Suppression of experimental proliferative vitreoretinopathy by sustained intraocular delivery of 5-FU

Abstract

Treatment of proliferative vitreoretinopathy (PVR) requires a multidimensional approach. Recent studies have focused on pharmacologic techniques to inhibit intraocular cell proliferation by applying antimetabolite drugs. Side effects associated with these drugs and difficulties in achieving effective concentration inside the eye make drug delivery an important and difficult part of this approach. We have developed a sustained-release bioerodible device with modifiable release properties for intraocular drug delivery. In this study, we evaluated the efficacy of the device with two different concentrations of 5-fluorouracil (5-FU) in an experimental model of PVR in rabbit eyes. Both devices showed significant (P < 0.05) efficacy in prevention of PVR. Devices containing 20% 5-FU (total of 1 mg) were 100% effective in prevention of tractional retinal detachment. No significant complications, other than mild vitreous hemorrhage in a few cases, were associated with this method. Because pharmacologic therapy is used as an augmenting method to surgical therapy, these devices can be easily implanted inside the eye through a sclerotomy at the completion of surgery without any discomfort to patients. Slow release of drug by this method reduces the incidence of toxicity and increases the efficacy by providing a constant concentration of drug during the active period of the disease.