Novel drug delivery platforms: Filling a ‘GAP’ in glaucoma


Medical therapy for glaucoma is not becoming obsolete, but it is evolving away from conventional topical administration.

Medical therapy for glaucoma is not becoming obsolete, but it is evolving away from conventional topical administration.

Considering the pace of innovation, Malik Y. Kahook, MD, suggested that drops will not be the primary method of treating glaucoma in 10 years. Dr. Kahook, professor of ophthalmology, The Slater Family Endowed Chair in Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, outlined drug delivery platforms at the Glaucoma Symposium during the 2017 Glaucoma 360 meeting.

“Medical therapy has real shortcomings, with adherence being its major limitation,” said Dr. Kahook. “The emergence of new surgical options has generated a debate over whether surgery for glaucoma management should be done sooner.

“Although it is being said more and more that medical therapy for glaucoma is becoming obsolete, I believe that its demise is greatly exaggerated,” he added.

Strategies introduced to address poor adherence with prescribed topical therapies have included various dosing and other aids to enable accurate instillation or overcoming forgetfulness. Individually, they have not factored in all of the issues that limit adherence.

“There is an unmet need for some ‘GAP’ (Guided Administration of Pharmaceuticals) therapy that would fit in a zone between topical medical therapy and laser or surgery–and provide 100% adherence along with satisfaction among both physicians and patients,” Dr. Kahook said.

GAP outlined


GAP outlined

Describing his wish list for this GAP therapy, Dr. Kahook said it should be patient-independent, physician-administered and monitored, and it should have a safety profile equal to or better than prostaglandin analogue topical therapy, a long duration of action (at least 6 months), and be repeatable over the patient’s lifetime.

GAP platforms in development include punctal plugs, subconjunctival depot injections, ocular surface inserts, and intraocular injectable depots. Reviewing the pros and cons of these approaches based on current iterations, Dr. Kahook concluded that none fulfills all of his wish list criteria.

“They are all able to provide 100% adherence and are patient-independent and physician-administered,” Dr. Kahook said. “Safety is an issue with the more invasive techniques, however, and long duration of efficacy is one of the biggest concerns.”

Regarding punctal plugs, the non-invasive nature of this approach is an advantage. However, retention has been an issue for most devices in this space, and based on publicly available data, punctal plug delivery of glaucoma medications has been less effective than topical timolol for lowering intraocular pressure (IOP).

“There are also questions about the long-term safety of a punctal plug,” Dr. Kahook said. “Considering all of these issues, this approach is not a perfect solution.”

The category of ocular surface devices includes the bimatoprost-laden silicone ocular surface ring (Helios, Allergan) that was shown in a phase II trial to have good retention and sustained IOP-lowering activity over 6 months.

“Discomfort does not seem to be a big issue because patients acclimate to the ring after a few days,” Dr. Kahook said. “An advantage of this device compared with punctal plugs is that patients will realize if the ocular surface ring falls out. A big unanswered question, however, is whether it can be as effective as a topical prostaglandin analogue.”




Subconjunctival injections–under development by several companies–represent an approach that can be delivered at the slit-lamp. However, it is still an invasive procedure and has been associated with inconsistent delivery and batch-to-batch reproducibility issues.

“Historically, frequent injections are needed,” Dr. Kahook pointed out. “That raises questions about the development of scarring that might preclude future glaucoma surgery.”

Data for intraocular injections of glaucoma medication depots show they have IOP-lowering efficacy approaching that of topical prostaglandin analogue. The approach, however, is invasive, and it is unclear whether it is a procedure that can be done at the slit-lamp.

“Administration of these injections is something that must be done with the patient lying on a bed in a procedure room, which is not available in every office,” Dr. Kahook said. “Data are needed to establish long-term drug delivery and safety.”

Patient perspectives


Patient perspectives

Patient acceptance will be an important factor influencing the adoption of alternative delivery methods. Dr. Kahook noted that data from a survey conducted at his center showed that while the majority of patients with glaucoma indicated a preference for drops over any other treatment options (including laser therapy, punctal plug drug depots, injections around or into the eye, implantable refillable reservoirs, or invasive surgery), 45% of patients said they would accept an approach more invasive than topical administration to reduce or eliminate the need for drop therapy.

“What if a patient needs two medications?" Dr. Kahook asked. “Will patients accept replacing one drop bottle, but not the other? What happens to the patient’s risk assessment if adverse effects begin to emerge when more patients are treated and repeated injections are given?”

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