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

Authors Kitchens, Kassem, Wood, Stone, Isernhagen, Wood, Hancock, Radovich, Waymire, Li, Schneider B

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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