2020–2021 BCSC Basic and Clinical Science Course™
Chapter 12: Medical Management of Glaucoma and Ocular Hypertension
Rho Kinase Inhibitors
Available Agents and Dosing Frequency
Ripasudil, a mixed ROCK1 and ROCK2 inhibitor, was the first Rho kinase inhibitor available for clinical use to lower IOP and has been approved in Japan. The only Rho kinase inhibitor approved for use in the United States is netarsudil, which was approved by the US Food and Drug Administration (FDA) in 2017. Like ripasudil, netarsudil is a mixed ROCK1 and ROCK2 inhibitor; however, it also is a norepinephrine transporter (NET) inhibitor. The NET inhibitor activity is thought to result in a reduction of episcleral venous pressure and may also decrease aqueous humor secretion, though the latter has not been demonstrated in humans. In clinical trials, its IOP-lowering efficacy was similar to or slightly lower than that of timolol. Some clinical trials were focused on eyes with fairly low baseline IOP because it was thought the drug might be particularly effective in such eyes. In 2 clinical trials in which the mean baseline diurnal IOP was approximately 22 mm Hg, the IOP reduction achieved with once-daily netarsudil 0.02% was approximately 20%. The drug lowers IOP by an additional 1.3–2.5 mm Hg when combined with latanoprost. Although mean IOP lowering with netarsudil used as monotherapy or in combination with latanoprost in clinical trials appears to be modest, some patients respond very well, experiencing substantial IOP lowering.
Netarsudil is used once daily. The hyperemia that commonly occurs with this class of agents is most intense during the first few hours after instillation; therefore, nighttime dosing is preferable.
Kahook MY, Serle JB, Mah FS, et al. Long-term safety and ocular hypotensive efficacy evaluation of netarsudil ophthalmic solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). Am J Ophthalmol. 2019;200:130–137.
Tanna AP, Johnson M. Rho kinase inhibitors as a novel treatment for glaucoma and ocular hypertension. Ophthalmology. 2018;125(11):1741–1756.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.