Misclassification can explain most apparent regression of age-related macular degeneration: results from multistate models with misclassification

Abstract

PURPOSE: 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.