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Based on several in vitro, in vivo, and clinical studies that have demonstrated the safety and efficacy of Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) inhibitors, this class has most recently been introduced as a novel therapy option in multiple ocular disorders including corneal epithelial and endothelial damage, retinal and choroidal neovascularization, diabetic macular edema, optic nerve disorders, and glaucoma.
ROCK inhibitors are thought to increase aqueous outflow by reversing structural and functional damage at the trabecular meshwork. Some ROCK inhibitors reduce episcleral venous pressure via a vasodilatory effect and others have been shown to increase endothelial counts. Due to these abilities, the drug class has particular interest for treatment of glaucoma.
Despite years of ongoing research, glaucoma’s pathogenesis is not fully understood. Conditions such as this that put patients at risk of blindness increase the importance of the role of ROCK inhibitors as another option to improve related health outcomes. By 2050, an estimated 7.32 million people in the US will have primary open-angle glaucoma. As the first new drug class in more than two decades for the reduction of intraocular pressure in patients with glaucoma or ocular hypertension, ROCK inhibitors are a major advancement in the treatment of glaucoma.
The FDA recently approved Rhopressa (netarsudil ophthalmic solution) 0.02% for the lowering of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Netarsudil is able to lower IOP by inhibiting both ROCK and the norepinephrine transporter. This results in enhanced trabecular outflow, reduced episcleral venous pressure, and decreased aqueous production. Since ROCK inhibitors such as netarsudil have a different mechanism of action than other common glaucoma treatments, it is possible for them to work synergistically with those options.
The most common side effect of netarsudil is ocular hyperemia, with an incidence of up to 53% in clinical trials. Other ocular adverse reactions observed during clinical trials were corneal verticillata, instillation-site pain, and conjunctival hemorrhage. ROCK inhibitors such as netarsudil expand the treatment options for glaucoma patients. There also is a great benefit to netarsudil’s once-daily dosing regimen, as the simplified schedule can help patients maintain compliance to their treatment plan.
Aerie Pharmaceuticals website. Press release. Aerie Pharmaceuticals Announces U.S. Launch of Rhopressa (netarsudil ophthalmic solution) 0.02%. http://investors.aeriepharma.com/news-releases/news-release-details/aerie-pharmaceuticals-announces-us-launch-rhopressar-netarsudil. Updated April 30, 2018. Accessed July 20, 2018.
DailyMed website. Rhopressa- netarsudil solution/drops drug label information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7d4f0e3a-5b86-4c43-982a-813b22ae7e22. Updated December 22, 2017. Accessed July 20, 2018.
Lin CW, et al. Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma. Journal of Ocular Pharmacology and Therapeutics. 2018;34, Numbers 1 and 2: 40-50.
Serle JB. Novel Addition for IOP Reduction. Glaucoma Today. September/October 2017;53,54,66.
Wang SK, Chang RT. An emerging treatment option for glaucoma: Rho kinase inhibitors. Clin Ophthalmol. 2014;8:883-890.
Weinreb R, et al. The Pathophysiology and Treatment of Glaucoma, JAMA. 2014;311(18):1901-1911.