EyeWorld Asia-Pacific September 2019 Issue

EWAP SEPTEMBER 2019 57 REFRACTIVE A new topical agent is coming closer than ever to improving the accommodative range for presbyopes. The agent, lipoic acid choline ester (UNR844, Novartis, formerly EV06), is a reducing agent that is purported to reduce ̅i `ˆÃՏw`i Lœ˜`à ̅>Ì vœÀ“ between lens proteins, thus increasing the deformability of the crystalline lens and increasing the accommodative amplitude. According to Michael Korenfeld, MD, who was an ˆ˜ÛiÃ̈}>̜À ˆ˜ ̅i wÀÃ̅Փ>˜ 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 ̅i i˜Ã wLiÀà ˆ˜Ãˆ`i ̅i i˜Ã capsule,” Dr. Korenfeld said in a presentation at the 36th Congress of the European Society of Cataract and Refractive Surgeons. “It is safe, well-tolerated, and showed ÃÌ>̈Ã̈V>Þ È}˜ˆwV>˜Ì ˜i>À ۈÃÕ> 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.” Targeting lens proteins Presbyopia is not just a matter of lens compliance. 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, >˜` ̅i i˜Ã œÃià ˆÌà yi݈LˆˆÌÞ° The hypothesis that drove the development of UNR844 >``ÀiÃÃi` i˜Ã yi݈LˆˆÌÞ œÀ ̅i lack thereof in presbyopia. When lens proteins become oxidized œÛiÀ ̈“i] `ˆÃՏw`i Lœ˜`à vœÀ“] 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 ̅iÃi `ˆÃՏw`i Lœ˜`Ã] ̅i proteins would regain increased degrees of freedom and allow a greater range of deformation of the lens, translating into a greater dynamic range of accommodation. Lipoic acid is a naturally occurring antioxidant and reducing agent,” Dr. Korenfeld said. To allow the reducing agent to >V…ˆiÛi ÃÕvwVˆi˜Ì Vœ˜Vi˜ÌÀ>̈œ˜ within the eye, researchers developed a prodrug to improve the compound’s penetration, allowing it to metabolize and convert to its active form (dihydrolipoic acid [DHLA]) once within the lens. DHLA reduces `ˆÃՏw`i Lœ˜`à LiÌÜii˜ i˜Ã proteins and restores lens “ˆVÀœyՈ`ˆVð Proof of concept was Vœ˜wÀ“i` ˆ˜ ۈÌÀœ ܈̅…Õ“>˜ cadaver lenses and in vivo in rabbit eyes, where in both trials the drug produced lens softening and an increase in lens deformability, Dr. Korenfeld said. Clinical trial The Phase 1/2 clinical study iÛ>Õ>Ìi` Ã>viÌÞ >˜` ivwV>VÞ of EV06 ophthalmic solution 1.5% in improving distance corrected near visual acuity (DCNVA) in subjects with presbyopia. The prospective, randomized, double-masked, placebo-controlled study included 75 patients (45–55 years) with hyperopia, myopia, or emmetropia and a diagnosis of presbyopia from four U.S. sites. Patients were randomized 2:1 (EV06=50: placebo=25). The study drug was given for 91 days and patients were monitored during a 7-month follow-up period. At baseline, the study patients had DCNVA below 20/40 in each eye, best corrected distance visual acuity (BCDVA) of Has presbyopia found an ‘encore’? by Stefanie Petrou Binder MD EyeWorld Contributing Writer Contact information Korenfeld: michaelskorenfeld@gmail.com This article originally appeared in the June 2019 issue of EyeWorld . It has been UNKIJVN[ OQFKƂGF CPF CRRGCTU JGTG YKVJ permission from the ASCRS Ophthalmic Services Corp. '8 NKRQKE CEKF EJQNKPG GUVGT KU C RTQFTWI '8 RGPGVTCVGU VJG EQTPGC CPF KU OGVCDQNK\GF KPVQ EJQNKPG CPF NKRQKE CEKF VYQ PCVWTCNN[ QEEWTTKPI UWDUVCPEGU 'P\[OGU YKVJKP NGPU ƂDGT EGNNU EJGOK - ECNN[ TGFWEG NKRQKE CEKF VQ CEVKXG HQTO FKJ[FTQNKRQKE CEKF &*.# &*.# TGFWEGU FKUWNƂFG DQPFU DGVYGGP NGPU RTQVGKPU CPF TGUVQTGU NGPU OKETQƃWKFKEU Source: Michael Korenfeld, MD