Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

Abstract

Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).METHODS. Donor eyes were classified as early to intermediate AMD (n = 25) and agematched controls (n = 54). In high-resolution histology, we assessed BLinD/soft drusen thickness at 836 and 1716 locations in AMD and control eyes, respectively. BLinD volume was estimated using solid geometry in donor eyes, one clinically characterized. RESULTS.BLinD, drusen, type 1 MNV, and fluid occupy the sub-RPE-basal laminar space. BLinD volume in a 3-mm diameter circle may be as much as 0.0315 mm 3 . Osmophilic lipid was more concentrated in BLinD/drusen than SDD. In the fovea, BLinD/drusen was prevalent in AMD eyes; pre-BLinD was prevalent in control eyes. SDD was low in the fovea and high in perifovea, especially in AMD eyes. CONCLUSIONS.Although invisible, BLinD may presage type 1 MNV. BLinD volume approaches the criterion OCT drusen volume of 0.03 mm 3 for AMD progression risk. BLinD culminates years of subfoveal lipid accumulation. SDD is detected relatively late in life, with currently unknown precursors. Deposit topography suggests one outer retinal lipid recycling system serving specialized cone and rod physiology, and its dysregulation in AMD is due to impaired transfer to the circulation.

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium

“…Characteristic extracellular deposits (drusen, subretinal drusenoid deposits) form between photoreceptors and their choroidal and retinal blood supplies. 3 …”

Longitudinal choriocapillaris changes in the presence of reticular pseudodrusen

“…Later, Greferath et al reported the first clinicopathologic correlation of RPD in an eye imaged with OCT during lifetime confirming that RPD represent subretinal deposits that extend through the outer nuclear layer and compromise photoreceptor integrity 4 . Unlike RPD, soft drusen are lipid-rich extracellular material localized between the basal lamina of the RPE and the inner collagenous layer of Bruch’s membrane 5 . The exact pathophysiology of RPD formation and the progressing of outer retinal degeneration spatially associated with RPD lesions are currently subject of intensive research 6 .…”

Hyperreflective foci, OCT progression indicators in age-related macular degeneration, include transdifferentiated retinal pigment epithelium

“…AMD affects vertically integrated cellular layers formed by light-sensing photoreceptors and support cells (retinal pigment epithelium (RPE), choriocapillaris, Müller glia). Characteristic extracellular deposits (drusen, subretinal drusenoid deposits) form between photoreceptors and their choroidal and retinal blood supplies ( 3 ). RPE cells supporting photoreceptors and vessels are central to, and impacted by, both atrophic and neovascular AMD.…”

“…Characteristic extracellular deposits (drusen, subretinal drusenoid deposits) form between photoreceptors and their choroidal and retinal blood supplies. 3 AMD is increasingly understood via clinical optical coherence tomography (OCT).…”