Eyeworld

NOV 2015

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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EW FEATURE 44 Glaucoma medical treatment • November 2015 by Maxine Lipner EyeWorld Senior Contributing Writer AT A GLANCE • Numerous medication strategies independent of patient compliance are being considered. • With long-term systems, investigators must deal with concerns about how the drug is released. • Approaches vary from non-invasive systems simply placed on the eye to drug depots inside the eye or even injectable nanoparticles. Surmounting challenges Developing a long-term drug deliv- ery product is very challenging, said Gary D. Novack, PhD, PharmaLogic Development, San Rafael, Calif. "I've worked on a number of drug deliv- ery systems in ophthalmology over the years, and it's more complicated than it seems," Dr. Novack said. "At a minimum doing drug delivery is adding another dimension to dose response." In addition to the usual concentration and frequency with these systems, investigators must consider just how the drug is being released, he explained. The idea of using such an approach for glaucoma has been around for some time. There was the Ocusert product (Alza, Moun- tain View, Calif.) for delivering the short-acting drug pilocarpine, Dr. Novack said. It was a great way to deliver the pilocarpine at a consis- tent, nearly zero-order rate for the life of the product, he said, adding that while it was very good for con- sistently releasing the drug, it did have a downside. "It created another problem, which was that this was something in the eye that could slide across the cornea," Dr. Novack said. This could be a real problem, particularly if people were driving. Now new options are being de- veloped. Dr. Kahook thinks that it is a very exciting stage in drug delivery for glaucoma. "We have all these different methods, whether they're devices that are inside or outside of the eye, or these drug depots under- neath the conjunctiva or inside the eye," Dr. Kahook said. When weigh- ing this long-term technology, his preferences range from less invasive to more invasive approaches. "If we had a way to insert a punctal plug that delivers an active ingredient over a long period of time, all else being equal, that would be better than methods that require invasive injection or implantation," he said. "I would prefer a subconjunctival implant over an intraocular implant if it gave me the same efficacy." Still, he would accept a more invasive delivery system in or around the eye if it ensured safety and efficacy. It's still too early to decide which approach works best. "Un- fortunately, right now it seems as if the less invasive versions have a lot of variability that requires further development," Dr. Kahook said. Extending the duration of glaucoma medications One long-term option may be glaucoma drug depots for underneath the conjunctiva or inside the eye. New formulations and delivery systems W hen it comes to long- term glaucoma ther- apy, the overarching theme comes down to enhancing adher- ence, according to Malik Y. Kahook, MD, Slater Family Endowed Chair in Ophthalmology and chief of the glaucoma service, University of Col- orado, Aurora, Colo. With approx- imately 50% of patients not taking their prescribed drops, it's a matter of figuring out how to heighten usage, he said. To help with this, investigators are examining different approaches of injecting or placing systems in or around the eye that wouldn't rely on the patient's com- pliance. EyeWorld has taken a closer look at this and is highlighting some of the options that are coming down the pike. Richard Lewis, MD, Sacramen- to Eye Consultants, Sacramento, Calif., pointed out that a variety of approaches are being considered. "Some are nanoparticles that are adherent to the implant or part of the implant," he said. "Others are reservoirs that are enclosed." The Ozurdex intravitreal implant (Allergan, Dublin, Ireland) is already available for delivering a cortico- steroid (dexamethasone) to the posterior segment, he noted, adding that now Allergan is working on an anterior segment implant as well. "The clinical data has shown these to be safe and effective, and it's just a question of how long the implant will deliver medications and how long we need to replenish it," Dr. Lewis said. " Unfortunately, right now it seems as if the less invasive versions have a lot of variability that requires further development. Meanwhile, we still need to prove that the duration of delivery from long-term depots and/or devices would be sufficient enough to outweigh the risk of the invasiveness. " –Malik Y. Kahook, MD "Meanwhile, we still need to prove that the duration of delivery from long-term depots and/or devices would be sufficient enough to out- weigh the risk of the invasiveness." For punctal plugs dispensing medication, there are two big issues. "First is that most of the punctal plug platforms I am aware of don't have a big enough reservoir to deliv- er a drug for long enough," he said. "Second is that the devices fall out at a high rate." A practitioner is not going to want to insert a punctal plug to dispense glaucoma medica- tion in an eye and tell the patient to come back in 3 months only to have the plug fall out after 2 weeks, perhaps unknowingly leaving the patient without necessary therapy for the duration.

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