Impact of Subretinal Drusenoid Deposits on Ellipsoid Zone-Related Thickness Metrics

Ellipsoid zone (EZ) attenuation is a widely used endpoint in retinal disease trials and is quantified as the distance between the EZ and retinal pigment epithelium (RPE). This study assessed the impact of subretinal drusenoid deposits (SDDs) on EZ-based quantitative metrics in nonneovascular age-related macular degeneration (AMD).

Spectral-domain optical coherence tomography volumes from 83 eyes (44 patients) with SDDs from the Amish Eye Study were analyzed. A semi-automated deep learning-based segmentation with manual correction delineated the inner EZ, inner RPE, and inner SDD surfaces. Photoreceptor outer segment (POS; EZ-SDD) thickness, SDD thickness, and EZ-RPE thickness were measured within Early Treatment Diabetic Retinopathy Study subfields. The proportional SDD contribution to EZ thickness (SDD/EZ ratio) and longitudinal changes over 2 years were evaluated.

Mean POS and EZ-RPE thickness were 24.4 ± 4.3 µm and 26.3 ± 5.1 µm, respectively. Mean SDD thickness was 1.95 ± 2.5 µm, increasing to 6.75 ± 3.9 µm in SDD-dominant regions. The SDD/EZ ratio averaged 6.9% ± 6.7% and exceeded 10% in 24% of eyes, mainly in the outer macular ring. Over 2 years, POS thickness and EZ-RPE thickness decreased significantly (ΔPOS = -2.59 µm; ΔEZ-RPE = -2.86 µm; P = 0.002, P = 0.006, respectively) with a strong correlation (R2 = 0.79), which weakened in eyes with high SDD burden (R2 = 0.16).

SDDs cause variable inflation of EZ-RPE thickness, particularly perifoveally. While EZ-RPE thinning reflects POS loss, its reliability may decrease with substantial SDDs. POS-specific metrics and SDD/EZ ratios may improve EZ-based endpoints in AMD trials.