Prediction of Age-related Macular Degeneration in the General Population The Three Continent AMD Consortium

Gabriëlle Buitendijk, E Rochtchina, C Myers, Cornelia Duijn, KE Lee, BEK Klein, SM Meuer, PTVM (Paulus) de Jong, EG Holliday, AG Tan, André Uitterlinden, TS Sivakumaran, J Attia, Bert Hofman, P Mitchell, Hans Vingerling, SK Iyengar, Cecile Janssens, JJ Wang, R KleinCaroline Klaver

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies. Design: Three population-based studies: the Rotterdam Study (RS), the Beaver Dam Eye Study (BDES), and the Blue Mountains Eye Study (BMES) from the Three Continent AMD Consortium (3CC). Participants: People (n = 10 106) with gradable fundus photographs, genotype data, and follow-up data without late AMD at baseline. Methods: Features of AMD were graded on fundus photographs using the 3CC AMD severity scale. Associations with known genetic and environmental AMD risk factors were tested using Cox proportional hazard analysis. In the RS, the prediction of AMD was estimated for multivariate models by area under receiver operating characteristic curves (AUCs). The best model was validated in the BDES and BMES, and associations of variables were re-estimated in the pooled data set. Beta coefficients were used to Main Outcome Measures: Incident late AMD determined per visit during a median follow-up period of 11.1 years with a total of 4 to 5 visits. Results: Overall, 363 participants developed incident late AMD, 3378 participants developed early AMD, and 6365 participants remained free of any AMD. The highest AUC was achieved with a model including age, sex, 26 single nucleotide polymorphisms in AMD risk genes, smoking, body mass index, and baseline AMD phenotype. The AUC of this model was 0.88 in the RS, 0.85 in the BDES and BMES at validation, and 0.87 in the pooled analysis. Individuals with low-risk scores had a hazard ratio (HR) of 0.0 Conclusions: Our prediction model is robust and distinguishes well between those who will develop late AMD and those who will not. Estimated risks were lower in these population-based studies than in previous case-control studies. (C) 2013 by the American Academy of Ophthalmology.
Original languageUndefined/Unknown
Pages (from-to)2644-2655
Number of pages12
JournalOphthalmology
Volume120
Issue number12
DOIs
Publication statusPublished - 2013

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