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

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.

Medical anti‐glaucoma therapy: Beyond the drop

“…Intracameral implants also further decreased IOP in dogs already receiving optimal dosages of topical bimatoprost 25,30 . This suggests that intracameral Bimatoprost SR implants lower IOP by mechanism(s) that are not activated with topical application 30 …”

“…However, an intracameral implant showed a consistently greater reduction in IOP as the dose increased from 8 to 120 μg and an implant ≥ 60 μg lowered IOP more than what was achievable with topical 0.03% bimatoprost (the peak of the topical dose‐response curve) 25,30 . Intracameral implants also further decreased IOP in dogs already receiving optimal dosages of topical bimatoprost 25,30 . This suggests that intracameral Bimatoprost SR implants lower IOP by mechanism(s) that are not activated with topical application 30 …”

“…In normotensive beagles, topical bimatoprost exhibited a U‐shaped dose‐response curve in which twice daily administration of 0.01% resulted in a greater decrease in IOP than either twice daily lower (0.001%) or higher (0.1%) concentrations 25 . However, an intracameral implant showed a consistently greater reduction in IOP as the dose increased from 8 to 120 μg and an implant ≥ 60 μg lowered IOP more than what was achievable with topical 0.03% bimatoprost (the peak of the topical dose‐response curve) 25,30 . Intracameral implants also further decreased IOP in dogs already receiving optimal dosages of topical bimatoprost 25,30 .…”

Episcleral Venous Pressure and the Ocular Hypotensive Effects of Topical and Intracameral Prostaglandin Analogs

“…A separate preclinical study was designed to see whether the bimatoprost intracameral implant could decrease IOP when added to a multidrug topical medication regimen that included a PGA 37. In this study, 6 normotensive, chair-trained monkeys were treated with the topical fixed combination dorzolamide 2%/timolol 0.5% (Cosopt, Merck) bid plus topical latanoprost 0.005% qd for 5 weeks.…”

“…Bimatoprost SR indicates bimatoprost intracameral implant; IOP, intraocular pressure. Reprinted from Lee et al37 under the terms of the CC BY license (https://creativecommons.org/licenses/by/4.0/).…”