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EW GLAUCOMA 72 July 2017 by Maxine Lipner EyeWorld Senior Contributing Writer that these punctal plugs can cause darkening of the skin around the punctum, where the eyelid meets the nose," he said. Also, there is po- tentially a high rate of tearing with the plugs since these are blocking two of the four puncta responsible for tear drainage. Another possible sustained-re- lease device under consideration is a ring containing bimatoprost that sits on the eye (Allergan, Dublin, Ireland), Dr. Budenz continued. "It fits under the upper and lower eyelid and is well-tolerated," he said. "The retention rate is 90% at 6 months, and the efficacy lasts for 4 to 6 months and has an excellent safety profile." The ring has undergone three different clinical trials, and of the study participants, 85% pre- ferred the ring to drops, he noted, adding that about 80% of the doc- tors preferred the ring to drops. As for the efficacy, at week 2, it lowered IOP 6 to 7 mm Hg and by month 6 had drifted upward to about 4 to 5 mm Hg, Dr. Budenz reported. There are two theories as to why this upward drift in pressure may be occurring with time. "One theory is that the concentration goes down as the ring loses its chemical," Dr. Budenz said. "The second is a biologic theory whereby continu- ous exposure of a receptor to a drug doesn't allow it to recover." If the latter is true, it means that pulse therapy may be important because there is down-regulation of the re- ceptor activity from the continuous elution of the drug, he explained, adding that this looks to be a prob- lem with all of these sustained-re- lease approaches. With the ring, after 6 months when investigators put in a new one to see if they once again got better pressure control, they did not see this, Dr. Budenz noted. "It may be this receptor recovery issue because the second phase of the trial reintro- ducing a new ring doesn't reproduce the great results at week 2 that were seen the first time around," he said. Another approach being tried is periocular injection of a subconjunc- tival bioerodible pellet known as Durasert (pSivida, Watertown, Mas- sachusetts). "There is no chance of Mati Therapeutics [Austin, Texas]," he said. "The Mati Therapeutics plug contains latanoprost and the Ocular Therapeutix plug has travo- prost." The Mati Therapeutics plug has a unique design that will not inadvertently migrate down into the canaliculus. "It has an arrow shape, whereas the Ocular Therapeu- tix plug is a typical tubular-shaped implant; if you shine a cobalt blue light on it you can see whether it is still in place or whether it has fallen out," Dr. Budenz said, adding that one past problem has been such plugs falling out or traveling down into the canaliculus where they are ineffective. Despite concerns about dis- placement, such drug-eluting plugs do have their advantages. "The nice thing about these is that they're non-invasive, they're easy to implant in the office, and they work pretty well," Dr. Budenz said. In Phase 2 FDA results with the Mati Therapeutics plug, at 1 week pres- sures were down by about 6 mm Hg; at 12 weeks there was a slight up- ward drift, with pressures still down by about 5 mm Hg, he noted. Another potential downside to the plugs may involve local skin-darkening from the prostaglan- dins, particularly in African Amer- icans, Dr. Budenz said. "I've heard glaucoma patients don't take their drops as prescribed for myriad rea- sons. "We desperately need to take the patient out of the equation," he said. "If they could just show up for their visits every 3 or 6 months, depending upon how long these sustained drugs are going to last, the drugs can be administered and the patient wouldn't have to remember to use them." Such devices are likely to have a huge impact on glaucoma-related blindness, Dr. Budenz thinks. "Much of the progression that we're seeing is due to the troughs of efficacy of these medications when patients forget to use their medications," he said, adding that this occurs in approximately 66% of patients. External approaches Currently there are two different punctal plugs being studied that can be filled with drugs, Dr. Aref noted. "It goes in the tiny drainage opening in the lower part of each eyelid," he said, adding that these are very similar to the punctal plugs current- ly being used to treat dry eye. Dr. Budenz pointed out that the two plugs have different designs and contain different prostaglandins. "There are at least two companies working on that—Ocular Therapeu- tix [Bedford, Massachusetts] and Intraocular and periocular external drug delivery systems P atient adherence to drops continues to be a point of contention for glaucoma practitioners. However, now innovative intraocular and periocular systems, from plug dispensers to injectable medications and more, are being studied to take the onus out of patients' hands, according to Ahmad Aref, MD, assistant professor and residency training program director, Illinois Eye and Ear Infirmary, Chicago. Dr. Aref views such innovations as something that glaucoma pa- tients sorely need. "I think that the ophthalmic community that treats glaucoma has come to realize that there are major problems with ad- herence to medications the way we currently prescribe them," he said. "Whether it's a physical inability to put the eye drop in or the financial toll that it takes on patients, these things compound each other." Donald Budenz, MD, professor and chairman of ophthalmology, University of North Carolina at Chapel Hill, likewise sees a huge need for such sustained delivery systems, stressing that two-thirds of Delivering on sustained promises for glaucoma External photograph demonstrating sustained release punctal plug insertion for the reduction of intraocular pressure. Source: Ocular Therapeutix Pharmaceutical focus continued on page 74

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