Classification and Correlation of SDOCT-visualized Drusen Substructures with Drusen Progression in Non-neovascular AMD

Abstract

 

Purpose

 

Intermediate age-related macular degeneration (AMD) is characterized by drusen in the retinal pigment epithelial (RPE) layer. Multiple studies suggest that drusen contain a variety of immumodulatory molecules, including those in the complement cascade, which may manifest as distinct drusen substructures on spectral domain optical coherence tomography (SDOCT). We performed a prospective, observational clinical study to learn how SDOCT-reflective drusen substructures at baseline predict progression of non-neovascular AMD.

 

Methods

 

Study participants from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT Study with intermediate AMD in one eye at baseline (n=314) were analyzed for presence of drusen substructures. Through review of SDOCT volumes across the macula, substructures at baseline were divided into 4 categories (see Figure 1). Presence of geographic atrophy (GA), total GA area, and visual acuity (VA) were assessed at baseline and year 2. These outcomes were compared between eyes with and without cores/debris at baseline using Fischer exact test and Wilcoxon rank sum test.

 

Results

 

Of 239 study eyes with sufficient image quality and follow-up, 58 (24%) had at least one drusen substructure (min 0, median 0, max 8). Of these, 29 (50%) had type L, 34 (59%) had type H, 11 (19%) had type S, and 12 (21%) had type C. At year 2, 49 eyes had GA. 33% of eyes with substructures (19 of 58) vs. 17% of eyes without substructures (30 of 181) progressed to GA at year 2 (p= 0.014). GA at year 2 may be specifically driven by presence of type H (32% of eyes with type H (11 of 34) vs. 19% of eyes without type H (38 of 205), p=0.071) and type C (67% of eyes with type C (8 of 12) vs. 18% of eyes without type C (41 of 227), p<0.001). Drusen substructures at baseline were not associated with total GA area or VA at baseline or year 2 (all p>0.05).

 

Conclusions

 

Intermediate AMD eyes with drusen substructures at baseline were more likely to have non-central GA at year 2. The presence of drusen cores and/or debris on SDOCT may be associated with development of early GA.  

 

Figure 1. Low-reflective Core (L). High-reflective Core (H). Split Low and High Reflective Core (S). Conical Debris (C).