Eccentricity-Dependent Reflectivity Rates-of-Change Across the Retina in Intermediate Age-Related Macular Degeneration

Purpose: The purpose of this study was to characterize reflectivity rates-of-change and eccentricity patterns across all retinal layers and bands in intermediate age-related macular degeneration (iAMD), using topographical optical coherence tomography (OCT) analysis. Methods: This retrospective, longitudinal study included 58 consecutive individuals with iAMD and no progression to late AMD. Linear reflectivity was derived from manually segmented OCT macular cubes (25 × 25 degrees) across 60 × 60 grids and normalized to vitreous reflectivity, for each reflective retinal layer from the retinal nerve fiber layer (RNFL) to Bruch's membrane (BM). This included the outer retinal bands, that is, the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), and the drusen layer (RPE-BM). Grids below large blood vessels, the optic nerve head, and above drusen were excluded. Reflectivity rates-of-change (median, interquartile range [IQR], %/year) and eccentricity patterns were evaluated, then compared with colocalized thickness using regression coefficient ratios. Results: RNFL and ganglion cell layer reflectivity decreased up to -10.2%/year, with para-foveal troughs at 1.5 to 1.6 mm eccentricity. Inner plexiform and outer plexiform layers showed more uniform decreases without eccentricity dependence. In the outer retina, EZ band reflectivity decreased with a parafoveal trough of -11.1%/year at 1.4 mm, whereas ELM band, RPE band, and drusen layer changes were smaller and spatially uniform (within ±3%/year). Reflectivity rates-of-change were up to 15 × [IQR = 1.47-28.53] faster than thickness (P < 0.05), although relationships (R2) were weak. Conclusions: In iAMD, reflectivity changes across all retinal layers, most prominently para-/centrally, and show minimal colocalization with thickness. Faster rates-of-change and distinct spatial profiles support reflectivity as a sensitive biomarker for early disease change over time.