EyeWorld India September 2017 Issue

Nonsurgical treatment of presbyopia by Maxine Lipner EyeWorld Senior Contributing Writer What drops can do I t’s one of the holy grails of ophthalmology: finding a way to restore near acuity to aging eyes without sacrificing distance vision. While many oph- thalmologists have looked strictly to the surgical route for answers, some are now investigating pharmaco- logic approaches, which they think could be key to more safely solving the problem of presbyopia. EyeWorld took a closer look at two different pharmacologic approaches on the cusp of potentially changing the world of presbyopia. True pinhole effect One of these two pharmacologic approaches, PRX-100 (Presbyopia Therapies, Coronado, California), employs the pinhole effect with a twist, according to Terry Kim, MD , professor of ophthalmol- ogy, Duke University Eye Center, Durham, North Carolina. “It has a proprietary mixture of two components, the combination of which results in miosis of the pupil without the accommodative effect,” he said, adding that agents such as pilocarpine also affect the ciliary muscle, but with a downside of blurred distance vision and other side effects such as brow ache. “The difference with this drop is that it totally disassociates miosis from the accommodation,” Dr. Kim said. “So you only get a true pinhole effect.” The pinhole effect is a power- ful remedy for presbyopia. “In any miotic pupil, you have an increased depth of field,” he explained, add- ing that near vision is markedly improved and sometimes even distance vision is as well. Because the pinhole effect also has the potential to reduce light scatter and glare, this makes PRX-100 a viable possibility for therapeutic use as well, including in patients who have corneal scars or who have had complications from refractive surgery, Dr. Kim said. “There are so many times a patient with a visual defect will say, ‘I can see through that pinhole and that’s the vision that I want,’” he said, adding that the drop pro- duces such effects for patients with pathology. PRX-100 acts within 30 minutes and has a duration of more than 5 hours. Preliminary clinical data from a pilot study performed by David Castillejos, MD , Tijuana, Mexico, on those with presbyopia was promising. In the trial of about 20 presbyopic patients, investigators saw marked improvement in near vision, Dr. Kim noted. They looked at corrected near visual acuity at 14 inches and found that after instill- ing the drop, there was one to five lines of improvement in patients’ near visual acuity. “I was impressed with how much near vision these patients had. I’ve tried it myself and there is definitely a ‘wow factor,’” Dr. Kim said. The only negative side effect reported was a dimming effect noticed by some in the beginning. “But that tends to fade away as you get used to the drop,” he said. Dr. Kim views this pharmaco- logic approach as having a host of advantages over surgical correction of presbyopia. “The reversibility aspect is huge,” he said. “If you don’t want the ef- fect, you just stop the drop.” He also considers this to be of considerably lower risk than surgery because it is simply a drop. “We’re not talking about any incision in the eye—no surgery at all,” Dr. Kim said, adding that there’s not even laser or ther- mal treatment involved. Most of the surgical treatments for presbyopia have side effects, including limited efficacy for this condition, which progresses with age. With a treatment such as con- ductive keratoplasty, patients end up with regression. “You’re not go- ing to see those issues with a drop like this,” Dr. Kim said. If all goes well in the ongoing Phase 2b clinical trials, he hopes PRX-100 will be available in about 2 years. Softening the lens Another drop, EV06 (lipoic acid choline ester, Novartis, Basel, Swit- zerland), uses a different approach, according to Richard Lindstrom, MD , adjunct professor emeritus, University of Minnesota, Minne- apolis. The idea with this drop is to soften the natural lens. “What happens as the natural lens ages is that it crosslinks,” Dr. Lindstrom said, adding that alpha-lipoic acid in the drop functions as an anti- crosslinker. It uncrosslinks collagen and makes the tissue more elastic, he explained. The idea with this is to restore natural accommodation. “We’ve known for years that even in a 70- or 80-year-old, when someone looks at a near target, the ciliary muscles are still working,” Dr. Lindstrom said. “Those muscles are still at- tached to the lens, it’s just that the lens has become inelastic, so it doesn’t change shape.” During the 90-day prospective randomized trial, 75 patients were administered either the EV06 drop or placebo four times a day, Dr. Lindstrom said, adding that 50 of the patients were treated with the EV06 and 25 served as controls. Those included were ages 45 to 55. At day 91, investigators saw 1 line of near vision improvement for 84% of those who received EV06 and 52% of those who re- ceived placebo. There were 2 lines or more of improvement in near vision for 53% of those who received the drop versus just 22% in the placebo group, Dr. Lindstrom reported. A 3-line or more improvement was seen in 22% of EV06 patients, and 12% saw a 4-line or more improvement. “At every one of these points, it continued on page 46 EWAP REFRACTIVE 45 September 2017