The Effect of Intracameral Ethacrynic Acid on the Intraocular Pressure of Living Monkeys

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Previous studies have shown that the sulfhydryl-reactive ethacrynic acid increases outflow facility in living monkeys when perfused via the anterior chamber. To study its potential clinical use further, living monkeys were intracamerally injected with 10 μl of ethacrynic acid, with concentrations ranging from 0.5 to 7.5 mmol/l. The fellow control eye was injected with 10 μl of diluent. The status of the anterior segment was monitored by slit-lamp biomicroscopy and the intraocular pressure was measured by pneumatonometry with the monkeys anesthetized with ketamine. The anterior segment of living monkeys tolerated injections up to 3.0-mmol/l ethacrynic acid without marked adverse effects. One of 13 monkey eyes injected with 3.0-mmol/l ethacrynic acid demonstrated mild reversible segmental corneal edema. The greatest mean intraocular pressure reduction in the 3.0- to 3.75-mmol/l group occurred at six hours, with the experimental intraocular pressure decreasing 2.9 mm Hg compared to a mean intraocular pressure increase of 0.1 mm Hg in the control group (n = 19). Concentrations of ethacrynic acid less than 3.0 mmol/l did not provide reliable reduction of intraocular pressure, whereas concentrations greater than 3.75 mmol/l caused a greater incidence and severity of corneal edema. We believe that the intracameral injection of ethacrynic acid can reliably and safely reduce intraocular pressure in living monkey eyes, and that this drug deserves further investigation as a potential antiglaucomatous agent.

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This study was supported in part by grant RO1 EY01894 from the National Eye Institute, Bethesda, Maryland (Dr. Epstein); and a grant from National Glaucoma Research, a program of the American Health Assistance Foundation, Rockville, Maryland (Dr. Epstein). Dr. Epstein has a proprietary interest in the development of ethacrynic acid and derivatives for the treatment of ocular hypertension and glaucoma through a patent (United States Patent 4,757,089) that was developed under research grant EY01894, and was assigned according to the National Institutes of Health directives, to the Massachusetts Eye and Ear Infirmary.

Reprint requests to David Epstein, M.D., Department of Ophthalmology, University of California Medical School, 10 Kirkham St., K-301, San Francisco, CA 94143-0730.

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