In vivo effects of 5-FU on ocular surface epithelium following corneal wounding

We evaluated the dose relationship between the antiproliferative and toxic effects of 5-fluorouracil (5-FU) on the ocular surface epithelium following experimental corneal epithelial wounding in rabbits. Central corneal epithelial defects 8 mm in diameter were made using n-heptanol. 5-FU (0.05 mg, 0.5 mg, or 5.0 mg per day in divided doses) or saline was applied topically for up to 18 days beginning on the day of wounding. The animals were sacrificed at 1, 7 or 14 days after wound closure. The effect on the ocular surface epithelium was assessed by observation of the clinical and histological appearance, and determination of the rate of corneal epithelial defect closure, corneal epithelial mitotic rate and conjunctival goblet cell frequency. A daily dose of 0.05 mg of topical 5-FU for 18 days had no discernable clinical or histopathological effect compared to wounded, saline treated controls. Treatment with 0.5 mg daily prevented the high mitotic rate typically noted 1 day immediately following defect closure, yet had no significant effect on clinical appearance, histological appearance, or healing rate. Daily topical application of 5.0 mg of 5-FU reduced the corneal epithelial mitotic rate to approximately 1% of the wounded controls, with persistent epithelial defects occurring in 22% of the eyes in this group. In those eyes which did heal, the corneal epithelium was markedly thinner than controls 1 day after defect closure. Fourteen days after healing, epithelial thickness in this group varied from 2 to 13 cells across each cornea, with the thickest area occurring centrally and tapering gradually to the limbus.(ABSTRACT TRUNCATED AT 250 WORDS)