Abstract
Purpose :
Medically-induced pupil dilation is a necessary tool for routine ophthalmoscopy, but the long recovering time impairs vision. We tested the hypothesis that a non-selective alpha antagonist, phentolamine mesylate ophthalmic solution (PM), can reduce the pupil diameter (PD) rapidly back to normal size.
Methods :
In this double-masked placebo-controlled randomized, 2-arm cross-over phase 2 study, we evaluated the effects of one drop of 1% PM bilaterally in 32 healthy subjects who had their pupils medically dilated by one drop of two common mydriatic agents, 2.5% phenylephrine and 1% tropicamide. The key endpoints were the percent of subjects that returned to baseline PD and to unchanged accommodation, and the change in PD from max pupil dilation at prespecified timepoints post-mydriatic agent. PROC GENMOD with a logit link and ANCOVA were used to analyze percent of subjects returning to baseline and change from max PD respectively.
Results :
Use of 1% PM resulted in faster time to recovery for subjects with medically-induced pupil dilation. More subjects had at least one eye returning to baseline PD at 2 hours (41.9% compared to 22.6%, p=0.016) and 4 hours (90.3% compared to 45.2%, p<0.0001) post-dilation in the PM group compared to placebo. Change from max pupil dilation was statistically significant for every timepoint beyond 30 min after max dilation, with mean changes between 0.5-1.1mm (p<0.0001), and independent of mydriatic agent. The biggest difference in PD change from placebo was seen in the phenylephrine treated group (1.4mm, p=0.0002 at 2 hours). More subjects treated with PM in the tropicamide subgroup had at least one eye returning to baseline accommodation at 2 hours (62.5% compared to 37.5%, p=0.0084). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours.
Conclusions :
1% PM reversed medically-induced pupil dilation more rapidly than vehicle treatment and the reversal was faster under both classes of mydriatics used (adrenergic agonists and cholinergic blockers) with limited ocular safety issues. Given the observed safety, higher dosing regimens such as two drops of 1% PM shall be tested for even faster time to reversal in registration studies.
This is a 2020 ARVO Annual Meeting abstract.