Effects of Topical Ethacrynic Acid Ointment vs Timolol on Intraocular Pressure in Glaucomatous Monkey Eyes

Objective: To evaluate the long-term effects of ethacrynic acid (ECA) ointment, compared with timolol maleate on intraocular pressure (IOP) in cynomolgus monkey eyes with argon laser-induced glaucoma. Methods: In a 5-day study, IOP was measured for 7 hours after once-daily topical applications of ECA ointment to four glaucomatous monkey eyes. For this study, ECA ointment was given in 0.5%, 1.0%, 1.5%, or 2.5% concentrations. In a separate 30-day study, IOP was measured after once-daily topical applications of ECA ointment in concentrations of 0.75% or 1.5%. The results were compared with IOP after the application of 0.5% timolol maleate administered twice daily on weekdays and once daily on weekends. Results: In the 5-day study, 2.5% ECA ointment had the greatest effect on lowering IOP, with a maximum reduction of 8.5±2.9 mm Hg (mean±SEM). A more pronounced reduction in IOP was observed on the fifth day of treatment for each of the four concentrations. In the 30-day study, 1.5% ECA ointment or 0.5% timolol maleate reduced IOP as much as 11.5±3.7 mm Hg and 14.0±4.5 mm Hg, respectively. With repetitive dosing, the effect on IOP after using 1.5% ECA ointment increased with time. Mild eyelid edema, conjunctival hyperemia, and discharge were observed in some eyes treated with the highest concentrations. One eye of four treated with 1.5% ECA ointment for 30 days developed a superficial corneal erosion in the 30-day study. Conclusions: The ECA ointment reduced IOP in glaucomatous monkey eyes. This reduction was evident by the fifth day of treatment with all the concentrations tested. The reduction in IOP produced by once-daily treatment with 1.5% ECA ointment was comparable with that of 0.5% timolol maleate administered twice daily. Therefore, drugs in this class of compound may prove to be useful in glaucoma therapy.