Topical axitinib is a potent inhibitor of corneal neovascularization

• Published in: Clinical & experimental ophthalmology 2018-12, Vol.46 (9), p.1063-1074
• Main Authors: Lledó Riquelme, Mariola, Campos‐Mollo, Ezequiel, Fernández‐Sánchez, Laura
• Format: Article
• Language: English
• Subjects: Administration, Topical; Angiogenesis; Animals; axitinib; Axitinib - administration & dosage; Cornea; Cornea - blood supply; Cornea - drug effects; Cornea - pathology; corneal neovascularization; Corneal Neovascularization - diagnosis; Corneal Neovascularization - drug therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme inhibitors; Follow-Up Studies; Growth factors; Microvessels - pathology; Ophthalmic Solutions - administration & dosage; Ophthalmology; Protein Kinase Inhibitors - administration & dosage; Protein-tyrosine kinase; Rabbits; Random Allocation; Silk; Sutures; Treatment Outcome; tyrosine kinase inhibitor; Vascular endothelial growth factor; Vascularization
• ISSN: 1442-6404; 1442-9071
• DOI: 10.1111/ceo.13333

Background This study evaluated the effects of topically applied axitinib, a tyrosine kinase inhibitor, in an experimental model of corneal neovascularization (CNV). Methods A total of 48 New Zealand rabbits were used. CNV was induced by placing five silk sutures in the upper cornea of one eye per rabbit. Rabbits were randomized into four groups (12 rabbits each): 0.9% saline (control group), 0.02 mg/mL axitinib, 0.35 mg/mL axitinib and 0.5 mg/mL axitinib groups. All treatments were administered three times daily for 14 days. Photographs were taken using a slit lamp on days 7 and 14. The area of neovascularization was measured in mm2, as the percentage of total corneal area and as the percentage of corneal surface covered by sutures (SCS). Results On day 14, the CNV area in the control group (31.50 ± 7.47 mm2; 115.00 ± 22.55% of the corneal SCS) was larger than that in the 0.02 mg/mL axitinib group (19.20 ± 8.92 mm2; 73.89 ± 34.98%), the 0.35 mg/mL axitinib group (8.83 ± 3.92 mm2; 31.90 ± 13.59%) and the 0.5 mg/mL axitinib group (5.12 ± 3.97 mm2; 18.38 ± 13.65%). Compared with saline, CNV was inhibited 39.04% by 0.02 mg/mL axitinib, 71.96% by 0.35 mg/mL axitinib and 84.73% by 0.5 mg/mL axitinib. Conclusion Topical administration of the three axitinib concentrations inhibited CNV in rabbits, blocking both vascular endothelial growth factor and platelet‐derived growth factor pathways. Axitinib at 0.5 mg/mL induced profound inhibition of corneal angiogenesis.