EyeWorld Asia-Pacific September 2020 Issue

GLAUCOMA EWAP SEPTEMBER 2020 47 effective at wide ranges of IOP.” Netarsudil is a rho kinase inhibitor—it inhibits rho- associated protein kinase (ROCK) and norepinephrine transporter (NET). “ROCKs induce the formation of stress fibers and focal adhesions, which result in increased contractility,” Dr. Lee said. ROCK inhibition “leads to relaxation of the TM and reduction of episcleral venous pressure, improving outflow to the proximal and distal conventional outflow pathway. NET inhibition leads to reduced aqueous production.” Netarsudil thus acts “directly at the cellular level,” Dr. Serle said, noting that episcleral venous pressure is the most distal resistance to trabecular outflow. “The primary mechanism is enhancing trabecular outflow and the secondary mechanism is lowering episcleral venous pressure.” She added that a small reduction in aqueous humor flow rates was identified in preclinical nonhuman primate studies as a third mechanism. Meanwhile, latanoprostene bunod is “currently the first and the only ocular hypotensive agent that is a nitric oxide donor,” Dr. Serle said. “Evidence for reduced levels of nitric oxide in the aqueous and plasma of glaucoma patients has been reported.” “When applied topically to the eye, Vyzulta breaks down into two metabolites: latanoprost acid and butanediol mononitrate,” Dr. Lee said. Butanediol mononitrate is a S eemingly, the glaucoma stars have aligned,” said Daniel Lee, MD. “Three novel medications received FDA approval in a very short window.” “Since November 2017, three new topical, IOP-lowering agents have been approved by the U.S. FDA,” said Janet Serle, MD. “Vyzulta [latanoprostene bunod, Bausch + Lomb] in November 2017, Rhopressa [netarsudil, Aerie Pharmaceuticals] in December 2017, and Rocklatan, the fixed-dose combination of netarsudil and latanoprost [Aerie Pharmaceuticals], in March 2019.” “Those new medications represent the first approved novel agents in more than 2 decades when prostaglandins and alpha agonists were approved in 1996,” said Albert Khouri, MD. “Since then, we have only had different formulations and combinations of existing agents.” EyeWorld spoke with Drs. Khouri, Lee, and Serle for a comprehensive overview of these three novel glaucoma medications. Mechanism of action “These new agents are thought to target the trabecular meshwork, which is the site of pathology leading to ocular hypertension in glaucoma,” Dr. Khouri said. “Because the new agents target the site of pathology, they seem to be An overview of new glaucoma medications by Chiles Samaniego EyeWorld Asia-Pacific Senior Staff Writer Contact information Khouri: khourias@njms.rutgers.edu Lee: daniellee@willseye.org Serle: janet.serle@mssm.edu This article originally appeared in the May 2020 issue of EyeWorld . It has been slightly modified and appears here with permission from the ASCRS Ophthalmic Services Corp. AT A GLANCE • The three recently approved agents for the treatment of glaucoma excluding sustained- release drugs are: –Latanoprostene bunod (Vyzulta, Bausch + Lomb) –Netarsudil (Rhopressa, Aerie Pharmaceuticals) –Fixed-combination netarsudil and latanoprost (Rocklatan, Aerie Pharmaceuticals) • Believed to target the site of pathology, these medications appear to be effective at a wide range of IOPs, including lower baseline IOPs. • FDA studies and limited real-world experience show these agents to be comparable to existing glaucoma medications at once- daily dosing with minimal, typically mild and self-limited side effects. • While challenges remain in terms of cost and insurance, clinically these drugs appear suitable for use as first-/second-line treatments or adjuncts to existing treatment.