PREVENTION OF EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY WITH A BIODEGRADABLE INTRAVITREAL IMPLANT FOR THE SUSTAINED-RELEASE OF FLUOROURACIL

Objective: To test the efficacy of a biodegradable device for the intr avitreal sustained release of fluorouracil in the treatment of tractio nal retinal detachment due to proliferative vitreoretinopathy. Methods : A 6 X 0.9-mm (20-gauge) cylindrical solid implant molded from copoly mers of lactide and glycolide admixed with 1 mg of fluorouracil was pl aced in the vitreous cavity of rabbits in which retinal detachment wit h proliferative vitreo-retinopathy had been initiated. Comparisons of the control (drug-free polymer) and experimental (fluorouracil polymer ) groups were made with weekly indirect ophthahnoscopic examinations. In another experiment, the intravitreal concentration of fluorouracil was tested at each time point. Results: Retinas of eight (89%) of nine rabbits that received the polymer with fluorouracil remained attached compared with only one animal (11%) that received the control polymer without the drug. The therapeutic effect of the drug containing impla nt was associated with sustained intravitreal concentrations of fluoro uracil between 1 and 13 mg/L for at least 14 days, and fluorouracil co ncentrations remained above 0.3 mug/mL for almost 21 days. No evidence of the toxic effects of the drug or polymer implant was observed with electroretinographic and histopathologic study. Conclusions: Intravit real implantation of biodegradable polymers containing fluorouracil ca n prevent proliferation of epiretinal membranes resulting in complicat ed retinal detachment in an animal model of proliferative vitreoretino pathy and indicate their possible usefulness for intravitreal delivery of therapeutic agents.