The Macular Burden of Calcified Drusen and the Onset of Large Choroidal Hypertransmission Defects in Intermediate AMD

This study used en face swept-source optical coherence tomography (SS-OCT) imaging to follow eyes with intermediate age-related macular degeneration (iAMD) in the presence and absence of calcified drusen (CaD) to determine if the presence and size of CaD increased the risk of forming large choroidal hypertransmission defects (hyperTDs).

Post hoc subgroup analysis of a prospective cohort study.

Eyes with iAMD were enrolled in a prospective SS-OCT study, and the onset of large hyperTDs was retrospectively analyzed. Imaging was performed using 6 × 6 mm SS-OCT angiography (SS-OCTA) scans at baseline and follow-up. Large hyperTDs were defined as bright lesions ≥250 µm in greatest linear dimension (GLD) on en face sub-retinal pigment epithelium (subRPE) slabs positioned 64 to 400 µm beneath Bruch's membrane (BM). CaD were identified as drusen with heterogeneous internal reflectivity projecting choroidal hypotransmission defects (hypoTDs) on the same subRPE slabs. CaD were distinguished from hyperreflective foci (HRF) by analyzing corresponding B-scans. Two independent graders used a semiautomated algorithm to refine CaD outlines and reach consensus, with disagreements adjudicated by a senior grader. CaD area, HRF area, and drusen volume were measured within 5-mm fovea-centered circles.

Median follow-up time for the 171 eyes from 121 patients followed in this study was 59.1 months (95% CI: 52.0-67.8 months), and 82 eyes developed at least one large hyperTD during follow-up. The mean baseline CaD area measurement was 0.037 mm² [range: 0-0.567 mm²] in eyes that developed hyperTDs, while in eyes that did not, it was 0.008 mm² [range: 0-0.360 mm²] (P = .01). Drusen volume, HRF area, and CaD area were predictors for hyperTD onset when considered alone, but only HRF area (P < .001) and CaD area (P =.008) remained significant predictors for hyperTD onset when using a multivariable Cox regression analysis. Regardless of area, the presence of any CaD increased the risk of hyperTD formation (P < .001).

In a multivariable Cox regression analysis, the area measurements of CaD and HRF in eyes with iAMD were significant predictors of hyperTD onset, and the presence of any CaD increased the risk of hyperTD formation.