1 Department of Ophthalmology, Mayo Clinic , Rochester, Minnesota.
2 Aerie Pharmaceuticals, Inc. , Bedminster, New Jersey.
J Ocul Pharmacol Ther. 2018 Jun;34(5):380-386. doi: 10.1089/jop.2017.0138. Epub 2018 Feb 22.
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.
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.
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.
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.
Rho 激酶抑制剂和去甲肾上腺素转运体抑制剂奈他舒地尔已被证明可降低开角型青光眼和高眼压症患者以及健康志愿者的眼内压（IOP）。在人类中，这种眼部降压作用的机制尚不清楚。
本研究旨在评估奈他舒地尔 0.02%对房水动力学（AHD）参数的影响。在这项双盲、对照、配对眼比较研究中，11 名健康志愿者每天接受奈他舒地尔滴眼液 0.02%或其载体一次，共 7 天（早晨给药）。主要终点是比较活性药物和载体处理眼之间 AHD 参数的变化。
在奈他舒地尔治疗的眼中，昼夜外流率从 0.27±0.10μL/min/mmHg 增加到 0.33±0.11μL/min/mmHg（增加 22%；P=0.02），经过 7 天的治疗。在安慰剂治疗的眼中，昼夜外流率没有显著变化（P=0.94）。奈他舒地尔和安慰剂眼中昼夜外流率变化的差异为 0.08μL/min/mmHg（P<0.001）。奈他舒地尔治疗眼的昼夜巩膜静脉压（EVP）从 7.9±1.2mmHg 降至 7.2±1.8mmHg（-10%；P=0.01）。奈他舒地尔和安慰剂治疗眼之间的昼夜 EVP 无显著差异。房水流出率呈下降趋势（-15%；P=0.08）。葡萄膜巩膜流出率没有观察到治疗变化。
奈他舒地尔滴眼液 0.02%每天一次给药可通过增加小梁流出率和降低 EVP 来降低 IOP。这表明影响近端和远端流出途径的机制相结合。
