Acquired blepharoptosis develops after the stretching, dehiscence, or disinsertion of the levator aponeurosis in the upper eyelid. A droopy lid can be cosmetically undesirable to some, but it can also have significant visual implications by causing a reduction in the superior visual field. Few interventions exist for acquired blepharoptosis outside of an invasive surgery, leaving many patients undertreated and unsatisfied.

Recently, a preservative-free 0.1% oxymetazoline hydrochloride ophthalmic solution (Upneeq, RVL Pharmaceuticals Inc.) was approved by the U.S. Food and Drug Administration for the treatment of acquired ptosis. This novel pharmacologic agent, a direct-acting alpha adrenergic receptor agonist, is thought to stimulate Müller muscle contraction, resulting in upper eyelid elevation (Figure 1).

In a pooled analysis of two randomized, double-masked, placebo-controlled Phase 3 clinical trials, significant improvements in upper lid position and ptosis-induced superior visual field defects were observed (Slonim et al, 2020). Adverse reactions were considered mild and included punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, eye irritation, and headache (Slonim et al, 2020; RVL Pharmaceuticals, 2020).

From what I’ve observed, patients are pleased to have an option for ptosis improvement despite it being an out-of-pocket expense. Time will tell whether it will maintain its effects, as current studies were only six weeks in duration, and evidence exists that prolonged stimulation of tissues by oxymetazoline can lead to tachyphylaxis, receptor desensitization, and rebound vessel dilation (Akinaga et al, 2013; Vaidyanathan et al, 2010).

Oxymetazoline is a sympathomimetic drug that can dry out mucus membranes and has been shown to reduce tear production for up to six hours (Göbbels et al, 1991). This is a potential limiting factor in Sjögren’s and dry eye disease patients.

Another consideration is the potential for increased ocular exposure to desiccating stressors from widening the palpebral aperture, and although clinical trials did not report any new cases of lagophthalmos with this therapy, artificially creating a partial blink or an ineffective lid seal could be another concern.

Lastly, I’ve observed that using Upneeq in only the ptotic eye for mild cases can sometimes result in reverse lid asymmetry, with the ptotic eye having a larger aperture compared to the non-affected eye.

Unintended Effects

As prescribers, we must be aware of the potential for unintended physiological effects and drug interactions. Even though there were no mean shifts from baseline in terms of vital signs or pupil dilation in Upneeq studies to-date, alpha-adrenergic agonists can impact blood pressure and increase pupil size. Caution is advised in patients taking beta blockers, anti-hypertensives, cardiac glycosides, and monoamine oxidase inhibitors (MAOIs) as well as in those who have untreated narrow angles.

Upneeq complements our pharmacological armamentarium for individuals who have acquired ptosis—in particular, those who aren’t quite ready for surgical intervention—however, patients must be chosen carefully. It may be prudent to prescribe Upneeq for periodic use only (i.e., important life events such as weddings, etc.) until longer-duration studies can provide more information on long-term safety, tachyphylaxis, and rebound effects. CLS

For references, please visit www.clspectrum.com/references and click on document #303.