INTRODUCTION
Rosacea is a common, chronic skin disorder affecting more than 16 million people in the United States.1,2 Typically affecting the central facial area including cheeks, chin, nose, and forehead, rosacea is characterized by flushing (or transient facial erythema), persistent facial erythema, papules and pustules, and/or telangiectasias.3-5 Various combinations of clinical features define 4 major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea. Although understanding of the pathophysiology is limited, data suggest 2 primary mechanisms: abnormal innate immune detection and neurovascular dysregulation. Activation of these pathways leads to specific clinical manifestations of rosacea.5,6 Acute and chronic facial vasodilation and an impaired stratum corneum permeability barrier have been documented in rosacea.6Although currently available treatments target some rosacea manifestations, none offers a cure.7-10 Goals are to alleviate signs and symptoms, improve the skin’s appearance, and delay or prevent disease progression. Treatment is selected based on the individual’s predominant signs and symptoms, and may comprise multiple modalities, including topical pharmacologic agents and nonpharmacologic options. Pharmacologic treatments for inflammatory lesions of rosacea include topical clindamycin, metronidazole, sulfacetamide, azelaic acid, or combination products,7,11-13 and oral antimicrobial agents.7,13Treatments for the persistent, diffuse erythema associated with rosacea are limited, but FDA-approved options include oxymetazoline and brimonidine.7,14-16 Because the cutaneous circulation is partially regulated by the sympathetic nervous system, it may be targeted by α-adrenoceptor agonists such as these to reduce erythema.14-16 Oxymetazoline binds selectively to α1A receptors, causing vasoconstriction and reduction of erythema following topical application.14 The Phase 3 REVEAL clinical trials demonstrated the efficacy, safety, and tolerability of oxymetazoline cream 1.0% applied topically once daily for 29 days in adults with moderate to severe persistent facial erythema associated with rosacea.17,18Oxymetazoline pharmacokinetics data are limited, but ocular absorption studies in rabbits have demonstrated that oxymetazoline is poorly absorbed,19 indicating low systemic exposure. Although intranasal oxymetazoline is believed to be an effective decongestant for up to 12 hours,20 intraocular administration of oxymetazoline to healthy adults lost its
