Vascular endothelial growth factor gene and the response to anti-vascular endothelial growth factor treatment for choroidal neovascularization in high myopia

Ophthalmology. 2014 Jan;121(1):225-233. doi: 10.1016/j.ophtha.2013.06.043. Epub 2013 Aug 14.


Purpose: To investigate the association between the vascular endothelial growth factor (VEGF) gene polymorphism and the response to anti-VEGF treatment for choroidal neovascularization (CNV) in highly myopic eyes.

Design: Retrospective cohort study.

Participants: A total of 357 unrelated highly myopic Japanese patients with axial lengths ≥26.0 mm in both eyes were eligible, and 83 patients who received anti-VEGF therapy for CNV and could be followed for more than 1 year were included.

Methods: We genotyped a functional single nucleotide polymorphism in the VEGF gene, rs2010963. The associations between the distribution of the rs2010963 genotype and the number of eyes with maintained or improved visual acuity (VA) were analyzed. Furthermore, multivariable logistic regression analysis was performed to adjust for 7 possible prognostic factors, including age, sex, CNV size, CNV location, administration of loading dose, pretreatment VA, and number of additional treatments.

Main outcome measures: The primary end point was maintenance of VA, and secondary end points were progression of chorioretinal atrophy (CRA) and recurrence of CNV.

Results: Mean age and mean axial length were not significantly different among 3 genotypes of rs2010963. The percentage of eyes with maintained or improved VA was significantly higher with the G allele of rs2010963 (P =0.016), and stepwise analysis revealed that both rs2010963 and CNV size were associated with VA maintenance (P =0.040 and 0.033, respectively). The secondary analysis revealed that administration of a loading dose was significantly associated with both CRA progression (P =0.031) and recurrence of CNV (P =0.020), whereas rs2010963 was not.

Conclusions: These results suggest that the VEGF polymorphism influences the VA prognosis in highly myopic eyes with CNV within 1 year after anti-VEGF treatment. This association was still observed after removing its confounding effect through CNV size. The rs2010963 polymorphism was not associated with CNV recurrence or CRA progression, which indicates that these changes are not tied to intrinsic factors and may be controllable by improving treatment methods.

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Aptamers, Nucleotide / therapeutic use
  • Axial Length, Eye / pathology
  • Bevacizumab
  • Choroidal Neovascularization / diagnosis
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / genetics
  • Female
  • Fluorescein Angiography
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myopia, Degenerative / diagnosis
  • Myopia, Degenerative / drug therapy*
  • Myopia, Degenerative / genetics
  • Ophthalmoscopy
  • Pharmacogenetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Ranibizumab
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics*
  • Visual Acuity / drug effects
  • Visual Acuity / physiology


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