Am Fam Physician. 2025;111(5):390B
Author disclosure: No relevant financial relationships.
To the Editor:
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.
In Reply:
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.
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.
