Increase in Outflow Facility With Unoprostone Treatment in Ocular HypertensivePatients

Abstract

To determine the mechanism by which 0.15% unoprostone isopropyl reduces intraocular pressure (IOP) by studying 33 patients with ocular hypertension or primary open-angle glaucoma.Methods: At baseline, IOP was determined by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, episcleral venous pressure by venomanometry, and uveoscleral outflow by mathematical calculation. Unoprostone was administered to one eye and placebo to the fellow eye of each patient twice daily in a randomized masked fashion. In patients who demonstrated an IOP reduction of 3 mm Hg or more in either eye on day 5±1 (n = 29), determinations were repeated on that day and on day 28 ± 2. Treated eyes were compared with control eyes, and treatment days were compared with baseline by paired t tests.Results: Compared with baseline, unoprostone significantly (PϽ.001) reduced IOP by a mean±SEM of 5.6±0.4 mm Hg and 4.8±0.6 mm Hg on days 5 and 28, respectively. The change from baseline with unoprostone was significantly (PϽ.001) greater than with placebo by 2.8±0.4 mm Hg on day 5 and by 3.2±0.5 mm Hg on day 28. Compared with baseline, unoprostone significantly (PՅ.001) increased outflow facility by 0.05±0.01 and 0.08±0.02 µL•min −1 •mm Hg −1 on days 5 and 28, respectively. The baseline-adjusted between-treatment differences were significant (PՅ.04) on day 28 (0.06±0.02 µL•min −1 •mm Hg −1 ). Other measures were not different from placebo. Conclusion:In responsive patients, unoprostone decreased IOP by increasing outflow facility.

Expansion of Schlemm's Canal by Travoprost in Healthy Subjects Determined by Fourier-Domain Optical Coherence Tomography

“…32,33 However, not only laboratory investigations but also clinical studies are suggesting that PGs may also affect conventional outflow facility. 3,[7][8][9]34,35 In the study of Bahler,34 latanoprost significantly increased outflow capacity in cultured human anterior segments. This capacity change occurred within one hour of drug treatment, which continued to increase over the first 12 hours.…”

Changes of the Retina and Intrinsic Survival Signals in a Rat Model of Glaucoma following Brinzolamide and Travoprost Treatments

“…Travoprost is a topical ocular isopropyl ester prodrug that is rapidly hydrolyzed by esterases in the cornea to the biologically active free acid. The IOP-lowering effect is explained by increases in uveoscleral outflow [25][26][27] , trabecular outflow facility [28] , or both [29][30][31] . There are also reports of vasodilating activity by travoprost and its ability to increase ocular blood flow to the optic nerve head [32,33] .…”

Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork

“…Recent pharmacological studies in BTM strips support the idea that docosanoids like unoprostone and prostaglandinanalogues such as PGF 2α and fluprostenol lower IOP by inhibiting ET-1 induced contraction of TM [9,10]. Accordingly, clinical observations indicate that unoprostone and fluprostenol lower IOP in ocular hypertensive patients additionally by increasing the facility of aqueous outflow through the trabecular meshwork [27,28]. Thus, inducing an endothelin-antagonism on TM contractility might be a possible pharmacological way to lower IOP.…”