Phentolamine Mesylate Drops Improved Night Vision, Glare, Halos in Trial

Medications so far used to lessen symptoms of dim light vision disturbances (DLDs) have, at times, produced inadequate results. Brimonidine may lose its miotic effect with successive doses, and pilocarpine can be associated with side effects, such as headaches. However, a phase 2 clinical trial exploring safety and effectiveness of phentolamine mesylate eye drops demonstrates improved contrast sensitivity and mesopic vision in patients with DLD, as reported in BMC Ophthalmology.

Investigators conducted the study at a private practice ophthalmic center in Lynwood, New York, recruiting 24 adult patients (48 eyes) with severe night vision disturbance and impaired mesopic low contrast visual acuity (LCVA). The placebo-controlled, double-masked trial was retrospectively registered in 2019 (ClinicalTrials.gov Identifier: NCT04004507). In 2:1 randomization, 16 patients, mean age 42.1 years received a single drop of 1.0% phentolamine mesylate ophthalmic solution (PMOS) in each eye; and 8 individuals, average age 47.4 years, underwent placebo lubricant drops.

Examinations occurred 2 to 3 hours after eye drop treatment. Pupil diameter for PMOS-treated participants was significantly reduced, mean change (SD) of -1.3 mm (0 to -2.8 mm, P <.0001), in relation to individuals in the control group, -0.2±0.5 mm (P =.08). Case patients displayed considerably improved contrast sensitivity in glare condition when responding to stimuli at 3, 6, 12, and 18 cycles per degree (P ≤.03), and improvement nearing significance at 1.5 cpd (P =.06). 

“Because contrast sensitivity at higher spatial frequencies correspond to the perception of smaller objects, PMOS could improve patients’ ability to recognize distant objects while performing activities in dim light conditions (e.g., driving at night),” the researchers explain, adding that present results involve conditions with glare, which can hinder night driving due to lowered motion sensitivity.

Post-treatment, the case group also read a greater number of letters through all assessments: mesopic and photopic distance high contrast visual acuity (mHCVA and pHCVA), and mesopic and photopic distance low contrast visual acuity (mLCVA and pLCVA), all statistically significant (P =.0001). Further, compared with 31% of individuals in the control group, 69% of treated participants improved in mLCVA measurement by 5 letters (P =.029). Similarly, mLCVA advanced by 10 letters in 6% of those receiving placebo vs 34% of those undergoing PMOS (P =.04), and by 15 letters in 0% of participants in the control group, compared with 19% of case patients (P =.16).

Post-hoc analysis showed that PMOS-treated patients with baseline pupil diameter of 6 mm or larger especially benefited, compared with similar individuals in the placebo set, in regard to 5-letter (P =.02) and 10-letter improvement (P =.004).

Wavefront aberrometry revealed that mean higher-order root-mean-square (HO RMS) error was reduced significantly in the PMOS cohort (P <.0001). Questionnaire ratings also reflected improvement — 69% of case individuals reported better vision, as opposed to 25% of those receiving placebo. No serious or systemic adverse events occurred, as well as no headaches. Mild to moderate hyperemia was experienced by 18.8% of the case set.

Limiting this trial was a small sample size which did not allow study of differences between DLD-associated subgroups such as those with keratoconus or prior refractive surgery. Also, contrast sensitivity and visual acuity were assessed post-eyedrop at one point in time only. Clinical testing may differ from real-world performance, as well. 

Disclosures: The trial was funded by Ocuphire Pharma, Inc. Several study authors have disclosed affiliations with Ocuphire Pharma, and/or biotech and pharmaceutical companies. Please see the original reference for complete disclosures.