AAO 2019: Topical Treatments for Presbyopia on the Horizon
Several investigational agents each employ one of two mechanisms of action
October 11, 2019—San Francisco, California—Topical agents that temporarily treat presbyopia without affecting other aspects of vision are on the cusp of becoming approved and available for widespread use, according to a presentation given here at the 2019 Annual Meeting of the American Academy of Ophthalmology, taking place from October 11 to 15.
“Presbyopia literally means ‘old eye’ and results in a gradual decrease in lens accommodation, leading to a significant lack of functional near vision,” said Sheri Rowen, MD of NVISION Eye Centers in Newport Beach, during her presentation. “It affects the majority of people over the age of 40, with a target population of 30 to 40 million in the United States, and we have no approved pharmacologic treatment.”
Currently, the mainstay of therapy includes reading glasses, contact lenses, and “a host of surgical procedures, which can be invasive and difficult to reverse,” she continued.
There are a number of new pharmaceutical agents currently being investigated for the treatment of this condition. They are based on two mechanisms of action. The first addresses the accommodative aspect of the lens itself. Products exploring this mechanism of action include UNR844 by Novartis.
The second mechanism of action is employed by a class of drugs known as pupillary miotics. They exert a pinhole effect, which increases the depth of field effect without affecting accommodation. Companies involved in development of products that employ this approach include Allergan, Presbyopia Therapies, and Orasis Pharmaceuticals.
In the young eye, normal sulfhydryl bonds allow cytosol displacement centrally, which produces lens accommodation. In the aging eye, oxidation-induced disulfide bonds form between the crystalline proteins, causing lens stiffening by preventing the cytosol from moving through it.
UNR844 contains a lipoic acid choline ester, which is hydrolyzed into choline and lipoic acid for better corneal penetration. It is then reduced to dihydrolipoic acid, which enters the lens and causes hydrolysis of proteins, creating a free flow of cytosol centrally and allowing the lens to change shape again.
In animal studies, UNR844 applied to one lens three times daily for 5 weeks resulted in 40% more elasticity of the lens, compared to the contralateral, untreated lens. The investigators also observed a dose-dependent reduction in lens protein sulfide, which coincided with lens elasticity and softness. The results of phase II trials in humans are forthcoming.
Regarding miotic drugs, the necessary features include comfort on installation; long enough duration of action; pupil modulation with correct, efficient size for depth of field without loss of night vision or other vision problems; excellent safety profile; and no degradation of distance vision, said Dr. Rowen.
Allergan plans to launch the first drop that produces pupillary miosis to enhance depth of focus without affecting accommodation for the treatment of presbyopia. The company completed advanced phase III trials in late 2018, and their current goal is to obtain regulatory approval in 2021. The once-daily drop is instilled in both eyes or in the non-dominant eye to provide a fast onset of action, improvement in near vision for multiple hours while remaining reversible, non-invasive, and well tolerated. Improvements are seen in near vision even in darkness and without compromising distance vision.
Presbyopia Therapies is making similar claims about its investigational product, called Liquid Vision. “High ratios of drops can affect [accommodation], so this is better for low-percentage myopia,” said Dr. Rowen about this product.
Finally, CSF-1, a pupillary miosis drop developed by Orasis, has some early compelling data to support it. Compared with placebo, it has been shown to substantially increase 2-line and 3-line improvement in visual acuity in both high and low illumination without impacting distance vision, the visual field, or comfort. The company just completed a phase IIb trial in 160 subjects treated at 7 sites, and these data are currently being analyzed. To date, it has an excellent safety profile, uses known and well-studied ingredients, and has a low concentration in the formulation.
“The landscape is changing for the medical treatment of presbyopia,” concluded Dr. Rowen. “Pupillary miotics will be the first to market. They appear safe, effective, and easy to use in early studies. We will learn which patient population will adopt the best. Many people will be able to work without glasses, [but] we will need to study the tolerability for long-term use. The lens-softening drops are hopefully now approaching the phase II studies.”
Click on any of these tags to subscribe to Topic Alerts. Once subscribed, you can get a single, daily email any time PracticeUpdate publishes content on the topics that interest you.
Visit your Preferences and Settings section to Manage All Topic Alerts