Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal implant for the sustained release of fluorouracil
P. E. Rubsamen, P. A. Davis, E. Hernandez, G. E. O'Grady and S. W. Cousins
Department of Ophthalmology, Bascom Palmer Eye Institute, School of Medicine, University of Miami, FL.
OBJECTIVE: 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.
METHODS: 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. 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 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. CONCLUSION: 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.
