Association of drusen substructure findings on SD-OCT with abnormal drusen volumes and progression to choroidal neovascularization in the AREDS2 Ancillary Study

Abstract

Purpose: To evaluate spectral domain optical coherence tomography (SDOCT) drusen substructures for association with drusen volume and progression to choroidal neovascularization (CNV)

Methods: Eyes with intermediate age related macular degeneration (AMD) from the multi-center prospective Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study were analyzed for presence of drusen substructures at baseline. Through qualitative SDOCT grading, substructures were divided into four types: low reflectivity core (L), high reflectivity core (H), split low and high reflectivity core (S), and conical debris (C). After semi-automated SDOCT segmentation, drusen volume within a 5-mm macular field was measured at baseline and year 2. Presence of CNV was assessed at year 2. Outcomes were compared using Wilcoxon rank sum and Fisher exact test.

Results: Of 314 baseline study eyes, 273 had SDOCT grading and CNV outcomes available. 226 had both baseline and year 2 drusen volume measurements. Eyes with any substructures were associated with greater drusen volume at baseline (0.094±0.115 mm³ vs. 0.067±0.168 mm³, p<0.001) and year 2. L-type, H-type, and S-type were correlated with higher drusen volume at baseline (L: 0.104±0.119 mm³ vs. 0.070±0.160 mm³ (p<0.001); H: 0.094±0.104 mm³ vs. 0.070±0.164 mm³ (p<0.001); S: 0.148±0.155 mm³vs. 0.070±0.155 (p<0.001)) and year 2. C-type did not correlate with drusen volume. At year 2, 75 eyes had significant increase in drusen volume. 44% of eyes with any drusen substructures (28 of 63) vs. 29% of eyes without substructures (47 of 163) had significant increase in drusen volume over 2 years (p=0.028). No individual substructure types were associated with drusen volume change. 36 of 273 developed CNV by year 2, but there was no difference in frequency of CNV between eyes with any substructures (14%) and eyes without (13%).

Conclusions: Drusen substructure presence may be associated with larger drusen volumes in patients with intermediate AMD. L and W type substructures may indicate a risk for both increased drusen volume and progression from intermediate AMD to CNV.