Retinal imaging in Alzheimer’s disease

Abstract

Identifying biomarkers of Alzheimer’s disease (AD) will accelerate the understanding of its pathophysiology, facilitate screening and risk stratification, and aid in developing new therapies. Developments in non-invasive retinal imaging technologies, including optical coherence tomography (OCT), OCT angiography and digital retinal photography, have provided a means to study neuronal and vascular structures in the retina in people with AD. Both qualitative and quantitative measurements from these retinal imaging technologies (eg, thinning of peripapillary retinal nerve fibre layer, inner retinal layer, and choroidal layer, reduced capillary density, abnormal vasodilatory response) have been shown to be associated with cognitive function impairment and risk of AD. The development of computer algorithms for respective retinal imaging methods has further enhanced the potential of retinal imaging as a viable tool for rapid, early detection and screening of AD. In this review, we present an update of current retinal imaging techniques and their potential applications in AD research. We also discuss the newer retinal imaging techniques and future directions in this expanding field.

Decreased Vessel Density in Retinal Capillary Plexus and Thinner Ganglion Cell Complex Associated With Cognitive Impairment

“…Collectively, studies to date have not shown a clear association between the RCP and cognitive impairment using OCTA ( Cheung et al, 2021 ; Rifai et al, 2021 ). Our findings showed that the vessel densities in the deep RCP, but not in the superficial RCP, were significantly associated with cognitive impairment.…”

“…Numerous studies using OCT have shown that a relatively thinner ganglion cell complex (GCC) or retinal nerve fiber layer (RNFL) was associated with cognitive impairment ( Cheung et al, 2015 ; Jones-Odeh and Hammond, 2015 ; Ko et al, 2018 ; Ito et al, 2020 ). However, only case-control and hospital-based studies using OCTA have investigated the vascular alternations in patients with AD using OCTA ( Zhang et al, 2020 ; Cheung et al, 2021 ; Peng et al, 2021 ). Findings from those studies were inconsistent and the effects of important sub-categorizations (i.e., sex, diabetes, hypertension) remain unknown ( Rifai et al, 2021 ).…”

Hypertensive eye disease

“…[127][128][129] These studies provide further support on the importance of microvascular pathophysiological pathways underlying cognitive impairment and dementia, and the potential use of retinal fundus photography for screening and risk stratification of neuro-cognitive disorders. 130 2.8 Relationship of hypertensive retinopathy with coronary heart disease and heart failure Prospective population-based studies have also demonstrated that various hypertensive retinopathy signs are associated with development of clinical CVD events such as coronary artery disease and heart failure (Table 3). 114,[131][132][133][134][135] In the ARIC study, patients with retinal HMA were also three times more likely to develop congestive heart failure than those without retinopathy, even after controlling for CVD risk factors.…”

Retinal Biomarkers for Alzheimer Disease: The Facts and the Future

“…Choroidal thinning in a cognitively normal patient compared to a patient with Alzheimer disease is demonstrated in (D) and (E), respectively (red arrows delineate the thickness of the choroid). Reproduced with permission from Ref 75 …”