O R I G I N A L A R T I C L E

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Mitomycin is an extremely toxic, non-cell-cycle-specific alkylating agent, which forms covalent

linkages with guanine residues in DNA. Systemic mit-omycin causes a marked late and often unpredictabletoxicity against all 3 formed blood elements, especial-ly the stem cells. The drug has been used intraopera-tively during trabeculectomy to improve the successrate of filtering surgery. However, it produces sideeffects such as ocular irritation, photophobia, delayedepithelial healing, and avascularity of the sclera. Pre-vious studies have shown that small amounts of mito-mycin injected intraocularly into rabbit eyes causespermanent hypotony, irreversible corneal edema, andloss of vision in most of these eyes.

Recent studies in rabbits1 and human subjects2

using subconjunctival mitomycin-C have reported adecrease in intraocular pressure (IOP), probably dueto a direct effect of mitomycin-C on the ciliary body.We carried out this study in eyes blinded by absoluteglaucoma to determine whether the IOP can bereduced in glaucomatous eyes with subconjunctivalmitomycin-C without having the local side effects ofthe drug.

Patients & MethodsTwenty patients with 1 eye blinded by glaucoma, whowere referred to the glaucoma service of our institu-tion, were enrolled in the study. The inclusion crite-ria were as follows: IOP greater than 30 mm Hg (on

Viney Gupta, MD, & H. C. Agarwal, MD

Intraocular Pressure Reduction AfterSubconjunctival Mitomycin-C inAbsolute Glaucomatous Eyes

This study investigated the intraocular pressure (IOP) lowering

effect of subconjunctival injection of mitomycin-C in human eyes

blinded by glaucoma. Twenty eyes received injection of 1 mg of mit-

omycin-C and were followed up for 2 months. A statistically signifi-

cant decline in IOP was observed until day 30 in all patients. The

IOP-lowering effect of 1 mg of subconjunctivally injected mitomycin

in patients with intractable glaucoma appears to be temporary.

A B S T R A C T

Reprints:H. C. Agarwal, MD, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All IndiaInstitute of Medical Sciences, New Delhi 110029 India.

The authors are from the Dr. Rajendra Prasad Center for Ophthalmic Sciences, AllIndia Institute of Medical Sciences, New Delhi, India.

ANN OPHTHALMOL. 2001;33(2) 123

diurnal variation), a visual acuity of no light percep-tion, and no previous filtration surgery. All patientswere informed about the possible adverse effects ofthis experimental treatment, and informed consentwas obtained.

The IOP (mean of the 2 highest values obtainedduring the 24-hour diurnal variation) was measuredwith an applanation tonometer in the absolute glauco-matous eye before injection (baseline) and then at 1, 7,15, 30, and 60 days. Biomicroscopic examination of thecornea along with specular microscopy was performedbefore and after the subconjunctival injection untilthe last follow-up.

After instillation of 4% lidocaine (Xylocaine) eye-drops, a subconjunctival injection of 0.5 mL of 0.2%mitomycin-C was given in the lower fornix. Antibioticointment was applied, and a patch was applied for 4hours. The patients continued their usual regimen oftopical medical therapy, which included 0.5% timololmaleate, 2% pilocarpine, and 0.1% dipivefrinhydrochloride (Propine), with the addition of ketorolactromethamine eyedrops 4 times daily in the injectedeye for 1 week. Overall changes in IOP were calculatedfrom comparison of baseline values with those at lastfollow-up. Successful control of IOP was said to occurwhen IOP declined to less than 22 mm Hg or when anIOP reduction of greater than 30% was observed.

Statistical analysis was performed using the analy-sis of variance and Wilcoxon signed rank test to com-pare the mean IOPs between the baseline and atdifferent days of follow-up.

ResultsThe average age of the patients was 48.3±13.3 years(range, 20 to 70 years). There were 13 men and 7women. The most common diagnostic group was thatof chronic angle-closure glaucoma (7 of 20 cases). Ofthe other eyes, 3 had neovascular glaucoma, 3 hadaphakic glaucoma, 3 had secondary glaucoma follow-ing uveitis, 2 had post-traumatic glaucoma, and 2 hadprimary open-angle glaucoma (POAG). The mean IOPrecorded at baseline was 44.7±5.9 mm Hg. The high-est mean IOP of all subgroups was in aphakic glauco-

ma (50±1.4 mm Hg), followed by neovascular glauco-ma (45.6±1.2 mm Hg), traumatic glaucoma (42.1±2.4mm Hg), chronic angle-closure glaucoma (40.6±1.5mm Hg), healed uveitis with secondary glaucoma (40.3±2.6 mm Hg), and POAG (40.1±2.8 mm Hg) (Fig 1).

The day after the subconjunctival injection, adecrease in IOP was observed in each of the injectedeyes (4.5±5.4 mm Hg), and this change was especiallypronounced by day 15 (10.9±6.5 mm Hg). However,the effect began to decline by day 30 and was negligi-ble by day 60 (1.3±2.2 mm Hg) (Fig 2). The IOPdecline seen at each follow-up visit was significant (P<.001) but not at day 60. However, at no point duringthe follow-up was the IOP decline below 22 mm Hg.Nor was an IOP reduction of greater than 30% noted inany of the eyes during follow-up (Fig 3).

Four patients experienced conjunctival congestionwith chemosis and redness of eyelids 4 to 5 days fol-lowing the subconjunctival injection, which lasted for6 to 10 days. This was probably an allergic reaction tothe drug because the patients’ symptoms wererelieved with betamethasone eyedrops 4 times dailyalong with systemic antihistamines. No significantcorneal epithelial and endothelial changes were noted.

DiscussionThe management of eyes with absolute glaucoma hav-ing symptoms of recurrent pain, redness, and wateringessentially consists of cyclodestructive procedures,which have the potential side effect of phthisis bulbi.Trabeculectomy with intraoperative use of mitomycinimproves the success rate of trabeculectomy in sucheyes. The application of mitomycin during filteringsurgery may produce complications such as a large,thin, avascular, cystic bleb with a propensity to leakand cause endophthalmitis.

We undertook this study to evaluate the effects ofsubconjunctival mitomycin-C on human eyes blindedby glaucoma. In our study, a single 1-mg dose of mito-mycin-C injected subconjunctivally produced a statis-tically significant lowering of IOP. The effect on IOPwas evident up to the first month of follow-up, afterwhich there was a rise of IOP to baseline levels.

Fig 1.—Mean IOP (y-axis) (mm Hg) before treatment with mitomycin-C and at lastfollow-up for each glaucoma diagnostic group (x-axis). Chr ACG indicates chronicangle-closure glaucoma; NVG, neovascular glaucoma; and OAG, primary open-angle glaucoma. Fig 2.—Mean IOP (y-axis) vs time after subconjunctival injection of mitomycin-C.

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Kirchof and Diestelhorst3 had pointed toward adecreased aqueous production as a probable mecha-nism for persistent hypotony and hypothesized thatmitomycin causes cyclodestruction. Mietz and associ-ates,4 in their histopathological study, found swellingof mitochondria, lysis of matrix, and perinuclear mem-brane-bound vacuoles in the ciliary epithelium of rab-bits after an episcleral application of mitomycin. Nuytset al,5 in a histopathologic study of trabeculectomizedeyes with persistent hypotony, showed that the pres-ence of toxicity to the ciliary body underlying the siteof mitomycin-C application might play a role in the ori-gin of persistent hypotony. Gandolfi et al2 performedsubconjunctival injections of mitomycin-C (1 mg) in 12eyes of patients with absolute glaucoma and noted anIOP decline that persisted for 2 months. They postu-lated that mitomycin has an effect on aqueous humordynamics, probably by a toxic effect on the ciliarybody. Suppression of aqueous humor flow has been

demonstrated experimentally by Kee et al6 in monkeyeyes after subconjunctival injection of mitomycin-C.

Because none of the eyes in our study had under-gone filtration surgery, it is unlikely that the effect ofmitomycin is due to inhibition of the subconjunctivalfibrosis. We believe that subconjunctival mitomycin-Cin a dose of 1 mg does cause lowering of IOP, probablydue to toxicity to the ciliary body, but that the effect istemporary (maximum of 1 month). The intraocularpenetration of the drug may also contribute to theearly postoperative hypotony seen after trabeculecto-my with mitomycin-C. Subsequent research usinghigher doses of mitomycin-C is necessary to find outwhether a decrease in IOP can be prolonged with asfew side effects as possible.

References1. Letchinger SL, Becker B, Wax MB. The effects of subconjunctival

administration of mitomycin-C on intraocular pressure in rabbits[abstract]. Invest Ophthalmol Vis Sci. 1992;33(suppl):736.

2. Gandolfi SA, Vecchi M, Braccio L. Decrease of intraocular pres-sure after subconjunctival injection of mitomycin in human glau-coma. Arch Ophthalmol. 1995;113:582–585.

3. Kirchof B, Diestelhorst M. The effect of mitomycin C on the aque-ous humor dynamics in glaucomatous eyes [abstract]. Invest Oph-thalmol Vis Sci. 1993;34(suppl):815.

4. Mietz H, Diestelhorst M, Addick K, Krieglstein GK. Toxic changesin the ciliary epithelium after episcleral application of mitomycinC: an experimental study [abstract]. Invest Ophthalmol Vis Sci.1993;34(suppl):997.

5. Nuyts RM, Felten PC, Pels E, et al. Histopathological effects ofmitomycin C after trabeculectomy in human glaucomatous eyeswith persistent hypotony. Am J Ophthalmol. 1994;118:225–237.

6. Kee C, Pelzek CD, Kaufman PL. Mitomycin C suppression ofaqueous humor flow in cynomolgus monkeys [abstract]. InvestOphthalmol Vis Sci. 1994;35(suppl):1899.

Fig 3.—Percentage decline of IOP after treatment with respect to baseline IOP.