Phentolamine Reverses Dilation With Acceptable Safety in Phase 2b Trial

Many patients express discomfort after ocular dilation, and some may delay routine appointments because they hesitate to be dilated, ultimately limiting the ability to perform a comprehensive eye exam. But, results from a phase 2b trial investigation of phentolamine mesylate ophthalmic solution demonstrate that the drop can reduce medication-induced mydriasis compared with placebo at every time point from 30 minutes to 6 hours (P <.05), according to the study published in Optometry & Vision Science.

The research evaluated 32 healthy participants (18 to 45 years old) with brown irides and randomly selected them to receive either 2.5% phenylephrine or 1.0% tropicamide as a mydriatic agent on 2 separate visits. An hour after the mydriatic, at maximum dilation and following, assessments such as pupil diameter, the patients were given 1 drop bilaterally of 1% phentolamine mesylate ophthalmic solution (PMOS) to reverse mydriasis during one of the 2 appointments, and placebo eye drops at the other. Trial sites comprised 4 optometry clinics in Kentucky, Ohio, Rhode Island, and Kansas, with visits scheduled during August and September 2019. 

At 2 hours after instilling PMOS drops, mean change from maximum pupil diameter was -1.69 mm, compared with -0.69 mm for placebo (P <.001). Reduction in pupil diameter was demonstrated after 1, 4, and 6 hours, all statistically significant versus placebo (P <.001). Further, at 2 hours, 29% of pupils treated with PMOS reached baseline diameter, compared with 13% who were given placebo (P =.03). At 4 hours, 68% of the treatment group reached baseline, in contrast with 23% receiving placebo (P <.001).

The safety profile for phentolamine mesylate at 1% solution proved consistent with previous trials. Eleven of the participants treated with PMOS displayed mild to moderate conjunctival hyperemia. The greatest level of hyperemia occurred at 30 minutes and 1 hour, but dropped steadily, and resolved in most patients by 6 hours. No other clinically relevant adverse events, such as changes in intraocular pressure or blood pressure were observed.

In the phenylephrine subset, a small, but significant increase in distance-corrected near acuity of -0.02 logMAR occurred after PMOS at 30 minutes (P <.04) and 1 hour (P <.05) compared with placebo. For those in the tropicamide subset, a similar, yet stronger effect of -0.08 logMAR was measured at 2 hours (P <.03), and 6 hours (P <.03) compared with placebo.

Phentolamine mesylate is an ɑ₁– and ɑ₂-adrenergic antagonist that reduces action of the iris dilator muscle. Thirty-one participants completed the trial, with 1 patient in the placebo-first group being excluded before the second visit due to pregnancy. A limitation of this study was the exclusion of irides colors other than brown, as well as individuals with ocular or systemic disease.

Phenylephrine and tropicamide work differently, thus eyes dilated with phenylephrine approached baseline diameter more rapidly. Overall, PMOS accelerated the time to normal productivity. The research team, which was headed by Paul Karpecki, OD, of the Kentucky College of Optometry said that 40% of the study’s participants with phenylephrine and 30% of those with tropicamide “achieved a time savings of ≥4 hours with phentolamine mesylate ophthalmic solution.” Further, 20% of those dilated with phenylephrine saved at least 6 hours.

Disclosure: The original study was sponsored by Ocuphire Pharma, Inc., and several researchers are now or have been employees, officers, or paid consultants for the clinical-stage ophthalmic biopharmaceutical company. Please see the original reference for a full list of authors’ disclosures.

Reference

Karpecki PM, Foster SA, Montaquila SM, et al. Phentolamine eye drops reverse pharmacologically induced mydiasis in a randomized Phase 2b trial. Optom Vis Sci. Published online February 26, 2021. doi:10.1097/OPX.0000000000001656