title: Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration.
abstract: Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression.
  
  
  
  Retrospective analysis in a prospective study.
  
  
  
  Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study.
  
  
  
  Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye.
  
  
  
  Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs.
  
  
  
  Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001-0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002-0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02-0.03) and (2) development of preatrophy changes at years 2 and 3 within the region (P = 0.008-0.05).
  
  
  
  Optical coherence tomography-reflective drusen substructures are optical coherence tomography-based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography-reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina. Electronic address: malini.veerappan@dm.duke.edu.
authors: Malini
authors: M
authors: Veerappan
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Abdul-Karim M
authors: AM
authors: El-Hage-Sleiman
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Vincent
authors: V
authors: Tai
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Stephanie J
authors: SJ
authors: Chiu
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Katrina P
authors: KP
authors: Winter
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Sandra S
authors: SS
authors: Stinnett
authors: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
authors: Thomas S
authors: TS
authors: Hwang
authors: Emory Eye Center, Emory University, Atlanta, Georgia.
authors: G Baker
authors: GB
authors: Hubbard
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Michelle
authors: M
authors: Michelson
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
authors: Randall
authors: R
authors: Gunther
authors: National Eye Institute, National Institute of Health, Bethesda, Maryland.
authors: Wai T
authors: WT
authors: Wong
authors: National Eye Institute, National Institute of Health, Bethesda, Maryland.
authors: Emily Y
authors: EY
authors: Chew
authors: Duke Eye Center, Duke University Medical Center, Durham, North Carolina; Department of Biomedical Engineering, Duke University, Durham, North Carolina.
authors: Cynthia A
authors: CA
authors: Toth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000473:pathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D057092:Geographic Atrophy / Q000175:diagnosis*; D006801:Humans; D008268:Macular Degeneration / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015593:Retinal Drusen / Q000175:diagnosis*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence / Q000379:methods*