Rapid and Sustained Eyelid Elevation in Acquired Blepharoptosis with Oxymetazoline 0.1%: Randomized Phase 3 Trial Results

Jason Bacharach,1 David L Wirta,2 Robert Smyth-Medina,3 Michael S Korenfeld,4 Shane R Kannarr,5 Shane Foster,6 Mark J Jaros,7 Charles B Slonim8 1North Bay Eye Associates, Petaluma, CA, USA; 2Aesthetic Eye Care Institute & Eye Research Foundation, Newport Beach, CA, USA; 3North Valley Eye Medical Group, Mission Hills, CA, USA; 4Comprehensive Eye Care, Ltd, Washington, MO, USA; 5Kannarr Eye Care, Pittsburg, KS, USA; 6Athens Eye Care, Athens, OH, USA; 7Summit Analytical, Denver, CO, USA; 8Department of Ophthalmology, University of South Florida Morsani College of Medicine, Tampa, FL, USACorrespondence: Jason BacharachNorth Bay Eye Associates, 104 Lynch Creek Way, Suite 15, Petaluma, CA, 94954, USATel +1 (707) 762-3573Fax +1 (707) 762-6873Email jbacharach@northbayeye.comPurpose: Oxymetazoline 0.1% is a novel ophthalmic agent for the treatment of acquired blepharoptosis in adults that has been shown to improve upper eyelid elevation and superior visual field deficits. This analysis characterized the rapid onset of upper eyelid elevation with once-daily oxymetazoline 0.1% and durability of this effect over 42 days.Materials and Methods: Pooling data from two prospective, randomized, placebo-controlled, phase 3 studies, change in marginal reflex distance 1 (MRD-1) was evaluated at a range of post-instillation time points on treatment days 1, 14, and 42. Onset of effect was assessed beginning at 5 minutes post-administration (one study) and through 6 hours at the first two visits (both studies). Overall, 203 subjects received oxymetazoline 0.1% and 101 received vehicle.Results: Oxymetazoline 0.1% demonstrated a rapid onset of action on all days evaluated. Mean changes from baseline 5 and 15 minutes post-oxymetazoline 0.1% instillation on day 1 were 0.59 ± 0.72 mm and 0.93 ± 0.81 mm, respectively (vs 0.20 ± 0.57 mm and 0.32 ± 0.64 mm with vehicle; both p< 0.001). On day 14, mean changes from baseline 5 and 15 minutes post-oxymetazoline 0.1% instillation were 0.77 ± 0.85 mm and 1.11 ± 0.92 mm, respectively (vs 0.42 ± 0.78 mm and 0.41 ± 0.83 mm with vehicle; both p< 0.05). This effect was also observed immediately post-instillation on day 42, where mean increases 5 and 15 minutes post-oxymetazoline 0.1% instillation were 0.86 ± 0.85 mm and 1.04 ± 0.91 mm, respectively (vs 0.42 ± 0.80 mm and 0.47 ± 0.93 mm with vehicle; both p< 0.005). Significant improvements vs vehicle (p< 0.001) were also observed at 2– 6 hours on days 1 and 14. At all time points, the proportion of subjects showing a positive response to treatment (> 0% MRD-1 increase) was > 15% greater in the oxymetazoline 0.1% group (range 16.6– 36.1% more responders vs vehicle), with the largest differences observed 2 and 6 hours post-instillation.Conclusion: Oxymetazoline 0.1% provided rapid and sustained upper eyelid elevation. Together with data demonstrating superior visual field improvement and a favorable safety profile, this analysis supports oxymetazoline 0.1% as an effective non-surgical treatment for acquired ptosis.Keywords: alpha adrenergic agonist, eye drop, Müller’s muscle, non-surgical, topical, pharmacologic