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A pharmacogenetics study to predict outcome in patients receiving anti-VEGF therapy in age related macular degeneration

Authors Kitchens JW, Kassem N, Wood W, Stone TW, Isernhagen R, Wood E, Hancock BA, Radovich M, Waymire J, Li L, Schneider BP

Received 27 October 2012

Accepted for publication 7 March 2013

Published 10 October 2013 Volume 2013:7 Pages 1987—1993

DOI https://doi.org/10.2147/OPTH.S39635

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

John W Kitchens,1,* Nawal Kassem,2,* William Wood,1 Thomas W Stone,1 Rick Isernhagen,1 Edward Wood,1 Brad A Hancock,2 Milan Radovich,2,4 Josh Waymire,4 Lang Li,3,4 Bryan P Schneider2,4

1Ophthalmology, Retina Associates of Kentucky, Lexington, KY; 2Department of Medicine, Divisions of Hematology/Oncology, 3Biostatistics, 4Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA

*
These authors contributed equally

Purpose: To ascertain whether single nucleotide polymorphisms (SNPs) in the Vascular Endothelial Growth factor (VEGFA), Complement Factor H (CFH), and LOC387715 genes could predict outcome to anti-VEGF therapy for patients with age related macular degeneration (AMD).
Methods: Patients with “wet” AMD were identified by chart review. Baseline optical coherence tomography (OCT) and visual acuity (VA) data, and at least 6 months of clinical follow up after 3 initial monthly injections of bevacizumab or ranibizumab were required for inclusion. Based on OCT and VA, patients were categorized into two possible clinical outcomes: (a) responders and (b) non-responders. DNA was extracted from saliva and genotyped for candidate SNPs in the VEGFA, LOC387715, and CFH genes. Clinical outcomes were statistically compared to patient genotypes.
Results: 101 patients were recruited, and one eye from each patient was included in the analysis. 97% of samples were successfully genotyped for all SNPs. We found a statistically significant association between the LOC387715 A69S TT genotype and outcome based on OCT.
Conclusion: Genetic variation may be associated with outcome in patients receiving anti-VEGF therapy.

Keywords: age related macular degeneration, ARMS2, bevacizumab, complement factor H (CFH), LOC387715, ranibizumab, single nucleotide polymorphisms, vascular endothelial growth factor

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