Topical Losartan in the Management of Corneal Scarring Fibrosis: Update on Dosage, Efficacy, and Potential Epithelial Toxicity

Losartan is an angiotensin II receptor blocker (ARB) that also inhibits transforming growth factor (TGF)-beta signaling by blocking the activation of extracellular signal-regulated kinase (ERK) in the noncanonical TGF-beta signaling pathway. Rabbit studies demonstrated the efficacy of topical losartan in reducing fibrotic scarring following a variety of corneal injuries, such as descemetorhexis, alkali burns, and photorefractive keratectomy (PRK). Several human case reports have subsequently shown the efficacy of topical losartan in treating scarring fibrosis resulting from surgical complications and infections. Since rabbit studies have also found concentration-dependent corneal epithelial toxicity associated with topical losartan, a lower concentration of 0.2 mg/mL administered 6 times daily is recommended in corneas with epithelial defects until epithelial closure is achieved before using standard 0.8 mg/mL losartan 6 times a day for the duration of treatment. For eyes with intact epithelium, a dose of 0.8 mg/mL 6 times daily is recommended throughout the treatment period. Doses of topical losartan above 0.8 mg/mL should be avoided due to dosage-related increases in persistent epithelial defects. Clinical studies are needed to further assess questions such as which corneal fibrotic disorders are most likely to respond to topical losartan treatment and whether a lower frequency of application leads to greater treatment failure.