title: Misclassification can explain most apparent regression of age-related macular degeneration: results from multistate models with misclassification.
abstract: OBJECTIVE
  To investigate the impact of misclassification of age-related macular degeneration (AMD) on the baseline intensity and estimated effects of age, sex, and the Y402H variant in the complement factor H (CFH) gene on incidence, progression, and regression of AMD.
  
  
  METHODS
  The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in the city and township of Beaver Dam, Wisconsin, performed examinations every 5 years during a 20-year period (1988-1990 through 2008-2010). Study participants (N = 4379) aged 43 to 86 years at the baseline examination had retinal photographs taken at baseline and up to four subsequent examinations. Multistate models with misclassification in continuous time were used to model the effects of age, sex, and CFH genotype on incidence, progression, and regression of AMD and mortality.
  
  
  RESULTS
  After accounting for AMD misclassification, the occurrence of any AMD regression was rare (1%-4%), while it was relatively common (14%-21%) in models that do not account for misclassification. Failure to account for misclassification attenuated estimated age effects on incidence and progression to moderately severe early AMD and attenuated estimated CFH effects on incidence and progressions to moderately severe and severe early AMD.
  
  
  CONCLUSIONS
  Apparent regression of AMD can largely, if not completely, be explained by misclassification. Estimated age effects on incidence and progression to moderately severe early AMD and estimated CFH effects on incidence and progressions to moderately severe and severe early AMD were attenuated in multistate models that did not account for misclassification.
authors.affiliation: Department of Biostatistics and Medical Informatics and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gangnon
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lee
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.forename: Theru A
authors.initials: TA
authors.lastname: Sivakumaran
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017242:Complement Factor H / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000145:classification* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D014922:Wisconsin / Q000453:epidemiology
chemical_list: D017242:Complement Factor H
keywords: CFH; age-related macular degeneration; epidemiology