Abstract
Abstract: :
Purpose:To investigate the effects of a biodegradable dexamethasone drug delivery system (DEX DDS) in two experimental models of choroidal neovascularization: FGF/LPS–induced CNV in rabbits and laser–induced CNV in rats. Methods: A PLA/PLGA biodegradable implant containing 60 µg of dexamethasone was delivered intravitreally in rabbits or rats. In rabbits, CNV was induced by subretinal injection of FGF/LPS. The development and growth of CNV was monitored by FITC–dextran angiography over a period of 4 weeks. The extent of neovascularization was quantified by image analysis. In rats, CNV was induced using a Zeiss Diode laser (90 mW, 100 ms, 100 µm diameter). Ten days later, rats were euthanized and perfused with high m.w. FITC–dextran. RPE–choroid–sclera was flat mounted and the lesions imaged with fluorescence microscopy. Results: In rabbits, eyes with the DEX DDS exhibited a significantly reduced formation of CNV: 69% inhibition at week 2 and 82% inhibition at week 4 compared to placebo control. In rats, the extent of CNV was similar in sham surgery and placebo groups. Eyes that received the DEX DDS showed an 89% inhibition compared to placebo and 91% inhibition compared to sham surgery. There were no observable contra–lateral (systemic) effects. Conclusions: These data demonstrate that a biodegradable corticosteroid drug–delivery system is highly effective in suppressing choroidal neovascularization and suggest a potential therapeutic approach for retinal diseases characterized by CNV.
Keywords: age-related macular degeneration • neovascularization • pharmacology