title: Role of vascular endothelial growth factor polymorphisms in the treatment success in patients with wet age-related macular degeneration.
abstract: OBJECTIVE
  Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial.
  
  
  METHODS
  All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms.
  
  
  METHODS
  Mean change in visual acuity at the end of the treatment period.
  
  
  RESULTS
  The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation.
  
  
  CONCLUSIONS
  The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Agnes
authors.initials: A
authors.lastname: Boltz
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiß
authors.forename: Jost B
authors.initials: JB
authors.lastname: Jonas
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.forename: Florian
authors.initials: F
authors.lastname: Rensch
authors.forename: Martin
authors.initials: M
authors.lastname: Weger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Garhöfer
authors.forename: Sophie
authors.initials: S
authors.lastname: Frantal
authors.forename: Yosuf
authors.initials: Y
authors.lastname: El-Shabrawi
authors.forename: Leopold
authors.initials: L
authors.lastname: Schmetterer
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D015331:Cohort Studies; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007429:Intraocular Pressure; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D041623:Tomography, Optical Coherence; 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