New Dual Action Glaucoma Medication Promising for Glaucoma Patients

In November 2017, the FDA approved Vyzulta, latanoprostene bunod (LBN), as a potential game-changer in the treatment of glaucoma.

Whenever a new Apple product is released, the media hype is immense and people will camp out for days just to be the first to own one. Ophthalmology is never going to be as interesting as iPhones but in our niche, we have a product launch that is as groundbreaking and innovative as this.

I’m talking about Vyzulta™ — one of the first new glaucoma drops to hit the market in two decades. Developed by Bausch & Lomb, this new medication is a dual action, once per day eye drop.

Over 70 million people worldwide are afflicted with glaucoma, a group of ocular diseases characterized by progressive, irreversible damage to the optic nerve in the back of the eye.

The internal fluid movements of the human eye can be viewed as analogous to a sink. Fluid, aqueous humor, is produced throughout one’s lifetime at a steady rate of about 2.5 microliters per minute — acting similar to the faucet in a sink turned on. Concurrently, fluid drains out of the eye, like the drain in a sink. The aqueous drainage is through two independent outflow tracts, the trabecular and uveoscleral pathways. Aqueous humor should be produced and drained out of the eye at very similar rates, providing internal pressure in the eye, called intraocular pressure (IOP). Unfortunately, at times the drain becomes partially clogged with ensuing years, causing damage to the optic nerve, and a resultant loss of vision. This proverbial clogging of the drain is caused by increased resistance to aqueous humor outflow.

IOP reduction continues to be the gold standard treatment for glaucoma patients. Very unfortunately, reducing IOP alone fails to halt disease progression and vision loss in some patients, but this is a relative rarity.

For glaucoma patients, the ultimate goal of therapy is to stop the disease progression in order to prevent further loss of vision. There are three distinct treatment options to treat chronic open angle glaucoma (COAG) consisting of medications, laser procedures, and surgery in the operating room. Over 95% of U.S. glaucoma patients are initially treated with eye drops. The eye drops can lower the IOP by decreasing aqueous production, increasing aqueous outflow, or by concurrently decreasing aqueous production and increasing outflow.

Currently, the glaucoma medications are divided into five classifications with each class having distinct mechanisms of action, therapeutic effects, and concomitant side effects. Prostaglandin analogs, referred to as PGAs, were the last of the five glaucoma medication class to be developed, with their inception being in the 1990’s. PGAs help open the drainage tracts to enhance outflow of the intraocular fluid, working almost exclusively on the uveoscleral outflow. PGAs have experienced a meteoric rise in popularity due to an excellent efficacy, safety, and the convenience with a once daily dosing schedule. As a result, the PGAs are by far the most frequently prescribed class of glaucoma drops in the U.S., with four PGA options approved for clinical use.

Since the advent of the PGAs in the 1990’s, an innovation lull in glaucoma medications has existed. While a few new combination drops, combining two existing classes of glaucoma medications in the same bottle have hit the market with success in recent years, the medical treatment of glaucoma has been essentially at a standstill.

In November 2017, the FDA approved Vyzulta, latanoprostene bunod (LBN), as a potential game-changer in the treatment of glaucoma. As mentioned, PGAs work to lower IOP by enhancing uveoscleral outflow. Importantly, while PGAs can lower IOP by 25-35%, their effect on the even more important trabecular outflow is minimal. It is the increased resistance to aqueous outflow through the trabecular meshwork and its adjacent structures that is an even greater factor in the development of elevated pressure in COAG.

Vyzulta is a first-in-class monotherapy eye drop that is dual action therapy working simultaneously on increasing trabecular and uveoscleral outflow. LBN, once it enters the eye, acts through two metabolites released during its intraocular hydrolysis, producing the release of latanoprost and butanediol mononitrates. Latanoprost, one of the four existing PGA glaucoma medications, again, works almost exclusively with the uveocleral pathway to increase aqueous humor outflow. The butanediol monontirate releases nitric oxide (NO) which increases trabecular outflow. As a dual action medication, Vyzulta, in clinical trials lowered IOP to an even greater extent than PGAs, thereby establishing this medication as a probable landmark breakthrough of enhanced efficacy compared to PGAs. In the meantime, Vyzulta’s clinical trials indicated identical common adverse ocular reactions such as redness and irritation. Vyzulta, very importantly, maintains the very popular once per day dosing.

Vyzulta is especially important because treatment response to PGAs varies, with some patients not achieving the requisite reduction of IOP in order to prevent disease progression. Alternate therapies have existed, as well as combination drops, but these medications have limitations, and commonly, more prevalent side effects, including systemic adverse reactions. About 50% of glaucoma patients need two or more different medications. Lengthy studies have demonstrated that individuals using two medications results in a reduced level of patient adherence to the prescribed regimen. Utilization of three or more eye medications results in worrisome steep decline in compliance taking the requisite eye drops. Therefore, a monotherapy such as Vyzulta, taken only once per day should propel excellent adherence to the regimen.

As the first new IOP-lowering agent with a novel mechanism of action since the introduction of latanoprost in the 1990’s, the imminent release of Vyzulta has resulted in a heightened level of interest in the ophthalmology community.

Seeing is believing so we shall wait and see how Vyzulta is received by those with glaucoma.

Article by Alan Mendelsohn, MD, FACS.
First posted January 18, 2018; Reviewed June 16, 2022.