Abstract
Abstract: :
Purpose: Topical Nepafenac readily penetrates the cornea and is metabolized to a potent cyclo-oxygenase-1 (COX-1) and COX-2 inhibitor, AL-6295A. In this study we tested the effect of topical nepafenac in two murine models of ocular neovascularization (NV). Methods: A masked trial was performed to compare the topical effects of vehicle with one of several concentrations of nepafenac (0.01, 0.03, 0.1, or 0.5%), 0.1% diclofenac, or 0.5% ketorolac tromethamine in mice with oxygen-induced ischemic retinopathy or mice with choroidal NV (CNV) due to laser-induced rupture of Bruch's membrane. Mice with ischemic retinopathy were given one drop four times a day between P12 and P17 and then preretinal NV was measured by image analysis. Starting one day after rupture of Bruch's membrane, mice were treated for two weeks with one drop 4 times a day and then the amount of CNV at each rupture site was measured. Results: Mice treated with 0.1% (n=16) or 0.5% (n=16) nepafenac had significantly less CNV (0.0072±0.0012 mm2, p=0.0037 and 0.0074±0.0015 mm2, p=0.0029, respectively) than vehicle-treated mice (0.0254±0.0060 mm2). In the ischemic retinopathy model, compared to vehicle-treated mice (n=7) in which the average area of preretinal NV was 0.0444±0.0079 mm2, mice treated with 0.1% (n=9) or 0.5% (n=13) nepafenac had significantly less preretinal NV (0.0165±0.0029 mm2, p=0.0011 and 0.0186±0.0043 mm2, p=0.0075). In additional studies, compared to vehicle-treated mice (CNV = 0.0279±0.0076 mm2), mice treated with 0.1% or 0.03% nepafenac had significantly less CNV (0.0181±0.0033 and 0.0133±0.0017 mm2, respectively) whereas eyes treated with 0.1% diclofenac had no significant difference (0.0232±0.0038 mm2, p=0.72). Mice treated with 0.5% ketorolac tromethamine for 14 days had high mortality, but when evaluated after 7 days of treatment showed no difference from mice treated with vehicle for 7 days. Conclusion: Topical nepafenac inhibits ocular NV.
Keywords: 346 choroid: neovascularization • 566 retinal neovascularization • 388 diabetic retinopathy