Purpose: The purpose of this study was to evaluate the efficacy and safety of higher dosages of topical losartan in an alkali-burn fibrosis model in rabbits.
Methods: In total, 18 rabbits had standardized alkali burns that trigger stromal fibrosis. Six eyes per group were treated with topical losartan (0.8 mg/mL, 8 mg/mL, or 40 mg/mL) 6 times per day. Slit-lamp photographs were obtained, and multiplex immunohistochemistry was performed for myofibroblast marker alpha-smooth muscle actin (α-SMA), mesenchymal cell marker vimentin, and basement membrane marker laminin alpha-5.
Results: Topical losartan at 40 mg/mL 6 times per day produced severe discomfort and ocular surface toxicity in all rabbits, and treatment was discontinued at nine days in this group. Topical losartan at 8 mg/mL 6 times per day caused less rabbit discomfort on application, but there were persistent epithelial defects and marked stromal opacity in 5 of 6 eyes after 1 month of treatment. Topical losartan 0.8 mg/mL was well tolerated by rabbits, and corneal opacity was markedly reduced at 1 month in 5 of 6 corneas compared with corneas in the 8 mg/mL and 40 mg/mL losartan groups. A persistent epithelial defect with opacity was noted in 1 cornea in the 0.8 mg/mL losartan group. Both total SMA-positive stromal cells per section (14.5 ± 2.8 vs. 3.5 ± 0.7, P = 0.04) and total stromal vimentin intensity units (310 ± 64 vs. 132 ± 35, P = 0.02) were significantly greater after 1 month of treatment in corneas treated with 8 mg/mL than corneas treated with 0.8 mg/mL of topical losartan.
Conclusions: Topical losartan dosages over 0.8 mg/mL should be used cautiously in patient eyes. In eyes with a current epithelial defect, it is recommended that 0.2 mg/mL losartan 6 times per day be used until the epithelium closes.
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