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Randomized Controlled Trial
. 2018 Jun;34(5):380-386.
doi: 10.1089/jop.2017.0138. Epub 2018 Feb 22.

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans

Arash Kazemi  1 , Jay W McLaren  1 , Casey C Kopczynski  2   3 , Theresa G Heah  2   3 , Gary D Novack  4   5 , Arthur J Sit  1
Affiliations
Randomized Controlled Trial

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans

Arash Kazemi et al. J Ocul Pharmacol Ther. 2018 Jun.

Abstract

Purpose: Netarsudil, an inhibitor of Rho kinase and a norepinephrine transporter, has been shown to lower elevated intraocular pressure (IOP) in controlled studies of patients with open-angle glaucoma and ocular hypertension, and in healthy volunteers. The mechanism of this ocular hypotensive effect in humans is unknown.

Methods: The objective of this study was to evaluate the effect of netarsudil 0.02% on aqueous humor dynamics (AHD) parameters. In this double-masked, vehicle-controlled, paired-eye comparison study, 11 healthy volunteers received topical netarsudil ophthalmic solution 0.02% or its vehicle once daily for 7 days (morning dosing). The primary endpoints were the change in AHD parameters, compared between active and vehicle-treated eyes.

Results: In netarsudil-treated eyes, diurnal outflow facility increased from 0.27 ± 0.10 μL/min/mmHg to 0.33 ± 0.11 μL/min/mmHg (+22%; P = 0.02) after 7 days of treatment. In placebo-treated eyes, diurnal outflow facility did not significantly change (P = 0.94). The difference between netarsudil and placebo eyes in diurnal change of outflow facility was 0.08 μL/min/mmHg (P < 0.001). Diurnal episcleral venous pressure (EVP) in netarsudil-treated eyes decreased from 7.9 ± 1.2 mmHg to 7.2 ± 1.8 (-10%; P = 0.01). Diurnal EVP was not significantly different between netarsudil- and placebo-treated eyes. There was a trend toward decreasing aqueous humor flow rate (-15%; P = 0.08). No treatment changes were seen in uveoscleral outflow rate.

Conclusions: Once-daily dosing of netarsudil ophthalmic solution 0.02% lowered IOP through increasing trabecular outflow facility and reducing EVP. This suggests a combination of mechanisms that affect both the proximal and distal outflow pathways.

Keywords: aqueous humor dynamics; glaucoma; netarsudil; outflow.

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Conflict of interest statement

Arthur J. Sit: Aerie Pharmaceuticals (Grant). Dr. Sit has received support from an unrestricted departmental grant from Research to Prevent Blindness. Dr. Sit is recipient of the Leonard and Mary Lou Hoeft Career Development Award, Mayo Foundation for Medical Education and Research.

Arash Kazemi, Aerie Pharmaceuticals (Grant); Jay W. McLaren, Aerie Pharmaceuticals (Grant); Casey C. Kopczynski, Aerie Pharmaceuticals (Employment, Stockholder, Patent); Theresa G. Heah, Aerie Pharmaceuticals (Employment, Stockholder); Gary D. Novack, (Consultant): Aerie, Allergan, Allysta, Annexon, DSM, Envisia, Eximore, Inotek, Nicox, Ocular Therapeutix, Peregrine Ophthalmics, Qooqoo, RHMM, Inc., and Sylentis.

The authors acknowledge the technical contributions of Swetha Mandeva, M.S.

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