Reviewed by Richard L. Lindstrom, MD
Topical administration of lipoic acid choline ester 1.5% (EV06, Encore Vision) shows promise as a treatment for restoring accommodation to patients with presbyopia, said Richard L. Lindstrom, MD. Acting via an “anti-crosslinking” mechanism, the treatment increases lens elasticity through reduction of lens protein disulfides, and was associated with impressive improvements in accommodative amplitude and near vision in an initial randomized, double-masked phase I-II clinical trial.
“The changes in near vision associated with topical EV06 were statistically significant compared with placebo and clinically meaningful,” said Dr. Lindstrom, founder, Minnesota Eye Consultants, Bloomington, MN, and adjunct professor emeritus, Department of Ophthalmology, University of Minnesota, Minneapolis. “Furthermore, the EV06 drops were well-tolerated and not associated with any significant adverse events. This is an early, relatively small proof of concept study. Efficacy and safety of EV06 for treating presbyopia need to be demonstrated in larger phase III trials, he noted. "However, this topical treatment is the first agent that has been shown in a clinical trial to restore natural accommodation, and it has exciting potential,” Dr. Lindstrom said.
EV06 targets the underlying cause of age-related increased lens stiffness—the disulfide bonds that form between the crystallin proteins within lens fiber cells. It is a prodrug that is able to penetrate the cornea. Inside the eye, however, EV06 is broken down into lipoic acid and choline, two naturally occurring substances. Within the lens, the lipoic acid is reduced to the active agent, dihydrolipoic acid, a potent antioxidant that breaks apart the disulfide bonds Initial ex vivo and in vivo animal studies provided proof that topical treatment with lipoic acid choline ester decreased lens protein disulfides and increased lens elasticity.
“I was somewhat skeptical about how the positive results in the preclinical studies would translate into clinical use,” Dr. Lindstrom said. “For that reason, I must admit that I was stunned to see the magnitude of the improvements achieved in accommodation and near vision in the clinical trial.”
Richard L. Lindstrom, MD
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Dr. Lindstrom is a board member, consultant to, and equity owner in Encore Vision.