WASHINGTON — Phentolamine ophthalmic solution improved near vision in adults with presbyopia, with over 20 hours of improvement from a single administration, the VEGA-3 trial showed.

With the drops, which relax the dilator muscle of the iris, 27.5% of patients gained at least 15 letters of near vision on vision testing without losing more than five letters of distance vision by day 8, a significant improvement compared with the 12% rate of that primary endpoint with placebo (P < .001).

“This is truly a once-a-day treatment where you use it in the evening and pupils get really long-lasting effects,” said William Trattler, MD, of the Center for Excellence in Eye Care in Miami, who presented the findings at the 2026 annual meeting of the American Society of Cataract and Refractive Surgery.

Phentolamine is a non-selective alpha-1 and alpha-2 adrenergic antagonist. As a vasodilator, it is FDA approved for several indications, including for the diagnosis of pheochromocytoma, treating extravasation, and as a reversal agent for dental anesthesia. 

In the ophthalmic setting, the drug has an indication for pharmacologically induced mydriasis produced by adrenergic agonists or parasympatholytic agents. The drug (sold as Ryzumvi) blocks alpha-1 receptors on the iris dilator muscle to decrease pupil size modestly without affecting the iris sphincter or ciliary muscles. 

The VEGA-3 findings follow positive results in the similarly designed VEGA-2 trial with phentolamine. Drug developers Opus Genetics and Viatris are using the two trials to support an application with the FDA for an expanded indication.

“This looks like a promising product,” said session co-chair Richard Tipperman, MD, a cataract specialist at Wills Eye Hospital in Philadelphia. 

The pool of patients who are presbyopic is “enormous,” Tipperman said, because almost everyone over age 45 has the condition. “And most people don't like wearing reading glasses, so if there was easy, simple, and very effective drop that worked well, it would probably be very successful,” he said.

While other eye drops, such as pilocarpine and aceclidine, are approved to treat presbyopia, those drugs affect the sphincter muscle and have typically shorter duration of action. 

The multicenter VEGA-3 trial included 569 patients with presbyopia randomized 3:2 to phentolamine ophthalmic solution 0.75% or placebo, given in the morning on the first day to look at the onset of action and then daily in the evening thereafter.

The trial included patients ages 45 to 64 years with a best-corrected distance visual acuity of 20/20 or better, distance-corrected near visual acuity of 20/50 to 20/100 in each eye and binocularly, and binocular best-corrected near visual acuity of 20/25 or better. They also had to have photopic pupil diameter of 4 mm or greater in either eye.

Secondary endpoints also showed a higher percentage gaining at least 10 letters of binocular distance-corrected near vision with phentolamine at day 1, day 3, and day 8 with a slight gain over that period to 55% vs 29% (P < .0001). All patients had improvements down to 20/15 vision, and 43% had 20/32 or better distance-corrected near vision. 

Intermediate vision, important for computer use, improved by at least 10 letters by day 8 in 31% of phentolamine-treated patients compared with 19% in the placebo group (P < .0001).

“That this is really helping all these patients overall,” Trattler said. “We get sequential improvements over time too as the patient continues to drop and they get more and more improvements over time.” 

In terms of duration of action, “this looks different than all the other drops we've had,” Trattler said. “This is a very long-acting agent.” The mean distance-corrected near vision impact lasted over 20 hours after administration of a single drop.

Conjunctival hyperemia occurred in 26% of patients (90% mild), instillation site irritation in 15% (98% mild), dysgeusia in 5.9%, eye irritation in 5.6%, and headache in 2.6%. No drug-related serious adverse events and no clinically meaningful decrease in mesopic high-contrast visual acuity occurred, according to the researchers.

No evidence of tachyphylaxis emerged through 6 weeks, Trattler said, although the vision impacts showed “no meaningful loss of effect” at that point.

VEGA-3 was supported by Ocuphire Pharma (now Opus Genetics). 

Trattler disclosed consulting for Opus Genetics, Lenz, Orasis, and Tenpoint Pharmaceuticals. 

Crystal Phend is an award-winning medical journalist with decades of experience reporting on clinical research and healthcare developments across specialties. When not walking the halls at a medical conference, she can be found at a keyboard in upstate New York.