This roundtable discussion series about sustained-release drug delivery for glaucoma includes Steven R. Sarkisian, Jr., MD, founder and CEO of Oklahoma Eye Surgeons, PLLC, in Oklahoma City, Oklahoma; Jacob Brubaker, MD, from Sacramento Eye Consultants in Sacramento, California; and E. Randy Craven, MD, FACS, Chief of Wilmer Eye Institute, Bethesda Location, Vice Chair for Wilmer Network of Locations, and an associate professor at Johns Hopkins University in Baltimore, Maryland. The third part of this series addresses sustained-release glaucoma therapies that are in preclinical studies and early-phase clinical studies.

Dr. Sarkisian: What are some of the other sustained-release technologies in development?

Dr. Craven: Here at Johns Hopkins, there is a lot of research going on into different microspheres and nanoparticles. I’m not sure what’s going to work. They’re still in the animal model phase, but there’s a lot of interest in that.¹ Another sustained-release product in development is the PolyActiva intracameral ocular implant, which delivers latanoprost for 6 months and then biodegrades.

Dr. Brubaker: I think we’re still having difficulty with something in the lacrimal duct. Anecdotally I have heard of issues with retention and efficacy compared to timolol.

Dr. Sarkisian: The Ocular Therapeutix OTX-TP travoprost intracanalicular implant recently failed in a phase 3 trial vs timolol. It’s possible that the FDA will allow the plug to market. However, plugs can come out, and having the drug on the ocular surface is not ideal.

Dr. Brubaker: The plugs are fluorescent, so you can check in the mirror with a blue light and see if they are retained, but from an efficacy standpoint, it wasn’t quite to target.

Dr. Sarkisian: It seems that we will still see topical side effects of sustained-release technologies that are on the surface of the eye, whether it’s Allergan’s bimatoprost ring, or Mati Therapeutics’ latanoprost punctal plug drug delivery system, or devices that can be put in the fornix. Is there a need for topical sustained release when we have good intracameral or angle-based sustained release?

Dr. Craven: It could be that we experiment with combinations to see what works best. We may put an implant inside of the eye and then use plugs to supplement.

Dr. Sarkisian: But if you have a prostaglandin inside the eye, you’re probably not going to put a prostaglandin on the surface of the eye, too.

Dr. Craven: If it’s waning and you want to buy some time, maybe.

Dr. Sarkisian: Are there any sustained-release technologies that are not prostaglandin?

Dr. Brubaker: I’m not aware of any. I think it has to do with the molecule itself. Certain molecules don’t lend themselves to being embedded in a sustained-release formulation. I do know that prostaglandins do well in that environment, but some of the other medications are lost too quickly, and so they can’t be incorporated, at least with our current technology, as easily into sustained release.

Editor’s note: Dr. Sarkisian reports consultancy to, advisory board membership with, speaker’s fees from, and grant support from Alcon; consultancy to, advisory board membership with, and speaker’s fees from Allergan and Bausch + Lomb; consultancy to and advisory board membership with Beaver-Visitec International, Katena Products, New World Medical, Omeros, and Santen; consultancy to, advisory board membership with, equity ownership with, and grant support from Sight Sciences; and consultancy to, advisory board membership with, and grant support from Glaukos. Dr. Brubaker reports consultancy to Glaukos and Allergan. Dr. Craven reports consultancy to and advisory board membership with Aerie Pharmaceuticals, Alcon, Allergan, Aqueous Biomedical, Ivantis, Santen, and W.L. Gore.

Reference

1. Pitha I, Kimball EC, Oglesby EN, et al. Sustained dorzolamide release prevents axonal and retinal ganglion cell loss in a rat model of IOP-glaucoma. Transl Vis Sci Tech. 2018;7(2):13.