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New Medical Therapies for Glaucoma

The only current treatment for glaucoma is to lower intraocular pressure (IOP), which can be achieved with eyedrops, laser, or incisional surgery. Eye drops are the most common treatment modality and, over time, patients may need to take multiple types of eye drops in order to stop progression of a disease that typically has no symptoms.

These drops lower IOP by reducing fluid formation or encouraging better drainage of fluid from the eye via one or both of two pathways: the trabecular meshwork/Schlemm's canal (TM/SC) and the uveoscleral pathway.

Currently in the US there are 5 families of eyedrops that are used to lower IOP. In the near future, new compounds that reduce IOP may become available and this article provides an overview of glaucoma medications "in the pipeline." These new compounds are often combined with a prostaglandin compound (a currently available class of medication) in the same bottle, or the compound itself has a prostaglandin "backbone," such that IOP is lowered via multiple mechanisms while maintaining a convenient, once daily dosing.

New Glaucoma Eyedrops on the Horizon

One new compound nearing commercial availability is Latanoprostene Bunod 0.024% (LBN). LBN reduces IOP by enhancing fluid outflow through both the TM/SC and uveoscleral pathways. LBN has 2 components: a prostaglandin, latanoprost, which reduces IOP by increasing uveoscleral outflow, and a nitric oxide donating component that enhances drainage via the TM/SC pathway. Once daily LBN performed well in clinical trials, showing superiority to both twice a day timolol and once daily latanoprost. The most common side effect was mild redness of the eyes.

Rhopressa (Netarsudil 0.02%) is another once daily molecule with 2 mechanisms of action and 2 targets. Rhopressa targets rho-kinase (ROCK) and a norepinephrine transporter (NET). Inhibiting ROCK can enhance fluid outflow through the conventional pathway. The second target, NET, reduces the production of fluid in the eye. This compound was as effective as twice a day timolol in a clinical trial. The most common side effect was mild redness of the eyes.

A combination product, Roclatan, is a once daily, combination of netarsudil 0.02% + latanoprost 0.005%. Thus, the product potentially acts on both outflow pathways and also reduces production of fluid in the eye. Results from clinical trials for these products should be available later in 2017.

Another compound in clinical trials is trabodenoson which is thought to work by opening the conventional outflow pathway through the trabecular meshwork by a unique mechanism. In addition, trabodenoson has been combined with latanoprost to further improve the drainage of fluid from the eye. Trials of this combination are also moving forward.

More Treatment Options in the Near Future

The goal of glaucoma treatment is to maintain functional vision through a person's lifetime. Novel medications with convenient once a day dosing and multiple, complimentary, mechanisms will be a welcome addition to the treatment options for glaucoma. The early trials are very encouraging and, if these early results prove to be reproducible, some of these agents may be available to help glaucoma patients in the near future.
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Article by Paul L. Kaufman, MD. Dr. Kaufman is the Ernst H. Bárány Professor of Ocular Pharmacology and immediate past Chair of the Department of Ophthalmology & Visual Sciences at the University of Wisconsin School of Medicine and Public Health, in Madison, Wisconsin. He has authored hundreds of original scientific articles and book chapters and received numerous honors and awards including the 2017 ARVO Friedenwald Award.

Last reviewed on October 29, 2017

This article appeared in the January 2017 issue of Gleams.

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