Effect of ticrynafen on aqueous humor dynamics in monkeys

Abstract

Objective: To determine the effect of ticrynafen, a non-sulfhydryl- reactive compound similar to ethacrynic acid, on outflow facility in normotensive monkey eyes and on intraocular pressure (IOP) in monkey eyes with laser-induced glaucoma. Methods: In normotensive eyes, facility (perfusion) was measured shortly before and after bolus or exchange intracameral infusion of ticrynafen or vehicle in opposite eyes, and 3.5 to 4.5 hours after 5 days of twice-daily 2% ticrynafen or vehicle ointment. In glaucomatous eyes, baseline and vehicle diurnal IOP curves were established, 2% ticrynafen ointment was given twice daily for 5 days, and IOP was measured immediately before and 0.5 to 6 hours after each morning treatment. Results: In normotensive eyes, exchange 2-mL infusion of 0.2-, 1-, or 4-mmol/L ticrynafen increased facility by 33% ± 6% (mean ± SEM), 73% ± 18%, and 60% ± 11%, respectively. Day 5 posttreatment facility was higher in the ticrynafen group than in controls by 28% ± 9%. In glaucomatous eyes, maximum IOP decline, from approximately 35 mm Hg, was 7.5 ± 2.0 mm Hg on day 4 and 9.82 ± 2.4 mm Hg on day 5 of twice-daily ticrynafen treatment. Conclusion: The facility-increasing, IOP-lowering action of ticrynafen, ethacrynic acid, and derivatives may not depend entirely on sulfhydryl reactivity. Clinical Relevance: Whether such drugs as ethacrynic acid and ticrynafen prove valuable for glaucoma therapy, at the least they are useful probes to study aqueous outflow mechanisms.