Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial.

Significance: After a dilated eye examination, many patients experience symptoms of prolonged light sensitivity, blurred vision, and cycloplegia associated with pharmacological mydriasis. Phentolamine mesylate ophthalmic solution (PMOS) may expedite the reversal of mydriasis in patients, potentially facilitating return to functional vision and reducing barriers to obtaining dilated eye examinations.
Purpose: The protracted reversal time after pharmacologically induced pupil dilation impairs vision. We tested the hypothesis that PMOS rapidly reduces pupil diameter in this acute indication.
Methods: In this double-masked placebo-controlled, randomized, two-arm crossover phase 2b trial, we evaluated the effects of one drop of 1% PMOS applied bilaterally in subjects who had their pupils dilated by one of two common mydriatic agents: 2.5% phenylephrine or 1% tropicamide. End points included change in pupil diameter, percent of subjects returning to baseline pupil diameter, and accommodative function at multiple time points.
Results: Thirty-one subjects completed the study (15 dilated with phenylephrine and 16 with tropicamide). Change in pupil diameter from baseline at 2 hours after maximal dilation with 1% PMOS was -1.69 mm and was significantly greater in magnitude compared with placebo for every time point beyond 30 minutes (P < .05). At 2 hours, a greater percentage of study eyes given 1% PMOS returned to baseline pupil diameter compared with placebo (29 vs. 13%, P = .03), which was this also seen at 4 hours (P < .001). More subjects treated with PMOS in the tropicamide subgroup had at least one eye returning to baseline accommodative amplitude at 2 hours (63 vs. 38%, P = .01). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours.
Conclusions: Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.
Competing Interests: Conflict of Interest Disclosure: The publication of this article was sponsored by Ocuphire Pharma, Inc. ARM, MPS, RMJ, KC, JEY, SAK, and ATA are or were employees, directors/officers, or paid consultants for Ocuphire Pharma. PMK, MBM, ESL, JSP, and GDH are on the medical advisory board for Ocuphire Pharma. PMK, SAF, SMM, and SRK were principal investigators for this clinical trial funded by Ocuphire Pharma. CBS serves as Chief Medical Officer of Oculos Development Services, LLC, which was the contract research organization for this clinical trial. The authors indicated that they have no other conflicts of interest with regard to the content of this article. The authors listed report a financial conflict of interest (PMK, SAF, SMM, SRK, CBS, ARM, MPS, RMJ, KC, JEY, SAK, ATA, MBM, GDH, ESL, and JSP). The sponsor (Ocuphire) provided financial and material support and participated in study design, analysis, and interpretation. The authors were responsible for the preparation of this article and the decision to submit this article for publication. Each of the authors had (full/limited) access to the study data and takes full responsibility for their presentation in this article.
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