Comparing Eye-Level and Site-Specific High-Risk Optical Coherence Tomography Biomarkers Preceding the Onset of Large Hypertransmission Defects.

Abstract

To compare the site-specific optical coherence tomography (OCT) biomarkers that appear before the formation of large hypertransmission defects (hyperTDs) with the eye-level OCT biomarkers that have been found to predict disease progression in eyes with intermediate age-related macular degeneration (iAMD). Retrospective subgroup analysis of a prospective cohort study. A prospectively enrolled cohort of eyes with iAMD imaged with swept-source OCT (SS-OCT) was retrospectively reviewed to identify eyes that developed large hyperTDs. Large hyperTDs were defined as bright lesions with a greatest linear dimension of ≥250 µm on an en face sub-retinal pigment epithelium slab image created using segmentation boundaries positioned 64 to 400 µm below the Bruch's membrane. All visits before the formation of the large hyperTDs were retrospectively reviewed to identify the OCT biomarker at the retinal location where the initial large hyperTD formed. Of 171 eyes, 82 (48%) with iAMD developed at least 1 large hyperTD. At the first visits when the large hyperTD developed, a total of 119 large hyperTDs were detected. Hyperreflective foci (HRF) were the most frequent OCT biomarker at the sites before the formation of hyperTDs (88/119, 74%). Soft drusenoid lesions were the second most frequent biomarker (77/119, 65%); however, 67 of these lesions occurred in conjunction with HRF. Calcified drusen (CaD) were present at 19 of the 119 sites (16%). Of these 19 CaD lesions, 7 contained hyporeflective cores and 11 were associated with HRF. Non-calcified hyporeflective core drusen were present at 16 of the 119 sites (13%), with 3 associated with HRF. Basal laminar deposits were present at 2 of the 119 sites (2%), both of which were associated with HRF. Single cases of a vitelliform lesion and a small hyperTD were also identified before the large hyperTDs. Site-specific analysis revealed that HRF were the most frequent OCT biomarker at the sites before the formation of large hyperTDs. Soft drusenoid lesions and HRF were frequently observed together, consistent with our previous eye-level multivariable analysis, which revealed that drusen volume was not independently predictive of the future formation of large hyperTDs.