Timolol: A Low-Cost Adjunctive Treatment for Erythematotelangiectatic Rosacea

We read with keen interest the article on rosacea by Frazier and colleagues published in American Family Physician.¹ In addition to the treatments they discussed, topical timolol maleate is a simple, low-cost, and well-tolerated option that has been overlooked and merits attention. As a nonselective beta-adrenergic receptor antagonist with anti-inflammatory properties, timolol can improve erythema and flushing in rosacea by reducing inflammation and constricting smooth muscles surrounding the blood vessels.²

A randomized split-face trial investigated the effectiveness of timolol maleate 0.5% eye drops applied once daily in 16 patients with mild to moderate erythematotelangiectatic rosacea and reported significant improvement in erythema, warmth, and burning at the 28-day follow-up appointment.³ No adverse effects were noted except for worsened redness on both sides of the face at day 1 in only one patient, which later resolved without additional treatment. In contrast, a second trial showed no statistically significant difference in flushing and erythema between the treated and untreated sides of the face in eight patients with timolol 0.5% gel-forming solution applied twice daily in the first 8 weeks.⁴ However, when applying the gel on both sides of the face, a significant improvement was noted at week 12 on the side that received continuous treatment for 16 weeks compared with the contralateral side, which was untreated for the first 8 weeks, followed by 8 weeks of treatment. During the 16-week treatment period, only one episode of transient lower eyelid sensitivity was reported, and rebound erythema was seen 4 weeks after timolol discontinuation.⁴ Another study of 58 patients treated for 8 weeks concluded that timolol maleate 0.5% is more effective in erythematotelangiectatic rosacea than in papulopustular rosacea with minimal adverse effects.⁵

Finally, a split-face case study of severe erythematotelangiectatic rosacea demonstrated a greater improvement in facial erythema, telangiectasias, and burning and stinging sensations when combining pulsed dye laser therapy with topical timolol 0.5% ophthalmic solution vs the side treated with timolol alone after 4 weeks.⁶

We encourage physicians to consider timolol as monotherapy or as an adjunct to pulsed dye laser treatment as a low-cost means to accelerate symptom resolution.

We appreciate your thoughtful response to our paper. Thank you for highlighting topical timolol 0.5% as a treatment option to treat the fixed erythema and flushing rosacea phenotypes. Topical timolol has robust evidence for treating infantile hemangiomas, but we could not find enough high-quality evidence to include it in our article.¹

The studies cited in your letter all had low sample sizes, ranging from one to 58 patients. Three of the studies evaluating topical timolol were split-face studies, which could impact the validity of the results due to potential spread of medication through the cutaneous vasculature.² The study evaluating 58 patients treated with topical timolol did not show a statistically significant improvement in rosacea symptoms after 8 weeks of treatment.³ Topical timolol appears to be safe, but one of the articles reported rebound erythema 4 weeks after medication discontinuation.⁴ After a careful review of the literature, we would consider recommending topical timolol only as adjunctive therapy for mild erythema.

In addition, the National Rosacea Society Expert Committee and the American Acne & Rosacea Society did not mention topical timolol as a treatment for rosacea in their most recent guidelines.^5,6

For treating fixed erythema and flushing, we recommended topical brimonidine and oxymetazoline, two safe, evidence-based therapies supported as first-line treatments by the National Rosacea Society Expert Committee. Our article also discussed two oral nonselective beta-adrenergic receptor antagonists (carvedilol [Coreg] and propranolol) that have clear evidence in reducing persistent erythema and flushing. These options all have greater supporting evidence in treating erythema and flushing compared with topical timolol.