Safety of Once-Daily Oxymetazoline HCl Ophthalmic Solution, 0.1% in Patients with Acquired Blepharoptosis: Results from Four Randomized, Double-Masked Clinical Trials

Abstract

Purpose: An oxymetazoline 0.1% ophthalmic solution was recently approved for treatment of acquired blepharoptosis in adults. This study's objective was to evaluate the safety profile of oxymetazoline 0.1% when administered once daily for 14-84 days. Patients and Methods: Pooled analysis examined safety outcomes from four randomized, double-masked, placebo-controlled clinical trials conducted at 6, 16, 27, and 35 sites, respectively, in the United States. In total, 568 participants with acquired blepharoptosis were evaluated. Median age was 66 years and 74.8% of participants were female. Overall, 375 participants self-administered oxymetazoline 0.1% to both eyes once/day and 193 self-administered placebo (vehicle) daily. Treatment-emergent adverse event (TEAE) rates, severity, and causality were evaluated in the overall population and within participant subgroups defined based on age, race, and ethnicity. Vital signs and ophthalmic findings were evaluated at predefined study visits. Patient-reported treatment tolerability was recorded at study end. Results: TEAE incidence was similar among participants using oxymetazoline 0.1% (31.2%) or vehicle (30.6%). Nearly all TEAEs were mild-to-moderate, and most were not suspected of being treatment related. Serious TEAEs occurred in four participants receiving oxymetazoline 0.1% and one participant receiving vehicle. Nine and two participants in the oxymetazoline 0.1% and vehicle groups, respectively, discontinued due to a TEAE. Ocular TEAEs occurring in ≥2% of participants receiving oxymetazoline 0.1% were punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, instillation site pain, and corneal vital dye staining, with none occurring in >3.5% of participants. TEAE rates were similar across subgroups based on age, race, and ethnicity. No clinically significant mean changes in vital signs or ophthalmologic findings occurred, and >98% of participants rated oxymetazoline 0.1% as causing no/mild discomfort. Conclusion: Once-daily oxymetazoline 0.1% was safe and well tolerated in participants with acquired blepharoptosis when used for 14-84 days. Safety did not appear to differ based on age, race, or ethnicity.

Topical Review: An Update of Diagnostic and Management Algorithms for Acquired Blepharoptosis

“…Clinical data indicate that oxymetazoline 0.1%, when used once daily, effectively elevates the upper eyelid and improves superior visual field deficits after administration in patients with acquired ptosis. It also has a favorable safety and tolerability profile 7,38,39 …”

“…It also has a favorable safety and tolerability profile. 7,38,39 Reports have also described the off-label use of topical α-adrenergic agents developed for other ophthalmic applications, such as apraclonidine, phenylephrine, brimonidine, and naphazoline, to raise the upper eyelid. These reports, however, are generally limited in scope, and these therapies have not undergone rigorous clinical trials to evaluate their utility for the treatment of ptosis.…”

“…Patients with acquired ptosis should be presented with the range of appropriate treatment options. Given its minimally invasive nature and clinical evidence of its efficacy and safety, 7,38,39 eye care practitioners should consider pharmacologic treatment with oxymetazoline 0.1% as the first treatment option for all appropriate patients with acquired ptosis. Although the clinical trial data regarding oxymetazoline 0.1% use seem to be promising, it is also important that practitioners continue to evaluate this novel treatment option based on their clinical experience and emerging data, including long-term efficacy outcomes.…”

A review of nonsurgical facial rejuvenation and the role of oxymetazoline hydrochloride ophthalmic solution, 0.1% in periorbital revitalization

“…25 From an anatomical standpoint, upper eyelid elevation is provided by the levator palpebrae superioris, a skeletal muscle that attaches to the superior tarsal plate, and the superior tarsal muscle (or Müller's muscle), a smooth muscle that originates from the levator muscle and inserts on the superior tarsal plate maintaining elevation and adding 2 to 3 mm of lift. 23,27 Aponeurotic ptosis involves the stretching or dehiscence of the levator muscle complex. 25 Corrective surgery is usually performed on Müller's muscle.…”

“…Mild instillation site pain was experienced by 2.1% of the participants receiving the active drug. 27 Alpha-adrenergic receptors are expressed in the aqueous outflow tract, the conjunctiva, the iris, and the ciliary body, which could account for these findings. 27,28 There were no clinically significant changes in heart rate, blood pressure, visual acuity (Snellen VA), intraocular pressure, pupil diameter, or corneal fluorescein staining (Figure 5).…”