Comparison of scattered hypocyanescent spots in age-related macular degeneration and healthy aging using late phase indocyanine green imaging

Abstract

Purpose : Age-related scattered hypocyanescent spots on late phase indocyanine green imaging (ASHS-LIA) have been associated with lipid accumulation (PMID35314773) in age-related macular degeneration (AMD). In this study, we expand upon our preliminary characterization of ASHS-LIA (PMID36115884) and evaluate the size and distribution of these hypocyanescent spots.

Methods : ASHS-LIA was identified using both conventional and adaptive optics enhanced indocyanine green images (ICG and AO-ICG, respectively), from which 12 eyes from 8 patients with ASHS-LIA were selected for further analysis (7 eyes with non-neovascular AMD and 5 eyes from healthy aged controls). Quantitative analysis performed included measurements of retinal pigment epithelial (RPE) cell spacing in controls, and the size of individual hypocyanescent spots and area of retinal coverage in both AMD and controls.

Results : ASHS-LIA was present in 39% of subjects >50 years of age compared to 0% in subjects <50 (n=226 eyes from 119 patients total) and was highly symmetric between eyes. In controls, RPE spacing was similar in hypocyanescent spots compared to normally-cyanescent areas (p=0.71, 3000 RPE cells from 5 eyes). Whereas ASHS-LIA was confined to the macula in controls, the retinal coverage of ASHS-LIA was greatly expanded by >6X in AMD (AMD 97±27mm², control 15±7mm², mean±SD; p<0.01, 12 eyes). In addition, the average diameter of individual hypocyanescent spots increased in AMD (AMD 548±121µm, control 404±82µm, p<0.01, 72 spots from 12 eyes). Longitudinal ICG imaging in AMD showed that both the retinal coverage and pattern of ASHS-LIA were stable over the course of study, despite retinal changes observed due to AMD progression (4 eyes followed for up to 3 years). In one eye which developed reticular pseudodrusen (RPD) between visits, 88% of the RPD lesions identified were spatially coincident with hypocyanescent spots.

Conclusions : The expanded spot size and retinal coverage of ASHS-LIA in AMD highlights the possibility for widespread lipid accumulation beyond what is expected for healthy aging and may serve as an early indicator for determining AMD onset and progression. The hypocyanescent spots appear to arise from reduced uptake of ICG into RPE (PMID27564519) consistent with a sub-RPE origin for ASHS-LIA. Late phase ICG may provide unique insights into the aging process of human eye.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.