Topographic distribution and progression of soft drusen in age-related macular degeneration (AMD) implicate foveal biology

Abstract

Purpose : Longitudinal studies using color fundus photography show focal high risk for progression to late AMD for drusen in the central 1 mm diameter (progression within 10 years, odds ratio=26.5; PMID 17198852). Using optical coherence tomography we investigated the distribution of soft drusen in the macular area in eyes with AMD and their topography-dependent growth rates over time.

Methods : Patients with early and intermediate AMD were examined in a 3-monthly interval. Macular 6x6 mm volume scans were acquired at each visit and soft drusen (dome-shaped, moderate homogeneous reflectivity) were marked manually on each eligible B-scan. Segmentation used a machine learning algorithm. Drusen volume, maximum height, and area covered were calculated for the central millimeter of the fovea (central region), as well as the area within rings with inner and outer radius 1 to 3 mm (inner region) and 3 to 6 mm (outer region) centered on the fovea. Mixed model ANOVAs were calculated to investigate topographic differences in soft drusen load, as well as growth rates for each area.

Results : 62 eyes of 44 patients were analyzed with a follow-up time of up to 78 months, resulting in 494 acquired measurements. Initial mean soft drusen volume was 32.69±41.83 nl/mm² for central, 14.22±16.27 nl/mm² for inner and 1.34±2.58 nl/mm² for outer regions, respectively. The area occupied by soft drusen at baseline was 43±31% for central, 24±20% for inner and 4±5.1% for outer regions, respectively. A significant difference of soft drusen load among the three regions was found (all p<0.01). Covered soft drusen area also revealed a significant difference between all areas (all p<0.001). Soft drusen volume grew 9.08±10.57 nl/mm²/year for the central, 3.74±3.95 nl/mm²/year for inner and 0.36±0.85 nl/mm²/year for outer ring with significant differences between all zones (all p<0.01). Growth in drusen area also showed significant differences between all regions (all p<0.01; 7±7.3%/year for central; 4±4.4%/year for inner and 1±1.4%/year for outer).

Conclusions : Soft drusen load is highest at the central 1 mm diameter and rapidly decreases with increasing eccentricity. Soft drusen growth rates are 2.5 to 25-fold higher in the central 1 mm compared to more eccentric areas, indicating a more rapid accumulation of lipoprotein-derived debris. This distribution resembles that of foveal cones and supporting Müller glia.

This is a 2020 ARVO Annual Meeting abstract.