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 r...

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Bibliographic Details
Published in:Survey of ophthalmology 2015-03, Vol.60 (2), p.138-152
Main Authors: Fauser, Sascha, MD, Lambrou, George N., MD, PhD
Format: Article
Language:English
Subjects:
age-related macular degeneration
Angiogenesis Inhibitors - therapeutic use
anti-VEGF
Antibodies, Monoclonal, Humanized - therapeutic use
Bevacizumab
biomarker
Genetic Markers
genetics
Humans
Macular Degeneration - drug therapy
Macular Degeneration - genetics
Ophthalmology
Polymorphism, Single Nucleotide - drug effects
Proteins - genetics
Ranibizumab
single nucleotide polymorphisms
Vascular Endothelial Growth Factor A - genetics
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Summary: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.
ISSN:0039-6257
1879-3304
DOI:10.1016/j.survophthal.2014.11.002