title: Predictive value of VEGF A and VEGFR2 polymorphisms in the response to intravitreal ranibizumab treatment for wet AMD.
abstract: BACKGROUND
  To determine whether gene polymorphisms of the vascular endothelial growth factor A (VEGF A) and its receptor (VEGFR) influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration.
  
  
  METHODS
  This prospective cohort study included 94 patients (94 eyes) with exudative age-related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (SUSTAIN). Injections were administered monthly during 3 months to all the patients diagnosed of neovascular AMD; reinjections were made when a patient lost 5 letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness measured by OCT. Genotypes (VEGF A (rs 699947, rs833061) and VEGFR (rs 2071559)) were analyzed using TaqMan probes. Best-corrected visual acuity (BCVA), subjective improvement, and macular thickness measured with OCT values were compared with VEGF A and VEGFR genotypes. Multiple regression analysis was used to assess the statistical significance.
  
  
  RESULTS
  We found statistically significant differences in allelic distribution of VEGF A rs833061 polymorphism in relation with the response to intravitreal ranibizumab regarding to visual acuity improvement [p = 0,.34; OR: 1.619 (1.098-2.386)]. Patients carrying "protector" genotype CC had higher probability of best corrected visual acuity improvement. When we analyzed VEGF A rs699947 polymorphism we found that patients expressing AA genotype had a higher chance of increasing their best corrected visual acuity [p:0,022; OR 1,532 (1,015-2,313)]. We did not find statistically significant differences reagarding VEGFR rs2071559 polymorphism and treatment response.
  
  
  CONCLUSIONS
  Polymorphisms of VEGF A seem to influence the different response to antiangiogenic treatment in patients with AMD in our population, although further investigation is needed to know the mechanisms of this relationship.
authors: Departamento de Oftalmología, Hospital Universitario de Salamanca, Salamanca, Spain, cruzgonzalez.fernando@gmail.com.
authors: Fernando
authors: F
authors: Cruz-Gonzalez
authors: Lucía
authors: L
authors: Cabrillo-Estévez
authors: Gloria
authors: G
authors: López-Valverde
authors: Clara
authors: C
authors: Cieza-Borrella
authors: Emiliano
authors: E
authors: Hernández-Galilea
authors: Rogelio
authors: R
authors: González-Sarmiento
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000069579:Ranibizumab; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / 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; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D000069579:Ranibizumab