New Drugs for Glaucoma

Educational Objectives

The goal of this program is to improve treatment of patients with glaucoma, particularly normal tension glaucoma. After hearing and assimilating this program, the clinician will be better able to:

1. Compare the mechanisms of action of the newly approved glaucoma medications.

Summary

Netarsudil ophthalmic (Rhopressa): rho kinase (ROCK) inhibitor acting at level of trabecular meshwork (TM); relaxes TM tissue to enhance outflow; ROCKET trials — clinical trials of glaucoma drugs must prove noninferiority to timolol; in ROCKET-1, patients with ocular hypertension or open-angle glaucoma randomized to timolol or netarsudil; noninferiority met when intraocular pressure (IOP) cutoff of 25 mm Hg used; noninferiority criterion met in ROCKET-2 and ROCKET-4; observed 25% to 30% reduction in IOP; in study, 20% reduction in IOP more common among patients with IOPs in low 20s

Speaker’s observations: performance difficult to evaluate when drug applied in late-stage disease; has tried netarsudil as first- or second-line drug, particularly for patients with secondary open-angle glaucoma; some patients have had significant responses while others have shown little improvement; best responses to netarsudil likely in patients with normal-tension glaucoma (NTG), possibly resulting from reduction in episcleral venous pressure; some patients with NTG achieved IOPs in low teens or single digits

Side effects: causes hyperemia in many patients; unlike redness caused by prostaglandins, that caused by netarsudil does not necessarily clear with time; verticillata — generally less pronounced than those caused by amiodarone; clear with discontinuation of drug; conjunctival hemorrhages may develop but usually resolve in few weeks

Netarsudil with latanoprost (Rocklatan): first combination agent that includes prostaglandin analogue; targets uveoscleral outflow and TM outflow; MERCURY-1 and -2 trials — first in United States to compare medication with prostaglandins in phase 3 trial; trials proved noninferiority to both components at all time points through 3 mo; many patients achieved 20% reduction in IOP (reductions ≤40% observed); adverse events similar to those with netarsudil; cost may prohibit use of drug as first-line agent; speaker has observed some good responses, but reserves netarsudil with latanoprost for patients with insufficient response to other medications for lowering IOP

Latanoprostene bunod (LBN; Vyzulta): increases outflow in TM via nitric oxide component; affects uveoscleral pathway via latanoprost; phase 3 studies — showed noninferiority to timolol and IOP reductions similar to those seen with netarsudil; comparison of LBN vs latanoprost found 1 to 1.5 mm Hg greater reduction in IOP with LBN; superiority over travatan or bimatoprost (Lumigan) unproven; speaker tends to prescribe it for patients with NTG, when aiming for improved outflow in TM

Bimatoprost sustained-release (SR): drop of bimatoprost on pellet injected into anterior chamber; study showed IOP reductions of ≤10 mm Hg from baseline of ≈25 mm Hg; issues — repeated treatments may damage corneal endothelium; when treating low-risk patients, any degree of endothelial cell loss intolerable; eyedrops may still be required; phase 3 data show good outcomes with injections alone in some patients; necessary frequency of injections not known; in phase 3 trials, ≈80% of patients with 3 injections in first year did not require rescue treatment during following year

Readings

Asrani S et al: Netarsudil/latanoprost fixed-dose combination for elevated intraocular pressure: 3-month data from a randomized phase 3 trial. Am J Ophthalmol 2019 Nov;207:248-257. doi: 10.1016/j.ajo.2019.06.016. Epub 2019 Jun 21; Craven ER et al: 24-Month phase I/II clinical trial of bimatoprost sustained-release implant (bimatoprost sr) in glaucoma patients. Drugs. 2019 Dec 28; Radell JE and Serle JB: Netarsudil/latanoprost fixed-dose combination for the treatment of open-angle glaucoma or ocular hypertension. Drugs Today (Barc). 2019 Sep;55(9):563-74; 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 ROCKET-2). Am J Ophthalmol. 2018 Feb;186:116-27.

Disclosures

For this program, the following has been disclosed: Dr. Panarelli is a consultant for Aerie, Allergan, Glaukos, New World Medical, and Santen. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Panarelli spoke at Current Concepts of Ophthalmology 2020, presented by NYU Langone Health, Department of Ophthalmology, and held January 3, 2020, in New York, NY. For information on upcoming CME activities presented by this sponsor, please visit med.nyu.edu. The Audio Digest Foundation thanks the speakers and NYU Langone Health for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP580704

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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