Soft Drusen Volume in AMD Parallels Macular Pigment Optical Density Distribution in Healthy Eyes

Researchers evaluate hypotheses about drusen biogenesis.

Normalized soft drusen volume in eyes with age-related macular degeneration (AMD) parallels macular pigment optical density (MPOD) distribution in healthy eyes, explains a study published in Investigative Ophthalmology & Visual Science.

Researchers conducted a prospective study that sought to refine estimates of soft drusen abundance in eyes with AMD and evaluate hypotheses about drusen biogenesis, the report says. The study involved, first, the identification of distribution and growth rates of soft drusen in eyes with AMD in optical coherence tomography (OCT) volumes by human observers and, subsequently, their analysis with computer assistance. 

Researchers performed imaging on a total of 62 eyes from 44 patients for periods of up to 78 months. The researchers also revisited published histologic data for macular cone densities (n=12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n=31).

The study’s results were compared with retinal features with similar topographies, such as cone density and macular pigment. It found that, in the central Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas, soft drusen volume per unit volume at baseline is 24.6-fold higher than in outer rings and 2.3-fold higher than in inner rings, and that it grows most prominently in the ETDRS subfield. It also found that, for cone density in donor eyes, corresponding ratios are 13.3-fold and 5.1-fold higher.

The researchers say that existing data on drusen volume support the present study’s metric for AMD risk assessment and clinical trial outcome measure. The study’s strengths include the comprehensive quantification of drusen volume, height, and area within ETDRS subfields through the use of human experts; full 3D drusen segmentation; and careful attention to drusen regression to find the peak of growth. Another strength was the study’s comparison to high-quality datasets for the spatial distribution of cones and MPOD under a novel hypothesis.

Study limitations include its small sample size and the absence of some measurements, including axial length in participants, which meant the lateral scale of the OCT images could not be corrected.

“Deposits other than soft drusen were not included and should be addressed in future studies to test the specificity of topographic effects,” the study explains. “Ideally, drusen volume, cone density, and macular pigment can all be measured in the same genotyped patients; imaging technology to allow such a study now exists and needs to be assembled in one place.”


Pollreisz A, Reiter GS, Bogunovic H, et al. Topographic distribution and progression of soft drusen volume in age-related macular degeneration implicate neurobiology of fovea. Invest Ophthalmol Vis Sci. 2021;62(2):26. doi:10.1167/iovs.62.2.26.