Zhichao Wu1, Chi D Luu1, Lauren N Ayton1, Jonathan K Goh1, Lucia M Lucci2, William C Hubbard2, Jill L Hageman2, Gregory S Hageman2, Robyn H Guymer3. 1. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia. 2. Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. 3. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia. Electronic address: rh.guymer@unimelb.edu.au.
Abstract
PURPOSE: To characterize the pathological changes preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Longitudinal and cross-sectional retrospective observational study. PARTICIPANTS: A total of 181 participants with intermediate AMD in at least 1 eye (141 unilateral, 40 bilateral) were assessed longitudinally. A total of 230 participants with bilateral intermediate AMD (40 longitudinal participants with an additional 190 participants) were analyzed cross-sectionally. METHODS: Spectral-domain OCT, color fundus photography (CFP), near-infrared reflectance, and fundus autofluorescence imaging were performed in all participants at cross-section and every 3 months for up to 30 months in the longitudinal study. Spectral-domain OCT volume scans were examined for features that portend the development of drusen-associated atrophy, and the topography, prevalence, and risk factors of these features were determined through cross-sectional analysis. MAIN OUTCOME MEASURES: The pathological features on SD-OCT preceding the development of drusen-associated atrophy and the characteristics of these features. RESULTS: Twenty areas from 16 eyes of 16 participants developed drusen-associated atrophy after an average of 20 months (range, 8-30 months). Spectral-domain OCT features unique in these areas included: subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), and development of a hyporeflective wedge-shaped band within the limits of the OPL. These characteristics were termed "nascent geographic atrophy" (nGA), describing features that portend the development of drusen-associated atrophy. Cross-sectional examination of participants with bilateral intermediate AMD revealed that independent risk factors for the presence of nGA included the presence of pigmentary changes (odds ratio [OR], 16.84; 95% confidence interval [CI], 2.42-117.24) and nGA in the fellow eye (OR, 4.15; 95% CI, 1.12-15.34); nGA was present in 21.9% of participants with drusen >125 μm and pigmentary changes in both eyes. CONCLUSIONS: This study identified pathological changes occurring before the development of drusen-associated atrophy using SD-OCT, which we defined as nGA. Although nGA is undetectable on CFP, it is important for determining the risk of future vision loss in AMD and could be used as an earlier surrogate end point in interventional trials targeting the early stages of AMD.
PURPOSE: To characterize the pathological changes preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Longitudinal and cross-sectional retrospective observational study. PARTICIPANTS: A total of 181 participants with intermediate AMD in at least 1 eye (141 unilateral, 40 bilateral) were assessed longitudinally. A total of 230 participants with bilateral intermediate AMD (40 longitudinal participants with an additional 190 participants) were analyzed cross-sectionally. METHODS: Spectral-domain OCT, color fundus photography (CFP), near-infrared reflectance, and fundus autofluorescence imaging were performed in all participants at cross-section and every 3 months for up to 30 months in the longitudinal study. Spectral-domain OCT volume scans were examined for features that portend the development of drusen-associated atrophy, and the topography, prevalence, and risk factors of these features were determined through cross-sectional analysis. MAIN OUTCOME MEASURES: The pathological features on SD-OCT preceding the development of drusen-associated atrophy and the characteristics of these features. RESULTS: Twenty areas from 16 eyes of 16 participants developed drusen-associated atrophy after an average of 20 months (range, 8-30 months). Spectral-domain OCT features unique in these areas included: subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), and development of a hyporeflective wedge-shaped band within the limits of the OPL. These characteristics were termed "nascent geographic atrophy" (nGA), describing features that portend the development of drusen-associated atrophy. Cross-sectional examination of participants with bilateral intermediate AMD revealed that independent risk factors for the presence of nGA included the presence of pigmentary changes (odds ratio [OR], 16.84; 95% confidence interval [CI], 2.42-117.24) and nGA in the fellow eye (OR, 4.15; 95% CI, 1.12-15.34); nGA was present in 21.9% of participants with drusen >125 μm and pigmentary changes in both eyes. CONCLUSIONS: This study identified pathological changes occurring before the development of drusen-associated atrophy using SD-OCT, which we defined as nGA. Although nGA is undetectable on CFP, it is important for determining the risk of future vision loss in AMD and could be used as an earlier surrogate end point in interventional trials targeting the early stages of AMD.
Authors: Zhichao Wu; Chi D Luu; Lauren N Ayton; Jonathan K Goh; Lucia M Lucci; William C Hubbard; Jill L Hageman; Gregory S Hageman; Robyn H Guymer Journal: Invest Ophthalmol Vis Sci Date: 2015-02-12 Impact factor: 4.799
Authors: Maximilian Pfau; Moritz Lindner; Martin Gliem; Julia S Steinberg; Sarah Thiele; Robert P Finger; Monika Fleckenstein; Frank G Holz; Steffen Schmitz-Valckenberg Journal: Eye (Lond) Date: 2018-08-01 Impact factor: 3.775
Authors: Robyn H Guymer; Philip J Rosenfeld; Christine A Curcio; Frank G Holz; Giovanni Staurenghi; K Bailey Freund; Steffen Schmitz-Valckenberg; Janet Sparrow; Richard F Spaide; Adnan Tufail; Usha Chakravarthy; Glenn J Jaffe; Karl Csaky; David Sarraf; Jordi M Monés; Ramin Tadayoni; Juan Grunwald; Ferdinando Bottoni; Sandra Liakopoulos; Daniel Pauleikhoff; Sergio Pagliarini; Emily Y Chew; Francesco Viola; Monika Fleckenstein; Barbara A Blodi; Tock Han Lim; Victor Chong; Jerry Lutty; Alan C Bird; Srinivas R Sadda Journal: Ophthalmology Date: 2019-09-30 Impact factor: 12.079
Authors: Emma C Zanzottera; Jeffrey D Messinger; Thomas Ach; R Theodore Smith; K Bailey Freund; Christine A Curcio Journal: Invest Ophthalmol Vis Sci Date: 2015-05 Impact factor: 4.799
Authors: Yue Yu; Eric M Moult; Siyu Chen; Qiushi Ren; Philip J Rosenfeld; Nadia K Waheed; James G Fujimoto Journal: Biomed Opt Express Date: 2020-08-20 Impact factor: 3.732
Authors: Emma C Zanzottera; Thomas Ach; Carrie Huisingh; Jeffrey D Messinger; Richard F Spaide; Christine A Curcio Journal: Retina Date: 2016-12 Impact factor: 4.256
Authors: Eric M Moult; Nadia K Waheed; Eduardo A Novais; WooJhon Choi; ByungKun Lee; Stefan B Ploner; Emily D Cole; Ricardo N Louzada; Chen D Lu; Philip J Rosenfeld; Jay S Duker; James G Fujimoto Journal: Retina Date: 2016-12 Impact factor: 4.256
Authors: Anna C S Tan; Polina Astroz; Kunal K Dansingani; Jason S Slakter; Lawrence A Yannuzzi; Christine A Curcio; K Bailey Freund Journal: Invest Ophthalmol Vis Sci Date: 2017-04-01 Impact factor: 4.799
Authors: Karl G Csaky; Praveen J Patel; Yasir J Sepah; David G Birch; Diana V Do; Michael S Ip; Robyn H Guymer; Chi D Luu; Shamika Gune; Hugh Lin; Daniela Ferrara Journal: Surv Ophthalmol Date: 2019-01-28 Impact factor: 6.048