A recommended “minimum data set” framework for SD‐OCT retinal image acquisition and analysis from the Atlas of Retinal Imaging in Alzheimer's Study (ARIAS)

Abstract

Introduction We propose a minimum data set framework for the acquisition and analysis of retinal images for the development of retinal Alzheimer's disease (AD) biomarkers. Our goal is to describe methodology that will increase concordance across laboratories, so that the broader research community is able to cross‐validate findings in parallel, accumulate large databases with normative data across the cognitive aging spectrum, and progress the application of this technology from the discovery stage to the validation stage in the search for sensitive and specific retinal biomarkers in AD. Methods The proposed minimum data set framework is based on the Atlas of Retinal Imaging Study (ARIAS), an ongoing, longitudinal, multi‐site observational cohort study. However, the ARIAS protocol has been edited and refined with the expertise of all co‐authors, representing 16 institutions, and research groups from three countries, as a first step to address a pressing need identified by experts in neuroscience, neurology, optometry, and ophthalmology at the Retinal Imaging in Alzheimer's Disease (RIAD) conference, convened by the Alzheimer's Association and held in Washington, DC, in May 2019. Results Our framework delineates specific imaging protocols and methods of analysis for imaging structural changes in retinal neuronal layers, with optional add‐on procedures of fundus autofluorescence to examine beta‐amyloid accumulation and optical coherence tomography angiography to examine AD‐related changes in the retinal vasculature. Discussion This minimum data set represents a first step toward the standardization of retinal imaging data acquisition and analysis in cognitive aging and AD. A standardized approach is essential to move from discovery to validation, and to examine which retinal AD biomarkers may be more sensitive and specific for the different stages of the disease severity spectrum. This approach has worked for other biomarkers in the AD field, such as magnetic resonance imaging; amyloid positron emission tomography; and, more recently, blood proteomics. Potential context of use for retinal AD biomarkers is discussed.

OCTA reveals remodeling of the peripheral capillary free zones in normal aging

“…In our current study, OCTA retinal imaging device from the same vendor (Spectralis HRA + OCT, Heidelberg Engineering, Heidelberg, Germany) was used to image both groups of participants. Comparing retinal vascular metrics from OCTA devices from different vendors at this point in the retinal imaging field is discouraged 31 . Montages of OCTA images can include 10 × 10-degree (3 mm × 3 mm; for our younger participants published previously) 17 and 20 × 20-degree (6 mm × 6 mm) images from the same vendor software.…”

“…Cognitively unimpaired older adults were recruited at Butler Hospital, Providence, RI, as part of the Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS, NCT03862222) and had best corrected visual acuity of at least 20/30 (LogMAR ~ 0.18), Montreal Cognitive Assessment (MoCA) scores of ≥ 26 27 , 28 , and Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS-U) Delayed Memory Index (DMI) scores of ≥ 85 29 , 30 . For all participants, further inclusion criteria involved: 1) absence of systemic diseases such as diabetes, hypertension, cancer or history of cancer; 2) absence of ophthalmic diseases such as diabetic retinopathy, retinal ischemic conditions, glaucoma, and age-related macular degeneration; and 3) absence of usage of retinotoxic drugs such as chloroquine, hydroxychloroquine, and oncologic therapeutics 31 . The estimated sample size of 20 per group (N = 40) was computed with a GPower 3.1 calculator 32 using the following input parameters; effect size (partial eta squared) of 0.28, α of 0.05, power of 0.80, 3 independent variables (sex, vessel type, distance from fovea), and two levels for sex (male, female) and vessel type (arteriole, venule) as done previously 17 .…”

“…We obtained 20 × 20-degree OCTA images consisting of 512 b-scans, 512 A-scans per b-scan, 12 micron spacing between the b-scans and 5 frames averaged per each b-scan location of the central fovea and of paired arterioles and venules with their surrounding capillaries inferior to the fovea (Spectralis HRA + OCT; Eye Explorer version 1.10.4.0; Heidelberg Engineering, Heidelberg, Germany) 31 . The signal quality values of all our OCTA images from the vendor software was at least 20 to ensure good image quality 31 . To ensure independence of sampling, only one eye was selected for the purpose of image analysis based on image signal quality.…”

Development and Validation of the Iranian Neonatal Prematurity Minimum Data Set (IMSPIMDS): A Systematic Review Using Focus Group Discussion and the Delphi Technique

“…Accordingly, designing and performing minimum data set (MDS) in health care organizations and institutions as a basic and essential step of disease information management is necessary and required (27). MDS is defined as a comprehensive, standardized account of the characteristics and needs of a system (28).…”

Alzheimer's team care approach—akin to diabetes—in the development, validation, and population assessment of retinal biomarkers for disease

“…We suggest the need for a major cross‐disciplinary effort in AD biomarker development, with diabetes risk monitoring as a perfect analogy. Multiple organizations such as the American Optometric Association (AOA), American Dental Association (ADA), International Neuropsychological Society (INS), American Neurological Association (ANA), and other patient and professional advocacy groups concerned with chronic brain disorders that affect memory, movement, and mood could strategize together to support working groups across disciplines, to develop and test basic standards, and produce minimum datasets that effectively allow comparison across labs and clinical sites with common imaging platforms, 9 to embrace and test novel innovations as they emerge, to accelerate AD prevention and quality improvement in real‐world care.…”