Arthur J Sit1, Divakar Gupta2, Arash Kazemi3, Hayley McKee4, Pratap Challa2, Katy C Liu2, Jae Lopez4, Casey Kopczynski4, Theresa Heah4. 1. From the Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: sit.arthur@mayo.edu. 2. Department of Ophthalmology, Duke University, Durham, North Carolina, USA. 3. From the Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. 4. Aerie Pharmaceuticals, Inc., Durham, North Carolina, USA.
Abstract
PURPOSE: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. DESIGN: Double-masked, randomized, vehicle-controlled, Phase 2 trial. METHODS:Netarsudil 0.02% was instilled in 1 eye and vehicle into the contralateral eye of 20 patients once daily in the morning for 7 days. The primary endpoint was change in mean diurnal outflow facility on day 8 versus that on day 1 (baseline). Outflow facility was measured by using Schiøtz tonography, IOP by pneumotonometry, and episcleral venous pressure (EVP) by automated venomanometry. RESULTS:Eighteen patients (90%) completed the study. Mean diurnal outflow facility increased 0.039 versus 0.007 µL/min/mm Hg from baseline in the netarsudil- and the vehicle-treated groups, respectively (P < .001 vs. baseline for netarsudil), a treatment difference of 0.03 µL/min/mm Hg (P ≤ .001). Mean diurnal IOP change from baseline at day 8 was -4.52 mm Hg for netarsudil versus -0.98 mm Hg for vehicle, a treatment difference of -3.54 mm Hg (P < .0001). Mean diurnal EVP change from baseline was -0.79 mm Hg in the netarsudil-treated group versus 0.10 mm Hg for vehicle, a treatment difference of -0.89 mm Hg (P < .001). All patients reporting an adverse event reported conjunctival hyperemia of mild or moderate severity. CONCLUSIONS:Netarsudil acts on the conventional outflow pathway, both proximal and distal, to significantly reduce IOP in POAG and OHT by improving trabecular outflow facility and decreasing EVP.
RCT Entities:
PURPOSE: 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. DESIGN: Double-masked, randomized, vehicle-controlled, Phase 2 trial. METHODS:Netarsudil 0.02% was instilled in 1 eye and vehicle into the contralateral eye of 20 patients once daily in the morning for 7 days. The primary endpoint was change in mean diurnal outflow facility on day 8 versus that on day 1 (baseline). Outflow facility was measured by using Schiøtz tonography, IOP by pneumotonometry, and episcleral venous pressure (EVP) by automated venomanometry. RESULTS: Eighteen patients (90%) completed the study. Mean diurnal outflow facility increased 0.039 versus 0.007 µL/min/mm Hg from baseline in the netarsudil- and the vehicle-treated groups, respectively (P < .001 vs. baseline for netarsudil), a treatment difference of 0.03 µL/min/mm Hg (P ≤ .001). Mean diurnal IOP change from baseline at day 8 was -4.52 mm Hg for netarsudil versus -0.98 mm Hg for vehicle, a treatment difference of -3.54 mm Hg (P < .0001). Mean diurnal EVP change from baseline was -0.79 mm Hg in the netarsudil-treated group versus 0.10 mm Hg for vehicle, a treatment difference of -0.89 mm Hg (P < .001). All patients reporting an adverse event reported conjunctival hyperemia of mild or moderate severity. CONCLUSIONS:Netarsudil acts on the conventional outflow pathway, both proximal and distal, to significantly reduce IOP in POAG and OHT by improving trabecular outflow facility and decreasing EVP.
Authors: Colleen M McDowell; Krishnakumar Kizhatil; Michael H Elliott; Darryl R Overby; Joseph van Batenburg-Sherwood; J Cameron Millar; Markus H Kuehn; Gulab Zode; Ted S Acott; Michael G Anderson; Sanjoy K Bhattacharya; Jacques A Bertrand; Terete Borras; Diane E Bovenkamp; Lin Cheng; John Danias; Michael Lucio De Ieso; Yiqin Du; Jennifer A Faralli; Rudolf Fuchshofer; Preethi S Ganapathy; Haiyan Gong; Samuel Herberg; Humberto Hernandez; Peter Humphries; Simon W M John; Paul L Kaufman; Kate E Keller; Mary J Kelley; Ruth A Kelly; David Krizaj; Ajay Kumar; Brian C Leonard; Raquel L Lieberman; Paloma Liton; Yutao Liu; Katy C Liu; Navita N Lopez; Weiming Mao; Timur Mavlyutov; Fiona McDonnell; Gillian J McLellan; Philip Mzyk; Andrews Nartey; Louis R Pasquale; Gaurang C Patel; Padmanabhan P Pattabiraman; Donna M Peters; Vijaykrishna Raghunathan; Ponugoti Vasantha Rao; Naga Rayana; Urmimala Raychaudhuri; Ester Reina-Torres; Ruiyi Ren; Douglas Rhee; Uttio Roy Chowdhury; John R Samples; E Griffen Samples; Najam Sharif; Joel S Schuman; Val C Sheffield; Cooper H Stevenson; Avinash Soundararajan; Preeti Subramanian; Chenna Kesavulu Sugali; Yang Sun; Carol B Toris; Karen Y Torrejon; Amir Vahabikashi; Janice A Vranka; Ting Wang; Colin E Willoughby; Chen Xin; Hongmin Yun; Hao F Zhang; Michael P Fautsch; Ernst R Tamm; Abbot F Clark; C Ross Ethier; W Daniel Stamer Journal: Invest Ophthalmol Vis Sci Date: 2022-02-01 Impact factor: 4.925