Detection of Hyporeflective Core Drusen and the Onset of Large Choroidal Hypertransmission Defects in Intermediate...

To investigate the association between hyporeflective core drusen (hypoRCD) and the formation of large choroidal hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration, we used swept-source optical coherence tomography (SS-OCT) imaging and a novel algorithm to detect and quantify hypoRCD before the onset of hyperTDs.

Posthoc subgroup analysis of a prospective cohort study.

Eyes with intermediate age-related macular degeneration enrolled in a prospective SS-OCT imaging study were retrospectively reviewed. SS-OCT angiography scans were obtained at baseline and follow-up. En face images derived from a retinal pigment epithelium (RPE) to Bruch's membrane slab identified hyporeflective cores (hypoRCs) within drusen as dark spots. A sub-RPE slab located 64 to 400 µm beneath Bruch's membrane was used to identify calcified drusen (CaD) based on their characteristic choroidal hypotransmission defects. hypoRCs associated with CaD (hypoRC-CaD) were identified. HypoRCs not associated with CaD were labeled as noncalcified hypoRCD and quantified separately. Large hyperTDs, defined as bright lesions with a greatest linear dimension ≥250 µm on the sub-RPE slab, were graded. A semiautomated algorithm measured the areas of hypoRC-CaD and noncalcified hypoRCD within a 5 mm circle centered on the fovea, and their association with hyperTD formation was analyzed. The risk attributed to CaD with and without hypoRCs was evaluated.

The study included 171 eyes from 121 patients with a median follow-up of 59.1 months (95% CI: 52.0-67.8). Eighty-two eyes developed at least one large hyperTD during follow-up. The total hypoRCD area at the time of hyperTD onset was 0.026 mm² (range: 0-0.349 mm²), compared to 0.015 mm² (range: 0-0.532 mm²) at the final visit in eyes that did not develop hyperTDs. When drusen volume, hyperreflective foci area, CaD area, and total hypoRCD area were studied as risk factors, the hypoRCD area was not a significant predictor of hyperTD onset in the univariable (P = .36) or multivariable (P = .60) Cox regression models.

HypoRCD alone was not predictive of progression to atrophy, but the risk of progression was found to be associated with CaD with or without hyporeflective cores.