Impact of Drusen Reduction on Quantitative Ellipsoid Zone Integrity Features in Intermediate Age-Related Macular Degeneration

Abstract

Purpose : Ellipsoid zone (EZ) integrity has been identified as an important biomarker for dry age-related macular degeneration (AMD). Questions remain regarding the impact of drusen on the feasibility of measuring overlying EZ integrity - specifically, whether EZ features over drusen may be artifactually attenuated on optical coherence tomography (OCT). If true, one would expect EZ integrity metrics to “improve” as drusen volume decreases, particularly in the absence of the development of geographic atrophy (GA). The purpose of this study was to evaluate the impact of drusen volume reduction on quantitative EZ integrity.

Methods : This was an IRB-approved retrospective longitudinal image analysis study that included patients with intermediate AMD without geographic atrophy (GA) with at least two years follow-up. All SD-OCT scans were analyzed using a machine learning-enhanced multi-layer retinal segmentation platform. EZ and retinal pigmented epithelium (RPE) segmentation were subsequently validated by certified reader review. Central macular (i.e., the 2 mm fovea-centered subfield) percentage of total EZ attenuation (EZ-RPE thickness = 0 μm) and partial EZ attenuation (EZ-RPE thickness ≤ 20μm) were evaluated. Reduction in drusen volume was defined as a reduction in the sub-RPE compartment volume by 20% or more over 2 years. Eyes were assessed for improvement, stability, or worsening of EZ integrity based on change in EZ attenuation (5% change threshold).

Results : Fifty-six eyes of 56 patients were identified that demonstrated significant reduction in drusen within the central 2 mm over 2 years. Following drusen reduction, 69.6% (n = 39) of these eyes maintained stable EZ integrity at year 2 (mean absolute change in total EZ attenuation in the central 2 mm: 0.05%), 28.6% (n = 16) experienced worsening EZ integrity (mean absolute change: 24.7%), and only 1.8% (n = 1) demonstrated improved EZ integrity (mean absolute change: -9.7%).

Conclusions : Most eyes that experience drusen reduction exhibit either stability or worsening of EZ integrity measures on SD-OCT. EZ integrity improvement following a reduction in drusen volume is uncommon. Given the lack of improvement with drusen reduction, these findings suggest that EZ integrity changes overlying drusen are most likely pathologic, reflecting the overall local impact of AMD on the photoreceptors.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.