title: Variants in the VEGFA gene and treatment outcome after anti-VEGF treatment for neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To determine the association of genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  A prospective cohort study.
  
  
  METHODS
  We included 201 consecutive patients receiving anti-VEGF injections for neovascular AMD.
  
  
  METHODS
  Patients were followed over 12 months. They were treated with 3 initial monthly ranibizumab or bevacizumab injections. Thereafter, the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate data analysis was used to determine the role of each tSNP in treatment outcome.
  
  
  METHODS
  The influence of selected VEGFA tSNPs on visual acuity (VA) outcome at 6 months.
  
  
  RESULTS
  Mean baseline VA was 51±17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA from baseline was +6.5±12, +4.4±13.4, and +2.3±14.6 letters at 3, 6, and 12 months, respectively. The tSNP rs3025000 was the only SNP significantly associated (P<1 × 10(-4)) with visual outcome at 6 months with multiple correction. The presence of the T allele (TC or TT genotypes) at this tSNP predicted a better outcome of +7 letters at 6 months compared with the CC genotype. In a subgroup analysis, presence of the T allele predicted a significantly higher chance of the patients belonging to the responder group (gain of ≥5 letters from baseline) after 3, 6, and 12 months treatment (odds ratio, 2.7, 3.5, and 2.4; 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27-4.57, respectively) than any other outcome group.
  
  
  CONCLUSIONS
  Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome at 6 months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at 3, 6, and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective in certain subgroups of patients.
  
  
  BACKGROUND
  The authors have no proprietary or commercial interest in any of the materials discussed in this article.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia. abedifarshad@yahoo.com
authors.forename: Farshad
authors.initials: F
authors.lastname: Abedi
authors.forename: Sanjeewa
authors.initials: S
authors.lastname: Wickremasinghe
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.forename: Enes
authors.initials: E
authors.lastname: Makalic
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schmidt
authors.forename: Sukhpal S
authors.initials: SS
authors.lastname: Sandhu
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000069579:Ranibizumab; D016324:Sequence Tagged Sites; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics*; D014792:Visual Acuity / Q000502:physiology*; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab