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Johanna M. Seddon, Robyn Reynolds, Yi Yu, Mark J. Daly, Bernard Rosner; Prediction Risk Modeling for Progression to Advanced Age-Related Macular Degeneration Using Baseline Demographic, Environmental, Genetic and Ocular Variables. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5235.
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To expand and further develop our predictive models for progression to advanced stages of AMD associated with visual loss based on demographic, environmental, genetic and ocular factors (1,2).
In this prospective evaluation of 2,937 individuals, 819 progressed to advanced AMD, including geographic atrophy and neovascular disease, during 12 years of follow-up. Subjects were participants in the Age-Related Eye Disease Study. Covariates included demographic and environmental factors, six variants in five genes, baseline macular drusen size, and presence and type of advanced AMD in one eye at baseline.Cox proportional hazards regression analyses were performed to calculate hazard ratios for progression to advanced AMD. To assess the ability of risk scores to discriminate between progressors and non-progressors, an algorithm was developed and receiver operating characteristic curves and area under the curves (AUC or C statistics) were calculated. To validate the overall model, the total sample was randomly subdivided into a derivation sample and a test sample. Then another model was built on the derivation sample and assessed for calibration and discrimination in the test sample.
In multivariate models, age, smoking, higher body mass index, ARMS2/HTRA1, C3, and two CFH genetic variants were associated with increased risk of progression, and C2 and CFB were associated with decreased risk of progression. Presence of AMD in one eye increased risk in the fellow eye, and increased drusen size increased risk of progression. Both genetic variables and drusen size remained highly predictive of AMD progression when they were mutually adjusted for each other. The AUC for progression at 10 years in the model with genetic factors, drusen size and environmental covariates was 0.915 in the total sample. In the test sample, based on a model estimated from the derivation sample the AUC was 0.908.
Factors reflective of nature and nurture have excellent ability to predict who will develop advanced disease associated with visual loss. These risk scores and progression rates are useful for AMD surveillance and for designing clinical trials.1. JAMA 2007;287:1793-1800.2. IOVS 2009;50:2044-53.
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