title: Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration.
abstract: Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.
authors.affiliation: Institute of Human Genetics, University of Regensburg, Regensburg, D-93053, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Grassmann
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, D-53127, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Fleckenstein
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1204, United States of America.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.affiliation: Institute of Human Genetics, University of Regensburg, Regensburg, D-93053, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Strunz
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, D-53127, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmitz-Valckenberg
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, D-53127, Germany.
authors.forename: Arno P
authors.initials: AP
authors.lastname: Göbel
authors.affiliation: Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, and Devers Eye Institute, Portland, Oregon 97239, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1204, United States of America.
authors.forename: Rinki
authors.initials: R
authors.lastname: Ratnapriya
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1204, United States of America.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, D-53127, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Holz
authors.affiliation: Institute of Human Genetics, University of Regensburg, Regensburg, D-93053, Germany.
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018450:Disease Progression; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D057092:Geographic Atrophy / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D011506:Proteins / Q000235:genetics
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins