Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration

Purpose: Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables in vivo visualization of micro-metric structural markers which differentially associate with normal aging versus age-related macular degener-ation (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging.Design: Prospective cross-sectional study.Participants: A total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects.Methods: Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band.Main Outcome Measures: Qualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (mm).Results: In young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls.Conclusions: Our imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/ hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology Science 2023;3:100277 & COPY; 2023 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).