title: Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  Longitudinal and cross-sectional retrospective observational study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia.
authors.forename: Chi D
authors.initials: CD
authors.lastname: Luu
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Ayton
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Goh
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Lucci
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.
authors.forename: William C
authors.initials: WC
authors.lastname: Hubbard
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Hageman
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Hageman
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia. Electronic address: rh.guymer@unimelb.edu.au.
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005451:Fluorescein Angiography; D057092:Geographic Atrophy / Q000175:diagnosis*; D006801:Humans; D008268:Macular Degeneration / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010781:Photography; D015593:Retinal Drusen / Q000175:diagnosis*; D012307:Risk Factors; D012720:Severity of Illness Index; D041623:Tomography, Optical Coherence