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

Abstract

Purpose

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

Data Sharing Statement

The authors do not intend to share individual deidentified study participant data.

Acknowledgments

Studies reported were funded by RVL Pharmaceuticals, Inc., an affiliate of Osmotica Pharmaceuticals plc (Bridgewater, NJ, USA). Editorial and administrative support was provided by BioScience Communications (New York, NY, USA) through funding provided by Osmotica Pharmaceuticals.

Disclosure

Jason Bacharach reports speaker fees from Aerie Pharmaceuticals, Alcon, Allergan, Bausch & Lomb, Glaukos, New World Medical, and Sun Pharmaceutical Industries, Inc.; consultant fees from Aerie Pharmaceuticals, Alcon, Allergan, Bausch & Lomb, Injectsense, New World Medical, Optovue, and Osmotica Pharmaceuticals; personal fees from Sun Pharmaceutical Industries, Inc.; research support from Aerie Pharmaceuticals, Allergan, Novartis, Glaukos, Optovue, and Ocular Therapeutix. David L. Wirta reports research support from RVL Pharmaceuticals, Inc., and Osmotica Pharmaceuticals. Robert Smyth-Medina reports personal fees from Sun Pharmaceutical Industries, Inc.; research support from Aerie Pharmaceuticals, Alcon, Allergan, Aurinia, Auven, Bausch & Lomb, Eleven, Encore, Evidera, Eyegate, Hi Tech Pharmacal, Inotek, Inspire, Ista, Kala, Novartis, OmegaD, Ono, OTX, RVL Pharmaceuticals, Inc., Santen, SARcode, Shire, Silk, Senju, Valeant, and Xigen. Michael S. Korenfeld reports consultant fees from Osmotica Pharmaceuticals. Shane R. Kannarr reports personal fees from Allergan, Alcon, Bausch & Lomb, Essilor, Johnson & Johnson, Novartis, Oculos, Optovue, and Osmotica Pharmaceuticals. Shane Foster reports consultant and speaker fees from Osmotica Pharmaceuticals. Mark J Jaros reports consultant fees from Osmotica Pharmaceuticals. Charles B. Slonim reports research support and consultant fees from RVL Pharmaceuticals, Inc. and Osmotica Pharmaceuticals. The authors report no other conflicts of interest in this work.