Abstract
Purpose :
Pharmacologically-induced mydriasis (PIM) typically lasts 6-24 hours, during which patients may experience ocular discomfort decreased visual performance. Pre-specified sub-group analyses of the MIRA-2 Phase 3 trial assessed the efficacy and safety of 0.75% phentolamine ophthalmic solution (POS) to expedite the reversal of PIM.
Methods :
The MIRA-2 trial was a randomized, double-masked, placebo-controlled, multi-center, 1 day Phase 3 clinical trial. Healthy subjects were randomized 1:1 to POS or Placebo (two drops in the study-eye, and one drop in the fellow-eye) one hour after PIM with phenylephrine, tropicamide, or Paremyd (hydroxyamphetamine and tropicamide combination), with 3:1:1 randomization to mydriatic agents, respectively. The primary efficacy endpoint was the percentage of subjects’ study eyes returning to ≤ 0.2 mm from baseline pupil diameter (PD) at 90 min post-treatment (with POS vs placebo, compared by logistic regression). Analyses of this efficacy endpoint were stratified by study- vs fellow-eye, by iris color, and by mydriatic agent.
Results :
Ninety-four subjects were randomized to POS (mean age 34 years, 62% female) and 91 were randomized to placebo (mean age 33 years, 55% female). More study-eyes treated with two drops of POS had reversal of mydriasis at 90 min compared to placebo (49% vs 7%; p<0.0001). This difference between POS and placebo was similar in fellow-eyes which received one drop (48.9% vs 5.5%; p < 0.0001). Significant differences were observed both in those with light (56% vs 2%; p < 0.0001) and dark (43% vs 11%; p < 0.0001) irides at 90 min. Significant differences between POS and placebo were seen with phenylephrine at all time points from 1 to 6 hours, including at 90 min (79% vs 18%; p < 0.0001); and in subjects dilated with longer lasting tropicamide or Paremyd at each time point from 2 hours (24% vs 0%; p < 0.05) to 6 hours (97% vs 28%; p < 0.0001).
Conclusions :
Both one and two drops of POS had rapid onset of effect, significantly reducing PD within 90 min or less. POS had benefits across common mydriatic agents and across iris colors, providing a potential treatment to reverse PIM.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.