Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration

• Type of Material: Article
• Authors: Malini Veerappan, Duke University; Abdul-Karim M. El-Hage-Sleiman, Duke University; Vincent Tai, Duke University; Stephanie J. Chiu, Duke University; Katrina P. Winter, Duke University; Sandra S. Stinnett, Duke University; Thomas S. Hwang, Oregon Health & Science University; G Baker Hubbard, Emory University; Michelle Michelson, Duke University; Randall Gunther, Duke University; Wai T. Wong, National Institute of Health; Emily Y. Chew, Duke University; Cynthia A. Toth, Duke University
• Language: English
• Date: 2016-12-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Academy of Ophthalmology
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ophtha.2016.08.047
• Title of Journal or Parent Work: Ophthalmology (Section 12 EMBASE)
• ISSN: 0014-4169
• Volume: 123
• Issue: 12
• Start Page: 2554
• End Page: 2570
• Grant/Funding Information: The AREDS2 was supported by the National Eye Institute of the National Institutes of Health, Bethesda, Maryland (National Institutes of Health 1R01EY023039 grant).; The following sponsors supported the AREDS2 Ancillary SD OCT Study and had no role in the design or conduct of this research: Genentech, San Francisco, California (research grant); Alcon, Fort Worth, Texas (research grant); and Bioptigen, Morrisville, North Carolina (research grant).; S.J.C.: Grants – National Eye Institute, Genentech, Alcon, and Bioptigen during the conduct of the study; and segmentation and identification of layered structures in images US 20110182517 A1 (patent).; C.A.T.: Royalties – Alcon; Research grants for this study – Alcon, Bioptigen, and Genentech.
• Keywords: Ophthalmology; COMPLEMENT ACTIVATION; IMAGES; PATHOLOGY; SDOCT; MACULOPATHY; Life Sciences & Biomedicine; IDENTIFICATION; EPITHELIUM; Science & Technology; AUTOMATIC SEGMENTATION; HYPERREFLECTIVE FOCI; EYE DISEASE
• Research Categories: Engineering, Biomedical; Health Sciences, Opthamology

Abstract

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.