Ocuphire Pharma (United States)

PurposeDim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD.MethodsIn this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed.ResultsEight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly − 1.3 mm (0 to − 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia.ConclusionPMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD.Trial registrationThe trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

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. 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. 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. 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. 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.