University of California, San Francisco, UCSF Medical Center
Learn about two new medications that were approved by the FDA in late 2017, and why they are so exciting to patients and ophthalmologists alike.
Prior to late 2017, the last new glaucoma medication was latanoprost, a prostaglandin analogue, approved by the FDA in 1996. This class of medications — which, in addition to latanoprost includes, travoprost, and bimatoprost — is highly effective at managing eye pressure. However, the glaucoma medication toolbox lacked a treatment that directly targeted the trabecular meshwork, the diseased tissue in glaucoma.
The trabecular meshwork is the spongy tissue located near the front of the eye through which eye fluid known as aqueous humor flows out of the eye. Targeting of diseased tissue directly holds great promise in lowering eye pressure.
First, let us discuss how current glaucoma medications lower eye pressure. If we think of eye pressure control as a plumbing problem or inflow/outflow problem, there are some medications that increase outflow (improve the drainage), and others that decrease inflow (turn down the faucet). While both types of medications result in lowered eye pressure, glaucoma is not really a problem of increased inflow but rather an issue of decreased outflow, and as mentioned above, none of the older glaucoma medications targets the trabecular meshwork.
The first new medication, produced by Bausch + Lomb, is latanoprostene bunod (Vyzulta) which was FDA approved in November 2017 and is now available to patients. It releases nitric oxide, which is thought to relax the trabecular meshwork to increase drainage of aqueous humor and improve aqueous humor outflow.
Vyzulta is the first nitric oxide-containing medication for glaucoma treatment worldwide. Interestingly, there have been genetic and laboratory studies suggesting that nitric oxide may play a role in glaucoma through effects on blood flow to the optic nerve, and thus the mechanism of Vyzulta may go beyond simply lowering eye pressure. However, this mechanism has not yet been proven in patients.
Clinical trials have been conducted comparing Vyzulta to latanoprost and timolol. Vyzulta results in greater eye pressure lowering compared to latanoprost and timolol. Side effects of Vyzulta are similar to that of prostaglandin analogues, since this new drug contains a prostaglandin analogue. Common side effects include redness of the conjunctiva, eyelash growth, eye irritation, and eye pain at the time of instilling the medication. Vyzulta is also used similarly to prostaglandin analogues, being dosed one drop in the evening. Patients who are already on prostaglandin analogues can talk with their eye doctor to see if switching to Vyzulta results in an improved lowering of eye pressure.
The second new medication is also a novel class of medications called rho-associated protein kinase inhibitors, or ROCK inhibitors. These inhibit Rho kinases, enzymes that control cellular structures involved in cell shape and movement. ROCK inhibitors are thought to lower eye pressure by relaxing the trabecular meshwork and connection passageway, called Schlemm’s canal. This canal drains the aqueous humor from the anterior chamber of the eye into the veins draining the eyeball.
This decreases the resistance to drainage or outflow in the conventional outflow pathway, thus lowering eye pressure. There are also some preliminary laboratory studies that suggest that ROCK inhibitors also have a role in promoting survival of the retinal ganglion cells, which are the cells that die in glaucoma. However, this mechanism has not yet been proven in patients.
The ROCK inhibitor that was approved by the FDA in December 2017 is produced by Aerie Pharmaceuticals, and is called netarsudil (Rhopressa), a small molecule inhibitor of Rho kinase. In addition to its effect on improving drainage through the trabecular meshwork and the conventional outflow pathway, Rhopressa also decreases aqueous humor production, possibly through a different mechanism.
Clinical trials comparing Rhopressa to latanoprost and timolol have shown that Rhopressa lowers eye pressure to a similar degree. The most frequent side effects include eye redness, small bleeds in the conjunctiva, and corneal changes. Rhopressa is dosed twice daily and was made available for those with access to Medicare or Medicaid in January of 2019.
Currently undergoing a clinical trial is a combination drop that combines the ROCK inhibitor netarsudil with latanoprost (Roclatan™). Preliminary studies demonstrate that this combination medication is superior to latanoprost and netarsudil alone. Roclatan is exciting because it will be a combination drop that is dosed only once a day, an option not currently available in the United States.
It is indeed an exciting time for glaucoma patients and ophthalmologists. These new medications hold great promise in lowering eye pressure by directly targeting the tissue that is diseased in glaucoma, the trabecular meshwork. Now we are eager to see how these new medications perform in a real-world setting in treating glaucoma patients.
Yvonne Ou, MD, is a board certified ophthalmologist who specializes in glaucoma, including medical, laser and surgical therapies; cataract evaluation and treatment including combined cataract and glaucoma surgery; glaucoma filtering and implant surgery; and newer procedures.
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