TOPICAL FORMULATIONS OF NOVEL ANGIOSTATIC STEROIDS INHIBIT RABBIT CORNEAL NEOVASCULARIZATION

Purpose. To evaluate the antiangiogenic potential of topical ophthalmi c formulations of the novel angiostatic steroids AL-3789 and AL-4940, using a rabbit model of corneal neovascularization. Methods. Neovascul arization was induced in the rabbit cornea by surgical implantation of a standard ethylene vinvl acetate copolymer (Elvas-40) pellet contain ing 1 mu g lipopolysaccharide. Coded formulations of the control vehic le or the following test agents were administered in prevention and in tervention treatment protocols: 1% formulations of AL-3789, AL-4930, a nd cortisol acetate as a positive drug control. Three doses of AL-3789 (0.01%, 0.1%, and 1%) were also evaluated in a prevention treatment p rotocol. Corneal responses were monitored throughout a 2-week treatmen t period, and 1 week after the last treatment close. Observations incl uded quantitative measurement of the area of new blood vessel growth a nd qualitative assessment of cellular infiltrate and edema. All treatm ents and observations were performed in a double-masked manner. Result s. All tested formulations, except the vehicle and the 0.01% AL-3789 p reparation, significantly inhibited corneal neovascularization and oth er lipopolysaccharide-induced responses in the various treatment proto cols employed. AL-4940, the free alcohol form of AL-3789, was slightly less effective than cortisol acetate or AL-3789. The extent of inhibi tion of the angiogenic response by the 1% and 0.1% AL-3789 suspensions ranged from 76% to 100% 1 week after the last treatment. Conclusions. The antiangiogenic steroid AL-3789 may be a therapeutically useful an giostatic agent for corneal neovascularization and potentially could b e effective in other ocular neovascular diseases.