Predicting non-response to ranibizumab in patients with neovascular age-related macular degeneration

Ophthalmic Epidemiol. 2014 Dec;21(6):347-55. doi: 10.3109/09286586.2014.949010. Epub 2014 Aug 26.


Purpose: 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.

Conclusion: 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.

Keywords: Age-related macular degeneration; anti-VEGF treatment; non-response; prediction model; response prediction.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alleles
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cohort Studies
  • Complement Factor H / genetics
  • Genotype
  • Humans
  • Macular Degeneration / pathology
  • Male
  • Mutant Chimeric Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Proteins / genetics*
  • Ranibizumab
  • Retinal Neovascularization / pathology
  • Retinal Neovascularization / therapy
  • Risk Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics*
  • Visual Acuity
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / genetics*
  • Wet Macular Degeneration / physiopathology
  • White People


  • ARMS2 protein, human
  • Antibodies, Monoclonal, Humanized
  • CFH-CFHL1 protein, human
  • Mutant Chimeric Proteins
  • Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Complement Factor H
  • Ranibizumab