DOI: 10.5301/ejo.

5000004

Eur J Ophthalmol 2012; 22 ( Suppl. 7 ): S5-S10

ORIGINAL ARTICLE

Topical cyclosporine A administration after pterygium

surgery
Kemal zlken, Mustafa Ko, Orhan Ayar, Hikmet Hasiripi
3rd Clinic of Ophthalmology, Ankara Numune Education and Research Hospital, Ankara - Turkey
3rd Clinic of Ophthalmology, Ankara Numune Education and Research Hospital, Ankara - Turkey
3rd Clinic of Ophthalmology, Ankara Numune Education and Research Hospital, Ankara - Turkey
3rd Clinic of Ophthalmology, Ankara Numune Education and Research Hospital, Ankara - Turkey

PURPOSE. To evaluate the success rate of topical cyclosporine A (tCsA) (Restasis, Allergan) in preventing the recurrence of pterygium excision and conjunctival flap rotation technique in patients applying
to our clinic and diagnosed with pterygium.
METHODS. A total of 56 eyes with primary pterygium in 56 patients were examined and operated with
pterygium excision and conjunctival flap rotation technique between October 2008 and September 2009.
A total of 26 eyes of these 56 patients were treated with tCsA (Restasis, Allergan) for 6 months during
the postoperative period and assigned as the treatment group. The other 30 eyes of 56 patients were
assigned as the control group. The operated patients were followed up for approximately 11 months.
RESULTS. The 2 groups were similar in age, sex, and pterygial size. The largest percentage of the patients were farmers (30.3%). The pterygium recurred in 8 (14.2%) of 56 patients; 2 of them were in the
treatment group (7.7%) and 6 of them were in the control group (20.0%). There was not any complication threatening vision among operated patients. Recurrence rates between the control and treatment
group were statistically significant (p<0.05). The complication and postoperative compliance rates
were lower in the treatment group than the control group. The difference between preoperative and
postoperative Schirmer I test results among the treatment and control group was statistically significant (p<0.05). The Schirmer I test results increased after tCsA treatment for patients assigned to the
treatment group.
CONCLUSIONS. The results suggest that tCsA (Restasis, Allergan) can be used safely and effectively
after pterygium surgery to obtain lower rates of recurrence.
KEY WORDS. Conjunctival flap rotation, Pterygium, Pterygium recurrence, Topical cyclosporine A
Accepted: May 12, 2011

INTRODUCTION
Pterygium is a common conjunctival disease where fibrovascular proliferation of the conjunctiva may involve the cornea.
For centuries, pterygium surgery, pathology, and treatment
have been controversial and ophthalmologists still have not
come to an agreement about the best treatment (1).
Pterygium is an external eye disease seen more frequently
in tropical and subtropical regions (2, 3). Although the exact
etiology is not known, in recent years, it is emphasized that
exposure to ultraviolet light can result in limbal inflammation and damage to the limbal stem cells (4-6).Moreover,
air pollution, dust, wind, and other environmental condi-

tions are important risk factors for pterygium formation by

causing conjunctival irritation (7, 9).
Pterygium treatment success rate is determined by low recurrence rate, good cosmetic results, decrease in irritation
symptoms, and conservation or correction of visual acuity
(8). To achieve these, many surgical techniques have been
developed. In recent years, adjuvant agents such as mitomycin C (MMC), 5 fluorouracil (5-FU), cyclosporine A (CsA),
and thiotepa have been used to lower recurrence rate (9).
Cyclosporine A is an immunosuppressive systemic drug
which is usually used in order to prevent tissue rejection
after transplantation, and also to treat psoriasis or rheumatoid arthritis (10). Mechanism of action of CsA in inflamma-

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Topical cyclosporine A after pterygium surgery

tory disorders is preventing T-cell activation (11). Recently,

topical CsA has been used to treat dry eye syndrome, vernal keratoconjunctivitis, corneal ulcers, herpetic stromal
keratitis, and several other eye disorders.
Our aim was to put forward the effect of a new adjuvant
agent, topical CsA (0.05%), on recurrence rate after surgical treatment of primary pterygium.

MATERIALS AND METHODS

The study is based on 56 eyes of 56 patients of the Ankara
Numune Education and Research Hospital and diagnosed
with primary pterygium and operated by pterygium excision and conjunctival flap rotation technique between October 2008 and September 2009. We planned the study in
a nonrandomized prospective manner.
Indications for pterygium surgeries were visual acuity problems, extension across pupillary region, and cosmetic problems. Before surgeries, pterygial tissues were evaluated in 3
grades: grade 1, small primary pterygium; grade 2, advanced
primary pterygium which has not arrived optical zone; grade
3, advanced primary pterygium which covered optical zone.
Patients with ocular or eyelid problems, glaucoma, vitreoretinal problems, or serious systemic disorders were not
included in this study. Schirmer I and fluorescein breakup time tests were performed preoperatively. The patients
were operated with primary excision and conjunctival flap
rotation technique.
In all cases after pterygium excision, the defective region
was covered with a flap prepared from superior or inferior
conjunctiva.
After the operation, the conjunctiva was coated with antibiotic ointments and patients were discharged with antibiotic drop regimen (trimethoprim + polymyxin b sulphate).
After the healing of the defect in corneal epithelium (usually
the postoperative first day), topical steroid treatment was
started (fluorometholone) and continued for 1 month. Steroid drops were gradually decreased. Because the sutures
were absorbable, they did not need to be extracted. After
the operation, the patients were examined monthly.
Fifty-six patients who were operated were divided into
2 groups. A total of 26 eyes of the patients were treated
with topical cyclosporine A (tCsA) (Restasis, Allergan) for 6
months during the postoperative period and assigned as the
treatment group (group 1). The other 30 eyes were assigned
as the control group (group 2). The insertion and preservaS6

tion of the eyedrops, especially topical cyclosporine A, were

explained in detail to the patients. All of the patients were
followed approximately 11 months for complications and
recurrence. The fibrovascular tissue exceeding the cornea
over 1 mm was regarded as recurrence.

Data analysis
Statistics of the study were analyzed with SPSS 11.5 at
the Hacettepe University Medical School Biostatistics Department. The differences between 2 groups for sex and
recurrence were analyzed with chi-square test; numerical
variables demonstrating normal distribution were analyzed
with Shapiro-Wilk test. In order to compare age distribution
between 2 groups, t test, and to compare the other variables, Mann-Whitney U test, was utilized. When p value
was smaller than 0.05, the difference between 2 groups
was regarded as statistically significant.

RESULTS
Fifty-six eyes of 56 patients who had applied to Ankara
Numune Education and Research Hospital between June
2008 and September 2009 and diagnosed with primary
pterygium were included in our study.
The average age in the treatment group was 56.6210.23,
while in the control group it was 53.2313.94 (p>0.05). A
total of 46.2% of the patients in the treatment group were
male; 46.7% of the patients in the control group were male
(p>0.05). The mean follow-up time was 12.193.64 months
in the treatment group, while it was 10.302.69 months in
the control group (p>0.05). A total of 17 (30.3%) of the patients included in our study were farmers, 9 of whom were
in the treatment group, and the rest in the control group. A
total of 16 (29.3%) were housewives, 9 (16.7%) were civil
servants, and 14 (23.7%) were retired. While most of the
farmer patients had pterygial tissues which were grade
3 (70.6%), in most of the civil servants, housewives, and
retired patients, the pterygial tissue grade was 2 (76.5%,
73.3%, 57.1%). Also, while 65.6% of patients in the treatment group had additional ocular pathologies, in the control group the percentage was 75.3. The most common
additional ocular pathology was pterygium in the contralateral eye. There was no statistically significant difference
between groups in patient characteristics such as gender,
occupation, follow-up time, additional ocular pathologies,

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zlken et al

TABLE I - COMPARISON BETWEEN PREOPERATIVE AND POSTOPERATIVE SCHIRMER I TEST VALUES AND COMPARISON
BETWEEN SCHIRMER I CHANGE AND TOPICAL CYCLOSPORINE A
Schirmer I (mm/5 min)

tCsA not applied (n=30)

tCsA applied (n=26)

p values

Preoperative

10.833.52

7.924.39

<0.05

Postoperative

11.063.80

10.802.71

<0.05

0.231.10

2.882.32

<0.05

Change
tCsA = topical cyclosporine A.

TABLE II - COMPARISON OF RECURRENCE RATES AND TOPICAL CYCLOSPORINE A APPLICATION

Recurrence

tCsA not applied (n=30), n (%)

tCsA applied (n=26), n (%)

p values

Detected

6 (20)

2 (7.7)

<0.05

Not detected

24 (80)

24 (92.3)

<0.05

tCsA = topical cyclosporine A.

TABLE III - COMPARISON OF COMPLICATIONS IN THE CONTROL AND TREATMENT GROUPS

Dellen

tCsA not applied (n=30), n (%)

tCsA applied (n=26), n (%)

p values

14 (46.7)

6 (23.1)

<0.05

Scleral thinning

2 (6.7)

0 (0.0)

<0.05

Pyogenic granuloma

2 (6.7)

0 (0.0)

<0.05

tCsA = topical cyclosporine A.

and preoperative grades of pterygium.

The average Schirmer I test result in the patients included
in our study was 9.48 mm/5 min. The average preoperative Schirmer I and fluorescein break-up time values of the
treatment group were 7.924.39 mm/5 min and 8.503.04
s. At the end of follow-up period, the average Schirmer I
test result was 10.82.71 mm/5 min. When preoperative
and postoperative Schirmer I test results were compared,
the average increase in the treatment group was 2.88,
while in the control group it was 0.23 (p<0.05).
No serious complication has been detected in any of the
cases in our study. The most common postoperative complication in our study was Dellen formation, 11 (36.6%) in
the control group and 9 (34.6%) in the treatment group.
There is no statistically significant difference between
groups in Dellen formation complication. In patients with
Dellen formation we reported sudden healing after treatment with preservative-free eyedrops. Pyogenic granuloma which healed with medical treatment was observed
in 2 patients in the control group (6.7%). Scleral ischemia
which has not caused any serious complications like scler-

al thinning was observed in 2 patients in the control group

(6.7%). There were no pyogenic granuloma and sclera thinning complications in the treatment group. This low rate of
scleral ischemia may have been related to not using excessive cauterization.
The recurrence rate in the treatment group was 7.7% (2
patients), while it was 20% (6 patients) in the control group.
The difference between the 2 groups was statistically significant (p<0.05). The mean recurrence time in the treatment group was 6.5 months, while in the control group it
was 3.11 months (p<0.05). A total of 24.1% of patients in
the treatment group had postoperative complications while
66.7% of the patients in the control group had complications (p<0.05).

DISCUSSION
Pterygium is a common degenerative corneal disease which
has multifactorial etiology (12, 13). As our country has many
environmental factors accepted as risk factors in the etio-

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Topical cyclosporine A after pterygium surgery

pathogenesis, such as climate conditions, pterygium is a

frequent serious corneal surface disease in our clinics.
The most effective method to eliminate cosmetic and visual discomfort developed by pterygium is surgery. The
main goals after surgery are to extinguish nonspecific
complaints such as lacrimation, burning, and stinging, and
also to achieve good cosmetic results (13).
Ethnic group, sex, ultraviolet lights, dry and hot climate
conditions, and occupation are the major risk factors for
pterygium etiopathogenesis. Based on all of these factors,
we can say that pterygium is a result of a nutrition defect
of the anterior layers of the cornea (13). The most frequent
postoperative complication is the recurrence of the pathologic tissue. When an overview of the literature of the last
20 years was done, we can see that the recurrence rates
vary between 0% and 88%. Furthermore, some techniques
are depicted by low recurrence rates.
Autologous conjunctival transplantation is one of the most
accepted surgery techniques. In this technique it is believed
that by contact inhibition and mechanical barrier, proliferation
and growth of the pterygial tissue is eliminated, and lower recurrence rates are obtained. It is harder and more dependent
on the experience of the surgeon. Moreover, this technique is
not suggested for glaucoma patients who can be candidates
for filtration surgery if defective region is very wide (14).
As in many other ocular surface disorders, amniotic membrane is an indispensable material for pterygium surgery.
Amniotic membrane anatomically consists of epithelium,
basement membrane, and avascular stroma. Basement
membrane contributes to the growth and differentiation of
the epithelium and also behaves as a barrier for pterygial
pathologic cells that can proliferate over the cornea. Theoretically, though it seems like an ideal material, practically it
does not achieve good clinical results every time (15).
During research about the pathogenesis of pterygium, it
became evident that pterygium is virtually a local deficiency of limbus. It is advocated that limbal barrier deteriorates
and results in proliferation of the pterygium over cornea.
In the study of Al Fayez (16) comparing recurrence rates of
conjunctival and limbal conjunctival autograft transplantation,
it was suggested that the difference between the 2 techniques
is not statistically significant but in the case of recurrent pterygium, limbal conjunctival transplantation is more effective.
In the literature, recurrence rate of conjunctival flap rotation technique varies between 0.75% and 35% (17). Some
advantages of flap rotation are easy suturing compared to
free flap and the possibility of wide excision of the pterygial
S8

tissue. Since blood is supplied to conjunctival flap from its

base, excessive cauterization should not be performed on
the subjacent sclera. Except for flap contracture and cyst
formation, no serious complication has been reported (18).
When literature review was done, it is found that the recurrence rate of conjunctival flap rotation technique is the
same as the rate of conjunctival autograft and adjuvant mitomycin C application.
Having analyzed all these data, we decided to use flap rotation technique, which has been proved to be safe and
effective, in all of the patients.
Like the grade of pterygium, many factors such as age,
gender, and occupation are very important in the recurrence rate of pterygium. Therefore we analyzed patient
characteristics and found that there was no significant
difference between groups in age, gender, occupation, or
grades of pterygium. Nonetheless, we found that the largest percentage of patients diagnosed with primary pterygium were farmers. We believe that this result is related to
increased exposure to ultraviolet light. We did not use any
objective test to measure sun exposure of patients. However, since there was no significant difference between the
number of farmers and pterygium grades in each group
and as the farmers are the group who are exposed to the
sun the most in our study, we suggest that there is no significant difference between the groups in sun exposure.
Adjuvant agents are treatment choices that help to eliminate recurrence after surgery and can be used easily.
Mitomycin C is the most commonly used adjuvant agent.
It is an alkylating antineoplastic drug that inhibits cell replication and division by inhibiting DNA synthesis. It is effective and safe when used intraoperatively with a concentration of 0.02% for 5 minutes. Mitomycin C application can
result in cataract, superficial punctuate keratitis, delay in
corneal healing, and rarely, serious complications such as
necrosis of the sclera, microbial keratitis, glaucoma, and
endophthalmitis. In cases with dry eye syndrome, herpetic
keratitis, and blepharitis, it should be used very carefully.
The recurrence rates of mitomycin C vary between 4% and
22% in the literature (19).
Thiotepa (triethylene cyclophosphamide) is a cytotoxic and
radiomimetic agent. It inhibits mitosis and cell division in
rapidly proliferating tissues. Recurrence rates with a concentration of 0.05% were between 0.8% and 22.4% in the
literature when used postoperatively for 68 weeks. Its usage is not very common because of formation of permanent eyelid depigmentation (20).

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zlken et al

Since pterygial epithelial tissue consists of T-lymphocyte,

inflammatory adhesion molecule 1, and HLA-DR infiltration, it is supported that cellular immunity and inflammatory response play a role in pterygium pathogenesis (21).
Cyclosporine A is a drug derived from fungal peptide that
inhibits the activation of translocation of cytoplasmic transcription factors which are fundamental for T-lymphocyte
activation and production of inflammatory cytokines (22).
The similarity between pterygium histopathology and action
of topical cyclosporine A supports that topical cyclosporine
A is effective in inhibition of the recurrence of pterygium.
There is very limited research in the literature on this subject.
Therefore we planned our study based on this hypothesis.
In a study conducted by Yalcn Tok et al (23), topical cyclosporine A (0.05%) was inserted twice a day for a period
of 6 months in 31 eyes after simple excision and primary
closure technique and 12.9% recurrence rate was reported.
Aydn et al used topical cyclosporine A (0.05%) twice a day
for 3 months in 60 patients after primary excision and limbal
conjunctival autotransplantation and they reported 3.4% recurrence (22).
Even though the relationship between dry eye syndrome
and pterygium is controversial, there are some studies defending that change in tear film layer can stimulate proliferation of subconjunctival fibrovascular tissue proliferation
(12). Gndz et al (24) evaluated tear function in pterygium
patients and compared it with the control group. The average Schirmer I test results were 10.31.8 mm/5 min in
pterygium patients while it was 18.73.1 mm/5 min in the
control group (p<0.05). The mean fluorescein break-up
time in the pterygium group was 9.11.5 seconds whereas
it was 10.01.3 seconds in the control group (p<0.05). Because Schirmer I and fluorescein break-up time test results
were lower in the pterygium group compared to the control
group, they stated that dry eye syndrome can play a role in
pterygium etiopathogenesis.
In our study, the mean Schirmer I test result of the 56 patients was 9.484.17 mm/5 seconds and mean fluorescein
break-up time was 9.182.74 seconds. There was no significant difference between the groups. When these tests
were repeated after the follow-up period, we found that the
increase in Schirmer I test results was statistically significant in 26 patients of the treatment group (p<0.05). Since
preoperative Schirmer I test results were low and in the
treatment group these values increased significantly, we
can say that dry eye syndrome has an important role in
pterygium formation. From this information we can state

that treatment of dry eye syndrome inhibits pterygium formation and lowers recurrence rates. Since in the patients
treated with topical cyclosporine A recurrence rates were
lower than in the control group, we can say that in addition
to its antiinflammatory effect, topical cyclosporine A helps
to correct tear film layer irregularities and consequently
treats dry eye syndrome and contributes to decrement of
recurrence rates of pterygium.
The most common postoperative complication in our study
was Dellen formation. This result is related to low average
Schirmer I test results and formation of corneal irregularity
in the early postoperative period. As expected, in patients
with Dellen formation, we reported sudden healing after
treatment with preservative-free eyedrops.
It is important to underscore the limitations of this study.
First, we were not able to select the same surgeon in every
case. Since the experience and surgical skills of each surgeon are not equal, we could not achieve homogeneity in
surgery. Second, there is no information about exact dosage and period of implementation of topical cyclosporine
A specific to our cases in literature. The desirable effects of
topical cyclosporine A might be obtained by lower dosage
and time of implementation; because of this, further prospective studies should be undertaken. Finally, there were
few cases in our study to identify the demographic features
of pterygium. In order to acquire this, large-scale studies
should be carried out to clarify exact relationship between
dry eye syndrome and pterygium disease.

CONCLUSIONS
In our study, all the patients diagnosed with primary pterygium were operated with conjunctival flap rotation technique.
Because we have not observed any serious complications,
we believe that conjunctival flap rotation technique is a safe
and practical method of choice in pterygium surgery.
Evaluating the occupations of the patients, we found that
approximately one-third of our patients were farmers who
had high exposure to ultraviolet light. Based on these data,
we conclude that ultraviolet light plays an important role in
pterygium etiology.
The mean Schirmer I test and the mean fluorescein breakup time results were low when compared with the normal
population, and we believe that dry eye syndrome is another important risk factor for pterygium etiology. We have not
observed any serious complications during treatment with

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Topical cyclosporine A after pterygium surgery

topical cyclosporine A. Thus topical cyclosporine A seems

to be a safe adjuvant drug in pterygium treatment. When
preoperative test results were compared with postoperative ones in the treatment group, the difference between
the two was statistically significant. Thus we conclude that
topical cyclosporine A treatment improves lacrimal secretion and helps in the treatment of pterygium.
The recurrence rate in the treatment group was lower than
in the control group. Based on this result, we can conclude
that topical cyclosporine A treatment lowers pterygium recurrence rate distinctly. The average recurrence time of the
treatment group was of longer duration than in the control
group, showing that topical cyclosporine A treatment prolongs recurrence-free time.
Based on our study, we suggest that topical cyclosporine
A is a safe, predictable, and effective option for prevention
of pterygium recurrence.

6.

The authors report no proprietary interest or financial support.

15.

Address for correspondence:

Kemal zlken, MD
Ankara Numune Education and Research Hospital
3rd Clinic of Ophthalmology
Ehlibeyt Mah
Ceyhun Atf Kansu Cad
1271 Sok No:35/11
Balgat 06100, Ankara, Turkey
kozulken@hotmail.com

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