April 2019

GLAUCOMA

Pharmaceutical Focus
Tailoring glaucoma medications for patients


by Maxine Lipner EyeWorld Senior Contributing Writer


Drawing on new agents, practitioners can better target therapy for patients with glaucoma.
Source: Janet Serle, MD

 

Currently there are several glaucoma treatment options that slow down the rate of progression and preserve vision. As of this writing, the new agent Roclatan (netarsudil/latanoprost, Aerie Pharmaceuticals) is on the cusp of approval, according to Janet Serle, MD. This combination agent, consisting of a rho kinase inhibitor and a prostaglandin agonist, is one of many tools practitioners will have to enable them to tailor treatment for patients. EyeWorld spoke with two specialists on how different agents can benefit unique glaucoma patients.
For those who need additional IOP reduction, the fixed combination Roclatan is promising since it is more efficacious than its individual components, Dr. Serle said, adding that IOP reductions in the Phase 3 clinical trials were 2 to 3 mm Hg greater than with either latanoprost or netarsudil alone. “More of the Roclatan-treated patients met or exceeded typical IOP target pressures of low to mid-teens and target percentage IOP reductions of greater than 30% than the patients treated with either of the components,” she said. The once-daily dosing also makes it an attractive treatment for those taking drops that require dosing two or three times daily, Dr. Serle said.
Jacob Brubaker, MD, agreed. “Not only is it a robust medication but it’s also convenient for patients,” he said. “They take it just once a day, at night.” Other fixed combination therapies such as Combigan (brimonidine/timolol, Allergan) or Cosopt (dorzolamide/timolol, Akorn) must be taken at least twice a day. “I think this will be good for patients on prostaglandins who need a little boost,” Dr. Brubaker said. He views this once-a-day agent as invaluable for those who may have difficulty remembering to take more than one eye drop.
However, the agent brings with it a nearly 58% chance of conjunctiva redness, so there will be those who can’t tolerate it. Fortunately, most of the time this is mild and not always constant.
For those with low tension glaucoma, Roclatan will also be a good option since it does such a good job of lowering IOP, Dr. Brubaker said. He cited the combined Mercury trials, which indicated that 31% of people had pressure lower than 14 mm Hg on Roclatan.
Other adjunctive medications may include the carbonic anhydrase inhibitors, beta blockers, and Alphagan (brimonidine, Allergan), Dr. Brubaker said. “The Low-Pressure Glaucoma Treatment Study showed a benefit to using Alphagan with low tension glaucoma1. When compared to timolol 0.5% there was a reduced likelihood of visual field progression even with the same IOP. Because of this there is a suggestion that Alphagan is neuroprotective. There are flaws to the study, however, as there was a high dropout in the Alphagan group. Additionally, some think that timolol, due to its potential systemic hypotensive effects at night, is actually to blame for the difference.” He views dorzolamide and Azopt (brinzolamide, Novartis) as other great adjunctive options. However, Dr. Brubaker tries to avoid timolol because of the aforementioned systemic hypotensive effects.
There are also now agents capable of enhancing trabecular outflow as well as influencing episcleral venous pressure (EVP). Dr. Serle noted that netarsudil has been confirmed to reduce episcleral venous pressures, due to the dilation of the episcleral vessels.2
There’s some thought that in cases where the trabecular meshwork has been bypassed with MIGS or trabecular function has been improved with SLT, pressure reduction may be enhanced with an agent that reduces EVP such as netarsudil, either alone or in combination, she noted. “Netarsudil improves outflow through the entire trabecular outflow pathway,” Dr. Serle said.
Since damage to the trabecular outflow pathways occurs over a lifetime for glaucoma patients, beginning them early on medications that directly affect trabecular tissues such as Rhopressa (netarsudil, Aerie Pharmaceuticals), Roclatan, and Vyzulta (latanoprostene bunod, Bausch + Lomb) may prevent, slow, or reverse trabecular pathway damage, she said.
For those who are on many medications, obtaining compounded drops in which these are mixed together can make the patient’s regimen easier. Dr. Brubaker has begun using this approach with a patient who was initially on four medications plus Rhopressa. “She told me she had to put one eye drop in and wait 5 minutes,” he said. “It would take about half an hour to get through her eye drop routine.” Now, she’s able to take just one compounded drop from Imprimis, as well as the Rhopressa, which is not available for compounding. The big question is whether the compounded product will be as effective as the individual ones, he noted, adding that use is still early.
Going forward, there is a new class of IOP-reducing compounds beginning Phase 3 trials in 2019, omidenepag isopropyl (EYBELIS, Santen), a selective prostaglandin EP2 receptor agonist, Dr. Serle noted, adding that devices implanted in the periocular or intraocular space with reservoirs for slow drug release will probably be the next major change, taking patient compliance out of the equation.

About the doctors
Jacob Brubaker, MD

Sacramento Eye Consultants
Sacramento, California

Janet Serle, MD
Professor emeritus of ophthalmology
Icahn School of Medicine
at Mount Sinai New York

References

1. Krupin T, et al. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011;151:671–81.

2. Li G, et al. Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes. Eur J Pharmacol. 2016;787:20–31.

Financial interests
Brubaker
: Aerie Pharmaceuticals, Alcon, Allergan
Serle: Aerie Pharmaceuticals, Allergan, Bausch + Lomb, Ocular Therapeutix

Contact information
Brubaker
: jbrubaker@gmailsaceye.com
Serle: janet.serle@mssm.edu

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