Drop speeds reversal of pharmacologically induced mydriasis
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Nyxol, an alpha 1/2 antagonist eye drop, helped reverse the effects of pharmacologically induced mydriasis in healthy subjects, according to a phase 3 study.
Jay S. Pepose, MD, PhD, told Ocular Surgery News that Nyxol (phentolamine mesylate ophthalmic solution 1%, Ocuphire) could present a unique treatment for patients following any of the 100 million yearly dilated eye exams in the United States every year.
“We know the impact on these patients in terms of glare and visual changes, and it’s problematic,” he said. “They want to get back to work if they’re dilated earlier in the day. Some of these dilating drops can last 6 to 8 hours. It would be great, I think, to have a drop that could speed up reversal of mydriasis, and perhaps this could be offered to patients as an option.”
Phentolamine interacts directly with the dilator muscle of the iris as opposed to cholinergic drugs, which interact with the sphincter muscle.
Researchers explored the efficacy and safety of the drug in a randomized, parallel-arm, double-masked phase 3 trial comprising 185 healthy individuals aged 12 years and older. All subjects first received one of three mydriatic agents before receiving either phentolamine drops, 94 subjects, or placebo, 91 subjects.
The primary endpoint of the study was the percentage of subjects returning to within 0.2 mm of their baseline pupil diameter (PD) at 90 minutes. The secondary outcomes were the percentage of subjects returning to baseline PD at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 24 hours. Researchers compared overall outcomes, as well as differences between mydriatic agents and by iris color. They also assessed the drug’s safety and tolerability.
The drug met the primary endpoint, with 49% of subjects achieving a return to baseline PD within 90 minutes compared with 7% in the placebo group (P < .0001). Additionally, a higher percentage of subjects who received phentolamine drops achieved a return to baseline PD at the 1-, 2-, 3-, 4- and 6-hour time points (all P < .0001) compared with placebo. Researchers also observed a return to baseline PD in the non-study eye in 49% of subjects who received phentolamine drops compared with 6% in the placebo group (P < .0001).
When comparing mydriatic agents, researchers found that subjects dilated with phenylephrine had the faster response, with 79% of subjects who received phentolamine drops achieving a return to baseline PD at 90 minutes compared with 11% who received placebo (P < .0001). Among subjects who received tropicamide or combined hydroxyamphetamine hydrobromide and tropicamide, as expected just 5% who received phentolamine drops achieved a return to baseline PD in 90 minutes. Rather, at 4 hours, 79% of phentolamine-treated subjects returned to baseline PD compared with 8% treated with placebo (P < .0001).
Although the drug demonstrated efficacy in eyes with both light and dark irides, a higher proportion of subjects with light irides returned to baseline PD at all time points.
Researchers observed no deaths, serious adverse events or withdrawals due to adverse events. The only adverse events that occurred in 5% or more of phentolamine-treated subjects were instillation site discomfort (38% vs. 9% placebo) and conjunctival hyperemia (13% vs. 0% placebo). Of the adverse events reported in the phentolamine group, 94% were mild.
In addition to this phase 3 study, phentolamine drops are being tested in a phase 3 study of patients with dim light or night vision disturbances and in a phase 2 study of patients with presbyopia, in which phentolamine is paired with 0.4% pilocarpine.
“I’m excited that these trials are ongoing,” Pepose said. “We don’t have a commercial product available to us yet, but I do think that there is an unmet need for reversal of mydriasis for our patients.”
Click here to watch a video discussion with Jay S. Pepose, MD, PhD.
- References:
- MIRA-2 phase 3 trial results conference call. https://d1io3yog0oux5.cloudfront.net/_b1cc65b0f8c428ef3067201d6734c715/ocuphire/db/357/3619/pdf/Ocuphire+MIRA-2+TopLine+Results+Presentation_3-15-2021%281%29.pdf. Published March 15, 2021. Accessed April 20, 2021.
- Pepose JS. VIDEO: Drop accelerates mydriasis reversal, reduces dim light disturbances. www.healio.com/news/ophthalmology/20210413/video-drop-accelerates-mydriasis-reversal-reduces-dim-light-disturbances. Published April 13, 2021. Accessed April 20, 2021.
- For more information:
- Jay S. Pepose, MD, PhD, can be reached at Pepose Vision Institute, 1815 Clarkson Road, Chesterfield, MO 63017; email: jpepose@peposevision.com.
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