Prevention of Experimental Proliferative Vitreoretinopathy With a Biodegradable Intravitreal Implant for the Sustained Release of Fluorouracil

Abstract

To test the efficacy of a biodegradable device for the intravitreal sustained release of fluorouracil in the treatment of tractional retinal detachment due to proliferative vitreoretinopathy. A 6 x 0.9-mm (20-gauge) cylindrical solid implant molded from copolymers of lactide and glycolide admixed with 1 mg of fluorouracil was placed in the vitreous cavity of rabbits in which retinal detachment with proliferative vitreoretinopathy had been initiated. Comparisons of the control (drug-free polymer) and experimental (fluorouracil polymer) groups were made with weekly indirect ophthalmoscopic examinations. In another experiment, the intravitreal concentration of fluorouracil was tested at each time point. 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 implant was associated with sustained intravitreal concentrations of fluorouracil between 1 and 13 mg/L for at least 14 days, and fluorouracil concentrations remained above 0.3 microgram/mL for almost 21 days. No evidence of the toxic effects of the drug or polymer implant was observed with electroretinographic and histopathologic study. Intravitreal implantation of biodegradable polymers containing fluorouracil can prevent proliferation of epiretinal membranes resulting in complicated retinal detachment in an animal model of proliferative vitreoretinopathy and indicate their possible usefulness for intravitreal delivery of therapeutic agents.