June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Age-related Macular Degeneration (AMD): Understanding the biological contributions of Aging and Sex
Author Affiliations & Notes
  • Christine A. Curcio
    Ophthalmology and Visual Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Christine Curcio Apellis, Code C (Consultant/Contractor), Astellas, Code C (Consultant/Contractor), Boehringer Ingelheim, Code C (Consultant/Contractor), Genentech/ Roche, Code F (Financial Support), Heidelberg Engineering, Code F (Financial Support)
  • Footnotes
    Support  NIH R01EY06109, R01EY029595, EyeSight Foundation of Alabama, Genentech/Roche; Heidelberg Engineering, anonymous donor
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4752. doi:
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      Christine A. Curcio; Age-related Macular Degeneration (AMD): Understanding the biological contributions of Aging and Sex. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4752.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Presentation Description : Aging is the largest risk factor for AMD onset. Fifteen years of managing neovascular AMD with optical coherence tomography (OCT) plus laboratory and observational studies of human eyes provided new insights. The precise layout of retinal cells and choroidal vasculature over the lifespan presents a solvable 4-dimensional puzzle. X,Y, in the retinal image plane: The area of highest known progression risk is small (ETDRS central subfield + inner ring), fovea-centered, and aligned with the distribution of soft drusen and macular xanthophyll pigment. An area conferring independent risk appears first at the ring of high rod density near the arcades. The earliest and most persistent visual dysfunction is delayed rod-mediated dark adaptation (RMDA) next to the fovea where rods are sparse. Z, for biologically distinct and increasingly visible layers: macular soft drusen below the retinal pigment epithelium (RPE) and subretinal drusenoid deposit (SDD), between the RPE and photoreceptors at the rod ring, are the basis of deposit-driven AMD, with distinct end-stages of atrophy and neovascularization (choroidal vs intraretinal, respectively). A model of soft drusen biogenesis involving lipoproteins of intraocular origin blocked from egress to the circulation by failed transport aging Bruch’s membrane (BrM) and choriocapillaris (ChC) is supported. How SDD form is being learned and may involve dysregulated outer retinal lipid cycling. Migration of RPE into the retina, visible as the OCT risk indicator hyperreflective foci, may represent distancing of RPE from ischemic ChC. T, time from eye-tracked OCT and age-series tissue studies: Soft drusen are a clinically visible culmination of lipid accumulation throughout adulthood, paralleling the time course of delayed RMDA, whereas SDD appear in generally older persons. Pathology is worst in the layer where it starts. All are most easily explained if the earliest dysfunction of aging appears in BrM-ChC, shown by multiple lines of laboratory and clinical evidence over decades. If proven, these considerations suggest that AMD is a fundamentally microvascular-metabolic-inflammatory disease of aging, with important molecular commonalities to cardiometabolic disease. The contribution of sex will be assessed in the context of this new information about aging, in reference to population-based studies using OCT-based multimodal imaging.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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