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M S Shapiro, R A Thoft, J Friend, R K Parrish, M G Gressel; 5-Fluorouracil toxicity to the ocular surface epithelium.. Invest. Ophthalmol. Vis. Sci. 1985;26(4):580-583.
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The antimetabolite, 5-fluorouracil (5-FU), has been used to control proliferation of retinal pigment epithelial cells and fibrocytes, and is currently the subject of a multicenter clinical trial of its value in the control of scarring after glaucoma operations. To evaluate possible ocular surface toxicity, the effect of 5-FU on the mitotic rate and differentiation of the ocular surface epithelium in rabbits was measured. 5-FU was instilled into eyes with 10-mm diameter central epithelial wounds and into nonwounded eyes at a dose of 9 mg per day for 4 days. Saline treated control wounded eyes healed within 4 days (n = 5) while 40% (4 of 10) of the 5-FU treated wounded eyes had defects at 4 days. The normal mitotic rate of the corneal epithelium was 1.0 +/- 0.3 (n = 4) tritiated thymidine labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Saline treated control wounded eyes had an increased mitotic rate, 7.1 +/- 1.3 (n = 5) labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Topical 5-FU decreased both of those rates to about 1% of normal. The normal conjunctival epithelial mitotic rate was 1.8 +/- 0.4 (n = 4) labeled cells per 60 basal cells after per 2.5 hr incubation. This rate was the same in wounded eyes, but was decreased in eyes treated with 5-FU. Thus, 5-FU (9 mg/day topically) has serious toxic effects to ocular surface epithelium which must be carefully considered if this drug is to be used clinically.
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