September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Spectral Domain Optical Coherence Tomography 2-Year Localized Precursors to New Onset Geographic Atrophy in Age-Related Macular Degeneration
Author Affiliations & Notes
  • Malini Veerappan
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Vincent Tai
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Stephanie Chiu
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Katrina Winter
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Abdul-Karim El-Hage-Sleiman
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Eleonora Lad
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Christopher Harrington
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Randall Gunther
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
  • Wai T Wong
    National Eye Institute , National Institutes of Health, Bethesda, Maryland, United States
  • Emily Y Chew
    National Eye Institute , National Institutes of Health, Bethesda, Maryland, United States
  • Cynthia A Toth
    Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States
    Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Malini Veerappan, None; Vincent Tai, None; Stephanie Chiu, Segmentation and identification of layered structures in images (US 20110182517 A1) (P); Katrina Winter, None; Abdul-Karim El-Hage-Sleiman, None; Eleonora Lad, Apellis FILLY (F), Hoffmann La Roche/Genentech (F); Christopher Harrington, None; Randall Gunther, None; Wai Wong, None; Emily Chew, None; Cynthia Toth, Alcon (P), Alcon (F), Bioptigen (F), Genentech (F), NIH EY023039 (F), Physical Sciences Inc (F), Thrombogenics (C)
  • Footnotes
    Support  Genentech (unrestricted research grant), NIH (1R01EY023039 grant), Alcon (research grant) and Bioptigen (research equipment)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3711. doi:
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      Malini Veerappan, Vincent Tai, Stephanie Chiu, Katrina Winter, Abdul-Karim El-Hage-Sleiman, Eleonora Lad, Christopher Harrington, Randall Gunther, Wai T Wong, Emily Y Chew, Cynthia A Toth; Spectral Domain Optical Coherence Tomography 2-Year Localized Precursors to New Onset Geographic Atrophy in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3711.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : There are few structural biomarkers that predict progression to geographic atrophy (GA) in age-related macular degeneration (AMD). Precursors to GA on color fundus photo (CFP) have been identified: large drusen formation and hyperpigmentation, followed by drusen regression and hypopigmentation (Klein et al). Guymer et al reported photoreceptor and RPE changes prior to drusen-associated atrophy on spectral domain optical coherence tomography (SDOCT). In this study, we evaluate the range of features on SDOCT that precede regions of new onset GA.

Methods : Eyes with intermediate AMD in one eye at baseline from participants in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Trial were analyzed. We selected 75 eyes that developed GA on color fundus photo during years 2 through 7 of the study. Using regions of interest (ROIs) of varying diameter, one location of new onset GA per eye was encircled on CFP and registered onto the corresponding SDOCT volume at the GA incident year and at 2 years prior (t-2). ROIs at t-2 were analyzed for qualitative changes in the retina and retinal pigment epithelium (RPE).

Results : Fifty-seven GA precursor (t-2) ROIs were identified, with mean diameter 1.11 mm (SD 0.67). Results are in Table 1. The main findings were photoreceptor and RPE abnormalities on SDOCT. Other notable findings were hyperreflective foci (HRF) above drusen and OCT-reflective drusen substructures (ODS) within drusen. The maximum RPE layer injury was categorized as disrupted in 35/57 (61.4%) of regions, absent in 22/57 (38.6%), and intact in none. Outer plexiform layer (OPL) dipping toward the RPE, a marker of photoreceptor loss, ranged from mild (n=10, 17.5% of regions) to moderate (n=19, 33.3%) to severe (n=8, 14.0%). These outcomes will be compared to non-GA precursor ROIs in the same GA eyes and in different non-GA AMD eyes.

Conclusions : Regions of new onset GA as identified on CFP in AMD eyes are preceded by RPE layer disruption/absence, ellipsoid and interdigitation zone loss, external limiting membrane disruption, OPL layer dipping toward the RPE, increased choroidal signal, and drusen with associated HRF and ODS, all on SDOCT imaging 2 years prior to GA onset. This suggests that the RPE, outer retina and regions above and within drusen are biologically active sites in atrophy pathogenesis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

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