Investigating Subtle Structural Changes in Eyes with Age-Related Macular Degeneration: A Pilot Study Using Ultrahigh-Resolution Optical Coherence Tomography

Abstract

Purpose : The outer retina, including the photoreceptors, retinal pigment epithelium (RPE), and Bruch’s membrane (BM), share a mutualistic relationship that is disrupted in age-related macular degeneration (AMD). We hypothesize that such disruption can be visualized in vivo using ultrahigh-resolution optical coherence tomography (OCT). We present an observational imaging study to identify potential structural markers for AMD progression.

Methods : We developed a high-speed, ultrahigh-resolution spectral-domain OCT prototype instrument for clinical imaging of AMD eyes. The axial resolution is ~2.7µm in tissue, about 2 times finer than existing commercial instruments. We dynamically matched the optical path length of the OCT reference arm to the curvature of the retina in the slow scan direction, extending the effective depth imaging range. Together with improved acquisition speed (128kHz A-scan rate), this new instrument allows rapid scans of multiple OCT volumes for correction of eye motion and improving signal-to-noise, as well as high-density scans that can reveal exquisite outer retinal structure. An exploratory marker, the RPE-BM complex thickness, was measured using B-scans in linear gray scale. Linear scale avoids feature broadening which occurs in standard OCT logarithmic scale used for extending display dynamic range.

Results : To date we have imaged 21 AMD eyes from 16 patients (age 78.1±8.1 years) as well as 11 normal eyes from 11 subjects (age 36.7±22.6 years). Structural B-scans revealed that AMD eyes had abnormalities in outer retina, especially in the region corresponding to the photoreceptor outer segments and rod/cone interdigitation zones. For instance, hyper reflective bands and a loss of distinctive layer boundaries are often characteristic of AMD retina. Representative measurements of RPE-BM thickness are shown.

Conclusions : New ultrahigh-resolution SD-OCT technology promises to be a useful tool for clinical imaging of AMD. Novel biomarkers that focuses on subtle structural changes in the outer retina can improve understanding of pathogenesis and may enable earlier assessment of disease and progression.

This is a 2020 ARVO Annual Meeting abstract.

 

High-density OCT B-scans from healthy (A) and AMD (B-C) eyes indicating disruption of fine outer retinal structures.

 

Subtle spatial variations in PRE-BM thickness can be measured using ultrahigh-resolution OCT as a marker for AMD.