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 over 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 4 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 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.
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ABSTRACT: Previous studies regarding the severity of age-related macular degeneration (AMD) in 1 eye and its prognostic implications for the fellow eye have focused on the incidence of neovascular AMD in the fellow eye of participants with neovascular AMD in the other eye. It is unclear to what extent the severity of AMD in 1 eye affects the incidence, progression, and regression of AMD in its fellow eye across the entire range of AMD severity.Jama Ophthalmology 10/2014; 133(2). DOI:10.1001/jamaophthalmol.2014.4252 · 3.83 Impact Factor