EYE-OPENING NEWS ABOUT OXYMETAZOLINE

By Warren R. Heymann, MD, FAAD
April 27, 2022
Vol. 4, No. 17

Certain articles have a "wow" factor that immediately impacts practice. In 2007, I recall being impressed by the 2 cases of erythematotelangiectatic rosacea reported by Shanler and Ondo that dramatically improved with the application of oxymetazoline hydrochloride 0.05%. (1) Oxymetazoline had been used for decades to treat nasal decongestion or to "get the red out" of the eyes; I thought the idea was brilliant. I have been recommending it ever since either as the over-the-counter product or the 1% prescription cream formulation released in 2017. (2)

Oxymetazoline is a potent vasoconstrictor that also demonstrates anti-inflammatory properties. It is a direct-acting, imidazoline-type sympathomimetic agonist that is highly selective for the α1A-adrenoceptor and is also a partially selective α2A-receptor agonist. (1) The drug's vasoconstrictive effects have been used to advantage for other dermatological conditions, including post-acne erythema (3,4), erythromelalgia of the knee (5), and hemostasis during dermatologic surgery. (6)

Oxymetazoline 0.1% ophthalmic solution is now available for the treatment of blepharoptosis (drooping of the eyelid, subsequently referred to as ptosis). This commentary will focus on the use of oxymetazoline for ptosis. (I have no financial or any other perceived conflict of interest with RVL Pharmaceuticals, Inc. the distributor of Upneeq.)

Ptosis may be a cosmetic concern but if significant enough, may interfere with vision. I have mild ptosis — people have told me to "wake up" during our conversations. (Sometimes they are correct and I am falling asleep!)

Ptosis is a physical sign, not a diagnosis. Ptosis may be congenital or acquired. Acquired adult ptosis is categorized as 1) aponeurotic (aka involutional; this is the most common form, usually presenting in the 5th-6th decade, most frequently due to dehiscence or disinsertion of the levator aponeurosis; 2) neurogenic (due to disruption of innervation of either the levator muscle or Muller muscle [a small smooth muscle arising from the striated levator muscle along with the aponeurosis] as may be seen with Horner syndrome or 3rd cranial nerve palsy; 3) myogenic (due to an abnormality of levator muscle itself, as seen with myasthenia gravis or myotonic dystrophy; 4) mechanical (secondary to any tumor causing increased eyelid weight, conjunctival scarring, and blepharochalasis); and 5) traumatic (due to direct or indirect injury to the levator muscle). (7) If there is any question about the etiology of ptosis an ophthalmological consultation should be sought.

Oxymetazoline elevates the eyelid by activating α-adrenergic receptors in the Muller muscle. Slonim et al reported the results of 2 industry-sponsored randomized placebo-controlled masked trials that assessed the efficacy of oxymetazoline, 0.1%, eyedrops for ptosis. A total of 304 patients with acquired ptosis to topical oxymetazoline HCl, 0.1%, vs vehicle in 2 trials were randomized. All participants had clinically relevant involutional (aponeurotic) ptosis defined by superior visual field loss and reduced eyelid height. Response to therapy was evaluated at 1 day and 14 days of treatment, and safety was evaluated over 42 days of follow-up. Using Leicester Humphrey Visual Field (HVF) static perimetry as the primary outcome, the authors showed a change in the oxymetazoline treatment arm of 4 to 5 points of superior visual field more than the change in the vehicle arm. The secondary outcome, change in upper eyelid height, increased by less than 0.5 mm in the treatment arm compared with the vehicle arm on day 1 and by 0.67 mm compared with vehicle on day 14.

Oxymetazoline HCl, 0.1%, was generally well tolerated, with no change in visual acuity or intraocular pressure but with somewhat higher rates of punctate keratitis, conjunctival hyperemia, and subjectively blurred vision in the study group. (8,9) In an editorial accompanying the article by Slonim at al, Bradley and Bradly opine; "It is unclear whether a gain of 4 to 5 points of superior visual field, or roughly half a line of points on the Leicester HVF, represents meaningful clinical change. The corresponding less than 1 mm of eyelid elevation produced by oxymetazoline compared with vehicle may also be of marginal clinical benefit. While it is possible that this degree of eyelid elevation yields substantial improvements in visual function and patient self-image, an assessment of health-related quality of life was not included in the study." Additionally, this study did not compare oxymetazoline with surgery, although when compared to historical data, the improvement with oxymetazoline is less than is usually observed with surgical repair. (9)

Wirta et al (with Slonim as senior author) evaluated the safety profile of oxymetazoline 0.1% when administered once daily for 14-84 days to assess treatment-emergent adverse events (TEAE). A total of 568 participants with acquired blepharoptosis were evaluated. The 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. 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 2 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, allowing the authors to conclude that oxymetazoline for ptosis is safe and well tolerated.

Wirta et al explain that oxymetazoline may affect α-adrenergic receptors expressed elsewhere in the eye (conjunctiva, iris-ciliary structures, aqueous outflow tract) that could explain the adverse reactions of punctate keratitis, conjunctival hyperemia, and dry eye. Finally, oxymetazoline may be associated with transient mydriasis and acute angle closure glaucoma – trials with oxymetazoline excluded such patients. (10)

Dermatologists may encounter ptosis due to localized spread of botulinum toxin when administered for treating glabellar lines. Oxymetazoline may be considered as convenient, rapid, safe, and effective treatment for this adverse reaction to botulinum toxin. (11)

Before prescribing oxymetazoline, I would encourage all to read the package insert. Avoid using the medication in those with a history of acute angle glaucoma and be judicious with its use in hypertensive patients.

I could not resist the temptation. I tried it, but my results were barely perceptible (see below, and please ignore the subconjunctival hemorrhage). Our practice manager, however, was delighted with her results that were observed within an hour (see below, with permission).