Abstract
Purpose :
Netarsudil mesylate (previously AR-13324) lowers intraocular pressure (IOP) in normal subjects, patients with ocular hypertension, and patients with open-angle glaucoma. It also lowers IOP in a fixed combination with latanoprost. In this study, we determined the effect of netarsudil mesylate ophthalmic solution 0.02%, which inhibits Rho Kinase as well as the norepinephrine transporter, on aqueous humor dynamics (AHD) in healthy human volunteers.
Methods :
In this double-masked, vehicle-controlled, paired-comparison study, healthy volunteers were randomized to receive netarsudil 0.02% in one eye and its vehicle in the contralateral eye, once daily in the morning for 7 days. Outflow facility was measured by digital Schiøtz tonography. Episcleral venous pressure (EVP) was measured by using an objective, computer-controlled venomanometer and image analysis software. Aqueous humor flow rate was measured by anterior segment fluorophotometry. AHD variables measured at 1 week were compared to those measured at baseline by using two-sample t-tests with statistical significance assumed for P <0.05.
Results :
Ten subjects (mean age 39 ± 14 yrs) completed the study. Mean IOP in the netarsudil-treated eyes decreased from 17.0 ± 2.5 to 12.4 ± 2.2 mmHg (mean ± SD), a decrease of 4.6 mm Hg, compared to a decrease of 0.7 mm Hg in the vehicle-treated eyes (Table). Netarsudil-treated eyes showed an increase in outflow facility of 19% (p = 0.02) and a decrease in EVP of 9% (p = 0.01). Outflow facility also increased in netarsudil-treated eyes (p < 0.001). Aqueous humor flow rate and uveoscleral flow rate did not change (p>0.05). For the vehicle treated eyes, there was no change in any AHD variables. Consistent with previous reports, subjects reported conjunctival hyperemia.
Conclusions :
In this study of normal volunteers, once-daily dosing of netarsudil mesylate ophthalmic solution 0.02% lowered IOP relative to baseline by increasing outflow facility and decreasing episcleral venous pressure.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.