mg/ml
Intravirteal dose200-400 g/ml.
The systemic use of gentamicin is recommended for
endophthalmitis, ocular injuries with retained foreign
bodies. Synergism between lactam antibiotics and
aminoglycosides has been shown. Topical gentamicin is
more effective at decreasing bacterial counts and
eliminating bacteria from the eye before surgery.
Aqueous levels of gentamicin as high as 0.8 ml can
be achieved by S/C injection of 0.5 ml of 0.3 percent
solution and 1.6 mg/ml by topical use of 0.3 percent
solution. Topical drops achieve sufficient conc. to treat
ocular surface injections while fortified drops may be
necessary to achieve therapeutic levels consistently in
the anterior chamber.
Intravitreal injection of 200-400 mg is recommended
for severe ocular injections like endophthalmitis. Gentamicin is more toxic to retina than amikacin. Fortified
drops can be formulated from intravenous preparations.
Fortified gentamicin in combination with a cephalosporin
or vancomycin is recommended as the initial empiric
treatment in bacterial corneal ulcers. Toxicity due to
subconjunctival gentamicin may be observed in form of
pupillary mydriasis, conjunctival paresthesias and delay
in corenal wound healing.

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Chapter 47: Update on Antibacterial Therapy 465


Tobramycin
It is obtained from cultures of Streptomyces tenebrainus.
Its bacterial spectrum and pharmcokinetics are similar
to gentamicin. It is active against 90 percent of
P aeuroginosa compared to 77 percent activity of gentamicin. Tobramycin use should be restricted to those injections not responding to gentamicin or antibacterial
sensitivity showing resistance to gentamicin. It may also
be used in the case of life-threatening or sight threatening
infection that has a high probability of being caused by
P. aeuroginosa because of the differential sensitivities of
two drugs and importance of optimum initial empiric
drug selection.
Dosage
Parenteral
Ophthalmic soln
Ophthalmic oint
S/C dose
Fortified drops
Intravitreal dose

:
:
:
:
:
:

3.5 mg/kg/day 8 hourly


0.3 percent
0.3 percent
2.5-40 mg in 0.5 ml isotonic
sodium chloride or sterile
water.
20 mg/ml (Shelf life 30 days)
150-200 g/ml.

Amikacin
Amikacin is acetylate kanamycin. This semisynthetic
additive prevents enzymatic destruction except by the
acetyl transferase bacterial enzyme.
It is active against many enteric gram-negative bacilli
that are resistant to gentamicin. Amikacin has lowest
frequency of resistant strains reported so far. It acts by
inhibiting microbial protein synthesis. Amikacin is
ineffective orally and is given IV/IM route.
Dosage
: 15 mg/kg/day 8-12 hourly.
Parenteral
Ophthalmic drops : 0.3 percent (10-50 mg/ml).
Fortified drops
: 20 mg/ml (shelf life 30 days)
S/C dose
: 20 mg/ml
I/V dose
: 400 mg in 0.10 ml of solution
The subconjunctival delivery gives bactericidal
anterior chamber conc without subjecting the patient to
systemic toxicity. Although amikacin is the aminogylicoside least frequently inactivated by bacterial enzymes,
principle of good antibiotic usage is applied to reduce
the rate of development of resistant organisms.
Amikacin is used as intravitreal antibiotic for the
treatment of postoperative bacterial endophthalmitis.
Intravitreal amikacin is recommended in combination
with vancomycin or cephalosporin. Intravitreal conc of
400 mg in 0.10 ml of solution has been shown to be non-

toxic to the retina. Retinal toxicity is found with a dose


of 1500 mg of amikacin. Compared with 400 mg of gentamicin or 800 mg of tobramycin. Therefore, in sight
threatening endophthalmitis, amikacin offers a broader
spectrum of action alongwith lower toxicity.
Topical use of amikacin in the treatment of bacterial
keratitis should be restructured to culture proven organisms resistant to gentamicin and tobramycin.
Sisomycin
It has antibacterial activity similar to gentamicin. It is
effective in gentamicin and tobramycin resistant strains.
Dosage
Ophthalmic soln
Fortified drops
Ophthalmic oint
S/C dose

:
:
:
:

0.3 percent
20 mg/ml (Shelf life 30 days)
0.3 percent
20-80 mg/ml

Neomycin
It is obtained from Streptomyces fradiae. It acts by inhibition of microbial protein synthesis, and is-bactericidal for many gram-positive and gram-negative organisms.
It is used in combination with polymixin B and
gramicidin as broad spectrum antibacterial combination solution. Neomycin is also used in combination
with polymixin B and bacitracin as an ointment (Fig.
47.1).
Dosage
Parenteral dose
Ophthalmic soln.
Ointment
Fortified drops
S/C dose

:
:
:
:
:

4-12 gm/day 6 hourly


0.17 percent
5 mg/gm
30-40 mg/ml/(shelf-life 7 days)
250-500 mg/ml

Various Combination
a. Neomycin/Polymixin B/Bacitracin Combination:
Topical ophthalmic Oint: 5000 units/gm Polymixin
B, 500 units/gm bacitracin and 5 mg/gm neomycin.
b Neomycin/Polymixin B Combination:
Ophthalmic Oint: 6000 units/gm Polymixin B and 5
mg/gm neomycin.
c. Neomycin/Polymixin B/Gramicidin Combination:
Topical ophthalmic solution: 1.75 mg neomycin, 10000
units of Polymixin B and 0.025 mg gramicidin/ml.
Netilmycin
It is N-ethyl derivative of sisomycin and has antibacterial
activity similar to that of tobramycin.

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466 Section V: Ocular Therapeutics

Fig. 47.1: Molecular structures of aminoglycosides [Neomycin (L) and paromomycin (R)]

Dosage
Parenteral dose
S/C dose

: 3-6.5 mg/kg/day 8 hourly.


: 20-40 mg/ml

Kanamycin
It is used for streptomycin resistant gram-negative
bacillary infections and resistant tuberculosis. But not
active against Pseudomonas.
Parenteral dosage
15 mg/kg/day 8 hourly
Fortified drops
10 mg/ml
Framycetin
Its antibacterial activity is similar to that of neomycin.
Dosage
Ophthalmic drops
Ophthalmic oint

0.5 percent
0.5 percent and 1.0 percent

Streptomycin
It is active against E.coli, Proteus, P. aeuroginosa, K. pneumoniae and H. influenzae. It is obtained from Streptomyces
griseus. It has limited bacterial spectrum and is not
commonly used in ophthalmic practice.
Tetracyclines
Tetracyclines have a broad spectrum bacteriostatic
activity against gram-positive organisms, gram-negative

Fig. 47.2: Molecular structure of tetracycline

bacilli, anaerobes, mycoplasmas. Actinomyces, rickettsia,


Chlamydia spirochaetes, however they are resistant to
Proteus, Serratia and P. aeuroginosa species.
They act by inhibiting protein synthesis at ribosome
in both gram +ve, gram -ve microorganisms (Fig. 47.2).
Adverse reactions
GI disturbancesnausea, vomiting and diarrhea
Rashes
Yellow discoloration of teeth in children
Photosensitization.
Nephrotoxicity
Benign intracranial hypertension.
Classification
1. Short-acting (1-2 gm dosage)
Chlortracycline
Oxytetracycline
2. Intermediate-acting (300 mg IBD dosage)
Methacycline
Demeclocycline

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Chapter 47: Update on Antibacterial Therapy 467


3. Long-acting: (100-200 mg IBD dosage)
Doxycycline
Minocycline

Phlyctenular keratoconjunctivitis Phlyctenular conjunctivitis responds well to systemic tetracycline because


phlyctenular keratoconjunctivitis is considered to be a
non-specific hypersensitive reaction to bacterial proteins.

Tetracycline

Toxoplasmosis A combination therapy with minocycline and sulfadiazine is effective for treatment of
active toxoplasmic retinochoroiditis.

Oral dose: 250-500 mg 6 hrly


Ophthalmic drops - 1 percent
Ophthalmic oint - 1 percent
Chlorcycline and oxycyclin are also used with the
same dosage.
Doxycycline
It is well absorbed from the gut highly effective against
gram +ve and gram -ve microorganisms.
Dosage 100-200 mg/dose 2-24 hourly

Spirochaetal infection Tetracycline or doxycycline is


recommended for the treatment of Lyme disease. Tetracycline is acceptable alternative in the treatment of
syphilis.
Persistent epithelial defects Persistent epithelial defects
are caused by tissue and leucocytic collagenases. Tetracyclines have an anticollagenolytic effect independent
of their antimicrobial properties. Systemic tetracyclines
have been useful in healing persistent epithelial defects.

Chlortetracycline Hydrocholorate
Dosage 250-500 mg/dose 6 hrly
Methacycline

Identification of neoplasms Oxytetracycline is preferentially concentrated in rapidly growing neoplastic


tissue. The presence of oxytetracycline in tissue can be
detected at the time of surgery by examination under
UV light which causes a brilliant yellow fluorescence.
This method of tumour detection is applicable to surgery
of orbital neoplasms. The dose of oxytetracycline for the
fluorescent detection of a neoplasms is 15 mg/kg/day
for three days.

Dosage 150-300 mg/dose 6-12 hourly


Minocycline
Dosage

Ocular rosacea Ocular rosacea treatment include one


gm of tetracycline per day for 4-6 weeks followed by a
slow taper to 250 mg every 1-2 days. The clinical
improvement results from reduced lipase production by
staphylococci as well as reduction in microflora.

200 mg/dose I/V.

Oxytetracycline
Dosage 500 mg 6 hrly
Ophthalmic oint 1 percent

Sulphonamides

Therapy of Ocular Infections (Tetracyclines)


Surface ocular infections caused by susceptible microorganisms respond well to topical tetracycline. Although
intraocular penetration of tetracycline is poor. Large oral
dosage (6-8 gm/day) produces demonstrable aqueous
conc and may be advised for the treatment of intraocular
infections.
Chlamydial disease Adult inclusion conjunctivitis
acquired from genital contract. Systemic tetracycline is
recommended for the patient. A three-week course of
tetracycline or minocycline is recommended and
effective.
A prophylactic use of topical tetracycline in newborn
is very effective against ophthalmia neonatorum
Acute trachoma may be cured by topical and systemic tetracycline. Treatment should be continued for
2-4 weeks.

The sulphonamides have played a major role in the


treatment and prophylaxis of bacterial eye infections but
now have been superceded by the newer antimicrobial
agents.
Sulphonamides are bacteriostatic against grampositive and gram-negative bacteria. These are structural
analogue of PABA competitively inhibit bacterial folate
synthetase. Sulphonamides are rapidly absorbed from
GI tract and are well distributed through all body compartments including eye. It is highly soluble and are of
value in the treatment of trachoma systemic treatment
with sulphonamides is not without side effects (Figs 47.3
and 47.4).
Sulphonamides used are:
Sulfacetamide
Sulfadiazine
Sulfalene
Sulphamethoxazole

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468 Section V: Ocular Therapeutics


vomiting and diarrhea, urticaria and hypersensitivity
reactions.
Local administration is relatively free of side effect
except of hypersensitivity reactions in suspected cases.
Chloramphenicol

Sulphamethoxazole
Fig. 47.3: Molecular structures of trimethoprim and
sulfamethoxazole

Fig. 47.4: Molecular structures of pyrimethamine


and sulfadiazine

Sulfisoxazole (Sulfafurazole)
Sulfinpyrazone
Out of these sulfacetamide is commonly used in eye
as topical eyedrops in conc of 10 percent, 20 percent and
30 percent and ophthalmic oint. in conc of 10 percent
and 30 percent.
Systemic doses of sulphonamides
Oral dose
: 2-4 gm/day 6 hourly
Parenteral dose
: 100 mg/kg/day 6-8 hourly
Systemic sulfonamide is an important supplement to
pyrimethamine in the treatment of toxoplasmic
retinochoroiditis.
Sulfisoxazole topical solution or ointment in conc of
4 percent is also used.
Adverse reactions Systemic administration may cause
rashes, Blood dyscrasias, GI disturbances like nausea,

It is one of the most widely used broad spectrum antibiotic in the treatment of ocular infections. It is effective
against a wide range of both gram-positive and gram ve organisms (except P. aeruginosa), anaerobes.
It is bacteriostatic and interferes with protein
synthesis.
Chloramphenicol is ideally suited for local application as it has little tendency to produce an allergic reaction
and it is highly fat soluble which allows good corneal
and intraocular penetration.
Systemic chloramphenicol is a very effective antibacterial agent. It penetrates into the aqueous following
systemic administration. But systemic chloramphenicol
has a number of side effect.
Dosage
It is available as topical solution in strength of 0.4 to
1 percent.
Ointment
: 0.5 percent
Fortified drops
: 5-10 mg/ml
Subconjunctival
Inj. dose
: 50-100 mg/ml
Intravitreal dose
: 2 mg/ml
Oral dose
: 30-50 mg/kg/day 6 hourly
Parenteral dose
: 30-100 mg/kg/day 6 hourly
Intracameral/
Intravitreal dosage : 1-2 mg in 0.2-0.5 ml of
isotonic sodium chloride
solution.
Adverse reactions
On systemic administration most common is
reversible dose-dependant bone marrow depression.
Aplastic anaemia
Superinfections
Agranulocytosis
In infants cause gray-baby syndrome (abdominal
distension pallid cyanosis, vasomotor collapse and
death).
Local application of chloramphenicol is relatively free
of side effects.
Microlides
It includes the following.
Erythromycin
It is bacteriostatic but in high doses, It is bactericidal. It
is effective against gram-positive cocci, H. influenzae,

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Chapter 47: Update on Antibacterial Therapy 469


Mycoplasma, E.coli, Salmonella, Legionella and Chlamydia,
streptococcal and staphylococcal infections and Mycoplasma and B. pertusis. It acts by inhibiting protein
synthesis by binding to the ribosome.
Dosage
Fortified drops
Ointment
Subconjunctival dose
Intravitreal dose
Oral dose
Parenteral dose

5 mg/ml
0.5 percent
100 mg/ml in isotonic
Sodium chloride solution
500 g/ml
1-2 gm/day 6 hourly
1-4 gm/day continuous drip.

Adverse reaction In systemic use GI disturbance like


epigastric distress, cholestatic jaundice, thrombophebitis
and allergic reactions.
Roxithromycin
It is new second generation macrolide with improved
pharmacokinetics, its antimicrobial spectrum is similar
to that of erythromycin but has better penetration into
bacterial cell and has bactericidal action and enhance host
defence mechanism.
Dosage Orally 150 mg BD before food intake. Subconjunctival dose 50-100 mg/ml of isotonic sodium
chloride solution.
Fortified drops
10 mg/ml
Intravitreal dose
50 g/ml.
Adverse reactions On systemic use it may cause nausea,
abdominal distress, diarrhea, malaise, anorexia, constipation and hypersensitivity reactions, dyspepsia,
dizziness, tinnitis, headache and vertigo.

Fig. 47.5: Molecular structure of clindamycin

It acts by inhibition of bacterial cell wall synthesis.


(Inhibition of glycopeptide depolymerization in the cell
wall). It is useful for treatment of staphylococcal infection
non-responsive to cephalosporins, methecillin resistant
staphylococci and Streptococcus viridans.
Dosage
Fortified drops
: 50 mg/ml
Subconjunctival dose
: 25 mg/ml
Intravitreal dose
: 1.0 mg/ml
Parenteral dose
: 2 gm/day 6-12 hourly.
Intravitreal vancomycin with an aminoglycoside has
been recommended as initial empiric therapy for exogenous endophthalmitis. A dose of 1 mg in 0.1ml intravitreally establishes intraocular levels significantly higher
than the MIC for most gram-positive organisms.
Adverse reactions On systemic use, thrombophlebitis,
allergic reactions, ototoxicity and nephrotoxicity and
hypersensitivity rashes.

Clindamycin
It is bacteriostatic agent but in higher doses it is bactericidal. It acts by inhibition of protein synthesis. It is active
against gram +ve organisms, Actinomyces species, B.
fragilis and toxoplasmoses (Fig. 47.5).
Dosage
Subconjunctival doses : 15-40 mg/ml
Oral doses
: 600 mg-1.8 gm/day 6 hourly
Parenteral dose
: 1-3 gm/day 6 hourly

Spiramycin
It is latest generation macrolide antibiotic. It is bacteriostatic by inhibition of bacterial protein synthesis. Suceptible organisms include staphylococci, streptococci,
Bordetella, Diphtheria, Branhamella, Listeria, anaerobes.
Gram-negative aerobic bacteria are not susceptible. Has
potential synergistic action with metronidazole against
organisms.

Hypersensitivity reactions, GI

Vancomycin

Dosage Oral Dose 6-9 million IU/day in 2-3 divided


doses for 5 days.
Fortified drops
: 10 mg/ml
Subconjunctival dose : 50-100 mg/ml

It is derived from cultures of Nacardia orientalis.


It is bactericidal for most gram-positive organisms
staphylcococci and Clostridium, enterococcal infections.

Adverse reactions Hypersensitivity reaction, nausea,


vomiting, abdominal pain, diarrhea urticaria, macular
rashes, benign Hepatitis.

Adverse reactions
disturbances.

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470 Section V: Ocular Therapeutics


Azithromycin
It is macrolide antimicrobial as active as erythromycin
against gram +ve organisms but is more active against
several gram-negative organisms. High conc are
achieved in tissues and in macrophages and polymorphs.
This makes azithromycin highly effective against
intracellular pathogens such as Mycoplasma, Chalamydia
and Legionella. The most exciting application for ophthalmic infection is in the treatment of Chlamaydia
trachomatis. Azithromycin is not active against Pseudomonas mode of action is by inhibition of protein synthesis.
Dosage Oral dose: 500 mg-1 gm once daily for three
days in chlamydial infections.
Azithromycin is a promising treatment for trachoma
because of difficulty of patient compliance with conventional treatment.
Adverse effects Hypersensitivity reaction, mild to
moderate nausea, vomiting, abdominal pain, diarrhea,
angioedema and photosensitivity reactions.

Dosage Ophthalmic drops 0-5 to 1, 0 percent (In combination with neomycin)


Fortified drops
: 1-2 mg/ml (Shelf life 7 days)
Ointment
: 1 to 1.5 mg/gm
Due to greater nephrotoxicity it is not systemically
given its use is restricted to topical use. Local adverse
effects, on topical use can lead to hypersensitivity, itching,
redness and edema of conjunctiva and eyelid.
Bacitracin
It is bactericidal against gram +ve and gram ve organisms, Sprirochaetes, E. histolytica and Actinomyces. It acts
by inhibition of cell wall synthesis.
Dosages
Fortified drops10000 units/ml
Subconjunctival dose10000 units
Ointment10000 units/gm.
It is also not systemically given due to potential
toxicity. It has few side effects, like itching, congestion,
edema of conjunctiva and eyelids.

Clarithromycin
It is one of the latest macrolide antibiotic investigated
for topical and systemic administration. Both topical and
systemic clarithromycin administration is effective
against infectious keratitis due to a typical mycobacteria
Mycobacteria chelonei and M. fortuitum. Clarithromycin is
10-50 times more active than erythromycin and 48 times
more active than azithromycin against 55 strains of
M. chelonei.
The 14-hydroxymetabolite is also active and act
synergistically. Pseudomonas and enterobacteriaceae are
not susceptible to clarithromycin.
Oral dosage

200-500 mg bid for a week.

Adverse reactions Pseudomembranous colitis, anaphylaxis, Stevens-Johnson syndrome, GI upset, headache,


hallucinations, rash, urticaria.
Another compound of macrolide group josamycin is
under investigation for ophthalmic application.
Polypeptides
Polymixin B
It is bactericidal against gram -ve organisms, E. coli,
Pseudomonas, Enterobacter, K.pneumoniae and H. influenzae.
It acts by the lysis of lipoprotein in the cell membrane, Proteus, gram-negative cocci, Neisseria and fungi
are resistant.

Antimicrobial Peptides
The antimicrobial peptide group of antibacterial agents
have been isolated from the immune defence of organisms such as insects, amphibians and mammals. It is
an exciting area for antimicrobial agent development for
clinical use. The antimicrobials of this group are:
Defensins
Defensins are a group of antimicrobial and cytotoxic
peptides with three distinct peptide families of defensinsclassical, beta and insect defensins determined
both by source and chemical structure of defensin. The
classical and beta defensins are derived mainly from
mammalian source.
These are active against a number of organisms
including gram-negative and gram-positive bacteria,
mycobacteria, fungi and viruses. Insect defensins are
active predominantly against gram-positive bacteria.
Classic and beta defensins are highly active against
human isolates from ulcerative keratitis. Organisms
tested includes an alpha hemolytic Streptococcus sp,
S. pneumoniae, P. aeruginosa and Morganella. At a concentration of 10 g/ml there was a marked bactericidal
effect.
Besides it classic and beta defensins have a possible
application as a microbicide in corneal stroage media.
A concentration of 200 g/ml successfully kill 99.9
percent of all three main organisms namely S. aureus,

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Chapter 47: Update on Antibacterial Therapy 471


S. pneumoniae and P. aeruginosa within 30 minutes at all
three temperatures (4oC, 23oC and 37oC). This bactericidal effect is impressive specially when the rapidity and
low temperatures are considered. Conventional antibiotics do not have significant effect on lower temperatures.
Cecropins
These are antimicrobial peptides produced by giant silk
moth (Hyalophora cecropia) in response to bacterial
challange. It is highly effective against various grampositive and negative bacteria, enveloped virus, fungi
and protozoa.
It has bactericidal effect against various organisms
S. pneumoniae, P. aeruginosa and S. aureus isolated from
ulcerative keratitis.
A synthetic cecropin analog D 5 C and natural
antimicrobial peptide have potential bactericidal effect
at conc of 100 g/ml at 4oC and 27oC. The cecropin D5C
has also been investigated as a possible antimicrobial
additive for contact lens disinfecting solutions. The
addition of D5C to leading disinfecting solutions did
enhance the bactericidal effect of solution for certain
specific organisms.
Megainins
The megainins were isolated from the skin of the frog
Xenopus laevis. They have broad spectrum activity
against a wide range of organisms including gram-positive and -negative bacteria, viruses, fungi and protozoa.
Initial investigations into the antimicrobial activity into
ocular infections is promising.
Another antimicrobial peptide discovered in rabbit
aqueous humor is under investigation for bactericidal
activity.
Fluoroquinolones
So far the most significant new antibiotics in ophthalmology are of fluoroquinolone group. In modern ophthalmic practice fluoroquinolone group antibiotics are
most commonly prescribed worldwide with excellent
response. The fluroquinolone constitutes a family of
antibacterial agents based on the original 4-quinolone
nalidixic acid a drug first marketed in 1962 for treating
UTI. The current quinolones have fluorine at position
six of the four quinolone nucleus. The new generation
fluoroquinolone derivatives have much wider spectrum
of antibacterial activity, better tissue penetration and are
associated with a lower rate of development of resistant
organisms.

The group includes norfloxacin, ciprofloxacin,


ofloxacilin, pefloxacilin, lomefloxacilin, sparfloxacilin
and clinafloxacilin. The mechanisms of action of the
fluoroquinolone is the inhibition of bacterial DNA gyrase
anenzyme important for DNA. Supercoiling and protein
synthesis. These are synthesized chemically.
Good aqueous humor concentrations of fluoroquinolones have been demonstrated in uninflamed human
eyes after systemic administration in addition to topical
route. It has been shown that fluoroquinolone ocular
penetration after systemic administration is related to
their relative degree of lipophilicity. Sparfloxacilin the
most lipophilic compound had excellant ocular penetration (55%) comparing vitreous and serum levels
followed by ofloxacilin (30%), pefloxacin (10%) and
ciprofloxacilin (5.5%).
The various drugs of this group used in ophthalmic
field are
Norfloxacin
It is bactercidal against gram-negative organism, E. coli,
Klebsiella, Enterobacter, proteus Cetobacter, Acinetobacter sp.
Pseudomonas aeruginosa, N. gonorrhoeae and gram-positive
organisms like staphylococci including methicillin
resistant strains, Enterococci and strep. agalactic. It acts
by its specific bacterial DNA gyrase blocker action.
Topically it is commonly used against superficial
infections of the eye.
Dosage
Ophthalmic soln
Ointment
Fortified drops
Orally
Parenteral

:
:
:
:
:

0.3 percent
0.3 percent
20 mg/ml (Shelf-life 14 days)
400 mg BD
200-400 mg/day 12 hourly.

Adverse reactions
Nausea, vomiting, heart burn, diarrhaea, headache,
dizziness, depression, insomnia and seizures, rash,
Drymouth, fever, arthralgia, eosinophilia, neutropenia,
etc.
On topical use, side effects are minimal. Topical
norfloxacilin has corneal epithelial toxicity greater than
ciprofloxacin.
Ciprofloxacin
This is one of the most potent fluoroquinolone derivative.
It is bactericidal and has extended broad spectrum
activity against most of gram-negative aerobic bacteria
including Pseudomonas, Chlamydia trachomatis, Haemophilus, Neisseriae and against gram-positive aerobic
bacteria including penicillinase producing and methicillin resistant staphylococci. However many strains

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472 Section V: Ocular Therapeutics


of streptococci are resistant to it. Streptococci pneumoniae is susceptible at higher concentration of ciprofloxacilin.
It act by inhibition of bacterial DNA gyrase an enzyme
essential in DNA supercoiling and replication.
It can be given topically or systemically. In topical
form it is commonly used to treat conjunctivitis, keratitis,
keratoconjunctivitis, corneal ulcers, blepharitis, dacrocystitis and preoperatively, etc.
Dosage
Ophthalmic solution : 0.3 percent
Fortified drops
: 20 mg/ml (shelf life 15 days)
Ophthalmic oint
: 0.3 percent
Subconjunctival inj. : 20-40 mg/ml
Intravitreal dose
: 200 mg/ml
Orally
: 500-1500 mg/day 6 hourly
Parenteral
: 5 -10 mg/kg/day 12 hourly.
Ciprofloxacin is available as topical, oral and intravenous forms. After systemic administration of ciprofloxacin, intraocular penetration in uninflamed eyes
occurs with levels of 10 percent of that achieved in the
patients serum and can reach intravitreal MIC for 90
percent of bacteria. Therefore, intravenous ciprofloxacin
is recommended in infectious endophthalmitis.
Topical ophthalmic use has excellent activity against
gram-positive and gram-negative organisms. Topical
ciprofloxacin (0.3%) is well tolerated with no significant
corneal or conjunctival epithelial toxicity as compare to
topical aminoglycosides which are significantly toxic to
corneal and conjunctival epithelium having the potential to cause conjunctival membrane formation. The
most common untoward effect of topical ciprofloxacin
for corneal ulcers is formation of white precipitate on
the cornea. This precipitate has the advantage of
providing a depot of the drug at the site of infection but
is potentially harmful as it sometimes decreases visualization of the corneal infiltrates deep to the precipitates.
Topical ciprofloxacin ointment is well tolerated by the
cornea and conjunctiva.
Systemic ciprofloxacin and other quinolones should
be avoided in children owing to the potential risk of
arthropathy.
Adverse reactions On systemic administration, Anaphylactoid reaction, GI disturbance on systemic use and
CNS disturbances, hypersensitivity reactions. Rashes
blurred vision, joint pains, hematological, hepatic and
renal disturbances. On local use side effects are minimal.
Ofloxacin
It is a newer potent fluorinated quinolone that has a broad
spectrum of antimicrobial activity (Figs 47.6A to C).

Ofloxacin posesses the widest spectrum of activity


against gram-positive and gram ve organisms (including resistant strains) as compared to ciprofloxacin and
norfloxacin.
It is potent bactericidal and acts by inhibiting the
bacterial DNA gyrase an essential enzyme that is a critical
catalyst in the duplication, transcription and repair of
bacterial DNA.
It is effective even against bacterial strains resistant
to ciprofloxacin. It can be given topically or systemically.
In topical form this is an excellent drug to treat various
infective conditions of eye.
Oral ofloxacin has a longer half-life and oral doses
achieve higher serum and aqueous humor concentrations
than ciprofloxacin. Ofloxacin is highly effective against
most of the pathogenic bacteria causing ocular infections.
Pharmacokinetic studies have shown that conc of
ofloxacin in the aqueous humor and tear fluids on topical
administration are above its MIC90 for ocular isolates.
After application of 0.3 percent ointment the conc of
ofloxacin in tear fluid are 300.0 + 58.7 mg/ml at half an
hour and in the cul-de-sac 0.62 + 0.14 mg/ml in aqueous
humor at 60 minutes.
Dosage
Ophthalmic soln

Ophthalmic ointment
Fortified drops

Subconjunctival dose
Intravitreal dose
Oral dose
Parenteral
IV infusion

0.3 percent
0.3 percent
20 mg/ml (Shelf-life
15 days)
20-40 mg/ml
200 mg/ml
200-400 mg 6 hourly
100-200 mg/day 12 hourly
200 mg infusion over
30 minutes bid.

Adverse reactions On systemic use nausea, vomiting,


abdominal pain, diarrhea, headache, leucopenia and
eosinophilia.
On topical use it is free of adverse effect except for
mild transient burning sensation and itching may occur.
Pefloxacin
It is a piperazine carboxylic acid derivative belong to this
promising class of fluoroquinolone antibacterials. It is
bactericidal and exhibits action by inhibition of bacterial
enzyme DNA gyrase. It also inhibits RNA synthesis. This
unique mode of action ensures, potent wide spectrum
bactericidal action and negligible resistance.
It is highly effective against gram +ve and gram -ve
organisms including difficult pathogens like Pseudomonas species and Chlamydia trachomatis, enterobacteriaceae, methicillin resistant strains of staphylococci and

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Chapter 47: Update on Antibacterial Therapy 473

Fig. 47.6A: Chemical structure of sparfloxacin

streptococci, Chlamydia and Mycoplasma. It is not active


against anaerobes. The facultative anaerobes are also
resistant.
It is also very effective against multidrug resistant
strains like beta-lactamase producing aminoglycoside
modifying and penicillinase producing N. gonorrhoeae.
It is deep acting antibacterial agent which in topical
use is highly effective against various infective conditions
of the eye. It has good intraocular penetration and has
an average level of 0.95 mg/ml of aqueous concentration.

Fig. 47.6B: Bacterial keratitis Streptococcus pneumonia


(Courtesy: FDC Limited)

Dosage
Ophthalmic soln
Fortified drops
Subconjunctival dose
Oral dose
IV infusion

0.3 percent
20 mg/ml (Shelf-life 15 days)
20-40 mg/ml
400 mg BD
400 mg in 100 ml of 5 percent
dextrose soln infusion over
1 hour.

Adverse reactions On systemic use nausea, vomiting,


diarrhea, dizziness, headache, allergic reactions.
Pseudomembranous colitis, superinfections on topical
use little adverse effects are reported except for transient
burning and itching.
Lomefloxacin

Fig. 47.6C: Bacterial keratitis Pseudomonas aeruginosa


(Courtesy: FDC Limited)

It is one of the latest derivative of fluoroquinolone


antimicrobial available for topical and systemic administration. Lomefloxacin is a difluorinated quinolone
derivative.
It is bactericidal and is bacterial DNA gyrase inhibitor
effective against a wide ranges of gram-positive and

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474 Section V: Ocular Therapeutics


gram-negative bacteria including resistant strains to
previous quinolone derivatives. It acts by inhibiting
bacterial DNA gyrase and on RNA synthesis. The target
molecule for lomefloxacin is the A subunit of bacterial
enzyme gyrase (tapoisomerase II). Plasmid mediated
transfer of resistance has not been observed. The
frequency of development of spontaneous mutation is
less than 10-8 to 10-9. No cross resistance has been reported
with lomefloxacin. Lomefloxacin inhibits bacterial DNA
related processes like replication, transcription
recombination, transposition, supercoiling and relaxation
of DNA.
Lomefloxacin is very effective against multidrug
resistant strains like beta-lactamase producing aminoglycoside modifying and penicillinase producing
N. gonorrhoeae. If is also highly effective against difficult
pathogens like Pseudomonas species and Chalamydia
trachomatis.
It is deep acting antibacterial agent which in topical
use is very effective against various infective conditions
of the eye. It has good intraocular penetration and has
an average level of 0.95 mg/ml of aqueous concentration.
After oral administration it has good aqueous humor
concentration due to its lypophilic activity. Lomefloxacin
is prescribed topically for external ocular infections of
the eye.
Dosage
Ophthalmic solution
Fortified drops
Subconjunctival dose
Intravitreal dose
Oral dose

: 0.3 percent
: 20 mg/ml (Shelf-life
15 days)
: 20-30 mg/ml
: 200 mg/ml
: 400 mg once daily

Adverse reactions On topical use adverse effects are


very low except transient burning and itching sensation,
occasional allergic reaction. Bacteriostatic ophthalmic
antibiotics should not be used concomitantly with topical
lomefloxacin.
On systemic use it is generally tolerated with mild to
moderate side effects. Adverse effects include gastrointestinal symptoms like nausea, diarrhea, pain, discomfort. Other side effects are: Stevens-Johnson syndrome, headache, dizziness, dermatological hypersensitivity reactions and photosensitivity.
Sparfloxacin
It is one of the latest derivative of fluoroquinolone group.
It has an excellent broad spectrum bactericidal effect on
gram-negative and gram-positive organisms including
anaerobes specially Bacteroids fragilis and multidrug
resistant enterococci. It is more active than ciprofloxacin
against Strep pneumoniae, Staph aureus (including MRSA),

Staph. epidermidis and Staph saprophyticus. It is also active


against Chlamydia trachomatis, Mycobacteria sps, Citrobacter, Aeromonas and Pseudomonas sp. It acts by inhibiting
the supercoiling activity of DNA replication. Sparfloxacin
as mentioned earlier that in addition to topical administration, it has excellent aqueous humor concentrations
after systemic administration.
Sparfloxacin is the most lipophilic compound tested
and had excellent ocular penetration (55%).
It is present at concentrations greater than 90 percent
minimal inhibitory concentration (MIC90) for most grampositive cocci for 18 hours.
Sparfloxacin is a promising new agent for its
intravitreal and systemic applications in ophthalmology.
Sparfloxacin is highly effective in the treatment of
endophthalmitis due to the strain G Streptococcus sps and
S. aureus.
Dosage
Ophthalmic soln
Oral dose
Intravitreal dose
Fortified Drops
Subconjunctival dose

0.3 percent
400 mg in divided doses
20-60 g/ml
20 mg/ml (Shelf-life-15 days)
20-40 mg/ml

Adverse effects On topical use no significant side effects


has been reported except for transient burning and
itching.
On systemic use diarrhea, abdominal pain, nausea,
vomiting, stomatitis, renal failure, Anaphylactoid
reaction, headache, dizziness etc.
LEVOFLOXACIN
It is recently introduced latest topical antibiotic of
fluoroquinolone group. It is the pure(s) enantiomer of
the recemic drug substance ofloxacin. Levofloxacin is a
fluorinated 4-quinolone containing a six member
(pyridobenzoxazine) ring from positions 1 to 8 of the
basic ring structure. It is L-isomer of the D, L-racemate
ofloxacin.
It has been highest bactericidal effect among all the
fluoroquinolone effective against a broad spectrum of
gram-positive and gram-negative microorganisms. It is
effective against Corynebacterium species, Staphylococcus
aureus, Staph epidermidis, Staph pneumoniae, Streptococcus,
Acinetobacter iwolffi, Haemophilus influenzae, Serratia
marcescens and Pseudomonas. Its mechanism of action
includes inhibition of supercoiling activity of DNA
replication.
It is highly lipophilic and has an excellent aqueous
humor concentration on both topical and systemic
administration. It is more soluble in water at neutral pH
than ofloxacin. As compare to other topical quinolones
levofloxacin is formulated at pH of 6.5.

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Chapter 47: Update on Antibacterial Therapy 475


Levofloxacin has an excellent clinical cure (82%) and
eradication rates (90%). It has best solubility by far, i.e.
35.8 mg/ml. This leads to a high drug concentration at
the site if infection after topical instillation. Due to highest
bactericidal effect of levofloxacin among fluoroquinolones results in rapid eradication of pathogens.
Levofloxacin is transported across the cornea in patt by
an active transport mechanism. Currently levofloxacin
is available as topical ophthalmic solution (0.5%) and is
available at higher concentration than other fluoroquinolones and is indicated for the treatment of bacterial
conjunctivitis caused by susceptible strains of grampositive and gram-negative microorganisms and also for
infection prophylaxis in ophthalmic surgical procedures.
Levofloxacin is safe and effective for use in pregnant
ladies and in children. It has high antibacterial potency
and good tolerability.
Adverse effects Levofloxacin has low incidence of
adverse events (1-3%). The most frequently reported
adverse effects on topical use are transient decrease in
vision, fever, foreign body sensation, headache, transient
ocular burning, ocular pain or discomfort, pharyngitis
and photophobia.
Contraindications Levofloxacin is contraindicated in
patients with history of hypersensitivity to quinolones
or to any of the components in this medication.
Table 47.2: Recommended nontoxic doses of
antimicrobial infusion fluids for vitrectomy
Agent
Aminoglyosides
Gentamicin
Tobramycin
Amikacin
Penicilins
Penicilin G
Methicillin
Oxacilin
Dicloxacillin
Clindamycin
Chloramphenicol
Lincomycin
Imipenem
Ciprofloxacin
Ofloxacin
Pefloxacin
Lomefloxacin
Sparfloxacin
Ceftazidine
Chloramphenicol
Vancomycin

Dose (mg/ml)
0.008
0.010
0.010
0.010
0.020
0.010
0.010
0.009
0.010
0.010
0.010
0.010
0.010
0.010
0.010
0.010
0.040
0.010
0.030

A number of other investigational fluoroquinolones


are on the horizon. These includes as follows:
Gatifloxacin
Moxifloxacin
Gemifloxacin
Clinafloxacin
Aqueous humor level studies of gatifloxacin, moxifloxacin and gemifloxacin have been conducted both in
oral and topical (0.3%) prototype solution with encouraging results.
High performance liquid chromatographic studies
have shown that gatifloxacin, moxifloxacin and gemifloxacin when given orally as well as topically achieved
significant aqueous concentrations. Because of their
excellent ocular penetration these fluoroquinolones may
be considered as an alternative or additional choice for
surgical prophylaxis and as an adjunctive therapy for
endophthalmitis. Topical ophthalmic preparations of
these new fluoroquinolones shall help in treating various
ocular infective conditions in a better way in near future.
Table 47.3: Recommended doses of intravitreal
antimicrobial agents
Agent
Aminoglycosides
Gentamicin
Tobramycin
Amikacin
Netilmicin
Kanamycin
Cephalosporins
Cefazolin
Cephalothin
Cephaloridine
Penicillins
Methicilin
Oxacilin
Carbnecilin
Ampicilin
Fluoroquinolones
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
Lomefloxacin
Sparfloxacin
Vancomycin
Clindamycin
Erythromycin
Roxithromycin
Clarithromycin
Chloramphenicol
Lincomycin
Imipenem

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Dose (mg/0.1ml)
0.10
0.10
0.40
0.10
0.40
2.25
2.0
0.25
2.0
0.50
2.0
5.0
0.10
0.10
0.10
0.10
0.08
0.08
1.0
0.45-1.0
0.50
0.50
0.50
2.0
1.5
0.50

476 Section V: Ocular Therapeutics


Table 47.4: Preparation of intravitreal antibiotic injections
Drug

Vial size
(Commercial)

Amount of
Initial
initial diluent conc
(per ml)

Aliquot
(ml)

Vol
nos.
(ml)

Final conc
(per ml)

Final
intravitreal
dose in (0.1 ml)

Amikacin
Ampicillin
Cefazolin
Chloramphenicol
Clindamycin
Gentamicin
Kanamycin
Vancomycin
Tobramycin

500 mg/2 ml
1gm
500 mg
1gm
300 mg/2 ml
80 mg/2 ml
500 mg/2 ml
500 mg
80 mg/2 ml

3.4
2.0
10.0

10.0

0.1
0.3
0.1
0.1
0.1
0.1
0.1
0.2
0.5 ml

6.15
1.2
0.9
0.4
1.4
1.9
4.9
0.8
0.5 ml

4 mg
50 mg
22.5 mg
20 mg
10 mg
2 mg
50 mg
10 mg
2 mg/ml

400 g
5 mg
2.25 mg
2 mg
1 mg
200 g
5 mg
1 mg
0.2 mg/0.1 ml

250 mg
250 mg
225 mg
100 mg
150 mg
40 mg
250 mg
50 mg
40 mg/ml

Table 47.5: Various topical antibiotic preparations (Fortified and Commercial with Dosages)
Antibiotic
preparation

Commercial
drops

Fortified
drops

Self life

Subconjunctival
(Final dosage)

Chloramphenicol
Penicilin

0.4%-1.0%
100000 units/ml

15 days
24 hours

100 mg
1 million units/ml

Framycetin
Gentamcin
Tobramicin
Amikacin
Sisomicin
Neomycin
Netilmicin
Kanamycin
Tetracycline
Polymixin B
Bacitracin
Erythromycin
Roxithromycin
Clarithromycin
Norfloxacin
Ciprofloxacin
Oxfloxacin
Pefloxacin
Lomefloxacin
Sparfloxacin
Cephaloridine
Cephamandole
Cephazolin
Cefoperazone
Cefadroxyl
Ceftriaxone
Ampicillin
Penicillin G
Methiclin
Carbenicillin
Vancomycin
Clindamycin
Ticarcillin

0.5%
0.3%
0.3%
0.3%
0.3%
0.17%
N.E.
N.E.
1.0
0.5-1.0%
N.E.
N.E.
N.E.
N.E.
0.3%
0.3%
0.3%
0.3 %
0.3%
0.3%
N.E.
N.E.
N.E.
N.E.
N.E.
N.E.
N.E.
N.E.
N.E.
N.E.
N.A.
N.A.
N.A.

5-10 mg/ml
0.15-0.30
lac IU/ml
N.E
20 mg/ml
20 mg/ml
10-20 mg/ml
20 mg/ml
30-40 mg/ml
15-20 mg/ml
10 mg/ml
N.E.
1-2 mg/ml
10000 units/ml
5 mg/ml
5 mg/ml
5 mg/ml
20 mg/ml
20 mg/ml
20 mg/ml
20 mg/ml
20 mg/ml
20 mg/ml
50 mg/ml
50 mg/ml
50 mg/ml
40-50 mg/ml
40-50 mg/ml
130 mg/ml
10 mg/ml
100000 units/ml
4 mg/ml
4 mg/ml
20 mg/ml
10 mg/ml
6 mg/ml

N.E.
30 days (RT)
30 days (RT)
30 days (RT)
30 days (RT)
7 days
7 days
7 days
N.E.
1 week
7 days
14 days (RT)
14 days (RT)
14 days (RT)
14 days
14 days
14 days
14 days
14 days
14 days
7 days
7 days
7 days
7 days
7 days
10 days
7 days
24 hours
7 days
7 days
1 week
7 days
7 days

20-40 mg
20-40 mg
25-50 mg
20-40 mg
250-500 mg

10000 units/ml
5000 units
100 mg/ml
100 mg/ml
100 mg/ml
20-40 mg/ml
20-40 mg/ml
20-40 mg/ml
20-40 mg/ml
20-40 mg/ml
20-40 mg/ml
100 mg/ml
100 mg
100 mg
100 mg
100 mg
100 mg

1 million units ml

100 mg
25 mg

RRefrigeration (at 4oC); RTRoom temperature; NENot established; NANot available


For fortified drops use BSS or isotonic saline (For 5% fortified drops, 50 mg/ml, dissolve 500 mg of salt in 10 CC of BSS)

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Chapter 47: Update on Antibacterial Therapy 477


Table 47.6: Initial topical antibiotic therapy choice for external ocular infections based on Grams stain findings
Bacteria
type

Drugs of choice (Fortified)

Alternative drug
(Fortified and non-fortified)

1. Gram-positive
cocci

Cefazolin 100 mg/ml

2. Gram-positive bacilli

Penicillin G 100000 units/ml

3. Gram-positive rods
4. Gram-negative cocci

Gentamicin 14 mg/ml
Ceftriaxone 50 mg/ml

5. Gram-negative
bacilli

Tobramycin 14 mg/ml
Amikacin 10 mg/ml
Ticarcillin - 6 mg/ml

Vancomycin 25 mg/ml
Bacitracin 10000 units/ml
Ciprofloxacin
Lomefloxacin
Vancomycin - 25-50 mg/ml
Bacitracin-1000 units/ml
Tobramycin- 14 mg/ml
Ofloxacin
Lomefloxacin
Sparfloxacin
Chloramphencol - 5 mg/ml
Gentamicin - 14 mg/ml
Polymixin B-50000 units/ml
Ciprofloxacin
Ofloxacin
Lomefloxacin
Gentamicin - 14 mg/ml
or Amikacin - 10 mg/ml
plus
Vancomycin - 25 mg/ml
or Lomefloxacin
Sparfloxacin

6. Bacteria suspected
(No organism seen)

Cefazolin 100 mg/ml


and tobramycin 14 mg/ml

20 mg/ml

20 mg/ml

20 mg/ml

20 mg/ml

Table 47.7: Topical antibiotic therapy for culture specific bacterial ulcers
Organism

Topical
(Fortified or non-fortified)

Subconjunctival

1. Pseudomonas

Tobramycin 14 mg/ml
or
Amikacin 10 mg/ml
Lomefloxacin
20 mg/ml
Sparfloxacin
Cefazolin 100 mg/ml
Vancomycin 25-50 mg/ml
or Bacitracin 10000 units/ml
Gentamicin 14 mg/ml
Tobramycin 14 mg/ml
Amikacin 10 mg/ml
Ceftriaxone 50 mg/ml
Tobramycin 14 mg/ml
Amikacin 10 mg/ml
Pefloxacin
Sparfloxacin
20-40 mg
Lomefloxacin

Tobramycin 40 mg (1 ml)
Amikacin 25 mg

2. Staphylococcus
3. Proteus

4. Enterobacter
E. coli
Klebsiella
Acinetobacter

Clinafloxacin is a new fluoroquinolone that has been


reported promising specially in ophthalmic use. It has
been found effective in vitro against multidrug resistant
enterococci, P. aeuroginosa, Xanthomonas maltophilia and
other Pseudomonas species.

Cefazolin 100 mg
Vancomycin 25 mg
Oxacilin 100 mg
Gentamicin 20-40 mg
Amikacin 25 mg
Carbenicin 100 mg
Tobramycin 40 mg
Amikacin 25 mg
Pefloxacin
Sparfloxacin
Lomefloxacin

20-40 mg

Another new Fluoroquinolone A-80556 is on the


horizon. It has extended activity against gram +ve and
gram -ve organisms and is reported effective when given
intravitreally in endophthalmitis due to S. aureus and
P. aeruginosa.

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478 Section V: Ocular Therapeutics


Table 47.8: Specific antibiotics therapy for the treatment of bacterial endophthalmitis
Microorganisms

Intravitreal
injection

Systemic therapy

Topical/subconjunctival

Staphylococcus
Streptococcus

Vancomycin/cefazolin
Vancomycin/cefazolin

Cafazolin/vancomycin
Cefazolin/vancomycin

Hemophilus

Chloramphenicol

Propionibacterium

Vancomycin

Corynebacterium

Clindamycin and
Gentamicin
Ciprofloxacin
Ampicillin

Clindamycin and
Gentamicin/
Cipro/sparfloxacin
Vancomycin

Clostridium

Vancomycin and
Cefazolin
Clindamycin and
Amikacin/
Vancomycin
Ampicillin and
Vancomycin
Clindamycin/Penicillin

Cefazolin
Cefazolin
and ampicillin
Ceftazidine/
Ciprofloxacilin
Penicillin/
Erythromycin
Cloxithromycin
Cefazolin

Nocardia
Pseudomonas

Amikacin
Amikacin/Ceftazidime

Clindamycin/
Penicillin
Cotrimoxazole
Sparfloxacin/
Ceftazidime

Enterobacter
Proteus
Serratia

Amikacin
Sisomycin and
Cefazolin
Amikacin

Klebsiella

Amikacin

Clindamycin/
Penicillin
Amikacin
Sparfloxacin/
Gentamicin/
lomefloxacin
Amikacin
Gentamicin
Ofloxacin
Gentamicin/
Lomefloxacin
Cefazolin/
Gentamicin

Bacillus

Listeria

Amikacin
Cefazolin and
Ofloxacin
Gentamicin/
Lomefloxacin
Cefazolin/
Gentamicin

Other derivatives Du-6859a, DV 7751a, BAY-Y3118 are


on trials with excellent antibacterial activity against a
broad spectrum of organisms including resistant species
in vitro.
Imidazole Derivatives
It includes the following.
Metronidazoles It is 5-nitro-midazole derivative. It is
potent bactericidal agent which interacts with DNA. It
is effective against anaerobic bactreria like B.fragilis,
clostridia, anaerobic streptococci, protozoa, entamoeba
histolytica and Guinea worm, Fusobacterium sps, Clostridium
sps, Peptococcus and Streptopeptococcus.
Dosage
Orally 400-800 mgm every 8 hourly.
IV onfusion: 15 mg/kg infusion over 30-60 minutes.
Adverse reactions Peripharal neuropathies, GI disturbances rash, seizures urticaria, pruritus, superinfection.

Lomefloxacin/
Ciprofloxacin
Vancomycin/
Penicillin
Cefazolin
Cefazolin

CNS disturbances, metallic taste, headache, dizziness


and glossitis.
Cotrimoxazole
It is combination of Trimethoprim and sulfamethaxazole.
It is bactericidal against all strains of Strep. pneumoniae,
C. diptheriae, N. meningitides 95 percent. Strains of Staph.
aureus, E. coli, Klebsiella, Brucella, Enterobacter and few
strains of Pseudomonas aeruginosa and Pneumocystis carinii
which are oppurtunistic pathogens in AIDS patients.
They act by competing with PABA for synthesis of folic
acid in the bacteria. It inhibits folic acid synthesis by the
pathogen but at different stages which results in
potentiation of action. It is given systemically.
Dosage Oral 1 tab ( double strength) BD (Trimethoprim
160 mg and sulphamethoxozole 800 mg).
Parenteral20 mg TMP/kg/day 8 hourly.
In AIDS patientsT20 + S100 mg in 3-4 divided doses
for 14-21 days.

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Chapter 47: Update on Antibacterial Therapy 479


Adverse reactions Most frequent are skin rashes, GI
disturbances, hypersensitivity reactions, blood dyscrasias
and hepatocellular necrosis, Stevens Johnson syndrome,
diarrhea and vomiting etc.
MISCELLANEOUS
Use of Antibiotics in Irrigating
Solutions for Intraocular Surgery
Antibiotics supplementation of intraocular infusions
recently has been subject of discussion and possible
widespread use.
Gentamicin (8 g/ml), vancomycin (20 g/ml) or
gentamicin and vancomycin combination (8 g/ml and
20 g/ml) are the most common antibacterial agents
investigated in this manner. Scientists have reported a
very low rate of endophthalmitis when gentamicin or
vancomycin were added to the cataract infusion solution and the infusion solution was filtered. It is being
depicted that antibiotic supplementation in infusion
solution kills bacteria and prevents endophthalmitis. On
examination of postcataract anterior chamber aspiration
after surgery in which gentamicin (8 and 80 g/ml) was
used in the irrigating solution, no organisms were
isolated. These results are encouraging, research is being
conducted on in vitro model to evaluate the potential
antimicrobial effects of piperacillin and tazobactam
(512 g and 64 g/ml respectively) used in the combination in irrigating solution. Preliminary results are
encouraging. Other antibiotic agents examined to determine their utility in intraocular infusions method of
administration are ofloxacin and sparfloxacin.
Intracameral perfusion at (20-60 g/ml) and infusion
conc from 40-1280 g/ml of ofloxacin have shown no
toxic effects in rabbit model.
However, extreme caution should be taken by
ophthalmologists against over use of antibiotics in
irrigating solution from the potential for increasing
antibiotic resistance which is becoming an increasingly
common menance. The increasing prevalence of
antibiotic resistance including the spectre of superresistant organisms is a very troublesome result of the
inappropriate overuse of antibiotics.
Intravitreal Antibiotics
Intravitreal administration of antibiotics has many
advantages in the treatment of localized ocular infection
such as endophthalmitis. Higher conc of antibiotics are
immediately achieved without systemic exposure.
Because of the advantages of intravitreal administration.
Research scientists recently have investigated some of

the newer antibiotics for intravitreal application. Sparfloxacin, pefloxacin, ciprofloxacin and imipenem have
been reported as possible antibacterial agents for
intravitreal administration from new generation of
antibiotics with excellent response. These agents appear
to have little toxicity when administered intravitreally.
Further studies are being done to evaluate the antibacterial action of these agents at the levels achievable by
intraviteal administration.
It ophthalmic practice the mode of administration is
much more significant as intraocular penetration of
antimicrobials differ considerably. Shelf life of the drugs
must be kept in view for optimum therapeutic effect and
convenience in their application specially for topical,
subconjunctival and intraocular therapy (Table 47.2).
FURTHER READING
1. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.
2. Bartlett. JD, Clinical Ocular Pharmacology, ed.4, Boston:
Butterworth-Heinemann, 2001
3. Bartlett. JD, Ophthalmic Drug Facts; Lippincott William and
Wilkins, 2001.
4. Crick. RP, Trimble RB, Textbook of Clinical Ophthalmology;
Hodder and Stoughton, 1986.
5. Duane. TD, Clinical Ophthalmology; ed. 4: Butterworth
Heinemann, 1999.
6. Duvall, Ophthalmic Medications and Pharmacology: Slack Inc,
1998.
7. Ellis. PP, Ocular Therapeutics and Pharmacology; ed. 7: C.V.
Mosby, 1985.
8. Fechner, Ocular Therapeutics; Slack Inc., 1998.
9. Fraunfelder, Current Ocular Therapy, ed. 5: W.B. Saunders, 2000.
10. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
11. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
12. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
13. Goodman. LS, Gilman. A, Pharmacological Basis of Therapeutics, ed.7, New York: Macmillan, 1985.
14. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.
15. Kanski, Clinical Ophthalmology, ed. 4: Butterworth
Heineman, 1999.
16. Kershner, Ophthalmic Medications and Pharmacology; Slack.
Inc., 1994.
17. Kucers A, Bennett NM, The Use of Antibiotics, ed.4,
Philadelphia: J.B. Lippincott Company, 1987.
18. Olin BR et.al., Drugs Facts and Comparisons: Facts and
Comparisons, St. Louis, 1997.
19. Onofrey, The Ocular Therapeutics; Lippincott-William and
Wilkins, 1997.
20. Rhee, The Wills Eye drug Guide; Lippincott William and
Wilkins, 1998.
21. Seal, Ocular Infection Management and Treatment; Martin
Dunitz, 1998.
22. Steven Podos, Textbook of Ophthalmology, New Delhi: Jaypee
Brothers Medical Publishers, 2001.
23. Zimmerman, Textbook of Ocular Pharmacology; Lippincott and
William and Wilkins, 1997.

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480 Section V: Ocular Therapeutics

48

Update on Anti-inflammatory Therapy


Ashok Garg

CORTICOSTEROID
NON-STEROIDAL
ANTI-INFLAMMATORY
DRUGS (NSAIDs)
IMMUNOSUPPRESSIVE AGENTS
IN OPHTHALMOLOGY

Various anti-inflammatory drugs developed so far have been directed


against various cellular and chemical mediators of inflammation, e.g. mast
cells, lymphocytes, leukocytes, complement histamine, plasma kinins,
proteolytic enzymes and various derivates of arachidonic acid. Antiinflammatory drugs can broadly be classified as
1. Corticosteroids
2. Non-steroidal anti-inflammatory drugs (NSAIDs)
3. Immunosuppressive agents.
CORTICOSTEROID
Since their introduction into ocular therapy, corticosteroids have been useful
in control of inflammatory and immunolgical diseases of the eye. The antiinflammatory effects of corticosteroids are nonspecific and they inhibit
inflammation without regard to cause. Topical corticosteroids exert an antiinflammatory action. Aspects of the inflammatory process such as
hyperemia, cellular infiltration, vascularisation and fibroblastic proliferation are suppressed. Steroids cause inhibition of inflammatory reponse
to inciting agents of mechanical, chemical or immunological nature. Topical
corticosteroids are effective in acute inflammatory conditions of
conjunctiva, sclera, cornea, lids, iris, ciliary body and anterior segment of
the globe. They are effective in ocular allergic conditions. In the treatment
of ocular diseases, the route depends on the site and extent of the disorder.
The mechanism of the anti-inflammatory action is shown to be
potentiation of epinephrine vasoconstriction, stabilisation of lysosomal
membranes, retardation of macrophage movement prevention of kinin
release, inhibition of lymphocyte and neutrophil function, inhibition of
prostaglandin synthesis and in prolonged use decrease of antibody
production. By inhibition fibroblastic profileration, symblepharon
formation in chemical and thermal burns may be prevented. Decreased
scarring with clearer corneas following topical corticosteroid therapy is
the result of inhibiting fibroblastic proliferation and vascularisation. The
use of cortico- steroids in ocular diseases remains largely empirical but
some general principles should be kept in mind.
1. Type and location of inflammation determines which route of
administration is appropriate.
2. Dosage is largely determined by clinical experience and should be
reassessed at frequent intervals during the course of therapy.
3. Therapy should be reduced gradually, not discontinued abruptly.
4. The minimum effective dose should be used for the shortest time
necessary.
5. Individualize dosage.

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Chapter 48: Update on Anti-inflammatory Therapy 481


6. Maintain close follow up to assess the effects of
therapy on the disease and possible adverse effects
to the patient.
7. Patient compliance watch with the drug regimen is
important in resolution of the inflammation.
Clinical use experience indicates that corticosteroids
differ in their ability to suppress inflammation. They fall
into three categories.
1. Glucocorticoids
2. Mineralocorticoids
3. Sex hormones
4. Only the glucocorticoids are of importance in ophthalmic field.
They have powerful anti-inflammatory action and it
is this property that has made them such an important
agent in the treatment of many ocular diseases. However
they have a number of adverse effects.
Steroids may be administered locally in the form of
eyedrops, ointments, injections (Subconjunctival, SubTenon, retroequatorial, retrobulbar, intracameral,
intravitreal and intralesional) and systemically in form
of tablets or injections.

Use higher strengths for moderate to severe inflammations. In difficult cases of anterior segment eye
diseases, systemic therapy may also be required in
addition.

Indications

Administration and Dosage

Topical corticosteroids are used for the treatment of


steroid responsive inflammatory conditions of the
palpebral and bulbar conjunctiva, lid, cornea and anterior
segment of the globe. Indications for topical use include
various allergic and hypersensitivity conditions of the
eye like.
Postoperative phase of Excimer Laser and Lasik
surgery
Iatrogenic inflammation of the eye
Contact dermatitis of eyelids
Pseudophakic inflammation and after phacoemulsification
Nonspecific superficial keratitis
Allergic conjunctivits and blepharitis
Vernal conunctivitis
Phlyctenular keratoconjunctivitis
Herpes zoster keratitis
Disciform and interstital keratitis
Corneal graft reactions
Anterior and panuveitis
Episcleritis and scleritis
Chlazion iritis, cyclitis
Hemangioma
Postkeratoplasty phase
Superficial punctate keratitis
Traumatic inflammation of eye
Corneal injury from chemical, radiation or thermal
burns.

Topical steroid treated duration varies with the type of


lesion and may extend from few days to several weeks
depending on therapeutic response. Relapse may occur
if therapy reduced too rapidly.
Taper over several days. Relapse more common in
chronic active lesions usually respond to retreatment.

Contraindications
Topical corticosteroids should not be used in acute
superficial herpes simplex keratitis, Fungal diseases of
ocular structures, vaccinia, varicella and other viral
diseases of cornea and conjunctiva, ocular tuberculosis,
hypersensitivity and after uncomplicated removal of
superficial corneal foreign body.
Topical steroids are not effective in Sjgrens keratoconjunctivitis. Acute purulent untreated eye infections
may be masked or activity enhanced by topical steroids.
Stromal herpes simplex keratitis treatment with
steroid medication require great caution.
Usage of topical steroids in pregnancy and lactation.
Safety of intensive or protracted use is not fully substantiated. Use with caution, when clearly needed and
when potential benefits outweigh potential hazards.

Topical solutions Instil 1-2 drops into the conjunctival


sac every hour during the day and every 2 hours during
the night in acute inflammatory conditions of the eye in
mild to moderate inflammation use dosage of 1 drops
every 4-6 hr.
Ointments Apply a thin coating in lower conjunctival
sac 3-4 times a day in severe inflammation. In mild to
moderate one application at bed time may be suffice to
control symptoms. Ointments are specially convenient
when eye pad is used and may be preparation of choice
when prolonged contact of drug with ocular tissues is
needed.
Various topical steroidal agents used in ophthalmology are:
(Dosage and duration of steroids is disease-specific).
Hydrocortisone
1. Acetate suspension0.5 to 2.5 percent
2. Acetate solution0.2 percent
3. Acetate ointment1.5 percent

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482 Section V: Ocular Therapeutics


Prednisolone
1. Acetate suspension0.12 percent, 0.25 percent and
1.0 percent
2. Sodium phosphate soln0.12 percent, 0.5 percent
and 1.0 percent
3. Phosphate soln0.5 percent
4. Phosphate ointment0.25 percent
Dexamethasone
1. Sodium phosphate soln0.1 percent, 0.05 percent,
0.01 percent
2. Suspension 0.1 percent
3. Sodium phosphate oint 0.05 percent
Betamethasone
1. Sodium phosphate solution0.1 percent
2. Sodium phosphate oint0.1 percent
Triamcinolone
Triamcinolone acetonide in form of suspension and
ointment0.1 percent
Progesterone like agents
1. Medrysone suspension 1 percent
2. Flurometholone suspension 0.1 percent (FML), 0.25
percent (FML Forte) and ointment (0.1%)
3. Fluorometholone acetate suspension 0.1 percent
Rimexolone ophthalmic suspension1 percent
Loteprednol etabonate ophthalmic soln1 percent
Some group of the steroidal drops have better intraocular
penetration than others. Dexamethasone and Betamethasone have better intraocular penetration than
triamcinolone and hydrocortisone. New generation
steroids like rimexolone, fluorometholone are powerful
corticosteroids with very low risk of IOP spikes.
Medrysones (Hydroxy methyl progesterone) have
poor intraocular penetration.
Full strength topical corticosteroids are indicated in
severe allergic or immunological responses, severe
uveitis with hypopyon but without corneal epithelial
break and microbial infective element, iatrogenic and
pseudophakic inflammation and in Post Excimer PRK
Laser and Lasik surgery phases.
In severe forms of anterior uveitis or iatrogenic
inflammation, topical steroid therapy may require

supplementation with periocular injection or systemic


steroids.
Medrysone is usually recommended for minor
reaction involving lids and conjunctiva. Its efficacy has
not been demonstrated in iritis or uveitis.
In certain ophthalmic inflammatory diseases where
full strength topical steroids are not indicated diluted
steroid regime should be used. Topical Dexamethasone
phosphate (0.01 diluted soln) is commonly prescribed
by the ophthalmologists. The diluted corticosteroids
(1:10) have clear advantages in the therapy of ophthalmic
disorders. These:
1. Enhance resistance to infection.
2. Possess effective anti-inflammatory response even
in 1:20 dilutions.
3. Do not enhance microbial fungal flora of their
lesions.
4. Do not produce ocular hypertension.
5. Do not delay healing when used in 1:10 dilution.
6. Do not enhance collagenase release.
7. Effective control of allergic conditions of conjunctiva.
8. Stabilise the corneal endothelial function.
9. Do not produce keratopathy.
10. Do not cause dry eye.
Thus advantages of diluted corticosteroids are nonpromotion of organismal growth, non-interference in
healing processes without compromising their therapeutic effects. Strict precaution should be taken that
topical steroid are never stopped suddenly to avoid high
chances of recurrence of disease and adverse effects
owing to tissue addiction. The therapy must be tapered
gradually in dose and frequency over a period of time.
The diluted corticostroid regime should be continued for
a period of one week after the clinical cure.
Since the advent of new generation topical corticostroid like rimexolone and fluorometholone topical
steroid therapy has revolutionised. Unlike topical dexamethasone, betamethasone, prednisolone and hydrocortisone ophthalmic solutions, these new generation
steroids have low incidence of adverse effect specially
rise of IOP spikes leading to steroid induced glaucoma.
Let me discuss these new generation topical steroids here.
Rimexolone
Rimexolone (Vexol) 1 percent ophthalmic suspension is
first new ocular steroid with classic steroid power in 20
years. With this unique new design rimexolone displays
a strong effinity for human glucocorticoid receptor and
high in vitro activity. It has powerful anti-inflammatory

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Chapter 48: Update on Anti-inflammatory Therapy 483


effect like other steroids but significantly with low risk
of IOP spikes similar to FML (0.1% soln.).
Its mechanism of action is similar to topical FML.

In topical suspension (0.1% and 0.25% FML forte) it


is available with liquifilm (polyvinyl alcohol). It is well
tolerated in ocular tissues and is distributed throughout
the ocular tissues rapidly.

Indications

Mechanism of Action

Topical rimexolone (1%) is


Highly effective in reducing postoperative inflammation of eye (Intraocular surgery). In postsurgery
inflammation following Excimer Laser PRK and Lasik
surgery
In pseudophakic inflammation of the eye.
Highly effective in treating anterior uveitis
Treating allergic conjunctivitis, keratoconjunctivitis.

Topical fluorometholone acts by inhibiting the inflammatory response to a variety of inciting agents. They
inhibit the edema, fibrin deposition, capillary dilation,
leukocyte migration, phagocytic activity. Capillary
proliferation, fibroblast proliferation, deposition of
collagan and scar formation associated with inflammation. It inhibits the synthesis of histamine within mast
cells. FML also decreases prostaglandin synthesis and
retard epithelial regeneration. The special character of
topical FML is that it has powerful anti-inflammatory
property similar to topical dexamethasone, betamethasone and Prednisolone (diluted and undiluted) but has
a significant lower propensity to increase intraocular
pressure which leads to steroid induced glaucoma.

Contraindications
It should not be used in
Dendritic keratitis
Vaccinia varicella
Mycobacterial infection of the eye
Fungal disease of the eye
Acute purulent untreated infections which may be
masked or enhanced by the presence of steroid
Persons with hypersensitivity to any component
Pregnancy, lactating mothers and in children.
Dosage
One percent ophthalmic sterile multidose suspension (5
ml and 10 ml vials). Patient is advised to put one drop in
the affected eye 3-4 times a day. Dosage can be safely
increased depending upon severity of the condition.
Rimexolone provides well tolerated, comfortable, ease
to use therapy.

Indications
For steroid responsive inflammation of the palpebral and
bulbar conjunctiva, cornea and anterior segment of the
globe.
In iatrogenic inflammation specially after Excimer
Laser PRK and Lasik Surgery, Pseudophakic inflammation.
In Phaco emulsification (Post surgical inflammation).
Disciform and interstitial Keratitis
Panuveitis
Scleritis and episcleritis
Traumatic inflammation of the eye.
Contraindications

Adverse Reactions
In addition to standard adverse effects of topical steroids
being discussed separately in details. Topical rimexolone
can cause blurred vision, discharge, discomfort, ocular
pain, foreign body sensation, hypremia, increased
fibrin, dry eye, conjunctival edema, corneal staining,
photophobia, non-ocular adverse effect although very
low can be headache, hypotension, rhinitis, taste perversion and phyryngitis.

Contraindications are similar to standard topical therapy


already mentioned in the chapter.
Precaution should be taken while prescribing topical
FML medication for herpes simplex Keratitis involving
stroma as it requires greater and frequent slit-lamp microscopy for adverse effects.
Topical FML should not be used for injection.
Dosage and Administration

Fluorometholone
FML is new generation topical corticosteroid being
prescribed maximally by ophthalmologists world wide.
It is powerful anti-inflammatory agent of steroidal group.
Chemically it is 9-fluor 11B, 17-dihydroxy-6-x-Methyl
pregna 1,4 diene 3, 20 dione.

FML is available as sterile suspension in 5 ml vials in


strength of 0.1 percent and 0.25 percent (FML forte).
Besides it, FML is also available as ophthalmic ointment
(0.1%) and as acetate suspension (0.1%).
Patients should be advised to instil one drop of topical
FML into conjunctival sac 2-4 times daily. During the

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484 Section V: Ocular Therapeutics


initial 24-48 hours the dosage may be safely increased to
two drops every hour depending upon severity of the
condition.
Care should be taken not to discontinue therapy prematurely and abruptly. Unique features of topical FML
suspension are
Its efficacy on ocular surface well established all over
the world.
It is safer than currently available low dose preparations which are upto 10 times diluted.
It is microfine suspension which ensures uniform
particle distribution, longer residence time and rapid
absorption.
Its liquifilm advantage soothes, cools, enhances
patient comfort and microfine suspension minimises
mechanical irritation.
Has least risk to raise IOP spikes established worldwide through clinical trials.
Due to these special features topical FML suspension
is most widely and frequently prescribed by ophthalmologists worldwide specially to control iatrogenic
inflammation in modern hightech ophthalmic surgery
of PRK, lasik and phacoemulsification.
Loteprednol Etabonate
Loteprednol etabonate (0.5% Ophthalmic soln) is latest
topical corticosteroid on the anvil.
It is a novel, site reactive corticosteroid with powerful
anti-inflammatory activity similar to dexamethasone and
FML with marked low propensity to increase IOP spike.
Loteprednol etabonate (0.5%) is structually similar
to other corticosteroids and is a soft drug. Soft drug is a
biologically active compound with predictable inactivation to nontoxic moieties after achieving its therapeutic
role. The design of this drug incorporates a Soft spot
into the structure that undergoes a predictable metabolic
inactivation leading to lower toxicity and more specific
action on target organ.
It has high lipophilicity with good intraocular
penetration and its predictable degradation is depicted
to provide an improved safety profile. That is the reason
it causes less increase in intraocular pressure than
dexamethasone.
Predictable intraocular conversion of the drug to an
inactive compound reduces the amount of active corticosteroid in the trabecular meshwork. Loteprednol
etabonate (0.5%) is indicated in steroid responsible
inflammatory condition of the eye, iatrogenic and
pseudophakic inflammation of the eye and in anterior
uveitis whereas Loteprednol 0.2 percent has been
approved for seasonal allergic conjunctivitis.

It is available as 0.2 percent and 0.5 percent ophthalmic suspension in 2.5, 5 and 10 ml vials.
The relatively low incidence, transient nature and
reversibility of ocular pressure increase reported with
loteprednol indicate that it can provide an additional
treatment choice for ocular inflammatory conditions.
In post PRK and lasik surgery inflammation its specific role is being clinically tried with initial encouraging
results. The advent of new anti-inflammatory drugs with
fewer side effects is the need of the hour and is a welcome
step. Several new drugs have been developed and clinical
trials show promising results. New drugs such as
loteprednol etabonate may be an important addition to
the therapeutic armamentarium of the practicing
ophthalmologist in near future.
Corticosteroids drops are used either in solo or in
combination of topical antibiotics to produce synergistic
effect.
Topical Steroid Antibiotic Combinations
Various topical steroid antibiotic combinations used in
ophthalmic field are.
1. Dexamethasone (0.1%) with neomycin (0.5%) in
solution form.
2. Dexamethasone (0.1%) with neomycin (0.35%) and
polymixin B (10000 units/ml) suspension or
ointment.
3. Dexamethasone (0.1%) with chloramphenicol (0.5
to 1%) soln.
4. Dexamethasone (0.1%) with framycetin (0.3%)
suspension.
5. Dexamethasone (0.1%) and tobramycin (0.3%)
suspension.
6. Dexamethasone (0.1%) with chloramphenicol (1%)
and polymixin B 5000 I.U. soln and oint.
7. Dexamethasone (0.1%) with gentamycin (0.3%)
soln.
8. Dexamethasone (0.1%) with ciprofloxacin (0.3%)
9. Dexamethasone (0.1%) with ofloxacin (0.3%)
10. Dexamethasone (0.1%) with lomefloxacin (0.3%)
11. Dexamethasone (0.1%) with sparfloxacin (0.3%)
12. Betamethasone (0.1%) with neomycin (0.5%) soln.
13. Betamethasone (0.1%) with chloramphenicol (0.5%)
in soln. and oint form.
14. Betamethasone (0.1%) with gentamycin (0.3%) in
soln.
15. Hydrocortisone (0.5%) with chloramphenicol
(0.5%) soln.
16. Hydrocortisone (0.5%) with neomycin (0.5%) oint
and soln.
17. Hydrocortisone (1.5%) and neomycin (0.5%)
ointment.

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Chapter 48: Update on Anti-inflammatory Therapy 485


18. Hydrocortisone 10 mg/gm, polymixin B 0.5 mg/
gm, bacitracin 400 units/gm and neomycin 5 mg/
gm ointment.
19. Hydrocortisone (1%) with gentamicin (0.3%)
Suspension.
20. Hydrocortisone (0.5%) with chloramphenicol
(1%)ointment.
21. Prednisolone (0.5%), neomycin 0.35% and Polymixin B 10000 units/ml suspension.
22. Prednisolone (1%) with gentamicin (0.3%)
suspension.
23. Prednisolone (0.2) with sulphacetamide (10%) and
phenylephrine (0.12%)soln.
24. Fluorometholone (0.1%) with neomycin (0.35%) in
solution.
25. Fluorometholone (0.1%) with gentamicin (0.9%) in
soln.
26. Fluorometholone (0.1%) with tobramycin (0.3%) in
soln.
Topical Antibiotic Steroid Combinations are Indicated
in
In treatment of anterior segment inflammatory
disorders which may be threatened with or complicated by bacteria sensitive to antibiotics.
In pre- and postoperative phase of intraocular
surgery where the possibility of infection with
susceptible organisms exists.
In chronic anterior uveitis and corneal injury from
chemical, radiation or thermal burns.

convenience with the added assurance that the appropriate dosage of both the drugs is administered. When
both the drugs are in the same formulation compatibility
of ingradients is assured and the correct volume of drug
is delivered and retained. In antibiotic steroid topical
combination, steroids provided powerful anti-inflammatory effect while associated antibiotic provide broad
spectrum bactericidal effect. Even pus, exudates and
bacteria growth products cannot inactivate the antibiotics
in such combinations.
Dosage and Administration
Patient is advised to put 1-2 drops in the conjunctival
sac 2-4 times daily. Care should be taken not to
discontinue the treatment prematurely and abruptly.
Adverse Reactions
In addition to topical steroid complications already
mentioned in this chapter, the most frequent reactions
reported are ocular discomfort, irritation upon instillation
of the medication and punctate keratitis. These reactions
resolve with the discontinuation of the medication.
In present day ophthalmic practice topical fluorometholone neomycin (FML-neo), dexamethasone
tobramycin and dexamethasoneneomycinpolymixin
B combinations are commonly prescribed as effective
treatment when infection and inflammation or injection
and allergy coexists.
Systemic Corticosteroids

Contraindications
In acute untreated purulent ocular infections caused
by microorganisms not sensitive to antibiotics in
steroid combination
Acute superficial herpes simplex (dendritic keratitis).
Vaccinia varicilla and other viral diseases of the
conjunctiva and cornea
Fungal diseases
Ocular tuberculosis
Hypersensitivity of drug
In diseases due to microorganisms resistant to associated antibiotic with concerned steroid combination,
infection may be masked enhanced or activated by
the steroid
Prolonged use may result in overgrowth of nonsusceptible organisms.
Topical steroid-antibiotic combination advantage is
that when decision is taken to administer such drugs
combination, there is greater patient compliance and

Systemic steroids are the mainstay of treatment of


inflammation of the posterior segment and orbit. They
are used as supplement to topical steroids in severe
inflammation of the anterior segment of the eye.
Anti-inflammatory effect of dexamethasone is 30-50
times more than that of cortisone, prednisolone is
5 times more potent than cortisone as an anti-inflammatory agent.
Indications for Systemic Steroids

Posterior uveitis.
Sympathetic ophthalmia
Papillitis and retrobulbar neuritis
Anterior ischemic optic neuropathy.
Scleritis
Severe anterior uveitis
Malignant exophthalmos
Orbital pseudotumor

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486 Section V: Ocular Therapeutics

Herpes zoster ophthalmicus


IOL implantation
Refractive keratotomy
Vogt Koyanagi Harada syndrome
Dosage, duration and type of systemic steroids use
depends upon the severity and type of ocular diseases
in which it is required.

NSAIDs
Oxicams

Complications of topical steroids are due to their intraocular penetration, collagenolytic and immunosuppressive properties.
Topical steroids must be used with caution in herpetic
keratitis and never stops steroid therapy abruptly.

NON-STEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAIDs)
Classification and Structure of NSAIDs (Fig. 48.1)
NSAIDs are chemically heterogenous group that can be
grouped into seven major classes.
Salicylates
Fenamates
Indoles

Pyrazolones

Piroxicam
Tenoxicam

Complications

Complications of topical steroids


Reduced resistance of viral, bacterial and fungal
infections
Cataract (Posterior subcapsular cataract type)
Raised intraocular pressure in susceptible patients
(Glaucoma open angle type) with optic nerve damage
defects in visual field and acuity
Secondary ocular infections from fungi and viruses
liberated from ocular tissues
Delayed wound healing
Dry eye
Ptosis
Mydriasis
Perforation of globe when used in conditions where
there is thinning of cornea and sclera
Systemic corticosteroids produce several ocular side
effects on extensive use. These are:
1. Posterior subcapsular cataract
2. Activation of infections
3. Glaucoma, exophthalmos, papilledema CRV.
Detailed adverse effects of topical and systemic
steroids are being discussed in a separate chapter in this
book.
The undesirable effects of steroids led to the development of non-steroidal anti-inflammatory agents which
are relatively free of serious side effects.

Carbolic acids

Salicylic

Propionic

Aspirin
Diflunisal
Benorylate

Ibuprofen
Fenoprofen
Fenbufen
Naproxen
Suprofen
Ketoprofen
Flubiprofen

Acetic

Fernamates
Meciofenamete
sodium
Mefanamic
acid

Indole acetic acid

Pyrrolacetic acid

Indomethacin
Sulindac

Tolmentin sodium
Phenylacetic acid
Diclofenac sodium

Fig. 48.1: Classification of nonsteroidal


anti-inflammatory drugs (NSAIDs)

Phenylalkanoic acids
Pyrazolones
Phenylacetates
Paraminophenols.
The chemical feature shared by all these classes is the
absence of cholesterol derived steroid nucleus hence the
term non-steroidal (Fig. 48.2). The pharmaceutical
emphasis has been on the indoles, phenylacetates and
phenylalkanoic acids because of instability in solution
and hence high ocular toxicity of salicylates. Fenamates
and pyrazolone derivatives. Specific drugs belonging to
each class are listed in Tables 48.1 and 48.2.
Mechanism of Action
NSAIDs act mainly as anti-inflammatory agents by
inhibiting cyclo-oxygenase and lipo-oxygenase enzymes
which lead to inhibition of products like prostaglandins,
thromboxane and leukotriens which induce inflammation (as shown in Figure 48.3). Ocular actions of
prostaglandins cause miosis, increased vascular
permeability, break down of blood-aqueous barrier,
conjunctival hyperemia and changes in Intraocular
pressure. Lipo-oxygenase products which are generated
form.

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Chapter 48: Update on Anti-inflammatory Therapy 487


quent prostaglandin synthesis. In recent time topical
NSAIDs have become commercially available
throughout the world as ocular eyedrops thus gaining
due acceptability in ophthalmology which are now
widely used in iatrogenic and other inflammatory
conditions of the eye.
Arachidonic acid include leukotriene and hydroperoxyeicosate traenoic acid (HPETES). These products
like prostaglandins also cause an inflammatory response
following tissue injury and have a potent effect on the
immune responses. Prostaglandins have also been
implicated in allergic reactions also.
Inhibition of Prostaglandin Synthesis
Synthesis of cyclo-oxygenase products can be inhibited
by non-steroidal anti-inflammatory drugs (NSAIDs).
Depending on step at which action is exerted they have
been categorised in two types:
Type I inhibitors These inhibit cyclo-oxygenase therefore
the cyclic endperoxide O2 and H2 are not formed, thus
the whole range of PG3 thromboxane A2 and PGI2 cannot
be synthesized. Examples of type I inhibitors include
Salicylates, the fenamates, propionic acid derivatives and
indomethacin.

Fig. 48.2: Chemical structures of various NSAIDs

In the treatment of ocular inflammation need of nonsteroidal anti-inflammatory drugs was felt due to severe
complications associated with more established
corticosteroid therapy. Although a overlap between the
mechanisms of action of both NSAIDs and steroids exists,
yet the use of NSAIDs in ophthalmology is safer than
the use of corticosteroids as NSAIDs are relatively free
of potential adverse effects of steroids.
The history of role of NSAIDs use in ophthalmology
dates back to 1971 when Vane and Smith established the
connection between the clinical effect of acetyesalicylates
and inhibition of prostaglandin synthesis.
Since the detection of presence of prostaglandins in
rabbit iris tissue in 1955, this substance has been
established in elevated levels in the anterior chamber that
have been associated with inflammation triggered by
trauma, uveitis, cataract, IOL surgery and laser iridotomy. It is now well known that NSAIDs produce their
clinical effect by inhibiting cyclo-oxygenase and subse-

Type II inhibitors These inhibit isomerases and reductases, i.e. the step from cyclic endoperoxide to PGE2, PGF2
etc. e.g. pyrazolones.
NSAIDs have free radical scavenging activity during
inflammation and thus help in the prevention of tissue
damage.
Arachidonic Acid (AA) Metabolites and Inflammation
A variety of phenomena in the inflammatory response
are mediated by three interrelated plasma derived factors
the complement, kinin and clotting system (As shown in
Figure 48.4).
The products derived from metabolism of AA affect
a variety of biological processes including inflammation
and hemostasis. AA metabolism proceeds along one of
two major pathways.
Lipo-oxygenase or cyclo-oxygenase. The cyclo-oxygenase
(Cox) enzymes exists in two forms Cox 1- and Cox-2.
Cox1 is found in most cells. It is thought that the
prostanoids it produces are involved in normal hemostasis. Cox2 is induced inflammatory cells by an inflammatory stimulus. Thus has relevance for the mechanisms
of action of present and future NSAIDs.

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488 Section V: Ocular Therapeutics


Table 48.1: Systemic non-steroidal anti-inflammatory agents
Drug class

Drug name

How supplied (mg)


(Commercially)

Typical adult
daily dose (mg)

Salicylates

Aspirin
Diflunisal
Choline magnesium
trisalicylate
Sodium salicylate
Mefenamate
Meclofenamate
Indomethacin
Sulindac
Tolmetin
Diclofenac
Fenoprofen
Ketoprofen
Piroxicam
Flurbiprofen
Ketorolac
Naproxen
Naproxen Na
Ibuprofen
Nabumetone
Phenyebutazone
Oxyphenyl butazole
Acitaminophen

325-925
250,500

650-975 mg q4h
250 qid

250,500
325-650
250
50,100
25,50,75 (slow release)
150,200
200,400,600
25,50,75
200,300,600
25,50,75
10,20
50,100
10
250, 375, 500
275,550
200,300,400,600, 800
250,300
100
100
80,325,500,650

1000-1500 mg bid
325-650 mg q3-4h
250 qid
50-100 qid
25,50 tid-qid,75 bid
150-200 bid
400 tid
50-75 bid
300-600 tid
75 tid-50 qid
10 bid, 20 daily
100 tid
10 qid
250-500 bid
275-550 bid
400-800 tid
1 g q night
100 tid-qid
100 tid-qid
650 q 4h

Fenamates
Indoles
Phenyl acetic acids
Phenyl alkanoic acids

Pyrazolones
Para-aminophenols

Table 48.2: Topical non-steroidal anti-inflammatory agents


Drug name

How supplied commercially

Typical dose

1. Flurbiprofen

0.03% solution

2. Suprofen

1.0% solution

3. Diclofenac
4. Ketorolac
5. Indomethacin

0.1% solution
0.5% solution
(a) 0.5-1.0% suspension
(b) 0.1% ophthalmic solution

1 drop every 30 minutes, 2 hours preoperatively (total


dose4 drops)
2 drops at 1,2 and 3 hours preoperatively or every
4 hours while awake on the day of surgery
-qid
-tid
-qid

1. Asprin
2. Acetyl salicylic acid
3. Diflunisol

Freshly prepared topical


NSAIDs
1.0% solution
0.03% solution
0.03% solution

-qid
-qid
-qid

OINTMENTS
1. Oxyphenbutazole
2. Phenylbutazone

10% ointment
10% ointment

HS-bid
HS-bid

Pharmacokinetics
NSAIDs are well absorbed after oral administration and
have measurable ocular penetration. NSAIDs are 90 to
99 percent protein bound and therefore are easily

recovered from ocular tissues. However topical NSAIDs


appear to penetrate the eye better than oral administration. Topical instillation of these drugs provides
adequate levels of agents in ocular tissue and aqueous
humour for inhibition of Prostaglandin Synthesis.

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Chapter 48: Update on Anti-inflammatory Therapy 489


Phospholipids
(Inhibited by corticosteroids)

Phospholipase A2

Arachidonic Acid

Cyclo-oxygenase

Lipo-oxygenases

Endoperoxidase

Leukotrienes

(PGG2, PGH2)

Thromboxane A2

PGE2

Prostacycline

PGF2

(PGI2)

PGD2
Fig. 48.3: Mechanism of action of NSAIDs

Cell membrane
Phospholipids
NSAIDs
(aspirin, indomethacin)

Inhibit

Phospholipases

Arachidonic acid

Steroids inhibit

Other lipo-oxygenases

HPETE HETES

Cyclo-oxygenase

5-Lipo-oxygenases
Prostaglanding G2 (PGG2)

5-HPETE
Zafirlukast
-X-inhibits

Prostaglanding H2 (PGH2)

Zileutin inhibits

5 HETE

(Chemotaxis)

Leukotriene A4 (LTA4)
Prostacyclin
(PGI2
(Causes vasodilation,
inhibits platelet aggregation)
PGD2

PGE2

Thromboxane A2
TXA2
(Causes vasoconstriction,
promotes platelet aggregation)
PGF2

Leukotrient C4 (LTC4)

(Vasoconstriction)

Leukotrient D4 (LTD4)

(Bronchospasm)

Leukotriene E4 (LTE4)

(Increased permeability)

(Cause vasodilation, potentiate edema)


Fig. 48.4: Arachidonic acid metabolites and their role in inflammation

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490 Section V: Ocular Therapeutics


However Topical NSAIDs can gain access to the systemic
circulation via mucosal absorption. Therefore even local
administration of NSAIDs can be accompanied
by systemic toxicity if nasolacrimal occlusion and eyelid
closure are not employed following eyedrop instillation.
NSAIDs have three type of effects:
Anti-inflammatory effect
Analgesic effect
Antipyretic effect
In ophthalmology these drugs are used primarily for
their anti-inflammatory effects and when required for
the analgesic effect.
NSAIDs are inhibitors of both isoenzymes Cox1 and
Cox2 though they vary in degree of inhibition of each.
The anti-inflammatory action is mediated by their
inhibition of Cox1. Drugs with selective action on Cox2
could bring in a major advancement. The anti-inflammatory effect of NSAIDs varies. Drug such as Indomethacin
and piroxicam are strongly anti-inflammatory some such
as naproxan, ibuprofen and nambumetone are moderately anti-inflammatory while drugs like paracetamol
have essentially no anti-inflammatory activity.
In ophthalmic Topical preparations flurbiprofen (0.03
percent) Diclofenac (0.1%), ketorolac (0.5%), Indomethacin (1%) and Suprofen (1%) are commonly used.
Topical NSAIDs when used stabilise the blood-ocular
barriers and are as effective in reducing iatrogenic
inflammation as topical cortico steroids. NSAIDs like
steroids are also used systemically specially when their
action needs to be combined with anti-inflammatory
effects or when higher intraocular levels are desirable
such as in CME or diffuse retinitis.
Topical NSAIDs like indomethacin (Indole derivative)
is commercially available as 1 percent aqueous suspension. A 0.1 percent indomethacin ophthalmic solution has
recently been commercially launched. The phenyl
alkanoic acids are water soluble and are formulated as
ophthalmic solutions. Flurbiprofen (0.03%) and suprofen
(1%) are approved by FDA (USA) for intraoperative use
to inhibit miosis during cataract surgery. Ketrolac
tromethamine (0.5%) has been approved for the
treatment of seasonal allergic conjunctivitis While topical
Diclofenac (1%) is a phenylacetic acid derivative that is
approved by FDA for use to minimise postoperative
inflammation after cataract surgery.

posterior segment procedures (Vitreo-retinal surgery).


Endogenous factors other than prostaglandins and
surgical techniques have been responsible for this
condition. NSAIDs use can cause pharmacological effect
on the pupil lessening intra operative miosis. NSAIDs
that are commonly used for this purpose include Topical
Flurbiprofen 0.3 percent. Suprofen 1 percent and Indomethacin 1 percent Suspension. Clinical datas have
shown that Topical Indomethacin 1 percent suspension
or 0.1 percent ophthalmic solution maintain pupillary
dilatation in statistically significant higher number of
patients undergoing cataract surgery. Topical
Flurbiprofen and Suprofen solutions are commonly used
by ophthalmologists to inhibit intra operative miosis.
This pharmacological activity of NSAIDs is of potential
clinical benefit because decreasing pupil size is a well
established risk factors for vitreous loss and zonular
breaks during ECCE with IOL implantation.

Ocular Indications for Use of NSAIDs

Cystoid macular edema (CME) is the most common cause


of visual decline following cataract surgery. Angiographically proven CME after cataract surgery occurs in 50 to
70 percent of patients undergoing ICCE and in 20-30
percent patients who undergo ECCE. The common denominator of all the CME is believed to be mainly prosta-

Maintenance of Intraoperative Mydriasis


Adequate pupillary dilatation specially its maintenance
during intraocular surgery undergoing ECCE and in

Reduction of Postoperative Inflammation


Topical NSAIDs drops are potentially useful in managing
postoperative inflammation following intraocular
surgery. Fluorophotometric analysis offers a quantitative
means of studying anterior chamber inflammation.
Several clinical studies have shown the efficacy of
NSAIDs specially indomethacin 1 percent, flurbiprofen
0.03 percent, ketorolac 0.5 percent and diclofenac
0.1 percent. On postoperative inflammation NSAIDs
positive effect has been reported both in intracapsular
and extracapsular cataract surgery. Fluorophotometry
study have shown that topical NSAIDs achieve better
inflammation control than the corticosteroids in double
masked randomised studies. Topical diclofenac 0.1
percent and indomethacin 1 percent suspension or 0.1
ophthalmic solution have been proved to be better in
controlling inflammation after cataract surgery. Latest
studies have strongly advocated the use of topical
diclofenac 0.1 percent four times daily starting 24 hours
after cataract surgery to control postoperative inflammation. It is possible practically to prescribe a topical
NSAIDs for a topical corticosteroid to control iatrogenic
inflammation specially in eyes with significant steroid
responsive glaucoma.
Prevention and Treatment of Aphakic and
Pseudophakic Cystoid Macular Edema

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Chapter 48: Update on Anti-inflammatory Therapy 491


glandin mediated breach of blood-retina barrier clinical
studies have shown that oral and topical NSAIDs are
effective in the prophylaxis of angiographic pseudophakic and aphakic CME.
Topical NSAIDs specially topical indomethacin 1
percent and flurbiprofen 0.03 percent when prescribed
to patients postoperatively undergoing cataract surgery
resulted in improved Snellan visual acuity and decrease
in the incidence of post surgical angiographic CME.
In summary:
a. Topical NSAIDs are effective in preventing postsurgical angiographic CME when topical or subTenon corticosteroid is given concurrently.
b. Prophylactic treatment with topical NSAIDs has a
beneficial effect on visual function.
c. Topical NSAIDs are also effective in the treatment of
angiographically documented subclinical CME and
this can turn into improved visical function.
d. Topical NSAIDs are also effective in treating chronic
symptomatic established CME (of 6 months or greater
duration) 1 percent Topical Fenoprofen and oral
indomethacin has been shown to be quite effective in
such condition. In the treatment of CME, standard
recommendation is to use combination of a topical
corticosteroid and topical NSAIDs and then tapering
of corticosteroid as the clinical situation improves.
Uveitis
In contrast to postsurgical inflammation, many forms of
uveitis require prolonged steroid therapy to control
inflammation. Of course, the risk of iatrogenic glaucoma
and cataract becomes substantial in these situations.
Therefore, NSAIDs are gaining a more secure position
in the treatment of certain uveitis.
Systemic NSAIDs have shown to prevent attacks of
juvenile rheumatoid arthritis associated iridocyclitis,
acute non-granulomatous anterior uveitis and chronic
iridocyclitis.
In cases of posterior uveitis and secondary vasculitis,
oral NSAIDs are shown to be effective in eliminating
macular edema and preventing recurrence. Standard
recommend regime is combination of topical corticosteroid and an oral NSAIDs (specially diclofenac 75 mg bd
daily) as initial therapy.
Scleritis and Episcleritis
Systemic NSAIDs are agents of choice in the treatment
of non-necrotising, simple diffuse and nodular scleritis
Furthermore when a steroid is needed, the duration and
dose of the steroid may be reduced with the adjunctive
use of an NSAID.

Allergic and Giant Papillary Conjunctivitis


Vernal keratoconjunctivitis most commonly occurs in
children and young adults. It shares with contact lens
associated giant papillary conjunctivitis (GPC) the
common finding of giant papillae. Ketorolac 0.5 percent
ophthalmic solution is effective in reducing eye itching
often associated with allergic conjunctivitis. It can also
be useful in cases of steroid induced open angle glaucoma
and also to prevent cataract formation. 1 percent Topical
suprofen has been shown to effective in the treatment of
contact lens related GPC.
Recent studies have shown that 1 percent acetyl
salicylate and 1 percent piroxicam solutions are effective
in treating seasonal allergic conjunctivitis.
Reduction of Discomfort after Refractive Surgery
Topical Kerotolac 0.5 percent has been reported to be
effective in the management of certain corneal conditions.
Well known analgesic effect of topical Ketorolac has been
shown to reduce corneal pain following Excimer Laser
PRK surgery.
Combination of topical diclofenac 1 percent and
topical steroid (FML) has been shown to be statistically
superior to corticosteroid alone in controlling post PRK
myopic regression.
Topical NSAIDs have been used to lessen pain and
inflammation after Nd Yag and photocoagulating lasers.
The use of topical Indomethacin 1 percent has been
found to be effective to treat symptoms associated with
corneal scars, edema, infiltrates and erosions.
Various Topical NSAIDs used Commonly in
Ophthalmic Practice Worldwide
Phenylalkanoic Acids
Flurbiprofen It is one of the most potent NSAIDs of this
group which is found to be very effective in various
ocular conditions. Topical Flurbiprofen is available as
0.03 percent in ophthalmic solution (5 ml pack). It is
indicated for the inhibition of intraoperative miosis. It is
also indicated for treatment of postoperative (iatrogenic)
and post laser trabeculoplasty, inflammation of anterior
segment of the eye. It has no significant effect on IOP.
Dosage For inhibition of intraoperative miosis, a total
of four drops of topical Flurbiprofen should be administered in the eye by instilling one drop every half hour
beginning two hours befor surgery.
One drop should be instilled into the conjunctival sac
every four hours for one week following laser trabeculoplasty or 2-3 weeks after other surgical procedures.

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492 Section V: Ocular Therapeutics


Topical Flurbiprofen is contraindicated in dendritic
keratitis and in individuals who are hypersensitive to
the drug. Precaution should be taken as there exists the
potential for cross-sensitivity to acetylsalicylic acid and
other NSAIDs a histidine drug.
Use of flurbiprofen sodium with an anti-infective
drug in the presence of ocular infections should be
monitored closely.
Adverse reactions The most frequent adverse reactions
reported with the use of Topical Flurbiprofen solution
are transient burning and stinging upon instillation and
other minor symptoms of ocular irritation.
It may cause an increased bleeding tendency of ocular
tissues in conjunction with surgery.
Ketorolac tromethamine It is recently introduced topical
NSAIDs. It is a new alpha substituted aryl acetic acid. It
has both analgesic and anti-inflammatory properties. It
is highly soluble in water (Fig. 48.5).

Fig. 48.5: Chemical structure of ketorolac tromethamine

As it is non-narcotic, nonsteroidal agent, its mechanism of action is by its ability to inhibit prostaglandin
biosynthesis. Ocular administration of Ketorolac reduces
prostaglandin E2 levels in aqueous humour clinical
studies have shown that the mean concentration of PGE2
was 80 pg/ ml in aqueous humour prior to start of Topical
Ketorolac treatment which was reduced drastically to 28
pg/ml in the eye receiving Ketorolac ophthalmic
solution. It has no significant effect upon intraocular
pressure.
Ketorolac ophthalmic solution has following salient
features.
It can be safely administered in conjunction with other
ophthalmic medications such as antibiotics, beta
blockers, carbonic anhydrase inhibitors, cycloplegic
and mydriatics.
Inhibits leukocyte accumulation even better than
dexamethasone.
Microfine suspension helps in uniform distribution
and rapid absorption.
Lesser propensity to raise IOP than low dose and
comparable dose dexamethasone.
Proven safety in children.

Indications and usage


Indicated for relief of ocular itching due to seasonal
allergic conjunctivitis. It significantly reduces conjunctival inflammation, lid edema, foreign body
sensation and photophobia.
Post-Excimer PRK surgery pain management.
Chronic conjunctivitis.
Iatrogenic inflammation of the eye.
Treating Aphakic and Pseudophakic CME.
For treating episcleritis, patients with corneal edema
or erosions.
For prophylaxis associated with retinal detachment
surgery.
Dosage and administration
Topical ketorolac tromethamine ophthalmic solution
is available in strength of 0.5 percent. The recommended dose is one drop four times a day in seasonal
allergic. Conjunctivitis, Post PRK pain management
and in iatrogenic inflammation of the eye. On topical
use it is distributed throughout ocular tissues.
Systemic 10 mg tablets (one tablet 3-4 times daily
depending upon the severity of pain.
Injection 1 ml ampoule containing 4.35 mg of
Ketorolac.
Precautions should be taken regarding its potential
for cross-sensitivity to acetylsalicylic acid, Phenylacetic acid derivatives and other NSAIDs.
There is report that it may cause increased bleeding
of ocular tissues including hyphema in conjunction
with ocular surgery as it has potential for increased
bleeding time due to interference with thrombocyte
aggregation.
Adverse reactions On topical use ketorolac is welltolerated except for transient stinging and burning
sensation on instillation. Other ocular adverse effects
reported are ocular irritation, allergic reactions,
superficial ocular infections and superficial keratitis. On
systemic use it can cause GIT disturbances like nausea,
vomiting, constipation, anorexia, pain and ulceration.
Dermatological and hypersensitivity reactions, CNS
effects like headache, dizziness, depressions, confusion
and insomnia.
Suprofen It is available as 1 percent topical ophthalmic
solution. Following topical application it achieves
significant intraocular levels and inhibit the release of
prostaglandin E2 and F2x and thromboxane B2 from the
inflamed cornea more effectively.
It is good NSAID in treating giant papillary conjunctivitis, iatrogenic inflammation of eye and in preventing
intraoperative miosis.

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Chapter 48: Update on Anti-inflammatory Therapy 493


Dosage It is available as 5 ml pack in 1 percent conc.
Patient is advised to put 2 drops at 1, 2, 3 hours preoperatively and four times a day postoperatively and in
other ocular inflammatory conditions. Besides these
NSAIDs, the other phenyl alkanoic acid derivative used
in topical form are:
Fenoprofen (0.3%)
Ibuprofen (0.5%)
Ketoprofen (1.0%)
Naproxen (0.5%)
Piroxicam (1%)
Fig. 48.6: Chemical structure of diclofenac

Indoles
Indomethacin Topical Indomethacin is used in the form
of 1 percent aqueous suspension and recently introduced
0.1 percent ophthalmic solution.
It is an excellent NSAID to treat Aphakic and Pseudophakic CME following cataract surgery and retinal
detachment surgery.
It has an excellent anti-inflammatory property in
treating iatrogenic inflammation, Episcleritis and
patients of corneal edema and erosions. It has good
intraocular penetration. Its mechanism of action and
adverse reactions are similar to other NSAIDs
mentioned earlier in this chapter. In other indole
NSAIDs used topically are:
1. Tolmetin (5% ophthalmic solution)
2. Surindac (1%)
Phenyllactin Acid
Diclofenac sodium is a potent non-steroidal anti-inflammatory drug with analgesic activity which inhibites
prostaglandin synthesis. Sodium salt of diclofenac is
commercially used. It is one of the most widely prescribed NSAID (Either topical or systemic) in ophthalmology.
It is most commonly used for its marked anti-inflammatory and analgesic activities in ophthalmology (Fig. 48.6).
Indications
1. In topical form it is most commonly prescribed in
iatrogenic inflammation, pseudophakic inflammation
of the eye following cataract and IOL surgery.
2. In aphakic, pseudophakic CME following intraocular surgery.
3. In reduction of post-excimer laser PRK surgery pain
in the patients.
4. Inhibition of surgically induced miosis during intraocular surgery.
Dosage and administration
In topical form it is used as ophthalmic solution in
strength varying from 0.1 to 1 percent. It has good

intraocular penetration. Patient is advised to put one


drop 4 times a day postoperatively till the complete
clinical cure is achieved. For preoperative use 1 drop
of topical diclofenac 0.1 percent solution may be
instilled in the affected eye 5 times during 3 hours
(prior to surgery).
In systemic form, it is available as tablet in the
strength of 25, 50 and 75 mg. Patient is given oral
dose in certain ocular condition where systemic
administration is warranted in addition to topical use.
It is also available in injection form as 75 mg/3ml
ampoule. In certain cases of severe postoperative
pain 1-2 deep intramuscular injection is indicated
following cataract surgery for analgesic effect.
Topical diclofenac does not cause rise in intraocular
pressure. It is contraindicated in patients allergic or
sensitive to asprin or other NSAIDs. Patients with blurred
vision should not drive or operate machinery and soft
contact lenses should not be worn during the treatment
period.
Place of ocular diclofenac in therapy As the world population ages, cataract becomes an even more common
problem facing clinicians and surgeons.
Indentification of effective pharmacological method
of treating or preventing acute inflammatory processes
associated with surgical extraction of cataract constitute an important goal of pre- and postoperative management.
NSAIDs have more recently become a focal point in
the search for an alternative anti-inflammatory adjunct
to cataract surgery. The activity of this class of drugs is
by inhibiting prostaglandin synthesis.
Topical diclofenac a potent NSAID has shown
equivalent efficacy (when formulated as 0.1% solution)
to dexamethasone 0.1 percent solution in attenuating
signs of ocular inflammation. The drug is similar to
indomethacin 0.1 percent in preventing elevation of IOP
following cataract surgery. The occurrence and severity

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494 Section V: Ocular Therapeutics


of cystoid macular edema is lessened with prophylactic
instillation of topical diclofenac and drugs appears to
prevent surgically induced miosis to greater degree.
Adverse reactions Topical diclofenac solution is well
tolerated except for a transient localised burning and
tingling sensation as reported by some patients.
On systemic use GIT disturbances, Headache,
dizziness, rash, pruritus, peripheral edema, GI bleeding
and peptic ulcer, etc.
General Local and Systemic Toxicity of NSAIDs
The most common adverse reactions after topical
instillation as already described in individual NSAIDs
pharmacokinetics are transient blurring, stinging and
hyperemia of the conjunctiva.
Manufacturers have used various new formulation
methods to minimise this potential discomfort.
Indomethacin solution in sesame seed oil was abandoned in favor of aqueous suspension or ophthalmic
solution. Suprofen is prepared with 1 percent caffeine
because it is less irritating in this form. Ketorolac is
formulated as tromethamine salt as its moiety enhances
the aqueous solubility and results in solution which is
less irritating to the eye.
In addition allergic and hypersensitive reactions have
been reported with topical NSAIDs. Systemic administration of NSAIDs can be accompanied by serious side
effects such as gastrointestinal, central nervous system,
hematological, renal, liver, dermatological and metabolic
changes. It appears though these effects are largely
avoided by topical administration.
Therefore, NSAID use much be carefully monitored
for adverse events as it is good practice with any new
drug treatment.
IMMUNOSUPPRESSIVE AGENTS IN
OPHTHALMOLOGY
Immunosuppressive drugs should be prescribed by
ophthalmologist preferably with greater caution and in
concert with an oncologist.
Till date there appears to have been very low
incidence of severe complications from the combined
regimen of corticosteroids and immunosuppressive
agents probably because of lower dosage use and better
general health of ophthalmic patients receiving them.
Patients should be fully informed as to potential risks
and benefits.
Selection of Patients
Selection involves those patients who have progressive, usually bilateral vision threatening disease.

Failed to respond to conventional corticosteroid


therapy or have unacceptable side effects from them.
Have Wegeners granulomatosis, polyarteritis nodosa
or Behcets disease (Drugs of first choice).
Have adequate follow-up.
Good compliance about following instructions.
Are ready to undergo therapy voluntarily with
knowledge of potential side effects.
May benefit certainly from the use of the drugs.
Have no primary contraindication like active tuberculosis, toxoplasmosis or other infectious process.
Immunosuppressive agents used in ocular inflammatory diseases are classified into three groups:
a. Alkylating agents
b. Antimetabolites
c. Antibiotics
Alkylating Agents
Common alkylating agents used in ophthalmic conditions are cyclophosphamide and chlorambucil. They
work by suppression of lymphocyte T cell (cell mediated
immunity) and to lesser extent B cell (antibodies)
function.
Clinical indications Behcets disease, sympathetic ophthalmia, rheumatoid arthritis, polyarteritis nodosa,
Wegeners granulomatosis, relapsing polychondritis,
bulluous pemphigoid and malignancy.
Dosage
Cyclophosphamide In adult patients start at 150-200
mg/day (1-2 mg/kg/day) taken empty stomach. A white
blood count (WBC) is taken at day 1 and after every 2-3
days until at about 7 days. At this point dosage is reduced
by 25-50 mg to stabilise the WBC at about 3000 cells/l.
WBC and CBC with differential are then followed weekly
and fortnightly once stabilised.
Chlorambucil dosage In adult patients start at 0.1-0.2
mg/kg/day and increased every 3-4 days to total dosage
of 10-12 mg/day if there is no idiosyncratic reaction. The
WBC and CBC with DLC are followed as for cyclophosphamide.
Adverse reactions Adverse side effects of alkylating
agents include
Thrombocytopenia
Anaemia and opportunistic infections
GIT disturbances
Alopecia, jaundice
Pulmonary interstitial fibrosis
Renal toxicity and testicular atrophy
Hemorrhagic cystitis is an indication for discontinuing the medication. There is report of increased

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incidence of myeloproliferative and lymphoproliferative malignancy in patients on these drugs.
The Antimetabolites
The antimetabolites used in ophthalmology are
1. Azathioprine which interferes with purine metabolism.
2. Methotrexate which interferes with folate action.
Both functions are essential for nucleic acid synthesis.
Clinical indications
In rheumatoid arthritis, pemphigoid and regional
ileitis.
Sympathetic ophthalmia and VKH syndrome
Pars planitis and Behcets disease.
Recalcitrant cases of intermediate uveitis.
Dosage
Azathioprine dosage starts at 1-2 mg/kg/day gradually
increasing to 2.5mg/kg/day. The usual dose range is 100200 mg/day in one or divided doses. Patient WBC, CBC
with differential are taken at regular intervals.
Adverse reactions
Uncontrolled leukopenia
Thrombocytopenia
Hyperuricemia
GIT disturbances.
Methotrexate dosage is variable due to high drug toxicity. Generally for 1-4 weeks oral, IM or IV dose of 2.5-15
mg is given over 36-48 hours until a therapeutic response
is noted and then maintained as per hematologic
(weekly) and renal and hepatic (monthly) monitoring.
Adverse effects of methotrexate
Leukopenia and thrombocytopenia
Hepatic and renal toxicity
GIT disturbances
Interstitial pneumonitis
CNS toxicity and sterility.
Hematological monitoring (WBC, CBC with differential) is similar to that of cyclophosphamide.
The Antibiotic Cyclosporin A
It probably interferes with T cell lymphocyte activation
and interleukin activity and dapsone may work by
lysosomal stabilisation.
Clinical indications for Cyclosporin A
Behcets disease (for which corticosteroids are contraindicated).

Birdshot chorioretinopathy
Sarcoid, VKH and sympathetic ophthalmia
Relative indications All noninfectious cases of uveitis
unresponsive to maximum tolerated steroid therapy.
Eales disease
Retinal vasculitis (non-infectious)
Serpiginous chroiditis.
Anterior segment diseases include pemphigoid,
Moorens ulcer, High risk corneal transplant rejection
and cataract surgery in uveitis patients.
Dosage 2.5-5 mg/kg/day given orally in an olive oilethanol solution with milk or juice. Maximum dose is
10 mg/kg/day.
Adverse effects
Systemic hypertension
Partially reversible renal toxicity
Opportunistic infections
Hyperuricemia
Hepatotoxicity
Monthly and if required weekly blood tests (CBC with
differential and WBC) should monitor these effects.
i. A combination of steroid and cyclosporine A
therapy augment each other such that addition of
prednisone (10-20 mg/day) or short-term 1 mg/
kg/day may allow a lowering of the cyclosporine
A dosage. (4-6 mg/kg/day) with no loss of therapeutic efficacy).
ii. Chlorambucil or cyclophosphamide and steroid
management module
It involves initial treatment with prednisone 1 mg/
kg/day along with cytotoxic drug at an appropriate dose.
This treatment should be continued for 4 weeks until the
disease is suppressed than steroids are tapered and
stopped over 2 months. The cytotoxic drug dose is
adjusted to keep the WBC at 3000-4000/ul and continued
for one year to induce remission before being stopped.
Monitor the CBC and urine analysis weekly until stable
than at every 2 weeks.
Ocular Drug Toxicity of Immunosuppressive Agents
used in Ophthalmic Conditions
Decrease in vision
Visual hallucinations
Lids or conjunctivaredness, conjunctivitis, subconjunctival hemorrhage and hypertrichosis
Eyelashes or brow losses
Retinal hemorrhages
Retinal pigment epithelium disturbances
Cortical blindness (cyclosporine).

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FURTHER READING
1. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi :
Jaypee Brothers Medical Publishers, 2002.
2. Bartlett JD, Clinical Ocular Pharmacology, ed.4, Boston :
Butterworth-Heinemann,2001
3. Bartlett JD, Ophthalmic Drug Facts; LippincottWilliam and
Wilkins, 2001.
4. Crick RP, Trimble RB, Textbook of Clinical Ophthalmology;
Hodder and Stoughton, 1986.
5. Duane TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
6. Duvall, Ophthalmic Medications and Pharmacology; Slack Inc,
1998.
7. Ellis PP, Ocular Therapeutics and Pharmacology, ed. 7 : C.V.
Mosby, 1985.
8. Fechner, Ocular Therapeutics; Slack Inc., 1998.
9. Flach AJ, Nonsteroidal Anti-inflammatory Drugs in Ophthalmology; Int. ophthalmol. Clinic, 1993; 33 : 1.
10. Franzie JP, Steroids; Int. Ophthalmol. Clinic, 1993; 33 : 9.
11. Fraunfelder, Current Ocular Therapy, ed. 5 : W.B. Saunders,
2000.
12. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.

13. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:


Jaypee Brothers Medical Publishers, 1996.
14. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi : 2002.
15. Goodman. LS, Gilman. A, Pharmacological Basis of Therapeutics, ed.7, New York : Macmillan, 1985.
16. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.
17. Kanski, Clinical Ophthalmology, ed. 4: Butterworth
Heineman, 1999.
18. Kershner, Ophthalmic Medications and Pharmacology; Slack.
Inc., 1994.
19. Leibowitz HM, Anti-inflammatory Medications : Int.
Ophthalmol. Clinic, 1980; 20 : 117.
20. Olin BR et.al., Drugs Facts and Comparisons : Facts and
Comparisons, St. Louis, 1997.
21. Onofrey, The Ocular Therapeutics; Lippincott-William and
Wilkins, 1997.
22. Rhee, The Wills Eye Drug Guide; Lippincott William and
Wilkins, 1998.
23. Steven Podos, Textbook of Ophthalmology, New Delhi : Jaypee
Brothers Medical Publishers, 2001.
24. Zimmerman, Textbook of Ocular Pharmacology; Lippincott and
William and Wilkins, 1997.

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Chapter 49: Update on Ophthalmic Dyes 497

49

Update on Ophthalmic Dyes


Ashok Garg

INTRODUCTION
FLUORESCEIN SODIUM
FLUOREXON
ROSE BENGAL
LISSAMINE GREEN
INDOCYANINE GREEN
TRYPAN BLUE
VERTEPORFIN (VISUDYNE)

INTRODUCTION
Ophthalmic dyes are one of the most useful diagnostic agents used in the
detection and management of disorders of the visual system.
Various dyes used in ophthalmology are:
1. Fluorescein sodium
2. Fluorexon
3. Rose bengal
4. Lissamine green
5. Indocyanine green.
Individual drug monograph is as follows:
FLUORESCEIN SODIUM
Fluorescein sodium is a yellow water soluble dibasic acid dye of the
xanthine series that produce intense green fluorescent color in alkaline
solution. Chemically it is C2H12O5Na (Molecular weight 376.27). It is orange
red in powder and yellow in solution.
It fluoresces yellow green in blue light and is most common staining
agent used in the ophthalmology.
Its peak absorption: 465490 nm
Peak emission: 520530 nm
Fluorescence increases with greater concentration upto 0.001 percent
and with greater pH upto pH 8. But at very high concentrations quenching
occurs. It demerises, polymerizes and emission shifts to longer
wavelengths. Fluorescein is used to demonstrate defects of corneal
epithelium. It does not actually stain the tissues but is used as an indicator
dye.
The normal precorneal tear film appears yellow or orange with
fluorescein. The intact corneal epithelium prevents penetration of water
soluble fluorescein and is not colored by it. Any break in the epithelium
barrier permits rapid fluorescein penetration occurring due to any trauma,
infection and other causes. Epithelial defects or cornea appear bright green
and is easily visualised. If epithelial loss is severe, topical fluorescein
penetrates into the aqueous and is readily visible biomicroscopically as a
green flare.
Fluorescein sodium exhibits a high degree of ionisation at physiological
pH. Therefore, it does not penetrate the intact corneal epithelium. Break
down of epithelium allows for stromal penetration. When exposed to light,
fluorescein absorbs certain wavelengths and emits fluorescent light of
longer wavelength. At pH 8 fluorescein reaches its maximum intensity.

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498 Section V: Ocular Therapeutics

Fig. 49.1: Fluorescein strips for evaluation of conjunctival


injuries and infections

Clinical characteristics
Stains epithelial defects bright green
Diffuses into inter cellular spaces
Will not stain devitalised cells or mucus
Tear film appears yellow orange
Can exhibit pseudoflare, Fisher-Schweizer mosaic
Promotes growth of Pseudomonas in solution
Will stain soft contact lenses.
Indications
49.7):

Fluorescein sodium is used for (Figs 49.1 to

Fig. 49.3: Fluorescein strips for applanation tonometry


(Courtesy: FDS Limited)

Fig. 49.2: Fluorescein strips for dry eye disorder (BUT)

Topical
Lacrimal testing (TBUT, Jones test)
Detection of corneal epithelial defects
Detection of penetration of globe (Seidels sign)
Applanation tonometry.
Contact lens/corneal fitting relationship
Fitting of rigid contact lenses
Retinal angiography.
Injection
Vitreous fluorophotometry.
Disgnostic aid in ophthalmic angiography including examination of fundus, evaluation of iris
vasculature, distinction between viable and nonviable tissue, observation of aqueous flow, differential diagnosis of malignant and non-malignant
tumours, determination of circulation time and
adequacy.
Unlabelled use
It can be administered orally as a diagnostic aid in the
detection of certain retinal vascular diseases.

Fig. 49.4: Fluorescein strips for evaluation of contact lens fitting

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Chapter 49: Update on Ophthalmic Dyes 499


Do not use topically with soft contact lenses as lenses
may get discolored.
Administration and dosage For topical use fluorescein
may be administered as a topical solution or by Fluorescein impregnated paper strips. Since fluorescein in
solution is susceptible to bacterial contamination,
multidose formulations are dispensed with a
preservative such as chlorobutanol or thimerosal. For
diagnostic purposes such as applanation tonometry, a
local anesthetic is included in the formulation.

Fig. 49.5: Fluorescein strips for evalution of corneal injuries


and infections

Fig. 49.6: Fluorescein dye test (Courtesy: FDS Limited)

Fig. 49.7: Fluorescein dye test (Courtesy: FDS Limited)

Contraindication
Hypersensitivity to active ingradient or any other
components

Topical formulations
a. In topical solution it is available as 2 percent solution
in (1, 2 and 15 ml packs).
To detect foreign bodies, corneal abrasions instill 1-2
drops of 2 percent solution. Allow a few seconds for
staining. Washout excess with sterile irrigating solution.
b. Topical solution containing
0.25 percent fluorescein sodium
0.1 percent proparacaine hydrochloride
in 5 ml
0.01 percent thimerosal preservative
pack
c. 0.25 fluorescein sodium
0.50 percent proparacaine hydrochloride
in 5 ml
0.01 percent thimerosal with povidone,
pack
boric acid and polysorbate 80.
0.25 percent fluorescein sodium
0.4 percent benoxinate hydrochloride
in 5 ml
1 percent chlorobutanol, povidone buffers pack
Fluorescein strips Fluorescein impregnanted strips are
useful for routine procedures such as contact lens fitting,
lacrimal system evaluation. Bacterial contamination is
minimised since the strips are stored in dry state. When
wetted with water or an irrigating solution, the dye is
released from the strips and can be applied to the eye by
gently touching the conjunctiva with sterile filter paper
impregnated with fluorescein of 1 percent or 2 percent
solution.
Various fluorescein strips preparations are:
1. 1 mg strips (boric acid, polysorbate 80 and 0.5
percent Chlorobutanol).
2. 9 mg strips (boric acid, polysorbate 80 and 0.5
percent Chlorobutanol).
3. 0.6 mg and 1 mg strips.
4. High molecular fluorescein (Higlo) strips for soft.
Contact lenses and it does not stain soft lenses.
Intravenous fluorescein (Fluorescein angiography) It is
used for the detection of vascular abnormalities of
fundus. Following injection into antecubetal vein, the dye
appears in central retinal artery. Integrity of retina and
choroid as well as arm to retinal circulation time may be

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500 Section V: Ocular Therapeutics


determined. For IV use fluorescein is available as 10
percent and 25 percent injections (in 2 ml, 5 ml ampoules
and in 10 ml disp. syringe).
Oral fluorescein It can be administered by mixing
fluorescein powder or several vials of 10 percent
injectables fluorescein in a citrus drink. Time of onset of
maximal fluorescence is 45-60 minutes as compared to
seconds via the injectable route. Oral fluorescence can
be used to study disorders characterised by late leakage
of dye such as cystoid macular edema, to study retinal
vascular abnormalties in young diabetic patients and to
document retinal pigment epithelial detachment, central
serous choroidopathy and optic disc edema.
Adverse reactions Topical application of fluorescein has
minimum adverse effects. Injection administration may
cause nausea, headache, GI distress, vomiting, syncope,
hypotension, signs of hypersensitivity, thrombophlebitis
at the injection site, severe shock, convulsions, temporary
yellowish skin discoloration, itching, anaphylaxis,
pyrexia, urticaria, puritis, angioneurotic edema.
Discoloration of skin disappear in 6-12 hours and urine.
Fluorescence fades in 24-36 hours. Extravasation at the
injection site causes intense pain, at the site and dull
aching pain in the injection arm.
Precautions
Exercise great caution in adminstering to patients
with a history of hypersensitivity, allergy or asthma.
Avoid extravasation during injection. The high pH
of the solution can result in severe local tissue
damage, sloughing of skin, superficial phlebitis,
subcutaneous granuloma and toxic neuritis along
with median curve in the antecubital area.
Avoid parenteral administration, in pregnant patients
specially in the first trimester.
FLUOREXON
It is N, N-bis (Carboxymethyl) aminoethyl, fluorescein
tetrasodium salt. Its molecular weight is 710.
With a molecular size nearly twice that of fluorescein,
it penetrates hydrophilic contact lens at a much slower
rate.
Upon ocular instillation, it yeilds a pale yellow brown
color.
Fluorexon is less brilliant than fluorescein and does
not increase linearly with increasing concentration.
It stains epithelial defects, devitalized cells and mucin
(less than fluorescein or rose bengal). It does not stain
most soft contact lenses and may stain high water (more
than 60%) contact lenses.

It promotes the growth of Pseudomonas. Fluorexon is


not recommended for use with high water soft contact
lenses since the chances of discolouration are greater and
more difficult to reverse than with lower water content
contact lenses.
For optimal fluorescence, a special yellow filter is
recommended. It generally causes little or no discomfort
when instilled into the eye. Due to its large molecular
size it is less effective stain for epithelial defects, erosions
and contact lens induced effects than fluorescein.
Indications Diagnostic and fitting aid for patients with
hydrogel (soft) contact lenses. Use in eye with or without
lens in place when fluorescein is contraindicated to avoid
staining lenses.
Evaluation of corneal integrity of patients wearing
hydrogel contact lenses.
Can be used in the place of sodium fluorescein when
conducting the tear break-up time (BUT) test.
For performing the Applanation tonometry without
removing the lens.
For detecting the lathe-cut index markings (Toric
lenses).
Dosage It is available as 0.35 percent topical solution
(in 0.5 ml pipettes). Instill one drop of fluorexon on the
concave surface of the lens and place the lens
immediately on the eye.
Alternatively instill 1-2 drops in the lower cul-de-sac
and ask the patient to blink several times. Additional
drop may be necessary during a prolonged examination.
Rinse both the eyes and lens with sterile irrigating
solution or saline following examination.
As the dye passes under the lens, observe a central
dark zone of 6-9 mm in diameter which forms after each
blink. The lens may be reinserted immediately as
compare to the long waiting period required after the
use of fluorescein.
Examination should be started immediately after
instillation of fluorexon drops because this material tends
to dissipate readily with the tear flow leading to a
progressive reduction in fluorescence.
Precaution Do not use solutions containing hydrogen
peroxide to clean or sterilise lenses until all traces of
fluorexon are removed. Hydrogen peroxide can bind
fluorescein molecules to the lens.
ROSE BENGAL
It is Iodine derivative of fluorescein chemically it is
4,5,6,7, tetrachloro 2,4,5,7 tetralodo fluorescein sodium.
It stains devitalised cells and mucin a brilliant red. It
also stains the mucus of precorneal tear film (Fig. 49.8).

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formulation is applied. Application of dye using commercially available filter paper strip usually results in less
discomfort. Rose bengal stains a line along the ciliary
margin on conjunctival tarsus in normal eyes.
Rose bengal can stain eyelids, cheeks, fingers and
clothing in a concentration dependent manner. Keep the
amount of dye at the minimum and irrigating the eye
help circumvent this problem.
LISSAMINE GREEN

Fig. 49.8: Rose bengal staining test


(Courtesy: FDS Limited)

Rose bengal stains the nucleus more than the cytoplasm and higher concentration stain more distinctly and
highlight more subtle defects. When applied as solution
or from a moistened filter paper strip, this dye is an
effective aid in the evaluation of keratoconjunctivitis
sicca, herpes simplex keratitis, corneal abrasions and
detection of foreign bodies. A correlation may exist
between intensity of staining and severity of cellular
defect.
There is no need of actual break in the epithelium for
positive staining with rose bengal. It has also antiviral
properties.
Indications As diagnostic agent for routine ocular
examination on when superficial corneal or conjunctival
tissue change is suspected. Effective aid for diagnosis of
keratitis, corrosions or abrasions and in detection of
foreign body. Contraindication is known hypersensitivity
to rose bengal.

Lissamine green stains degenerated cells, dead cells and


mucous fibrils in the same manner as rose bengal. The
cell nucleus is stained more intensly than the cytoplasm.
Vacuoles in the mucous thread remains unstained.
Indications As diagnostic agent for routine ocular
examination on when supercial corneal or conjunctival
tissue change is suspected. Helpful in the diagnosis of
keratitis, corrosions or abrasions and in detection of
foreign body.
Contraindication is known hypersensitivity to
Lissamine green.
Dosage It is available as sterile ophthalmic strips. Each
strip contain approx 15 mg of Lissamine green (pack of
100 strips).
Direction for use Moisten impregnated tip with sterile
water or normal saline. While the patient looks up, stroke
the tip across the bulbar conjunctiva. The patient should
than blink several times to obtain best results.
Adverse reactions It can cause ocular discomfort and
irritation following instillation.
INDOCYANINE GREEN

Strips Thoroughly saturate tip of strip with sterile


irrigating solution, remove excess before application.
Touch conjunctiva or lower fornix with moistened strip.
The patient should blink several times after application.

It is a unique ophthalmic dye due to its high protein


binding capacity and near infrared fluorescence. It is a
sterile, water soluble tricarbocyanine dye with a peak
spectral absorption at 800-810 nm in blood or blood
plasma. Chemically indocyanine green, contains
< 5 percent sodium iodide.
Indocyanine green has unique characteristic for
recording of indicator-dilution curves for both diagnosis
and research purposes independent of oxygen saturation
fluctuations. In dye dilution curves dye is injected as a
single bolus as rapidly as possible.

Adverse reaction Rose bengal can cause marked ocular


irritation and discomfort following instillation specially
in more severly diseased eyes and with the use of higher
concentrations of dye. A topical anesthetic shall be used
to alleviate the discomfort specially topical solution

Pharmacokinetics The peak absorption and emission


of indocyanine green lie in 800-850 nm where
transmission of energy by the pigment epithelium is more
efficient than in the visible light energy region.
Indocyanine green is about 98 percent bound to plasma

Dosage It is available as topical 1 percent solution


containing 1 percent rose bengal with povidone, sodium
borate, PEG p-isooctylphenol 10 and 0.01 percent
thimerosal in 5 ml pack. It is also available as 1.3 mg
strip. Topically instill 1-2 drops into the conjunctival sac
before examination.

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502 Section V: Ocular Therapeutics


protein so excessive dye extravasation does not take place
in the highly fenestrated choroidal vasculature. It is
highly useful in both absorption and fluorescence
infrared angiography of the choroidal vasculature when
using proper filters and film in a fundus camera.
Following IV injection indocyanine green is rapidly
bound to plasma protein of which albumin is the
principle carrier (95%). Indocyanine green undergoes no
significant extrahepatic or enterohepatic circulation.
Indocyanine green is taken up from the plasma almost
exclusively by the hepatic parenchymal cells and is
secreted entirely into the bile.
Indications
Indocyanine green is used for ophthalmic angiography.
It is indicated for digital indocyanine green videoangiography (ICG-V) and ICG-angiography guided
laser photocoagulation.
ICG-V is a new technique using indocyanine green
as fluorescein dye that enhances imaging of choroid,
its associated pathology and has been shown to be
useful in better delineating occult choroidal neovascularization into well demarcated ones. This enhanced
imaging of choroid and well demarcation of choroidal
neovascularization is specifically due to indocyanine
green special properties of high protein binding
capacity and near infrared fluorescence.
Indocyanine green videoangiography is a predictive
indicator of future exudative changes in eyes with
drusen.
ICG-V can detect subgroups of patients with drusen
who are at higher risk of having exudative changes
developed.
Indocyanine green angiography guided laser
photocoagulation increases the proportion of patients
with well defined or treatable neovascularization in
cases of ARMD. ICG angiography may allow identification and treatment of feeder vessel in a small
percentage of eyes with subfoveal neovascularization
which may allow treatment and resolution of
neovascularization of previously untreatable eyes.
ICG provides additional information regarding the
presence, location, filling patterns and leakage from
choroidal neovascularization.
Administration and dosage It is available as powder for
injection in 25 mg and 50 mg strengths alongwith
aqueous solvents (pH 5.5 6.5) in 10 ml ampoules
aqueous solvent is specially prepared sterile water for
injection to dissolve indocyanine green.
Dosage Generally 40 mg dye in 2 ml of aqueous solvent
is given. Immediately follow the injected dye bolus with

a 5 ml bolus of normal saline. This injection regimen


provides the optimal concentration of spatially limited
dye bolus to the choroidal vasculature following IV
injection. This dye is nontoxic on IV administration. In
certain patients half the volume of ICG has been found
to produce angiograms of comparable resolution.
Compatibility must be ensured before injecting
indocyanine green. Use only the aqueous solvent (pH
5.5-6.5) provided with the dye which is specially prepared sterile water of injection to dissolve indocyanine
green because there are certain reports of incompatibility
with certain commercially available water for injections.
Indocyanine green is unstable in aqueous solution
and should be used within 10 hours. However dye is
stable in plasma and whole blood. Use sterile techniques
in handling the dye solution and in the performance of
the dilution curves.
Indocyanine green powder may cling to the vial or
lump together because it is freeze dried in vials. This is
certainly not due to the presence of water.
Precautions
As indocyanine green contains sodium iodide so use
it with caution in individuals who have history of
allergy to iodides.
Excessive caution should be taken when indocyanine
green is administered in pregnant woman or to a
nursing woman. Give ICG only if clearly indicated.
Do not perform radioactive iodine uptake studies for
atleast a week following the use of indocyanine green.
Heparin preparations containing sodium bisulfite
reduce the absorption peak of indocyanine green in
blood and hence contraindicated.
Adverse reactions Anaphylactic or urticarial reactions
have been reported in patients without history of allergy
to iodides. If such reactions occur treat with suitable
agents (e.g. Epinephrine, antihistamines or corticosteroids).
TRYPAN BLUE
Trypan blue is a dye which safely stains the anterior lens
capsule and is mainly used in cataract surgery (ECCE,
IOL surgery and phacosurgery).
Trypan blue is a capsule stainer which reduces the
risk of complication due to unrecognised radial capsule
by facilitating the performance of the capsulorehexis in
the absencec of red fundus reflex specially in the cases
of matured cataract. Special feature of trypan blue is that
it stains the anterior capsule without affecting the corneal
endothelium. So blue stained capsule can be easily
identified from the underlying unstained lenticular

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Chapter 49: Update on Ophthalmic Dyes 503


tissue. It helps the eye surgeon to see capsule clearly thus
eliminates the chances of hitting the outline with the
phacotip during phacoemulsification.
Mechanism of action Trypan blue is used to enhance
the visualisation of the anterior lens capsule of the eye
during removal of cataractous lens replacement procedures. Trypan blue provides a clear, visible staining at
low amounts without diffusing into or through concerned
tissues. So it facilitates the controlled opening of anterior
capsule and reduces the risk of inadvertent damage to
the capsule specially radial tear towards or beyond the
equator of the lens. Besides, it has low toxicity profile.
Pharmacokinetics Trypan blue solution concentration
is more preferred in the range of 0.01-0.1 percent. In this
range an optimal staining effect is achieved, while at the
same time the risk of possible damage to the eye or any
part thereof due to the toxicity of the dye is minimised.
After few drops instillation of trypan blue dye on to
anterior lens capsule, it selectively stains the anterior lens
capsule whereas the lenticular material beneath the
anterior lens capsule is not stained. No traces of the dye
are present in ocular tissues shortly after the cataract
extraction procedure has been completed.
Indications Trypan blue is indicated for facilitating
surgical procedures for cataract extraction (IOL surgery
and phacosurgery) and as a staining agent.
Administration and dosage It is available as 1 ml single
use ampoule commercially. Each ml contains 0.6 mg
trypan blue, 1.9 mg of sodium mono-hydrogen orthophosphate, 0.3 mg of sodium dihydrogen orthophosphate, 8.2 mg of sodium chloride and sodium hydroxide
for adjusting the pH and water for injection.
For trypan blue administration, first step of procedure
is to inject air into the anterior chamber using a 26 gauge
needle in the area where the second site is made. This
prevents the water like dilution of the trypan blue. Then
trypan blue is withdrawn from the ampoule into the
tuberculin syringe and is injected by needle into the
anterior chamber between the airbubble and the lens
capsule. Use the bevel down of the needle and see to it
that the injection is made in a drop format so that the
whole capsule gets stained. If some portion is left
unstained, inject a drop in that area till it gets stained. It
is kept lie in this position for a minute for complete
staining of the anterior capsule to occur. Thereafter
viscoelastic is injected into the anterior chamber. This will
distend the eye so that during clear corneal incision eye
shall be tense and one can create a good valve. Now one
can use a straight rod to stabilise the eye with the left
hand and with the right hand clear corneal or scleral

incision can be made. Inject viscoelastic inside the eye to


remove the air bubble and trypan blue. Now rhexis can
be started with a needle or Forceps (Surgeon choice). One
can see the contrast between the capsule which has been
stained and the cortex which is unstained. The rhexis is
continued and finally completed. After rhexis completion
we can see the stained anterior capsule lying in the
anterior chamber.
Contraindication Trypan blue is contraindicated in
patients with a hypersensitivity to the dye or any of its
components.
Adverse reactions
Clinical literature reports are not certain if extended
contact of trypan blue with the corneal endothelium
produces corneal damage or not. At present no case
has been reported as the trypan blue is washed off
with the viscoeleastic and the BSS fluid.
Mild postsurgical inflammatory reactions and some
bullous keratopathy have been reported to occur after
using trypan blue in certain cases.
Trypan blue solution should be given to a pregnant
woman only if the benefits clearly outweigh any
possible risks.
On the whole trypan blue is well tolerated following
injection into the anterior chamber of the eye during
cataract surgery.
VERTEPORFIN (VISUDYNE)
Visudyne (Verteporfin) is a photosensitive second generation porphyrin (benzoporphyrin), mono acid derivative
which has been recently approved by FDA (Food and
Drug administration) USA for the photodynamic therapy
(PDT) the drug/light combination for the treatment of
wet age related macular degeneration (ARMD).
Pharmacokinetics Verteporfin is a chlorin type molecule and exists as an equal mixture of two regio isomers
each of which consists of an enantiomeric pair that
demonstrate similar pharmacological activity in vitro and
in vivo. It has a molecular formula of C41H42N4O8 and a
molecular weight of 718.81 (Fig. 49.9). Verteporfin is
formulated in a lipid based preparatioin that augments
solubility in the blood.
It is a lipophilic molecule that selectively accumulates
in vascular endothelial cells such as the neovascular
tissues of AMD possibly due to increased concentration
of low density lipoprotein (LDL) receptors in the
membrane of these cells.
Verteporfin has a long absorption wavelength with
several peaks including a strong absorption peak in the

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504 Section V: Ocular Therapeutics

Fig. 49.9: Chemical structure of verteporfin (Courtesy: Novartis ophthalmics)

680-695 mm region. It absorbs light efficiently at a


wavelength of 689 nm (red light) which can penetrate a
thin layer of blood, melanin or fibrotic tissue. This absorption peak does not interfere with any of the absorption
peaks of naturally presents substances. Due to its peak
absorption at a long wavelength enables the laser light
to penetrate deep into the target tissue.
Association of verteporfin with lipoprotein provides
selectivity for neovascular tissues and enhances the
photodynamic effect. It is cleared rapidly from the
plasma with an elimination half-life of 5-6 hours.
Verteporfin is excreted almost exclusively in the feces
primarily with in 24 hours of administration.
The selective uptake and retention of verteporfin in
CNV (Chroidal neovascularization) is important because
it limits the extent of damage to surrounding normal
healthy tissues uptake of verteporfin is rapid reaching
maximum levels within 30 minutes.
Indications Verteporfin is indicated for the treatment
of age-related macular degeneration in patients with
predominantly classic subfoveal choroidal neovascularization (Wet type).
Administration and dosage Verteporfin (Visudyne) is
commercially available in single use 15 mg vials as a
sterile, lipid based, freeze dried powder that requires
reconstitution with sterile water and dilution with 5
percent dextrose solution before administration. It is
available for intravenous infusion only. Verteporfin
should be stored at room temperature between 20-25oC
and shall be protected from light.

Reconstitution For a total volume of 7.5 ml of reconstituted drug 7.0 ml of sterile water for injection has to be
injected into the verteporfin vial which should then be
gently agitated until the powder is completely dissolved.
The reconstituted solution must be protected from light
and used with in 4 hours. Saline solution should not be
used because verteporfin precipitates in saline.
Dilution Further dilution with 5 percent dextrose for
injection is required to achieve a drug dose of 6 mg/m2
BSA and a total infusion volume of 30 ml. BSA can be
determined using a nomogram or a graphic algorithm.
Dosage and mechanism of action Verteporfin therapy
is a two-step process involving administration of a nontoxic light activated drug and its subsequent activation
by a specific wavelength of light using a non-thermal
diode laser device.
Verteporfin is activated at a long wavelength that
optimizes energy absorption of the drug (Figs 49.10 to
49.12). The most suitable light source for verteporfin
therapy is diode laser operating at a wavelength of
689 + 3 nm. At the power used to activate verteporfin
the laser causes no thermal damage to retinal tissues.
The laser beam is delivered through a slit lamp to the
affected area in the retina and the light is targeted to the
desired area by means of a low intensity helium-neon
(HeNe) beam through a standard ophthalmological
contact lens.
The optimal regimen of verteporfin therapy recommended internationally is as follows:

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Chapter 49: Update on Ophthalmic Dyes 505


Visudyne therapymechanism of action

(A) Circulating visudyne complexes with


LDL

(B) Visudyne selectively accumulates in


neovascular tissue which is rich in LDL
receptors

(C) Light-activated visudyne produces


reactive forms of oxygen which cause
structural and functional cell damage

(D) Visudyne selectively occludes neovascular tissue, while sparing overlying retinal
cells and Bruchs membrane

Fig. 49.10: Schematic illustration of 4 stages of mechanism of action of verteporfin (Courtesy: Novartis ophthalmics)

Verteporfin
Dose

: 6 mg/m2 body surface


area (BSA)
Infusion rate
: 3 mL/min
Duration of infusion : 10 minutes
Height (m) weight (kg)
Formula for m2 BSA : ________________________________
6
Light application
: Interval after start of
verteporfin infusion: 5 min.
Wavelength
: 689 nm
Dose
: 50 J/cm2
Intensity
: 600 mw/cm2
Resulting duration of
light application
: 835
Strict adherence to this regimen is necessary for safe
and effective treatment.

Mechanism of action of verteporfin Verteporfin is a


potent photosensitizer which is administered intravenously as a liposomal preparation. Immediately after

intravenous administration, verteporfin partitions into


the lipoproteins in the blood, particularly the LDL
fraction. It selectively accumulates within neovasculature
including neovascular endothelial tissue probably due
to increased uptake of LDL and increased expression of
LDL receptors on rapidly proliferating cells. Once
verteporfin has bound to surface receptors on endothelial
cell membranes, it is taken up into the cell and binds to
intracellular or cytoplasmic components. This is thought
to be a major mechanism of selective accumulation and
retention of verteporfin in these tissues.
Application of the nonthermal diode laser to the
target tissues (689 nm) causes verteporfin to transform
from a ground singlet state to an excited triplet state.
Verteporfin initiates photochemical reactions either
directly via the formation of reactive free radicals (typeI mechanism) or indirectly via the transfer of its energy
into ground state oxygen (3O2) and highly reactive singlet
oxygen (IO2) type-II mechanism.

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506 Section V: Ocular Therapeutics

Fig. 49.11: Verteporfin mechanism of action (Courtesy: Novartis ophthalmics)

Both photochemical reactions can occur simultaneously and both causes direct cytotoxicity. Both
reactions cause damage or death to cells in which

verteporfin has accumulated. Damage to endothelial cells


leads to platelet adhesion, platelet aggregation and
thrombus formation and this process results in occlusion

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Chapter 49: Update on Ophthalmic Dyes 507

Fig. 49.12: Pathophysiology of AMD (Courtesy: Novartis ophthalmics)

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508 Section V: Ocular Therapeutics


of the leaking CNV. Occlusion of CNV can be safely
reproduced without any negative effect on the overlying
retinal tissue.
So the primary mechanism of visudyne therapy may
be damage to the fibrovascular tissue through the inductioin of neovascular occlusion. Histologically the
endothelial cells lining the vessels are damaged, they are
swollen and the nuclear membrane breaks. Other nearby
vessels remain intact and there is minimal damage to
adjacent retinal structures such as overlying photoreceptors and RPE, therapy maintaining function of the retina
and helps to increase the chances of stable vision.
The abnormal blood vessels may return after several
months. However verteporfin therapy can be reapplied
at upto 3 months intervals if necessary.
Adverse reactions Usually verteporfin therapy is well
tolerated. Most adverse events are mild to moderate and
transient in nature.
a. Ocular Adverse Events
Transient vision disturbances (Decreased vision
and visual field defects).
Cataract
Conjunctivitis
Eye pain
Lacrimation disorder
Photophobia
Subretinal hemorrhage
Vitreous hemorrhage.
Patients in whom such symptoms appear should
therefore not drive or operate machinery for as long
as these symptoms persists.
To provide safe and effective treatment the recommended light dose of 50 J/cm 2 should not be
exceeded.
b. Systemic Adverse Reactions
Back pain
Abdominal pain
Asthenia
Flu syndrome
Headache
Injection site adverse reactions like edema, extravasation, fibrosis, hemorrhage, hypersensitivity,
inflammation and pain.
Photosensitivity reactions.
Digestive adverse reactions like diarrhea, dyspepsia, nausea and vomiting.
Metabolic and nutritional adverse reactions like
glycosuria, hypokalemia, ketosis and hypercholesterolemia.
Dizziness
Rhinitis and pruritus.
Injection site adverse events can be limited by
compliance with IV procedures. Photosensitivity

reactions can be limited by compliance with


precautionary, guidelines immediately after
verteporfin therapy patients should take the
following precautions.
Avoid exposure to direct sunlight or bright indoor
lighting.
Wear dark sunglasses while outdoors during the
first 48 hours.
Reschedule dental or elective hospital surgery to
avoid exposure to powerful operating lights.
Exposure to low levels of indoor light should be
encouraged to promote photobleaching and rapid
drug elimination.

Contraindications Verteporfin therapy is contraindicated in patients with porphyria or patients with known
hypersensitivity to verteporfin or any other component
of the lipid based formulation.
Precautions Caution should be taken in treating
patients with uncontrolled hypertension, unstable
cardiovascular disease, active hepatitis or moderately
severe or severe liver disease. Advanced cataracts and
retinal tears should be treated before initiation of
verteporfin therapy.
Overdose Overdose of drug and /or light in the treated
eye may result in nonperfusion of normal retinal vessels
with the possibility of a severe decrease in vision that
could be permanent. An overdose of visudyne may also
result in the prolongation of the period during which
the patient remains photosensitive to bright light. In such
cases photosensitivity precautions are extended for a time
proportional to the overdose.
FURTHER READING
1. AAO, Ophthalmology Monograph on Fluorescein and Indocyanine Green, 2001.
2. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.
3. Bartlett JD, Clinical Ocular Pharmacology, ed.4, Boston:
Butterworth-Heinemann,2001
4. Bartlett JD, Ophthalmic Drug Facts, Lippincott William and
Wilkins, 2001.
5. Berkow JW et al, Fluorescein and Indocyanine Green Angiography Techniques, ed 2: American Academy of Ophthalmology, 1997.
6. Crick RP, Trimble RB, Textbook of Clinical Ophthalmology,
Hodder and Stoughton, 1986.
7. Duane TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
8. Duvall, Ophthalmic Medications and Pharmacology, Slack Inc,
1998.
9. Ellis. PP, Ocular Therapeutics and Pharmacology, ed. 7: C.V.
Mosby, 1985.
10. Fechner, Ocular Therapeutics, Slack Inc., 1998.
11. Feenstra et. al., Comparison of Fluorescein and Rose Bengal
Staining, Arch. Ophthalmol., 1992; 99: 605.

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Chapter 49: Update on Ophthalmic Dyes 509


12. Fraunfelder, Current Ocular Therapy, ed. 5: W.B. Saunders, 2000.
13. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
14. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
15. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
16. Goodman. LS, Gilman. A, Pharmacological Basis of Therapeutics, ed.7, New York: Macmillan, 1985.
17. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.
18. Kanski, Clinical Ophthalmology, ed. 4: Butterworth
Heineman, 1999.
19. Kershner, Ophthalmic Medications and Pharmacology, Slack.
Inc., 1994.

20. Olin BR et.al., Drugs Facts and Comparisons: Facts and Comparisons, St. Louis, 1997.
21. Onofrey, The Ocular Therapeutics; Lippincott-William and
Wilkins, 1997.
22. Reichel, Atlas of Indocyanine Green Angiography, Lippincott
William and Wilkins, 1995.
23. Rhee, The Wills Eye Drug Guide: Lippincott William and
Wilkins, 1998.
24. Steven Podos, Textbook of Ophthalmology, New Delhi: Jaypee
Brothers Medical Publishers, 2001.
25. Yannuzzi LA et al., Digital Indocyanine Green Video Angiography and Choroidal Neovascularization, Retina, 1992; 12: 191.
26. Zimmerman, Textbook of Ocular Pharmacology, Lippincott and
William and Wilkins, 1997.

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510 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

50

Commercial packing

Quick Look Ocular


TherapeuticsAn Update
Ashok Garg

ANTIBACTERIALS
COMBINATION ANTIBIOTICS
ANTIINFLAMMATORY DRUGS
TOPICAL STEROID-ANTIBIOTIC
COMBINATIONS
ANTIVIRAL THERAPY
ANTIFUNGAL THERAPY
ANTIALLERGY THERAPY
ANTIGLAUCOMA THERAPY
LOCAL ANESTHETIC AGENTS
LOCAL ANESTHETIC
COMBINATIONS
MYDRIATICS AND CYCLOPLEGICS
OPHTHALMIC VISCOSURGICAL
DEVICES (OVD) AND SURGICAL
ADJUNCTS
OPHTHALMIC DYES
LUBRICANTS AND ARTIFICIAL
TEAR SOLUTIONS
TOPICAL IMMUNE THERAPY
TOPICAL HYPEROSMOTIC
AGENTS
CONTACT LENS CARE PRODUCTS
REWETTING SOLUTIONS
(SOFT LENSES)
NONSURGICAL ADJUNCTS
DISINFECTIVE AND ANTISEPTIC
AGENTS IN OPHTHALMOLOGY

ANTIBACTERIALS
Drug name
(Generic)
a. Aminoglycosides
Gentamicin sulfate
Tobramycin
Sisomicin
Neomycin
Framycetin

b. Tetracyclines
Oxytetracycline
c. Sulphacetamide

Dosage
form/strength

Solution 0.3% (3 mg/ ml) In 5 and 10 ml


dropper vials
Ointment 3 mg/g
3.5 g and 5 g tubes
Solution 0.3% (3 mg/ ml) In 3 and 5 ml
dropper vials
Ointment 3 mg/g
3 g and 5g tubes
Solution 0.3%
In 3 and 5 ml
dropper vials
Ointment 3 mg/g
3 g and 5g tubes
Solution 0.17%
In 5 and 10 ml
Ointment 5 mg/gm
dropper vials
3 g and 5 g tubes
Solution 0.5 %
In 5 and 10 ml
Ointment 0.5% and 1%
dropper vials
3 and 5 gm tubes
Solution 1%
Ointment 1%
Ointment 1%

In 5 ml dropper vial
3 and 5 gm tubes
3 and 5 gm tubes

Solution 10%,20%, 30%

In 5 and 10 ml
dropper vial
3 and 5 gm tubes
In 10 and 15 ml
dropper vial
3,5 and 10 ml
dropper vial
3 and 5 gm tubes

Ointment 10% and 30%


Sulfasoxazole Diolamine Solution 4%
d. Chloramphenicol

Commercial
packing

Solution 0.4-1%
Ointment 5 mg/g and
10 mg/g
Powder for solution/
Injection 25 mg/vial

Preservative free
15 ml pack with diluent

e. Microlides
Erythromycin
Roxithromycin

Ointment 0.5%(5 mg/g)


Ointment 0.5%

In 3 and 5gm tubes


In 3 and 5 gm tubes

f. Polypeptides
Polymixin B

Solution 0.5-1%

5 and 10 ml dropper
vial
Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 511


Drug name (Generic)

Dosage form/strength

Commercial packing

Ointment 1-1.5 mg/gm


Powder for solution
500,000 units
Ointment 500 units/g and
10000 units/gm

3 and 5 gm tubes
In 20 ml vial
Preservative free
in 3 and 5 gm tubes

Levofloxacin

Solution 0.3%
Ointment 3 mg/g(0.3%)
Solution 0.3%
Ointment 3 mg/g
Solution 0.3%
Ointment 3 mg/g
Solution 0.3%
Solution 0.3%
Ointment 3 mg/g
Solution 0.3%
Ointment 3 mg/g
Solution 0.5%

In 5 and 10 ml dropper vials


3 and 5 gm tubes
In 5 and 10 ml dropper vials
3 and 5 gm tubes
In 5 and 10 ml dropper vials
3 and 5 gm tubes
In 5 ml dropper vials
In 5 ml dropper vials
3 and 5 gm tubes
In 5 ml dropper vials
3 gm tubes
In 5 ml dropper vials

Under Clinical Trials


Moxifloxacin
Gemifloxacin
Gatifloxacin
Clinafloxacin

Solution 0.3%
Solution 0.3%
Solution 0.3%
Solution 0.3%

Bacitracin
g. Fluoroquinolones
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
Lomefloxacin
Sparfloxacin

COMBINATION ANTIBIOTICS
Bacitracin, Neomycin and
Polymixin B

Neomycin Sulfate,
Polymixin B Sulfate
Gramicidin
Bacitracin Zinc and
Polymixin B Sulfate
Polymixin B Sulfate and
Oxytetracycline
Trimethoprim Sulfate
and Polymixin B
Sodium Sulphacetamide
and Phenylephirine

Combination Solution/
Ointment containing
Polymixin B Sulfate
10000 units/g
Neomycin sulfate 3.5 mg/g
Bacitracin 400 Units/g
Combi solution/oint.
containing Polymixin
B sulfate 10000 units/g,
Neomycin sulfate 1.75 mg/g
Gramicidin 0.025 mg/ml
Combi solution/ointment
Polymixin B sulfate
10000 units/g
Bacitracin Zinc 500 units/g
Ointment containing
Polymixin B sulfate
10000 units/g and
Oxytetracycline HCl 5 mg/g
Combi solution containing
Polymixing B sulfate
10000 units/g
Trimethoprim: 1 mg/ ml
Combination solution containing
Sulphacetamide 15%
Phenylephrine
HCl 0.125%

In 5 ml and 10 ml
dropper vials
In 5 mg tube
In 5 and 10 ml
dropper vials
In 3 and 5 gm tubes
In 5 and 10 ml
dropper vials
In 5 gm tube
In 3 and 5 gm tubes

In 5 and 10 ml dropper vials

In 5 and 15 ml dropper vials

Contd...

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512 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Gentamicin and
Vancomycin

Combination solution
containing
Gentamicin 8 g/ ml
Vancomycin 20 g/ ml

Commercial packing

In 5 ml dropper vials

ANTI-INFLAMMATORY DRUGS
Topical Steroidal Agents

Medrysone

as
Acetate solution 2%
Acetate suspension
0.5-2.5%
Acetate ointment 1.5%
as
Acetate suspension
0.12%, 0.25% and 1%
Sodium Phosphate soln
0.12%, 0.5% and 1.0%
Phosphate Oint.-0.25%
as
Sodium Phosphate
Solution-0.1%,
0.05% and 0.01%
Suspension 0.1%,
Sodium Phosphate
Ointment 0.05%
Sodium Phosphate
Solution 0.1%
Sodium Phosphate
Ointment 0.1%
Suspension 0.1%
Ointment 0.1%
Suspension 1%

Fluorometholone

Suspension 0.1%,0.25%

Rimexolone

Ointment 0.1%
Suspension 0.1%

Loteprednol etabonate

Solution 0.2% and 0.5%

Hydrocortisone

Prednisolone

Dexamethasone

Betamethasone

Triamcinolone acetonide

3 and 5 ml dropper vials


3 and 5 ml dropper vials
3 and 5gm tubes
5 ml dropper vials
5 ml dropper vials
3 and 5 gm tubes
5 ml dropper vial
5 ml dropper vial
3 and 5 gm tubes
In 5 and 10 ml dropper
vial
3 and 5 gm tubes
5 ml dropper vials
3 and 5 gm tubes
In 5 and 10 ml
dropper vials
In 5,10 and 15 ml
dropper vials
3 and 5 gm tubes
5 ml and 10 ml
dropper vials
In 2.5, 5 and 10 ml
dropper vials

Nonsteroidal Antiinflammatory Agents


Flurbiprofen

Solution 0.03%

Ketorolac tromethamine

Solution 0.5%

Suprofen

Solution 1%

Diclofenac sodium

Solution 0.1%

in 2.5, 5 and 10 ml
dropper vials
In 5 ml dropper
Vial and Single
Use 0.4 ml minims
In 2.5 and 5 ml
dropper vials
In 2.5 and 5 ml
dropper vials
Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 513


Drug name (Generic)

Dosage form/strength

Commercial packing

Indomethacin

Suspension 1%

Aspirin
Fenoprofen
Ibuprofen
Ketoprofen
Naproxen
Piroxicam
Diflunisol
Phenyl butazone
Oxyphenbutazone

Solution 0.1%
Solution 1%
Solution 0.3%
Solution 0.5%
Solution 1.0%
Solution 0.5%
Solution 1%
Solution 0.03%
Ointment 10%
Ointment 10%

In 3 and 5 ml
dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
3 and 5 gm tubes
3 and 5 gm tubes

TOPICAL STEROID ANTIBIOTIC COMBINATIONS


Dexamethasone
Sodium phosphate and
Neomycin Sulfate
Dexamethasone
Sodium phosphate
Neomycin Sulfate and
Polymixin B

Steroid per g/ ml
Soln.0.1%

Antibiotic per g/ ml
0.5%

Oint.0.1%
Susp.0.1%

0.5%
0.35
(Neomycin)

Oint. 0.1%

Dexamethasone
Sodium Phosphate and
Chloramphenicol
Dexamethasone Sodium
Phosphate and Framycetin
Dexamethasone Sodium
Phosphate and Tobramycin
Dexamethasone Sodium
Phosphate, Chloramphenicol
and Polymixin B Sulfate

Dexamethasone Sodium
Phosphate and Gentamicin
Dexamethasone Sodium
Phosphate and Ciprofloxacin
Dexamethasone Sodium
Phosphate and Ofloxacin
Dexamethasone Sodium
Phosphate and Lomefloxacin
Dexamethasone Sodium
Phosphate and Sparfloxacin
Betamethasone with Neomycin

10000 units/ ml
Polymixin B
0.35
(Neomycin)

In 5 ml dropper vial
3 and 5 gm tubes
In 5 ml dropper vial

3 and 5 gm tubes

Soln. 0.1%

10000 units/ ml
Polymixin B
0.5-1%

In 5 ml dropper vial

Susp.0.1%

0.3%

In 5 ml dropper vial

Susp.0.1%
Oint. 0.1%
Soln 0.1%

In 5 ml dropper vial
3 and 5 gm tubes
In 5 ml dropper vial

5000 IU
Soln.0.1%

0.3%
0.3%
1%
Chloramphenicol
Polymixin-B
1%
Chloramphenicol
Polymixin-B
0.3%

In 5 ml dropper vial

Soln..0.1%
Oint. 0.1%
Soln..0.1%

0.3%
0.3%
0.3%

In 5 ml dropper vial
In 3 and 5 gm tubes
In 5 ml dropper vial

Soln..0.1%

0.3%

In 5 ml dropper vial

Soln.0.1%

0.3%

In 5 ml dropper vial

Soln.0.1%

0.5%

In 5 ml dropper vial

5000 IU
Ointment 0.1

In 3 and 5 gm tubes

Contd...

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514 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Betamethasone with
Chloramphenicol
Betamethasone and
Gentamicin
Hydrocortisone and
Neomycin

Soln. 0.1%
Oint. 0.1%
Soln. 0.1%

0.5%
0.5%
0.3%

In 5 ml dropper vial
In 3 and 5 gm tubes
In 5 ml droper vial

Soln. 0.5%
1.5%
Oint. 0.5-1.5%
Soln. 10 mg/g

0.5%
0.5%
0.5%
0.5 mg/g
Polymixin
Bacitracin
Neomycin
0.5 mg/g
Polymixin
Bacitracin
Neomycin
0.3%
1%
1%
0.5%
0.5%
0.3%
10% (Sulpha)

In 5 ml dropper vial

10% (Sulpha)
0.35%
(Neomycin)
10000 units
(Polymixin)
0.35%
0.9%
0.3%
1%

In 3 and 5 gm tubes
In 5 and 10 ml
dropper vials

Hydrocortisone, Polymixin
B, Bacitracin and Neomycin

Hydrocortisone and Gentamicin


Hydrocortisone and
Chloramphenicol
Hydrocortisone and
Oxytetracycline
Prednisolone and Gentamicin
Prednisolone and sulpha-Cetamide

Prednisolone, Neomycin
and Polymixin B

Fluorometholone and Neomycin


Fluorometholone and Gentamicin
Flurometholone and Tobramycin
Fluorometholone and
Sodium Sulfacetamide

400 units/g
5 mg/g
Oint. 10 mg/g
400 units/g
5 mg/g
Susp. 1%
Soln. 0.5%
Oint. 0.5%
Susp. 1.5%
Oint. 1.5%
Susp.1%
Soln.0.2%
to 0.5%
Oint. 0.5%
Susp. 0.5%

Soln.0.1%
Soln.0.1%
Soln.0.1%
Susp. 0.1%

Commercial packing

3 and 5 gm tubes
In 5 ml dropper vial

In 5 gm tube

In 5 ml dropper vial
In 5 ml dropper vial
In 5 g tube
In 5 ml dropper vial
In 3 and 5 gm tube
In 5 ml dropper vial
In 5 ml dropper vial

In 5 ml dropper vial
In 5 ml dropper vial
In 5 ml dropper vial
In 5 and 10 ml
dropper vials

ANTIVIRAL THERAPY
First Generation Drugs
Indoxuridine (IDU)
Vidarabine (Are-A)
Trifluridine (TFT)
Cytarabine

Solution 0.1%
Ointment 0.5%
Ointment 0.3%
Intravenous infusion
200 mg/ ml
Solution 1%
Ointment 1%
Injection form -100 mg,
500 mg and 1000 mg/ ml

In 5 ml dropper vial
3 and 5 gm tubes
In 5 gm tubes
In 250 ml bottle
In 5 ml and 10 ml
dropper vials
In 5 gm tube
1 ml and 2 ml ampoules
and vials.

Second Generation Drugs


Acyclovir

Ointment 3%
Oral tablet 200 mg,
400 mg and 800 mg
Powder 250 mg

In 5 gm tube
Tablets in a pack
of 50/100
In pack of 100 mg/
200 g/500 mg
Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 515


Drug name (Generic)

Dosage form/strength

Commercial packing

Bromo-vinyl deoxyuridine (BVDU)


Interferons

Solution 0.1%
Parenteral 30-400
Million/ ml
100 mg capsule
100 and 200 mg tab.
Oral 250 mg capsule
Powder for injection
Lyophilized 500 mg/vial
Ganciclovir sodium
Intravitreal implant
Minimum 4.5 mg
Injection 24 mg/ml
Injection 6.6 mg/ml
Injection 75 mg/ml
Oral 100 and 200 mg tab.
Oral 100 and 200 mg tab.
Oral 100 and 200 mg tab.
Oral 100 and 200 mg tab.
Oral 100 and 200 mg tab.
Oral 100 and 200 mg tab.

In 5 ml dropper vial
In 2 ml and 5 ml vials

Zidovudine (AZT)
Famciclovir
Ganciclovir(DHPG)

Foscarnet sodium
Fomivirsen
Cidofovir (HPMPC)
Lobucavir
Indinavir
Ritonavir
Saquinavir
Nelfinavir
Valaciclovir

Pack of 50/100 Cap.


In a pack of 50/100 Tab.
in 100 cap pack
in 10 ml vial
In individual unit boxes in a
Sterile types package
In 250 and 500 ml bottles
In 0.25 ml single use vial.
5 ml ampoule
Box of 100 tablets
Box of 100 tablets
Box of 100 tablets
Box of 100 tablets
Box of 100 tablets
Box of 100 tablets

ANTIFUNGAL THERAPY
Polyenes
Nystatin
Amphotericin B
Natamycin

Ointment containing
100000 IU of Nystatin
Soln. 0.75 3%
Suspension 5%

3 and 5 gm tubes

Solution 1%
Solution 1%
Applicaps 1%
Solution 1%
Ointment 1%
Oral tab. 200 and 400 mg
Fresh solution 1-5%
Solution 0.3%
Oral tab. 100 and 200 mg
Oral tablet 200 mg

in 5 ml dropper vial
in 5 ml dropper vial
In a pack of 30 applicaps
In 5 ml
in 3 and 5 gm tubes
In a pack of 100 tab.
In 5 ml dropper vial
5 ml dropper vial
Pack of 100 tablets
Pack of 100 tablets

Oral as 250 and 500 mg capsules


Solution 1%

Pack of 100 cap.


5 ml dropper vial

Solution 1%
Applicaps 1%

5 ml dropper vial
A pack of 30 applicaps

Oral tablet of 125 mg and 250 mg.

A pack of 100 tabs.

in 5 and 10 ml vials
in 5, 10 and 15 ml dropper vial

Imidazole Derivatives
Clotrimazole
Miconazole
Econazole
Ketconazole
Fluconazole
Itraconazole

Fluorinated Pyrimidines
Flucytosine

Silver Sulphadiazine

Terbinafine

Contd...

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516 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Solution 2% and 4%
Solution 2%
Solution 01.%
Suspension
Solution 1%
Solution 0.05% and 1%
Solution 0.05%
Solution 0.025%
(0.25 mg/ ml)

2,5 and 10 ml dropper vials


5 and 10 ml dropper vials
5 and 10 ml
dropper vials
5 ml dropper vial
5 ml dropper vial
5 ml dropper vial
5 ml and 7 ml
dropper vials

Suspension 0.05%
Suspension 0.05%
Solution 0.3%
As 5 mg tablet (Dosage 5 mg
orally once or twice daily)
As 5 mg tablet (Dosage 5 mg orally
once daily)

In 2.5, 5 and 10 ml dropper vials


5 ml opaque plastic Vial
5 ml and 10 ml dropper vials
In a strip of 10 tablets

Solution 0.125-0.12%

In 5, 10 and 15 ml dropper vials

Solution 0.012-0.1%
Solution 0.05%
Solution 0.025%
Solution 0.05%
Solution (Aqueous
infusion in 7.5 ml with
0.1% thimerosal)

In 5, 10 and 15 ml dropper vials


In 5,10 ,15 and 20 ml dropper vials
In 10,15 and 30 ml dropper vials
5 and 10 ml dropper vials
In 5 and 10 ml
dropper vials

ANTIALLERGY THERAPY
Mast Cell Inhibitors
Cromolyn Sodium
Disodium Cromoglycate (DSCG)
Lodoxamide Tromethamine
Nedocromil
Olopatadine HCl
Azelastine HCl
Ketotifen fumarate

Antihistamines
Levocarbastine HCl
Emedastine Difumarate
Pheniramine maleate
Levocetrizine
Desloratidine

In a strip of 10 tablets

Decongestants
Phenyleprine HCl
Imidazole derivatives
Naphazoline HCl
Tetrahydrozoline
Oxymetazoline HCl
Ephedrine
Rose petal aqueous
Infusion

Decongestants and Antihistamines Combination


Pheniramine maleate
and Naphazoline HCl
Pheniramine maleate
and Phenylephrine
Pyrilamine maleate,
Phenylephrine HCl and
Antipyrine
Antazoline Phosphate
and Naphazoline HCl
Tetrahydrozoline and
Zinc Sulphate

Antihistamine
0.3% (Pheni)
0.5%

Decongestant
0.025%
(Napha)
0.125%

Pyrilamine
Phenylephrine
0.1%
0.12%
and Antipyrine (0.1%)
0.5% (Anta)

0.05%(Napha)

0.25%
(Zinc)

0.05%
(Tetrahydrozoline)

In 5,10 and 15 ml
dropper vials
In 5,10 and 15 ml
dropper vials
In 5,10 and 15
ml dropper vials

In 10 and 15 ml
dropper vials
In 10 and 15 ml
dropper vials

Topical NSAIDs and Topical Steroids See Anti-inflammatory Tables


Topical Immunosuppressors
Cyclosporine

Solution 2%

In 5 ml dropper vials
Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 517


Drug name (Generic)

Dosage form/strength

Commercial packing

Acetyl choline chloride

Fresh solution (1:100) acetyechlorine


when reconstitued

Pilocarpine HCl

Solution 0.25%, 0.50%,


1%,2%,3%,4%,6%,8% and 10%
Solution 1%,2% and 4%
Gel 4%
Ocusert Pilo-20 releases 20 mcg
pilocarpine per hour for one week
Ocusert Pilo-40 releases
40 mcg pilocarpine per
hour for one week

In 2 ml dual chamber univial


alongwith diluent and sterile
water
In 2,5, 10 and 15 ml
dropper vials
In 5,10 and 15 ml dropper vials
In 3 and 5 gm tubes
In a pack of 8 individual sterile
system
In a pack of 8
individual sterile
system

ANTIGLAUCOMA THERAPY
Miotics
Cholinergic Agents

Pilocarpine Nitrate
Pilocarpine HCl
Pilocarpine Ocular
Therapeutic system (Ocusert)

Pilocarpine Combinations
Pilocarpine HCl and
Epinephrine

Pilocarpine HCl and


Physostigmine
Pilocarpine nitrate
and clonidine
Carbachol

Solution containing
Pilocarpine 1-6% and
Epinephrine (1%)
(Epilo1 Epilo6)
Solution having Pilocarpine (2%) and
Physostigmine 0.25%
Solution having Pilocarpine nitrate (1%) and
clonidine(0.125%)
Solution 0.75%, 1.5%, 2.25% and 3%
Intraocular solution 0.01%

In 5 and 10 ml dropper
vials

In 5 ml dropper vials
In 5 ml dropper vials
In 5,10 and 15 ml drop tainers
In 1.5 ml ampoules/vials

Anticholinesterase Agents
Physostigmine sulfate
Demecarium bromide
Echothiophate

Isofluorophate

Solution 0.25% and 0.5%


Ointment 0.25%
Solution 0.125% and 0.25%
as Powder for Reconstitution 1.5 mg to make
Solution 0.03% other
Strengths are 0.06%,
0.125% and 0.25%
Ointment 0.025% in poly
Ethylene mineral oil gel.

5 ml dropper vial
3.5 gm tube
5 ml dropper vial
Powder pack with
5 ml diluent

Solution 0.5% and 1%


Solution 0.125%, 0.25% and 0.5%
Solution 0.2%
Solution 0.15%
Solution having 0.2%
Brimonidine and 0.5%
Timolol maleate
Powder Lyophilized
25 mg (0.5%) solution
when reconstituted

In 5 and 10 ml dropper vials


In 5 ml dropper vial
In 5 and 10 ml dropper vials
In 5 and 10 ml dropper vials
In 5 ml dropper vial

3 and 5 gm tubes

Alpha Adrenergic Agonists


Apraclonidine
Clonidine
Brimonidine tartrate (Alphagan)
Brimonidine purite (Alphagan P)
Brimonidine tartrate
and Timolol maleate
Dapiprazole HCl

In vial with 5 ml
diluent and dropper
Contd...

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518 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Solution 0.5% - 2%
Available as Epinephrine hydrochloride,
Borate and bitartate
Solution 0.1%

In 2, 7.5 and 10 ml dropper vials

Betaxolol HCl

Solution 0.25% and 0.50%

Carteolol HCl
Levobunolol
Metipranolol HCl

Solution 1%
Solution 0.25% and 0.50%
Solution 0.1%, 0.3% and 0.6%

Timolol maleate

Solution 0.25% and 0.5%


Gel 0.25% and 0.5% (GFS)

In 2.5, 5, 10 and 15 ml
dropper vials
In 5 and 10 ml dropper vials
In 5, 10 and 15 ml dropper vials
In 5 ml and 10 ml
dropper vials
In 5,10 and 15 ml dropper vials
5 gm tube

Sympathomimetics
Epinephrine
Dipivefrin HCl
vials

In 2, 5, 10 and 15 ml dropper

Beta Blockers

Carbonic Anhydrase Inhibitors


Acetazolamide

Dichlorphenamide
Methazolamide
Dorzolamide
Dorzolamide and Timolol

Solution 5%
Tablet 125 mg, 250 mg
and sustained release
(500 mg) capsule
Powder for injection
Lyophilized 500 mg
Tablet 50 mg
Tablet as 25 mg and 50 mg
Solution 2%

Brinzolamide

Solution having 2%
Dorzolamide and 0.5% Timolol
Suspension 1%

Ethoxazolamide

Oral 125 mg tab.

In 5 ml dropper vial
In a pack of 100 tab.
In 30 and 100 cap.
packing in vials
Pack of 100 tab.
Pack of 100 tab.
In 5 and 10 ml
dropper vials
In 5 and 10 ml
dropper vials
In 2.5, 5, 10 and
15 ml dropper vials
In a pack of 100 tab.

Prostaglandins
Latanoprost (Xalantan)

Solution 0.005%

Latanoprost and Timolol


(Xalcom)
Unoprostone (Rescula)

Solution having 0.005%


Latanoprost and 0.5% Timolol
Solution 0.15%

Bimatoprost (Lumigan)

Solution 0.03%

Travoprost (Travatan)

Solution 0.004%

In 2.5 ml plastic
Bottle with dropper tip
In 3 ml plastic bottle with
dropper vials
In 3 ml polypack
with dropper tip
In 3 ml poly pack
with dropper tip
In 3 ml poly pack
with dropper tip

Hyperosmotic Agents
Glycerine
Isosorbide

Oral Solution as 50% and 70%


Ointment 40%
Oral solution as 45%
(10 g per 220 ml)

In 7.5 ml and 15 ml pack


In 3.5 gm tube
In 220 ml pack
Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 519


Drug name (Generic)

Dosage form/strength

Commercial packing

Mannitol

As injection solution
5-25%
As 30% solution

In 50, 250, 500 and


1000 ml bottles
In 100 ml bottle

Solution 0.01%

In 5 ml and 10 ml dropper vials

As powder and reconstituted


soln (0.5 c.c. of solution contain
5 mgm of 5 FU)
3 x 2 mm cellular
Sponge moistened with 0.02-0.04 mg/ ml
of Mitomycin C
4 x 4 mm cellulose
Sponge soaked in
Daunorubicin (0.2 mg/ ml)

Available as 50 mg/ml to
10 mg/ml in physiological saline

Solution 1%
Solution 0.5-2%
Solution 0.25-2%

In 2 ml ampoules
2 ml ampoule
30 ml vial

Injection 0.5-4%

In 5 ml prefilled
Syringe and 30 ml pack
In 35 gm tube
2 ml ampoule

Urea powder

Ocular Hypotensive Lipid (OHL)

Antimetabolites
5-Fluorouracil (5FU)
Mitomycin C
Daunorubicin

as powder with diluent


Powder with diluent

LOCAL ANESTHETIC AGENTS


Injectable Agents
Esters
Procaine
Chloroprocaine
Tetracaine

Amides
Lidocaine HCl

Lidocaine with Epinephrine


Lidocaine with Dextrose
Prilocaine
Mepivacaine
Bupivacaine
Bupivacaine and Epinephrine
Etidocaine
Etidocaine and Epinephrine
Centbucridine

Ointment 5%
Ampoule 1%(Preservative
free) for intracameral use.
Combi soln. having 0.5-2%
Lidocaine and 1:100000/vials
200000 epinephrine
Combi soln containing
1.5-5% Lidocaine
and 7.5% Dextrose
Solution 0.5-3%
Injectable soln 1-2%
Injectable solution 0.25-0.75%
Solution having 0.75%
(Bupi) and 1:200000
Epinephrine Solution
as 0.5-1%
Solution having 1.0-1.5%
Etidocaine and 1:200000
Epinephrine
Injectable solution 0.5%

In 10 ml ampoule and 20, 30


and 50 ml vials
In 2 ml ampoule
In 2 ml ampoule and
30 ml vial
In 30 and 50 ml vials
In 30 ml vials
In 2 ml ampoules and
In 30 ml vials
In 30 ml vials
In 30 ml vials
In 30 ml vials
Contd...

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520 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Topical solution 0.4%


Solution 0.5% and 0.75%
Solution 0.5% and 1%
Solution 4%
Solution 1%
Solution 2%
Solution 1%
Solution 2.5%
Solution 2%
Solution 0.1%
Solution 2-4%
Solution 2%

In 5 and 15 ml dropper vials


In 10 and 15 ml dropper vials
In 10 and 15 ml dropper vials
In 10 and 30 ml dropper vials
In 10 and 15 ml dropper vials
In 10 and 15 ml dropper vials
In 10 and 15 ml dropper vials
In 10 ml dropper vials
In 10 ml dropper vials
In 5 and 10 ml dropper vials
In 10 ml dropper vials
In 10 ml dropper vials

Topical Anesthetic Agents


Benoxinate HCl
Proparacaine HCl
Tetracaine HCl
Lidocaine HCl
Centbucridine HCl
Coccaine
Phenocaine
Dimethocaine
Piperocaine
Dibucaine
Naepaine
Butacaine

LOCAL ANESTHETIC COMBINATIONS


Proparacaine and
Fluorescein sodium
Benoxinate and
Fluorescein sodium

Combi solution having


0.5% Proparacaine
and 0.25% Fluorescein sodium
Combi solution having
0.4% benoxinate and
0.25% Fluorescein sodium

In 5 ml dropper vial
In 5 ml dropper vial

MYDRIATICS AND CYCLOPLEGICS


Mydriatic Adrenergic Agents
Adrenaline (Epinephrine)
Coccaine HCl
Phenylephrine
Hydroxy amphetamine

Solution 1:1000
Solution 2% and 4%
Solution 2.5% and 10%
Solution 1%

2 ml ampoule and 5 ml vials


5 ml and 10 ml dropper vials
2, 5 and 15 ml dropper vials
5 ml vial

Cholinergic Antagonist as Cycloplegic Mydriatics


Atropine sulphate
Homatropine
Scopolamine
Cyclopentolate HCl
Tropicamide

Solution 0.5%,1%,2%and 3%
Ointment 0.5% and 1%
Solution 2% and 5%
Solution 0.25%
Solution 0.05%, 1% and 2%
Solution 0.5%, 1%

In 2,5 and 10 ml vials


3.5 and 5 gm tubes
2,5,10 and 15 ml dropper vials
In 5 and 15 ml dropper vials
2,5,10 and 15 ml dropper vials
3, 5 and 10 ml dropper vials

Combi solution having


0.2-1% Cyclopentolate
1-5% phenylephrine
Combi solution having
0.3% scopolamine and
10% Phenylephrine
Combi Solution containing
1% hydroxyamphetamine
and 0.25% tropicamide
Combi solution having
Phenylephrine 5% and
Tropicamide 0.8%

In 2 and 5 ml dropper vials


In 2 and 5 ml dropper
vials
5 ml dropper vial

Mydriatic Combinations
Phenylephrine HCl and
Cyclopentolate HCl
Scopolamine HBr and
Phenylephrine HCl
Tropicamide and
Hydroxyamphetamine
HBr.
Phenylephrine HCl
and Tropicamide

In 5 and 15 ml
dropper vial
In 5 and 10 ml
dropper vial
Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 521


Drug name (Generic)

Dosage form/strength

Commercial packing

Cyclopentolate HCl
and Dexamethasone
Sodium phosphate

Combi solution having


1% cyclopentolate and
and 0.1%Dexamethasone

In 5 ml and 10 ml
dropper vials

OPHTHALMIC VISCOSURGICAL DEVICES (OVD) AND SURGICAL ADJUNCTS


Viscoelastic Substances
Sodium Hyaluronate
cannula

Sodium Hyaluronate and


Chondroitin sulfate

Sodium Hyaluronate and


Fluorescein Sodium
Chondrotin Sulfate
Polyacrylamide (oscolon)
Hydroxy propyl methyl
Cellulose (HPMC)
Poly TEGMA (Triethylenglycol
monomethacrylate)
Collagen

Injection 10 mg/ ml,


12 mg/ ml, 14 mg/ ml,
16 mg/ ml and 30 mg/ ml

In 0.4,0.55,0.85 and
2 ml preloaded disp.
syringes with 27G or 30 G

Highly viscous 1%
Solution of sodium
Hyaluronate of lower
Molecular weight
Injection Solution
Containing (3.1 mixture)
Of 3% sodium hyaluronate,
4% chondrotin sulfate with syringe
0.45 mg sodium dihydrogen phosphate
hydrate and 4.3 mg NaCl per ml
Solution containing 10 mg
sodium hyaluronate, 0.005 mg
Fluorescein Sodium per ml.
Injection solution 20%

2 ml preloaded
disposable syringe

Injection solution
4.5 mg/ ml
Injection solution
2% and 2.5%
Injection solution as 40%
Injection solution
1.4% collagen type IV

0.5 ml in preloaded disposable

In 0.55 or 0.85 ml preloaded


disposable syringe cannula
In 2 ml vial with
30 G cannula.
2 ml vial with
27G cannula
In 2 ml or 15 ml
vial or 2 ml prefilled sterile
disposable syringe with
27G cannula
In 2 ml prefilled disposable
syringe with cannula
In 2 ml disposable
syringe with cannula

Irrigating Solutions
Intraocular Irrigating Solutions
BSS (Balanced
Salt solution)

BSS plus
(Mix aseptically
just before use)

Solution containing
0.64 NaCl, 0.75% KCl,
0.3% magnesium chloride,
0.43% calcium chloride,
0.39% Sodium acetate
0.17% Sodium citrate
and Sodium hydroxide
Solution having
Part-I(480 ml) containing
7.44 mg NaCl, 0.395 mg
KCl, 0.433 mg sodium
Phosphate, 2.19 mg
Sodium bicarbonate

In 15,30, 300 and 500


ml sterile packs

Preservative free in
10 ml, 30,50 and 500
ml packs.

Contd...

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522 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Hydrochloric acid or Sodium bicarbonate


Hydrochloric acid or Sodium hydroxide/ ml
Part II(20 ml) containing 3.85 mg
Calcium Chloride dehydrate, 5 mg
Magnesium chloride hexahydrate,
23 mg dextrose and 4.6 mg
glutathione disulfide/ml

Extraocular Irrigating Solutions (EIS)


EIS Type I

EIS Type II

EIS Type III

EIS Type IV

EIS Type V

EIS Type VI

Eye wash

Solution containing
0.49% NaCl,0.075% KCl
0.048%Cacl,0.03% mgcl
0.39% Sodium acetate,
0.17% Sodium citrate and
0.013% Benzalkonium chloride
Solution containing
Boric acid, Sodium borate
With 0.004% phenyl
Mercuric nitrate or
0.002% Thimerosal
Solution containing 1.2%
Boric acid, 0.38% KCl,
0.014% Sodium carbonate anhydrous,
0.05% EDTA and 0.01%
Benzalkonium Chloride
Solution containing
0.05% tetrahydrozoline
HCl with NaCl,Sodium
Borate, Boric acid,
0.01% Benzalkonium
Chloride and 0.1% EDTA
Solution containing
NaCl, Sodium proprionate, Sodium borate,
Boric acid, glycerin, Rose water,
camphor, Extract of witch hazel,
Berbrine bisulfate and
Benzalkonium chloride
Solution having
0.49 NaCl, 0.4% Sodium biphosphate,
0.45% sodium phosphate with
0.005% Benzalkonium chloride
Solution containing
NaCl, mono or dibasic Sodium phosphate,
Benzalkonium chloride and EDTA.

In 15,30 and 120 ml


packs

In 15,30,120 and
180 ml packs
In 30 ml and 120 ml
packs

In 15 ml pack

In 60 and 180 ml
packs

In 180 ml pack

In 120 ml pack with eye cup

Surgical Enzymes
Alpha Chymotrypsin

Available as powder
Containing 150 units Or 300 units
of alpha Chymotrypsin with
2 ml sodium chloride diluent per dual
chamber univial

As Powder pack of
750 units per vial
with 9 ml BSS diluent

Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 523


Drug name (Generic)

Dosage form/strength

Commercial packing

Urokinase

As powder 5000 units of


Urokinase are dissolved in
2 ml normal saline
Fluffy powder containing 300 units
of activity/mg

Powder pack with 9 ml BSS


diluent

Solution containing
0.01% sodium EDTA
Solution containing
0.2% calcium EDTA
As solution in conc. of
5%, 10% and 20% can be diluted
in artificial tears or Physiological saline.
Solution in conc. of
0.1-0.2 molar of Laevocysteine

In 5 ml and 10 ml
dropper vials
In 5 ml and 10 ml
dropper vials
In 10 and 15 ml dropper
vials

Solution as 100% alcohol


Solution as 2%

In 60 and 120 ml pack


In 30 and 60 ml pack

As liquid tissue adhesive

In 15 and 30 gm tubes

Fractionated Purified
Silicone Oil

Injection Silicone oil

Polydimethyl Siloxane
(Silicone Oil)
Botulinum Toxin
Type A

Injection (Poly dimethyl


Siloxane oil)
Powder for injection
(Lyphilized) 100 units of Lyophilized
Clostridium
Botulinum Toxin Type A
Solution containing
5% povidone iodine.
Sterile film in sizes of
100 x 125 mm and
25 x 50 mm

10 ml vial with
Special flip off seal
In a sterile pouch (single use)
In sterile single use
10 and 15 ml vials
Preservative free
Powder in vial along
with 0.05 mg albumin and 0.9 mg
sodium chloride in vials
In 15 and 50 ml packs

Hyaluronidase

Ampoule containing 1500 IU

Chelating Agents and Mycolytics


Sodium EDTA
Calcium EDTA
Acetyl cysteine
Laevo cysteine

In 10 and 15 ml vials

Caustic Preparations
Pure Alcohol
Hydrogen peroxide

Cyanoacrylate Tissue Adhesive

Surgical Adjuncts

Povidone Iodine
Absorbable gelatin film sterile

Single sterile pack and


pack of 6 sterile films

OPHTHALMIC DYES
Fluorescein sodium

Topical solution 2% contains


0.25% Fluorescein sodium
0.1% Proparacaine HCl or
0.4% Benoxinate HCl
0.01% Thimerosal preservative
Topical Solution 2%
Fluorescein sodium plain
Topical solution containing
0.25% Fluorescein sodium

In 5 ml pack

In 1, 2 and 15 ml
packs

Contd...

ophthalmologyebooks.com

524 Section V: Ocular Therapeutics


Drug name (Generic)

Fluorexon
Rose Bengal

Lissamine Green
Indocyanine Green
Trypan Blue

Verteporfin (Visudyne)

Dosage form/strength

Commercial packing

0.05% Proparacaine HCl


0.01% Thimerosal with
povidone, boric acid and
polysorbate 80
Injection 10% and 25%
Fluorescein sodium
Fluorescein strips as
0.6 mg, 1 mg and 9 mg
strips (with Boric acid,
polysorbate 80 and 0.5%
Chlorbutanol) and High
Molecular Fluorescein (Higlo)
Strips for soft contact lenses
Solution as 0.35% (12N)
Topical solution 1%
Containing 1% Rose Bengal with
povidone, Sodium borate PEG10
and 0.01% thimerosal
As 1.3 mg strip.
Solution 0.1%, 0.5% and 1%
Sterile strips containing
15 mg of Lissamine green.
Powder for injection
As 25 mg and 50 mg

In 5 ml pack

Solution containing 0.6 mg Trypan


Blue, 1.9 mg of Sodium mono
hydrogen orthophosphate, 0.3 mg
of sodium dihydrogen ortho
phosphate, 8.2 mg sodium chloride
and sodium hydroxide
As Sterile lipid based
Freeze dried powder
Requires reconstitution
With sterile water and
Dilution with 5% Dextrose
Before infusion.

In 1,2, 5, 10 and 15 ml
packs
In a pack containing
100 or 300 strips
Pack of 100 strips
In 0.5 ml pipette
5 ml dropper vial
Pack of 100 strips
5 ml dropper vial
Pack of 100 strips
Powder pack with
10 ml ampoule
of aqueous solvent
1 ml ampoule (Pack of 10
ampoules)
As Single use
15 mg vial with
sterile water
and ampoules

LUBRICANTS AND ARTIFICIAL TEAR SOLUTIONS


Methylcellulose and Ethylcellulose Base
Hydroxy propyl methyl
Cellulose (HPMC)

Solution containing
0.5 or 1% HPMC and
0.01% Benzalkonium chloride.
Solution containing
0.5%, HPMC, Gelatin A, vials.
Chlorbutanol 0.5%,
NaCl and polysorbate 80
Solution containing
0.5% HPMC, boric acid,
NaCl, KCl, Phosphoric
Acid and sodium Perborate

In 10,15 ml dropper vials


In 10,15 and 30 ml

In 15 ml vials

Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 525


Drug name (Generic)

Hydroxy ethyl cellulose (HEC)

Carboxy methylcellulose (CMC)

Dosage form/strength

Commercial packing

Solution containing 0.5% HPMC,


Dextran 40 (0.1%).
0.01% Benzalkonium Cl EDTA,
NaCl and Boric acid solution
0.5% HPMC, Dextran
70 (0.1%) Benzalkonium
Chloride (0.01%) and EDTA
Solution: HPMC 1%,
Propyleneglycol, NaCl,
Boric acid and paraben
Solution 0.8% HPMC, 0.1%
Dextran 70, Sodium Phosphate,
KCl, NaCl, Dextrose
Solution: 0.3% HPMC 2910, 0.1%
Dextran 70, NaCl, KCl Sodium
Bicarbonate
Solution: 0.4%HPMC
2910, Diabasic phosphate,
Potassium chloride, NaCl and
0.01% Benzalkonium Cl.
Solution:0.3%HPMC
2910, 0.1% Dextran,
0.01% polyquarterrnium-1
NaCl, KCl, Sodium borate.
Solution containing 0.5% Hydroxy
ethyl cellulose (HEC), 1.67%
Povidone with water soluble polymers,
Thimerosal 0.004% and EDTA (1%).
Solution:0.5% HEC, Polyvinyl
alcohol 1% and 0.01% Benzalkonium
chloride, EDTA and NaCl
Solution: 0.5% HEC in a hypertonic
base, 0.25% Sorbic acid 0.01% EDTA.
Solution: 0.5% HEC 0.44% NaCl.
Solution containing 1% CMC,
NaCl, KCl and Sodium lactate
Soluiton: 0.25% Sodium
carboxymethylcellulose,
NaCl, KCl and Sodium phosphate
Solution: 0.5% CMC, KCl, NaCl

In 10 and 15 ml vials

Solution: 0.5% CMC,


Boric acid, Cacl, KCl,
NaCl and Magnesium chloride

In 15 ml vials
In 10 and 15 ml vials
Preservative free in 0.5 ml single
dose containers (28s)
Preservative free in single use
0.45 ml packs (28s)
In 15 ml dropper vial

In 15 and 30 ml
dropper vials.
In 10 and 15 ml vials

In 15 ml vials
In 10 and 15 ml vials
In 10 and 15 ml vials
Preservative free in 0.3 ml
minims (30 single dose pack)
Preservative free
in 0.6 ml single
dose containers
Preservative free containers
in 0.3 ml single use
In 15 ml vial

Polyvinyl Alcohol Base Solutions


Solution containing 1.4%
Polyvinylalcohol (PVA) and
0.6% Povidine, 0.5% chlorbutanol
and NaCl.
Solution: 1.4%, 0.6% Povidone,
retinyl palmitate, Boric acid, 0.09%
EDTA, 0.001% WSCP, NaCl, KCl.

In 15 ml vials

In 15 ml dropper vials.

Contd...

ophthalmologyebooks.com

526 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Solution: 1% PVA, PEG-400, 1%


Dextrose, 0.01% Benzalkonium, EDTA
Solution: 1.4% PVA, 0.5%
Chlorbutanol, NaCl
Solution: 0.5% PVA, 0.6%
Povidone, Benzalkonium Cl,
Dextrose, EDTA, NaCl,
Sodium bicarbonate and
Sodium phosphate.
Solution: 1.4% PVA, 0.6%
Povidone and NaCl

In 15 and 30 ml vials

Solution: 3% PVA, 0.002%


Thimerosal, NaCl and EDTA.

In 15 x 30 ml vials
In 15 and 30 ml vials

Preservative free
in 0.3 ml single
dose containers (30 and 50 UD)
In 15 ml vial

Miscellaneous Artificial Tear Solutions


Solution: Polysorbate 80,
Sodium Chloride, EDTA,
Retinyl Palmitate, Mannitol,
Sodium citrate and pyruvate.
Solution: 0.3% Glycerin,
NaCl, KCl, Sodium citrate and
Sodium phosphate
Solution: 0.25% Glycerin, EDTA,
Sodium chloride and
Benzalkonium Cl.
Adsorbonac NaCl 2% or 5%
solution
Ointments

Ocular Inserts
Lacriset

Ointment containing
Petrolatum (55.5%)
Lanolin (2%) and Mineral
Oil (42.5%)
Ointment:2% HPMC, NaCl,
KCl, CaCl, MgCl, Sodium acetate
and Sodium citrate
Lubricant gel Carbopal 980
(Polyacryclic acid) which
Transforms from gel to liquid
in contact with ocular tissue.
Gel: 0.3% HPMC
Ointment: 56.8% White
petrolatum, 42.5% Mineral oil,
Chlorobutanol, Lanolin alcohols.
Ointment: White petrolatum
Ointment:55% White petrolatum,
32% Mineral oil, Boric acid, Stearic
acid and wheat germ oil
Polymeric insert having
5 mg of HPMC

Preservative free in
10 and 15 ml packs
Preservative free
in 0.3 ml (UD 32s)
In 15 ml vial
In 5 and 10 ml vials
Preservative free
in 3.5 and 5 gm tubes
Preservative free in
3.5 and 5 gm tubes
In 5 gm tube

In 10 ml pack
In 3.5 and 7gm tubes
Preservative free in 0.5 gm pack
In 3.5gm tube

Preservative free in
60s with applicator
Contd...

ophthalmologyebooks.com

Chapter 50: Quick Look Ocular TherapeuticsAn Update 527


Drug name (Generic)
Punctal Plugs
Collagen implant

Silicone plugs
Lubricant for Artificial Eyes

Dosage form/strength

Commercial packing

Intracanalicular collagen implant


Consists of 0.2, 0.3, 0.4, 0.5 and 0.6 mm
diameter inserts packed at the edge of a
foam strip.
Punctum silicone Plug in 1.6,
2 and 2.8 mm sizes
Solution containing
0.25% Tyloxapol and
0.02% Benzalkonium chloride
Solution containing 2.5% HPMC
with 0.004 Thimerosal
and 0.1% EDTA

In a pack of 10 or 72 plugs with


inserter tool.

Ophthalmic solution
Containing 0.1% each
of IgA, IgG and IgM in
fixed concentrations

Preservative free
In 5 and 10 ml dropper vial with
controlled tip.

Solution as 2% or
5% NaCl with 0.004%
water soluble polymer
Thimerosal and 0.1% EDTA.
Topical NaCl solution 2% or
5% with HPMC and parabens.
Topical 5% NaCl Solution with
Propylene Glycol, Sodium borate
and Boric acid
Ointment containing 6% NaCl
gel with Petrolatum and Lanolin.
Topical solution as 50%
(0.6 g glycerine/ ml)
with 0.55% Chlorobutanol
Ointment as 40% with Petrolatum
and Lanolin parabens

In 10 and 15 ml dropper vials

In a pack of 2 or 10 plugs with


inserter tool
In 15 ml dropper vials
In 15 ml dropper vials for
gonioscopic exam.

TOPICAL IMMUNE THERAPY


Aspac (Topical)

TOPICAL HYPEROSMOTIC AGENTS


Sodium Chloride (Hypertonic)

Glycerine

In 10 and 15 ml dropper vials


In 10 ml dropper vials
In 3.5 and 5 gm tubes
In 7.5 ml vial

CONTACT LENS CARE PRODUCTS


Hard Lenses
Cleaning/Soaking/Wetting Solutions for Hard lenses (Complete)
Total solution

Containing Buffered Isotonic


Polyvinyl Alcohol, Benzalkonium
chloride, EDTA

In 60 and 120 ml packs

Solution containing
0.004% Benzalkonium
Cl, EDTA, HPMC, NaCl,
KCl and Polyvinyl alcohol

In 60 ml pack

Wetting Solutions (Hard Lenses)

Contd...

ophthalmologyebooks.com

528 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Solution: Buffered 0.1% EDTA,


0.01% Benzalkonium Cl

In 60 and 120 ml packs

Wetting/Soaking Solutions (Hard Lenses)


Solution containing buffered
isotonic 0.1% EDTA and 0.05%
Benzalkonium Cl
Solution: Buffered isotonic
0.003%
Benzalkonium chloride,
Polyvinyl alcohol and EDTA

In 120 ml pack

Solution containing Povidone,


Water Soluble polymers,
Sorbic acid and EDTA (Isotonic).
Solution (Isotonic) Hydroxyethyl
cellulose Sorbic acid, Poloxamer
407, 0.1% EDTA, NaCl, KCl, Sodium
borate, Boric acid
Solution: Isotonic
0.04%,Thimerosal,0.1%,
EDTA, Povidone and
Polyoxyethylene
Solution: Isotonic 0.1% EDTA,
0.001% Polyquaterniuml-1,
Dextran, NaCl, KCl, and HPMC
Solution: Buffered, Isotonic NaCl,
Carbamide, Poloxamer 407,
0.2% EDTA, 0.15% Sorbic acid.
Buffered Solution with
Polyoxyl 40 stearate PEG 300 and
0.5% Chlorobutanol

In 15 ml pack

Solution with anionic sulfate


surfactant, Friction enhancing
Agents and NaCl
Solution: 15.7% Isopropyl alcohol,
Poloxamer 407 and Amphoteric 10
Solution: Buffered isotonic Tween 21,
Polymeric cleaners, 0.1% EDTA and
0.001% Polyquaternium-1.
Buffered solution Cocoampho carboxy
Glycinate, Sodium lauryl Sulfate,
Hexylene glycol, Alkyl ether sulfate,
Fatty acid amide surfactants
Solution:Cocoampho diacetate, glycol,
0.1% EDTA and 0.01% Benzalkonium Cl.
Solution with poloxamer 188, 0.01%
Benzalkonium Chloride and 0.2%
EDTA

In 15 and 60 ml pack

In 120 and 180 ml pack

Rewetting Solutions (Hard Lenses)

In 5, 15 and 30 ml packs

In 15 ml pack

Thimerosal free in 15 ml pack


In 15 ml pack
In 15 ml pack

Cleaning solutions (Hard Lenses)

Preservative free in 12 ml
Thimerosal free
in 12 and 20 ml packs
Preservative free in 30 ml pack

In 60 ml pack
In 15 and 30 ml

Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 529


Drug name (Generic)

Dosage form/strength

Commercial packing

Solution with Hydrophilic


In 15 and 30 ml packs
polyelectrolyte, Polyvinyl alcohol,
Hydroxy ethyl cellulose, Chlorhexidine
Gluconate and EDTA.

Cleaning and Soaking Solution (Hard Lenses)


Solution Buffered surfactant cleaning
agent with 0.004%Phenylmercuric
nitrate

In 120 ml pack

Rigid Gas Permeable (RGP) Lenses


Wetting/Soaking Solutions (RGP Lenses)
Buffered solution containing 0.0015%
Polyaminopropyl biguanide 0.05%
EDTA, Cationic cellular Derivative
polymer
Buffered Solution Low viscosity, 0.5%
EDTA, 0.006% Chlorhexidine gluconate,
Cationic cellulose Derivative polymer as
Wetting agent
Solution having EDTA and
Chlorhexidine
Solution: Isotonic Hydroxyethyl
cellulose, 0.006% polixetonium
chloride
Buffered Solution: 0.005%
Chlorhexidine gluconate, 0.02% EDTA
Octylphenoxy, Ethanol, Povidone,
polyvinyl alcohol, Propylene glycol
and HEC, NaCl.
Buffered Solution: Sodium and
Potassium Chloride, PVA, PVP,
HEC, Sodium bisulfite, 0.02%, Benzyl
alcohol 0.1%, Sorbic acid 0.05%
and Disodium edetate 0.1%
Buffered isotonic, 0.003% Benzalkonium chloride, Polyvinyl alcohol, EDTA

In 120 ml pack

In 120 ml pack

In 120 ml pack
Thimerosal free in 120 ml pack
In 120 and 240 ml packs

In 120 ml pack

In 120 and 180 ml packs

Disinfecting/Cleaning Solutions (RGP Lenses)


Buffered isotonic sterile saline
In 350 ml pack
solution having sodium edetate
with biguanide copolymer 0.0031%
Solution: Lauryl sulfate salt of imidaThimerosal free in 120 ml pack
zoline Octylphenoxy, 0.3% Benzyl
alcohol and 0.5% Trisodium EDTA
Solution: Lauryl sulfate salt, Benzyl
In 120 ml pack
alcohol 0.1% and Disodium edetate 0.5%
Buffered solution; Sorbitan monolaurate, In 120 ml pack
betaine surfactant, Silicone glycol, Polythylene glycol, 0.003% Chlorhexidine
gluconate, 0.005% Polyamino propyl
biguanide and 0.05% edetate disodium
Contd...

ophthalmologyebooks.com

530 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Surfactant Cleaning Solutions (RGP Lenses)


Solution: Concentrated homogenous
surfactant, Alkyl ether sulfate,
Ethoxylated alkylphenol, Cocoa
based phospholipid silica gel
Surfactant solution with Alkyl
ether sulfate silica gel
Buffered isotonic solution 0.004%
Thimerosal 0.1% EDTA, Tween21,
Hydroxyethyl cellulose and
Polymeric cleaners.
Solution: Edetate disodium 0.1%,
Polyquad packs 0.001%, Tween 21,
Polymeric cleaning agents
Buffered isotonic solution 0.1%,
EDTA, 0.001% Polyquaternium-1,
Polymeric cleaners, Tween-21.

In 30 ml pack

Liquid containing subtilism and


glycerol
Tablets: Highly Purified
post-pancreatin
Tablet: Papain,NaCl, Sodium
carbonate, Sodium borate and EDTA
Liquid: Preservative free containing
propylene glycol Sodium borate and
pancreatin

Preservative free in 1 ml pack

Solution containing Polyquad 0.1%,


Edetate Disodium, Citrate buffer
Dextran NaCl, KCl.
Solution: Sorbic acid 0.1%,edetate
disodium 0.2%, HEC, Sodium
borate, Boric acid and NaCl.
Solution: Buffered, hypertonic 0.006%,
Chlorhexidine gluconate, 0.05% EDTA,
Cationic cellulose derivative
polymer as-wetting agent.

In 15 ml pack

In 30 ml pack
In 12 and 20 ml pack

In 12 and 118 ml
Thimerosal free in 12 and 20 ml
packs

Enzymatic Cleaners (RGP Lenses)

Pack of 24 and 36
tablets
Pack of 16 and 24 tablets

Rewetting Solutions (RGP Lenses)

In 15 ml pack
In 10 ml pack

Soft Lenses (Hydrogel)


Disinfection Non-hydrogen Peroxide Soft Lenses
Buffered solution containing NaCl,
0.0001% polyhexamethylene
biguanide,Tromethamine, Tyloxapol
and EDTA
Buffered isotonic solution 0.005%
Chlorhexidine 0.1% EDTA, 0.001%
Thimerosal, NaCl, Sodium borate and
Boric acid.

Thimerosal free 120 and 360 ml


packs
In 360 ml pack

Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 531


Drug name (Generic)

Dosage form/strength

Commercial packing

Buffered isotonic solution 0.05%


EDTA, 0.001% Polyquaternium-1
sodium citrate and NaCl
Solution: Isotonic 0.00005% Polyamino
propyl biguanide, 0.01% EDTA,
NaCl sodium Borate, Boric acid
and Poloxamine

In 120 ml pack
In 120 and 355 ml pack

Disinfection Hydrogen Peroxide Soft Lenses


Disinfectant/Soaking
Solution 3% hydrogen Peroxide,
0.85% stabilized with Phosphonic
acid, phosphate buffer and
Cleaner/Rinser isotonic
Boric acid, sodium
Borate sodium perborate,
0.006% Hydrogen peroxide.

In 120, 240 and 360 ml pack

In 12 ml pack

Saline Solutions (Preserved) Soft Lenses


Solution, Buffered isotonic, 0.01%
EDTA, 0.001% Thimerosal, NaCl,
Sodium hexameta phosphate, Boric
acid and Sodium borate
Solution: Isotonic 0.1% EDTA, 0.001%
Polyquaternium-1, NaCl, borate
Solution, Buffered isotonic 0.1% Sorbic
acid, 0.025% EDTA, NaCl, Boric acid,
Sodium borate.
Buffer solution 0.1% Sorbic acid,
Boric buffer, EDTA, NaCl.
Isotonic solution: NaCl, Boric acid,
Sodium borate, Sodium perborate,
Hydrogen peroxide, Phosphoric acid

In 240 and 360 ml packs

Thimerosal free in 360 ml pack


Thimerosal free in 120, 240 and
360 ml packs
In 60 and 360 ml packs
In 120, 240 and 360 ml packs

Preservative Free Saline Solutions (Soft Lenses)


Buffer solution containing NaCl, Boric
acid and sodium borate
Buffered isotonic solution: NaCl,
catalytic neutralizing agent, EDTA,
mono and dibasic Sodium phosphates

In 120, 240 and 360 ml packs


In 15 ml single use containers

Rinsing/Storage Solutions(Soft Lenses)


Solution containing NaCl, Sodium
hexameta phosphate, Sodium
Hydroxide, boric acid, Sodium borate
0.001% EDTA and 0.001% thimerosal
Isotonic buffered solution of NaCl,
boric acid, 0.0003% Polyaminopropyl
biguanide and EDTA
Isotonic solution with 0.9% NaCl

120 and 240 ml packs

In 120 and 340 ml pack


Preservative free 120 and 240 ml
packs
Contd...

ophthalmologyebooks.com

532 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Buffered isotonic with NaCl and EDTA


or NaCl with boric
acid and Sodium borate

Preservative free
120 and 240 ml packs

Surfactant Cleaning Solutions (Soft Lenses)


Solution containing 0.001% Thimerosal,
EDTA.
Buffered isotonic solution NaCl,
Sodium phosphate, Tyloxapol,
Hydroxyl ethyl cellulose, Polyvinyl
alcohol, EDTA, Sorbic acid
Solution with Cocoamphor carboxy
glycinate, Sodium lauryl sulfate,
Hexylene glycol,0.1% Sorbic
acid, 0.2% EDTA
Solution: 15.7% Isopropyl alcohol,
Poloxamer 407, Amphoteric 10.
Solution: Buffered isotonic: 0.15%
Sorbic acid, 0.1% EDTA, Boric acid,
Poloxamine, Sodium borate, NaCl
Solution: Propylene glycol,
Sodium borate, highly purified
porcine pancreatin enzymes
Solution:0.25% Sorbic acid, 0.5%
EDTA NaCl, KCl, Poloxamer 407

In 15 and 60 ml pack
In 30 ml pack

In 15 ml pack

Thimerosal free in 15 and 30 ml


packs
In 240 ml pack
Preservative free in 5 ml and
10 ml packs
In 25 ml pack

Enzymatic Cleaners (Soft Lenses)


Tablet containing Papain, NaCl,
Sodium Carbonate, Sodium
Borate, EDTA
Tablet containing Subtilisin A,
Polyethylene glycol, Sodium
carbonate, NaCl and Tartaric acid
Tablets: Effervescing buffering
and tableting agents Subtilisin A. To
make solution for soaking dilute in 3%
Hydrogen peroxide solution

In pack of 12, 24, 36 and 48


tablets
In pack of 8 tablets
In pack of 5,10,15,and 20 tablets

Disinfecting/Wetting/Soaking Solution (Soft Lenses)


ReNu Multiplus

Solution containing Hydranate,


Boric acid Edetate sodium,
Sodium borate, NaCl, Dymed
(polyamino-Propyl biguanide)
0.001% and 1% poloxamine
Solution: 0.001% Polyhexamethylene
Biguanide (PHMB), 0.025% Tyloxapol,
1.2% Tromethamine and 0.05% edetate
disodium

In 120, 240 and 360 ml packs

In 120, 240 and 360 ml packs

Contd...

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Chapter 50: Quick Look Ocular TherapeuticsAn Update 533


Drug name (Generic)

Dosage form/strength

Commercial packing

REWETTING SOLUTIONS (SOFT LENSES)


Isotonic solution containing 0.25%
Sorbic acid, 0.1% EDTA, Borate buffer,
NaCl, HPMC and glycerin
Isotonic solution NaCl, KCl,
Hydroxyethyl cellulose, Poloxamer
407, Sodium borate, Boric acid,
Sorbic acid and EDTA
Buffered isotonic solution NaCl,
0.0001% Polyhexamethylene
biguanide, Tromethamine, Tyloxapol,
EDTA
Solution: Sorbic acid, 0.15% and
Edetate disodium 0.2%
Buffered isotonic NaCl, Boric acid
Isotonic solution: citrate buffer, NaCl,
0.05% EDTA, 0.001% Polyquaternium-1
Solution: Sorbic acid 0.1% and
edetate disodium
Isotonic solution with NaCl, 0.13%
Potassium sorbate and 0.025% EDTA

Thimerosal free in 15 ml pack

Solution containing PET-200 glyceryl


Tallowate, disodium Laureth sulfosucinate cocoamido propyl amine
oxide, PEG-78 glyceryl cocoate, benzyl
alcohol and EDTA
Solution: PEG 80 sorbitan Laurate,
sodium trideceth sulfate, PEG-150
distearate, Cocoamido propyl
hydroxy sutlaine,
Lauroamphacarboxy-Glycinate, sodium
Laureth 13 carboxylate PEG-15 tallow
polyamine, quaternium-15

In a pack of 30/60 pads and


solution (120 ml)

Thimerosal free in 5,15 and 30 ml


packs
In 15 ml pack

In 15 ml pack
Preservative free in 0.035 ml pack
In 10 and 20 ml packs
In 15 ml pack
Thimerosal free in 15 ml pack

NONSURGICAL ADJUNCTS
Lid Scrubs

Alcohol free. In 30,120 and 240 ml


pack compliance kit
(120 ml and 100 pads)

Tear Test Strips


Schirmer Test Strip
Snostrips
Zone Quick

Sterile Test Strips


Sterile Tear Flow test Strips
Phenol red threads (PRT)

Pack of 250 strips


In a pack of 100 strips
In 50 aluminium packing sets
(100 threads)

Solution containing aqueous and


Glycerin solution of senecio Compositae,
Hamamelis water and Boric acid

In 7 ml vial

As powder

In a pack of 15 gm powder

Hamamelis Water

Boric Acid

Contd...

ophthalmologyebooks.com

534 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Zinc Sulphate 0.12%


Boric acid 1.25%
Naphazoline HCl 0.056%
and Chlorpheniramine maleate 0.01%
Zinc Sulphate 0.25%
Tetrahydrozoline 0.05%
EDTA and Benzalkonium Cl. (0.004%)
Zinc Sulphate 0.1%
Bolax 0.05%, Boric acid
1.9%, Sodium Chloride
0.45%, KCl 0.45, HPMC
0.7%

In 5 and 10 ml dropper vials

Astringent Ophthalmic Solution

In 10 and 15 ml dropper vials


In 10 ml dropper
vial and 120 ml bottle

Vitamin and Antioxidants


Vitamin A palmitate

Antioxidants

Tablets/Cap. containing
In pack of 100/
5000 IU/10000 IU/
250 Tab./Cap.
15000 IU/ 25000 IU
Vitamin-A
Capsule containing
In a pack of 100
vitamin A 6000 IU, Zinc
Capsules
30 mg, Copper 1.5 mg,
Selenium 60 mcg,
Manganese 5 mg,
Vitamin B12 20 mg
Vitamin C 200 mg and
Vitamin E 60 IU
Mixcarotin cap. containing 15.44 mg
Soft gel capsules (in a pack of
Of mixed carotenoids in oily
100 capsules)
suspension (Alpha carotene , betacarotene, lutein, cryptoxanthin and
Zeaxanthine) equivalent to 25000 IU
of Vitamin A.
Tablets containing 5000 IU BetacaroIn a pack of 100/250 tablets
tene, 150 IU E, 20 mg B1, B2, B6 each,
10mcg B12, 15 mg elemental Zn,
50 mcg, Selenium, 20 mg Calcium
pantothenate, 40 mg Glutathion 40 mg B3
100 mg C, 75 mg L-cysteine
Capsule: 5000 IU Vitamin A, 400 mg C, In a pack of 60 capsules
200 IU E, 40 mg Zn, 5 mg L-glutathione,
3 mg Sodium pyruvate, 2 mg Copper and
40 mcg Selenium.
Capsules softgel: Vitamin A 5000 IU,
In a pack of 50 capsules
200 IU, Vitamin E, 200 mg Vitamin C,
7.5 mg Zinc, 1 mg Copper , 15 mcg Selenium and 1.5 mg Mn.
Tablets: 5000 Vitamin A 30 IU
Film coated tab. in a pack of 60.
Vitamin E, 60 mg Vitamin C,
40 mg Zinc, 2 mg Copper and 40 mcg
Selenium
Contd...

ophthalmologyebooks.com

Chapter 50: Quick Look Ocular TherapeuticsAn Update 535


Drug name (Generic)

Dosage form/strength

Commercial packing

Solution containing
Pyridophenoxazine
(catalin) in concentration
of 0.75 mg/15 ml solvent
Solution containing large
quantity of Organic potassium
Solution containing 3.3%
Potassium iodide,
0.83% NaCl and 1.0%
Calcium chloride
Topical solution as 1%
Capsule containing
100/200 mg of Vitamin
E (alpha tocopherol)

Pack of Tablet alongwith


15 ml solvent

Topical Anticataract Therapy


Catalin

Cineraria
Anticataract solution

Aspirin
Vitamin E Therapy

In 15 ml dropper vial
In 10 ml dropper vial

In 15 ml dropper vial
In a pack of
100 capsules

Medical Therapy for Diabetic Retinopathy

D400
Calcium debesilate
Aspirin
Dipyridamol
Ticlopidine
Cyclandelate
Ponalrestat
Sulindac

Tablet: Herbomineral preparation


Capsule (500 mg)
Tablet (325 mg)
Tablet (225 mg)
Tablet (500 mg)
Capsule (400 mg)
Tablet (600 mg)
Tablet (250 mg)

In a pack of 100 tablets


In a pack of 50 capsules
In a pack of 100 tab.
In a pack of 60 tablets
In a pack of 100 tablets
In a pack of 100 capsules
In a pack of 50 tablets
In a pack of 100 tablets

DISINFECTIVE AND ANTISEPTIC AGENTS IN OPHTHALMOLOGY


Formaldehyde (Formalin)

As 10% aqueous soln

Ethylene oxide
Glutaraldehyde

As 10% tablets
As 3% colorless liquid
2% solution

Sodium hypochlorite

As 1% solution

Isopropyl alcohol

As 70% isopropyl alcohol

Biguanides
Polyhexanide (PHMB)

Chlorhexidine

Povidone iodine (Halogens)


Acetone
Cetrimide

As stock 20% solution


For ocular conditions
diluted solution (1:1000)
As 0.02% is prepared
as 5% stock solution
0.2% diluted solution
is prepared in isotonic
saline for ophthalmic use
5% sterile prep. solution
As 58.8% solution
and 1 litre packings
10% solution

In 60 ml, 400 ml
1 litre and 5 litre packings.
In a pack of 60/100 tablets
In 400 ml and 1 litre packing
As 60 ml, 400 ml and
1 litre packings
and 1 litre packings.
In 60 ml and 400 ml
Presterilized individual swabs
(A pack of 100 swabs)
In 60 ml, 100 ml and
400 ml packings
In 100 ml, 400 ml and
1 litre packings
In 5 ml, 15 ml dropper vials
In 60 ml, 100 ml, 400 ml
In 400 ml and 1 litre packings
Contd...

ophthalmologyebooks.com

536 Section V: Ocular Therapeutics


Drug name (Generic)

Dosage form/strength

Commercial packing

Beta propiolactone (BPL)

0.2% solution/condensed
product of Ketone and Formaldehyde
As solution containing
2-propanol 45.0 g
1- propanol 30.0g
100 ml
Ethyl hexadecyl -2 g
Dimethyl ammonium Ethyl sulfate
As solution containing
2-propanaol -63 g
Benzalko10 g
nium Cl-0.025g
As solution containing
(Each 100 gm contains)
Glutaraldehyde
7.0 g
Formaldehyde
8.2 g
Polymethylol urea
derivative
17.6 g
As solution
(Each 100 gm contains)
Ethanol 10 gm
2-Propanol-9 gm
1-Propanol- 6 gm
As solution (Each 100 gm
contains)
Propylene Glycol 0.52%
Sodium salicylate 0.46%
Sodium Lauryl
Sulphate 4.08%
Sodium Benzoate 5.9%
with Coco Glucoside,
PEG 120, Glycerine,
Glycol stearate and
sodium citrate
Solution containing
45 g 2-propanol,
30 g. 1-propanol,
0.2 g Mecetronium
ethyl sulfate (INN)
as stock solution (6%)
For ophthalmic use
can be diluted to 3%.

On 100 ml, 400 ml and 1 litre


packings
In 100 ml pack

Alcoholic rub-in-hand
Disinfectant (Sterillium)
Cutasept (Antiseptic)

Korsolex disinfectant

Bacillol disinfectant

Baktolin (Antiseptic)

HIV disinfectant

Hydrogen peroxide

ophthalmologyebooks.com

100 ml and 500 ml


pack

as 500 ml pack

As 200 ml pack
with spray

As 500 ml pack with


dispenser

In 500 ml and 1 litre packs

In 100 ml, 500 ml packs

Chapter 51: Future Drugs in Ophthalmology

537

51

Future Drugs in Ophthalmology


Ashok Garg

INTRODUCTION
INVESTIGATIONAL DRUGS

INTRODUCTION
Here I shall describe investigational new drugs (INDs), future drugs which
are of great interest to ophthalmologists worldwide. These INDs are in the
final stages of various clinical trials and shall shortly be approved by Food
and Drug AdministrationFDA (USA) for the commercial use in the
ophthalmology.
The investigational new drug (IND) has to pass the following phases of
trials before FDA approve it for commercial use.
These stages are
Preclinical Trials
In this stage initial Drug Research and Development and animal testing
takes place.
IND Filing
Human testing and interstate transport of IND is allowed in this phase.
Clinical Trials
It has three phases
Phase-I In this phase drug safety and tolerance is evaluated. Pharmacokinetics are tested in 20-100 normal adult males.
Phase-II In this crucial phase IND is evaluated in 100-200 concerned
disease patients to determine effectiveness and dose response
Phase-III In this final phase IND efficacy and safety is determined in 8001000 concerned disease patients. Drugs interactions are also recorded in
this phase.
NDA Review
New drugs analysis (NDA) is submitted to FDA for approval of IND
marketing.
Post-market Surveillance
This is a ongoing process and in this phase adverse reactions reporting,
survey, sampling and inspections are carried out.
INVESTIGATIONAL DRUGS
Various investigational new drugs (INDs) which are under various phases
of clinical trials and shall be of great use in ophthalmology in near future
are tabulated as below:

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538 Section V: Ocular Therapeutics


Table 51.1: Investigational drugs (topical ophthalmic formulations)
S.No. Drug name
(Generic)
1. ADL2-1294
2.
3.
4.
5.
6.
7.
8.
9.

Alpha-I Anti-chymotrypsin
Piroxicam
Nimesulide
Rofecoxib
Tenoxicam
Celecoxib
Mitomycin C
Adaprolol maleate

10. AGN-192151
11. AGA
12. Brimonidinex
13. Collagenase
14. Dexanabinol (HU-211)
15. Dronabinol
16. Fibroblast growth factor
17. Glutamate ion
channel blockers
18. Memantine
19. Pilocarpine

20. Verapamil HCl


21. Bromhexine
22. Cyclosporine ophthalmic
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.

Dehydrax
INS 365
N. Acetyl cysteine (NAC)
OcuNex
Acid implant (intravitreal)
Filgrastim
Monoclonal antibody to
cytomegalovirus
Curdlan Sulfate
Fomi virsen
GEM-132
Aromatic polycyclic
dione (APD-1)
ISIS-13312
Sevirumab
Valganciclovir
Topical clemastine
Cyproheptadine

Indications for use

Category

For treatment of ocular


inflammatory pain
Inflammatory diseases of the eye
Inflammatory diseases of the eye
Inflammatory disease of the eye
Inflammatory disease of the eye
Inflammatory disease of the eye
Inflammatory disease of the eye
To treat refractory glaucoma
Site active targeted delivery
system for glaucoma
Hypotensive lipid (OHL) for glaucoma
Site specific formulation for glaucoma
Alpha-2 agonist (neuroprotective for
optic nerve in glaucoma)
Purified collagenase for glaucoma
treatment
Treatment of glaucoma
and optic neuropathies
Treatment of glaucoma
Topical glaucoma therapy
Combination blockers
for glaucoma
Neuroprotective in glaucoma
Treatment of glaucoma using
submicron emulsion (SME)
delivery system and Durasite
sustained release delivery system
Treatment of glaucoma
Mild to moderate keratoconjunctivitis sicca
Treatment of severe keratoconjunctivitis in Sjgrens syndrome
Recurrent corneal erosions and dry eye
Ocular surface diseases as dry eye
Severe dry eye syndrome
Dry eye syndrome
Cytomegalovirus retinitis
CMV retinitis
CMV retinitis

Anti-inflammatory
NSAID
NSAID
NSAID
NSAID
NSAID
NSAID
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma
Anti-glaucoma

Anti-glaucoma
Ocular lubricant
Ocular lubricant
Ocular lubricant
Ocular lubricant
Ocular lubricant
Ocular lubricant
Anti-retroviral drug
Anti-retroviral drug
Anti-retroviral drug

CMV infections
CMV retinitis
CMV retinitis
CMV retinitis

Anti-retroviral drug
Anti-retroviral drug
Anti-retroviral drug
Anti-retroviral drug

CMV retinitis
CMV retinitis
CMV retinitis
Seasonal allergic conjunctivitis
Seasonal allergic conjunctivitis

Anti-retroviral drug
Anti-retroviral drug
Anti-retroviral drug
Anti-allergic
Anti-allergic
Contd...

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Chapter 51: Future Drugs in Ophthalmology

539

contd...
S.No. Drug name
(Generic)
39. Embramine
40. Methdilazine
41. Lexipafant
42. Procaterol
43. Tryptase inhibitor
(Second generation)
44. Amino caproic acid
45. Clostridium botulinum
toxin type A
46. Clostridium botulinum
toxin type F
47. Chlorhexidine 0.02%
48. Propamidine isethionate
49. Chondroitinase
50. Fibroblast growth factor
51. HylanA
52. Vitrase
53. Epidermal growth factor
54. Fibronectin
55. Matrix metalloproteinase
56. Urogastrone
57. Permeability increasing protein
58. Batimastat
59. Cell adhesion molecule
inhibitors
60. Dehydrex
61. Enzyme based
Iodine preparation
62. GM6001
63. Insulin like growth factor
64. Povidine iodine (2.5%)
65. XMP 200
66. Ciliary neurotrophic factor
67. CNS-1237
68. CNS-5065
69. Tyrosin kinase antagonist
70. FIK-I RTK antagonist

Indications for use

Category

Seasonal allergic conjunctivitis


Seasonal allergic conjunctivitis
Allergic conjunctivitis
using durasite delivery
Allergic conjunctivitis
Allergic conjunctivitis

Anti-allergic
Anti-allergic
Anti-allergic

Topical treatment of traumatic


hyphema of the eye

Anti-hemorrhagic

Treatment of ocular muscle


disorders (Blepharospasm)
Treatment of ocular
muscle disorders (Blepharospasm)
Treatment of acanthamoeba
keratitis
Treatment of acanthamoeba keratitis
Treating patients undergoing vitrectomy
To prevent lens clouding following
ECCE/Phaco
Ophthalmic viscosurgery
Treatment of vitreous hemorrhage
Treatment of recurrent
corneal erosions
Treatment of nonhealing
corneal ulcers
Treatment of nonhealing
corneal ulcers
Acceleration of corneal
epithelial regeneration
Treatment of corneal ulcers
Prevention of post-surgical
recurrence of pterygium
Treatment of ophthalmic
infectious diseases
Treatment of recurrent
corneal erosions
Treatment of infective
eye diseases
Treatment of infective eye diseases
Treatment of infective eye diseases
Treatment of infective eye diseases
Bactericidal
Treatment of macular degeneration
and retinitis pigmentosa
Protection for retinal degeneration
Protection for retinal degeneration
Treatment of ARMD
and diabetic retinopathy
Treatment of ARMD
and diabetic retinopathy

Anti-hemorrhagic

Anti-allergic
Anti-allergic

Anti-hemorrhagic
Anti-infective
Anti-infective
Surgical adjunct
Surgical adjunct
Surgical adjunct
Surgical adjunct
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Anti-infective
Retinal adjunct
Retinal adjunct
Retinal adjunct
Retinal adjunct
Retinal adjunct
Contd...

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540 Section V: Ocular Therapeutics


contd...
S.No. Drug name
(Generic)
71. Gene therapy
72. Hormone growth receptor
antagonist
73. Lisinopril
74. LGD-1550
75. Neurotrophic factors
76. NRT technology
77. Oligonucleotide
antisense compounds
78.
79.
80.
81.
82.
83.

Retinal pigment cells


Tazarotene
Tin ethyl etiopurpurin
Zopolrestat
Zenarestat
Cysteamine hydrochloride

84. SU-101
85. Corneaplasty

Indications for use

Category

For traction retinal detachment


Diabetic retinopathy

Retinal adjunct
Retinal adjunct

Diabetic retinopathy
Retinal degenerative conditions
Neurodegenerative conditions
of the eye
Neurodegenerative conditions
of the eye
To treat vascular endothelial
growth factor (VEGF) in various
retinopathies
Treatment of ARMD
Receptor selective retinoid
Photodynamic therapy for ARMD
Treatment of retinopathies
Treatment of diabetic cataract
Treatment of corneal cystine
crystal accumulation in cystinosis
Treatment of malignant glioma
Refractive correction

Retinal adjunct
Retinal adjunct
Retinal adjunct

ophthalmologyebooks.com

Retinal adjunct
Retinal adjunct
Retinal adjunct
Retinal adjunct
Retinal adjunct
Retinal adjunct
Anti-cataract
Miscellaneous
Anti-cancer in ophthalmology
Miscellaneous

Section VI

Miscellaneous
52. Dry Eye and Its ManagementAn Update
Ashok Garg
53. Update on Toric Contact Lenses
Ashok Garg
54. Plastic Surgery and Laser Treatment in Ophthalmology
Alice Handzel
55. Sterilization, Disinfection and Antiseptics In OphthalmologyAn Update
Ashok Garg

ophthalmologyebooks.com

ophthalmologyebooks.com

52

Dry Eye and


Its ManagementAn Update
Ashok Garg

INTRODUCTION
CAUSES OF REDUCED TEAR
PRODUCTION (ETIOLOGY)
CLINICAL EVALUATION
DIAGNOSTIC TEAR FILM TESTS
(FOR TEAR HYPOSECRETIONS)
MANAGEMENT OF
DRY EYE

INTRODUCTION
Dry eyes (keratoconjunctivitis sicca) are one of the most common causes of
chronic low-grade burning, irritation and discomfort of the eyes specially
in the elderly population. Dry eye as such is not a disease entity but a
symptom complex occurring as a sequelae to deficiency or abnormalities
of the tear film.
A reduction in tear flow in the absence of ocular disease is common in
the older age group. Pathological reduction of tear flow results in corneal
drying and this causes dry eye symptoms to develop. Dry eye is a significant
clinical problem in ophthalmology today. In more than 50 percent of elderly
people, dry eye is associated with systemic diseases particularly collagen
diseases.
CAUSES OF REDUCED TEAR PRODUCTION (ETIOLOGY)
Idiopathic Many patients with chronic low-grade mild symptoms of dry
eye shall demonstrate no systemic or ocular disease to account for the
lacrimal insufficiency. It is important to exclude drug-induced tear
hyposecretion as seen with a number of drugs specially antihistamines,
oral contraceptives, phenothiazines antihypertensives, antidepressants,
antiulcer drugs, antimuscle spasmodics, nasal decongestants and
anticholinergics.
Aqueous tear deficiency is seen in conditions like congenital alacrimia
(although rare) and in atrophy and fibrosis of lacrimal tissue due to a
destructive infiltration by mononuclear cells as seen in
Pure keratoconjunctivitis sicca (KCS) as characterized by the
involvement of lacrimal glands alone.
Sjgrens syndrome: It is an autoimmune disease which consists of a
triad of KCS, xerostomia and rheumatoid arthritis (Fig. 52.1). It may
be associated with widespread systemic collagen diseases. Sjgrens
syndrome is characterized by the frequent presence of hypergamma
globulinemia (50% cases), rheumatoid factor (70-90% cases) and antinuclear antibody (in 80% of cases). Other findings include the
presence of antibody of DNA, salivary gland tissue, smooth muscle
and gastric parietal cells. When these features occur alone the
condition is referred as primary Sjgrens syndrome or the sicca
complex when they are associated with connective tissue disorder
the condition is known as secondary Sjgrens syndrome.

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544 Section VI: Miscellaneous

Fig. 52.1: Keratitis filamentosa (dry eye in Sjgren


syndrome type-I (primary type)

Fig. 52.2: Ocular cicatricial pemphigus (cicatricial dry eye)

Damage or destruction of lacrimal tissue as a result of


trauma to the lacrimal gland may result in a loss of
tear production.
Sarcoidosis: The granuloma of lacrimal gland lead to
diminished tear secretion as seen with Rose Bengal
staining of the conjunctiva and cornea.
Lacrimal gland tumors may cause reduced tear
secretion which is sometimes very severe.
Neoplastic lesions or mixed tumors which is
locally invasive causes symptoms due to its size
and may displace the globe.
Adenocarcinoma which is an invasive malignant
tumor and causes widespread local destruction
of the bone and other tissues and leads to
decreased tear secretion. Chronic inflammatory
(pseudotumor) also leads to decreased tear
secretion.
Blockage of excretory ducts of lacrimal gland by
scarring of the conjunctiva also leads to decreased
tear secretion. Scarring of conjunctiva is seen in
trachoma, pemphigoid and erythema multiforme
Stevens-Johnson syndrome (Fig. 52.2).
Benign mucous membrane pemphigoid causes
essential shrinkage of conjunctiva. Chronic lowgrade irritation is a common feature in this
disease. The more severe dry eye is seen late in
the disease after significant scarring of the accessory lacrimal glands and ducts has occurred.
The postinflammatory mucosal scarring that
occurs as a result of an acute attack of StevensJohnson syndrome involving the eyes can result
in chronic dry eye. Resolution of the acute mucosal
necrosis leads to symblepharon and scarring of
the accessory lacrimal glands and the ducts of the
main lacrimal gland.

Neurogenic lesions and meibomian gland dysfunction


may lead to decreased tear secretion.
Infection of lacrimal gland (Dacryoadenitis) may cause
decreased tear secretion. It may be complication of
measles or mumps.
Both systemic and diskoid lupus erythematosus can result
in the complex of keratoconjunctivitis sicca and xerostomia due to infiltration of the lacrimal and salivary
gland. Dry eye is associated with superficial punctate
epitheliopathy and corneal erosions.
Conditions like scleroderma and periarteritis nodosa can
lead to KCS as a late development.
Status postexcision of the lacrimal gland may lead to
decreased tear secretion.
Mikuliczs syndrome can result from a variety of causes
like tuberculosis, leukemia, Hodgkins disease, amyloid, etc.
Other systemic diseases associated with dry eye include
graft versus host, polymyositis, post-head and postneck radiation, HIV, hepatitis B and C, Syphilis, TBC
and seventh nerve palsy.
Mucin deficiency dry eye occurs when goblet cells are
damaged as in hypovitaminosis A (xerophthalmia)
and conjunctival scarring diseases such as erythema
multiformae, trachoma, chemical burns, radiations
and ocular pemphigoid, etc.
Lipid deficiency and abnormalities although rare but has
been seen in some cases of congenital anhydrotic ectodermal dysplasia alongwith absence of meibomian
glands.
Ocular conditions associated with impaired eyelid function
as seen in exposure keratitis, dellen, symblepharon,
pterygium, Bells palsy, nocturnal lagophthalmos and
ectropion.

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Chapter 52: Dry Eye and Its ManagementAn Update 545


Epitheliopathies due to intimate relationship between
the corneal surface and the tear film affect the stability
of tear film.
CLINICAL EVALUATION

Precorneal Tear Film


One of the earliest signs of dry eye is the presence of an
increased amount of mucin strands and debris in the
precorneal tear film. In dry eye lipid contaminated mucin
accumulates in the precorneal tear film.

Symptoms
The most common symptoms of dry eye are
Irritation of eyes without pain or blurred vision
Ocular discomfort (nonspecific)
Burning and itching sensation
Foreign body sensation (Sandy type)
Photosensitivity
Grittiness
Complaint of burning sensation when exposed to
conditions associated with increased evaporation of
tears like heat, prolonged reading, air-conditioning,
etc.
Some patients may complain of dry eye and lack of
emotional tears.
Most susceptible group of patients for dry eye include
Postmenopausal women
Patients of 50 years plus group
Patients on diuretics, beta-blockers, psychotropics or
oral acne medications
Rheumatoid arthritis patients
People exposed to heat, dust, etc.
Signs
Signs of dry eye include presence of stingy mucus and
particulate matter in the tear film, lusterless ocular surface, conjunctival xerosis, Bitot spots (Fig. 52.3), reduced
or marginal tear strip and corneal changes.

Marginal Tear Strip


In dry eye marginal tear film is reduced in height (less
than 0.3 mm) and is concave and contains mucus and
debris. In severe cases of dry eye it may be absent
altogether.
Corneal Changes
In moderate to severe cases of dry eye the following
corneal changes may be present.
Punctate epithelial erosions involving the inferior
cornea which are best shown following instillation
of fluorescein into the inferior conjunctival fornix.
Filaments appear as small comma-shaped opacities
with the free end hanging over the cornea and moving
with each blink (Figs 52.4A and B). These filaments
are composed of central mucus core encased by
epithelial cells and are best shown on rose bengal dye
staining.
Mucus plaques appear as semitranslucent whitish
grey, slightly elevated lesions of varying shape and
size. They consist of mucus, epithelial cells and proteinaceous/lipoidal material. These plaques are usually
seen in association with corneal filaments (Figs 52.5A
and B).
Dellen unassociated with limbal elevations may be
seen in cases of severe KCS.
Corneal thinning and rarely perforation may occur
in cases of severe dry eye.
DIAGNOSTIC TEAR FILM TESTS
(FOR TEAR HYPOSECRETIONS)
Tear Film Break-up Time (BUT)

Fig. 52.3: Bitots spots (dry areas on the bulbar conjunctiva


in the interpalpebral fissure)

The tear break-up time is a simple physiological test to


assess the stability of precorneal tear film. This test is
performed by instilling fluorescein into the lower fornix,
taking precaution not to touch the cornea. The patient is
asked to blink several times and then to refrain from
blinking. The tear film is scanned with a broad beam and
cobalt blue filter. After an interval of time black spots or
line indicating dry spots appear in the tear film. BUT is
the interval between the last blink and appearance of
the firm randomly distributed dry spot (Fig. 52.6). Ideally
average of three measurements is taken. A normal BUT
is more than 10 seconds and a BUT of less than 10 seconds

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546 Section VI: Miscellaneous

Fig. 52.4A: Normal vs damaged tear film in dry eye


(Courtesy: FDC Limited)

Fig. 52.4B: Corneal filaments and plaques (left), and localized area of thinning (right) (Courtesy: Kanski Clinical Ophthalmology, Butterworth International edition)

is considered abnormal (Fig. 52.7). This test may also be


abnormal in eyes with mucin or lipid deficiency.
Schirmers Test
The rate of tear formation is estimated by measuring the
amount of wetting on a special filter paper which is 5
mm wide and 35 mm long.
Previously Schirmers test 1 and 2 were used in diagnostic practice but nowadays modified Schirmer-I test is
employed. This test is performed as follows (Fig. 52.8).

Fig. 52.5A: Diagnostic tests for dry eye


(Courtesy: FDC Limited)

Fig. 52.5B: Mucous threads and corneal filaments in dry eye


(rose Bengal staining) (Courtesy: Kanski Clinical Ophthalmology, Butterworth International edition)

Schirmer strips are prepared by cutting out Whatman


filter paper No. 41 into the strips of 5 mm 35 mm
dimensions. A 5 mm tab is folded over at one end. Before
use, these strips are autoclaved.
The bent end is placed into lower conjunctival sac at
the junction of lateral one-third and medial two-third of
lower eyelid so that 5 mm bent end rests on the palpebral
conjunctiva and the folding crease lay over the eyelid
margin. This test is usually performed in the sitting
posture in dim light.

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Chapter 52: Dry Eye and Its ManagementAn Update 547


The patient is asked to keep the eyelid open and look
slightly upwards at a fixation point. Blinking is allowed
while the patient gazes at the fixation point.
After one minute, the strips are carefully removed
and moistening of the exposed portion of the strip is measured in millimeters with the help of a millimeter ruler.
The measurements are made from the notch at the
bend of the Schirmer strip to the distal end of the wetting
on the strip (excluding the folded over tab). The amount
of wetting of the Schirmer strip in one minute is
multiplied by three to correspond roughly to the amount
of wetting that would have occurred in 5 minutes (Jones,
1972). It is a measure of the rate of tear secretion in a 5minute period.
A normal eye will wet between 10 mm and 25 mm
during that period. Measurements between 5 mm and
10 mm are considered borderline and values less than
5 mm is indicative of impaired secretion.

Fig. 52.6: Tear film break up

Vital Dye Staining


Rose bengal 1 percent has an affinity for devitalized
epithelial cells and mucus in contrast to fluorescein
which remains extracellular and is more useful in
showing up epithelial defects. Rose bengal is very useful in detecting even mild cases of keratoconjunctivitis
sicca (KCS) by staining the interpalpebral conjunctiva
in the form of two triangle with their basis at the
limbus (Figs 52.9 and 52.10).
Fig. 52.7: Tear film break-up mechanism
(Courtesy: Allergan India Limited)

Fig. 52.9: Staining of conjunctiva with rose bangal

Fig. 52.8: Modified Schirmer testdiagnostic test for dry


eye (Courtesy: Garg et al internationale Ophthalmologica)

The only disadvantage with rose bengal staining is


that it may cause ocular irritation specially in eyes
with severe KCS.
In order to reduce that amount of irritation, only a
small drop should be instilled into the eye. A topical
anesthetic should not be used prior to the instillation

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548 Section VI: Miscellaneous

Fig. 52.10A: Rose Bengal staining in Keratoconjunctivitis


sicca (Courtesy: FDC Limited)

Fig. 52.11: Rose Bengal tincture (degenerated corneal and


conjunctival cells in the dry eye)

Tear Globulin Assay


Tear IgA levels are measured in this test. This test is also
based on the principle that decreased tear formation will
lead to decreased IgA (immunoglobulin A) levels in tears
(Fig. 52.11). This test is performed on a specific tripartigan immunodiffusion plates containing specific agar
gel in wells. Twenty microliter of tear samples is put into
these wells and plates are incubated for 48 hours. The
diffusion of rings around wells are measured to nearest
0.1 mm with partigen ruler. The ring will be reduced if
the concentration of IgA in tears is decreased.
This is a reliable test for measuring tear globulins.
Fig. 52.10B: Rose Bengal staining in Keratoconjunctivitis
sicca (Courtesy: FDC Limited)

of rose bengal as it may produce a false-positive


result.
Alcian blue has the similar properties as rose bengal
and is less irritant but it is not generally available.
Lysozyme Assay
Lysozyme assay test is based on the fact that in hyposecretion of tears, there may be reduction in the
concentration of lysozyme. This test is performed by
placing the wetted filter strip into an agar plate
containing specific bacteria. The plate is then incubated
for 24 hours and the zone of the lysis is measured. The
zone will be reduced if the concentration of lysozyme in
the tears is decreased.

Tear Osmolarity
Tear osmolarity is increased in cases of hyposecretion.
Biopsy of Conjunctiva
Biopsy of the conjunctiva and an estimation of the
number of goblet cells are other tests which can be
done. In mucin deficiency states, the number of goblet
cells shall be decreased.
Conjunctival Impression Cytology
Conjunctival impression cytology is a microscopic test
to study the health of conjunctival cells. In this mapping
cells from the conjunctiva are directly taken on to a slide
and studied under microscope after staining. In dry eye
condition cells appear fewer, irregular in size and shape
and take up straining less uniformly confirming the
condition (Fig. 52.12).

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Chapter 52: Dry Eye and Its ManagementAn Update 549


Tear Substitutes (Tear Replacement)
Artificial tears and lubricants are the mainstay in the
treatment of dry eye. Ophthalmic lubricants represent
the cornerstone of the management of ocular surface
disease. A number of new formulations have been available commercially which have additional advantage of
limiting preservative toxicity while enhancing epithelial
cell growth.
Various tear substitutes available are as follows.
Artificial Tear Solutions (Eyedrops)
Fig. 52.12: Various treatment modalities for dry eye
(Courtesy: FDC Limited)

MANAGEMENT OF DRY EYE


Although at present there is no satisfactory cure for dry
eye, a number of therapeutic modalities are available to
relieve symptoms. Before starting the treatment it is
important to prepare the patient psychologically about
the chronic nature of the condition, while reassuring him
that with appropriate treatment permanent damage to
vision is unlikely.
Before treating, accurate diagnosis of the underlying
cause is important as it may give an indication of
prognosis. Sometimes the underlying cause may require
treatment in addition to topical treatment given in dry
eye cases.
Following treatment modalities are being used to treat
dry eye patients.
Tear Conservation
Preservation of existing tears by reducing evaporation
is initial sequence of therapy indicated. Evaporation of
tears is dependant upon temperature of air at air-tear
interface, humidity of air at the air-tear interface, air flow
over the ocular surface, surface area of the interpalpebral
fissure and integrity of the lipid layer of the precorneal
tear film. Following measures may be helpful in
decreasing the evaporation of tears.
Reduction of room temperature
Use of a room humidifier or moist chamber
Use of protective glasses with side pieces may protect
the eye from the effect of wind, dust, etc. in the
outdoor settings
In cases of severe KCS associated with corneal thinning partial tarsorrhaphy may be helpful by decreasing
the surface area of the interpalpebral fissure.

Tear substitute drops are the mainstay of treatment of


mild to moderate KCS. It is important that the patient
should use these drops quite regularly and frequently.
The frequency of instillation vary on the basis of severity
of KCS signs and symptoms in the patient. In severe dry
eye cases the patient is advised to put these drops at
hourly intervals while in moderate cases 4 to 6 times a
day frequency is recommended. However the main
drawback to topical drops is its short duration of action.
Artificial tear solutions usually contain inorganic electrolytes, preservatives and water soluble polymeric system.
In addition to polymers, lipids and vitamin A have been
added into new ocular lubricants. Vitamin A topical
preparations are shown to be effective in severe forms of
dry eye syndrome.
Following groups of topical hypotonic solutions are
available for treating dry eye cases.
Cellulose derivative These topical hypotonic solutions
contain methylcellulose or ethylcellulose (0.1 to 1%) and
0.3 to 1 percent hypromellose.
A new topical tear solution of cellulose group
commercially available is Refresh Tears (containing 0.5%
of carboxymethylcellulose sodium.) The added
advantage of this solution is that carboxymethylcellulose
(CMC) possesses strong mucoadhesive bonding which
closely adheres to the epithelial surface. Carboxymethylcellulose solution closely resembles the composition of natural tears. It contains unique preservative
sodium perborate which breaks down to water and
oxygen upon contact.
Polyvinyl alcohol base solutions These topical solutions
contain 1.4 percent polyvinyl alcohol and 0.6 percent
povidine. These two polymers enhance comfort and
maintain corneal health.
Specific properties of polyvinyl alcohol are it
smoothes and cools the dry irritated scratchy eyes,
provides needed moisture to dry ocular surface and does
not blur vision. It lubricates to prevent further irritation
and enhances patient comfort.

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550 Section VI: Miscellaneous


Topical Solution Containing Longer
Lasting Mucoadhesive

Soft Contact Lens Therapy

Topical solution containing longer lasting mucoadhesive


or increased viscosity agents like Polycarbophil and
Dextran. On topical instillation these solutions have
better duration of action (contact time).
Polyvinyl pyrrolidone polymer base tear solution provides a longer contact time.
Ointments
The second most common method for ocular lubricant
is protrolatum, Lanolin and mineral oil topical ointments.
When instilled into the eye, they dissolve at the temperature of the ocular tissue and disperse with tear fluids.
A major advantage of ointment is that it is retained in
the cul-de-sac longer than artificial tear solutions.
Ointment is generally applied directly to the inferior
conjunctival sac (0.25-0.50 inch ribbon) preferably at bed
time. However depending upon the severity of the
conditions, it can also be used more frequently during
the day time also.
For treatment of moderate to severe dry eye a new
lubricant eye gel is commercially available which is a
clear gel that liquefies and spreads rapidly upon contact
with the eye. It contains carbopal 980 (polyacryclic acid)
a gel with high water binding power that transforms gel
to liquid upon contact with the ocular tissue. It minimizes
blurring and streaking common with thick tears and
ointments.
Carbomer gel is also available commercially which
has markedly longer residence time and has significant
increase in the tear film break-up time at 10 minutes.
Ocular Inserts (Solid Devices)
For the relief of dry eye symptoms, preservative-free
water-soluble polymeric insert is also available. The cylindrical rod which contains 5 mg hydroxypropylmethylcellulose (HPMC) (1 mm 3 mm) is placed in the lower
cul-de-sac (slow dissolving polymers). It imbibes fluid
and swells. It starts dissolving within 6 to 8 hours releasing
the polymer to the ocular surface for 12 to 24 hours.
However, patient tolerance and acceptance are variable.
Gel Tears and Sodium Hyaluronate (0.1%)
Gel tears consist of clear, semisolid formulation of synthetic, high molecular weight polymers of acrylic acid. This
gel remains in the conjunctiva for several hour after
instillation and dissolves very slowly.
Topical sodium hyaluronate (0.1%) solution has been
shown to have properties similar to those of normal tears.
This solution has a possible role in the dry eye cases.

Hydrophilic bandage lenses often provide a tear reservoir


but it should be used in conjunction with replacement
tears. Caution should be taken because such patients are
prone to contact lens intolerance and superinfections.
Forniceal scarring may dislodge the lenses.
Punctal Plugs (Tear Drainage Reduction)
Mechanical occlusion of the lacrimal puncta has become
an accepted method of block tear drainage and thereby
prolong action of natural tears alongwith artificial tear
preparations. Two types of punctal plugs are currently
usedsilicone-based plug and temporary absorbable
collagen implant. Temporary punctal occlusion can be
performed by inserting 0.2 to 0.4 mm collagen plugs. The
main aim of temporary occlusion is to ensure that excessive wetness does not occur following permanent
occlusion.
Punctum silicone plugs are also available in 1.6, 2.0
and 2.8 mm sizes. Placement of implant in all four canaliculi is recommended to prevent a false-negative response
and patient is examined after one week. If it causes epiphora then upper plugs are removed.
Permanent punctal occlusion is recommended only
in patients with severe dry eye symptoms. Permanent
occlusion should be avoided in young patients as their
tear secretion tends to fluctuate more than in the elderly
patients.
Permanent occlusion is achieved by electrocautery
after local anesthesia. Following successful punctal occlusion it is important to watch for the signs of recanalization.
Argon laser canaliculoplasty is new method of permanent
occlusion which can be easily reversed.
Mucolytics
Topical 5 percent Acetylcysteine drops are recommended
for instillation four times a day. It is effective in eyes with
excessive mucus. It helps by dispersing the mucous
threads and decreasing tear viscosity.
Topical Retinoids
Topical retinoids have been shown to be effective in
reversing the cellular changes occurring in the
conjunctiva of dry eye patients.
Systemic Therapy
Systemic corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) may help in low-grade inflammation of the lacrimal gland in dry eye patients.
Treatment of underlying systemic disease in patients with

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Chapter 52: Dry Eye and Its ManagementAn Update 551


secondary syndrome with corticosteroids or NSAIDs
may ameliorate the symptoms of KCS.
Oral Bromhexine
Oral bromhexine (32 mg/day) has been reported to be
effective in the treatment of dry eye cases bromhexine
has been clinically tried to stimulate tear production.
Such compounds require the presence of normal lacrimal
gland that responds to stimulation.
Treatment of Associated Conditions
Blepharitis
Interference with normal lubrication cleansing function
of the tears as well as the decreased lysozyme content
put dry eye patients at risk for chronic low-grade infections. Such infections of the eyelid margin can aggravate
the underlying tear deficiency. So, blepharitis should be
treated with adequate lid hygiene and antibiotic therapy
when necessary.
Infections
Dry eye patients are exposed to increased risk of infection
so special care should be taken when cataract surgery is
contemplated on a dry eye. Corneal grafting is also difficult in patients with severe dry eye as is wearing of
contact lenses.

2. Bartlett JD, Clinical Ocular Pharmacology, ed.4, Boston:


Butterworth-Heinemann, 2001.
3. Bartlett JD, Ophthalmic Drug Facts, LippincottWilliam and
Wilkins, 2001.
4. Crick RP, Trimble RB, Textbook of Clinical Ophthalmology,
Hodder and Stoughton, 1986.
5. Duane TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
6. Duvall, Ophthalmic Medications and Pharmacology, Slack Inc,
1998.
7. Ellis PP, Ocular Therapeutics and Pharmacology, ed. 7: C.V.
Mosby, 1985.
8. Fechner, Ocular Therapeutics: Slack Inc., 1998.
9. Fraunfelder, Current Ocular Therapy, ed. 5: W.B. Saunders, 2000.
10. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
11. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
12. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
13. Goodman LS, Gilman A, Pharmacological Basis of Therapeutics, ed.7, New York: Macmillan, 1985.
14. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.
15. Kanski, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.
16. Kershner, Ophthalmic Medications and Pharmacology, Slack.
Inc., 1994.
17. Olin BR et al, Drugs Facts and Comparisons: Facts and Comparisons, St. Louis, 1997.
18. Onofrey, The Ocular Therapeutics, Lippincott-William and
Wilkins, 1997.
19. Rhee, The Wills Eye Drug Guide, LippincottWilliam and
Wilkins, 1998.
20. Steven Podos, Textbook of Ophthalmology, New Delhi: Jaypee
Brothers Medical Publishers, 2001.
21. Zimmerman, Textbook of Ocular Pharmacology, Lippincott and
William and Wilkins, 1997.

FURTHER READING
1. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.

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552 Section VI: Miscellaneous

53

Update on Toric Contact Lenses

Ashok Garg

ASTIGMATISM
TORIC SOFT CONTACT LENS
FITTING
RIGID TORIC CONTACT LENS
BITORIC RGP LENS

Toric contact lens is a spherocylindrical lens used to correct Astigmatism or


cylindrical number (as it contains cylindrical component) which standard
soft contact lenses do not have. They differ from spherical lenses in that
toric lenses have different radii of curvature in opposing 90o meridians.
Generally three types of Toric lenses are available.
a. Front surface toric lenses which have two different radii of curvature
on the anterior surface of the contact lens while the posterior surface is
spherical.
b. Back surface toric lenses: In these lenses two different radii of curvatures
are found on the posterior surface of the contact lens while the anterior
surface is spherical.
c. Bitoric lenses have different radii of curvature on the anterior and
posterior surfaces.
Before going into details of toric lenses let me discuss in brief the
Astigmatism for which these lenses are primarily used.
ASTIGMATISM
Astigmatism develops when the cornea does not have a spherical surface
and two corneal curvatures produce two focal points in the back of the eye.
There are three types of astigmatism (Figs 53.1 and 53.2).
1. Corneal
2. Lenticular
3. Mixed
1. Corneal Astigmatism is of 2 types
a. With the rule Astigmatism: In with the rule Astigmatism Vertical
meridian (90 degrees) is steeper (more curved) than Horizontal
meridian.
b. Against the rule Astigmatism: In against the rule Astigmatism
Horizontal meridian (180 degrees) is steeper (more curved) than the
vertical meridian.
2. Lenticular Astigmatism is the result of an unequal bending of light by
the crystalline lens. It is not related to the cornea.
3. Mixed Astigmatism include
i. oblique astigmatism where two Principal meridians are other than
90o or 180o (or very close to those meridians).
ii. In Regular Astigmatism two principal meridians are perpendicular
to each other. Regular Astigmatism is correctable by spherocylindrical
lenses.
iii. Irregular Astigmatism is seen when the cornea is scarred, inflamed or
of irregular shape and focus light on to multiple points on the retina.
iv. Residual Astigmatism: This is the Astigmatism that remains after
corneal Astigmatism has been corrected (left after a well fitted and

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Chapter 53: Update on Toric Contact Lenses 553

Fig. 53.3: Toric lens (Courtesy: Bausch and Lomb, India)


Fig. 53.1: Astigmatism (Courtesy: Bausch and Lomb, India)

Lenticular astigmatism is the result of an unequal


bending of light by the crystalline lens
Not related to the cornea
Fig. 53.2: Lenticular astigmatism
(Courtesy: Bausch and Lomb, India)

well centered lens). It may be same or different


compared to prefitting astigmatism. This is
primarily based on lens moulding on the cornea at
its back and initial front surface curvature. More
residual Astigmatism is the result of a toric
crystalline lens. Generally a small amount of
residual astigmatism (upto 0.50 D) is ignored unless
the patient complains about vision or when the
corrected visual acuity is poorer than 20/30 20/
40.

Contact Lens Correction of Astigmatism


There are essentially three ways by which Astigmatism
may be corrected with contact lenses.
a. Spherical soft lenses
b. Toric Soft lenses
c. Rigid Gas permeable lenses (RGPs)
a. Spherical Soft Lenses can be used for small degree of
Astigmatism. If the total astigmatism (upto 1 D) is
not more than 1/3rd of the spherical correction than
spherical soft lenses are usually adequate. When
spherical soft lenses are used to correct astigmatism,
generally standard thickness lenses are perferred over
thinner lenses because thicker lenses maintain their
shape and shall correct more corneal cylinder. Almost
50 percent of visually corrected population have
significant amount of astigmatism (0.75 D or more).
b. Toric Lenses: Toric soft contact lenses are used to
correct Astigmatism of more than 1D (Fig. 53.3). Toric
lenses may be useful for correcting corneal lenticular
astigmatism or a combination of two types and mixed
astigmatism. Soft toric lenses are contraindicated in
cases of irregular Astigmatism as a result of corneal
scarring and in lid closure abnormalities such as Bells
palsy. Generally Toric Lenses are recommended to
those patients who are unable to tolerate rigid lenses,
who have unsatisfactory vision with spherical soft
lenses.
A Toric soft lens is fitted like any other soft contact
lens with the additional task of selecting a lens
stabilizing system so that lens remains properly
oriented. Lens stabilization is the most important and
crucial part in toric contact lens fitting.
Toric Lens Stabilization Method
A toric lens must show meridional stability. This will keep
the cylinder at proper axis to ensure proper visual results.

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554 Section VI: Miscellaneous

Fig. 53.4: Prism ballasting


(Courtesy: Bausch and Lomb, India)

Fig. 53.5: Truncation (Courtesy: Bausch and Lomb, India)

Fig. 53.6: Periballasting


(Courtesy: Bausch and Lomb, India)

Stabilizing systems for Toric Lenses include (Figs 53.4 to


53.7).
I. Prism Ballasting
II. Truncation
III. Ballast Combined with Truncation
IV. Periballast
V. Posterior Toric Surface
VI. Dynamic Stabilization (Double slab off).
VII. Aspheric back surface
VIII. Orientation grooves
IX. Carrier flange (Bioflange)Thicker inferior edge.
X. Combination of all.
I. Prism ballasting: Prism ballasting is convenient for
patients with flat corneas, tight lids or oblique
astigmatism. Generally Prism ballast of 0.75-1.50
prism Diopters (PD) is used to increase the weight
of the bottom edge of the lens. This heavier bottom
edge will stabilize in the 6 O clock position reducing rotation. Increased thickness from apex to base
of lens provides excellent axis stabilization. Prism
ballasting provides consistent thickness profile

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Chapter 53: Update on Toric Contact Lenses 555

Fig. 53.7: Posterior toric curvature


(Courtesy: Bausch and Lomb, India)

across all the sphere powers and consistent rotational stability and fitting performance. This is the
most common used method of Toric lens
stabilization.
II. Truncation:In a truncated contact lens 0.5-1.5 mm
section of the lower portion of the lens is removed.
Sometimes both the upper and lower portions of
lens are truncated. Truncation can be combined
with prism ballasting to reduce the weight and
thickness of the prism ballasted edge. A truncated
lens edge should be smoothly leveled so that it can
aligns comfortably with lower lid. Usually truncated lenses are less comfortable because truncation
loosens the fit.
III. Periballasting: For patients whose astigmatism is
caused by a toric cornea, contact lenses can be
stabilized by making the posterior surface of toric
lens. This technique is generally recommended for
astigmatism where the cylinder correction is greater
than spherical correction. The lens is most stable
when its steepest curve is aligned with the steepest
part of he cornea. Posterior toric curvature lenses
are produced with a spherical anterior surface and
toric back surface to aid stabilization by matching
back surface to configuration of toric cornea.
IV. Dynamic stabilization (Double Slab off): This process
involves creation of thin zones on the inferior and
superior portions of the lens. This is most comfortable of lens orientation systems but it lacks less
stability than Truncation. With dynamic stabilization the lens rotates so that the thin zones are
positioned at top and bottom. Pressure from eye
lids maintains this position. Trial lens fitting is
recommended to determine the parameters for
correct lens positioning.

V. When an aspheric posterior surface is combined


with prism ballasting or truncation, lens stabilization is enhanced. This is due to increased drag as
a result of aspheric surface reducing rotational
movement.
For evaluation of lens rotation on the eye, toric soft
contact lenses have etch or laser marks at the 3 and 9 O
clock positions or at 6O clock position.
TORIC SOFT CONTACT LENS FITTING
Pre Fitting Assessment
Following parameters should be kept in mind before toric
soft lens fitting.
Refraction
Corneal Health
Tear film assessment
Parameter availability
Patient comprehension and compliance
Parameters for Successful Fit

Lens must centre well over the cornea.


Movements should not be more than 1.5 mm
Rotation of axis should not be more than 15o
Visual acuity should be normal, stable before, during
and after the blink.

Toric Lens Fitting


Three fitting techniques are generally used:
Diagnostic
Trial
Empirical

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556 Section VI: Miscellaneous


Fitting procedure steps include:
Initial lens power selection
Clinical assessment
Final lens power selection
Follow up care
Initial Lens Power Selection
Empirical trial fitting: Spherical lens is first tried (found
to closest cylindrical power). Refraction and cylinder in
minus cylinder form is calculated. Here unlike spherical
lenses there is no need to do spherical equivalent. Vertex
distance compensation of the sphere and cylinder is done
separately.
Fitting of the toric lens is done with trial lens which
has the same criteria of successful fit as for soft lenses.
For in office Diagnostic fitting and trial fitting always
select sphere/cylinder closest to final prescription and
also vertex sphere and cylinder.
Determine trial lens diameter by adding 2-2.5 mm to
the visible iris diameter (VID). All toric contact lenses
have base curve. So select a base curve by converting
the mean of the K readings to millimeters and add 0.7
mm in general or add 0.80 mm to the flattest meridian or
highest reading in mm.
Perform an over correction (recorded in minus cylinder form). Cylinder is determined doing over refraction.
The diagnostic toric lens is a sphere with orientation
marks.
Select a trial lens as close as possible to spectacle cylindrical axis (i.e. 170 degrees). For double slab off lenses
select the base curve by subtracting 4D from the flattest
K reading. Evaluate the fit and perform the over refraction.
Give the trial lens fit to the patient. Wait for 15-20
minutes before assessing fit of the lens. Assess fit of lens
by assessing.
Full corneal coverage
Centration
Movement
Comfort
Check rotation of lens by means of the etch or laser
marks at 3 and 9 O clock positions or at 6 O clock
position. Rotation can be evaluated by :
Visual examination
Trial frame that is aligned with the lens markings
Slit Lamp Exam with reticule that can be lined up
with lens marking
It is not always possible to show vision to a patient
as trial lens axis might not match spectacle axis. If three
factors (full corneal coverage, centration and movement)
are fine then axis finalisation is done. For axis finalisation

concentrate on the three laser guide marks at the inferior


or lower portion of the lens. Three things can happen
while assessing toric lens rotation.
No rotation or minimal rotation of 5 degrees.
Rotation to L.H.S.
Rotation to R.H.S.
General formula for Toric axis finalisation is LARS
Method.
L
A
R
S
Left
Add
Right
Subtract
If there is no rotation or minimal rotation of 5 degrees
than there is no change in spectacle axis hence the
prescription remains the same.
When there is rotation to LHS (clockwise left rotation) than add amount of deviation to the spectacle
cylinder axis.
If there is rotation to RHS (counter clockwise rotation) than subtract amount of deviation from the
cylinder axis of the spectacle correction. This is LARS
Method of axis rotation compensation. After axis
finalisation the final toric lens order is given. The
ordered lens should orient itself on the eye like the
trial lens did. Manually rotate the lens, with normal
blinking it should reorient with in a minute. When
the lens assumes its final position rotation on blinking
should be less than 5o. Movement in the same direction on successive blinks indicates a tight fit. Loose
fit is marked by excessive random rotation.
Toric soft contact lens should be fit slightly tight if
possible. A large diameter lens is suggested to achieve
better centration. Double slab off lenses are the most
comfortable toric lenses. Thinner lenses and high water
content lenses also provide comfort and oxygen
permeability. Optimum stability is achieved by using a
prism ballasted lens with a beveled truncation. A good
fit is easier to achieve when corneal astigmatism is close
to 90o or 180o. A normal blink pattern helps to stabilize
the lens making a successful toric fit more likely. Failure
with the soft toric lenses is most often related to discomfort or poor vision. Discomfort may be related to
excess movement contact with the lower lid or lens itself
causing foreign body sensation. Poor vision is often
caused by the inability of the lens to stabilize properly.
Corneal edema or stippling, destabilized lens, edge lift
off, decentration, poor movement or limbal compression
are signs of a potential bad toric lens fit.
Useful Tips for Toric Lens Fitting
Do not make changes in trial lens axis.
Trial lens (Diagnostic lens) fitting is a very reliable
and scientific method of fitting toric lenses.

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Chapter 53: Update on Toric Contact Lenses 557


Choose trial lens axis as close as possible to spectacle
axis.
If trial lens axis and spectacle axis are different then
do not try over refraction as it can lead to confusion.
Final lens base curve should be same as trial lens base
curve.
Final lens would also show similar rotation as trial
lens.
Dispensing and Follow up Care of Toric Lenses
(Care and Maintenance)
Instruct patients for proper wear and care procedures.
Schedule patients visits at 3/4 days, 10 days, 1 month,
3 month and every 6 months.
Ask the patient to wear their lenses at least 4 hours
prior to the visit.
Evaluate visual acuity, lens fit and Slit Lamp Exam
with and without fluorescein.
Discuss and reinforce proper patient compliance.
While removing the toric lens instruct the patient to
either pinch the lens from the center or else rotate the
lens in either direction (L or R) to avoid lens damage
along lens markings.
Care and maintenance of toric lenses is similar to
standard soft contact lenses.
Multi purpose solutions are recommended solutions
for best results.
Proper insertion and removal to be taught to the
patient to avoid lens damage (Fig. 53.8).
RIGID TORIC CONTACT LENS
If the spherical RGP (Rigid Gas permeable) lens fits
poorly because of decentration, poor alignment or dis-

Fig. 53.8: Optima toric lens


(Courtesy: Bausch and Lomb India)

comfort the next choice is an RGP lens with a posterior


toric surface (Back surface toric). The front surface of this
lens is spherical. The rule of quarters can be used to
determine the base curve of a back surface toric lens. To
select the base curve take one quarter of the total astigmatism and add this value to flattest K reading then take
the same value and subtract it from the steepest K
reading. Rigid toric lenses are used to correct significant
corneal astigmatism. These lenses are indicated when.
There is decentration of the spherical RGP lenses.
Residual astigmatism becomes evident after fitting a
spherical lens.
BITORIC RGP LENS
In a bitoric lens, the posterior surface is derived from the
corneal shape while the front surface is shaped to correct
any residual astigmatism. The posterior curvature is
determined by the rule of quarters. Lens diameter is
selected as for a rigid spherical lens. When the lens fits
well, an over refraction is done (recorded in minus
cylinder form). This correction is then added to the front
surface.
Front Surface Toric RGP Lens
If after achieving a good fit with a spherical RGP lens
their exists residual astigmatism sufficient to affect vision
a front surface toric RGP lens is recommended. These
lenses have a spherical posterior curvature and toric
anterior surface. A trial lens is used for over refraction.
Prism ballasting (0.751.50 PD) is added to the bottom
of the lens to keep the cylinder properly aligned. Various
Toric lenses are available commercially in various powers
in spheres and cylinders.
Internationally a number of next generation toric
contact lenses are available commercially. Out of these
soflens 66 Toric (Bausch and Lomb) is of excellant quality
(Fig. 53.9).
It has unique Lo-Torque designTM (Minimal rotational
force) to provide optimal visual acuity and ease of fit.
It is recommended for daily wear and provides the
convenience of planned replacement disposable (PRD)
Lenses. It is made from formcast process (cast molded)
which provides a high degree of rotational stability and
consistency ensuring exceptional visual acuity and
comfort to the patient (Fig. 53.10).
Soflens 66 Toric lens is made of Alphafilcon A
material. Its water content is 66 percent - high DK (32.0)
and provides high oxygen transmission specially in high
minus/plus power. It has ideal balance between DK and
dehydration resistance which optimizes corneal health.

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558 Section VI: Miscellaneous


Table 53.1: Toric lenses
Commercial lens
Name

Company

%water

Spherical power range (Diopters)

Cylindrical Power range


(Diopters)

Optima Toric Range Bausch and lomb

45%

Plano to 6.00 (in 0.25 steps)


-6.00-9.00 (in 0.50 steps)
optic zone-8 mm
Diameter 14 mm

-0.75-3.25 (in 0.50


steps) Prism ballast

SL 66 Torics range

Bausch and Lomb

66%

Plano to 9.00 (till 6.00 in


0.25 steps ) and -6.00 to
9.00 in 0.50 steps)
Optic zone 8.0 mm
Diameter 14.5 mm

-0.75, -1.25 and -1.75


Prism ballast

Miracon

Bausch and Lomb

45%

Plano to 6.00 (in 0.25 steps)


Diameter 14.0 mm

-1.25 and -1.75

Torisoft

Ciba Vision

38%

Plano to 6.00
(Diameter 14.5 mm)

-1.00 and -1.75

Focus Toric

Ciba Vision

NA

NA

NA

Hydron

American Hydron

38%

+ 20.00 to -20.00 (Diameter


13.5, 14 and 14.5 mm)

-0.50 to -6.00

Hydrocurve

Soft lenses

45%

+3.00 to 6.00
(Diameter 14.5 mm )

-1.25 and -2.00

Hydrocurve II

Soft Lenses

55%

Plano to 25.00
(Diameter 13.5 and 14.5 mm)

-1.25 and -2.00

Dura Soft TT
Standard

Wesley Jessen

30 and 38%

+1.00 to 6.00
(Diameter 12.8 and 13.5 mm )

-1.25 and -2.00

Cushion

Wesley Jessen

30 and 38 %

+20.00 to 20.00
Diameter (13 and 13.5 mm)

-0.75 to 4.00

Balflange

Salvatori

43%

Plano 0.75 to 4.00


(Diameter 13.5 and 14 mm)

-1.25 and - 2.00

Silk Toric

Silk Lens

NA

NA

NA

Hydromarc

Frontier

43%

Plano to 4.50
Diameter 14.5 mm

-0.75 to 1.50

Alphafilcon A is non ionic high water (Group II FDA)


material which is a patented strengthening monomer
(Fig. 53.11) and it enhances tear strength, handling and
low protein uptake which reduces the risk of adverse
responses.
Soflens 60 Toric LO-Torque Lens design has following
salient features (Figs 53.12 to 53.20).
I. Prism ballasting stabilizing geometry increased
thickness from apex to base of lens provides excellent axis stabilization.
II. Refined optic zone: Anterior and posterior optic
zone diameters are adjusted to minimise variations
in thickness providing optimal stability.
III. 360o Comfort Chamfer: Reduces lens mass for rotational stability. Comfort chamfer peripheral curve
ensures even thickness distribution from top to

bottom of lens. It enhances prism ballasting stabilization and maximizes comfort for all lens powers.
IV. Balanced vertical thickness profile Uniform Midperipheral thickness at apex, centre and base of
optic Zone enhances rotational stability.
V. Unique bicurve posterior design: flatter centre and
steep periphery for optimum centration and visual
acuity.
VI. Rounded edge design: consistent rounded edge
thickness provides consistent comfort plus smooth
optimal movement over conjunctival tissue.
Soflens 66 toric has three orientation indicator
at 5, 6 and 7 O clock position (30o apart). Its toric
location is Back Surface and centre thickness is 0.195
mm.

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Chapter 53: Update on Toric Contact Lenses 559

Fig. 53.9: Soflens 66 Toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.11: Alfafilcon A material (patented


strengthening monomer)
(Courtesy: Bausch and Lomb India)

FURTHER READING

Fig. 53.10: Brom case process (cast moulded)


soflens 66 Toric lens (Courtesy: Bausch and Lomb India)

1. Amar Agarwal et. al.; 4 Volume Text book of Ophthalmology,


Jaypee Medical Publishers (India), 2002.
2. Harold A. Stein et. al., contact lenses fundamentals and clinical
use, Jaypee Medical Publishers (India), 1997.
3. Tylers et. al., Soft contact lens Parameter Guide, Slack, 1996.
4. V.K. Dada. Text book of contact lenses, Jaypee Medical
Publishers (India), 1996.

Prism balasting stabilizing geometryincreased thickness from apex to base


of lens offers excellent axis stabilization
Refined optic zoneanterior and posterior optic zone diameters are adjusted
to minimize variations in thickness providing optimal stability
360comfort chamferreduces lens mass for rotational stability
Balanced vertical thickness profileuniform mid-peripheral thickness at
apex, center, and base of optic zone enhances rotational stability
Unique bicurve posterior designflatter center and steep periphery for
optimum centration and visual acuity
Rounded edgesprovide comfort plus optimal movement over conjunctival
tissue
Fig. 53.12: Toric lo-torque lens design soflens 66 toric lens) (Courtesy: Bausch and Lomb India)

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560 Section VI: Miscellaneous

Fig. 53.13: Prism ballasting soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.14: Refined optic zone soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.15: 360 comfort chamfer soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.16: Balanced vertical thickness soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

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Chapter 53: Update on Toric Contact Lenses 561

Fig. 53.17: Bicurve posterior design soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.18: Rounded edge design soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.19: Mold alignment softlens 66 toric lens


(Courtesy: Bausch and Lomb India)

Fig. 53.20: Axia adjustment soflens 66 toric lens


(Courtesy: Bausch and Lomb India)

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562 Section VI: Miscellaneous

54

Plastic Surgery and Laser


Treatment in Ophthalmology
Alice Handzel

INTRODUCTION
AGING OF THE FACE
LASERS USED FOR COSMETIC
TREATMENT
LASER-ASSISTED UPPER LID
BLEPHAROPLASTY
LASER-ASSISTED
LOWER EYELID
BLEPHAROPLASTY
FULL FACE BY CO2 LASER
TECHNIQUE AND
LASER SETTING
PREOPERATIVE AND
POSTOPERATIVE TREATMENT
COMPLICATIONS

INTRODUCTION
As eye doctors dealing with plastic, reconstructive and functional lid
surgery, we are increasingly confronted with a large variety of lasers for
different treatment.
The market is huge and is dynamically growing. Each surgeon has to
scrutinize the different technologies to choose the most suitable machine
for his area of interest.
Patient profile and appearance of different lesions have to be analyzed.
Although a two-in-one laser is desirable, the dual laser technology does
not meet our demands and works only in some small lesions like
telangiectasias and solar lentigines. The combined lasers are even more
susceptible to malfunctions because of two different technologies. One
should investigate the cost and effectiveness of the different laser systems,
as well as the durability and reliability of the laser company regarding the
future service and warranty.
Therefore, thoroughly informing oneself about the features of the
individual machines and their application areas is very important.
Carbon dioxide laser skin resurfacing has revolutionized cosmetic
surgery especially in the face and eyelid area. The only aim of aesthetic
plastic surgery is to make the patient look better, younger and/or more
attractive, giving the patient an invisible correction of any problems. When
operating eyelids, one should consider the look of the entire face. As
surgeons we have the obligation of learning special methods and techniques
in order to be able to offer the best possible treatment to our patients. My
results of the surgical treatment of blepharochalasis, including removal of
the orbital fat hernia are much better with the CO2 laser support, compared
to procedures in which the conventional, purely surgical approach is taken.
The laser-supported surgical cosmetic treatment is today the state-ofthe-art method in the face and eyelid area. Since this method does not leave
any visible marks, it has definite advantages over the conventional technique
using the scalpel, especially for forehead lift , for transconjunctival lower
lid blepharoplasty and as a support in upper lid blepharoplasty for the
eyebrow lifting.
Already in early stages of CO2 laser application, surgeons reported and
confirmed at several international conferences that a forehead lift using
CO2 laser skin resurfacing treatment can replace a conventional surgical
method.
After twenty years of performing cosmetic and reconstructive eyelid
surgery I am glad to sum up the results achieved during the last six years
with the use of a CO2 laser.

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There are a great number of different CO 2 lasers
available for this procedure. Obtaining an overview is
very difficult for a beginner. Talks with colleagues,
company representatives and an overwhelming amount
of information about different and yet similar machines
are confusing at the beginning.
The CO2 machines can be roughly classified as pulsed
and non-pulsed lasers with a continuous beam. The
treatment with pulsed lasers is gentle, as the skin surface
is exposed to the laser beams for only short intervals
which minimizes the thermal damage. They are superior
to the continuous wave CO2 lasers, which are more likely
to cause tissue fibrosis and scar formation. They accomplish stronger effects with a very short time of exposure
whereby the thermal effects on the surrounding tissue
can be controlled more precisely. The quality of a CO2
laser depends on the duration of the pulse. The potential
for thermal damages and scar formation decreases with
the pulse interval, which also helps to minimize postoperative redness and a more rapid healing.
In my opinion the reason why laser treatment is
highly advantageous is that it preserves the natural
appearance of the patients, face.
The deep mimic wrinkles cannot be completely
removed but a significant reduction and improvement
is possible.
In cases of distinct double chin or massive cosmetic
problems in the neck area, which require a conventional
surgical treatment, cooperation of a plastic surgeon who
can take care of these problems is sought to perform a
surgical facelift. If needed, the treatment in such a case
could be a surgical facelift, combined with a CO2 laser
procedure.
Using a CO2 laser it is highly unlikely to give the
patient an unnatural look as can happen in case of an
overcorrected surgical procedure. However, in case of
overcorrection with a CO2 laser, a too aggressive treatment can cause scars and/or pigment disorder.
A cautious treatment which is individually adapted
to the type of skin is another obvious prerequisite for
good results. An adequate training is self evident.
AGING OF THE FACE
Our face changes as it ages in the same way that other
parts of our body do. In the face area, it is especially the
skin which is affected, as it is continuously exposed to
the environment (sun, cold, heat, wind, dry air). Our skin
should be considered as an organ which has an important
functional as well as an aesthetic role. Here we can
observe several visible signs of skin aging:
wrinkles, skin thinning, slackness and loss of skin
tension,
epidermal pigmented lesions such as lentigines, cafeau-lait spots, other hyper- or hypopigmentations and
other irregularities (verrucae, acne scars, etc.)

sinking of the whole facial skin caused by reduced


tension of the skin layers, among others of collagen
fibers which are important in this context, and by
weakening of the facial muscles.
Of course we perceive the face as a whole which is
visibly affected even to the non-professional observers
specially in the areas of the eyebrows, upper and lower
lids, cheek sinking and wrinkles in this area.
LASERS USED FOR COSMETIC TREATMENT
We use two lasers for cosmetic treatment in our clinic:
Coherent Ultrapuls 5000 C - CO2 - Laser for:
Skin resurfacing and skin rejuvenation
single wrinkle removal, and
cutting the skin for eyelid surgery.
Aesculap Meditec Argon laser for:
removal of facial telangiectasia, and
removal of facial hemangioma.
Treatment Effect of the CO2 Laser
The CO2 laser achieves the treatment effect through:
1. The removal of the upper skin layers in the range of
the epidermis including wrinkles, unevenness, scars,
pigmented lesions such as lentigines, cafe-au-lait
spots, verrucae and acne scars. This has the effect of
skin renewal or resurfacing.
2. The other effect is the so called skin rejuvenation. It
is caused by shrinking of the collagen fibers under
the thermal shock which leads to skin contraction and
rejuvenation.
Both effects support each other, as, for example,
removal of pigment lesions gives a rejuvenated look.
Treatment Effect of the Argon Laser
Removal of facial telangiectasias or/and facial
hemangioma.
A nice side effect to have as an ophthalmologist,
doing plastic surgery, an argon laser is his effectiveness
in removing of telangiectasias. In adequate power this
laser can be used for effective microcoagulation of those
facial skin vessels.
The major advantage in this treatment of facial vascular lesions with laser, we use for the retinal procedures
(Fig. 54.1) is that there is no need to use any magnifying
and protecting glasses, because the protection for the
treating person is built into the laser. Moreover, we have
an excellent magnification in the slit lamp, making the
coagulation much easier, more exact and more efficient
than with a handpiece. It makes the procedure very
comfortable.
The results of removing the vascular lesions on the
face by argon laser are very good.

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564 Section VI: Miscellaneous

Fig. 54.1: Retinal foramen treated with argon laserslit lamp


view

Fig. 54.3A: Same patient other area before treatment

Fig. 54.2A: Facial telangiectasias before partial argon


treatmentcheek area

Fig. 54.2B: Same cheek area two and half week after
partial argon treatment

Fig. 54.3B: Same patient two and half week after treatment.
Laser setting: 50 m spot diameter/0.15 second duration
time/0.81.0 Watt energy/blue-green wavelength

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Fig. 54.4A: Nasal small hemangioma and facial telangiectasias before argon treatment

Fig. 54.5B: Same case immediately after treatmentslit


lamp view with visible coagulation effects

Fig. 54.4B: Same patient after treatment

Fig. 54.6A: Telangiectasias before treatmentslit lamp view

Fig. 54.5A: Telangiectasias before


treatmentslit lamp view

Fig. 54.6B: Same case immediately after


treatmentslit lamp view

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566 Section VI: Miscellaneous

Fig. 54.7A: Telangiectasias before treatmentslit lamp view

Fig. 54.8A: Female with blepharochalasis preoperative

Fig. 54.7B: Same case immediately after


treatmentslit lamp view

Fig. 54.8B: After only upper lid surgical blepharoplasty

Conventional Surgical Blepharoplasty versus CO2


Laser Supported Treatment and Forehead Lifting
With and without Forehead Lifting
One should notice the difference between the photographs, taken before and after only surgical blapharoplasty and before/after the combined procedure:
blepharoplasty plus eyelids skin resurfacing and the CO2
laser forehead lifting.
The resulting eyebrow lifting is a very important
aesthetic component of this treatment.
Of course we also did a good job before we got the
opportunity to work with the CO2 laser and started to
use it for the combined procedure. However, without any
doubt the final results are better with than without the
laser.
The advantages of using the laser in the cutting mode
are those of simultaneously cutting and coagulating

with less bleeding during and after the procedure, less


swelling and bruising, following this, less trauma to the
tissue; and in summary, a shorter recovery time; last but
not the least reduced surgery time.
The greatest advantage in my opinion is to lift the
eyebrows by the skin resurfacing of the forehead by CO2
laser to counteract the sinking of the eyebrows.
The disadvantages result also from the simultaneous
coagulation. Because of the wound edge coagulation
wound healing is delayed, so it is recommendable to
remove the sutures after 7-8 days in contrast to surgical
treatment when the sutures can be removed already on
the fourth postoperative day.
In addition safety precautions should be followed like
adequate protection of the eyeball against perforation
or other injury by coagulation of the tear gland, sclera,
muscles, levator aponeurosis with subsequent malfunction. A special training is necessary. The eyeball has to

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 567

Fig. 54.9A: Schematic drawing of treated area in cases with


skin resurfacing of forehead, eyelids and temple (details see
section laser setting)

Fig. 54.9B: Schematic blepharoplasty incision and placement of vermilion border treatment with 3 mm collimated
handpiece for single spots (see laser setting) in cases of full
face skin resurfacing and/or perioral rhytides

be protected by a special metal shield against an


inadvertent exposure to the laser beam.
The same applies to all safety rules and precautions
contained in the usual guidelines for personal behavior
and for operating room equipment as well as laser-using
issues like avoiding fire, injuries, etc.
Further, the learning curve in visually recognizing the
depth of the incision or appropriate laser setting should
not be underestimated. Last but not least the expenses
are considerable.

commitment, holidays, restricted or forbidden sun


exposure and also for financial reasons.
As a result, we have today a possibility of a direct
comparison of the outcomes of both treatments,
consequently we are very satisfied to be able to offer our
patients the combined procedure as an improvement to
previous conventional treatment.
The CO 2 laser-supported treatment has several
advantages: the abrasion of the skin surface by the CO2
laser removes, as already mentioned above, the visible
signs of skin aging, like excess of skin and, to some extent,
wrinkles. The shrinking effect allows us to tighten the
skin and give our patients a rejuvenated skin look.
When upper lid blepharoplasty is performed, a
supplementary CO2 laser skin resurfacing of the forehead
is recommended. It effects a lifting of the eyebrows which
has a very impressive rejuvenating effect. The upper lid
skin is also rejuvenated. The temple area is equally
treated in this manner (rejuvenated) and in most cases
the lower lid skin (Fig. 54.9A)
If there is a large excess of lid skin a surgical treatment
is needed which means that the excess parts of the skin
must be removed, since the laser ability to shrink the skin

LASER-ASSISTED UPPER LID BLEPHAROPLASTY


Many plastic surgeons who work with a scalpel only,
as I also did before, have been offering a surgical forehead
lift to their patients, as an aesthetically indicated
extension of an upper lid surgery. This procedure
counteracts the sinking of the eyebrows and it significantly improves the outcome of an upper lid surgery.
Despite the recommendation not all of the patients
undergo the combined procedure for reasons like work

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568 Section VI: Miscellaneous

Fig. 54.10A: CPG scanning spots directly after their


application on the forehead before washing (lying patient)

Fig. 54.11A: Marking of the upper lid crease


and the incision

Fig. 54.11B: Repeated checking of eyelid closure


and of skin excess

Fig. 54.10B: Patient with forehead, upper, lower eyelids and


temple skin resurfacing with CO2 laser and transconjunctival
lower lid blepharoplasty, immediately after the treatment

is limited.
Our treatment
Checking preoperatively if skin and orbital fat
removal is necessary. In some mild cases forehead and
eyelid treatment by the CO2 laser only is sufficient.
Photo documentation in all cases (also in single
lentigines or cafe-au-lait spots treatment)
If surgical treatment is also necessary we mark the
incision on the eyelid skin in the upper eyelid crease

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Fig. 54.11C: Correction

Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 569

Fig. 54.12A: After injection

Fig. 54.12C: Skin removal

Fig. 54.12B: Laser cut

Fig. 54.12D: Fat removal (middle part)

(Figs 54.11A to C), paying attention to the different


distance from the crease to the eyelid edge in male
and female patients. In female 10 mm from the lid
margin, and not less than 10 mm below the eyebrow
in female patients. We try to place the incision
individually in every patient recognizing his or her

own crease and paying attention to the present skin


surplus.
Technique of upper lid blepharoplasty with CO2
laser in cutting mode.
In nearly all cases at our clinic we do the combined
procedure and in our opinion we obtain with it the

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570 Section VI: Miscellaneous

Fig. 54.13A: 58-year-old female with upper lid


blepharochalasis and orbital fat deposits

Fig. 54.12E: Localization of the nasal fat part by gentle


pressure

Fig. 54.13B: Same patient after surgical upper lid blepharoplasty with fat removal plus forehead, lower eyelid and temple
skin resurfacing

3. CO2 laser skin resurfacing in lower lid skin area


for a similar appearance of the skin in upper and
lower lid area.
LASER-ASSISTED LOWER EYELID
BLEPHAROPLASTY
Fig. 54.12F: Visible tear gland after fat removal (other eye)

optimal cosmetic results for upper lid blepharoplasty.


1. CO 2 laser skin resurfacing of the forehead plus
temple.
2. Surgical blepharoplasty (if it is necessary) by laser,
combined with orbital fat removal ( in cutting mode)
and with upper lid skin resurfacing by CPG.

The lower lid blepharoplasty treatment has undergone


a really revolutionary development, since it is possible
to treat this area through the conjunctiva without any
visible signs of surgery. The orbital fat is transconjunctivally removed. The surplus skin is smoothened and
shrinks as a result of the resurfacing laser treatment. The
eyes retain their natural appearance and the skin need
not be cut from outside. Also the potential for complications, e.g. an overcorrection and ectropion is smaller.

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 571

Fig. 54.14A: A 59-year-old female with upper lid


blepharochalasis

Fig. 54.14B: Same patient after surgical upper lid blepharoplasty with fat removal plus forehead, upper eyelid, lower lid
and temple skin resurfacing 3 months after treatment (see
complications Fig. 54.30)

Fig. 54.15A: A 59-year-old female with upper lid


blepharochalasis

Fig. 54.15B: Same patient after surgical upper lid


blepharoplasty with fat removal plus forehead, upper eyelid,
lower lid and temple skin resurfacing 3 months after treatment (see complications, Fig. 54.30)

Fig. 54.16A: A 61-year-old female with upper lid blepharochalasis, after a slightly overcorrected lower lid blepharoplasty,
which was not performed in our clinic

Fig. 54.16B: Same patient after surgical upper lid blepharoplasty with fat removal plus forehead, upper eyelid, temple
skin and in this case -very careful -lower lid skin resurfacing,
1 month after treatment

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572 Section VI: Miscellaneous


Since we use the CO2 laser, all our cases are done by
the transconjunctival procedure. In these patients the
laser is used in a cutting mode of 4.5-5 watt power (Fig.
54.16A). For better separation of the conjunctiva from
the lower eye lid we use, additionally to a retractor, a
thread placed in the cut edge from the conjunctiva (Fig.
54.16B) for better holding and easier visibility of the
orbital fat (Fig. 54.16C) for removal (Fig. 54.16D).
Technique of Lower Lid Blepharoplasty

Fig. 54.17C: Localization of the nasal fat part by gentle


pressure

Fig. 54.17A: Transconjunctival cut

Fig. 54.17D: Fat removal in defocussed cutting mode

Fig. 54.17B: A thread placed in the edge of the cut in the


conjunctiva

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 573

Fig. 54.17E: Removed fat deposit

Fig. 54.19A: A 55-yearold woman shown preoperatively

Fig. 54.18A: A 55-year-old woman shown preoperatively

Fig. 54.19B: One month after the surgery

Fig. 54.18B: Same patient 1 week after upper eyelid


blepharoplasty combined with a transconjunctival lower eyelid blepharoplasty and skin resurfacing of the upper and lower
lids, forehead and temples. Visible erythema

Fig. 54.20A: A 56-year-old woman shown preoperatively


(upper lid blepharoplasty done 5 years before), looking straight
and up

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574 Section VI: Miscellaneous

Fig. 54.20B: Same woman after transconjunctival lower


eyelid blepharoplasty and lower lid skin resurfacing

Fig. 54.22A: A 54-year-old woman with preoperatively lower


lid dermatochalasis and fat prolaps

Fig. 54.21A: A 56-year-old woman shown preoperatively


(upper lid blepharoplasty done 5 years before), looking straight
and up

Fig. 54.22B: Same woman after transconjunctival lower eyelid blepharoplasty and lower lid skin resurfacing, 3 month
after surgery

FULL FACE BY CO2 LASER


Combined with Upper and/or Lower
Eyelid Blepharoplasty
Some of our patients have already undergone a lid plastic
surgery procedure before and they only need an additional CO2 laser full face treatment for skin rejuvenation.
In others the combined procedure is necessary. In the
section on the upper and lower lid treatment we
described the particular procedures we use. We want to
show you the corresponding slides in this section.
In following slides we show the clinical documentation, but also the way we do photographs preoperatively in a case of a full face treatment.
Fig. 54.21B: Same woman after transconjunctival lower
eyelid blepharoplasty and lower lid skin resurfacing

TECHNIQUE AND LASER SETTING


We use the Coherent Ultrapulse 5000 C CO2 Laser with:

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 575

Fig. 54.23A: A 56-year-old woman with lower lid dermatochalasis and fat prolaps, glabellar folds, wrinkles, facial skin
aging, preoperatively (upper lid blepharoplasty done 6 months
before in other clinic)

Fig. 54.23B: One month after transconjunctival lower eyelid


blepharoplasty and full face skin resurfacing

Fig. 54.23C: Same patientright eye preoperatively

Fig. 54.23D: Same patientright eye one month


postoperatively

Cutting handpiece for the cutting mode for upper lid


cutaneus and lower lid transconjunctival cuts.
Scanning handpieceCPG (Computer Pattern Generator) with scanning mode for skin resurfacing and
rejuvenation.
3 mm collimated handpiece for single spots.

Blepharoplasty and Skin Resurfacing


For cutting we use a special handpiece with a 0.1 or 0.2
mm with focussed beam in continuous wave mode-CW
- power 4.5 to 5 watts.

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576 Section VI: Miscellaneous

Fig. 54.23E: Same patientleft eye preoperatively

Fig. 54.23F: Same patientleft eye one month postoperatively

Fig. 54.23G: Same patientglabellar folds and eye area


preoperatively

Fig. 54.23H: Same patientsame area one month postoperatively

Fig. 54.23I: Same patientcheek, lips and chin area


preoperatively

Fig. 54.23J: Same patient cheek, lips and chin area one
month postoperatively

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 577

Fig. 54.24A: A 56-year-old woman with lower lid


blepharochalasis, fat deposits and facial skin aging

Fig. 54.24D: Same patient perioral area one month


postoperatively

Fig. 54.24B: Same patient one month after transconjunctival


lower eyelid blepharoplasty and full face skin resurfacing

Fig. 54.25A: A 46-year-old woman with lower lid


blepharochalasis, fat deposits and facial skin aging

Fig. 54.24C: Same patient perioral area preoperatively

As a basis for classifying the different skin types, we


use the Fitzpatrick table.
For skin resurfacing we decide about the laser setting,
depending on the depth of the wrinkles and the expected
postoperative skin reaction like redness, swelling, etc.
which depend on the skin type.

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578 Section VI: Miscellaneous

Fig. 54.25D: Same patient left eye preoperatively

Fig. 54.25B: Same patient one week after the


procedure mild erythema

Fig. 54.25E: Same patientleft eye one week


postoperatively

Fig. 54.25C: Same patient four weeks after the procedure

Fig. 54.25F: Same patientleft eye four


weeks postoperatively

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 579

Fig. 54.25G: Same patient perioral area preoperatively


(notice the chin scar)

Fig. 54.25J: Same patient forehead and eye area 2


weeks postoperatively (notice the eyebrow lift)

Fig. 54.25H: Same patient perioral area 2 weeks


postoperatively (notice the chin scar)

Fig. 54.26A: A 56-year-old woman with lower lid


blepharochalasis, fat deposits and facial skin aging

Fig. 54.25I: Same patient forehead and eye area


preoperatively

Fig. 54.26B: Same patient postoperative picture

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580 Section VI: Miscellaneous

Fig. 54.27A: A 57-year-old womanfull face treatment


preoperative picture perioral area

Fig. 54.28B: Same patient, same areapostoperative


picture

Fig. 54.27B: Same patient 2 months postoperatively

Fig. 54.28C: Same patientfull face viewpreoperatively

Fig. 54.28A: A 58-year-old female with facial skin aging,


preoperative picture of periorbital and forehead area (eyelid
surgery performed years before in other clinic)

In routine procedures, considering the skin type, we


apply 250 300 mJ = 50 60 watts power, density 5 (in
thinner skin, very seldom, density 4 ) and 4-6 passes for
the whole face skin area (forehead, cheeks, chin, nose,
temple), except the eyelids and lips. The forehead and
perioral area usually have a thick skin and are suitable
for a generous ablation.

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 581

Fig. 54.28D: Same patientfull face viewpostoperatively

Fig. 54.28F: Same patient perioral area


(side view) postoperatively

Fig. 54.28G: Same patient perioral area preoperatively

Fig. 54.28E: Same patientperioral area


(side view)preoperatively

For eyelids skin we set 150 mJ, density 5 with 3-4


passes. Very seldom we perform 5 passes and then the
last one with lower density.
Ablation borders are treated with CPG 300 mJ, for
example in the chin shadow area, with the handpiece
held in a bigger distance, defocusing it for feathering.
The scanner pattern gives nearly single spots with
distances between them. The same effect can be achieved
with a 3 mm collimated handpiece for single spots.

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582 Section VI: Miscellaneous


often forget the extent of their conditions before the
procedure, so it is helpful to have an evidence of their
preoperative appearance for comparison. Modern
technology gives us the option to save the digital images
and to pass them directly in the computer, so they are
immediately available for patient viewing and after the
procedures in side-by-side mode.
All complications during the healing period should
be documented in detail by the photographs.
In all procedures combined with CO 2 laser skin
resurfacing like partial face, eyelid or full face treatment
the postoperative conservative treatment is as important
as the precise setting of the laser parameters.
Preoperatively
Fig. 54.28H: Same patient perioral area postoperatively

At the end of the full face or the perioral rhytides


procedure we treat the vermilion border on the skin side
with 3 mm collimated handpiece, 250300 mJ energy,
2-3 passes. This causes an everting of the lips, which gives
a very advantageous cosmetic effect, giving the lips fuller
look (see figures with the perioral area).
Vermilion border is treated with an additional 3
passes using a 3 mm spot at 250 300 mJ to underline
and evert the lips.
For the lips we use 150 mJ, density 5, 1-2 passes.
Removal of Facial Telangiectasias or/and
Hemangioma with an Argon Laser
These patients we treat with an argon laser. For the
treatment of the telangiectasias in the face we use the 50
m spot diameter. In some cases with the thicker skin
part in the nasal or perinasal area and bigger vessels
100 m diameter. Further we usually set 0.15 second
duration time, 0.81.2 Watt energy and bluegreen
wavelength.
PREOPERATIVE AND POSTOPERATIVE
TREATMENT
Patient Education
First of all it is very important to educate the patient about
the expected results creating realistic expectations. Deep
wrinkles do not completely disappear or they reappear
after the swelling of the skin has ceased.
Photo documentation in all cases (also in single
lentigines or cafe-au-lait spots treatment). Clinical
photographs taken before and after the treatment enable
our patients to assess the progress of healing. Patients

Preoperatively, a thorough history is very important. If


the patient has a history of wound healing disorders and
a tendency towards scar formation, he cannot undergo
laser treatment.
Additionally, we have to find out if the patient has a
history of herpes infection. In such a case we apply a
pretreatment three days before the surgery administering
Acyclovir 400-800 mg 4-5 times daily depending on the
placement and time since the last infection.
Postoperatively we administer Acyclovir 800 mg five
times daily for 5 to 7 days in case of a herpes history, in
any case at least for the time until the skin surface is
closed again, i.e. on the average for 5 days. Patients
without a herpes infection history are given 3 x 400 mg
Acyclovir for the above mentioned time period.
Postoperatively
Postoperatively all patients are given tetracycline for 5
to 7 days to prevent infections. Here, we also have to
check if the patient is allergic to this medication.
Locally we use the Silon foil (Fig. 54.28) to cover all
laser treated areas. The foil adheres to the open skin and
it supports the regeneration of the new skin surface. It
also alleviates the burning sensation. On the areas which
cannot be covered by the foil we use vaseline or eye
vaseline in order to lubricate and protect the skin.
Additionally we prescribe an antibiotic and virostatic
ointment (Acyclovir) 3 times a day. When the skin surface
closes the foil does not adhere to it any more. After
removal of the foil the healing accelerates rapidly and
the patients subjective feeling is much better. Intensive
skin care is necessary during this time. The skin should
not be rubbed under any circumstance in order to avoid
a damage of the freshly healing, thin, new epidermis.
Depending on the type of the skin, the reactive skin
redness can persist up to 3 month with a decreasing
tendency. An intensive sun protection of SPF Nr.60 has
to be used for 6 month.

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Fig. 54.29: A 58-year-old femaledirectly after full face


laser skin resurfacing, covered with Silon foil

Fig. 54.30B: One week after CO2 laser skin resurfacing of


perioral, nasolabial and chin area using CPG 250-300 mJ/
pulse 5-6 passes, density 5

COMPLICATIONS
In the following section, we show some complications,
which we had and present the corresponding
photographs.
Again a photo documentation in all cases is very
important and necessary especially in cases of complications.
Hyperpigmentation
This can occur

Fig. 54.30C: Same woman with hyperpigmentation one


month after perioral resurfacing

Fig. 54.30A: Perioral rhytides and solar damage in a


61-year-old womanpreoperatively

Fig. 54.30D: After improvement by treatment with 4%


hydroquinone cream 2 weeks later

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584 Section VI: Miscellaneous


Erythema
This can occur

Fig. 54.31C: Blepharochalasis and periorbital wrinkles


Fig. 54.31A: Blepharochalasis and periorbital wrinkles

Fig. 54.31B: Same patientsevere erythema one week after


upper eyelid blepharoplasty with lower, upper lid, temple and
forehead skin resurfacing

Fig. 54.31D: Same patientsevere erythema one week after


upper eyelid blepharoplasty with lower, upper lid, temple and
forehead skin resurfacing

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Chapter 54: Plastic Surgery and Laser Treatment in Ophthalmology 585


Wound Complication

Fig. 54.32A: A 50-year-old female with


blepharochalasis preoperatively

Fig. 54.32B: One week after surgical procedure without skin


resurfacing, but the cut done by the CO2 laser (cutting mode).
Notice the injury inflicted by the patient with a hairbrush after
suture removal

Fig. 54.32C: One month after retreatment

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586 Section VI: Miscellaneous

55

Sterilization, Disinfection and


Antiseptics in OphthalmologyAn Update
Ashok Garg

PHYSICAL METHODS
CHEMICAL METHODS
SOAKING IN LIQUID
CHEMICALS
AIDS AND DISINFECTION IN
RELATION TO OPHTHALMOLOGY

Sterilization is defined as the process by which an article, surface or medium


is freed of all micro-organisms either in vegetative or spore state.
Disinfection is defined as destruction of all pathogenic organisms or
organisms capable of giving rise to infection.
Chemical disinfectants which can safely be applied to skin or mucous
membrane surfaces and are used to prevent infection by inhibiting the
growth of bacteria are called antiseptics. Bactericidal agents are those which
are able to kill bacteria.
Bacteriostatic agents are those which only prevent the multiplication of
bacteria which may remain alive. A particular chemical may be bactericidal
or bacteriostatic at different concentrations.
Sterilization methods depend on the purpose for which sterilization is
carried out, the material which has to be sterilized and the nature of microorganisms that are to be removed or destroyed. The most important factor
in decision making is to recognise that the methods of sterilization and
disinfection chosen must be appropriate to the individual situation, in terms
of cost and availability as well in terms of clinical needs. Re-evaluation is
necessary from time to time because, inspite of most stringent following of
rules and safest of practice, complications still occur, sometimes to the
deteriment of patient care and staff safety. Various methods of sterilization
and disinfection used in ophthalmology are as follows.
PHYSICAL METHODS
1.
2.
3.
4.

Dry heat
Moist heat
Filtration
Ionising radiation.

Dry Heat
Flaming
Inoculating wires, loops, points of forceps and searing spatulas may be
held in bunsen flame till they become red hot for sterilizing them.
Incineration
This method is used for rapidly destroying materials such as soiled dressing,
waste and animal caracases.
Hot Air Oven
This is one of the most widely used method for sterilization by dry heat in
ophthalmology. These fan-assisted ovens sterilize by dry heat and are often

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Sterilization

High level
disinfection

Sterilization

Ionizing
irradiation

Boiling

Ethylene
oxide
C2 H4 O

According to Bacteria
manufactur- Spores
ers
Viruses
Fungi

Bacteria
Spores
Viruses
Fungi
Bacteria
Viruses
Fungi

Bacteria
Spores
Viruses
Fungi

Bacteria
Spores
Viruses
Fungi

Bacteria
Spores
Viruses
Fungi

Bacteria
Spores
Viruses
Fungi

Kills

According to
manufacturers

Minimum of
10 minutes

2 hour cycle

Sterilization

20 minutes
cycle

Hot air
ovens

Sterilization

Little
Sister
autoclave

Approx 45
minutes
Follow manufacturers
instructions

Minimum of
15 minutes
Follow manufacturers
instructions

Sterilization

General
autoclave

Time

Portable
Sterilization
autoclave/
Domestic
pressure
cooker

Achieves

Method

Power source

Electric
(single phase)
Gas
Kerosene
Paraffin
Charcoal
Wood
Electric with
C2H4O gas cartridges

Gamma rays

Electric
(single phase)
Gas
Kerosene
Paraffin
Charcoal
Wood
Electric
(single phase)

Electric
(single phase)

Difficult to obtain spare Electric (single


parts in developing
or three phase)
countries
Kerosene
Paraffin

Disadvantages/
Cautions

High running cost

Difficult to obtain spare


parts in developing
countries
No drying cycle
Sensitive to voltage
fluctuations
Low running cost
Drying cycle unreliable
Quick and efficient
Sensitive to voltage
Suitable for mobile units
fluctuations

Spare parts usually


Relatively small

readily available
Various manufacturers
Minimal maintenance
whose instructions

must be followed

Drying cycle
Expensive

Minimal maintenance
Slow
Instruments get
extremely hot and cannot be used immediately
Must not be used in
confined space
Bulk quantities
Usually only available
Suitable for delicate items commercially and used
and items which must be
by large manufacturing
kept dry and not soaked
companies
Low running cost
Does not kill spores

Quick and efficient


Blunts scissors and
Easy to teach
knives

Suitable for all situa Causes rusting of

tions
instruments

Minimal maintenance

Readily available

Bulk quantities
Very expensive

Suitable for delicate


Dangerous-explosive
items and items which
Carcinogenic
must be kept dry and
Only suitable for large
not soaked
tertiary centres with
appropriate facilities

Low running cost


Minimal maintenance
Suitable for busy unit
Drying cycle

Quick and efficient


Small-bench top size
Suitable for busy unit

Advantages

Table 55.1: Sterilization and disinfection methods


Min.
Temp.

All metal instruments 121C


Drapes
Gowns
Dressings
Toughened plastic
Glass

Needles
Syringes
Sutures
Toughened plastic
Heavy metal
instruments
Plastic
Glass
Sutures
Needles
Plastic eye shields
Ophthalmic instruments and probes
Delicate tubing

Contd...

Varies
with
type of
equipment
used

100C

All metal instruments 180C


Toughened plastic
Glass

All metal instruments 121C


Drapes
Gowns
Dressings
Toughened plastic
Glass
All metal instru134C
ments
Toughened plastic
Glass

Suitable for

Chapter 55: Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update


587

ophthalmologyebooks.com
Disinfection

Disinfection

Chlorhexidine

Povidone
iodine

10 minutes

Note The

quantity used
for soaking
must be
changed daily
10 minutes

Note The

quantity used
for soaking
must be
changed daily
10 minutes

Note The

quantity used
for soaking

must be
changed daily
Low cost
Readily available

Bacteria Low cost


Spores
Readily available
Fungi
Versatile
Viruses (see
exceptions*)

Bacteria
Spores
Fungi

Low running costs


Suitable for delicate
items susceptible to
rust
A cabinet can hold a
large quantity of instruments
Formalin tablets usually
readily available
Becoming more readily
available

Advantages

Disadvantages/
Cautions

Power source

Stains fabric and surfaces


Discolours instruments
Solution is darkdifficult to see items
in soak
Irritant to skin
Does not kill entero or adeno virus*

Evaporates
Does not kill viruses
Blunts scissors and knives

Plastic
Rubber
Metal instruments
Wiping Schiotz tonometer
plate and applanation prism tip

Indirect ophthalmoscope
lenses
Applanation prism tip only
may sit in solution

All metal instruments


Wiping Schiotz tonometer
plate and applanation prism
tip
Indirect ophthalmoscope
lenses

All metal instruments


Sutures
Blades

*Room
temperature
20C
Well
ventilated

Min.
Temp.

All metal instruments


Airways and endo-tracheal
tubes
Plastic
Glass

All metal instruments


Toughened plastic
Glass
Delicate
Tubing

Suitable for

Airtight containers
Electric (single
required
phase) if an old
Irritant to skin, eyes
refrigerator is
and if inhaled
adapted as a
Gloves and eye proteccabinet

tion advisable

Items must be rinsed in


sterile water before use
Slow
Bacteria
Relatively expensive

Spores
Irritant to skin, eyes

Viruses
and if inhaled
Fungi
Gloves and eye protec
tion advisable

May leave greasy residue


Items must be rinsed
and lumens irrigated
thoroughly before use
Bacteria Low cost
Highly inflammable

Spores
Readily available
Corrosivedo not leave metal instruments
Viruses
Good for use on indirect
soaking longer than 10 minutes
(see excep- ophthalmoscope lens Tonometry items must be rinsed and wiped
*
es as evaporation
dry before use

tions )
avoids smearing
Evaporates
Does not kill entero and adeno viruses*
Bacteria Becoming more readily Highly volatile and corrosivedo not use
Spores
available
metal container to soak items
Viruses
Reasonable cost
Bleach

Applanation prisms must be rinsed and


wiped dry before use

Bacteria
Spores
Viruses
Fungi

Kills

10 minutes

Note The

quantity used
for soaking
must be
changed daily

Follow manufacturers
instructionsseveral trade
names now
available

12 hours

Time

Authors: Sue Stevens and Ingrid Cox, First published in Journal of Community Eye Health, Volume 9, issue no. 19, 36-41, 1996.
[Courtesy: DANPCB (Danish Assistance to the National Programme for control of Blindness)] Indian Supplement, New Delhi.

Disinfection

Sodium
Hypochlorite

Sterilization
in 10 hours
Disinfection
in 10 minutes

Glutaraldehyde
2%

Disinfection

Sterilization

Formalin

Isopropyl
Alcohol
70%

Achieves

Method

Table 55.1 Contd...

588 Section VI: Miscellaneous

Chapter 55: Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update

Table 55.2: Sterilization methods in ocular surgery

Sterilization methods
Linen (gowns, caps, masks, drapes)
Autoclaving
Glassware (e.g. syringes)
Hot air oven
(Dry heat), ETO
Metal instrument:
Moisture labile (sharp instruments)
Dry heat/ETO
(Vannas scissors/keratome)
Moisture resistant
Autoclaving/ETO
Plastic instruments (Components)
ETO
Intraocular implants
ETO
Sutures (including monofilament nylon)
Can be autoclaved
Diathermy/Cautery electrodes
Autoclaving
Endoilluminators/Probes
ETO
Lenses (Indirect/Optical)
Chemical disinfection
Silicone buckles/sponges
Autoclaving
Silicone oil
Hot air oven
Perfluorocarbon liquids
ETO/Millipore filter
(0.2 )

Recommended temperature, pressure and duration


Autoclave
Flash autoclave
Hot air oven
ETO
Cidex

121C
134C
150C

15-30 lb psi

OT sterilization
Method 1
Wash theatre with copious amount
of water.
Fumigate with formalin vapour (30
ml of 40% formalin dissolved in 90
ml of clean water for 1000 cu. ft)
Keep room closed for 6 hours.
Carbolize with 2 percent carbolic
acid (takes about 24 hours for the
pungent smell of formalin and
carbolic acid to dissipate).
Method 2
Dissolve 325 ml of aldekol (6%
formaldehyde + 6% glutaraldehyde
+ 5% benzalconium chloride) in 150
ml of water. Spray as aerosol for 30
min.
Close room for 2 hours.
Allow fumes to clear (turn on
exhaust/air conditioning)
(Takes only about 3 hours to sterilize
the OT).

45 min
20 min
2 hours

55 lb psi
Bactericidal 10-30 min
Sporicidal 3-10 hrs

Sterile technique: principles


Keep microorganism load to an irreducible mini Gowns are considered sterile only from waist to
mum if they cannot be fully eradicated.
shoulder in front and upto the sleeves
If there is any doubt regarding sterility of any
Keep nonsterile personnel or visitors to a minimum.
article, consider it to be unsterile.
Only sterile personnel should touch sterile articles. Dont
Sterile persons should avoid leaning over an un rush through while scrubbing.
sterile area, while nonsterile persons should
wear same footwear from an unrestricted area to
avoid reaching over a sterile field.
a restricted area.
Tables are sterile only at table level.
let a mask hang loose around the neck and reuse
The edge of anything that encloses sterile contents
the same.
is not considered sterile.
wear a cap that does not fully cover the scalp hair
Sterile persons should keep well within the sterile
and a mask that does not snugly cover the nose.
area; nonsterile persons should keep away from
move about with hands folded or within gown
the sterile area.
pockets.
Moisture is a potential source of contamination;
throw around soiled linen and unsterile covers.
so avoid using moisture soaked linen packages.

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589

590 Section VI: Miscellaneous


used in larger and central medical centres. The sterilizing
time is 2 hours but complete cycle is 4 hours. Hot air
ovens are useful for drying washed instruments. For
sterilization static temperature of 160oc for one hour is
used.
It can be used to sterilize
Glassware
Sharp instruments
Forceps, scissors, scalpels and all glass syringes.
Swabs, fats, grease etc.
Rubber materials should not be sterilized as they will
not stand this high temperature. For sharp instruments
sterilization time is 2 hours at static 150oc (Control by
thermostat) is recommended to prevent blunting. The
oven must be allowed to cool slowly for about 2 hours
the door is opened.

Temperature above 100oC (Autoclaving) The principal


of autoclave is that when pressure inside a closed vessel
increases, the temperature at which water boils and that
of steam it forms also increases. Saturated steam has great
penetrative power. The temperature setting and
sterilizing time is dependant on the type of autoclave
and articles being treated. The condensed water insures
moist condition for killing the microbe present.
Sterilization by steam under pressure is carried out at
temperature between 108oc-147oc.
By using the appropriate time and temperature, a
variety of materials such as dressings, instruments,
Laboratory ware, media, pharmacological products and
OT clothes can be sterilized. Heat is conducted through
the walls of sealed containers until the temperature of
the material inside is in equilibrium with the steam
outside.

Moist Heat
Temperature below

Table 55.3: Autoclave sterilization

100oC

The temperature employed is either 60oc for 30 minutes


or 72oc for 15-20 minutes (Flash method) followed by
rapid cooling. By this process all non-sporing pathogens
such as mycobacteria brucella and salmonella are
destroyed.
Temperature at 100oC
Boiling High level disinfection is achieved by boiling.
Vegetative bacteria are killed almost immediately at 90100oc but sporing bacteria require considerable period
of boiling. Boiling is not recommended for sterilization
of instruments used for surgical procedure. Nothing short
of autoclaving at high pressure can destroy spores and
ensure sterilization.
Instruments must be completely immersed in already
boiling water in a container preferably with a lid. Boil at
100oc for at least 10-20 minutes.
Although boiling is the most readily available method
it has the distinct disadvantage of blunting instruments.
Instruments must not be placed on top of each other. A
silicon mat on the bottom of container will help to protect
the instruments. Silicone tubing will also protect the tips
of fine instruments.
Boiling kills bacteria, fungi, viruses including the
AIDS virus but not spores. Chelate forceps are used to
remove articles from boiler.
Steaming at 100oC An atmosphere of steam is used to
sterilize culture media which may decompose if subjected
to higher temperature.

Steam pressure
Lb/in 2
(min.)
0
10
15
30

Temperature
in 0oc

Holding time for


sterilization

100
115
121
134

45
15
3

The complete cycle can take up to 45 minutes which


includes drying time. Articles can be placed in metal
sterilizing drums with holes to allow for steam penetration.
If dampness of drapes and gowns, etc. is noted when
they are removed from the autoclaves they must not be
used as this indicates a faulty cycle and sterility has not
been achieved.
Little sister autoclaves are also available for sterilization using steam under pressure. These autocalves are
small enough to place on a work surface, bench top, shelf
or trolly and are specially useful for resterilizing
instruments during operating sessions, e.g. if contamination occurs or for subsequent cases.
Portable autoclaves are also useful in theaters for
sterilizing sets of instruments. They are very quick,
efficient and popular in rural and camp areas.
Precautions during Autoclaving
Because of varying sterilization times for different
items it is recommended that similar items are placed
together.

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Chapter 55: Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update


Instruments must not be left in an autoclave for longer
than necessary as it will cause corrosion.
The steam must penetrate the contents so autoclave
must not be packed tightly.
Instruments tips should be protected with silicone
tubing.
Sterilizing drums must open during the cycle and
closed on completion.
Porous load items must be double wrapped.
Spare parts shall always be available.
Filtration
This method is used to sterilize heat labile liquids. This
is useful for antibiotic solutions, sera, carbohydrate
solutions, etc.
Various types of filter used are
Berkefeld earthenware candles.
Asbestos disc filters
Sintered glass filters
Colloiden or membrane filters
Ionising Radiation
This method of sterilization is used commercially by large
companies specially for syringes, needles and suture
material. Nonionising and ionising radiations are being
widely used for mass sterilization. Infra-red and ultraviolet rays are of nonionising type while gamma ray and
high energy electrons are of high energy ionising type.
Gamma radiation is used for sterilization of most
plastics, syringes, swabs, culture plates, various types of
rubber products, card board, fabric metal, foils, etc.
CHEMICAL METHODS
It includes Gas
Vapour
Soaking in liquid chemicals
There are a large number of chemical agents available
for use as antiseptics and disinfectants. Their main mode
of action is:
Proteins coagulation
Disruption of cell membrane
Removal of free sulphydryl groups which are
essential for functioning of the cell.
Substrate competition
The factors which determine the potency of disinfectants are:
Concentration of substance
Time of action
pH of medium
Temperature
Nature of the organisms
Presence of extraneous material.

591

Ethylene Oxide (C2H4O)


It is a colorless liquid with a boiling point of 10.7oc and
at normal temperature and pressure it is very penetrating
gas with a sweet smell. It is highly inflammable and in
concentration greater than 3 percent in air, it is highly
explosive. Its explosive tendency is eliminated by mixing
it with inert gases such as CO2 or nitrogen in 10 percent
concentration.
It is lethal to micro-organisms due to its power of
alkylating the amino, carboxyl, hydroxyl and sulphadryl
group in the protein molecule. In addition it reacts with
DNA and RNA.
It diffuses through many types of porous materials
and readily penetrates the plastics. It is specially used
for sterilizing
Sutures
Intraocular lenses
Clothing
Glassware
Plastic products
This gas is effective for almost all instruments and
materials and specially for those which do not tolerate
heat sterilization or soaking in chemicals. It is used for
eye shields, ophthalmic probes, tubing and vitrectomy
equipment. The sterilizing cycle is lengthy (12 hours) and
it is enormously expensive to set up and run.
All micro-organisms are destroyed including the
AIDS virus.
Formalin
Formaldehyde (Formalin) in aqueous solution is markedly bactericidal and sporicidal and also has an effect
on viruses. Formalin is mainly used for sterilizing (Fumigating) operation theater rooms. Ten percent formalin is
used to sterilize clean metal instruments. Formalin gas
is used for sterilizing heat sensitive catheters, sick room
wards and laboratories. Under properly controlled
conditions, clothing, bedding, furniture, cryoprobe,
various parts of operating microscopes are satisfactorily
disinfected. This gas is irritant to the eyes and skin and
precautions must be taken in handling. It is known
carcinogenic. Eye protection if available should be worn.
Precautions when using Formalin

Instruments must be dismantled where possible.


Requires 7 gram of formalin per cubic meter
Room temperature must be kept at 20oc.
Instruments must be rinsed in sterile water before use.
Good practice achieves destruction of all microorganisms including the AIDS virus.

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592 Section VI: Miscellaneous


SOAKING IN LIQUID CHEMICALS
This method is used when alternative methods are
unavailable or known to damage instruments and other
materials. On long-term use it can cause staining,
corrosion and blunting of instruments. Soaked instruments should be rinsed under a stream of sterile water
before being used. It is not advisable to use chemical
soaking for syringes, needles and other skin cutting
instruments.
Here I am discussing commonly used liquids in
ophthalmic practice.
Glutaraldehyde
Two percent glutaraldehyde is used when heat sterilization is impractical and other methods are unavailable.
It has an action similar to formaldehyde. It is less toxic
and irritant to the eyes and skin. It has no deleterious
effect on lenses of instruments, rubber anesthetic tubes,
plastic wares, polythene tubine etc.
Items must be totally immersed with no air bubbles
present in a covered container for a minimum of 10
minutes which achieves disinfection. Sterilization take
10 hours. Thorough rinsing under stream of sterile water
is important. Because glutaraldehyde is a corrosive
chemical and severe irritant if its vapour is inhaled or it
comes into contact with skin. The area should be well
ventilated. Corneal edema has been reported in patients
following the use of glutaraldehyde to sterile cannulae
used during cataract surgery. These cannulae and all
lumens should be thoroughly irrigated and rinsed.
Shelf life (once activated) is 14-28 days. It disinfects
in just 10 minutes killing both gram-positive and gramnegative micro-organisms and viruses including HIV and
hepatitis B. It sterilizes in 4 hours killing all forms of
microbial life including resistant bacterial spoks. It is
highly resistant to inactivation by organic soil and is
compatible with common surgical materials including
carbon, steel, copper, brass, nickel, chrome plate and
aluminium.

Isopropyl alcohol swabs are commercially available


for use as skin disinfectant when soaking, it is a rapid
method taking only 2 minutes in a covered container.
The quantity used for soaking must be changed daily.
Extreme caution should be taken as this agent is highly
inflammable. It kills bacteria, spores some viruses
including AIDS virus but not entero or adeno viruses or
fungi.
Sodium Hypochlorite
It is readily available commercially. It is prepared by
adding 500 ml of sodium hypochlorite 1 percent to 1 litre
of boiled water. This makes a total quantity of 1.5 litres.
Shelf Life is 7-14 days. The quantity used for soaking
must be changed daily. Use plastic or glass containers
only metal containers for shelf or soaking storage are not
suitable as sodium hypochlorite is a bleach, highly
volatile and corrosive. It should not be used for disinfecting Schiotz tonometer.
Items must be completely immersed in a covered
container for a minimum of 10 minutes and rinsed under
a stream of sterile water before use.
Sodium hypochlorite kills bacterias, spores and
viruses including the AIDS virus but not fungi.
Biguanides (Polyhexanide and Chlorhexidine)
The biguanides were first synthesized in 1940. Chlorhexidine was first developed in 1950 and polyhexa methylene
biguanide (polyhexanide), PHMB was developed in
1960s.
Commercial preparations of PHMB may be composed
of a mixture of various lengths of polymer chains. The

Isopropyl Alcohol
Isopropyl alcohol 70 percent and ethyl alcohol (ethanol)
are commonly used as skin antiseptics. These act by
denaturing bacterial protein. Methyl alcohol is also
effective against fungal spores.
Isopropyl alcohol 70 percent is available at low cost
and ready to use for disinfecting indirect ophthalmoscope
lenses and metal instruments including sharps. It can also
be used to disinfect the plunger and plate of a Schiotz
tonometer and the tip of applanation prisms.

Fig. 55.1: Chemical structures of chlorhexidine


and polyhexanide

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Chapter 55: Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update


degree of polymerization may relate to microbicidal
activity.
The optimal anti-amebic concentration for ocular use
has not been determined yet 0.02 percent concentration
is commonly used. A 0.00005 percent concentration of
PHMB in contact lens disinfectant (ReNu) is present and
that is too low concentration.
Chlorhexidine is commercially available as a skin
disinfectant in a detergent or alcohol and for use as a
mucosal rinse. A concentration of 0.02 percent in isotonic
saline or artificial tears has been used successfully in
treating Acanthamoeba keratitis.
Biguanide disinfectants interrupt microbial DNA
function by complexing with intracellular phosphated
molecules such as adenosine triphosphate and nucleic
acids.
It is suitable for disinfecting plastic, rubber and metal
instruments but can cause blunting of scissors and knives.
Items shall be completely immersed in a covered
container for a minimum of 10 minutes and they must
be rinsed under a stream of sterile water before use.
Four percent chlorhexidine has broad spectrum kill.
It is effective in presence of organic matter. It has reduced
surfactant content so no damage to skin. No-animal fat
emollients keeps the skin soft and protects it from
detergents. It is effective against bacteria, spores and
fungi but does not kill viruses.
Povidone Iodine (Halogens)
Iodine is aqueous and alcoholic solutions has been used
as skin disinfectant. It is an active bactericidal agent with
a moderate activity against spores. Chlorine and its
compounds have been used as disinfectants. Commercially it is available as 5 percent sterile ophthalmic prep
solution. It contains 5 percent povidone iodine (0.5%
available iodine) stabilized by glycerin.
It is indicated in the eye for prepping of the periocular
region (lids, brow and cheek) and irrigation of the ocular
surfaces (cornea, conjunctiva and palpebral fornices)
prior to any ocular surgery.
This topical solution is an isotonically balanced preoperative microbicidal solution that can safely be used
directly on the cornea and conjunctival cul-de-sac as well
as on periocular region. This solution is strictly used for
external use only. It is not used for intraocular injection
or irrigation.
Salient features of this topical solution are:
Assure asepsis in less than 60 seconds and stained
skin is virtually impossible to reinfect for at least
1 hour.
It is nontoxic, has excellent skin tolerance and does
not burn the skin.

593

It has broad spectrum of action sporicidal, bactericidal, antimycotic, viricidal and protozocidal.
It decreases the incidence of postoperative endophthalmitis.
How to Use this Solution
First squeeze the entire content of bottle into a sterile
prep cup.
Saturate sterile cotton tipped applicator or sponge to
prep lashes and lid margins using one or more
applicatords per lid. Repeat once.
Saturate sterile prep sponge to prep lids, brow and
cheek in circular ever expanding fashion until the
entire field is covered. Repeat prep three times.
Irrigate the cornea, conjunctiva and palpebral fornices
with this solution using a sterile disposable syringe.
After the prepping solution has been left in contact
for two minutes. Sterile saline solution in a syringe
should be used to flush the residual prepping solution
from the cornea, conjunctiva and palpebral fornices.
Topical solution is safe and effective for use and occasional local sensitivity reaction has been reported.
Povidone-iodine is effective against bacteria,
spores, fungi, some viruses including AIDS virus but
not entero or adenovirus.
It is also available commercially as following
i. Betadine antiseptic solution 10 percent for prepping
skin sites.
ii. Betadine surgical scrub 7.5 percenta soap used
for hand scrubbing.
Phenols
Phenols cause cell membrane damage causing lysis and
are powerful microbial substances lysol and cresols are
good general disinfectants.
Acetone
Acetone is one of the most commonly used potent
bactericidal agent. It is used for sterilization of sharp
cutting instruments. It has wide action against grampositive and gram-negative microorganisms.
Cetrimide
It is used as 10 percent cetrimide solution (in 1:10
dilution) for disinfection of hands in routine OPD
procedure in ophthalmology.
Betapropiolactone (BPL)
It is condensed product of Ketane and formaldehyde with
a boiling point of 163oc. It has rapid biocidal action. 0.2

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594 Section VI: Miscellaneous


percent BPL solution is used for sterilization of biological
products. It is capable of killing all micro-organisms and
is very active against viruses.
Alcoholic Rub-in Hand Disinfectant
It is a liquid disinfectant containing
(Each 100 ml contains)
45.0 g
2 - propanol
1 - propanol
30.0 g
Ethyl hexadecyl dimethyl
0.2 g
Ammonium ethylsulfate
(Skin protection substance).
It is broad spectrum bactericidal, fungicidal and
viricidal. It is also effective against AIDS virus and
hepatitis B virus.
It is entirely new concept in hand disinfection, completely eliminating the need for frequent washing. The
liquid is rubbed on hands which penetrates deep into
the skin forming an inner protective film that does not
affect sweating functions while destroying transient
pathogens and resident skin flora. It is gentle on skin,
acts instantaneously and provides optimally sustained
activity without requiring a soap scrub beforehand. It
penetrates the crypts of the skin into the lower lying
horny layers and there forms a defensive barrier against
microbes with the result germ count on the hands remains
low for several hours.
Alcoholic rubs contain specific quaternary ammonium compounds which are related to its broad spectrum
of action for disinfection of hands in ocular surgery.
Alcoholic rubs assure asepsis, protection of natural
skin film and skin lipids and prevents spread of nosocomial infections. Ideally rub 3 ml of alcoholic rub
disinfectant in one push well over hands and nail grooves
for 30 seconds. It is used with a specially designed elbow
dispenser to prevent contamination. This pump is calibrated to dispense the exact dosage required. Such 3
consecutive pushes are taken and rub into hands, grooves
and up to elbows for 5 minutes. It is nonsticky and give
comfortable feel and total protection in perforated gloves
also.
Commercially it is available as 100 ml and 500 ml
bottle packs.

gistic effect on each other. 2-Propanol is a potent broad


spectrum microbicidal serves as the glide path for
Benzalkonium chloride which has residual effect,
inhibiting intraoperative bacterial growth. It has potent
action against microbes, viruses including HIV and
hepatitis B, fungi bacteria.
It has rapid onset and good residual effect and deep
penetration inhibits intraoperative bacterial growth in
the incision folds of the skin.
It is mainly used in ophthalmology for periocular
prep preparation. Cutasept is painted in operative and
perioperative area for 2 minutes with a sterile swab
dipped in the solution. Allow the area to dry or about 30
seconds, repaint the entire area as before and allow to
dry. Cover the disinfected area with sterile eyesheet
leaving the incision site open.
Commercially it is available as 100 ml and 500 ml
bottle packs.
Concentrated Cold Sterilizer
It is an ideal solution for sterilization of thermolabile and
thermostable instruments like metals, glass, stainless
steel, porcelain, plastic, ceramics and rubber. Due to high
degree of compatibility of this solution with material
surfaces, it can be used for disinfection/sterilization of
all kinds of precleaned instruments.
Each 100 g contains
Glutaraldehyde
7g
1,6 Dihydroxy 2-5
8.2 g
Dioxahexane
Polymethyl urea derivatives
17.6 g
Rust inhibitors
Usually 5 percent and 10 percent dilution solutions
are used. Five percent solution gives disinfection within
one hour while 10 percent solution provides disinfection
in 15 minutes. For total sterilization immerse the items
in 10 percent solution for 5 hours.
This solution has potent bactericidal, fungicidal, sporicidal and viricidal activity. It is effective against AIDS
virus and hepatitis-B virus. This solution has long shelf
life and rapid action suitable for emergency disinfection.
Commercially it is available as 250 ml and 500 ml
bottle packs.

Cutasept
It is an ideal two component antiseptic for skin.
Each 10 g contains
63 g
2- Propanol
Benzalkonium cl
0.025 g
It is an ideal surgical antiseptic which serves to clean
the skin as disinfect it. Its two components have a syner-

Bacillocid
It is specially used as conc. surface and environmental
disinfectant with cleansers. It is recommended in 2
percent and 0.5 percent dilution specially for disinfection/fumigation of operation theaters. It has broad
spectrum of activity and is a bactericidal MRSA,

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Chapter 55: Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update


sporicidal, fungicidal, tuberculocidal, viricidal including
hepatitis B and HIV virus. As it contains corrosion
inhibitors so it is safe for all surfaces. It is effective within
30-60 minutes. Commercially it is available as 100 ml and
500 ml packs.
Bacillol 25
It is aldehyde free, quick acting alcoholic spray surface
disinfectant. Chemically each 100 gms of the spray
contains:
10 gm
Ethanol
2-Propanol
9 gm
1-Propanol
6 gm and corrosion inhibitors.
It is recommended for disinfection of tonometers,
operating microscopes, scan probes and operation
theaters in between surgeries. Bacillol is effective against
all type of bacteria, fungi, viruses including HIV and rota
virus.
Contact time for the spray on the surface is 25 seconds
to 5 minutes. Commercially it is available as 250 ml bottle
with spray.
Baktolin 5.5
It is complete and effective hygenic nonsoap wash lotion
which does not disturb the natural pH of the skin. It is
specially designed for frequent hand washes.
Chemically it containssodium laureth sulfate,
sodium chloride, PEG-7/glyceryl cocoate, cocamidopropyl betaine, glycerin, Disodium Laureth, Sulfosuccinate, PEG-120/Methyl glucose dioleate, Sodium
benzoate, Sodium Salicyclate, Propylene glycol, Parfum
and Sodium Citrate.
These combinations of ingradients produce a germ
inhibiting effect (RF.3 log).
Baktolin has same pH as that of skin (no change in
natural balance of skin pH) so the skin remains smooth
and well nourished even after prolonged use (unlike use
of soaps which may strip the skin of its protective lipid
layer and deplete the acid mantle and skin may become
dry and cracked and more susceptible to infections).
Commercially it is available as 500 ml bottle with
dispenser.
Recommended dosage for each hand wash is 0.5 ml.
AIDS AND DISINFECTION IN
RELATION TO OPHTHALMOLOGY
Recently, the media worldwide has devoted considerable
space to the problem of AIDS leading to insecurity and
panic in persons outside the group of those at risk. Fear

595

of AIDS spread has risen specially among peoples


employed in health care profession Doctors, dentists,
nurses and laboratory personnel. Every health
professional is prospectively subjected to contact with
AIDS patietns and thus with carriers of HIV virus.
Classified as a Lipophilic retrovirus, the HIV virus may
be considered labile. Outside the host organism, it quickly
loses its activity. Due to its sensitivity the virus is very
quickly destroyed by virucidal disinfectants outside the
body. Twenty-five percent ehyl alcohol, 1 percent glutaraldehyde and 0.2 percent sodium hypochlorite are
adequate disinfectants for instruments and contaminated
surfaces. These findings have led to development of
preparations containing alcohol or aldehyde and
aldehyde derivatives are well suited for disinfection in
AIDS prophylaxis.
The presence of HIV particles in tear fluid, on the
conjunctival surface or in the contact lenses of patients
has made it necessary to establish better guide lines for
decontamination of instruments during ophthalmological procedures. Following decontamination procedures should be followed during ophthalmological
procedure.
a. The applanation tonometer prisms are cleaned by
wiping them gently with cotton, moistened with
isopropanol. After cleaning tonometer is wiped dry.
After each working day the prisms are kept dry
in the holder after rinsing them in 0.15 percent
glutaraldehyde solution for 5 minutes.
b. The Schiotz tonometer is disinfected in the autoclaves
using ethylene oxide. Alternative method is to
immerse in isopropyl alcohol for 5 minutes or in 1:10
dilution of sodium hypochlorite for 5-10 minutes or
1:1000 merthiolate wiped dry and then emerged in
pure water, carefully rinsed and again wiped dry. All
present disinfection solutions known to be effective
against HIV are toxic to the cornea. They are easily
retained by Schiotz tonometer after immersion,
autoclave disinfection is the measure of choice.
c. Goldmans and other contact lenses and gonioscopes
are washed in running water and then gently wiped
with cotton moistened with 70 percent isopropyl
alcohol or 3 percent hydrogen peroxide. Following
this the lens is again rinsed with water and wiped
dry.
Neither tonometers nor contact lenses can be
emerged in isopropanol without serious damage to
the instruments.
d. Gloves are not used in routine examinations but if
the patient is known to be an HIV carrier and
whenever the skin of the investigator is not intact the
use of gloves is recommended. When an HIV positive

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596 Section VI: Miscellaneous


Table 55.4: Disinfection process vs items
Item group
classification

Process classification

1. Critical
(Enters sterile tissue)
2. Semi-critical
(Touches mucous
membrane)
3. Non-critical
(Touches intact skin)

Sterilization by sporicidal
chemical
High level disinfection by
sporicidal chemical
Intermediate or low level
disinfection

Table 55.5: Disinfectant classification and


recommended concentration
Recommended concentration
a. High Level
Glutaraldehyde
Formaldehyde
Hydrogen peroxide
Demand release chlorine dioxide
b. Intermediate Level
Chlorine 1000 ppm
Phenol
Iodophor
c. Lower level
Alcohol
Sodium Hypochlorite 100 ppm
Phenoli and Iodophoric
germicidal detergent
Quaternary ammonium
compounds

2 percent
6 percent
6 percent
MR
MR
MR
MR
70-90 percent
MR
MR
MR

*MR - Manufacturers recommendations.

patients is examined, use of a face mask during the


examination is also advised. Disinfection of the hands
is the most important step for prevention of infection.
Hands should be disinfected following every cutaneous contact with AIDS patients and contaminated
instruments. The safest, simplest method for skin is
alcoholic rubs. This enables hands to be disinfected
hygienically at any time independent from wash
basin and water faucet.
Suitable disinfectant for HIV prophylaxis contains
45 g 2-propanol, 30 g 1-propanol and 0.2 g mecetronium ethylsulfate (INN), application 3 ml for 1
minute.
e. Instruments that come into direct contact with external surfaces of the eye should be wiped clean and
disinfected by 5-10 minutes exposure to a fresh
solution of 3 percent hydrogen peroxide or a fresh

solution containing 5000 parts per million (mg/l) free


available chlorine1:10 dilution of sodium hypochlorite or 70 percent ethanol or 70 percent isopropanol. The device should be thoroughly rinsed in tap
water and dried before use.
f. Contact lenses used in trial fittings should be disinfected between each fitting by following regimens.
i. Disinfection of soft lenses with a commercially
hydrogen peroxide contact lens disinfecting
system. Alternatively soft lenses can be disinfected
with the standard heat disinfection (78-80oc for
10 minutes).
ii. Rigid gas permeable (RGP) trial fitting lenses can
be disinfected using hydrogen peroxide disinfection system. RGP lenses may warp if they are heat
disinfected.
g. Whenever possible, perform tonometry with Schiotz
tonometer and then sterilize (autoclave or ethylene
oxide) prior to the subsequent use.
h. If it is necessary to perform applanation tonometry,
remove the applanation tonometer prism and wash
it with warm water and a surface cleaner 0.004
percent thimerosal. Protein cleaning is beneficial
before glutaraldehyde treatment which would
denaturate proteins at the tonometer surface.
The clean tonometer prism is then soaked for 10
minutes in 2 percent glutaraldehyde. The tonometer
prism is removed after 10 minutes. Thoroughly rinse the
prism with water and thimerosal until the surface is no
longer slippery. This rinse is extremely important and
should continue till all the disinfectant is removed to
prevent potential ocular damage. When the prism is clean
it can be dried with cotton and replaced in the tonometer
holder.
The decontamination procedures selected for ophthalmological examinations should be estimated to be
effective enough. Spread of infections bacterial and viral
is known through the use of diagnostic ophthalmic equipment like tonometers and Gonioscopes. Spread of adenovirus, HSV, AIDS virus and hepatitis virus is possible.
FURTHER READING
1. Agarwal Amar, Textbook of Ophthalmology, ed.1, New Delhi:
Jaypee Brothers Medical Publishers, 2002.
2. Bartlett JD, Clinical Ocular Pharmacology, ed.4, Boston:
Butterworth-Heinemann,2001
3. Bartlett JD, Ophthalmic Drug Facts, Lippincott William and
Wilkins, 2001.
4. Crick RP, Trimble RB, Textbook of Clinical Ophthalmology,
Hodder and Stoughton, 1986.
5. Duane TD, Clinical Ophthalmology, ed. 4: Butterworth
Heinemann, 1999.

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Chapter 55: Sterilization, Disinfection and Antiseptics in OphthalmologyAn Update


6. Duvall, Ophthalmic Medications and Pharmacology, Slack Inc,
1998.
7. Ellis PP, Ocular Therapeutics and Pharmacology, ed. 7: C.V.
Mosby, 1985.
8. Fechner, Ocular Therapeutics, Slack Inc., 1998.
9. Fraunfelder, Current Ocular Therapy, ed. 5: W.B. Saunders, 2000.
10. Garg Ashok, Current Trends in Ophthalmology, ed. 1, New
Delhi: Jaypee Brothers Medical Publishers, 1997.
11. Garg Ashok, Manual of Ocular Therapeutics, ed. 1, New Delhi:
Jaypee Brothers Medical Publishers, 1996.
12. Garg Ashok, Ready Reckoner of Ocular Therapeutics, ed.1, New
Delhi: 2002.
13. Goodman LS, Gilman A, Pharmacological Basis of Therapeutics,
ed.7, New York : Macmillan, 1985.
14. Haveners, Ocular Pharmacology, ed. 6: C.V. Mosby, 1994.

597

15. Kanski, Clinical Ophthalmology, ed. 4: Butterworth


Heinemann, 1999.
16. Kershner, Ophthalmic Medications and Pharmacology, Slack.
Inc., 1994.
17. Olin BR et al, Drugs Facts and Comparisons: Facts and Comparisons, St. Louis, 1997.
18. Onofrey, The Ocular Therapeutics; Lippincott-William and
Wilkins, 1997.
19. Rhee, The Wills Eye Drug Guide, Lippincott William and
Wilkins, 1998.
20. Steven Podos, Textbook of Ophthalmology, New Delhi : Jaypee
Brothers Medical Publishers, 2001.
21. Zimmerman, Text book of Ocular Pharmacology, Lippincott and
William and Wilkins, 1997.

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Index
A
Aberrations 282
Aberrometer 283
Aberropia 271
Aberropia patients 272
Acritec IOL 56
Age-related macular degeneration 389, 394,
436
advances in management 437
alternate laser techniques 438
antiangiogenic agents 441
feeder vessel therapy 438
photodynamic therapy 439
radiation therapy 441
transpupillary thermotherapy 440
patient education 446
prevention studies 446
primary prevention 445
surgical care 442
AIDS and disinfection 595
Air pump 118, 119
Alternate laser techniques 438
Amblyopia 96
AMPPE 398
Anesthesia 298
Anesthesia for children 5
Anterior lens capsule retention 63
Anti-chamber collapser 46
Anti-inflammatory drugs
corticosteroid 480
administration and dosage 481
betamethasone 482
contraindications 481
dexamethasone 482
fluorometholone 483
hydrocortisone 481
indications 481
loteprednol etabonate 482
loteprednol etabonate 484
rimexolone 482
systemic 485
triamcinolone 482
immunosuppressive agents 494
antibiotic cyclosporin A 495
azathioprine 495
chlorambucil 494
cyclophosphamide 494
ocular drug toxicity 495
selection of patients 494

nonsteroidal antiinflammatory agents 512


non-steroidal anti-inflammatory drugs 486
arachidonic acid 487
chemical structures 487
classification 486
flurbiprofen 491
general local and systemic toxicity 494
indoles 493
indomethacin 493
ketorolac tromethamine 492
mechanism of action 486
ocular indications 490
pharmacokinetics 488
prostaglandin synthesis 487
suprofen 492
systemic 488
topical 488
topical steroidal agents 512
Antiallergy therapy 516
Antiangiogenic agents 441
Antibacterial drugs 461
aminoglycosides 464
amikacin 465
framycetin 466
gentamicin 464
kanamycin 466
netilmycin 465
sisomycin 465
streptomycin 466
tobramycin 465
antimicrobial peptides 470
cecropins 471
defensins 470
megainins 471
beta-lactams
amoxycillin 462
ampicillin 462
benzyl penicillin 462
cephalosporins 462
methicillin 462
penicillins 462
semisynthetic penicillin 462
chloramphenicol 468
cotrimoxazole 478
fluoroquinolones 471
ciprofloxacin 471
levofloxacin 474
lomefloxacin 473
norfloxacin 471

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ofloxacin 472
pefloxacin 472
sparfloxacin 474
imidazole derivatives 478
metronidazoles 478
microlides 468
clarithromycin 470
clindamycin 469
erythromycin 468
roxithromycin 469
spiramycin 469
vancomycin 469
polypeptides
bacitracin 470
polymixin B 470
sulphonamides 467
tetracyclines 466
doxycycline 467
minocycline 467
oxytetracycline 467
Antibacterials 510
Antifungal therapy 515
Antiglaucoma drug 348
adrenergic blocking agents (beta blockers)
360
betaxolol 361
carteolol 362
levobunolol 362
metipranolol 363
timolol maleate 363
alpha-adrenergic agonists
apraclonidine 355
brimonidine tartrate (alphagan) 355
clonidine 358
dapiprazole 358
anticholinesterase agents 352, 353
demecarium bromide 352
echothiophate iodine 354
isoflurophate 354
ocular side effects 354
physostigmine 352
systemic side effects 355
antimetabolites (anti-fibroproliferative
agents) 374
5-fluorouracil (5FU) 374
mitomycin C 375
calcium channel blockers 374
carbonic anhydrase inhibitors 364
acetazolamide 364
brinzolamide 366

600 Advances in Ophthalmology1


dichlorphenamide 365
dorzolamide 365
ethoxazolamide 367
methazolamide 365
cholinergic agents
acetylcholine chloride 349
pilocarpine 350
pilocarpine and epinephrine
combinations 351
pilocarpine and physostigmine
combination 351
daunorubicin 375
future directions 378
miotics 349
prostaglandins 367
bimatoprost (lumigan) 372
latanoprost (xalantan) 367
travoprost (travatan) 373
unoprostone (rescula) 373
recent advances 375
alpha-2 agonists 377
eliprodil 377
L-deprenyl 378
neuroprotective agents 376
NMDA antagonists 377
ocular hypotensive lipids 376
riluzole 377
unoprostone 376
sympathomimetics 358
dipivalyl epinephrine 360
epinephrine 359
the role of neuroregeneration 379
Antiglaucoma therapy 348, 517
Antimicrobial therapy 460
Antiviral therapy
first generation drugs 514
second generation drugs 514
Aphakia 341
Artificial tear inserts 456
Astigmatism 279, 552
contact lens correction 553
Atkinson block 7
Autoclaving 590

B
Bandage contact lens 288
Bird shot retinochoroidopathy 396
Bitoric RGP lens 557
Blepharoplasty and skin resurfacing 575
Blind-years 164, 165

C
Capsular bag opacification 92
Capsular tension ring 66, 67, 70-72
Capsulorhexis 39, 69, 131
ideal 40
Cardiovascular disease 4
Cataract density 20
Cataract extraction 4
Cataract formation 291

Cataract surgery 17, 18, 35, 263


anesthetic techniques 18
evolution of anesthetic techniques 17
evolution of techniques 17
large incision and implantation of rigid
lenses 215
small incision and implantation of
foldable lenses 215
surgical technique 18
ultra small incision and implantation of
rollable lenses 215
Cataract surgery in children 74
indications 77
Cell density 27
Central serous chorioretinopathy 395
Centration 300
Childhood cataract blindness 164
financial burden 164
global perspective 164
management 165
industrialized versus developing
nations 165
surgery
anesthesia method 166
endotracheal intubation and
laryngeal mask airway 166
ketamine anesthesia 166
surgical modalities 166
ECCE, PPC, AV and IOL 167
pars plana approach to PPC and AV
after anterior approach ECCE 169
recommended surgical steps 169
Choroiditis 396
Clear corneal incision 19, 36, 122, 339
Clear corneal phacoemulsification 16
Closure of incision 340
Collagen shield 288
Coloboma ring 72
Combination antibiotics 511
Combined astigmatism 297
Computerized videokeratography 262
Concept of lasers 151
Contact lens care products 527
Contact lens fitting in RK surgery 315
after photorefractive keratectomy 317
choice of RGP trial lenses 317
fitting procedure 315
fitting technique 317
in LASIK surgery 318
before LASIK 319
post-LASIK phase 319
Contact lenses 456
Cornea 261, 279
normal 263
prolate and oblate 279
Corneal barrier 452
Corneal decompensation 27
Corneal edema 92
Corneal shields 456
Corneal topography in phakonit 159
astigmatism 160
surgical technique 159
topographic analysis 160

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Corneal topography machine 262


Corneal warpage 319
Cortical aspiration 37, 70, 125
Cortical clean-up 190
Cortisone subconjunctival injection 301
Cotton pledgets 456
Cryoanalgesia 35, 36
Cystoid macular edema 96

D
Deposits on IOL surface 94
Diabetes mellitus 4, 412
Diabetic retinopathy 413
classifications 414
differential diagnosis 419
management 420
aminoguanidine 428
clinical trials 420
role of aldose reductase inhibitors 428
medical care
non-proliferative 422
proliferative 423
microscopic changes 414
non-proliferative 415
cotton-wool spots 416
diabetic maculopathy 416
hard exudates and retinal edema 416
intraretinal microvascular abnormalities 417
microaneurysms 415
retinal hemorrhages 416
venous caliber abnormalities 417
pathogenesis 413
prognosis 422
proliferative 417
recent advances in management 429
angiotensin converting enzyme (ACE)
inhibitors 430
anticoagulants 430
gene therapy 429
inhibitors of intracellular signaling 430
inhibitors of toxic effects of macular
edema 430
measurement of retinal blood flow 430
medical advances 429
pancreatic and islet transplants 431
prevention of generation of vasoactive
agents 430
protein kinase 430
pyruvate 430
surgical advances 430
triamcinolone 431
use of tPA (tissue plasminogen
activator) 431
vascular endothelial growth factor 429
vitamin E 430
risk factors 418
sex predilection 415
surgical care 425
peripheral cryotherapy 426
vitrectomy 425

Index 601
Disinfective and antiseptic agents 535
Drug delivery system 451
Drug impregnated inserts 452
Dry eyes (keratoconjunctivitis sicca) 543
Dry heat 586
Dye enhanced diode laser photocoagulation
395
Dye-enhanced pediatric cataract surgery 88
Dye-enhanced phacoemulsification
critical steps 188
surgical technique 188
Dye-enhanced posterior capsulorhexis 191
Dystrophia myotonica 4

E
Emmetropization 77
Endocapsular ring 66
Endophthalmitis 92
Endothelial cell analysis 32
Endothelial cell areas 27
Endothelial cell count 27
Endothelial cell difference 33
Endothelial cell protection techniques 30
Endothelial microscope
contact endothelial 26
non-contact endothelial 27
Endothelium evaluation 26
Epikeratophakia 79
Epiretinal membrane removal 409
Equator ring 66
Etiology of subluxated lenses 68
Excimer laser techniques 278
Explanted lenses 248
Extracapsular cataract extraction 16, 263
Eyelid blepharoplasty
laser-assisted lower 570
laser-assisted upper 567

F
Favit 104
advantages 107
complication 106
disadvantage 107
surgical technique 105
Feeder vessel 395
Feeder vessel therapy 438
Filter paper strips 456
Filtration 591
Fitzpatrick table 577
Flaming 586
Fluorescein angiography 419
Foldable IOL 264
Fragmenter 63
Freezing solution 31
Front surface toric RGP lens 557

G
25 gauge IOL forceps 111
Gels 456

Gene therapy 445


General anesthesia 4
complications 5
Gilis-Loyd modified retrobulbar block 9
Glaucoma 95
Glaucoma surgery 331
complications 334
methods 332
Grieshaber snare 110

H
Halves of the nucleus 124
Health planning and surgeons 174
Hema hood
material 31
surgical technique 31
insertion of hood 32
phacoemulsification procedures 32
postsurgical evaluation 32
preparation of hood 31
removal of hood 32
Hema intracameral endothelial contact lens
31
Hemorrhage retinopathy 96
Hot air oven 586
Hyaluronidase 3
Hydrodelamination 132
Hydrodelineation 69
Hydrodissection 69, 124, 132, 149
Hydrodissection/hydrodelineation 189
Hydrogel contact lens delivery 453
Hyperopic eye 280

I
Idiopathic polypoidal choroidal vasculopathy
395
Implantable miniaturised telescope 446
Incineration 586
Incision 39, 298, 299
Incision closure 37, 301
Increased astigmatism 264
Indocyanine green angiography
advantages 393
digital subtraction 394
pharmacology 394
realtime 393
technique 394
toxicity 394
various phases 394
wide angle image 394
Indocyanine green dye 126
Infantile cataracts 80
Infiltration anesthesia 13
Infusion bottle 119
Infusion option 63
Insertion 298
Intact posterior capsule 145
Intracameral subcapsular injection 187
Intraocular implants 114
Intraocular lens 71

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Intraocular lens fixation


anterior chamber 109
external approach 110
internal approach 110
posterior chamber 109
Intraocular lens implantation 42
Intraocular tumors 395
Intravitreal antibiotics 479
Investigational drugs 537, 538
IOL decentration 37, 94, 340
IOL power selection 81
Ionising radiation 591
Iridectomy 298, 299, 301
Iridectomy forceps 299
Iridodialysis 72

K
Keratoconus 323
Keratometry 261, 279
Keratoscopy 262

L
Laser 298
Laser cataract surgery 152
advantages 156
instrumentation 153
pioneers 153
procedure 156
Laser cataract system 156
Laser phaco incision 155
Laser phaco probe 155
Laser phakonit 340
Laser photon 155
Laser photon machine 152
Laser sclerotomy 339
phakic 340
with Nd:YAG 338
LASIK surgery 293
phases of healing 294
therapeutic medications
post-procedure 293
preprocedure 293
Laws of refraction 401
Lens capsule removal 63
Lens implantation in the sulcus 63
Lens insertion 300
Lensectomy
endocapsular 62, 64
pars plana 62
Lid scrubs 456
Local anesthesia 6
Local anesthetic agents 519
Local anesthetic combinations 520
Local application of drugs 451
Lubricants and artificial tear solution 524

M
Macular photocoagulation study 389
Macular translocation 442

602 Advances in Ophthalmology1


Mean age 20
Medications 298
Membrane bound devices 452
Membrane bound inserts 457
MEWDS 398
Moist heat 590
Multifocal choroiditis 397
Mydriatics and cycloplegics 520
Myopia with amblyopia 297

N
Nadbath block 8
Nd:YAG laser 338
Nd:YAG posterior capsulotomy rates 232
No anesthesia cataract surgery 15, 42, 120
No anesthesia clear corneal phacoemulsification surgery
anatomical factors 23
surgical factor 23
No anesthesia clear lens extraction 42
Non-foldable IOL 264
Noninfectious inflammation 92
Nonsurgical adjuncts 533
Nuclear emulsification 190

O
O Briens technique 7
Ocular and refractive growth 82
Ocular infections 467
Ocular surgery news 23
Ocusert system 452
Ointments 455
Opacification 245, 250
Bausch and Lomb: hydroview 251
clinicopathological analyses 253
crystalline 247
delayed 247
delayed postoperative 250
energy dispersive X-ray spectroscopy 254
foldable hydrophilic acrylic lenses 250
gross and light microscopic analyses 253
histochemical stainings 254
medical developmental research 251
pathological mechanism 254
rigid and foldable lenses 246
scanning electron microscopy 254
snowflake 245, 247
Ophthalmic dyes 180, 497
fluorescein sodium 497
fluorescein strips 499
intravenous fluorescein 499
oral fluorescein 500
topical formulations 499
fluorexon 500
indocyanine green 501
indications 502
pharmacokinetics 501
lissamine green 501
rose bengal 500
preparation 180

trypan blue 502


use of 180
verteporfin 505
verteporfin (visudyne) 503
visudyne 505
Ophthalmic dyes for posterior capsulorhexis
191
Ophthalmic innovations 252
Ophthalmic medications 457
Ophthalmic viscosurgical devices 198
classification 199, 200
high viscouscohesive 199
lower viscositydispersive 201
super viscouscohesive 199
viscoadaptive 201
clinical applications 202
capsular bag filling 204
capsulorhexis 202
cataract surgery 202
cataract surgery in pediatric patient 204
cleavage of lens structure 202
glaucoma surgery 204
intraocular delivery of dyes 206
IOL implantation 204
irrigation and aspiration 204
nuclear emulsification 203
topical ophthalmic anesthesia 206
viscocanalostomy 204
viscostaining of the anterior lens capsule
206
complications 207
capsular bag distension syndrome 210
capsular block syndrome 210
crystallization on the IOL surfaces 207
increase in intraocular pressure 207
pseudo-anterior uveitis 212
removal 207
soft shell technique 201
Ophthalmic viscosurgical devices 521
Optical physiology 305
magnification of the retinal image 306
emmetrope 307
myope 308
materials and methods 310
ocular accommodation 305
ocular convergence 306
optical aberrations 306
visual field 306
Orbicularis oculi akinesia 7
Orbscan 263, 283, 323
Osmotic pumps 453

P
Pachymetry 279
Parabulbar (Flush) akinesia 13
Paracentesis 19, 36, 300, 339
Paralysis of the superior rectus muscle 13
Pars plana techniques 63, 110
Patching 288
Patients discomfort due to ability to move
the eye 22

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Patients discomfort due to microscope


light 21
Patients discomfort due to sense of
touching the eye 22
Pediatric cataract IOL surgery
future 243
past 238
present 240
Pediatric cataract surgery 80, 168, 170, 174,
175, 194
anesthesia 84
anterior capsule management 85
bipolar radiofrequency capsulotomy
85
manual continuous curvilinear
capsulorhexis 85
vitrectorhexis 85
bilateral or immediately sequential 173
evolution 83
eye care model 172
intraocular lens implantation 86
IOL power selection 171
lens substance removal 86
management of the posterior capsule 86
anterior vitrectomy 86
Nd:YAG laser posterior capsulotomy
88
posterior capsulorhexis with intraocular lens optic capture 87
posterior capsulotomy 86
ophthalmic dyes for 194
role of ophthalmologists from industrialized nations 173
techniques 83
use of IOLs 170
viscoelastic substances 84
wound construction 84
Pediatric cataracts 74
aphakic glasses 78
characteristics 77
contact lenses 78
intraocular lens implantation 79
optical rehabilitation 78
Pediatric traumatic cataracts
etiology 89
postoperative complications 89
surgical management 89
Perfluorocarbon liquid 110, 400
complications 407
indications 404
dislocated crystalline lenses or intraocular lenses 406
giant tears 404
proliferative diabetic retinopathy 406
proliferative vitreoretinopathy 406
medical applications 407
physical properties 400
boiling point 404
density 400
refractive index 401
relative density or specific gravity 401
surface tension 402

Index 603
vapor pressure 404
viscosity 403
types 400
Perforation of the globe 10
Periballasting 555
Peribulbar (periocular) technique 11
Peribulbar injection 3
Periocular anesthesia 11
Peripheral iridectomy 340
Phaco anesthesia 16
Phaco chop technique 41, 143
Phaco incision 154
Phaco probe 124
Phacoemulsification 37, 41, 63, 70, 133, 137
complications at various phases 139
clear corneal incision 139
during capsulorhexis 139
impending rupture of the posterior
capsule 141
managing complication with
hydrodissection 141
managing the ruptured capsule after
hydrodissection 141
prevention of complications with
hydrodissection 140
problem with capsulorhexis 140
problem with nucleo-fractis 142
problem with side port incision 139
problem with the phaco chop
techniques 143
preventive aspects prior commencing 137
aspiration of excess fluid 138
checking IOP 137
fresh air under the drapes 138
placement of the lid retractor 138
position of the patient 137
Phakic refractive lens 295
Phakonit 16, 44, 46, 268
hydrodissection 46
incision 45
laser 51
lens-insertion technique 51
principle 44
rhexis 45
surge 48
technique 45, 48
three port 52
topography 51
Phakonit thinoptxrollable IOL 49
Phakonit with acritec IOL 54
incision 55
laser phakonit 59
lens insertion technique 59
lens loading technique 56
phaconit 56
principle 54
rhexis 55
technique 54
Photodynamic therapy 389, 439
post-treatment regime 391
preparation of the patient 391
principle 389

procedure 392
technique 390
Photorefractive keratectomy 287
postoperative therapeutics 288
epithelial defect closure 288
modulation of refractive and visual
results 289
post PRK management 288
preoperative ocular therapeutics 287
dosage 288
topical anesthesia 287
recent update in post PRK medications
clinical symptoms 290
complications of topical steroids 290
treatment 290
Physical endothelial cell protection 31
Piggy-back foldable intraocular lenses 96
Pilocarpine ocular therapeutic system 350
Plano eye 280
Plastic surgery 562
aging of the face 563
complications 583
conventional surgical blepharoplasty 566
lasers used for cosmetic treatment
argon laser 563
CO2 laser 563
preoperative and postoperative treatment
582
Polishing cannula 145
Posterior capsule opacification 218, 220
clinical manifestations 223
etiopathogenesis 221
factors in clinical studies 226
pharmacological prevention 227
prevention 224
three IOL-related factors
barrier effect of the IOL optic 226
biocompatibility 226
maximal IOL optic posterior capsule
contact 226
three surgery related factors 224
capsulorhexis edge on IOL surface 225
hydrodissection-enhanced cortical
clean-up 224
in-the-bag (capsular) fixation 224
Posterior capsulotomy 145
Premedication 4
Preoperative orbscan 275
Presbyopia 278
Presbyopic LASIK technique 279
Preventive endothelial cell loss 27
iced irrigating solution 28
irrigating solution 28
preservative free intracameral solutions 28
surgeons special care 29
Primary posterior corneal elevation
general quad map of an eye 324
three-dimensional anterior float 326
three-dimensional normal band scale map
325
three-dimensional posterior corneal
elevation 326

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Prism ballasting 554


PRL power calculation
Holladay refraction formula 297
Russian method: vertex chart 297
Pseudophakia 341
Pseudophakic ametropia correction 302
Pulse phaco 31, 125
Pupil constriction 301
Pupillary capture 93

R
Radiation therapy 441
Reduced tear production 543
diagnostic tear film tests 545
biopsy of conjunctiva 548
conjunctival impression cytology 548
lysozyme assay 548
Schirmers test 546
tear film break-up time 545
tear globulin assay 548
tear osmolarity 548
vital dye staining 547
etiology 543
management
artificial tear solutions 549
cellulose derivative 549
gel tears and sodium hyaluronate 550
mucolytics 550
ocular inserts (solid devices) 550
ointments 550
oral bromhexine 551
polyvinyl alcohol base solutions 549
punctal plugs (tear drainage reduction)
550
soft contact lens therapy 550
systemic therapy 550
tear conservation 549
tear replacement 549
tear substitutes 549
topical retinoids 550
topical solution 550
signs
corneal changes 545
marginal tear strip 545
precorneal tear film 545
symptoms 545
Residual refractive error 96
Retinal detachment 96
Retinal prosthesis implantation 444
Retinal vascular obstruction 11
Retro-ocular (retrobulbar) injection 9
Retrobulbar hemorrhage 10
Retrobulbar injection
complications 10
Retrobulbar route 453
Retroiris placement 300
Rewetting solutions 533
Rhexis in mature cataracts
technique 121
Rigid toric contact lens 557
Rollable IOL 159

604 Advances in Ophthalmology1


Rollector 51
RPE transplantation 443
Rupture of the posterior capsule
signs 146
with hyaloid face rupture 147
without hyaloid face rupture 147

Subconjunctival route 453


Subluxated cataracts 66
Surge 48, 118
Surgeons discomfort due to patients ability
to move the eye 22
Surgical time 20
Systemic administration of drugs 455

S
Saddle rump 144
Scale of pain 21
Scleral barrier 452
Scleral loop fixation 110
Secondary cataract 220
Secondary membrane formation 93
Serpiginous choroiditis 396
Shelling 144
Silicone plane plate IOL 114
Snowflake lesion 248
Solutions and suspensions 455
Spaeth block 8
Sprays 456
Staining the anterior capsule
evaluation of the dyes and techniques
used 183
characteristics of the three dyes used
185
characteristics of the two techniques
used 185
for phacoemulsification 187
using fluorescent sodium 186
Stellate burst 40
Sterilization 586
chemical methods 591
acetone 593
bacillocid 594
baktolin 5.5 595
betapropiolactone (BPL) 593
biguanides 592
cetrimide 593
concentrated cold sterilizer 594
cutasept 594
ethylene oxide 591
formalin 591
glutaraldehyde 592
isopropyl alcohol 592
phenols 593
povidone iodine 593
sodium hypochlorite 592
Sterilization and disinfection methods 587
in ocular surgery 589
Steroid induced glaucoma 290
Stress for the surgeon during surgery 22
Subarachnoid injection 11

T
Technique and laser setting 574
Temporary haptic externalization 111, 113,
114
Tenons capsule 13
The Sunita Agarwal laser phaco probe 153
Tip placement 31
Tissue plasminogen activator 443
Topical anesthesia 14, 293
advantages 14
complication 15
conversion from topical to peribulbar 14
indication 14
Topical hyperosmotic agents 527
Topical immune therapy 527
Topical ocular anesthetics 18
side effects and complications 18
Topical steroid 513
Topography 261
Toric contact lens 552
Toric lens fitting 555
useful tips 556
Toric lens stabilization 553
Toric soft contact lens 555
Trabeculectomy 380
completing the trabeculectomy 382
phaco 380
postoperative care 384
preparation of the scleral flap 380
Transplanted RPE cells 444
Transpupillary thermotherapy 440
Truncation 555
Trypan blue 121

Vertical hubbing phacoemulsification


anesthesia technique 127
capsulorhexis 131
corneal entry 130
draping of the eye 128
hydrodelamination 132
hydrosissection 132
incisions 129
indications 135
monitoring patients in the theatre 129
operative procedure 129
preferred phacoemulsifier 128
preoperative preparation 127
techniques
coring the nucleus 133
nuclear stabilization 133
pulse aspiration of the ring 134
snapping the periphery 134
Viscoat 149
Viscocanalostomy 342
complications 344
astigmatism 344
bleb formation 345
Descemets window 345
exposure of the ciliary body 344
fibrotic closure of the ostiae 345
hyphema 344
iris adhesions 345
rupture of Descemets membrane 344
operative technique 342
results in two groups of patients
Cologne-group 345
Pretoria-group 345
the Spanish experience 347
Viscoelastic insertion 300
Viscoelastic protection 30
Viscoelastic removal 301
Viscoelastic substances 30, 198
Viscosurgery 198
Visual cortex prosthesis 445
Vitrectomy 105, 149
Vitrectorhexis 169, 243
Vogt Koyanagi Harada disease 398

U
Uveitis 91

V
Van Lints akinesia 7
Verteporfin 390
Vertex
amplification 309
magnification 307

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Z
Zero order kinetics 452
Zero suction 30
Zonular dehiscence 68
Zonular weakness 68
Zylink 283
Zyoptix 272, 282
Zyoptix laser 282

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