Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT

• Published in: Ophthalmology retina Vol. 5; no. 5; p. 396
• Main Authors: Pasricha, Malini Veerappan, Tai, Vincent, Sleiman, Karim, Winter, Katrina, Chiu, Stephanie J, Farsiu, Sina, Stinnett, Sandra S, Lad, Eleonora M, Wong, Wai T, Chew, Emily Y, Toth, Cynthia A
• Format: Journal Article
• Language: English
• Published: United States 01.05.2021
• Subjects: Aged; Aged, 80 and over; Female; Follow-Up Studies; Geographic Atrophy - diagnosis; Geographic Atrophy - etiology; Humans; Macula Lutea - diagnostic imaging; Macular Degeneration - complications; Macular Degeneration - diagnosis; Male; Middle Aged; Prospective Studies; Retinal Pigment Epithelium - diagnostic imaging; Time Factors; Tomography, Optical Coherence - methods; Geographic atrophy; Spectral-domain OCT; Age-Related Eye Disease Study 2; Age-related macular degeneration; Localized precursors
• ISSN: 2468-6530
• DOI: 10.1016/j.oret.2020.12.010

In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset. Retrospective study. Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants. We analyzed longitudinally captured SD OCT images and color photographs from 488 eyes of 488 participants with intermediate AMD at baseline. Sixty-two eyes with sufficient image quality demonstrated new-onset GA on color photographs during study years 2 through 7. The area of new-onset GA and one size-matched control region in the same eye were segmented separately, and corresponding spatial volumes on registered SD OCT images at the GA incident year and at 2, 3, and 4 years previously were defined. Differences in SD OCT features between paired precursor regions were evaluated through matched-pairs analyses. Localized SD OCT features 2 years before GA onset. Compared with paired control regions, GA precursor regions at 2, 3, and 4 years before (n = 54, 33, and 25, respectively) showed greater drusen volume (P = 0.01, P = 0.003, and P = 0.003, respectively). At 2 and 3 years before GA onset, they were associated with the presence of hypertransmission (P < 0.001 and P = 0.03, respectively), hyperreflective foci (P < 0.001 and P = 0.045, respectively), OCT-reflective drusen substructures (P = 0.004 and P = 0.03, respectively), and loss or disruption of the photoreceptor zone, ellipsoid zone, and retinal pigment epithelium (RPE, P < 0.001 and P = 0.005-0.045, respectively). At 4 years before GA onset, precursor regions were associated with photoreceptor zone thinning (P = 0.007) and interdigitation zone loss (P = 0.045). Evolution to GA is heralded by early local photoreceptor changes and drusen accumulation, detectable 4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable 1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials.