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Considering New Treatments for Neovascularization

Research on rats may yield a new treatment for this corneal condition.
By RCCL Staff

6/15/2016

Aflibercept may be a better alternative than bevacizumab in regulating the advancement of corneal neovascularization, reports research published online in the journal Cornea.1 Previous studies have investigated whether targeting vascular endothelial growth factor—a key cytokine in the development of blood vessels in both normal and abnormal patients (i.e., in the case of a tumor or in tissues undergoing abnormal angiogenesis)—is a good way to possibly treat this condition. 

Researchers from Tel Aviv University in Israel investigated the effects of aflibercept or bevacizumab administered to Sprague-Dawley rats with induced chemical burns. Thirty-one animals were randomized to receive either subconjunctival injections of 0.08mL aflibercept (25mg/mL), 0.05mL bevacizumab (25mg/mL) or 0.05mL physiologic saline using a 30-G needle applied 1mm distal to the limbus at the 6 o’clock and 12 o’clock positions. Aflibercept is a VEGF-trap molecule that is both known to act as a receptor decoy for all isoforms of VEGF-A and also bind VEGF-B and placental growth factors 1 and 2 to enhance the antiangiogenic response, while bevacizumab has previously been confirmed to inhibit chemically-induced neovascularization via its own action on VEGF-A.2,3 

Degree of corneal neovascularization was evaluated on post-injury days one, three, seven, nine and 13 via corneal photography, with burn area measuring 2mm in diameter and comprising approximately 15% of the total corneal area. Corneal samples were collected on day 21 for histological and flat-mount immunofluorescence analyses. Results in all three groups indicated that neovascular sprouting began at the limbal area on day three following injury and reached maximum intensity around days seven through nine; however, those subjects treated with aflibercept exhibited a significantly smaller relative area of neovascularization than either the control or the bevacizumab groups. Additionally, a difference in the rate of change of the neovascularized area over time between the aflibercept group and both the control and bevacizumab groups was observed, but not between the control and bevacizumab groups, suggesting the latter is not as effective in this application. 

“In conclusion, this suggests that aflibercept may hold promise as an effective modality for use in patients with corneal neovascularization,” the researchers conclude. As such, “further investigation is warranted to determine the efficacy of subconjunctival aflibercept in inducing regression of preformed versus mature corneal vessels, its minimum effective dose and safety profile and other possible modes of application in animals and humans.”  

1. Gal-Or O, Livny E, Sella R, et al. Efficacy of subconjunctival aflibercept versus bevacizumab for preventional of corneal neovascularization in a rat model. 
2. Sener E, Yuksel N, Yildiz DK, et al. The impact of subconjunctivally injected EGF and VEGF inhibitors on experimental corneal neovascularization in rat model. Curr Eye Res. 2011;36:1005-1013.
3. Oner V, Kucukerdonmez C, Akova YA, et al. Topical and subconjunctival bevacizumab for corneal neovascularization in an experimental rat model. Ophthalmic Res. 2012;48:118-123.



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