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To capture nonlinear progression in a flexible way, we systematically assess Box-Cox transformations with different transformation parameters<jats:italic>\u03bb<\/jats:italic>. Model evaluation is performed on data collected for two longitudinal, prospective multi-center cohort studies on GA size progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A transformation parameter of<jats:italic>\u03bb<\/jats:italic>=0.45 yielded the best model fit regarding the Akaike information criterion (AIC). When hypertension and hypercholesterolemia were included as risk factors in the model, they showed an association with progression of GA size. The mean estimated age-of-onset in this model was 67.21\u00b16.49 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We provide a comprehensive framework for modeling the course of uni- or bilateral GA size progression in longitudinal observational studies. Specifically, the model allows for age-of-onset estimation, identification of risk factors and prediction of future GA size. 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Data presented here are from the <i>Fundus Autofluorescence in AMD<\/i> (FAM) study (ClinicalTrials.gov Identifier: NCT00393692) and the <i>Directional Spread in Geographic Atrophy<\/i> (DSGA) study (ClinicalTrials.gov Identifier: NCT02051998). The FAM study was approved by the human ethics committees at the University of Bonn and the local Institutional Review Boards and the local ethics committees at the study centers (University of Bonn, University of Heidelberg, University of Leipzig, Ludwig-Maximilians-University Munich, St. Franziskus Hospital M\u00fcnster, University of W\u00fcrzburg). The human ethics committees at the University of Bonn approved the DSGA study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read and approved the submission of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Financial disclosures:S. Schmitz-Valckenberg reports grants from Acucela\/Kubota Vision, personal fees from Apellis, grants and personal fees from Novartis, grants and personal fees from Allergan, grants and personal fees from Bayer, grants and personal fees from Bioeq\/Formycon, grants, personal fees and non-financial support from Carl Zeiss MediTec AG, grants and non-financial support from Centervue, personal fees from Galimedix, grants, personal fees and non-financial support from Heidelberg Engineering, grants from Katairo, non-financial support from Optos, personal fees from Oxurion, outside the submitted work.M. Fleckenstein reports grants, personal fees and non-financial support from Heidelberg Engineering, non-financial support from Zeiss Meditech, grants and non-financial support from Optos, personal fees and grant from Novartis, personal fees from Bayer, grants and personal fees from Genentech, from Roche, outside the submitted work; In addition, Dr. Fleckenstein has a patent US20140303013 A1 pending.F.G. Holz reports grants and personal fees from Acucela, Allergan, Apellis, Bayer, Bioeq\/Formycon, Roche\/Genentech, Geuder, Heidelberg Engineering, ivericbio, Kanghong, Novartis, Zeiss; personal fees from Boehringer-Ingelheim, Grayburg Vision, LinBioscience, Pixium Vision, Stealth BioTherapeutics, Aerie, Oxurion outside the submitted work.M. Schmid reports personal fees from Pixium Vision.The remaining authors have no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"170"}}