Punctal plug-based delivery systems for sustained delivery of glaucoma medications represent new and versatile technology that is under development.
The hope is it can help with the problem of patient compliance when managing mild-moderate glaucoma, said Marlene Moster, MD, during Glaucoma Subspecialty Day at the 2017 meeting of the American Academy of Ophthalmology
“We know that compliance matters in glaucoma therapy,” said Dr. Moster, private practice, Bala Cynwyd, PA, and an attending surgeon, Wills Eye Hospital, Philadelphia.
“But, one study of glaucoma monotherapy found that 25% of patients took less than 75% of doses and almost 20% of patients took less than 50% of their doses, even though they knew they were being monitored electronically.”
While there is also interest in developing intraocular and extraocular platforms for sustained delivery of glaucoma medications, punctal plug delivery offers some attractive features.
First, they represent a non-invasive intervention, and there is huge experience with punctal plugs in ophthalmology.
“Punctal plugs for dry eye have become a well-accepted therapeutic solution when topical preparations are not effective,” Dr. Moster said.
In addition, punctal plugs can be removed, made to dissolve, and if one configuration does not work, another shape can be tried. They can also be made to fit all sizes of puncta.
Currently, two companies—Mati Therapeutics and Ocular Therapeutix—are performing clinical trials of punctal plug delivery systems for glaucoma medications.
The Mati Therapeutics platform (Evolute) has an L-shaped design and is inserted into the nasolacrimal duct. The device is cosmetically invisible, but can be easily seen with eversion of the lower lid.
The device that was studied for glaucoma has a core of latanoprost-polymer matrix that is surrounded by silicone, and it delivers the medication into the tear film at a constant rate.
In a phase II clinical trial, the latanoprost punctal plug was found to be comfortable. It was associated with a 20% lowering from baseline IOP over a 3-month period, and in two separate clinical trials, it had a retention rate of 92% and 96%, respectively.
The Ocular Therapeutix technology is a dissolving intracanalicular depot. The plug is invisible to the patient, but is fluorescent at the slit lamp.
“Because this plug is intracanaliuclar, it is a little more difficult to remove than the other device, and the removal may require irrigation or physical manipulation” Dr. Moster said.
A clinical trial was conducted evaluating a travoprost punctum plug composed of the prostaglandin analogue encapsulated in polyactide microparticles in a resorbable hydrogel rod.
Upon exposure to the tear film, the rod swells within the canaliculus, causing hydrolysis of the microparticles and sustained release of the drug load into the tear film.
A phase II study randomly assigned 73 patients into two groups to receive either the travoprost plug with twice daily artificial tears or timolol 0.5% twice daily with placement of a drug-free punctal plug.
At 90 days, there was a 4.5 to 5.7 mm Hg reduction from baseline IOP in patients who had the travoprost punctal plug, which was clinically meaningful.
However, the control group had an average IOP lowering of 6.4 to 7.6 mm Hg.
“It was thought that the more significant IOP reduction in the control group was explained by longer contact time of the beta blocker on the ocular surface because of the ‘dummy’ plug in the puncta,” Dr. Moster said.
The safety profile was good—no hyperemia was seen. The retention rate at 60, 75, and 90 days was 91%, 88%, and 48%, respectively.
Dr. Moster has no financial interest in the products she discussed.