EyeWorld Asia-Pacific September 2020 Issue

GLAUCOMA 48 EWAP SEPTEMBER 2020 nitric oxide-donating moiety. “Nitric oxide is proposed to relax trabecular meshwork cells by working at the intracellular level (suggested mechanisms of action include inhibiting actin- myosin interaction and release of intracellular calcium, among others),” Dr. Khouri said. “For clinicians, the desired effect is lowering IOP with a well- tolerated side effect profile.” Given this proposed mechanism, “Vyzulta is thought to lower IOP by increasing aqueous humor outflow through both the trabecular meshwork via nitric oxide, and the uveoscleral route via latanoprost,” Dr. Serle said. Efficacy Vyzulta and Rocklatan “have the additional punch of a prostaglandin. Rocklatan in MERCURY trials delivered 40% reduction in about a third of patients,” Dr. Khouri said. In particular, he noted how by netarsudil’s effect on episcleral venous pressure, “these agents work even when baseline pressures are lower. Such effects were observed in multiple studies with new agents including ROCKET, MERCURY, and JUPITER trials.” “Phase 3 pivotal clinical trials, which led to the U.S. FDA approval of these drugs, confirmed the relative efficacy of these three new agents to topical medications commonly used to treat elevated IOP,” Dr. Serle said. Pooled data from the APOLLO and LUNAR trials comparing once-daily latanoprostene bunod with twice-daily timolol 0.5% in 831 patients with open angle glaucoma demonstrated greater (p<0.001) IOP lowering with latanoprostene bunod at all nine measured time points, with mean IOP reductions of 7.5–9.1 mmHg from baseline through 3 months of treatment. 1 In VOYAGER, latanoprostene bunod was superior to latanoprost with mean IOP reductions of about 9 mmHg at 4 weeks. 2 The pooled data including 1,621 patients from ROCKET-1, -2, and -4 showed that IOP lowering with netarsudil 0.02% once daily (17.5–19.5 mmHg) was comparable to that with timolol 0.5% twice daily (17.6–18.4 mmHg) at nine time points through 3 months of treatment. 3,4 The MERCURY trials had three arms testing the fixed- dosed combination of netarsudil 0.02%/latanoprost 0.005%, netarsudil alone, and latanoprost alone. IOP reductions with the fixed-dose combination ranged from 7.2–9.2 mmHg (31–36%) from baseline—reductions up to 3 mmHg greater than with the individual components. Furthermore, efficacy through 12 months of dosing were consistent with 3-month results. 5 Real-world experience has also been reported. Dr. Serle cited a retrospective review of netarsudil in 172 eyes of 108 patients that confirmed that netarsudil is additive to other medications used to treat glaucoma. 6 “This study suggests netarsudil is efficacious early in the disease when patients are presumably receiving fewer medications as well as later in the disease when patients tend to be on more medications to control intraocular pressure,” she said. Meanwhile, a retrospective review of 95 eyes of 52 patients in which latanoprostene bunod was substituted for prostaglandin demonstrated that latanoprostene bunod was more efficacious than a prostaglandin that does not contain nitric oxide and found that latanoprostene bunod is additive in patients on multiple ocular hypotensive medications. 7 Side effects The doctors all agreed that latanoprostene bunod has a similar side effect profile to latanoprost and other prostaglandin analogues, including periocular side effects, occasional ocular irritation, pain on instillation, and hyperemia, Dr. Serle said. Hyperemia was also the most commonly reported side effect with netarsudil-based products. Dr. Khouri said that it was mostly mild and not always present. He thinks this is partly due to how netarsudil works—the dilation of episcleral veins leading to reduction of episcleral venous pressure. “Newer agents are very safe systemically with no cardiac or pulmonary side effects,” he added. At Wills Eye, Dr. Lee said that a “small percentage of those receiving Rhopressa and Rocklatan experience unique side effects not seen in prior classes—subconjunctival hemorrhages and corneal verticillata”—also seen by Drs. Khouri and Serle. Fortunately, Dr. Lee said, none of the corneal verticillata seen in 5–9% of their patients were visually significant. The subconjunctival hemorrhages were generally mild, self-limited, and “mostly described as small and petechial hemorrhages,” he said. Source: Bausch + Lomb Source: Aerie Pharmaceuticals