Association between CFH, CFB, ARMS2, SERPINF1, VEGFR1 and VEGF polymorphisms and anatomical and functional response to ranibizumab treatment in neovascular age-related macular degeneration

Acta Ophthalmol. 2018 Mar;96(2):e201-e212. doi: 10.1111/aos.13519. Epub 2017 Sep 19.


Purpose: We sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response to ranibizumab in neovascular age-related macular degeneration (AMD).

Methods: A total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from six different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors (gender, smoking habit and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT) and fluid criteria (fluid/no fluid measured by OCT).

Results: Hypertension was the environmental factor with the strongest poor response association with ranibizumab in the anatomical measure after the loading phase (p = 0.0004; OR 3.7; 95% CI, 2.4-5.8) and after 12 months of treatment (p = 10-5 ; OR 2.3; 95% CI, 1.5-3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a good response, while rs12603486 and rs1136287 (SERPINF1) were associated with a poor response. The protective genotype of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048).

Conclusion: All these data suggest that genetics play an important role in treatment response in AMD patients.

Keywords: age-related macular degeneration; choroidal neovascularization; pharmacogenetic study; ranibizumab.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Complement Factor B / genetics
  • Complement Factor H / genetics
  • Eye Proteins / genetics*
  • Female
  • Fluorescein Angiography
  • Genotyping Techniques
  • Humans
  • Intravitreal Injections
  • Male
  • Nerve Growth Factors / genetics
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics
  • Ranibizumab / therapeutic use*
  • Retrospective Studies
  • Serpins / genetics
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Visual Acuity / physiology
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / genetics
  • Wet Macular Degeneration / physiopathology


  • ARMS2 protein, human
  • Angiogenesis Inhibitors
  • Eye Proteins
  • Nerve Growth Factors
  • Proteins
  • Serpins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • complement factor H, human
  • pigment epithelium-derived factor
  • Complement Factor H
  • Vascular Endothelial Growth Factor Receptor-1
  • Complement Factor B
  • Ranibizumab