Spectral Domain Optical Coherence Tomography 2-Year Localized Precursors to New Onset Geographic Atrophy in Age-Related Macular Degeneration

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.