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

Abstract

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, detectable4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials.