A Systematic Review on Retinal Biomarkers to Diagnose Dementia from OCT/OCTA Images

Abstract

Background: Traditional methods for diagnosing dementia are costly, time-consuming, and somewhat invasive. Since the retina shares significant anatomical similarities with the brain, retinal abnormalities detected via optical coherence tomography (OCT) and OCT angiography (OCTA) have been studied as a potential non-invasive diagnostic tool for neurodegenerative disorders; however, the most effective retinal changes remain a mystery to be unraveled in this review.

Objective: This study aims to explore the relationship between retinal abnormalities in OCT/OCTA images and cognitive decline as well as evaluating biomarkers' effectiveness in detecting neurodegenerative diseases.

Methods: A systematic search was conducted on PubMed, Web of Science, and Scopus until December 2022, resulted in 64 papers using agreed search keywords, and inclusion/exclusion criteria.

Results: The superior peripapillary retinal nerve fiber layer (pRNFL) is a trustworthy biomarker to identify most Alzheimer's disease (AD) cases; however, it is inefficient when dealing with mild AD and mild cognitive impairment (MCI). The global pRNFL (pRNFL-G) is another reliable biomarker to discriminate frontotemporal dementia from mild AD and healthy controls (HCs), moderate AD and MCI from HCs, as well as identifing pathological Aβ₄₂/tau in cognitively healthy individuals. Conversely, pRNFL-G fails to realize mild AD and the progression of AD. The average pRNFL thickness variation is considered a viable biomarker to monitor the progression of AD. Finally, the superior and average pRNFL thicknesses are considered consistent for advanced AD but not for early/mild AD.

Conclusions: Retinal changes may indicate dementia, but further research is needed to confirm the most effective biomarkers for early and mild AD.

Keywords: Alzheimer’s disease; dementia; mild cognitive impairment; neurodegenerative disorders; optical coherence tomography; optical coherence tomography angiography; retinal biomarkers.

Fig. 1

Literature review process flowchart.

Fig. 2

Retinal layers in a spectral domain optical coherence tomography b-scan image: unlabeled (top), labelled (bottom).

Fig. 3

Anatomic layers, previous and new optical coherence tomography angiography (OCTA) segmentation names [15]. PR, photoreceptor layer.

Fig. 4

Examples of optical coherence tomography angiography (OCTA) scans: A1) superficial vascular complex (SVC), B1) deep vascular complex (DVC), C1) inner vascular complex (IVC), and their corresponding manual foveal avascular zone (FAZ) segmentation.

Fig. 5

HD Angio Disc mode (optic disc) Report Layout Legend: a) Garway-Heath (GH) map [31]; b) Hemisphere Maps; 2) Angio Retina mode (macular) Report Layout Legend: c, d) Hemisphere and Quadrant Maps [32].

Fig. 6

Microvascular network sections in superficial capillary plexuses (SCP) (adapted from [21]).