Safety profile of topical VEGF-neutralization at the cornea

¹ IZKF A9, Augenklinik Erlangen, Nurnberg, Germany
² Department of Ophthalmology, University of Erlangen-Nuernberg, Erlangen, Germany
³ University of Erlangen, Erlangen, Germany

^* To whom correspondence should be addressed. E-mail: felix.bock{at}augen.imed.uni-erlangen.de.

	Abstract

Purpose: Bevacizumab (Avastin) eye drops inhibit corneal neovascularization. Purpose of this study was to analyze the safety profile of VEGF-A neutralization at the ocular surface. Methods: Bevacizumab eye drops and an anti-murine VEGF-A antibody were applied to normal murine corneas 5x/day for 7 and 14 days. Subsequently corneas were analyzed for morphological changes by light and electron microscopy. In a mouse model of corneal epithelial abrasion the effects of topically applied anti-VEGF antibodies on epithelial wound healing were analyzed: the treatment group received Bevacizumab or the anti-murine VEGF-A antibody as eye drops and the control group an equal volume of saline solution. After 12, 18 and 24 h corneas were photographed in vivo with and without fluorescein staining for morphometry. Afterwards the mice were sacrificed and eyes were removed for histology, immunohistochemistry with Ki67/DAPI and electron microscopy. The effect of mid term anti-VEGF therapy on corneal nerve density was assessed by staining corneas treated with a FITC-conjugated anti-neurofilament antibody and morphometrical analysis. Results: Murine corneas treated with two different anti-VEGF antibody eye drops did not show obvious corneal morphological changes at the light and electron microscopical level. Furthermore, anti-VEGF antibody eye drops had no significant impact on the wound healing process after corneal epithelial injury and on normal murine corneal nerve fiber density. Conclusions: Topical neutralization of VEGF-A at the corneal surface does not have significant side-effects on normal corneal epithelial wound healing, normal corneal integrity or normal nerve fiber density. Therefore, anti-VEGF eye drops seem to be a relatively safe option to treat corneal neovascularization.

Key Words: corneal wound healing, drug delivery, corneal epithelium, growth factors, neovascularization, neurotrophins

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