Treatment Guidelines for

Management of Dry Eye:

Role and Relevance of
Formulations
 Goals of management
– Establish the diagnosis of dry eye,
differentiating it from other causes of irritation
and redness,
– Identify the causes of dry eye,
– Establish appropriate therapy,
– Relieve discomfort,
– Prevent complications, such as loss of visual
function, infection, and structural damage,
– Educate and involve the patient in the
management of this disease.
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 Treatment – Principles
1. Hydrating and Lubricating the ocular
surface
2. Suppressing the inflammatory response
of the ocular surface

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 Cycle of Inflammation
Artificial Tears
Cyclosporin
Punctal Corticosteroids
Occulusion
Secretogogues Tetracyclines
Serum/Plasma

Irritation Inflammation

Tear deficiency/ instability

Artificial Tears
Punctal Occulusion
Serum/ Plasma
Tetracyclin
Secretogogues

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 Therapy Involves
1. Eliminating Exacerbating Factors
2. Support of Functional unit
3. Hydrating, stabilizing and lubricating
Therapy
4. Secretogogues
5. Punctal Occlusion
6. Anti-Inflammatory Therapy
7. Use of contact Lens
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 Eliminating Exacerbating Factors

• The factors that decrease tear production

or increase tear evaporation such as use
of systemic anticholinergic medications
and desiccating environmental stresses
should be minimized or eliminated

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 Support of Functional unit
• Aimed at normalizing tear secretion by secretory
glands and promoting normal growth and
differentiation of the ocular surface epithelia.
Androgen receptors are present in tear secreting
glands , meibomian glands, corneal and
conjunctival epithelia and accessory lacrimal
glands. Andrgens appear to attenuate auto-
immune reaction. Clinical trials of topical
administration of androgen for therapy of dry eye
are currently in progress.
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 Support of Functional unit
• Hormone replacement therapy in post-
menopausal women is associated with
increased prevalence of dry eye
symptoms
• Testosteron, 120 mg/day for two months
results in improvement in Schirmer test
value and reduction in ocular surface
Rose Bengal staining.

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 Support of Functional unit
• Autologous Serum – It contains several
growth factors that are present in tears
including Vitamin A , epidermal growth
factor, TGF beta and fibronectin. It
contains potential inhibitors of
inflammatory cytokines (e.g. IL-1) and
Matrix metalloproteinase.

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 Autologous Serum
• Use of diluted serum 1:3 with normal saline
resulted in significant improvement in symptoms
of ocular irritation and decrease in ocular surface
Rose Bengal staining, ocular surface fluorescein
staining and increase the expression of MUC 1
mucin by conjunctival epithelium. In addition it
may provide anti-inflammatory effect by
inhibiting inflammatory cascades.
• (Fox RI et al, Arthritis Rheum 1984 and Tsubota
K, et al , BJO 1999)
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 Autologous Serum
• In contrast others have observed no
difference between serum and control of
dry eye.

(Tananuva TN and coworkers , Arch of

Ophthalmology 1988)

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 Hydrating, Stabilizing, and
Lubricating Therapies
• There is reduced tear volume, elevated
tear osmolality , increased tear
electrolytes and decreased tear film
stability in cases of aqueous tear
deficiency. These alterations can be
treated with artificial tear, secretogogues
and punctal occlusions

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 Artificial Tear Polymers
Polymer Properties
-----------------------------------------------------------
Cellulose esters Viscoelastic
polysacchrides increase
the viscocity of tears
(hypermellose, increase in viscocity when
hydroxyethylcellulose, concentration is moderately
Methycellulose, increased
Carboxymethylcellulose)

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Polymer Properties
-----------------------------------------------------------
Polyvinyl alcohol Low Viscocity ,
optimal wetting
characteristics at 1.4%
Povidone Superior wetting when
(polyvinyl pyprolidone) co-formulated with
polyvinyl alcohol
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Polymer Properties
-----------------------------------------------------------
Carbomers High molecular weight polymers
(polyacrylic acid) of acrylic acid: high viscocity
when eye is static, thinning
during blinking or eye
movement, maximizes
thickness of tear film while
minimizing drag; longer
retention time than polyvinyl
alcohol

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Polymer Properties
-----------------------------------------------------------
Hyluronic acid, Glycosaminoglycan
chondroitin sulfate dissacharide
biopolymer
exhibiting non-
Newtonian properties
and longer retention
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times
Dr Sanjay Shrivastava 16
 Tolerance – merit wise
1. Carboxymethylcellulose (CMC-U),
2. Unpreserved, polyvinyl alcohol-based product
(PVA-U),
3. Hydroxypropylmethylcellulose formulation
(HPMC-P) that contains edetate disodium
(EDTA).
4. Preserved formulation (PVA-P), using polyvinyl
alcohol as the polymer and containing EDTA
and benzalkonium chloride (BAK),

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• Frequent instillation of artificial tears with
reduced tears turnover makes patients of
aqueous tear deficiency susceptible to
ocular surface epithelial toxicity from
preservatives particularly Benzalkonium
chloride. Preservative free lubricants
allows patients to use these artificial tear
preparations as frequently as necessary
without toxicity. Such preparations should
be considered in patients who requires
drugs for more than 4 times.
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• More recent addition is the use of
disappearing preservatives such as
Sodium Perborate and Purite ™. These
preservatives decompose into water,
oxygen or sodium upon contact with tears
film or with light.
• Lubricating ointments are useful for
bedtime application , they contain oily
substances such as Lanolin, Petrolatum.
• Lipid emulsions may have promising role,
further studies are needed to determine its
role in management of KCS.
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 Secretogogues
• Stimulates endogenous tear production. They
are:
a. Oral Pilocarpine (SALAGEN tablets) 5 mgm
four times (side effects- excessive sweating,
nausea and intestinal cramping)
b. Cevilemine (Evoxac tablets) 90 mg/d and is
tolerated at doses up to 180 mg/d.
These agents (Cholinergic agonist) are found to
improve irritation and tear production.

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 Secretogogues
• Currently P2Y2 receptor agonist Diuridine
Tetraphosphate is under phase III clinical
trial of FDA. Preliminary results have
shown increase in Schirmer test score,
decrease fluorescein stain and improve
the worst irritation symptoms (Tauber J ,
Invest Ophthalmol Vis Sci 2003) .
Stimulation of P2Y2 receptors induce
secretion of mucin by conjunctival cells.
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 Punctal Occlusion
• Semitransparent silicon Themolabile polymers
• Punctal Plugs/ Canalicular implant (gelatin
plugs / rods)

(http://www.agingeye.net/dryeyes/plugsetc.php
#)
c. Thermocautery
d. Radiofrequency needle
e. Suture
f. Argon Laser
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 Surgical Treatment
To decrease the exposure and
evaporative loss of tears, side panels
and moist inserts on eyeglasses may be
tried OR surgical methods:
• Tarsorrhaphy: Lateral and /or median
• Type A Botulinum toxin into the LPS
muscle induces a temporary (6-8 weeks)
complete ptosis of the upper eyelid.
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3. Salivery Gland Transplantation-
a. Parotid duct transposed and redirected to
drain into inferior fornix.
b. Transplantation of minor salivery glands into
inferior tarsal or fornicial conjunctiva
c. Transplantation of a portion of
submandibular gland with its duct into temporal
fossa, duct is transplanted in superior temporal
fornix.

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 Anti-inflammatory Therapy
This therapy targets one or more
components of the inflammatory response
to dry eye . Anti-inflammatory therapy may
be considered for patients with stagnated
and unstable tear film who continue to
have symptoms or have corneal disease
on aqueous enhancement therapies.

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 Cyclosporin A
Is reported to be effective in dry eye and
keratoconjunctivitis sicca. It prevents the
activation of transcription factors that are
necessary for T cell activation and the
production of IL 2
Cyclosporin A act by inhibiting epithelial
apoptosis and T cell activation. The density of
goblet cells on ocular surface also increases.
Used as 0.05% drops twice daily. It significantly
decrease conjunctival Rose Bengal Staining,
SPK and Ocular irritation symptoms
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 Corticosteroids
Corticosteroids have been reported to improve
both symptoms and signs of dry eye. Irritative
symptoms and corneal fluorescein staining
improves.
Occasionally severe cases of Sjogren’s syndrome
improve with alternate day oral Prednisolon (40
mgm) therapy. Improvement in Schirmer test ,
decrease in Rose Bengal Staining and elevation
of tear lysozyme enzyme level is observed.

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 Tetracycline
Tetracycline or Doxycycline are effective for
treating ocular surface inflammatory
diseases. They inhibit the production and
activity of inflammatory cytokines and
other inflammatory reaction modulators.
Doxycycline is particularly effective in
treating dry eye associated with
meibomian gland disease.

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 Recommendations for use of Anti-
inflammatory therapy of Dry Eye
Constant ocular irritation from tear film instability
that is not relieved by artificial tears and patients
who develops corneal epithelial disease from dry
eye, are the situations where anti-inflammatory
therapy is indicated.
CsA is started , if patient does not respond then
add topical steroids and oral tetracycline, topical
steroids are best used in short pulses 1-4
weeks, then frequency is decreased to once or
twice or replaced with Loteprednol or
Fluoromethalone
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 Autologous Serum

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 Essential Fatty Acids
• Recent research has shown that oral therapy
with polyunsaturated fatty acids reduces ocular
surface inflammation and improves dry eye
symptoms (Cornea 2003;22:97-101). In this
study patients received tablets containing 28.5
mg linoleic (omega-6 fatty acid) and 15 mg
gamma-linolenic acid (omega-3 fatty acid) twice
daily for 45 days. Both of these are
polyunsaturated fats. Use of these agents shows
improvement in ocular irritation symptoms,
decrease ocular surface Lissamine staining
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 Use of Contact Lens
Soft bandage contact lens (DK Silicon or
Hydrogel) and Gas permeable scleral hard
lens have shown improvement in patients
with KCS with epitheliopathy or recurrent
filamentary keratitis. CL are indicated in
few selected cases.

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 COUNSELING/REFERRAL

• The most important aspects of caring for

patients with dry eye are to educate them
about the chronic nature of the disease
process and to provide specific
instructions for therapeutic regimens.

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 Summary

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 Cycle of Inflammation
Artificial Tears
Cyclosporin
Punctal Occulusion Corticosteroids
Secretogogue Tetracyclines
s Serum/Plasma

Irritation Inflammation

Tear deficiency/ instability

Artificial Tears
Punctal Occulusion
Serum/ Plasma
Tetracyclin
Secretogogues

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 Summary
1. Multipronged approach
2. Systemic and environmental stresses should
be minimized
3. Artificial Tears
4. Systemic cholinergic agonists
5. Preservation of natural tears and punctal
occlusion
6. Cyclosporin A
7. Topical Steroids
8. Environmental correction / Counseling

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 References
1. Ali R. Djalilian, Pedram Hamrah, Stephen C Plugfilder.
Dry Eye, p 521-541, in Cornea- fundamentals, Diagnosis
and Management – Vol- 1 , Krachmer, Mannis, Holland,
Elsevier Mosby- 2005.
2. Stephen C Pflugfelder and Abraham Soloman, Dry Eye-
P 49-57, in Ocular Surface Diseases, Medical and
Surgical Management, Edward J Holland and Mark J
Mannis, Springer 2002
3. Stephen C Pflugfelder and Michael E Stern. Therapy of
Lacrimal Keratoconjunctivitis. In Dry Eye and Ocular
Surface Disorders ed by Stephen C Pflugfelder, Roger
W. Beuerman, Michael E Stern, p 309-325, Marcel
Dekker, Inc ,2005

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 References … Contd.
• Ocular Surface Disease Index questionnaire is
available on site

www.agape1.com/Questionnaires/Ocular%20S
urface%20Disease.pdf
• Dry Eye Syndrome Preferred Practice Pattern™

http://www.aao.org/education/library/ppp/dryeye_new
• Artificial Tears

http://www.agingeye.net/dryeyes/dryeyesdrugtre
atment.php
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• Thanks you

Thank you
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