1. Dec 20, 2019

Two Glaucoma Treatment Takeaways From AAO 2019

Last winter we reported the latest on important second-line medication treatments for glaucoma.

How do things stand nearly a year later? We caught up with a couple of experts at the American Academy of Ophthalmology’s 2019 annual meeting in San Francisco. Two important takeaways:

  • It appears that you can use the rho-kinase inhibitor netarsudil safely in eyes that are being treated with multiple classes of medications—up to four, in fact
  • Once approved (expected in 2020), the bimatoprost sustained-release implant is looking like a useful alternative for patients in whom medication adherence is a problem

Netarsudil 0.02% became available in the US in the spring of 2018. A year later, the fixed-dose combination of netarsudil 0.02% and latanoprost 0.5% was approved. Netarsudil lowers intraocular pressure (IOP) via enhanced outflow through the trabecular pathway. “The drug decreases outflow resistance at the meshwork and lowers episcleral venous pressure,” explained Janet B. Serle, MD, professor emeritus of ophthalmology, Icahn School of Medicine at Mount Sinai in New York. “There is also a small reduction in aqueous flow rates.”

She added that when the prostaglandin latanoprost is added to netarsudil, “we get a fourth mechanism: enhanced uveoscleral outflow. This is novel. None of the drugs we previously had work specifically at the trabecular pathway.”

Real-World Experience

Safety and efficacy of both medications were demonstrated in the ROCKET and MERCURY trials, which have been previously reported. “But what has happened since the drugs were approved?” asked Dr. Serle. In other words, what is the real-world experience?

In a retrospective analysis involving 172 eyes in 108 individuals, netarsudil was added to the glaucoma medication regimens patients were already taking. Investigators observed an average reduction in IOP of 3.7 mmHg at 1 month and 3.9 mmHg at 3 months. Importantly, there was no significant difference in IOP change in patients taking less than three medications or three or more medications at month 3. “This confirms that this drug is additive to other classes of medications that patients are taking for glaucoma,” said Dr. Serle.

In terms of side effects, conjunctival hyperemia was reported in 23%, and blurred visual acuity in 8%. However, there was no change in best corrected visual acuity. Seventeen percent of patients stopped using the medication due to adverse effects and insufficient efficacy.

Dr. Serle reported on the experience of one of her own patients to highlight the ability of netarsudil to lower IOP and satisfy patient expectations. This 75-year-old woman had laser iridotomies and selective laser trabeculoplasty in both eyes. She also had a well-controlled mitomycin trabeculectomy in the left eye, and the right eye was receiving four medications: latanoprost, timolol, brimonidine, and brinzolamide. Gonioscopy showed scattered synechiae in both eyes and a patent sclerostomy in the right eye. She was on no other medications except celecoxib for back pain. IOP in the right eye was 19 mmHg.

“At this point, she was not really interested in additional glaucoma surgery in her right eye,” noted Dr. Serle. “In such situations you really have to go with what your patient prefers.” So she began taking netarsudil at bedtime. Her pressure decreased in the ensuing months and was at 15 mmHg in the right eye at month 7. “Remember, this is the fifth drug added to this eye, and so far IOP is adequately controlled.”

Dr. Serle said that when she treats similar patients going forward, she will use the fixed dose combination of netarsudil and latanoprost (which was not yet available when treating this particular patient).

Sustained-Release Implant Can Improve Adherence

Bimatoprost sustained release is a biodegradable implant designed to lower IOP in patients with primary open-angle glaucoma. Earl Randy Craven, MD, chief, Wilmer Eye Institute in Bethesda, MD, and associate professor of ophthalmology at Johns Hopkins Medicine, reported results of the Phase 3 ARTEMIS trial. Participants received either bimatoprost 10 µg or timolol 0.5% BID.

Bimatoprost was implanted at baseline, week 16, and week 32. Results through week 12 showed the implant to be noninferior to timolol. Pressure was reduced up to 7.7 mmHg.

“But then the truly remarkable thing to me is what we saw [as] time went on,” explained Dr. Craven. Twenty weeks after the third implant was put in at week 32, “80% of the time, patients experienced sustained control that did not require rescue or retreatment.”

“One of the primary [issues] all of us struggle with is medication adherence—it is a huge problem,” said Dr. Craven. He said he believes that adding sustained release options will help ophthalmologists increase compliance and improve outcomes.

References:

Serle J. Update on rho kinase inhibitors after first year in practice. Presented at: AAO 2019 annual meeting; October 12-15, 2019; San Francisco, CA.

Craven E. Phase 3 evaluation of bimatoprost sustained-release implant in patients with glaucoma or OHT: Results at primary database lock. Presented at: AAO 2019 annual meeting; October 12-15, 2019; San Francisco, CA.