Abstract
Abstract: :
Purpose: To determine the mechanism by which topical unoprostone isopropyl ester reduces intraocular pressure (IOP) in patients with ocular hypertension or primary open angle glaucoma. Methods: Thirty-three patients were scheduled for 3 visits following screening. On baseline day, IOP was determined by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, episcleral venous pressure by venomanometry and uveoscleral outflow by mathematical calculation. One drop of unoprostone 0.15% was dosed to one eye and vehicle to the fellow eye twice-daily in a randomized, double-masked fashion. Measurements were repeated on day 5±2 of treatment if at least a 3 mmHg reduction in IOP was found in either eye. In the 29 responders, determinations were repeated again on day 28±2 of treatment. Treated eyes were compared with contralateral control eyes and treatment days were compared with the baseline day using paired t-tests. Results: Compared with a baseline IOP of 22.4±0.6 mmHg (mean±SEM), unoprostone significantly reduced IOP by 5.2±0.4 (P<0.001) and 4.8±0.6 mmHg (P<0.001) at 5 and 28 days of treatment, respectively, in responders. The IOP change from baseline was statistically significantly greater with unoprostone than with placebo at days 5 (2.7±0.4 mmHg; P<0.001) and 28 (3.3±0.5 mmHg; P<0.001). Compared with a baseline outflow facility of 0.09±0.01µl/min/mmHg, unoprostone significantly increased outflow facility by 0.05±0.01 and 0.08±0.02 µl/min/mmHg (P<0.001) at 5 and 28 days of treatment, respectively. The change from baseline in the placebo-treated eyes was not significant. The baseline-adjusted between-treatment differences in outflow facility were statistically significant at 28 days of treatment (increase of 0.06±0.02 µl/min/mmHg; P=0.04). The effects of unoprostone on aqueous flow, uveoscleral outflow and episcleral venous pressure were not different from that of placebo. Conclusion: In responsive patients in this study, the predominant mechanism by which unoprostone reduces IOP at 28 days of treatment appears to be an increase in outflow facility.
Keywords: intraocular pressure • pharmacology • outflow: trabecular meshwork