Subretinal Drusenoid Deposits and Soft Drusen

Abstract

Purpose: Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks, and associated systemic diseases.Methods: One hundred and twenty-six subjects with AMD were classified as SDD (with or without soft drusen) or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke.Results: There were 62 subjects with SDD and 64 non-SDD subjects, of whom 51 had CVD or stroke. SDD correlated significantly with lower mean serum high-density lipoprotein (61 ± 18 vs. 69 ± 22 mg/dL, P = 0.038, t-test), CVD and stroke (34 of 51 SDD, P = 0.001, chi square), ARMS2 risk allele (P = 0.019, chi square), but not with CFH risk allele (P = 0.66). Non-SDD (drusen only) correlated/trended with APOE2 (P = 0.032) and CETP (P = 0.072) risk alleles (chi square). Multivariate independent risks for SDD were CVD and stroke (P = 0.008) and ARMS2 homozygous risk (P = 0.038).Conclusion: Subjects with subretinal drusenoid deposits and non-SDD subjects have distinct systemic associations and serum and genetic risks. Subretinal drusenoid deposits are associated with CVD and stroke, ARMS2 risk, and lower high-density lipoprotein; non-SDDs are associated with higher high-density lipoprotein, CFH risk, and two lipid risk genes. These and other distinct associations suggest that these lesions are markers for distinct diseases.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank

“…Recent scientific investigations have been devoted to exploring the subretinal drusenoid deposit as a critical factor linking AMD and ASCVD. In a study conducted by Thomson et al,52 subretinal drusenoid deposits were found to have a robust association with CHD and stroke, whereas no such association was observed for drusen. A cross-sectional study of 200 well-characterized intermediate patients with AMD also suggested that specific high-risk vascular diseases were even more strongly associated with subretinal drusenoid deposits than drusen 53.…”

Insights into human health from phenome- and genome-wide analyses of UK Biobank retinal optical coherence tomography phenotypes

“…From a cardiometabolic perspective, while a large body of evidence supports the value of retinal microvasculature metrics from fundus photography (27,30,(71)(72)(73) in determining cardiometabolic risk, few publications examine the associations between different layers from retinal OCT data and cardiovascular events and/or risk factors. A recent study in a small cohort identified that subretinal drusenoid deposits, one of the pathways to advanced AMD, are associated with cardiovascular disease and stroke (74). Several other studies have similarly identified associations between AMD and risk of heart failure (75) and cardiometabolic disease (76).…”

Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health

“…The incident analyses also corroborated these findings showing that a thinner PS layer is associated with future incident cardiometabolic, renal, and pulmonary disease, suggesting that individuals with thinner PS layers already have some existing undiagnosed preclinical cardiometabolic or pulmonary disease (e.g., prediabetes and metabolic disease) that makes them at higher risk for becoming diagnosed with incident disease. A recent study in a small cohort identified that subretinal drusenoid deposits, one of the pathways to advanced AMD, are associated with cardiovascular disease and stroke ( 39 ). Several other studies have similarly identified associations between AMD and risk of heart failure ( 40 ) and cardiometabolic disease ( 41 ).…”