[Downloaded free from http://www.jcor.in on Saturday, November 12, 2016, IP: 125.162.175.

253]

Original Article

A prospective study of incidence and risk factors for secondary glaucoma after
penetrating keratoplasty

Aruna Kumari R. Gupta, Roopam Kumar R. Gupta1

Aim: To carry out a prospective study to analyze the incidence and risk factors for secondary glaucoma after penetrating Access this article online
keratoplasty(PK). Materials and Methods: Three hundred and eleven consecutive penetrating keratoplasties that Website:
were performed between January 1, 2006, and December 31, 2008, with a followup of 12 months were prospectively www.jcor.in
analyzed to determine the factors associated with postoperative glaucoma. Results: Of 311 eyes, secondary glaucoma DOI:
developed in 57 cases. This yields an incidence of 18.3%. In conditions, such as aphakic bullous keratopathy, the 10.4103/2320-3897.190794
incidence of postPK glaucoma was 3.0%; in pseudophakic bullous keratopathy 14.0%, and in cases of failed graft Quick Response Code:
16.0%, while in cases of corneal ulcer and corneal opacity it was 49.0% and 18.0%, respectively. Conclusion: We
conclude in our study that the incidence of glaucoma developing postPK was highest in phakic eyes, which may be
due to the formation of posterior synechiae and development of intumescent cataract. Higher incidence of glaucoma
developing in infective cases could be due to recipient hot eye and the high incidence in cases of large graft could be
attributed to the formation of peripheral anterior synechiae.

Key words: Graft size, indications, penetrating keratoplasty, phakic status, secondary glaucoma

The association between penetrating keratoplasty(PK) and
the development of postoperative increase in intraocular
pressure(IOP) has been first noted by Irvine and Kaufman.[1]
Since then, various authors have reported the incidence of
glaucoma following PK to be from 9% to 31% in the early
postoperative period[24] and from 18 to 35% in the late
postoperative period.[5,6]
A variety of factors has been studied for a better
understanding of the mechanisms involved in the elevation
of IOP following PK. Graft size[610] suture technique[6,8,11]
and iridocorneal compression[6,11] have been implicated for
postoperative secondary glaucoma. Other factors, especially
aphakia[2,7] have also been studied.
Timely diagnosis of postPK glaucoma(PPKG) with initiation
of appropriate treatment is mandatory to preserve optimal
graft clarity and optic nerve head function.[12] The purpose of
this paper was to determine the incidence and risk factors for
secondary glaucoma after PK.
Materials and Methods
Between January 1, 2006, and December 31, 2008, a prospective
study was conducted of consecutive PKs performed at our
institution. The cases had a followup of 12 months. PK was
performed following the ethical guidelines for biomedical
research on human subjects issued by the Indian Council of
Medical Research in 2000. The institutional ethics committee
Departments of Ophthalmology and 1Anatomy, C.U. Shah Medical
College and Hospital, Surendranagar, Gujarat, India
Address for correspondence: Dr.Aruna Kumari R. Gupta,
Department of Ophthalmology, C.U. Shah Medical College
and Hospital, Surendranagar363001, Gujarat, India.
Email:arunagupta.eye@gmail.com
Manuscript received: 15.07.2015; Revision accepted: 26.04.2016
had cleared the project. All the patients had given their
informed consent.
Preoperative examination of the recipients included their
details, chief complaints, and the presence of any predisposing
factors such as ocular surface disorders, trauma, contact lens
use, previous history of graft infection, systemic illness, and
history of any ocular surgery.
Clinical examination included uncorrected visual acuity,
best corrected visual acuity, cycloplegic refraction(not done in
infective keratitis cases); slit lamp biomicroscopy to determine
any ocular pathology, applanation tonometry(not done in
infective keratitis cases). In cases where the recording of IOP
was not possible by Goldman applanation tonometry, digital
tonometry was done. Dilated fundus examination was done
for disc evaluation where media was clear and to rule out any
posterior segment pathology.
Investigations included tear film status, gonioscopy, sac
syringing, routine blood investigations such as complete
blood count, ESR, urine routine and microbiology, blood
urea and serum creatinine, fasting blood sugar and fasting
urine sugar, serology to screen for infectious diseases such
as AIDS(S.HIV), hepatitis(S.HbsAg), and sexually transmitted
diseases(S.VDRL). Blood pressure and ultrasonography of
This is an open access article distributed under the terms of the Creative
Commons AttributionNonCommercialShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work noncommercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
Cite this article as: Gupta AR, Gupta RR. A prospective study of incidence
and risk factors for secondary glaucoma after penetrating keratoplasty. J Clin
Ophthalmol Res 2016;4:123-6.

2016 Journal of Clinical Ophthalmology and Research | Published by Wolters Kluwer -Medknow 123
[Downloaded free from http://www.jcor.in on Saturday, November 12, 2016, IP: 125.162.175.253]
Gupta and Gupta: Incidence and risk factors for secondary glaucoma
the posterior segment was performed to rule out vitreous
exudation suggestive of endophthalmitis. The medical records
were reviewed for the indication for which PK was done and
the IOP measurements in each case were noted.
Patients who had a previous history of glaucoma were
excluded from the study. All PK were performed by standard
surgical technique under local anesthesia except in children
where general anesthesia was used. Donor button oversized
by 0.5 mm was used, except in cases of keratoconus, where
the graft of the same size as the recipient was used. Anterior
vitrectomy was performed when required. Donor cornea
was sutured to recipient cornea with interrupted 10.0 nylon
monofilament sutures with adjustable suture technique. All
cases received amikacin(25 mg), cefazolin(100 mg), and
dexamethasone (4 mg) subconjunctivally at the end of the
operation. In cases of infective keratitis, dexamethasone was
not given. Intraoperative data recording included the details of
the surgical procedure, type of surgery, i.e.,whether combined
with cataract extraction, intraocular lens removal, secondary
intraocular lens implantation, and anterior vitrectomy.
Postoperatively, the eyes were patched, and topical steroid
was administered once the epithelium was intact over the
transplant, except in cases of infective keratitis. Topical
steroid(prednisolone) was instilled in the operated eye
four times a day initially, and the frequency was increased
or decreased depending on the degree of inflammation.
Topical antibiotics(ofloxacin or gatifloxacin) were given four
times in the initial period. At the end of 1 month following
surgery, most of the patients were shifted to weaker antibiotic
steroids combination(tobramycin and fluorometholone)
four times a day. This dosage of medication was tapered
during the postoperative period to once after 1year. In
eyes where inflammatory signs persisted, topical steroids
were continued longer at higher dosage. If there was sign
of graft rejection, then intensive topical steroids were given.
Cycloplegic(cyclopentolate 1%) was given twice daily till iritis
subsided and was discontinued after 1week. Topical antibiotics
and antifungals were continued till there was no suspicion
of infection. Topical antiglaucoma medication(timolol 0.5%)
twice daily and lubricants(carboxymethyl cellulose) four times
were given during the initial period.
The patients were evaluated on every followup in the
same manner as the preoperative assessment including the
condition of the corneal graft was also noted. The raised
IOP was controlled either medically or surgically. Medical
treatment included oral acetazolamide 250 mg four times
and liquid glycerol 30 cc twice a day and topical antiglaucoma
drops were given. Patients not responding to full medical
treatment were treated surgically. Surgical methods included
filtration procedure and/or by cyclocryotherapy as per the
case. The patients were evaluated on the 1st day, at the end of
1st week, 1st month, third and 6 months and then after 1year
postoperatively. Statistical analysis was done using paired
and unpaired ttest.
124 Journal of Clinical Ophthalmology and Research - Sep-Dec 2016 - Volume 4 - Issue 3
Results
Three hundred and eleven PKs were performed between the
study period on observing the demographic details mean
age of the patients was 43.04 17.67 (range 6 years to
78years). Maximum number of patients was in 4150years
group (24.0%). In this study, the male recipients were
more(64.0%) than female recipients(36.0%). Right eyes were
operated more(59.0%) than the left eyes(41.0%).
Of the 311 eyes, secondary glaucoma developed in 57cases.
This yields an incidence of 18.3%. Average preoperative IOP
was 15.11 mmHg(range 12.220.6). The IOP(mmHg)
measured on postoperative days averaged 23.58 after 1st week,
25.20 after 1st month, 26.77 after 3rd month, 23.52 after
6 months, and 23.12 after 1year. Maximum increase was seen
at 3 months(P=0.001). Mean IOP was 24.597.87 mmHg
(range 22.450.6 mmHg).
The study of the medical records of these 57 patients
showed that in conditions of keratoconus the incidence of
PPKG was 0%, aphakic bullous keratopathy(ABK) 3%; in
pseudophakic bullous keratopathy 14%, failed graft 16.0%,
corneal opacity 18.0%, and in cases of corneal ulcer 49.0%.
Among corneal ulcer cases the incidence was 26.0% in cases
of bacterial keratitis and 23.0% in cases of fungal keratitis.
The records of the phakic status of these 57patients showed
that 25patients(44.0%) were phakic, 17patients(30.0%) were
aphakic, and 15patients(26.0%) were pseudophakic.
We studied the incidence of PPKG with respect to the graft
size and found that with 7 mm graft size the incidence was
8%, with 7.5 mm graft size it was 26.0%, with 8 mm graft size
8%, 8.5 mm graft size 12.0%, 9 mm graft size 12.0%, 9.5 mm
graft size 13.0%, 10 mm graft size 13.0%, 10.5 mm graft size
3.0%, and with 11 mm graft size 5%.
Discussion
The definition of PPKG is an elevated IOP(>21 mmHg)
following PK, with or without optic nerve damage and visual
field changes. The etiology of PPKG is multifactorial such
as distortion of the angle with collapse of the trabecular
meshwork, suturing technique, and peripheral anterior
synechiae(PAS). Other factors that contribute to postoperative
glaucoma are preexisting glaucoma, use of viscoelastic
substances, steroidinduced glaucoma,[5] and the presence of
ocular inflammation in the preor postoperative period.[1315]
The leading cause for late PPKG, however, is synechial angle
closure,[16] PAS formation preoperatively or as a consequence of
a preceding intraocular surgery[1719] and floppy atrophic iris.[20]
The purpose of our study was to determine the incidence and
risk factors for secondary glaucoma after PK at our center.
In the present series, the incidence of PPKG was 18.3%.
Other studies reported the incidence of PPKG to be 18%,[5]
21.5% by Frana et al.,[13] and 27.4% by Sekhar et al.[21] In
another study by Karadag etal.[22] IOP increased in the early
[Downloaded free from http://www.jcor.in on Saturday, November 12, 2016, IP: 125.162.175.253]
Gupta and Gupta: Incidence and risk factors for secondary glaucoma
postoperative period in 5.5% of cases and chronically elevated
IOP was reported in 16.6% of cases.
This study shows that the incidence of glaucoma after
PK differ significantly based on the indication for PK
(from a low of 0% for keratoconus to a high of 49.0% after
Infectious keratitis). Our observation of higher incidence
of secondary glaucoma in infectious keratitis cases may be
due to preoperative and postoperative inflammation and
the development of PAS as also reported by Kirkness and
Moshegov.[19] Other studies also reported the rate of chronic
glaucoma after PK differed significantly based on the indication
from a low of 012% for keratoconus to a high of 75% after
infectious keratitis.[5,9,12] When the incidence of glaucoma was
studied based on microbiology, i.e.,bacterial or fungal there
was no significant difference in incidence of glaucoma in our
study. Studies by Goldberg etal.[2] Simmons etal.,[18] Kirkness
and Moshegov[19] and Polack,[23] also reported a low incidence
of secondary glaucoma after PK in keratoconus similar to our
findings. Goldberg etal.[2] reported increased IOP in cases of
ABK. In some studies, bullous keratopathy, graft rejection,
history of glaucoma, and trauma were reported to be highrisk
factors for IOP elevation following PK.[18,19,23] Wagoner etal.[24]
reported that eyes with corneal edema were significantly more
likely to develop glaucoma than those with stromal scarring
dissimilar to our findings.
The study of association of glaucoma with phakic status
found that out of 57patients 25patients(44.0%) were phakic,
17patients(30.0%) were aphakic, and 15patients(26.0%) were
pseudophakic. In this study, the incidence of glaucoma was
more in phakic eyes whereas other studies reported aphakic
eyes[7,12] at much higher risk of developing glaucoma. The
proposed mechanism of glaucoma in aphakic cases was more
manipulation of eye structures leading to more inflammation
by Goldberg etal.,[2] Karesh etal.,[3] and Zimmerman etal.,[7]
angle distortion by Olson and Kaufman,[6] and mechanical
collapse of the trabecular meshwork by Zimmerman etal.[11]
Some studies reported that aphakic and pseudophakic eyes in
the presence of PAS had a greater tendency to develop PPKG
when compared to phakic eyes,[5,18,21,23] while other studies
found no difference between aphakic and pseudophakic eyes
but reported a higher incidence of PPKG in pseudophakic
and aphakic eyes as compared to phakic eyes.[22] As the
incidence in our study was more in phakic cases, we propose
that the formation of posterior synechiae and development
of intumescent cataract leads to the higher incidence of
secondary glaucoma in phakic eyes.
In our study, 5 phakic eyes of corneal abscess were rendered
aphakic, 3 corneal opacity cases phakic to pseudophakic,
2 failed graft cases phakic to aphakic, and 1 descematocoel
case phakic to pseudophakic. We did not find any statistically
significant increase in IOP in cases where combined surgery
was done similar to other studies,[8,12,25] while many studies
reported an increase in the relative risk associated with PPKG
following combined surgical procedure with PK.[2,10]
Journal of Clinical Ophthalmology and Research - Sep-Dec 2016 - Volume 4 - Issue 3 125
The relationship between donor button size and host bed
size has also been the subject of several studies.[2,10,11] On
comparing the graft size with the outcome, we observed that
with graft size of 8 mm and above there was increased incidence
of secondary glaucoma which may be due to the formation of
PAS at the hostgraft junction. Adonor button 0.5 mm larger
than the host bed has been shown to be associated with a lower
incidence of postoperative glaucoma[10,11] but in our study this
was not assessed as we used donor button oversized by 0.5 mm
in all cases except in cases of keratoconus, where the graft of
same size as the recipient was used. In our study, incidence of
glaucoma in cases with difference in suturing technique was
not studied. Studies by Pramanik etal.,[26] Erdurmus etal.[27] and
Fan etal.[28] found IOP elevation related to steroid use following
PK, but in our study, we did not observe any steroid responders
so this factor was not evaluated.
Conclusion
PPKG glaucoma continues to be a clinical problem that can
be sight threatening in its ultimate outcome. However,
recognition of the risk factors, controlling the inflammatory
response judiciously, and more frequent monitoring of IOP
may yield better results. We conclude in our study that the
incidence of glaucoma developing postPK was highest in
phakic eyes, which may be due to the formation of posterior
synechiae and development of intumescent cataract. Higher
incidence of glaucoma developing in infective cases could be
due to recipient hot eye and the high incidence in cases of
large graft could be attributed to formation of PAS.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. IrvineAR, KaufmanHE. Intraolar pressure following penetrating
keratoplasty. Am J Ophthalmol 1969;68:83544.
2. GoldbergDB, SchanzlinDJ, BrownSI. Incidence of increased
intraocular pressure after keratoplasty. Am J Ophthalmol
1981;92:3727.
3. KareshJW, NirankariVS. Factors associated with glaucoma after
penetrating keratoplasty. Am J Ophthalmol 1983;96:1604.
4. Chien AM, Schmidt CM, Cohen EJ, Rajpal RK, Sperber LT,
RapuanoCJ, etal. Glaucoma in the immediate postoperative period
after penetrating keratoplasty. Am J Ophthalmol 1993;115:7114.
5. FoulksGN. Glaucoma associated with penetrating keratoplasty.
Ophthalmology 1987;94:8714.
6. OlsonRJ, KaufmanHE. Amathematical description of causative
factors and prevention of elevated intraocular pressure after
keratoplasty. Invest Ophthalmol Vis Sci 1977;16:108592.
7. ZimmermanT, OlsonR, WaltmanS, KaufmanH. Transplant
size and elevated intraocular pressure. Postkeratoplasty. Arch
Ophthalmol 1978;96:22313.
8. OlsonRJ. Aphakic keratoplasty. Determining donor tissue
size to avoid elevated intraocular pressure. Arch Ophthalmol
1978;96:22746.
9. BourneWM, DavisonJA, OFallonWM. The effects of oversize donor
[Downloaded free from http://www.jcor.in on Saturday, November 12, 2016, IP: 125.162.175.253]

Gupta and Gupta: Incidence and risk factors for secondary glaucoma

buttons on postoperative intraocular pressure and corneal curvature
in aphakic penetrating keratoplasty. Ophthalmology 1982;89:2426.
10. FoulksGN, PerryHD, DohlmanCH. Oversize corneal donor grafts
in penetrating keratoplasty. Ophthalmology 1979;86:4904.
11. ZimmermanTJ, KrupinT, GrodzkiW, WaltmanSR. The effect of
suture depth on outflow facility in penetrating keratoplasty. Arch
Ophthalmol 1978;96:5056.
12. WilsonSE, KaufmanHE. Graft failure after penetrating
keratoplasty. Surv Ophthalmol 1990;34:32556.
13. Frana ET, ArcieriES, ArcieriRS, RochaFJ. Astudy of glaucoma
after penetrating keratoplasty. Cornea 2002;21:2848.
14. Redbrake C, Arend O. Corneal transplantation and glaucoma.
Ophthalmologe 2000;97:5526.
15. ColemanAL. Glaucoma. Lancet 1999;354:180310.
16. Lass JH, PavanLangston D. Timolol therapy in secondary
angleclosure glaucoma post penetrating keratoplasty.
Ophthalmology 1979;86:519.
17. Kirkness CM, Ficker LA. Risk factors for the development of
postkeratoplasty glaucoma. Cornea 1992;11:42732.
18. SimmonsRB, SternRA, TeekhasaeneeC, KenyonKR. Elevated
intraocular pressure following penetrating keratoplasty. Trans
Am Ophthalmol Soc 1989;87:7991.
19. KirknessCM, MoshegovC. Postkeratoplasty glaucoma.
Eye(Lond) 1988;2Suppl: S1926.
20. CohenEJ, KenyonKR, DohlmanCH. Iridoplasty for prevention of
postkeratoplasty angle closure and glaucoma. Ophthalmic Surg
1982;13:9946.
21. SekharGC, VyasP, NagarajanR, MandalAK, GuptaS.
Postpenetrating keratoplasty glaucoma. Indian J Ophthalmol
1993;41:1814.
22. KaradagO, KuguS, ErdoganG, KandemirB, Eraslan OzdilS,
DoganOK. Incidence of and risk factors for increased intraocular
pressure after penetrating keratoplasty. Cornea 2010;29:27882.
23. PolackFM. Glaucoma in keratoplasty. Cornea 1988;7:679.
24. Wagoner MD, BaAbbad R, AlMohaimeed M, AlSwailem S,
Zimmerman MB; King Khaled Eye Specialist Hospital Corneal
Transplant Study Group. Postoperative complications after
primary adult optical penetrating keratoplasty: Prevalence and
impact on graft survival. Cornea 2009;28:38594.
25. SeitzB, LangenbucherA, NguyenNX, Kchle M, NaumannGO.
Longterm followup of intraocular pressure after penetrating
keratoplasty for keratoconus and Fuchs dystrophy: mparison
of mechanical and excimer laser trephination. Cornea
2002;21:36873.
26. PramanikS, MuschDC, SutphinJE, FarjoAA. Extended
longterm outcomes of penetrating keratoplasty for keratoconus.
Ophthalmology 2006;113:16338.
27. ErdurmusM, CohenEJ, YildizEH, HammersmithKM, LaibsonPR,
VarssanoD, etal. Steroidinduced intraocular pressure elevation
or glaucoma after penetrating keratoplasty in patients with
keratoconus or Fuchs dystrophy. Cornea 2009;28:75964.
28. FanJC, ChowK, PatelDV, McGheeCN. Corticosteroidinduced
intraocular pressure elevation in keratoconus is common
following uncomplicated penetrating keratoplasty. Eye (Lond)
2009;23:205662.

Author Help: Online submission of the manuscripts

Articles can be submitted online from http://www.journalonweb.com. For online submission, the articles should be prepared in two files (first
page file and article file). Images should be submitted separately.
1) First Page File:
Prepare the title page, covering letter, acknowledgement etc. using a word processor program. All information related to your identity should
be included here. Use text/rtf/doc/pdf files. Do not zip the files.
2) Article File:
The main text of the article, beginning with the Abstract to References (including tables) should be in this file. Do not include any informa-
tion (such as acknowledgement, your names in page headers etc.) in this file. Use text/rtf/doc/pdf files. Do not zip the files. Limit the file
size to 1 MB. Do not incorporate images in the file. If file size is large, graphs can be submitted separately as images, without their being
incorporated in the article file. This will reduce the size of the file.
3) Images:
Submit good quality color images. Each image should be less than 4096 kb (4 MB) in size. The size of the image can be reduced by decreas-
ing the actual height and width of the images (keep up to about 6 inches and up to about 1800 x 1200 pixels). JPEG is the most suitable
file format. The image quality should be good enough to judge the scientific value of the image. For the purpose of printing, always retain a
good quality, high resolution image. This high resolution image should be sent to the editorial office at the time of sending a revised article.
4) Legends:
Legends for the figures/images should be included at the end of the article file.

126 Journal of Clinical Ophthalmology and Research - Sep-Dec 2016 - Volume 4 - Issue 3