Orly Gal-Or1, Eitan Livny, Ruti Sella, Yael Nisgav, Dov Weinberger, Tami Livnat, Irit Bahar. 1. *Department of Ophthalmology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and ‡Laboratory of Eye Research, Felsenstein Medical Research Center, Beilinson Campus, Petach Tikva, Israel.
Abstract
PURPOSE: We aimed to evaluate the efficacy of subconjunctival aflibercept, a vascular endothelial growth factor trap compound, for the treatment of corneal neovascularization in a rat model. METHODS: Chemical burn was produced in the central cornea of 31 male Sprague-Dawley rats. Animals were randomized to receive treatment with subconjunctival injection of 0.08 mL aflibercept (25 mg/mL), 0.05 mL bevacizumab (25 mg/mL), or 0.05 mL physiologic saline. Corneal neovascularization was evaluated on postinjury days 1, 3, 7, 9, and 13 by corneal photographs. The rats were killed on day 21 and samples were collected for histological and flat-mount immunofluorescence analyses. RESULTS: In all rats, vascular sprouting began on day 3, reached maximum density on days 7-9, and spontaneously regressed thereafter. Mean burn area in the central cornea comprised ∼15% of the total corneal area. The aflibercept group had a significantly smaller relative area of neovascularization than both control group (P < 0.05, 12.27 ± 9.91, 29.66 ± 9.96 days 7) and bevacizumab group (P < 0.05, 12.27 ± 9.91, 21.27 ± 8.19 days 7 and 15.5 ± 10.25, 32.38 ± 9.44 days 9; Mann-Whitney test). On histological study, hematoxylin and eosin staining revealed blood vessels extending to the central cornea in the control and bevacizumab groups and limited to the periphery in the aflibercept group. Immunofluorescence study with an endothelial marker revealed a smaller area of staining in the aflibercept group. CONCLUSIONS: Aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn-induced neovascularization and warrants further study for potential use in humans.
PURPOSE: We aimed to evaluate the efficacy of subconjunctival aflibercept, a vascular endothelial growth factor trap compound, for the treatment of corneal neovascularization in a rat model. METHODS: Chemical burn was produced in the central cornea of 31 male Sprague-Dawley rats. Animals were randomized to receive treatment with subconjunctival injection of 0.08 mL aflibercept (25 mg/mL), 0.05 mL bevacizumab (25 mg/mL), or 0.05 mL physiologic saline. Corneal neovascularization was evaluated on postinjury days 1, 3, 7, 9, and 13 by corneal photographs. The rats were killed on day 21 and samples were collected for histological and flat-mount immunofluorescence analyses. RESULTS: In all rats, vascular sprouting began on day 3, reached maximum density on days 7-9, and spontaneously regressed thereafter. Mean burn area in the central cornea comprised ∼15% of the total corneal area. The aflibercept group had a significantly smaller relative area of neovascularization than both control group (P < 0.05, 12.27 ± 9.91, 29.66 ± 9.96 days 7) and bevacizumab group (P < 0.05, 12.27 ± 9.91, 21.27 ± 8.19 days 7 and 15.5 ± 10.25, 32.38 ± 9.44 days 9; Mann-Whitney test). On histological study, hematoxylin and eosin staining revealed blood vessels extending to the central cornea in the control and bevacizumab groups and limited to the periphery in the aflibercept group. Immunofluorescence study with an endothelial marker revealed a smaller area of staining in the aflibercept group. CONCLUSIONS: Aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn-induced neovascularization and warrants further study for potential use in humans.