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

Abstract

There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular hypotensive efficacy with topical dosing. Intracameral PGA dosing with a bimatoprost implant, however, does not exhibit the same intraocular pressure (IOP)-lowering plateau at studied concentrations, and the maximum-achievable ocular hypotensive effects are not yet known. This suggests that the bimatoprost intracameral implant may activate another mechanism of action in addition to the mechanism(s) activated by topical application. Episcleral venous pressure (EVP) is a key determinant of IOP, and experimental manipulation of the episcleral vasculature can change both EVP and IOP. The recent observation that topical and intracameral PGA drug delivery routes produce different patterns of conjunctival hyperemia suggested that the differences in the IOP-lowering profiles may be caused by differing effects on the episcleral vasculature. Recent experiments in animals have shown that topical PGAs increase EVP, while the bimatoprost intracameral implant causes a smaller, transient increase in EVP, followed by a sustained decrease. The increase in EVP could be limiting the IOP-lowering efficacy of topical PGAs. In contrast, the decrease in EVP associated with the bimatoprost implant could explain its enhanced IOP-lowering effects. Further research on EVP as a target for IOP lowering is indicated to improve our understanding of this potentially important pathway for treating patients with glaucoma.

Matrix Metalloproteinases and Glaucoma Treatment

“…102 It is of interest that twice-daily topical dosing of either latanoprost 103 or bimatoprost 104 lowering efficacy compared with once-daily dosing. In contrast, nonclinical 105,106 and clinical 100 studies with Bimatoprost SR have not shown diminished IOP-lowering effects with higher drug release rates from the implant. A possible explanation is that the intraocular drug levels achieved with intracameral delivery, 102 and the subsequent MMP upregulation in target tissues, far exceed that achieved with topical dosing, and this may overcome the ceiling effect on IOP reduction that is observed with topical dosing.…”

Short-Term Effects of Different Types of Anti-Glaucoma Eyedrop on the Sclero-Conjunctival Vasculature Assessed Using Anterior Segment OCTA in Normal Human Eyes: A Pilot Study

“…There are numerous arterio-venous anastomoses (AVAs) in the episcleral vasculature that control the flow of blood between arterioles and venules [ 23 ]. Although it has been suggested that general vasodilation of the episcleral vasculature, including the AVAs, causes an increase in both episcleral venous pressure (EVP) and IOP, it also has been hypothesized that AVA closure, which reduces blood flow from the arteriole to the venule side, could cause a reduction in EVP and IOP and that ROCK inhibitor-induced vasodilation of the episcleral vasculatures might reduce the resistance of AHO and IOP [ 22 , 24 , 25 ]. Further studies are needed to clarify the association between ESV dilation and IOP.…”

“…The reason for this association is, however, unclear. Episcleral vasculature is thought to be a key determinant of IOP, although its role in the response to ocular hypotensive therapies is not well understood [ 25 ]. Our previous report showed that a higher deep VD was significantly associated with higher IOP in treated eyes with glaucoma [ 13 ].…”

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract

“…Outflow vessel dilation by nitric oxide correlated to a 61.5% increased outflow in porcine [9] and human eyes [10] . Recent studies of intracameral bimatoprost suggest similar effects [11] .…”