Genetic predictive biomarkers of anti-VEGF treatment response in patients with neovascular age-related macular degeneration.

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have proven efficacy at a study-population level, although individual patient responses vary, with most of the patients responding well to anti-VEGF therapies, while a few respond poorly. The pathogenesis of AMD is known to have a genetic component, but it is unclear if any particular genotype can predict response to anti-VEGF therapy. With the advent of less expensive genotyping technology, there have been numerous studies within this area. Here we analyze potential biomarker candidates identified that could be used in a clinical setting to predict response to anti-VEGF treatment of nAMD. We analyze single nucleotide polymorphisms (SNPs) identified from 39 publications. The SNPs that appeared to be of most importance fell into two main groups: those previously associated with AMD pathogenesis and those within the signaling pathway targeted by anti-VEGF therapies. A number of small studies found evidence supporting an association between anti-VEGF treatment response and two SNPs, CFH rs1061170 and VEGFA rs699947, but results from randomized controlled trials found no such association. It is possible that, in the future, the cumulative effect of several high-risk SNPs may prove useful in a clinical setting and that other genetic biomarkers may emerge.

• Authors: Sascha Fauser, George N Lambrou
• Journal: Survey of ophthalmology (Surv Ophthalmol) 2015 Mar-Apr Vol. 60 Issue 2 Pg. 138-52 ISSN: 1879-3304 [Electronic] United States
• PMID: 25596882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• ARMS2 protein, human
• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Genetic Markers
• Proteins
• Vascular Endothelial Growth Factor A
• Bevacizumab
• Ranibizumab

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Bevacizumab
• Genetic Markers
• Humans
• Macular Degeneration (drug therapy, genetics)
• Polymorphism, Single Nucleotide (drug effects)
• Proteins (genetics)
• Ranibizumab
• Vascular Endothelial Growth Factor A (genetics)