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Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept

Authors Stewart M

Received 27 April 2012

Accepted for publication 18 May 2012

Published 26 July 2012 Volume 2012:6 Pages 1175—1186

DOI https://doi.org/10.2147/OPTH.S33372

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2


Michael W Stewart

College of Medicine, Mayo Clinic, Jacksonville, FL, USA

Abstract: Age-related macular degeneration (AMD) has become a major public health problem and a leading cause of blindness in industrialized nations. AMD results from the ageing eye's inability to metabolize and dispose completely of photoreceptor outer segments and other waste products. As a result, lipids, particularly apolipoproteins, accumulate within Bruch's membrane, leading to chronic ischemia and inflammation. The subsequent upregulation of inflammatory cytokines and growth factors, including vascular endothelial growth factor (VEGF), induces the growth of neovascular membranes from the choriocapillaris into the subretinal or subretinal pigment epithelium spaces. To counter this, intravitreally administered drugs (pegaptanib, bevacizumab, ranibizumab) that specifically target VEGF have become the standard treatment for exudative AMD. Aflibercept, a recently approved fusion protein, binds to all isoforms of both VEGF-A and placental growth factor with high affinity. Phase III trials showed that monthly or every other month injections of aflibercept prevent vision loss (fewer than 15 letters) in 95% of patients. Additionally, aflibercept injections every 4 or 8 weeks produce average vision gains of 6.9 letters to 10.9 letters, comparable with those achieved with monthly ranibizumab. After one year of regularly administered aflibercept injections, patients required an average of only 4.2 injections during the second year. Aflibercept promises to decrease the injection frequency required for many patients and appears to serve as an effective “salvage” therapy for patients who respond poorly to other anti-VEGF drugs.

Keywords: age-related macular degeneration, choroidal neovascularization, vascular endothelial growth factor, aflibercept, ranibizumab, bevacizumab, VEGF trap

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