Antiangiogenic Effect of Itraconazole on Corneal Neovascularization: A Pilot Experimental Investigation

Abstract

Purpose: To investigate the antiangiogenic effect of itraconazole for the prevention of experimentally induced corneal neovascularization and whether the efficacy depends on the route of administration. Materials and Methods: Thirty-six rats were randomly divided into 6 groups with 6 rats in each group. Chemical cauterization of the cornea was performed using silver nitrate/potassium nitrate sticks, and the rats were subsequently treated daily with topical (10 mg/ml), subconjunctival (10 mg/ml) or intraperitoneal (19 mg/kg) itraconazole for 7 days. Control rats received topical, subconjunctival or intraperitoneal 0.9% saline. On the 8th day of the experiment, the rat corneas were photographed to determine the percentage area of the cornea covered by neovascularization. The maximum density of corneal neovascularization was determined by microscopy. Results: The median percentage of corneal neovascularization for group 1 was 31.5% (95% confidence interval, 27.5-35.5%); in group 3, it was 32% (23.5-39.8%); in group 5, it was 47% (36.3-60.0%). The percentages of corneal neovascularization in groups 2, 4 and 6 (the control groups) were 70% (95% confidence interval, 60.7-77.3%), 69% (63.0-77.7%) and 68% (56.5-78.5%), respectively. The area of neovascularization was smaller after itraconazole treatment as compared to saline treatment. Further, the area of neovascularization was smaller after topical and subconjunctival administration than after intraperitoneal administration. Histological evaluation of the corneas showed the most extensive corneal neovascularization in the control group. No local or systemic adverse effects were seen from either treatment group. Conclusion: Itraconazole reduces corneal neovascularization shortly after chemical burn. However, a larger experimental study is necessary to confirm the data of this investigation.