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EW GLAUCOMA 50 July 2018 4. Weinreb RN, et al. A randomised, con- trolled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glau- coma: the VOYAGER study. Br J Ophthalmol. 2015;99:738–45. 5. Kawase K, et al. Long-term safety and efficacy of latanoprostene bunod 0.024% in Japanese subjects with open-angle glaucoma or ocular hypertension: the JUPITER study. Adv Ther. 2016;33:1612–27. 6. Lin CW, et al. Discovery and preclinical de- velopment of netarsudil, a novel ocular hypo- tensive agent for the treatment of glaucoma. J Ocul Pharmacol Ther. 2018;34:40–51. 7. Kazemi A, et al. The effects of netarsudil ophthalmic solution on aqueous humor dynamics in a randomized study in humans. J Ocul Pharmacol Ther. 2018. Epub ahead of print. 8. Serle JB, et al. Two phase 3 clinical trials comparing the safety and efficacy of netarsudil to timolol in patients with elevated intraocular pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCK- ET-2). Am J Ophthalmol. 2018;186:116–127. 9. Serle J. 3-month interim report of a prospective 12-month safety and efficacy study of topical PG324 (fixed combination of netarsudil 0.02% and latanoprost 0.005%) compared to the individual components in subjects with elevated intraocular pressure (MERCURY 1). Paper presented at the 2017 Association for Research in Vision and Oph- thalmology annual meeting. Editors' note: Dr. Bacharach has financial interests with Bausch + Lomb and Aerie Pharmaceuticals (Durham, North, Carolina). Dr. Serle has related financial interests with Aerie Pharma- ceuticals, Allergan (Dublin, Ireland), Bausch + Lomb, and Ocular Therapeu- tix (Bedford, Massachusetts). Contact information Bacharach: jbacharach@northbayeye.com Serle: janet.serle@mssm.edu Both netarsudil and Roclatan were well tolerated with the most frequent side effect being conjuncti- val hyperemia, which Dr. Serle noted is attributed to the drug's vasodilato- ry effect. "This side effect observed in 50–60% of patients is mild, sporadic, and occurred at every visit in only 10% of patients during the clinical trials," she said. 8 Integrating outflow medications From a clinical perspective, Dr. Bacharach pointed out that having these new agents available can im- prove the clinician's ability to offer novel treatments for patients who need additional pressure reduction. "Approximately half of all treated glaucoma patients need at least two medications to control their IOP, and we have had no new options other than fixed combinations of commonly utilized classes over the past two decades," Dr. Bacharach said, adding it's possible that these outflow drugs can serve as first-line agents as well as having a possible adjunctive role. Such agents may also be benefi- cial in the long run for maintaining and improving the health of the diseased tissue. "This could also be advantageous for a patient who in the future may undergo a trabec- ular-based MIGS procedure," Dr. Bacharach said. "Similar to keeping flow going through a sink drain, it may theoretically potentiate the effects of a physical stent or scaffold placed into Schlemm's canal at a later point in time." Dr. Serle noted how such agents could increase the value of MIGS, which themselves only influence a small area of the trabecular mesh- work. "Maintaining the health and function of the trabecular outflow pathways may allow the addition of MIGS procedures to result in better IOP control," Dr. Serle said, adding that with these medications improv- ing outflow throughout the mesh- work, this could enhance the reach of the MIGS procedure and make additional IOP reductions possible. Dr. Bacharach thinks that prac- titioners who want to incorporate these new agents can do so confi- dently. "These agents have excel- lent systemic safety profiles and no restrictions on when to prescribe; whether this be first-line or adjunc- tive, there are minimal limitations to a prescribing physician interested in implementing these into their armamentarium," Dr. Bacharach said. "The biggest hurdle we will encounter here is navigating the formulary restrictions that burden our practices and hamper patients' access to these novel options." This may make cost an issue for many, However, manufacturers are aware of such possible hurdles and have implemented multiple techniques to make these drugs easier to prescribe, Dr. Bacharach said. Even with such barriers, as well as the fact that there are sever- al glaucoma agents generically available on the market, Dr. Serle is optimistic that these agents will find a place in practice. "The once-daily dosing of these agents makes them extremely attractive for patients and physicians," she said, adding that the fact that efficacy is in the range of timolol and latanoprost, two of the most effective agents, is some- thing to contemplate as well. While neither of the agents have the systemic issues of the beta blockers, practitioners need to be aware of other potential side effects in prescribing these and should discuss them with patients, Dr. Serle stressed. "The side effect profile of the latanoprostene bunod is similar to prostaglandins," she said. It includes ocular and periocular pigment and orbital changes. The side effect profile of netarsudil is different and includes typically mild ocular side effects that are reversible once the drug is discontinued. Dr. Serle has found that in practice latanoprostene bunod is an excellent substitute in some patients for latanoprost and other prostaglandins in those who need additional IOP control. Netarsudil has also been very effective in some patients in her practice. She views netarsudil as a new medication that can be offered as a first-line agent as it is similar in efficacy to timolol and latanoprost. "Both can be used as adjunctive therapy to the other classes of compounds available, with different mechanisms of IOP reduc- tion," Dr. Serle said. Overall, these outflow agents represent a breakthrough, Dr. Serle stressed. "More than 20 years of research has gone into discovering two new classes of medications for lowering IOP," she said. "These drugs will benefit our patients by reducing the rate of progression and vision loss from glaucoma." Excit- ing research in the management of glaucoma continues, which hopeful- ly will lead to additional treatments, she concluded. EW References 1. Stamer WD, Acott TS. Current under- standing of conventional outflow dysfunc- tion in glaucoma. Curr Opin Ophthalmol. 2013;23:135–43. 2. Cavet ME, DeCory HH. The role of nitric oxide in the intraocular pressure lowering efficacy of latanoprostene bunod: review of nonclinical studies. J Ocul Pharmacol Ther. 2018;34:52–60. 3. Weinreb RN, et al. Latanoprostene bunod 0.024% in subjects with open-angle glauco- ma or ocular hypertension: pooled phase 3 study findings. J Glaucoma. 2018;27:7–15. An inside continued from page 48 ASOAnalytics.com