Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil

The purpose of this study is to assess the influence of the antiproliferative agents, 5-fluorouracil (5-FU) and mitomycin C (MMC), on the intact corneal epithelium and on epithelial wound healing in the rabbit cornea.

Using an eye cup made of polymethylmethacrylate, the intact rabbit corneas were bathed for 5 or 15 minutes with either MMC (in concentrations of 0.0016%, 0.008%, 0.04%, and 0.2%) or 5-FU (in concentrations of 1% and 5%). The same concentrations of MMC or 5-FU were applied to the cornea with the eye cup in which epithelial cells were mechanically removed. The contralateral fellow eyes, which were bathed in balanced salt solution in the eye cup, had the cornea intact or mechanically abraded and served as controls. Five to six animals were used only once for each concentration of MMC or 5-FU.

Neither MMC nor 5-FU caused any discernible changes in the intact cornea of any of the eyes. The epithelial healing was retarded by mitomycin in a dose-related manner, and ID50 was calculated to be 0.06%. Five-fluorouracil 5% significantly delayed epithelial healing, but 1% failed to do so. Mitomycin C was estimated to be at least 125 times as potent as 5-FU in inhibiting corneal epithelial healing.

These results indicate that particular care should be taken to minimize corneal contact with MMC in the clinical setting, particularly when epithelial defects are present.