LYNX-1: A Phase 3 Study of 0.75% Phentolamine Ophthalmic Solution in Subjects with Dim Light Vision Disturbances.

Abstract

To evaluate the efficacy and safety of 0.75% phentolamine ophthalmic solution (POS) for the treatment of dim light disturbances (DLD) in subjects with reduced mesopic low-contrast vision, including post-keratorefractive subjects. Phase 3, multicenter, double-masked, randomized, placebo-controlled trial SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: 145 subjects with self-reported symptoms of DLD, mesopic pupil diameter of ≥5 mm, and 30 ETDRS letters (equivalent to 20/63 Snellen) or worse mesopic low-contrast best-corrected distance visual acuity (mLCVA) in the study eye, were randomized 1:1 to receive POS or placebo. The largest subset (25) of the enrolled subjects was status post-keratorefractive surgery. One drop of POS or placebo was self-administered in each eye once nightly for 14 days. Assessments included visual acuity testing, pupil diameter measurement, wavefront aberrometry, intraocular pressure (IOP), slit-lamp biomicroscopy, and a questionnaire assessing visual symptoms. POS-treated subjects demonstrated significant improvement in mLCVA at Day 8 (13% vs. 3% placebo; p<0.05) and Day 15 (21% vs. 3% placebo; p<0.01). Subjects receiving POS reported significant reduction in overall severity of DLD (on a scale of 1-7), and photic phenomena including glare, halos and starburst (on a scale of 0-3) at Day 8 and 15 (p<0.01). There was no significant difference between arms in conjunctival hyperemia or vital signs. Results from post-hoc analysis of post-keratorefractive surgery patients also showed significant improvement in mLCVA at Day 8 and 15 and significant improvement in patient reported outcome measures, such as overall severity of DLD. POS significantly improved mesopic low-contrast best-corrected distance visual acuity in subjects with reduced mesopic vision and dim light disturbances of varying etiologies, including post-keratorefractive patients. Treatment-emergent adverse events were predominantly mild and transient. These findings suggest POS may warrant further clinical investigation as a potential pharmacologic approach for patients experiencing dim light disturbances associated with reduced mesopic low-contrast visual acuity and photic symptoms.