Effect of Latanoprost on Aqueous Humor Dynamics with an Objective Method of Episcleral Venous Pressure Measurement in Normal Eyes

Abstract

Purpose : Mechanisms of action of latanoprost have not been completely understood. Its primary action appears to be on the uveoscleral outflow pathway, but some studies have also suggested increased outflow facility. As well, the effect of latanoprost on episcleral venous pressure (EVP) remains poorly understood. In this study we evaluated the effect of latanoprost on all aqueous humor dynamic (AHD) parameters in normal subjects.

Methods : Forty-eight eyes from 24 normal subjects (6 males, 18 females; 52±8 years, mean±SD) were included as part of a larger study (NCT01677507, ClinicalTrials.gov) to examine the variation of IOP response. The following AHD parameters were assessed: IOP by pneumatonometry; EVP by using a computer-controlled episcleral venomanometer with video recording and processing to determine the pressure required to initiate collapse of the vein; aqueous humor flow by fluorophotometry; outflow facility by 2-minute pneumatonography and uveoscleral outflow calculated by using the modified Goldmann equation. After 7 days treatment with latanoprost 0.005% OU daily, AHD parameters were remeasured. Changes in IOP, EVP, outflow facility and aqueous flow in response to latanoprost were analyzed by using generalized estimating equation models to account for possible correlation between fellow eyes of the same subject.

Results : IOP decreased from 13.2 ± 2.2 mmHg to 11.4 ± 1.6 (mean ± SD, P<0.001), and EVP decreased from 6.6 ± 1.5 mmHg to 6.1 ± 1.6 (P=0.047). Tonographic outflow facility increased from 0.21 ± 0.07 μl/min/mmHg to 0.26 ± 0.08 (P<0.001). There was no significant change in either aqueous humor flow rate (2.64 ± 0.52 μl/min at baseline and 2.62 ± 0.65 after treatment, P=0.9) or uveoscleral outflow rate (1.31 ± 0.9 μl/min at baseline and 1.24 ±1.0 after treatment, P=0.7).

Conclusions : Our complete assessment of AHD parameters indicates that latanoprost increases tonographic outflow facility but not the pressure-insensitive uveoscleral outflow rate. This suggests that any changes in the uveoscleral pathway with latanoprost treatment may be related to the development of IOP-dependent (not pressure-insensitive) flow. The small decrease in EVP is possibly due to vasodilation of episcleral veins. Future AHD studies in ocular hypertensive and glaucoma patients are required to better understand if the mechanisms of action are similar in other patient populations.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.