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

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 Schneider<sup>2,4

1</sup>Ophthalmology, 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