Topical treatment options for conjunctival neoplasms patients to discontinue treatment prematurely due to severe effect was easily controlled with topical steroid drops given keratoconjunctivitis (Demirci et al 2000). Not surprisingly, for 5–6 days. When Yeatts modiﬁed the 5-FU protocol into patients receiving shorter courses of MMC appear to expe- a pulsed dosing regimen, he obtained similar clinical results rience less severe keratoconjunctivitis than those receiving to the Midena protocol, but no adverse ocular reactions were longer courses. Lower concentrations of MMC (0.02%) also noted. Scarring of the lacrimal drainage apparatus reported appear to cause fewer side effects (Prabhasawat et al 2005). with systemic 5-FU (Shapiro et al 1985), has not been found Therefore, it appears that ocular surface toxicity occurs in with topical administration. The cytologic changes in the a predictable, dosage-dependent pattern. When used as an epithelium associated with MMC have not been observed adjunct to surgical excision, several authors have noted that with topical 5-FU. postoperative MMC does not prevent wound closure or cause wound dehiscence, if instituted after epithelial healing has Ocular toxicity of interferon occurred (Shields et al 2001). Despite the ocular surface In general, topical interferon is thought to have fewer side disease, almost all of the patients treated with topical MMC effects compared with other agents. No patient in the study maintain their pretreatment visual acuity (Demirci et al 2000; published by Boehm experienced any side effects, despite Pe’er and Frucht-Pery 2005). Permanent ocular side effects prolonged use of topical interferon (Boehm and Huang 2004). with topical MMC therapy are unusual. One of the patients in Schecter and colleagues (2002) reported localized conjunc- Kurli’s series developed corneal pannus and lost seven lines tival injection and folliculosis in 4 of 7 patients treated with of vision (Kurli and Finger 2005). Recurrent epithelial defects topical interferon, which they attributed to the vehicle used and/or pannus formation may occur secondary to limbal stem in their topical preparation. Kobayashi and colleagues (2002) cell deﬁciency, and caution is warranted in treating patients also reported superﬁcial punctuate keratopathy in one case who have had surgical alteration of this area (Dudney and treated with interferon. Transient fever and muscle pain have Malecha 2004). Two patients in Kurli’s series also gradually been reported as side effects of subconjunctival interferon developed cataracts 2–3 years after topical MMC therapy, (Vann and Karp 1999; Kobayashi et al 2002). although direct causation was not proven. Intumescent cata- ract after topical mitomycin for conjunctival melanomas has been reported, possibly due to intraocular penetration of the drug (Sacu et al 2003). No cases of scleral or corneal melting have been reported, as has occurred following intraoperative application of MMC in glaucoma and pterygium surgery. An intact epithelium probably prevents absorption of these drugs into deeper tissue layers, and therefore topical MMC should not be given to any patient with a corneal or conjunctival epithelial defect. Epiphora secondary to punctal stenosis has been reported (Khong and Muecke 2006), emphasizing the need to place temporary punctal plugs or to have patients to occlude the lower punctum for at least ﬁve minutes after instilling the topical mitomycin. Occluding the punctum also minimizes the potential for inducing adverse changes in the nasopharyngeal epithelium with topical MMC therapy. Ocular toxicity of 5-Fluorouracil Although the side effect proﬁle of topical 5-FU has not been extensively studied, clinical studies performed to date have reported no long-term side effects with the ocular admin- istration of this drug. When used continuously for 28 days in the study by Midena and colleagues (2000), transient conjunctivitis and superﬁcial keratitis were observed in all patients during the third or fourth week of treatment. This side Clinical Ophthalmology 2008:2(3) References Akpek EK, Ertoy D, Kalayci D, et al. 1999. Postoperative topical mitomycin C in conjunctival squamous cell neoplasia. Cornea, 18:59–62. Baron S, Tyring SK, Fleischmann Jr. WR, et al. 1991. The interferons. Mechanisms of action and clinical applications. JAMA, 266:1375–83. Blodi FC. 1973. Squamous cell carcinoma of the conjunctiva. Doc Ophthalmol, 34:93–108. Boehm MD, Huang AJ. 2004. Treatment of recurrent corneal and conjunc- tival intraepithelial neoplasia with topical interferon alfa 2b. 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