Insights from animal studies exploring the efficacy and safety of topical losartan, in prophylaxis and treatment of corneal scarring fibrosis.

Several studies in rabbits demonstrated the efficacy and safety of topical losartan, an angiotensin II receptor blockers (ARB) that modulates the TGF-β intracellular signaling pathways by inhibiting the activation of Extracellular Signal-regulated Kinase (ERK), in preventing or treating stromal fibrosis after a range of injuries such as Descemetorhexis, alkali burns, incisions, and photorefractive keratectomy (PRK). Several case reports have shown that topical losartan treatment is also efficacious and safe in humans to prevent or treat stromal fibrosis after many different injuries or diseases. Topical losartan penetrates the full thickness of the cornea and, therefore, can treat both anterior and posterior stromal fibrosis. These rabbit studies have demonstrated that there can be epithelial and stromal toxicity to losartan at dosages greater than 0.8 mg/ml and that higher dosages will not accelerate the return to transparency of fibrotic corneas. In corneas with an epithelial defect, it is likely safer to use 0.2 mg/ml losartan six times a day until the epithelium closes to further decrease the risk of epithelial toxicity before going to the 0.8 mg/ml six times a day dosage. Future clinical studies will explore additional questions, such as whether four times a day dosing is less effective than six times a day dosing in the treatment of stromal fibrosis.