Eyeworld

42 | EYEWORLD | JUNE 2019 R EFRACTIVE Contact information Korenfeld: michaelskorenfeld@gmail.com by Stefanie Petrou Binder, MD EyeWorld Contributing Writer Targeting lens proteins Presbyopia is not just a matter of lens com- pliance. It is caused by a few different events, each of which constitutes a potential treatment target: the crystalline lens enlarges over time (ectoderm), the ciliary body undergoes atrophic changes, the vitreous becomes less viscous, and the lens loses its flexibility. The hypothesis that drove the development of UNR844 addressed lens flexibility or the lack thereof in presbyopia. When lens proteins be- come oxidized over time, disulfide bonds form, rendering them less able to move relative to one another during the act of accommodation. "The theory was that if we had a way to chemically reduce these disulfide bonds, the proteins would regain increased degrees of free- dom and allow a greater range of deformation of the lens, translating into a greater dynamic range of accommodation. Lipoic acid is a natu- rally occurring antioxidant and reducing agent," Dr. Korenfeld said. To allow the reducing agent to achieve sufficient concentration within the eye, re- searchers developed a prodrug to improve the compound's penetration, allowing it to metabo- lize and convert to its active form (dihydrolipoic A new topical agent is coming closer than ever to improving the accom- modative range for presbyopes. The agent, lipoic acid choline ester (UNR844, Novartis, formerly EV06), is a reducing agent that is purported to reduce the disulfide bonds that form between lens proteins, thus in- creasing the deformability of the crystalline lens and increasing the accommodative amplitude. According to Michael Korenfeld, MD, who was an investigator in the first human clinical trial using UNR844 in presbyopes, the drug is safe, robust, and persistent, even after the regimen is stopped. "This chemical was designed to improve the internal rheology of the cytosol within the lens fibers inside the lens capsule," Dr. Koren- feld said in a presentation at the 36th Congress of the European Society of Cataract and Refractive Surgeons. "It is safe, well-tolerated, and showed statistically significant near visual acuity improvement in clinical trials compared to placebo. The widespread use of this drug stands to radically alter the visual performance of humans within our lifetimes." Has presbyopia found an "encore"? About the doctor Michael Korenfeld, MD Department of Ophthalmology and Visual Sciences Washington University St. Louis Financial interests Korenfeld: Novartis topical NSAID to reduce inflammation, pain, and the potential risk of clinically significant CME. He puts patients on nepafenac (Nevanac, Novartis) once a day or if that's not available, bromfenac (Prolensa, Bausch + Lomb) also once a day or in some cases BromSite (Sun Pharmaceuticals) twice a day. If cost is a factor, he will turn to generic ketorolac. Although it is labeled as a four-times-a-day agent, he has pa- tients use it twice a day for 2 weeks, then once a day until the bottle is gone. In some cases, he may use a single bottle of compounded drops that can contain an antibiotic, a steroid, and an NSAID. Dr. Donnenfeld still frequently prescribes postoperative drops, predominantly in cases involving corneal incisions. He generally likes besifloxacin because it has the best activity against methicillin-resistant Staphylococcus aureus of all of the fluoroquinolones. "I use that twice a day, and if a patient wants a generic, I tend to use ofloxacin," he said. The use of intracameral antibiotics in the U.S. is not yet the standard of care as it is in Europe, Dr. Donnenfeld said, adding that the real difference is its approval in Europe. "An ASCRS study looked at the reason ophthalmol- ogists don't use intracameral, and it's because it is not FDA approved," he said. "I think this will become the standard of care in the future once it is FDA approved." continued from page 41 PRESENTATION SPOTLIGHT

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