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April - June 2006

Original Article

111

Low dose Mitomycin-C in severe vernal keratoconjunctivitis:

A randomized prospective double blind study

Arun K Jain, MD; Jaspreet Sukhija, MS

Purpose: To study the efficacy and safety of low dose topical Mitomycin C (MMC) in severe Vernal
keratoconjunctivitis (VKC).
Design: Placebo controlled double masked randomized clinical trial.
Materials and Methods: Twenty-eight patients with severe VKC were randomly assigned to receive either
topical MMC (0.01%) (n=17) or distilled water (n=11) three times daily for a period of two weeks. Signs and
symptoms were recorded on day of presentation and at the end of treatment period (2 weeks). Mann
Whitney test was used to analyze the signs and symptoms in the two groups.
Results: No statistically significant difference was observed in terms of severity of symptoms at
presentation. At two weeks patients in the MMC group showed significant decrease in tearing, foreign body
sensation, discharge, hyperemia, punctate keratitis, limbal edema and trantas spots. No adverse effect of
MMC was observed.
Conclusion: Short term low dose topical MMC is an effective and safe drug to control acute exacerbations
in patients of severe VKC refractory to conventional treatment.
Key words: Mitomycin-C, vernal keratoconjunctivitis.
Indian J Ophthalmol 2006;54:111-16

Vernal keratoconjunctivitis (VKC) is a bilateral recurrent

inflammatory disorder of the conjunctiva and cornea. It is
thought to be more complex than a simple type 1
hypersensitivity reaction. The trophic changes are due to
enhanced fibroblast proliferation and collagen deposition in
epithelium and substantia propria caused by eosinophil and
mast cell degranulation.1
The signs and symptoms of VKC usually occur from April
to August, although some patients have a perennial form of
the disease.2 The spectrum of disease differs in tropical and
temperate countries. 3 The reported risk of visual loss is
generally greater in tropical countries which is about 10%.4-7
Corneal morbidity along with steroid related complications
may lead to permanent visual impairment. Therefore there is
need for an alternative, effective, safe drug which can decrease
the morbidity from this potentially blinding disease. Topical
Mitomycin - C (MMC) has been used in the management of
allergic conjunctivitis.8,9
MMC inhibits cell proliferation and is non cell cycle specific.10
It has been previously used in pterygium surgery11 glaucoma
Cornea and External Diseases Section, Department of
Ophthalmology, Post Graduate institute of Medical Education
and Research, (PGIMER), Chandigarh, India
Correspondence to A. K. Jain, Dept of Ophthalmology, PGIMER,
Sector 12, Chandigarh - 160 012, India. E-mail:
<arooonjain@hotmail.com>
Manuscript received: 25.3.05; Revision accepted: 5.12.05

filtration procedures12 and in management of conjunctival

squamous cell neoplasia.13-16
On literature search (Medline) we found only one study
from Turkey, which has temperate climate, showing use of
topical MMC in management of recalcitrant VKC.8 The purpose
of this study was to evaluate the effect of 0.01% MMC eye
drops in patients of Indian origin [India has mostly tropical
climate], with severe VKC refractory to topical steroid and
mast cell stabilizers.

Materials and Methods

The study was undertaken at the Post Graduate Institute of
Medical Education and Research, Chandigarh, India after
approval from the institutional review board. Twenty-eight
patients with a history of severe VKC who provided informed
consent were included in the study. All cases had been
previously treated with a variety of topical drops in the form
of mast cell stabilizers, antihistamines, anti-inflammatory
drugs and steroids for at least one year before enrollment
and all were refractory to this mode of treatment. Patients
with shield ulcer, epithelial defect, associated ocular or systemic
diseases, those taking oral medicines were excluded from the
study. All patients had a wash out period of one week in
which they were advised not to instill any eye drop. Only
commercially available saline was given to the patients to be
instilled if needed. After this period, patients underwent a
detailed ophthalmic examination with specific note being made
of itching, tearing, photophobia, mucous discharge and foreign
body sensation. Specific signs looked for on slit lamp

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I NDIAN J OURNAL OF OPHTHALMOLOGY

biomicroscopic examination included conjunctival hyperemia,

punctuate keratitis, trantas dots, limbal edema and papillae.
The grading system followed for categorizing symptoms and
signs of VKC, is shown in Table 1. These were graded on a
scale of 0-3 using the method described by Bleik et al.17 Patients
subjectively graded their symptoms and the questionnaire
was completed by the masked examiner (AKJ) who recorded
the signs [Tables 2 and 3].
Patients were assigned at random to placebo or treatment
with topical 0.01% MMC three times a day for 2 weeks in both
eyes. A prespecified randomization scheme was followed in
which patients seen on Tuesday and Friday were assigned to
placebo group and those seen on Monday and Thursday
received MMC drops. By using this randomization technique,
17 patients were assigned to MMC group and 11 cases to
placebo group. Coding was done wherein patients in the MMC
group were assigned code 1 and those in placebo group as
code 2. The examiner was masked to this code which was
revealed only at the end of the study. MMC was prepared by
dissolving commercially available injectable MMC (2 mg vial,
MitOnco, Neon Antibiotics Private Ltd, Thane, India) in 20 ml
sterile distilled water without adding preservative. The pH of
the resulting solution was kept at 6.2. Patients in the placebo
group received only distilled water. Both MMC and placebo
eye drops were dispensed in identical multodose plastic bottles
and appearance of the medication was same in both as clear
fluid. To ensure activity of MMC, fresh solution was prepared
every third day. All cases remained masked to treatment till
the end of trial. Signs and symptoms were recorded at the
end of 1 and 2 week of the two week treatment period by a
single, masked examiner (AKJ).
At the end of two weeks patients were given saline drops
and were observed for another 4 weeks to monitor the course
of the disease and to observe for any complications.
Retreatment with topical steroids and mast cell stabilizers was
started either on patients request as a result of severe
symptoms or if one 3 + sign was observed by the examiner
excluding the preexisting tarsal giant papillae in the
observation period of 4 weeks. Also any difference between
the requirement for medication in both the groups was noted.

Vol. 54 No. 2

Mann Whiteny test was used to compare the change in the

severity of symptoms and signs from baseline to the two
week follow-up of treatment period in the MMC and placebo
group. A level of P 0.01 was taken as statistically significant.
Patient reports of symptoms of VKC were not eye specific,
therefore individuals were considered the unit of analysis for
comparison of symptoms. However, the signs of VKC were
graded separately for each eye. Wilcoxan test was used to
calculate the significant value between the two groups in terms
of improvement after 2 weeks. The Fisher exact test was used
to compare the cases in the two groups who required
medication during the one month post treatment follow up.

Results
Twenty eight patients met the criteria for inclusion in this
clinical trial. There were twenty four males and four females.
Mean patient age was 12.29 years (range 6-22 years). Patients
in the MMC group did not differ much in age from the placebo
group (Mean age 12.94 vs 11.64). There was no statistically
significant difference between the two groups in terms of
severity of symptoms at presentation except for photophobia
which was severe in the placebo group.(P=0.003).Signs of the
disease did not differ significantly at presentation. Only
punctate keratitis was significantly severe in the placebo group
at presentation. (P=0.01).
At the end of the two week treatment period patients
assigned to the MMC group showed greater improvement in
symptoms and signs of VKC compared with the placebo group
[Table 4]. Significantly greater improvement was observed
for tearing (P=0.001), foreign body sensation (P=0.004),
discharge (P=0.001), hyperemia (P<0.001), punctate keratitis
(P<0.001), limbal edema (P<0.001) and trantas spots (P<0.001).
No adverse effects of treatment with MMC were noted.
Only 2 cases had punctate keratitis which disappeared after the
drug was stopped. During the 4 week post treatment follow up
none of the 17 patients in the MMC group required medicine
for VKC. Nine out of eleven cases in the placebo group required
mast cell stabilizers or steroids or both within one week of
commencement of the observation period. (P<0.001)

Table 1:Table shows the grading system used for giving individual scores (0-3) to each symptom and sign.
Signs
Grading score

Conjunctival hyperemia

No evidence of

Mild

Moderate

Severe
Severe (>1 mm)

bulbar hyperemia
Papillae

No papillary hypertrophy

Mild (0.2 mm or less)

Moderate (0.3-1 mm)

Punctate keratitis

Absent

One Quadrant

Two Quadrant

Three or more Quadrant

Trantas spots

Absent

1-2

3-4

>4

Limbal edema

Absent

< 90 limbal

>90 <180 limbal

>180 limbal

circumference

circumference

circumference

SYMPTOMS
Grading (0 3)
0 = No Symptoms
+1 = Mild Symptoms of disease / discomfort which were just noticeable
+2 = Moderate discomfort, but does not interfere with daily routine
+3 = Severe symptoms: Disruption of daily routine activity and patient staying home most of the time.

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Jain et al. Low dose Mitomycin-C in severe vernal keratoconjunctivitis

113

Table 2: Table shows the individual score of symptom of each patient in MMC and placebo group before and after treatment at
2 weeks. (0 no symptom, 1-mild, 2-moderate, 3- severe)
Symptoms
Start

2 wks

start

2 wks

start

2 wks

start

2 wks

start

2 wks

itch

itch

Tearing

Tearing

FB* sens

FB sens

Photophb**

Photophb

Disch***

Disch

Placebo group
3

MMC group

itch - itching
*FB sens - Foreign body sensation
**Photophb - Photophobia
***Disch - Discharge

Discussion
The present trial suggests that MMC is beneficial in severe
VKC. The improvement noted was greater than in the placebo
group. Statistically significant differences were observed for
tearing, foreign body sensation, discharge, hyperemia,
punctate keratitis, limbal edema and trantas spots. The results
of present study were not very much different from earlier
study.8
VKC is a poorly understood allergic disorder commonly
seen in the young males. In arid climates there is an increased
incidence of the limbal form of the disease. Additionally in
these countries VKC has a more perennial nature and less
tendency to regress. 18,19 Corneal changes in VKC are
considered to gauge the severity of the disease.20 In temperate

climate 20% patients have severe disease.21 Untreated corneal

complications as well as prolonged treatment with steroids
lead to permanent impairment of vision. As the disease is self
limiting, management is aimed at preventing these
complications.
VKC is considered primarily an IgE mediated disease,22
but IgG response is also seen.Th-2 like helper cells present in
the conjunctiva of patients with VKC produce cytokines and
chemokines that account for most of the pathophysiological
aspects of allergic disorders including production of
immunoglobulin E antibodies, recruitment or activation of
mast cell, basophils, eosinophils, mucus hypersecretion,
subepithelial fibrosis and tissue remodeling.23 The active
participation of various inflammatory cells in VKC related
conjunctival inflammation along with their mediators and

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I NDIAN J OURNAL OF OPHTHALMOLOGY

Vol. 54 No. 2

Table 3: Table shows the individual scores of right (OD) and left (OS) eye clinical signs of each patient in placebo and MMC
group before and after treatment at 2 weeks.(0 no sign,1-mild,2-moderate,3- severe)
SIGNS

Placebo
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
MMC
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS
OD
OS

Start

2 wks

Start

2 wks

Start

2 wks

Start

2 wks

Start

2 wks

*Conj Hyp

Conj Hyp

**Pun Kert

Pun Kert

***Limb ed

Limb ed

Trantas

Trantas

Papillae

Papillae

2
2
3
3
2
1
3
3
2
2
2
2
2
2
3
3
0
0
1
1
2
2

2
2
2
2
2
2
3
3
3
2
3
3
3
2
3
3
0
0
1
1
3
3

3
2
1
1
1
2
2
2
1
1
1
2
1
1
1
1
0
0
3
3
3
3

3
2
2
2
3
3
2
2
1
1
3
3
1
1
1
2
0
0
1
1
3
3

2
1
3
3
1
1
3
2
2
3
2
3
3
3
2
2
0
1
3
3
3
3

2
1
2
2
2
2
3
2
3
3
3
3
3
3
2
2
0
0
1
1
3
3

2
1
2
2
0
1
2
2
2
3
2
3
2
2
1
2
2
1
3
3
3
3

3
1
1
0
0
1
1
1
3
3
3
3
2
3
1
2
0
0
0
0
3
3

2
2
1
1
3
3
1
1
1
1
2
2
3
2
2
2
1
1
1
1
1
1

2
2
1
1
3
3
1
2
2
2
2
2
2
2
2
2
0
0
1
1
2
2

2
3
3
3
3
3
3
3
2
3
1
1
1
1
3
3
2
2
3
4
3
3
2
1
2
2
0
0
3
3
2
2
1
1

2
2
1
1
0
0
2
1
1
1
1
0
0
0
1
1
1
1
2
2
3
3
0
0
1
1
0
0
2
2
1
1
0
0

0
0
1
1
0
0
0
0
0
0
1
2
0
0
3
3
0
0
0
0
0
0
0
0
3
3
0
0
0
0
3
3
2
2

0
0
0
0
0
0
1
1
0
0
0
1
1
1
2
3
0
0
0
0
0
0
0
0
1
1
0
0
0
0
2
2
0
0

2
2
1
1
3
3
3
3
2
2
2
2
3
3
2
2
1
1
2
2
3
3
1
1
2
3
0
0
3
3
2
2
3
3

1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
0
0
1
1
3
3
0
0
1
1
0
0
2
2
1
1
1
1

3
3
3
3
2
2
2
3
2
2
1
1
2
2
1
1
1
1
2
1
3
3
0
0
1
1
0
0
2
2
0
0
2
2

1
1
1
0
0
0
1
1
0
0
0
0
0
0
1
0
0
1
0
0
4
4
0
0
0
0
0
0
0
0
0
0
0
0

2
2
2
2
2
2
1
1
2
2
2
2
0
0
3
3
2
2
2
2
0
0
3
3
3
3
3
3
2
2
3
3
3
3

2
2
1
1
1
1
1
1
1
1
1
1
0
0
3
3
1
1
1
1
0
0
3
3
1
1
3
3
1
1
3
3
3
3

*Conj Hyp-Conjunctival hyperemia

**Pun Kert-punctate keratitis
***Limb ed-Limbal edema

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Jain et al. Low dose Mitomycin-C in severe vernal keratoconjunctivitis

Table 4: Table shows the comparison of severity of symptoms

and signs in the placebo group and MMC group before
starting treatment and after treatment at 2 weeks.
Placebo (n=11)
Before

after

Mitomycin C (n=17)
Before

after

Symptoms
Itching

2.8

2.2

2.9

Tearing

2.4

1.8

2.2

0.6*

Fb** sensation

1.8

1.4

1.7

0.6*

Photophobia

1.5*

1.9

2.5

0.9

Discharge

2.1

1.5

2.2

0.5*

Hyperemia

1.95

2.18

2.18

1*

Punctate keratitis

1.59*

1.82

0.79

0.47*

Limbal edema

2.23

2.09

2.09

0.85*

Trantas spots

1.55

1.59

0.44*

1.59

1.68

2.06

1.53

Signs

Papillae
**Foreign body
*Statistically significant

The numbers show the average grading scores of each sign/symptom. The
severity grades of sign in right and left eye were averaged for each patient.

adhesion molecules result in ocular surface inflammation.

Management of VKC in tropical countries like ours is not
easy because of the safety and cost as well as the easy
availability of over the counter medicines. Mast cell stabilizers
have not shown good results from Middle east and Africa.24,25
Topical steroids are effective but unsupervised treatment leads
to unsuspected steroid induced glaucoma and cataract.26-28
Bonini et al observed an incidence of 2% steroid induced
glaucoma.29 Cyclosporine 2% is not a good alternative as 60%
patients relapse soon after treatment is stopped. 17
Antihistamines, mucolytics and non steroidal anti
inflammatory drugs have not gained much importance. Other
modalities of treatment such as cryotherapy, Beta radiation
have been used with limited success.20,30-32
MMC selectively inhibits DNA synthesis and is non cell
cycle specific. At high concentration cellular RNA and protein
synthesis is also suppressed. Rapidly dividing cells are the
most sensitive. MMC 0.04% has been successfully used in
conjunctival and corneal intraepithelial neoplasia. 14-16
Encouraging results have been seen in atopic
keratoconjunctivitis by Akova et al.33 Sodhi et al in his study
showed topical MMC to be more effective than topical
azelastine in the treatment of allergic conjunctivitis both in
terms of relief of symptoms and resolution of signs.9 The use
of topical MMC in low doses did not cause any significant
adverse effect in this study.9 Tanaka et al reported significant
improvement in ocular condition where intra-operative MMC
was used after excision of papillae.34 No adverse effect was
seen in any of his patients. Topical MMC has been reported to
be safe at low doses.11,35,36 Frucht-Pery and Iksan did not
observe any significant side effects with 0.01% MMC topical
drops after pterygium surgery.11 In none of these studies any
adverse systemic side effect was noted. Intravesical instillation
of MMC for bladder cancer did not result in systemic toxicity.37

115

In present study no ocular or systemic side effects were

observed. Akpek et al observed punctate keratitis in 2 patients
treated with MMC.8 Previous studies have also reported this
side effect.14-16 MMC has previously been demonstrated to
delay wound healing by inhibiting cell proliferation.38
Newer mast cell stabilizers like lodoxamide and
nedocromial sodium have shown to be better than sodium
cromoglycate for treatment of VKC but these are at present
not available in our country.39,40 Corticosteroids are potent
anti-inflammatory agents. They can modulate human T
lymphocyte response. Gene expression and protein secretion
of Th-2 and Th-1 clones are down regulated in a concentration
dependent manner by corticosteroids.41 Successful treatment
of severe VKC can be achieved with control of ocular
inflammation with steroids. However, long term use of topical
steroids in severe VKC particularly in such a young age group
is not desirable. Supratarsal injection of steroid has been used
with success in severe cases of VKC.42 However this is an
invasive procedure and there is a risk of developing glaucoma
or/and cataract. Moreover this procedure has to be carried
out under general anesthesia in most of the cases depending
on the age of the child. Also it is difficult to monitor the
intraocular pressure in young children. Steroids are easily
available over the counter in India and it is possible that
unsupervised use may lead to complications.
MMC is a non selective inhibitor of cell migration and
proliferation. We used topical MMC in VKC for its non-specific
inhibitory effect on the migration and proliferation of
inflammatory cells and fibroblasts causing the symptoms and
signs and eventual tissue remodeling associated with VKC.
None of our cases had shield ulcer or an epithelial defect. We
do not recommend use of MMC in such cases as it can
aggravate the problem. Although mast cell stabilizers, steroids
are the first line therapy of severe VKC we recommend use
of topical MMC 0.01% in recalcitrant and severe cases of VKC
not responding to other drugs rather than increasing the dose
and strength of topical steroids. Side effects are minimal and
there is marked improvement in the signs and symptoms of
VKC. Once the acute phase of severity of symptoms and signs
of the disease is controlled by use of topical MMC, patients
can be switched to mast cell stabilizers for maintenance.

References
1.

Smolin G. OConnor. Ocular Immunology. 3rd ed. Little Brown:

Boston; 1986. p. 135-92.

2.

Friedlaender MH. Allergy and Immunology of the Eye. Harper

and Row: Hagerstown; 1979. p. 185-8.

3.

Tuft SJ, Cree IA, Woods M, Yorston D. Limbal Vernal

Keratoconjunctivitis in the Tropics. Ophthalmology
1998;105:1489-93.

4.

Sandford-Smith JH. Vernal eye disease in North Nigeria. Trop

Geogr Med 1979;31:321-8.

5.

Baryishak YR, Zavaro A, Monselise M, Samra Z, Sompolinsky

D. Venal keratoconjunctivitis in an Israeli group of patients
and its treatment with sodium cromogylate. Br J Ophthalmol
1982;66:118-22.

6.

Dahan E, Appel L. Vernal keratoconjunctivitis in the black child

and its response to therapy. Br J Ophthalmol 1983;67:688-92.

7.

BenEzra D, Peer J, Brodsky M, Cohen E. Cyclosporine eye

drops for the treatment of severe vernal keratoconjunctivitis.

115 CMYK

[Downloaded free from http://www.ijo.in on Saturday, January 23, 2016, IP: 202.67.40.50]

116

I NDIAN J OURNAL OF OPHTHALMOLOGY

Am J Ophthalmol 1986;101:278-82.

Vol. 54 No. 2

27. Sandford-Smith JH. Vernal eye disease in Northern Nigeria.

Trop Geogr Med 1979;31:321-8.

8.

Akpek EK, Hasiripi H, Christen WG, Kaletyei D. A

Randomised Trial of Low-Dose, Topical Mitomycin-C in the
Treatment of Severe Vernal Keratoconjunctivitis.
Ophthalmology 2000;107:263-8.

9.

Sodhi PK, Pandey RM, Ratan SK. Efficacy and safety of topical
azelastine compared with topical mitomycin C in patients
with allergic conjunctivitis. Cornea 2003;22:210-3.

29. Bonini S, Bonini S, Lambiase A, Marchi S, Pasqualetti P,

Zuccaro O, et al. Vernal keratoconjunctivitis revisited.
Ophthalmology 2000;107:1157-63.

10. Bowman WC, Rand NJ. Textbook of Pharmacology. 2nd ed.

Blackwell scientific Publication: Oxford; By Blackwell Mosby
Book Distributors: St. Lous; 1980. p. 14-5.

30. Diallo JS. Tropical endemic limboconjunctivitis. Rev Int Trach

1976;53:71-80.

11. Frucht-Pery J, Ilsar M. The use of low dose Mitomycin-C for

prevention of recurrent pterygium. Ophthalmology
1994;101:759-62.
12. Palmer SS. Mitomycin as adjunct chemotherapy with
trabeculectomy. Ophthalmology 1991;98;317-21.
13. Frucht-Pery J, Rozenman Y. Mitomycin-C therapy for corneal
intraepithelial neoplasia. Am J Ophthalmol 1994;117:164-8.
14. Heigle TJ, Stulting RD, Palay DA. Treatment of recurrent
conjunctival epithelial neoplasia with topical Mitomycin-C.
Am J Ophthalmol 1997;124:397-9.
15. Wilson MW, Hungerford JL, George SM, Maldreperla SA.
Topical mitomycin-c for the treatment of conjunctival and
corneal intraepithelial neoplasia. Am J Ophthalmol
1997;124:303-11.
16. Akpek EK, Etroy D, Kalayei D, Hasripi H. Postoperative
topical Mitomycin C in conjunctival squamous cell neoplasia.
Cornea 1999;18:59-62.
17. Bleik JH, Tabbara KF. Topical cyclosporine in vernal
keratoconjunctivitis. Ophthalmology 1993;98:1679-84.
18. Beigelman MN. Vernal conjunctivitis. University of Southern
California Press: Los Angeles; 1950.
19. Allansmith MB. Vernal conjunctivitis. In: Duane T, ed. Clin
Ophthalmol. Harper & Row: New York; 1978. p. 1-8.
20. Buckley RJ. Vernal keratoconjunctivitis. Int Ophthalmol Clin
1988;28:303-8.
21. Collum LM. Vernal Keratoconjunctivitis. Acta Ophthalmol Scand
1999;24:14-7.
22. Grunert G, Porcia M, Neumann G, Sepulveda S, Tchernitchin
AN. Progesterone interaction with eosinophils and by
responses already induced by oestrogens in the uterus. J
Endocrinol 1984;102:295-303.
23. Romagnani S. The role of lymphocytes in allergic disease
(review). J Allergy Clin Immunol 2000;105:399-408.
24. Abu el-Astar AM, Van den Oord JJ, Geboes K, Missotten L,
Emarah MH, Desmet V. Immunopathological study of vernal
keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol
1989;227:374-9.
25. Easty D, Rice NS, Jones BR. Disodium cromogylate in the
treatment of vernal keratoconjunctivitis. Trans Ophthalmol Soc
UK 1971;91:191-9.
26. Abiose A. Pediatric ophthalmic problems in Nigeraia. J Trop
Pediatr 1985;31:30-5.

116 CMYK

28. Khan MD, Kundi N, Saeed N. A study of 530 cases of vernal

conjunctivitis from the North Western Frontier Province of
Pakistan. Pak J Ophthalmol 1986;2:111-4.

31. Calabresi P, Chabner BA. Antiproliferative agents and drugs

used for immunosuppression. In: Goodman Gilman A, Rall
TW, Nies AS, Taylor, editors. Goodman and Gilmans The
Pharmacological Basis of Therapeutics. 8th ed. Pergamon Press:
New York; 1990. p. 1247-8.
32. Erlichman C, Kerr IG. Antineoplastic drugs. In: Kalan TH,
Roschlau WH, editors. Principles of Medical Pharmacology.
5 th ed. Mo, Mosby: Toronto: Philadelphia: Decker: St. Louis;
1989. p. 604-14.
33. Akova YA, Jabbur NS, Neumann R, Foster CS. Atypical ocular
atopy. Ophthalmology 1993;100:1367-71.
34. Tanaka M, Takano Y, Dogru M, Fukagawa K, Asano-Kato N,
Tsubota K, et al. A comparative evaluation of the efficacy of
intraoperative mitomycin C use after the excision of
cobblestone-like papillae in severe atopic and vernal
keratoconjunctivitis. Cornea 2004;23:326-9.
35. Hayasaka S, Noda S, Yamamato Y, Setogawa T. Postoperative
instillation of low dose Mitomycin-C in the treatment of
primary pterygium. Am J Ophthalmol 1988;106:715-8.
36. Rosenthal G, Shokam A, Lifshitz T, Biedner B, Yassur Y. The
use of mitomycin in pterygium surgery. Ann Ophthalmol
1993;25:427-8.
37. Dalton TJ, Wientjes MG, Bandalament RA, Drago JR, Au JL.
Pharmacokinetics of intravesical mitomycin-c in superficial
bladder cancer patients. Cancer Res 1991;51:5144-52.
38. Resnikoff S, Cornand G, Filliard G, Hugard L. Limbal
vernalkeratoconjunctivitis in the tropics. Rev Int Trach Pathol
Ocul Trop Subtrop Sante Publique 1988;65:21-72.
39. Verin PH, Dicker ID, Mortemousque B. Nedocromial sodium
eyedrops are more effective than sodium cromogylate eyedrops
for long term management of vernal keratoconjunctivitis. Clin
Exp Aller 1999;29:529-36.
40. Caldwell DR, Verin P, Hartwich-Young R, Meyer SM, Drake
MM. Efficacy and safety of lodoxamide 0.1% vs cromolyn
sodium 4% in patients with vernal keraoconjunctivitis. Am J
Ophthalmol 1992;113:632-7.
41. Braun CM, Huang SK, Bashian GG, Kagey-Sobotka A,
Lichtenstein LM, Essayan DM. Corticosteroid modulatin of
human, antigen-specific Th1 and Th2 responses. J Aller Clin
Immunol 1997;100:400-7.
42. Saini JS, Gupta P, Pandey SK, Gupta V, Gupta P. Efficacy of
supratarsal dexamethasone versus triamcinolone injection in
recalcitrant vernal keratoconjunctivitis. Acta Ophthalmol Scand
1999;77:515-8.