title: Risk assessment model for development of advanced age-related macular degeneration.
abstract: OBJECTIVE
  To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors.
  
  
  METHODS
  We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial.
  
  
  RESULTS
  The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component.
  
  
  CONCLUSIONS
  We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239, USA. kleinm@ohsu.edu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Francis
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Sara C
authors.initials: SC
authors.lastname: Hamon
authors.forename: Traci E
authors.initials: TE
authors.lastname: Clemons
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D003175:Complement C2 / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008962:Models, Theoretical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011506:Proteins / Q000235:genetics; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D014792:Visual Acuity / Q000502:physiology
chemical_list: C514392:ARMS2 protein, human; D001057:Apolipoproteins E; C493495:CFH protein, human; D003175:Complement C2; D003176:Complement C3; D011506:Proteins; D017242:Complement Factor H