The application of optical coherence tomography angiography in Alzheimer's disease: A systematic review

Abstract

Introduction: Discovering non-invasive and easily acquired biomarkers that are conducive to the accurate diagnosis of dementia is an urgent area of ongoing clinical research. One promising approach is retinal imaging, as there is homology between retinal and cerebral vasculature. Recently, optical coherence tomography angiography (OCT-A) has emerged as a promising new technology for imaging the microvasculature of the retina.

Methods: A systematic review and meta-analysis was conducted to examine the application of OCT-A in dementia.

Results: Fourteen studies assessing OCT-A in preclinical Alzheimer's disease (AD), mild cognitive impairment, or AD were included. Exploratory meta-analyses revealed a significant increase in the foveal avascular zone area and a significant decrease in superficial parafoveal and whole vessel density in AD, although there was significant heterogeneity between studies.

Discussion: Although certain OCT-A metrics may have the potential to serve as biomarkers for AD, the field requires further standardization to allow conclusions to be reached regarding their clinical utility.

Keywords: Alzheimer's disease; dementia; diagnostic tool; foveal avascular zone; mild cognitive impairment; optical coherence tomography angiography; perfusion density; preclinical; retinal imaging; retinal vasculature; vessel density.

FIGURE 1

Regions measured for perfusion or vessel density by included studies compared to the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. A) Illustration of the fundus showing the location of the macula (blue) and optic disc (green) where OCT‐A scans are commonly acquired and an ETDRS grid to compare with B. B) Macular (blue) regions and optic disc (green) regions measured in each study. * indicates studies that used an Optovue machine, † indicates studies that used a Zeiss machine, and ‡ indicates studies that used a Topcon machine. A dotted overlay indicates whole measurements. Dashed lines indicate the use of a regional boundary inconsistent with those of the ETDRS grid. A dotted line indicates that boundary measurements were not described (Bulut et al.). A striped center indicates that FAZ area was subtracted from the outer regions to calculate the boundary. C) A diagram of the anatomical layers of the retina with drawn vascular plexuses in red, currently used and proposed 4‐layer OCT‐A segmentation based on microvasculature (adapted from Campbell et al. with information from Munk et al. ⁴⁷ , ⁴⁸ ). Automatic segmentation of superficial and deep layers by Optovue, Zeiss, and Topcon OCT‐A machines are shown in red, green, and black respectively. DCP, deep capillary plexus; DVC, deep vascular complex; GCL, ganglion cell layer; ICP, intermediate capillary plexus; INL, inner nuclear layer; IPL, inner plexiform layer; NFL, nerve fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer; PR, photoreceptor layers; RPC, radial peripapillary capillaries; RPCP, radial peripapillary capillary plexus; RPE, retinal pigment epithelium; S, superficial; SCP, superficial capillary plexus; SVC, superficial vascular complex; SVP, superficial vascular plexus.

FIGURE 2

Meta‐analysis of foveal avascular zone (FAZ) measurements (mm ² ) for Alzheimer's disease (AD), mild cognitive impairment (MCI), and preclinical AD (preAD) participants versus controls (C) and AD versus MCI. Mean and standard deviation (SD) are included, with 95% confidence intervals (CIs), heterogeneity scores, and overall effect in an inverse variance (IV) random effects model. The green square size represents the weight attributed to each study based on relative sample size. N.B. Results from van de Kreeke et al. are unadjusted and were obtained through personal correspondence with authors.

FIGURE 3

Meta‐analysis of superficial parafoveal and whole vessel density (%) for participants with Alzheimer's disease (AD) and participants with mild cognitive impairment (MCI) versus controls (C). Mean and standard deviation (SD) are included, with 95% confidence intervals (CIs), heterogeneity scores, and overall effect in an inverse variance (IV) random effects model. The green square size represents the weight attributed to each study based on relative sample size.

FIGURE 4

Recommendations for standardization of studies using optical coherence tomography angiography (OCT‐A) to detect changes in the retinal microvasculature in preclinical Alzheimer's disease (AD), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Abbreviations: Aβ+, amyloid beta‐positive; ETDRS, Early Treatment Diabetic Retinopathy Study; MMSE, Mini Mental State Examination; MoCA, Montreal Cognitive Assessment; NIA‐AA, National Institute on Aging and Alzheimer's Association; NINCDS‐ADRDA, National Institute of Neurological, Communicative Disorders and Stroke‐Alzheimer Disease and Related Disorders Association; STROBE, Strengthening the Reporting of Observational Studies in Epidemiology.