May 2020


Revolution in Glaucoma Medications
Sustained-release making inroads in glaucoma

by Liz Hillman Editorial Co-Director

The Durysta sustained-release implant in the anterior chamber
Source: © 2020 Allergan. Used with permission. All rights reserved.

First, glaucoma saw an explosion in MIGS innovation. Is sustained release for medications next?
Few areas of ophthalmology could benefit more from sustained-release medications than the glaucoma community. Compliance estimates for traditional drop therapy vary, but most physicians in the 2019 ASCRS Clinical Survey think 31% of patients, on average, are noncompliant on one topical glaucoma therapy. Such noncompliance can result in progression of the disease, potentially leading to irreversible vision loss.
There is only one FDA-approved sustained- release product for glaucoma treatment, but several are in the pipeline.
“Nearly zero percent of patients are 100% compliant,” said Blake Williamson, MD. “When you have the ability to take that out of their hands, it’s going to be a win every time.”

First FDA-approved product

Durysta (Allergan) received FDA approval in March as an intracameral bimatoprost implant. According to the company, the biodegradable pellet contains 10 mcg of the prostaglandin analog, which is delivered via a preloaded, single-use injector.
Clinical trials with the product showed that it performed similarly to 0.5% timolol drops for patients with open angle glaucoma or ocular hypertension, and it resulted in a 5–8 mm Hg IOP reduction from a mean 24.5 mm Hg baseline. In terms of safety, the most common adverse event was conjunctival hyperemia (27% of patients).
Dr. Williamson said what’s nice about Durysta is that it can be placed at the slit lamp in the office.
“The idea is patients can go every 3–4 months to see their eyecare provider, pop in one of these pellets, and you have sustained-release prostaglandin analog in the eye,” he said.
Lama Al-Aswad, MD, was involved in early clinical trials for Durysta and said she would be using it on some of her glaucoma patients now that it’s FDA approved.
“I think it’s the way of the future, and I like to offer my patients something that can manage their glaucoma and make it easier for them to adhere to treatment,” she said.

Products in the pipeline

In addition to Durysta, there are other products that hope to provide sustained-release medication to glaucoma patients in the future through different modes of delivery.
One is iDose (Glaukos), a travoprost-eluting implant that is injected into the anterior chamber. Phase 2 data shows an average IOP reduction of 7.9–8.5 mm Hg 12 months after injection.1 According to the company’s study, the group that received timolol required 31% more medications compared to those in fast-elution and slow-elution iDose cohorts. iDose is expected to be introduced in the U.S. market in 2021–22, Dr. Williamson said.
Dr. Williamson said that iDose will at least require taking a patient into a minor procedure room, because it is injected under a gonioscopic view of the angle through the trabecular meshwork into Schlemm’s canal.
“It’s very similar to how an iStent inject [Glaukos] is delivered,” he said, adding that there is promising data that this device could be eluting the IOP-lowering drug beyond 1 year.
Another drug delivery option in the works is a bimatoprost-eluting ring (Allergan), an ocular surface insert that fits around the ocular fornix. This ring completed Phase 2 clinical trials a few years ago, with data published in 2016, showing a reduction of 3.2–6.4 mm Hg from baseline (compared to a reduction of 4.2–6.4 mm Hg in the timolol group) over a 6-month period.2 In addition, Brandt et al. looked at 13 months of two cycles of using the bimatoprost ring.3 Safety, according to the study authors, was good, and patients reported the ring to be comfortable or at least tolerable. The median IOP reduction in the 13 months of follow-up was 4 mm Hg.
Punctal plugs are already being used to elute steroids after cataract surgery for management of pain and postop inflammation, but they could someday be used for glaucoma therapy as well. Ocular Therapeutix is in Phase 3 testing stages with OTX-TP, a travoprost insert designed to deliver the drug for up to 90 days. Mati Therapeutics with Evolute is in clinical trials to deliver latanoprost through an intracanalicular insert.
Similar to Durysta’s delivery as an intracameral implant is Envisia Therapeutics’ ENV515, which is in Phase 2 trials to release travoprost over an 11-month period. Ocular Therapeutix’s OTX-TIC, an intracameral travoprost implant with a targeted drug duration of 4–6 months, is also under clinical evaluation, recently completing its Phase 1 clinical trial.
Further work is being done on a range of injectable drugs (Clearside Biomedical/Santen, IBI-60089, EyePoint Pharmaceuticals, GB-401, Graybug Vision), gel-forming drops (SoliDrop, Otero Therapeutics), intrascleral implants (Ophthalmic MicroPump System, Replenish), and latanoprost-eluting contact lenses, among the other possible sustained-release drug delivery options.

Stratifying products

As with MIGS when many options were coming to the market, Dr. Al-Aswad said she thinks there will be a place for various modes of delivery.
“I think we’re going to see what survives from these, how will they work, their side effects, the compliance with them, and the complication rates. According to that, we will decide what will work for us,” Dr. Al-Aswad said. “In addition, by having all of these options, we can tailor it to the patient’s needs. … Depending on their needs and other factors, that might push us in one direction or another.”
Dr. Williamson envisioned a product like iDose being paired with MIGS procedures, because the surgeon would already be inside the eye. In terms of the day to day clinic, that’s where he thinks products like Durysta would come into play.
As with any procedure and medication, there will be risks, but Dr. Williamson said it’s important to think about it in terms of the benefit-risk profile.
“Does the potential risk of having an implant outweigh the risk of the alternative, which is topical therapy that they’re not taking? I would argue that the risk of not taking a drug and risking further visual field loss and blindness is worse than any potential issue with the implant or biodegradable itself,” he said.
Dr. Williamson said sustained drug delivery is the future for glaucoma pharmacologic therapy.
“I don’t think anyone is going to be using eye drops in our traditional form 25 years from now. It’s my prediction that everything is going to be moving toward drug elution or surgical solutions,” he said.
Another thing he said he would look forward to in the future is a sustained drug delivery option that addresses inflow. “If we’re combining drug elution with MIGS, all of the MIGS devices work on outflow, so it would be cool to pair that with a drug-eluting device that works on inflow,” Dr. Williamson said.
Dr. Al-Aswad said sustained-release has the potential to change how physicians think about glaucoma. For example, does a patient really need two medications to lower/maintain IOP or will improved compliance with a sustained-release option allow patients to use only one drug? What’s more, she said it truly has the potential to change a patient’s quality of life.
“One time I had a patient who was taking four types of drops for glaucoma and I did surgery and he said, ‘You don’t understand how much you’ve freed me. I have now free time that I don’t know what to do with,’” Dr. Al-Aswad said, speculating that sustained-release drugs could have a similar effect.
Dr. Al-Aswad said she thinks patients will be comfortable with sustained-release options because they’re already becoming more familiar with them for other ocular conditions that they or their friends might have. Dr. Williamson said the potential to improve compliance and lower IOP without a surgical procedure will be attractive to patients as well.
“In my practice and in other surgeons’ practices who like the idea of having 100% compliance every time for glaucoma therapy, I think this is going to be a first-line treatment,” Dr. Williamson said.

At a glance

• The first sustained-release medication for glaucoma, an intracameral implant, was approved by the FDA in March.
• Other products in the pipeline are looking at sustained drug delivery in the form of a ring, punctal plugs, gel-forming drops, injectable drugs, and more.
• Ophthalmologists think that many options for sustained drug delivery will allow them to tailor choices to meet patient needs.

About the doctors

Lama Al-Aswad, MD
Professor of ophthalmology Director of teleophthalmology, artificial intelligence and innovation
New York University Langone
Eye Center
New York, New York

Blake Williamson, MD
Williamson Eye Center
Baton Rouge, Louisiana



1. Glaukos. Accessed March 11, 2020.
2. Brandt JD, et al. Six-month intraocular pressure reduction with a topical bimatoprost ocular insert: results of a Phase II randomized controlled study. Ophthalmology. 2016;123:1685–1694.
3. Brandt JD, et al. Long-term safety and efficacy of a sustained-release bimatoprost ocular ring. Ophthalmology. 2017;124:1565–1566.

Relevant disclosures

Al-Aswad: None
Williamson: Allergan, Glaukos


Sustained-release making inroads in glaucoma Sustained-release making inroads in glaucoma
Ophthalmology News - EyeWorld Magazine
283 110
220 118
True, 5