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Susan S Lee, Alexandra S P Almazan, Huajiang Li, Alazar N Ghebremeskel, Patrick M Hughes, Michael R Robinson, James A Burke; Additive ocular hypotensive effects of Bimatoprost Sustained-Release intracameral implant on potent topical therapy in monkeys. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3006. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Approximately 50% of patients with glaucoma require multiple topical antihypertensive medications in order to achieve target intraocular pressures (IOPs). This is a burden for patients and makes treatment adherence difficult. The biodegradable Bimatoprost Sustained-Release intracameral implant (Bimatoprost SR) slowly releases bimatoprost into the anterior chamber for 4 to 6 months, and was shown to be safe and to produce IOP-lowering comparable to once daily topical bimatoprost 0.03% in a phase 1/2 clinical trial. This experimental study was designed to determine if Bimatoprost SR 20 µg could produce additional IOP-lowering in normotensive monkeys concurrently treated with multiple topical IOP-lowering medications.
Six eyes from 6 female, normotensive (after washout), cynomolgus monkeys were treated with topical latanoprost 0.005% QD plus fixed combination dorzolomide 2%/timolol 0.5% BID. At week 5, topical latanoprost was switched to topical bimatoprost 0.03% QD (while dorzolomide 2%/timolol 0.5% BID continued). At week 8, Bimatoprost SR was administered to 3 eyes and topical therapy continued in all eyes. At week 12, topical therapy was discontinued in all eyes and the animals monitored for an additional 4 weeks. IOP was measured weekly for a total of 16 weeks (animals trained for IOP measurements without anesthesia).
Figure 1 shows that combination therapy with topical ocular hypotensive medications alone produced an IOP decrease of approximately 3 to 6 mm Hg (P ≤ 0.0005 vs baseline at weeks 1 through 5). The addition of Bimatoprost SR to topical therapy produced an additional 2 to 4 mm Hg of IOP-lowering (P ≤ 0.0117 vs topical alone at weeks 9, 11, and 12). When topical therapy was discontinued, the IOP in eyes treated with Bimatoprost SR remained below that of unmedicated eyes (P ≤ 0.0117).
Bimatoprost SR may have the potential to provide additional IOP-lowering in eyes that are concurrently treated with topical antihypertensive medications. Since Bimatoprost SR may be additive to topical bimatoprost, an additional mechanism of action of IOP lowering may be occurring when bimatoprost is delivered directly into the intracameral space.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Figure 1: Effect of Bimatoprost SR and topical ocular hypotensive therapy on IOP in monkeys.
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