title: Predicting non-response to ranibizumab in patients with neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To validate known and determine new predictors of non-response to ranibizumab in patients with neovascular age-related macular degeneration (AMD) and to incorporate these factors into a prediction rule.
  
  
  METHODS
  This multicenter, observational cohort study included 391 patients treated with ranibizumab for neovascular AMD. We performed genetic analysis for single nucleotide polymorphisms in AMD-associated genes and collected questionnaires regarding environmental factors and disease history. The primary outcome was non-response to treatment, defined as a loss of visual acuity ≥30% of letters.
  
  
  RESULTS
  Of the 391 patients, 47 were classified as non-responsive. Independent predictors for non-response were age, baseline visual acuity, diabetes mellitus and accumulation of risk alleles in the CFH, ARMS2 and VEGF-A genes. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval 0.70-0.84). We derived a clinical prediction rule, with possible total risk scores ranging from 0-19 points. The absolute risk of non-response varied from 3-52% between risk score groups.
  
  
  CONCLUSIONS
  This is an important step towards a clinical prediction rule that can aid clinicians in identifying AMD patients with increased likelihood of non-response, and consequently contribute to making shared treatment decisions.
authors.affiliation: Department of Ophthalmology and.
authors.forename: Freekje
authors.initials: F
authors.lastname: van Asten
authors.forename: Maroeska M
authors.initials: MM
authors.lastname: Rovers
authors.forename: Yara T E
authors.initials: YT
authors.lastname: Lechanteur
authors.forename: Dzenita
authors.initials: D
authors.lastname: Smailhodzic
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Muether
authors.forename: John
authors.initials: J
authors.lastname: Chen
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: van der Wilt
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
mesh_terms: D000369:Aged, 80 and over; D000483:Alleles; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000473:pathology; D008297:Male; D050506:Mutant Chimeric Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D000069579:Ranibizumab; D015861:Retinal Neovascularization / Q000473:pathology / Q000628:therapy; D012307:Risk Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D044465:White People
chemical_list: C514392:ARMS2 protein, human; D061067:Antibodies, Monoclonal, Humanized; C517622:CFH-CFHL1 protein, human; D050506:Mutant Chimeric Proteins; D011506:Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D000069579:Ranibizumab
keywords: Age-related macular degeneration; anti-VEGF treatment; non-response; prediction model; response prediction