Ocular toxicity of mitomycin C and 5-fluorouracil in the rabbit

We studied the histotoxic effects of mitomycin C and 5-fluorouracil (5-FU) in the eyes of New Zealand white rabbits using light microscopy. Twenty-four eyes of 24 rabbits received subconjunctival injections of mitomycin C (0.025, 0.05, 0.10, 0.20, 0.40 or 0.80 mg/mL) or 5-FU (10.0 mg/mL), either alone (0.25 mL) or in combination with anterior chamber injections (0.05 mL), once daily for 4 consecutive days. Two eyes of two rabbits received subconjunctival and anterior chamber injections of unpreserved sterile saline. The eyes were examined regularly for external signs of toxicity and were enucleated 4 weeks after the last injection. Mitomycin C produced considerable tissue damage in the anterior segment, the severity being related to both the concentration and the route of administration. Eyes that received both subconjunctival and anterior chamber injections showed more damage than those that received subconjunctival injections alone. At the highest concentration of mitomycin C the cornea was inflamed, with stromal necrosis and marked endothelial loss. Hemorrhagic iris necrosis was also seen. In contrast, the 5-FU-treated eyes showed no microscopic evidence of toxicity. We conclude that there is greater risk of toxic anterior segment effects when mitomycin C is used as adjunctive therapy following filtration or pterygium surgery.