Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model

The aim of this experimental study was to compare the efficacy of topical aflibercept and topical bevacizumab in preventing corneal neovascularization. A chemical burn was created in the right central cornea of male Sprague-Dawley rats, followed immediately by instillation of one drop (25 mg/ml, 20 mu l volume) of aflibercept (15 eyes), bevacizumab (14 eyes), or saline (15 eyes). Treatment was repeated twice daily for 7 days. Corneal neovascularization was determined using corneal photographs (ImageJ) on days 1, 4, 7, 10, and histological and immunofluorescence studies, on day 10. Stromal immunoreactivity was evaluated 2 days after injury in 6 rats treated singly with bevacizumab or aflibercept. Corneal neovascularization was observed clinically on day 4 in all groups. In the aflibercept group, the area of neovascularization increased from 738 +/- 2.23% on day 4 to 21.73 +/- 14.59% on day 7 and 31.0 +/- 23.61% on day 10. Corresponding values in the bevacizumab group were 6.04% +/- 1.81%, 51.27 +/- 15.50%, and 54.4 +/- 11.33%, and in the control group, 8.99 +/- 1.93%, 42.6 +/- 19.59%, and 55.15 +/- 11.54%. The area of neovascularization was significantly smaller on days 7 and 10 in the aflibercept group than in the control and bevacizumab groups (P < 0.001, all analyses), with no significant differences between the latter two groups (day 7, P = 0.868; day 10, P = 0.213). Clinical findings were compatible with the histological data and supported by immunofluorescence and corneal flat-mount staining. Both drugs demonstrated variable penetration into the corneal stroma. Topical aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn. These findings may have important therapeutic implications for humans. (c) 2016 Elsevier Ltd. All rights reserved.