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.

PurposeIt is not known if outflow facilities measured by pneumatonography and Schiøtz tonography are interchangeable. In this study we compared outflow facility measured by pneumatonography to outflow facility measured by digital Schiøtz tonography.MethodsFifty-six eyes from 28 healthy participants, ages 41 to 68 years, were included. Intraocular pressure (IOP) was measured in the sitting and supine positions with a pneumatonometer. With the subject in the supine position, IOP was recorded for 2 minutes by using a pneumatonometer with a 10-g weight and for 4 minutes by using a custom digital Schiøtz tonometer. Outflow facility was determined from the changes in pressure and intraocular volume and a standard assumed ocular rigidity coefficient for each instrument, respectively, and by using an ocular rigidity coefficient calculated by measuring pressure without and with a weight added to the pneumatonometer tip.ResultsThe outflow facility was 0.29 ± 0.09 μL/min/mm Hg by Schiøtz tonography and 0.24 ± 0.08 μL/min/mm Hg by pneumatonography (P < 0.001) when using the standard assumed constant ocular rigidity coefficient. Mean calculated ocular rigidity coefficient was 0.028 ± 0.01 μL−1, and outflow facility determined by using this coefficient was 0.23 ± 0.08 μL/min/mm Hg by Schiøtz tonography and 0.21 ± 0.07 μL/min/mm Hg by pneumatonography (P = 0.003). Outflow facilities measured by the two devices were correlated when the ocular rigidity was assumed (r = 0.60, P < 0.001) or calculated (r = 0.70, P < 0.001).ConclusionsOutflow facilities measured by pneumatonography were correlated with those measured by Schiøtz tonography, but Schiøtz tonography reported approximately 10% to 20% higher facilities when using the standard method. When ocular rigidity was determined for each eye, differences were smaller. Measurements from these devices cannot be compared directly.

Intraocular pressure (IOP) reduction is key to controlling primary open angle glaucoma (POAG).Pharmacotherapies for POAG or ocular hypertension (OHT) commonly lower IOP by increasing uveoscleral outflow or decreasing aqueous humor production. Netarsudil (Rhopressa), a Rho kinase inhibitor, reduces IOP by improving trabecular outflow facility, which is reduced in POAG. We investigated the effects of netarsudil on aqueous humor dynamics in patients with POAG or OHT.

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Purpose: Hyposecretion of aqueous humor has been postulated to adversely affect trabecular meshwork health and outflow resistance. However, the effect of medications that reduce aqueous humor production on outflow facility in living human eyes is unclear. In this study we evaluated the effect of timolol, an aqueous humor flow suppressant, on outflow facility in healthy eyes.Design: Prospective, before-and-after study. Methods:In a multicenter study, 113 healthy participants over age 40 years were included. Intraocular pressure (IOP) was measured in the sitting position by using a pneumatonometer and outflow facility was measured in the supine position by 2-minute pneumatonography. After one week of self-administering timolol 0.05% twice daily in each eye, both measurements were repeated.Results: Mean IOP decreased from 15.1 ± 3.0 mmHg at baseline to 12.4 ± 2.4 mmHg (P < 0.001) after one week of timolol use. Mean outflow facility decreased from 0.23 ± 0.08 μL/min/ mmHg at baseline to 0.18 ± 0.08 μL/min/mmHg (P < 0.001) after timolol. The change in outflow facility was negatively correlated with baseline outflow facility (r = −0.51, P < 0.001). Conclusion:Timolol reduces outflow facility in healthy human eyes, and this effect is greater in eyes with higher baseline outflow facility. This phenomenon may be related to reduced aqueous humor flow, but the precise mechanism remains to be determined.