Efficacy of Low Concentrations of Ketorolac Tromethamine in Animal Models of Ocular Inflammation

Abstract

Purpose: To determine if topical ophthalmic application of ketorolac tromethamine concentrations below 0.5% can block the biochemical and physiological processes associated with chemically induced ocular inflammation in rabbits. Methods: Ocular inflammation was induced in rabbits by intravenous (i.v.) injection of endotoxin (2.5 μg/kg) isolated from Salmonella typhimurium, or by a topical application of arachidonic acid (1.0%). The effect of ketorolac (at concentrations ranging from 0.001%–0.5%) on ocular inflammation was determined by measuring changes in the blood-aqueous barrier, using fluorophotometry (dextran-isothiocyanate-fluorescein; FITC-dextran 2%) and by measuring changes in aqueous humor protein concentrations. Changes in aqueous humor prostaglandin E₂ (PGE₂) concentrations were also measured. Results: Ketorolac 0.01%–0.5% produced substantial decreases in endotoxin-induced fluorescein leakage into the aqueous humor. The decrease produced by ketorolac 0.1% was comparable to that produced by ketorolac 0.5%. Ketorolac 0.1%–0.5% produced substantial decreases in endotoxin-induced increases in prostaglandin concentrations in the aqueous humor, and in arachidonic acid-induced protein leakage into the aqueous humor. Conclusions: Topical application of ketorolac concentrations as low as 0.01%–0.1% significantly reduce chemically induced ocular inflammation in rabbits.