Intraocular Pressure Effects and Mechanism of Action of Topical Versus Sustained-Release Bimatoprost.

Sherri Decker,Michael R Robinson,Alazar N Ghebremeskel,James A Burke,Alexandra Almazan,Robert N Weinreb,Patrick Hughes,Susan S Lee,Yan Zhong

doi:10.1167/tvst.8.1.15

Sherri Decker, Michael R Robinson + Show 7 more

Open Access

https://doi.org/10.1167/tvst.8.1.15

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Abstract

PurposeTo assess the intraocular pressure (IOP)-lowering effects of bimatoprost sustained-release implant (BimSR) in normotensive monkeys receiving topical bimatoprost.MethodsSix eyes from six female, normotensive, cynomolgus monkeys were treated with once-daily topical latanoprost 0.005% plus twice-daily fixed-combination dorzolamide 2%/timolol 0.5%. At week 5, topical latanoprost was switched to once-daily topical bimatoprost 0.03% and twice-daily dorzolamide 2%/timolol 0.5% was continued. At week 8, BimSR 20 μg was administered intracamerally to three eyes and topical therapy was continued in all eyes. At week 12, all topical therapy was discontinued and animals were monitored for another 4 weeks. IOP was measured with a TonoVet rebound tonometer in nonsedated animals weekly for 16 weeks.ResultsAverage mean (standard deviation) IOP was 19.8 (1.6) mm Hg at baseline, 15.7 (0.9) mm Hg during treatment with topical latanoprost/dorzolamide/timolol from weeks 1 to 5, and 14.2 (0.5) mm Hg during weeks 6 to 8 after topical latanoprost was switched to topical bimatoprost. After BimSR was added, average mean IOP during weeks 9 to 12 was 10.8 (1.3) mm Hg, a decrease of 3.9 mm Hg compared with the topical-only arm. When topical therapy was discontinued, IOP in BimSR-treated eyes remained below that in unmedicated eyes (15.8 [0.9] vs. 20.2 [0.2] mm Hg at weeks 14–16).ConclusionsIntracameral BimSR has IOP-lowering effects additive to those of topical bimatoprost, suggesting an additional mechanism of action with intracameral drug delivery.Translational RelevanceCompared with topical bimatoprost, intracameral BimSR may have an additional mechanism of action of IOP lowering.

Highlights

Topical medical therapy with prostaglandin analogs (PGAs) is the most common first-line treatment for primary open-angle glaucoma.[1]
An additional 1 mm Hg of mean intraocular pressure (IOP) lowering was observed 1 week later (Table 1), confirming that topical bimatoprost exhibited a similar difference in efficacy compared with latanoprost as when used in humans, which increases confidence in the translatability of the study results
When bimatoprost SR was added to this triple combination in half of the monkeys (n 1⁄4 3), there was an additional, statistically significant decrease in average mean IOP during weeks 9–12 to 10.8 6 1.3 mm Hg (P 0.01 vs. topical alone at weeks 9, 11, and 12), which was an additional decrease of 3.9 mm Hg compared to the topical-only group

Summary

Introduction

Topical medical therapy with prostaglandin analogs (PGAs) is the most common first-line treatment for primary open-angle glaucoma.[1]. Increasing the dose of topical bimatoprost or latanoprost from once- to twice-daily dosing results in a significant decrease in overall IOP-lowering efficacy.[5,6,7,8]. Bimatoprost sustained-release intracameral implant (bimatoprost SR) is a biodegradable polymer drug delivery system designed to slowly release bimatoprost into the anterior chamber over a period of 4 to 6 months, while the matrix slowly degrades to inert compounds (Fig. 1).[9] In a preclinical doseranging study, the IOP-lowering efficacy of several doses of bimatoprost SR (8–120 lg) was compared with that of topical bimatoprost 0.03% in ocular

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