Evaluation of Toxicity and Efficacy of a Combination of Antineoplastic Agents in the Prevention of PVR

The retinal toxicity of a combination of antineoplastic drugs in free and liposome-encapsulated form was determined in the rabbit eye. Bleomycin sulfate and 5-fluorouridine were evaluated by clinical observation, electroretinogram, and histological study. Forty-five eyes were injected with combinations of various doses of bleomycin and 5-FUR in free and encapsulated form; 10 eyes served as controls. The nontoxic free dose was found to be 3.5 micrograms bleomycin and 150 micrograms 5-FUR. Liposome encapsulation increased the nontoxic dose to 4.7 micrograms bleomycin and 200 micrograms 5-FUR. Four groups of rabbits in which proliferative vitreoretinopathy had been induced were used for the efficacy study; the control group received an injection of PBS; the second group was injected with a combination of 3.5 micrograms bleomycin and 150 micrograms 5-FUR in free form; the third group was injected with the identical doses in liposome-encapsulated form; and the fourth group received encapsulated bleomycin (4.7 micrograms) and 5-FUR (200 micrograms). The dose used in Group 4 was significantly more effective (P < 0.01) in preventing tractional retinal detachment and marginally more effective (P = 0.054) in preventing neovascularization.