September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Histologically guided metrics for semi-automated analysis of fundus autofluorescence (FAF) in aging and age-related macular degeneration (AMD)
Author Affiliations & Notes
  • Kenneth R Sloan
    Department of Computer and Information Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Anna V Zarubina
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Carrie Huisingh
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Fazila Aseem
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
    School of Medicine, Wake Forest University, Winston-Salem, North Carolina, United States
  • Mark Clark
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Gerald McGwin
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
    Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Yuhua Zhang
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
    Department of Biomedical Engineering, University of Alamaba at Birmingham, Birmingham, Alabama, United States
  • Cynthia Owsley
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Christine A Curcio
    Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Kenneth Sloan, Spouse - Genentech (C), Spouse - Janssen Cell Therapy (C), Spouse - Merck (C), Spouse - Novartis (C); Anna Zarubina, None; Carrie Huisingh, None; Fazila Aseem, None; Mark Clark, None; Gerald McGwin, None; Yuhua Zhang, None; Cynthia Owsley, Genentech (F); Christine Curcio, Genentech (C), Janssen Cell Therapy (C), Merck (C), Novartis (C)
  • Footnotes
    Support  NIA R01AG04212; EyeSight Foundation of Alabama; Research to Prevent Blindness; NEI EY06109; R01EY024378
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1618. doi:
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      Kenneth R Sloan, Anna V Zarubina, Carrie Huisingh, Fazila Aseem, Mark Clark, Gerald McGwin, Yuhua Zhang, Cynthia Owsley, Christine A Curcio; Histologically guided metrics for semi-automated analysis of fundus autofluorescence (FAF) in aging and age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2016;57(12):1618.

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

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Abstract

Purpose : The retinal pigment epithelium (RPE) is the major signal source for blue FAF. New histology of human RPE in AMD revealed variable cell morphologies, layer thickening, and re-distribution and loss of AF granules [1-4]. Guided by these findings, we tested whether automated analysis of FAF intensity variation could elucidate RPE health in aging and early AMD.

Methods : The Alabama Study of Early Age-Related Macular Degeneration prospectively tested functional biomarkers of incident AMD at 3 years [5]. Participants (n=544; 410 normal, 134 AMD, via AREDS 9-step scale) underwent multimodal imaging with FAF using a Spectralis without an internal AF reference [6]. In baseline and follow-up images, the vasculature and optic nerve head were masked semi-automatically to reduce variability from non-AF structures. In masked images, we computed standard deviation/ mean intensity (coefficient of variation, CV), previously used for Stargardt disease [7], within the ETDRS grid and sectors (central subfield, C1; inner ring, R3; outer ring; R6). Associations with age and AMD severity were examined by Spearman correlation coefficients (SCC). Changes in FAF metrics between baseline and follow-up were checked with general linear models.

Results : Table 1 shows that at baseline, CV was positively and significantly associated with age in C1, R6, and the whole grid. There was a nominal association of CV with age in R3. CV was positively and significantly associated with AREDS grade in C1, R3, and the whole grid. Table 2 shows that at 3 years, CV increased significantly with time for the entire cohort, for the ETDRS grid and all sectors.

Conclusions : In initial analyses of one histologically informed metric, we find that CV of FAF intensity in ETDRS sectors exhibits biologically plausible features suggestive of strong internal validity. These features include positive associations at baseline with age and AREDS grade, in a regionally specific manner (i.e., central 3 mm where Bruch’s membrane lipids are prominent), and an overall increase, although small, over time. Other metrics are also under consideration.
1. Rudolf. Ophthalmology. 2013;120:821.
2. Ach. IOVS. 2014;55:4832.
3. Ach. IOVS. 2015;56:3242.
4. Zanzottera. IOVS. 2015;56:3253.
5. Owsley. Ophthalmology. 2015;2015.
6. Delori. IOVS. 2011;52:9379.
7. Cideciyan. Hum Mol Genet. 2004;13:525.

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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