PMID- 27793356
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20220331
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Print)
IS  - 0161-6420 (Linking)
VI  - 123
IP  - 12
DP  - 2016 Dec
TI  - Optical Coherence Tomography Reflective Drusen Substructures Predict Progression 
      to Geographic Atrophy in Age-related Macular Degeneration.
PG  - 2554-2570
LID - S0161-6420(16)31094-6 [pii]
LID - 10.1016/j.ophtha.2016.08.047 [doi]
AB  - PURPOSE: 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. DESIGN: Retrospective analysis in a prospective study. 
      PARTICIPANTS: 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. METHODS: 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. MAIN 
      OUTCOME MEASURES: Preatrophy SD OCT changes and GA, central GA, and choroidal 
      neovascularization (CNV) from color photographs. RESULTS: 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). CONCLUSIONS: 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.
CI  - Copyright (c) 2016 American Academy of Ophthalmology. All rights reserved.
FAU - Veerappan, Malini
AU  - Veerappan M
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina. 
      Electronic address: malini.veerappan@dm.duke.edu.
FAU - El-Hage-Sleiman, Abdul-Karim M
AU  - El-Hage-Sleiman AM
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Tai, Vincent
AU  - Tai V
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Chiu, Stephanie J
AU  - Chiu SJ
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Winter, Katrina P
AU  - Winter KP
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Stinnett, Sandra S
AU  - Stinnett SS
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Hwang, Thomas S
AU  - Hwang TS
AD  - Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
FAU - Hubbard, G Baker 3rd
AU  - Hubbard GB 3rd
AD  - Emory Eye Center, Emory University, Atlanta, Georgia.
FAU - Michelson, Michelle
AU  - Michelson M
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Gunther, Randall
AU  - Gunther R
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina.
FAU - Wong, Wai T
AU  - Wong WT
AD  - National Eye Institute, National Institute of Health, Bethesda, Maryland.
FAU - Chew, Emily Y
AU  - Chew EY
AD  - National Eye Institute, National Institute of Health, Bethesda, Maryland.
FAU - Toth, Cynthia A
AU  - Toth CA
AD  - Duke Eye Center, Duke University Medical Center, Durham, North Carolina; 
      Department of Biomedical Engineering, Duke University, Durham, North Carolina.
CN  - Age-related Eye Disease Study 2 Ancillary Spectral Domain Optical Coherence 
      Tomography Study Group
LA  - eng
GR  - R01 EY023039/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161025
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Choroidal Neovascularization/pathology
MH  - Cross-Sectional Studies
MH  - Disease Progression
MH  - Female
MH  - Fluorescein Angiography
MH  - Geographic Atrophy/*diagnosis
MH  - Humans
MH  - Macular Degeneration/pathology
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Retinal Drusen/*diagnosis
MH  - Retinal Pigment Epithelium/pathology
MH  - Retrospective Studies
MH  - Tomography, Optical Coherence/*methods
PMC - PMC5125946
MID - NIHMS815007
FIR - Toth, Cynthia A
IR  - Toth CA
FIR - Wong, Wai
IR  - Wong W
FIR - Hwang, Thomas
IR  - Hwang T
FIR - Hubbard, G Baker
IR  - Hubbard GB
FIR - Srivastava, Sunil
IR  - Srivastava S
FIR - McCall, Michelle
IR  - McCall M
FIR - Winter, Katrina
IR  - Winter K
FIR - Sarin, Neeru
IR  - Sarin N
FIR - Hall, Katherine
IR  - Hall K
FIR - McCollum, Patti
IR  - McCollum P
FIR - Curtis, Linda
IR  - Curtis L
FIR - Schuman, Stefanie
IR  - Schuman S
FIR - Chiu, Stephanie J
IR  - Chiu SJ
FIR - Farsiu, Sina
IR  - Farsiu S
FIR - Tai, Vincent
IR  - Tai V
FIR - Sevilla, Monica
IR  - Sevilla M
FIR - Harrington, Christopher
IR  - Harrington C
FIR - Gunther, Randall
IR  - Gunther R
FIR - Tran-Viet, Du
IR  - Tran-Viet D
FIR - Folgar, Francisco
IR  - Folgar F
FIR - Yuan, Eric
IR  - Yuan E
FIR - Clemons, Traci
IR  - Clemons T
FIR - Harrington, Molly
IR  - Harrington M
FIR - Chew, Emily
IR  - Chew E
EDAT- 2016/10/30 06:00
MHDA- 2017/06/27 06:00
PMCR- 2017/12/01
CRDT- 2016/10/30 06:00
PHST- 2016/03/10 00:00 [received]
PHST- 2016/08/21 00:00 [revised]
PHST- 2016/08/29 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
PHST- 2016/10/30 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - S0161-6420(16)31094-6 [pii]
AID - 10.1016/j.ophtha.2016.08.047 [doi]
PST - ppublish
SO  - Ophthalmology. 2016 Dec;123(12):2554-2570. doi: 10.1016/j.ophtha.2016.08.047. 
      Epub 2016 Oct 25.