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Originally published In Press as doi:10.1167/iovs.07-1129 on January 17, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:2095-2102.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.07-1129
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Safety Profile of Topical VEGF Neutralization at the Cornea

Felix Bock, Jasmine Onderka, Carmen Rummelt, Tina Dietrich, Björn Bachmann, Friedrich E. Kruse, Ursula Schlötzer-Schrehardt, and Claus Cursiefen

From the Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany.

PURPOSE. Bevacizumab eyedrops inhibit corneal neovascularization. The purpose of this study was to analyze the safety profile of VEGF-A neutralization at the ocular surface.

METHODS. Bevacizumab eyedrops (5 mg/mL) and an antimurine VEGF-A antibody (250 µg/mL) were applied to normal murine corneas five times a day for 7 and 14 days. Subsequently, corneas were analyzed for morphologic 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 (5 mg/mL) or the antimurine VEGF-A antibody (250 µg/mL) as eyedrops, and the control group received an equal volume of saline solution. After 12, 18, and 24 hours, corneas were photographed in vivo with and without fluorescein staining for morphometry. Afterwards the mice were killed, and eyes were removed for histology, immunohistochemistry with Ki67/DAPI, and electron microscopy. The effect of midterm anti-VEGF therapy on corneal nerve density was assessed by staining corneas treated with an FITC-conjugated anti-neurofilament antibody and morphometric analysis.

RESULTS. Murine corneas treated with two different types of anti-VEGF antibody eyedrops did not show obvious corneal morphologic changes at the light and electron microscopic levels. Furthermore, anti-VEGF antibody eyedrops had no significant impact on the wound healing process after corneal epithelial injury or 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 eyedrops seem to be a relatively safe option to treat corneal neovascularization.




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S. H. Byeon, S. C. Lee, S. H. Choi, H.-K. Lee, J. H. Lee, Y. K. Chu, and O. W. Kwon
Vascular Endothelial Growth Factor as an Autocrine Survival Factor for Retinal Pigment Epithelial Cells under Oxidative Stress via the VEGF-R2/PI3K/Akt
Invest. Ophthalmol. Vis. Sci., February 1, 2010; 51(2): 1190 - 1197.
[Abstract] [Full Text] [PDF]


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