November 2019


Pharmaceutical focus
Evaluating surface-based sustained delivery platforms for glaucoma

by Maxine Lipner EyeWorld Senior Contributing Writer

“In a perfect world, we would have an external device that is 100% retained and free of adverse events...”
—Malik Kahook, MD

The Evolute Punctal Plug Delivery System (Mati Pharmaceuticals) is a surface device that fits in the tear drainage system.
Source: Mati Pharmaceuticals


These days a variety of surface-based systems for delivering glaucoma medication to the eye are being explored to overcome patient adherence problems, peak and trough delivery, and other issues. Among these are devices such as punctal plugs, contact lenses, ring delivery systems, micro-particle platforms, and more. EyeWorld asked two specialists to consider what these options have to offer.
Such systems fall under the umbrella of platforms that are external to the eye, dubbed eGAPs (external-guided administration of pharmaceuticals), according to Jason Bacharach, MD. Meanwhile, the other type of sustained delivery system—iGAPs (internal-guided administration of pharmaceuticals)—may include things such as the sustained-release bimatoprost (Bimatoprost SR, Allergan) and iDose (Glaukos). “Each of those two systems have their limitations,” Dr. Bacharach said. With iGAPS, efficacy is great, but there are safety concerns, he noted, adding that eGAPS tend to be safer but with an efficacy tradeoff.

Innovative surface devices

One device currently being explored is the Punctal Plug Delivery System (PPDS, Mati Therapeutics), according to Malik Kahook, MD. “The Mati plug fits in the tear drainage system and slowly elutes drug from the faceplate to the tear film in a passive manner,” Dr. Kahook said. It is minimally invasive to insert and has the ability to deliver commonly used topical drops to the ocular surface, he noted. “Drawbacks include unreliable retention of the plugs, as well as the small medication loads that each plug can carry,” he said. This also requires a robust tear film that can retain the drug.
There is also a travoprost-loaded punctal plug (Ocular Therapeutix). This system also resides in the punctum and canaliculus. It is a polymer-carrying system that delivers drug slowly to the tear film in a similar fashion to the Mati plug, Dr. Kahook explained, adding that in this case, however, the plug does not have a faceplate and swells in place after insertion. Unfortunately, the plug may migrate into the distal outflow system without anyone recognizing this, thereby affecting efficacy, Dr. Kahook continued.
A third option, the bimatoprost ring (Allergan), elutes the drug directly into the tear film, Dr. Kahook said. It is placed noninvasively over the eye in a manner similar to a large-diameter contact lens, and can carry a larger drug load than the plugs, he continued. Meanwhile, the cons include potential discomfort due to rubbing on the ocular tissue, as well as cosmetic issues since the device is visible along the medial canthus, Dr. Kahook said.
Yet another modality is the topical drug delivery device (TODDD, Amphorex Therapeutic), which Dr. Bacharach describes as similar to the ring. “This is a soft elastomeric structure that floats atop the sclera underneath the eyelid,” he said. “It elutes drug from different reservoirs and you can do multiple drugs.”
An early attempt at iGAP was the subconjunctival use of anecortave acetate (Graybug Vision). This involves microparticles that can deliver the drug over several weeks to several months via a subconjunctival injection, Dr. Bacharach noted.

What to expect

Efficacy with all of these surface systems can be somewhat limited. “To date, external devices, such as plugs and rings, have not achieved prostaglandin-like efficacy, with most achieving timolol-like efficacy or exhibiting efficacy slightly worse than timolol over months of therapy,” Dr. Kahook said. Meanwhile, Dr. Bacharach noted that there was an approximately 20% reduction in IOP for both the Mati plug and the bimatoprost ring.
When putting in one of these devices, there has to be a comfort level for all types of practitioners, Dr. Bacharach stressed. “I think that, in general, we might see optometric doctors gravitate more to the external, non-surgical delivery devices like plugs and rings and you might see a comprehensive ophthalmologist use everything, both external and internal,” Dr. Bacharach said, adding that tertiary-care specialists would probably use more efficacious platforms that have more associated risks such as intracameral delivery devices.
For many patients who need mild-to-moderate reductions of IOP, these eGAPs may give patients enough of a decrease, he noted, adding that this may be a way to overcome some of the challenges of adherence, peak and trough effects of drops, and acquisition costs of the medicine. “It’s a potentially safe treatment option that will give you reasonable efficacy,” Dr. Bacharach said.
Going forward, Dr. Bacharach believes that there will be winners and losers with all of this kind of nascent technology. “But I think that pushing the envelope here is where we’re headed,” he said. Early on, practitioners may opt for an external delivery system and then later decide to move more internally, he noted.
Likewise, Dr. Kahook also believes that all safe and effective options are needed. “In a perfect world, we would have an external device that is 100% retained and free of adverse events, with the ability to deliver drugs over at least 6 months, while being totally independent from patient interactions,” he said. “We are not there today, but future devices might get us closer to my wish list.”

About the doctors

Jason Bacharach, MD

Medical director, founding partner
North Bay Eye Associates
Co-director, Glaucoma Services
California Pacific Medical Center
San Francisco

Malik Kahook, MD
Slater Family Endowed Chair in Ophthalmology
Professor of ophthalmology
Vice Chair for Translational Research
Director, Glaucoma Service
UCHealth Sue Anschutz Rodgers Eye Center
Aurora, Colorado

Relevant financial interests

Bacharach: Allergan, Ocular Therapeutix, Glaukos, Equinox, New World Medical
Kahook: Alcon, Aurea Medical, Equinox, Fluent Ophthalmics, Ivantis, New World Medical, Johnson & Johnson Vision, ShapeTech, SpyGlass

Contact information


Evaluating surface-based sustained delivery platforms for glaucoma Evaluating surface-based sustained delivery platforms for glaucoma
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