5-FU as adjuvant
CO Bekibele, AM Baiyeroju, BA Olusanya,
AO Ashaye and TS Oluleye
adjunctantimetabolitetherapy has been shown to
be effective in preventing pterygium recurrence.
Objective To compare 5 fluorouracil (5-FU) to
conjunctival autograft in the treatment of
large, fleshy pterygium.
MethodsA randomised controlled
prospective study of outcome of pterygium
treatment using 5-FU as adjuvant treatment
compared to conjunctiva autograft. Thirty-five
eyes with large pterygium treated with bare
sclera conjunctival excision plus 5-FU were
compared with 33 eyes treated with excision
and conjunctival autograft alone.
ResultsPost-operative pterygium recurrence
was observed in four (11.4%) eyes treated with
5-FU and 4 (12.1%) eyes treated with conjunc-
tiva autograft (P40.05). The post-operative
complications included, granuloma formation
11.4% for 5-FU and 3.0% for autograft and
conjunctival discharge 5.7% for 5-FU group only.
Conclusion5-FU is marginally superior to
conjunctival autograft in the prevention of
pterygium recurrence but neither gives a more
desirable single digit recurrence rate. Rando-
mised studies combining both conjunctival
autograft and 5-FU in pterygium treatment is
advocated to further explore their effect.
Eye (2008) 22, 31–34; doi:10.1038/sj.eye.6702480;
published online 16 June 2006
The use of conjunctiva autograft,
Keywords: fleshy pterygium; pterygium
recurrence; 5-fluorouracil; conjunctival
Pterygium is a degenerative lesion presenting as
a fibro vascular conjunctival growth in the
palpebral aperture of the eye with corneal
extension. The aetiology of pterygium has been
linked to exposure to ultraviolet irradiation,
chronic irritation by dust, wind, and other
environmental factors.1Thus, it is more
commonly seen among outdoor workers in
tropical countries.2Pterygium may be
responsible for disturbance of vision by its
astigmatic effect or by growing so large as to
occlude the visual axis. It could also be a cause
of much ocular irritation as well as being
cosmetically unacceptable for many people
especially when fleshy or inflamed. The
treatment for pterygium is surgical excision.
However, due to high recurrence rate with
simple excision which could be as high as 40%
in some cases,3the use of adjunct therapy such
as beta radiation, antimetabolites such as
mitomycin-C and 5-fluorouracil (5-FU), and
conjunctiva autograft have been advocated.4,5
Both mitomycin-C and 5-FU have been
shown to cause a reduction in recurrence rate of
pterygium but they are both potentially toxic to
ocular tissues and have been associated with
some complications.6Conjunctiva autograft on
the other hand has been said to be free of
complications and although takes longer to
perform is said to be associated with little
or no recurrence.7
The main objective of this study was to
compare 5-FU to conjunctival autograft in the
treatment of large, fleshy pterygium in terms of
preventing recurrence as well as relative safety
and complication rate.
Materials and methods
A randomised controlled and prospective study
of outcome of pterygium treatment using 5-FU
as adjuvant treatment compared to conjunctiva
Received: 25 January 2006
Accepted in revised form:
9 May 2006
Published online: 16 June
college Hospital Ibadanu,
CO Bekibele, Department of
of Ibadan, Queen Elizabeth
Road, University college
Hospital Ibadanu, Ibadan,
Tel: þ2 34 803Eþ12;
Fax: þ234 2 2413545.
Eye (2008) 22, 31–34
& 2008 Nature Publishing Group All rights reserved 0950-222X/08 $30.00
autograft carried out at the University College Hospital
Ibadan, between May 2003 and June 2005.
Selection of patients
All patients seen with fleshy pterygium encroaching
2mm or more into cornea were selected and randomised
into one of the two groups.
Sample size was calculated from estimation of
proportions with assumption of success rate of about
80% for 5-FU and expected success rate of 100% for
conjuctival autograft, alpha error, 0.05%, and a power
N ¼Za=P0ð1 ? P0Þ ? Zb=P1ð1 ? P1Þ2
P1 ? P0
The sample size was increased to 80 to take care of
dropouts. Following adequate explanation and obtaining
of consent, the subjects were randomised into their
respective groups using a ‘lucky dip’ technique. Small
folded sheets of paper numbered 1–40 and 41–80 were
kept in two separate envelopes (for male patients and
female patients, respectively). Male and female patients
who met the selection criteria were requested to pick one
folded sheet of paper from the appropriate envelope as
they presented to the clinic consecutively. Those who
picked odd numbers were assigned to 5-FU while even
numbers were assigned to conjunctiva autograph. For
patients with bilateral pterygium, the worse eye was
randomised first and the other eye was assigned to the
alternative group as a control.
Data collection and operation procedure
Information obtained from subjects using a structured
questionnaire included age, sex, occupation, eye affected,
location, morphology, size of pterygium from limbus
(measured with a slit lamp), vision of eye to be operated,
information on previous pterygium surgery performed.
All patients received sub-conjunctival 2% lignocaine
with adrenaline, for local anaesthesia. Pterygium tissue
was excised from cornea with bard parker blade under
microscope and was subsequently bluntly dissected from
over lying conjunctiva and underlying sclera. The use of
cautery too was minimised.
The 5-FU group after an initial pterygium excision had
the bare scleral area of the pterygium bed exposed to a
section of a Weck-cel sponge soaked in 50mg/ml of 5-FU
for 5min during which there was intermittent wetting of
the sponge every minute with a drop of 5-FU, at the end
of 5min, the sponge was removed and discarded and the
eye copiously irrigated with saline solution for about
1min. The cut conjunctiva ends were anchored to sclera
with 8–0 silk suture.
Conjunctiva graft procedure
The conjunctiva autograft group after an initial
pterygium excision had a conjunctiva free graft of a size
equivalent to the scleral defect excised from the
pterygium free superior 12 O’-clock bulbar conjunctiva
inclusive of limbal conjunctiva and 0.5mm of clear
cornea of the same eye. There after the free graft was
sutured to the recipient bed with interrupted 8–0 sutures
taking care to ensure proper orientation of the ends of the
graft (cornea end of the graft sutured to the recipient
Postoperatively, both groups had instillation of
antibiotic ointment and dexametasone (steroid) drops
postoperatively for between 8 and 10 weeks, depending
on duration of inflammation. Follow-up visits were at
post op days 1, 7, 21, monthly for 2 months and every
3months for between 1 and 2 years.
Recurrence of pterygium was defined as growth of
fibro vascular tissue 1mm or more into cornea as
observed with a slit lamp.
Data collected were analysed with the aid of a personal
computer using SPSS version 10.
A total of 68 eyes of 62 subjects where studied. 12 eyes
that were initially randomised and included in the study
did not show up for surgery. Thirty-five eyes were
treated with 5-FU (16 male patients and 19 female
patients) while 33 eyes were treated with conjuctival
autograft (19 male patients and 14 female patients). The
mean age of the 5-FU group was 49 years while that for
the autograft group was 45.7 years (P40.05). All the
treated pterygia where large and fleshy, and extended
from 2mm to over 4mm into the cornea in size. About
57.2% of eyes treated with 5-FU compared to 90% of
those treated by autograft ranged from 2 to 4mm in size
while the remainder were over 4mm in size. There were
five recurrent pterygia included in the study, two were
treated by 5-FU while three were treated by autograft.
Postoperatively pterygium recurrence was observed in
four (11.4%) eyes treated with 5-FU and four (12.1%) eyes
treated with conjunctiva autograft (P40.05). All
recurrences were observed between the third and fifth
postoperative visits (2–8 months post op) for conjunctiva
autograft and between fourth and fifth post op visit (3–8
months post op) for the 5-FU group. Examination of the
Pterygium treatment using 5-FU
CO Bekibele et al
profile of eyes with pterygium recurrence showed that
five out of the eight were between 2 and 4mm in size pre
op, while 2 were over 4mm in size pre op, all were fleshy
but 2 were also inflamed while only one (from the
autograft group) had previously been operated by the
bare sclera technique. Table 1 shows the detailed profile
of eyes that developed pterygium recurrence.
Postoperative complications observed among the
studied eyes included granuloma formation 11.4% for
5-FU and 3.0% for autograft and surface infection 5.7%
for 5 FU only (Table 2).
This study has observed comparable rates of 88.6 and
87.9%, respectively, for the successful treatment of large
and fleshy pterygia using either 5-FU or conjunctival
autograft. Although 5-FU appears to be marginally
superior to conjunctival autograft in preventing
recurrence, both are however, far from having desirable
success rates of 100%. The recurrence rate of 11.4%
obtained by intraoperative application of 50mg/ml of
5-FU for 5min was marginally better than 12.4%
observed for conjuctival autograft, the difference was
however, not statistically significant. Less time is also
spent in applying 5-FU (5min) than conjunctiva
autograft (20–30min, although this could be reduced
with use of fibrin tissue glue when it is available).
Conjunctiva autograft, however, has an edge over 5-FU
in that it is much cheaper and has fewer complications
associated with it.
The recurrence rate from 5-FU observed in this study is
lower than the 14% recurrence observed by Akarsu et al8
from combined intraoperative (3min) application and
postoperative injection of 25mg/ml of 5-FU. The
recurrence rate following autograft was also lower than
18% reported by Wang and Law9and 14.6% for recurrent
pterygium by Mutlu et al.10Mitomycin C is reported11to
be more effective in preventing pterygium recurrence
than conjunctiva autograft but cost and associated side
effects are factors, which could limit its use. 5-FU is
cheaper than mitimycin C and is associated with fewer
side effects. Although 5-FU appears to be marginally
superior to conjunctiva autograft in the prevention of
pterygium neither gives a recurrence of near zero
percent. Thus more randomised studies possibly
combining 5-FU with autograft are desirable. Such a
combination may have fewer side effects than
treatment with mitomycin C but possibly better
prevention of pterygium recurrence than either
5-FU or autograft alone.
Five subjects with previous pterygium recurrence
following use of other surgical methods were included in
the study because excluding them would have reduced
the number of cases available for analysis. Their presence
is, however, not likely to bias the study because they
were evenly distributed between the two study groups.
Profile of subjects with recurrent pterygium following treatment with 5-FU as adjuvant treatment compared to conjunctiva
Characteristic5-FU Conjunctival autograft
RecurrenceNo recurrenceRecurrence No recurrence
49 years49 years 41.3 years46.3 years
2–4mm in size
44mm in size
adjuvant treatment compared to conjunctiva autograft
Complications of pterygium treatment using 5-FU as
Complication5-FU Conjunctival autograft
Early post op inflammation
Pterygium treatment using 5-FU
CO Bekibele et al
5-FU is marginally superior to conjunctiva autograft in
the prevention of pterygium recurrence but neither gives
100% success rate, randomised studies combining both
conjuctival autograft and 5-FU in pterygium treatment
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Pterygium treatment using 5-FU
CO Bekibele et al