JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS ORIGINAL ARTICLE

Volume 00, Number 00, 2015

Mary Ann Liebert, Inc.
DOI: 10.1089/jop.2014.0150

Preoperative Versus Intraoperative Subpterygial

Mitomycin C Injection for Prevention
of Pterygium Recurrence

Sameh Saad Mandour, Hatem M. Marey, Hassan Gamal El Din Farahat, and Hala Mosa Mohamed

Abstract

Purpose: To evaluate postoperative outcome and recurrence rate after primary pterygium excision using
preoperative versus intraoperative subpterygial Mitomycin C (MMC) injection.
Methods: Eighty-three eyes with primary pterygium were divided into 2 groups. Group A (35 eyes) was
operated upon with pterygium excision 5 min after subpterygial injection of 0.1 mL 0.015% MMC in the same
operative setting. Group B (48 eyes) was operated upon with pterygium excision 1 month after subpterygial
injection of the same amount and concentration of MMC as in group A. Pterygium regrowth over the cornea for
1 mm or more was considered as a recurrence.
Results: The mean follow-up was 30.66 4.48 months in group A and 29.5 4.3 months in group B. In group A,
the reported recurrence rate was 5.7%, while it was 4.2% in group B. No serious postoperative complications
were reported. There was no statistically significant difference between both groups regarding the recurrence
rate as well as the complication rate.
Conclusion: Both techniques proved to be effective in reducing the recurrence rate after excision of primary
nasal pterygium with minimal postoperative complications, with no need of a second surgery for patients in
group A.

Introduction We present our experience for control of postoperative

D ue to the high recurrence rates (30%80%) after
pterygium excision using the bare sclera technique, a
variety of other treatment modalities have been proposed.1
Adjunctive treatment after a bare sclera excision with top-
ical mitomycin C (MMC) is effective in reducing the re-
currence rate (0.5%16%).24 However, site-threatening
side effects after topical MMC have raised a major concern
about its topical application.5
In an attempt to decrease the ocular surface exposure to
topical MMC, a subpterygial injection of MMC has been
proposed by many authors studying its effect on the recur-
rence rate.68 In a previous work, we investigated the re-
currence rate after preoperative subpterygial injection of
MMC 0.015% 1 month before the pterygium excision and
proved effective.9 However, this technique needs 2 opera-
tive sessions, which may not be desirable by some patients.
Therefore, in this work, we injected MMC in the sub-
pterygial tissue before pterygium excision in the same op-
erative session.
pterygium recurrence by using subpterygial MMC injection
using 2 different techniques on 2 groups of patients with
primary nasal pterygia. Then, we compared the postopera-
tive outcome in both groups.
Methods
This was a prospective randomized study conducted on
83 eyes of 83 patients with primary nasal pterygium, who
attended the health service in Menoufia University Hospitals
in Shebin El Kom and Manshiet Soltan during the period
between January 2009 and January 2013.
The patients were randomly enrolled into 2 groups. The
first group A underwent an injection of 0.1 mL of 0.15 mg/
mL MMC into the body of pterygium that was removed
5 min later in the same operative session. The second group
B underwent an injection of the same amount and concen-
tration of MMC in the body of pterygium 1 month before
surgical excision. In both groups, the primary pterygium
was removed using the bare scleral technique.

Department of Ophthalmology, Menoufia Faculty of Medicine, Shebin El Kom, Egypt.

1
2 MANDOUR ET AL.

All patients of the study had a primary nasal pterygium Table 1. Descriptive Data for Group A and B
encroached on the surface of the cornea with no other ocular
pathology. A comprehensive ophthalmic examination, in- Variable Group A Group B P-value
cluding best-corrected visual acuity testing, slit-lamp ex- Age (years) mean 53.31 11.39 55 10 0.475a
amination, Goldmann applanation tonometry, fundus standard deviation
examination, and examination of ocular motility, was car- Sex 0.925b
ried out for all patients. Consents were taken from all pa- Male 18 24
tients and research was approved by the institutional review Female 17 24
board. All measures were in accordance with the tenets of Extension (mm) mean 3.37 0.74 3.04 10.8 0.123a
the Declaration of Helsinki. standard deviation
Width (mm) mean 4.01 1.12 4.46 1.44 0.128a
standard deviation
Surgical technique Follow-up (months) 30.66 4.48 29.5 4.3 0.237a
Preparation of MMC. Mutamycin (Bristol-Myers- mean standard
Squibb) vial containing 5 mg powder of mitomycin was deviation
reconstituted with 33 mL balanced salt solution to get a a
t-Test.
concentration of 0.15 mg/mL for injection. b
Chi-square test.

Technique of MMC injection. In both groups, topical

anesthesia (benoxinate hydrochloride 0.4%) was first applied
in the involved eye followed by a subconjunctival injection of
0.1 mL of 0.15 mg/mL MMC into the neck of pterygium at
the limbus using a 27-gauge needle on an insulin syringe. A
cotton-tipped applicator was applied to the site of injection
upon withdrawal of the needle to prevent reflux of the in-
jected drug. Thorough rinsing of the ocular surface with sa-
line was performed to remove any residual of MMC.
Bare scleral excision of the pterygium. In group A,
subconjunctival Lidocaine 2% with epinephrine 1:100,000
was injected beneath the body of the pterygium using a 27-
gauge needle.
A Bard Barker knife No. 15 or crescent knife was used to
dissect the head of pterygium starting at 0.5-mm temporal to
the advancing edge until the limbus. A blunt Wesscot
scissor was used to undermine the planned conjunctival
resection and to dissect the pterygium 5 mm from the limbus
leaving the peripheral base to avoid medial rectus tendon
damage. Excision of the pterygium did not extend to or
involve the plica semilunaris. When there was a large bare
sclera, the conjunctiva was sutured to the episcleral 3 mm
from the limbus using an interrupted 8/0 Vicryl Suture.
In group B, after injection, patients received topical
combined antibioticsteroid eye drops (4 times daily) and an
ointment (at bed time) for 1 week. Patients were seen at 1
day, 1 week, and 1 month after the subconjunctival injection
of MMC. A complete ophthalmic examination was per-
formed at each visit. One month after the injection, the
patient underwent a bare scleral excision of the pterygium in
the same manner as in group A.
tion was done. It was judged that the pterygium has re-
curred if there was fibrovascular growth over the cornea for
1 mm or more.
Statistical analysis was carried out with SPSS version 15
(SPSS Science, Inc., Chicago, IL) using students t-test, chi-
square, and Fishers exact test with a level of significance
at 95%.
Results
Eighty-three eyes of 83 patients were enrolled in the
study, with 35 eyes in group A and 48 eyes in group B.
There were 18 (51.4%) males and 17 (48.6%) females in
groups A and 24 (50%) males and 24 (50%) females in
group B. The mean age of patients in group A was
53.31 11.39 years, while in group B it was 55 10 years.
The mean of extension of pterygia onto the cornea was
3.37 0.74 mm in group A and 3.04 10.8 mm in group B.
The mean width of the pterygia on the limbus was
4.01 1.12 mm in group A and 4.46 1.44 mm in group B,
as shown in Table 1.
The mean follow-up period in group A was 30.66 4.48
months, while in group B, it was 29.5 4.3 months.
The visual acuity in group A was improved 13 lines in
15 eyes (42.9%), while in group B, the improvement in
visual acuity was recorded in 18 eyes (37.5%) for 13 lines.
Other cases in both groups showed no improvement, as
shown in Table 2.
In group A, a recurrence was found in 2 (5.7%) eyes.
The time interval from surgery to recurrence was 3 months
in 1 case and 5 months in the other one. Two (4.2%)

The postoperative care and follow-up. Topical com- Table 2. Postoperative Results
and Complications of Group A and B
bined antibioticsteroid eye drops (4 times daily) and ointment
(at bed time) were applied until all signs of inflammation Group A Group B
disappeared for an average of 4 weeks. An eye pad was applied Variable (%) (%) P-value
till complete reepithelialization. Sutures were removed after
healing of the wound or if they became loose. Recurrence 2 (5.7) 2 (4.2) 1.0a
In both groups, patients were examined 1 day postop- Subconjunctival hemorrhage 4 (11.4) 6 (12.5) 1.0a
erative and then after 1 week for evaluation of the healing Conjunctival vascularization 2 (5.7) 2 (4.2) 1.0a
Visual acuity 15 (42.9) 18 (37.5) 0.791b
process and detection of early postoperative complications. improvement 13 lines
Patients were reexamined at 1, 3, 6, 9, and 12 month
a
postoperatively and then every 6 months in the following Fishers exact test.
b
years. During each visit, a complete ophthalmic examina- Chi-square test.
PREVENTION OF PTERYGIUM RECURRENCE
showed a recurrence in group B, with a time interval from
surgery to recurrence being 5 months in 1 case and 6
months in the other one. There was no statistically sig-
nificant difference between the 2 groups regarding the re-
currence rate (P = 1.0).
Regarding the postoperative complications in group A,
there was subconjunctival hemorrhage in 4 cases (11.4%).
There were no patients with delayed epithelial healing,
dellen, or scleral melting. In group B, there was sub-
conjunctival hemorrhage in 6 cases (12.5%). Conjunctival
vascularization was reported in 2 cases (5.7%) in group A
and in 2 cases (4.2%) in group B. However, it was away
from the limbus and was not considered as a recurrence. No
serious postoperative complications were reported.
Discussion
MMC is an alkalizing agent and a potent fibroblast inhib-
itor, which causes irreversible damage to the DNA structures
of the cell. It inhibits both migration of fibroblast and syn-
thesis of new collagen and therefore affects wound healing.10
12
Subconjunctival MMC is known to decrease the number of
stromal fibroblast cells. There is also morphological and
structural damage to vascular endothelial cells.8
MMC used to be applied topically either intraoperatively
or postoperatively. Topical MMC application at the time of
surgery leads to direct contact of MMC with corneal and
conjunctival epithelium, which causes persistent corneal or
conjunctival defects. MMC which comes in direct contact
with the cornea has a negative effect on corneal endothe-
lium. Postoperative MMC application in the form of eye
drops has the same adverse events. Moreover, the surgeon
has to rely on the patient to correctly self-administer a toxic
chemotherapeutic agent at home.1,12
Subpterygial MMC injection has an advantage of more
precise titration of the drug and its direct delivery to the site
of the pathology with no contact with the corneal surface.
The drug is applied directly to the activated fibroblasts in the
subconjunctival space, where it can work directly on the
cells responsible for the pterygium recurrence without
damaging the surface epithelium stem cells, that has no role
in pterygium formation or recurrence. This may diminish
long-term healing difficulties associated with MMC.6
Preoperative subpterygial injection of low-dose MMC
was suggested by Donnenfeld et al.,6 who recorded 6% re-
currence rate in their series. They injected 0.015% MMC
subconjunctivally 1 month before the bare sclera pterygium
excision in 36 patients with a follow-up of 24 months. We
adopted this technique with the same concentration
(0.015%) in a previous work and proved it equally effective
as a limbal conjunctival autograft transplantation in pre-
vention of recurrence.9 Another study used subpterygial
MMC injection 1 month before the pterygium excision, but
with a higher concentration (0.02%) and compared it with
conjunctival rotational flap with intraoperative 0.02% MMC
for 2 min. They reported no recurrence in the subpterygial
injection group, with minimal side effects.7
However, a 2-stage surgery with 1 month apart may not
be favorable for many patients especially in developing
countries, in which health services may not be readily
available all the time. And unfortunately, most pterygium
patients live in these localities. Therefore, in the current
work, the authors tried to overcome this pitfall in order not
3
to lose any patient in our communities. In group A, in the
current study, we injected MMC in the subpterygial space
5 min before the bare sclera excision of the primary pter-
ygium and the results were comparable to the 2-stage sur-
gery in our previous work. To our current knowledge, there
is no previous work discussing the role of intraoperative
subpterygial MMC injection in recurrence prevention.
We injected the same concentration and volume of MMC
in both groups. Therefore, the only difference between both
groups was in the timing of pterygium excision after MMC
injection, with no statistically significant difference between
both groups regarding the recurrence rate, which is the main
goal in this work.
We think that MMC diffuses after its subpterygial in-
jection into the nearby conjunctival tissue. Therefore, after
pterygium excision, MMC persists in sufficient concentra-
tion in the peripterygial conjunctival tissue inhibiting further
abnormal growth. However, laboratory and histopathologic
examination of peripterygial conjunctival tissue after some
time from surgery is needed to confirm the effect of MMC.
Unfortunately, it is not easy to convince postoperative pa-
tients to take a specimen from their conjunctival tissue in the
vicinity of the removed pterygium. This may be suitable to
be done in experimental studies instead. Therefore, we de-
pended solely on the clinical bases in determining the effi-
cacy of intraoperative subpterygial MMC injection.
Moreover, a longer follow-up time is needed in group A to
confirm the long-term effect of intraoperative injection of
MMC on prevention of pterygium recurrence.
Although the safety of the procedure had been addressed
previously in animal research13 and in human study for
treatment of glaucoma,14 ocular cicatricial pemphigoid,15
and pterygium,6,16 the issue of safety of local MMC injec-
tion is still a matter of concern. In the current study, no
dangerous or sight-threatening complication was found in
any group during the relatively short follow-up period of the
study. However, more work is needed to confirm the long-
term safety over several years. Until then, surgeons should
be cautious regarding the dosing and the technique of MMC
application, and patients should be informed about the im-
portance of follow-up to detect and treat potential compli-
cations early.
We concluded that both techniques used in the current
study proved to be effective in reducing the recurrence
rate after excision of primary nasal pterygium with mini-
mal complications in the short- and intermediate-term
postoperatively.
Author Disclosure Statement
No competing financial interests exist.
References
1. Oguz, H., Basar, E., and Gurler, B. Intraoperative application
versus postoperative mitomycin C drops in pterygium sur-
gery. Acta Ophthalmol. Scand. 77:147150, 1999.
2. Lam, D.S., Wong, A.K., Fan, D.S., et al. Intraoperative
mitomycin C to prevent recurrence of pterygium after ex-
cision: a 30-month follow-up study. Ophthalmology. 105:
901904, 1998.
3. Raiskup, F., Solomon, A., Landau, D., et al. Mitomycin C
for pterygium: long term evaluation. Br. J. Ophthalmol.
88:14251428, 2004.
4 MANDOUR ET AL.
4. Yanyali, A.C., Talu, H., Alp, B.N., et al. Intraoperative
mitomycin C in the treatment of pterygium. Cornea. 19:
471473, 2000.
5. Ti, S.E., and Tan, D.T. Tectonic corneal lamellar grafting
for severe scleral melting after pterygium surgery. Oph-
thalmology. 110:11261136, 2003.
6. Donnenfeld, E.D., Perry, H.D., Former, S., and Doshi, S.
Subconjunctival mitomycin C as adjunctive therapy be-
fore pterygium excision. Ophthalmology. 110:10121016,
2003.
7. Khakshoor, H., Razavi, M.E., Daneshvar, R., et al. Pre-
operative subpterygeal injection vs intraoperative mito-
mycin C for pterygium removal: comparison of results and
complications. Am. J. Ophthalmol. 150:193198, 2010.
8. Chang, Y.S., Chen, W.C., Tseng, S.H., Sze, C.I., and Wu,
C.L. Subconjunctival mitomycin C before pterygium
excision: an ultrastructural study. Cornea. 27:471475,
2008.
9. Mandour, S.S., Farahat, H.G., and Mohamed, H.M. Pre-
operative subpterygial mitomycin C injection versus limbal
conjunctival autograft transplantation for prevention of
pterygium recurrence. J. Ocul. Pharmacol. Ther. 27:481
485, 2011.
10. Frucht-Pery, J., Siganos, C.S., and Ilsar, M. Intraoperative
application of topical mitomycin C for pterygium surgery.
Ophthalmology. 103:674677, 1996.
11. Singh, G., Wilson, M.R., and Foster, C.S. Mitomycin eye
drops as treatment for pterygium. Ophthalmology. 95:813
821, 1988.
12. Caliskan, S., Orhan, M., and Irkec, M. Intraoperative and
postoperative use of mitomycin-C in the treatment of primary
pterygium. Ophthalmic Surg. Lasers. 27:600604, 1996.
13. Kee, C., Pelzek, C.D., and Kaufman, P.L. Mitomycin C
suppresses aqueous humor flow in cynomolgus monkeys.
Arch. Ophthalmol. 113:239242, 1995.
14. Gandolfi, S,A., Vecchi, M., and Braccio, L. Decrease of in-
traocular pressure after subconjunctival injection of mitomycin
in human glaucoma. Arch. Ophthalmol. 113:582585, 1995.
15. Donnenfeld, E.D., Perry, H.D., Wallerstein, A., et al.
Subconjunctival mitomycin C for the treatment of ocular
cicatricial pemphigoid. Ophthalmology. 106:7278, 1999.
16. Avisar, R., Bar, S., and Weinberger, D. Preoperative in-
jection of mitomycin C in combined pterygium and cataract
surgery. Cornea. 24:406409, 2005.
Received: November 24, 2014
Accepted: April 1, 2015
Address correspondence to:
Dr. Sameh Saad Mandour
Department of Ophthalmology
Menoufia Faculty of Medicine
17 El Gendi Street
Meet Khaqan Road
Shebin El Kom 32111-13
Egypt
E-mail: dr_ssmandour@hotmail.com