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Pharmacological solutions for presbyopes under development
Investigators are evaluating novel, nonsurgical options for treating presbyopia, with promising results.
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Patients in the U.S. with presbyopia are currently treated with spectacles, multifocal contact lenses or multifocal IOLs, with a number of other surgical treatments not yet approved. However, at least three companies are investigating noninvasive options for treating presbyopia with topical drops.
Liquid Vision
Presbyopia Therapies is investigating Liquid Vision, a drop that creates miosis without accommodative spasm.
“The mechanism of action is completely through the small aperture optics of the pinhole effect,” Steven J. Dell, MD, a consultant and shareholder at Presbyopia Therapies, told Primary Care Optometry News. “Much like an AcuFocus inlay, but without surgery, the drops create a pupil of about 1.6 mm. They are used bilaterally and typically last 8 hours.
Steven J.
Dell
“Drugs such as pilocarpine create miosis, but unfortunately create accommodation, resulting in brow ache and a myopic shift with reduced distance vision,” he continued. “Those side effects do not occur with this drop. In fact, the distance vision with liquid vision tends to improve somewhat due to the pinhole effect, but the real benefit is good uncorrected near vision.”
Dell was unable to disclose the composition of Liquid Vision, which is still undergoing clinical trials.
“A clinical trial in presbyopes an average of 51 years old was conducted in Tijuana, Mexico, by David Castillejos, MD,” Dell reported. “The average near acuity through the full distance correction was 20/22.”
Dell said that a phase 2 clinical trial is anticipated for 2015.
The Benozzi method
In Medical Hypothesis, Discovery & Innovation Ophthalmology Journal, Jorge Benozzi, MD, proposed and tested the Benozzi method for presbyopes.
“It is well known that when parasympathetic stimulation takes place with pilocarpine, the generation of ciliary muscle spasmodic contraction occurs, and lens thickness increases, which in turn increases the focus depth,” Benozzi and colleagues wrote. “This situation improves near vision but decreases distance vision because the lens cannot change its thickness or position. Combining nonsteroidal anti-inflammatory drugs with parasympathetic agonists, the intensity of the contraction of the pupil and the ciliary muscle was decreased, allowing the lens to change shape and position for good vision at all distances.”
As detailed in the study, the researchers treated and evaluated 200 emmetropic eyes of 100 patients with presbyopia over a duration of 5 years. Participants were dosed with 1% pilocarpine and 0.1% diclofenac.
“In the first year of treatment, the enhanced accommodation improved near vision, and this improved vision was maintained for 5 years,” they stated. “Distance vision remained at 20/20 and was unchanged during the same period. The combination of a muscarinic cholinergic agonist and NSAIDs allowed the chronic use of topical treatment to restore accommodation with good near and far vision.”
The researchers reported that 1% of participants stopped treatment due to ocular burning and discomfort, and 4% preferred glasses instead.
Additionally, they recognized the broader implications of the results.
The researchers concluded: “The possibility of this pharmacological treatment opens a new therapeutic approach for presbyopic patients, allowing them good accommodation over time,” the researchers concluded. “It is possible that, in the future, new pharmacological treatments can also be used to treat other refractive problems that depend on accommodation.”
Dioptin
Encore Vision Inc. was founded specifically to develop a treatment for presbyopia that would target its cause, according to the company’s website.
“We have a proposed mechanism of action, which is intracellular redox,” William R. Burns, president and CEO of Encore Vision, told PCON. “Lens proteins cross-link with aging, causing the lens to become hard. Our eye drop ‘breaks’ these cross-links to partially restore the lens to an earlier functional state.”
Burns, along with several colleagues, presented posters at the Association for Research in Vision and Ophthalmology meeting in May 2014 that explained the profile of Dioptin.
“Dioptin contains the proprietary active pharmaceutical ingredient, EV06 (lipoic acid choline ester), which is a prodrug of lipoic acid (LA), enhancing LA corneal permeability,” the poster stated.
“The drops are composed of a patented compound that improves penetration of a natural compound to the lens to soften and restore accommodative amplitude,” Burns said. “This is consistent with the Helmholtz theory.”
He explained that while other drop treatments for presbyopia offer a brief period of recovery, Dioptin is a longer term solution.
“With our unique product, after 30-day twice daily treatment, the effects should be ‘more permanent’ but still would be subject to natural near vision loss, due to aging of the lens again,” Burns said. “It just sets the clock back. Recovery of about +2 D is the objective measure depending on the age of the patient.”
He also noted that the active compound in Dioptin has an established safety profile.
“We established in vivo proof-of-concept in an animal model and the toxicology profile on rabbits,” he said, referencing the ARVO presentations.
According to Burns, the company currently has completed a pre-Investigational New Drug (IND) meeting with the U.S. Food and Drug Administration. He noted that Encore Vision anticipates filing an IND in the first half of 2015 to begin a phase 1/2 clinical trial.
“We are currently at the preclinical Good Manufacturing Practices stage to prepare clinical test drops,” he said. “We must get all the development components together for the IND submission before starting trials.”
Importance of technology
Dell explained that while ophthalmologists have effectively addressed a variety of refractive errors with surgical remedies, “laser vision correction for myopia, astigmatism and hyperopia has arguably reached a relative plateau of high-quality visual correction. Incremental improvements will inevitably occur, but the latest generation of lasers is producing extraordinary results. Additional technologies such as phakic IOLs, corneal intrastromal lenticule extraction and refractive lens exchange are carving out their place as well.”
He said that presbyopia correction remains an area of “relative weakness” in a surgeon’s armamentarium, with accommodating or multifocal IOLs the only treatments available in the U.S.
“A reliable, high-quality treatment for presbyopia would be a true game-changing event,” Dell said. – by Chelsea Frajerman