Variants in the VEGFA gene and treatment outcome after anti-VEGF treatment for neovascular age-related macular degeneration

Ophthalmology. 2013 Jan;120(1):115-21. doi: 10.1016/j.ophtha.2012.10.006. Epub 2012 Nov 11.


Purpose: 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).

Design: A prospective cohort study.

Participants: 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.

Main outcome measures: 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.

Financial disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Female
  • Genotype
  • Genotyping Techniques
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Ranibizumab
  • Sequence Tagged Sites
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics*
  • Visual Acuity / physiology*
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / genetics
  • Wet Macular Degeneration / physiopathology


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Ranibizumab