Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of senile dementia. It impairs the quality of life of a person and their family, posing a serious economic and social threat in developed countries. The fact that the diagnosis can only be definitively made post‐mortem, or when the disease is fairly advanced, presents a serious problem if novel therapeutic interventions are to be devised and used early in the course of the disease. There is therefore a pressing need for more sensitive and specific diagnostic tests with which we can detect AD in the preclinical stage. The tau proteins and beta‐amyloid proteins start to accumulate 20 years before the symptoms begin to manifest. Detecting them in the preclinical stage would be a potential breakthrough in the management of AD. A high degree of clinical suspicion is needed to correlate problems in cognition with the changes in the eye, particularly the retina, pupil and ocular movements, so that the disease can be detected early and managed in the prodromal phase. In this systematic review, we ask the question whether the retina can be used to make a specific and early diagnosis of AD.

Oculo‐visual abnormalities in Parkinson's disease: Possible value as biomarkers

“…The eye–brain connection and the development of novel techniques and biomarkers to assess ocular manifestations have already been explored in greater depth in Alzheimer's disease. Indeed, besides more conclusive evidence for the use of OCT for early diagnosis, several additional techniques to monitor ocular manifestations of Alzheimer's have been/are being developed; including assessing the neurovascular unit (oximetry, OCT‐angiography, Doppler‐OCT, dynamic retinal vessel analysis), amyloid aggregation status and phosphorylated tau (hyperspectral imaging, confocal scanning laser ophthalmoscopy of autofluorescent or curcumin‐labelled amyloid, fluorescent ligand eye‐scanning system, fluorescence lifetime imaging ophthalmoscopy), and RGC apoptosis (DARC) . Furthermore, we have only just entered an era of ground‐breaking imaging techniques, with novel developments such as (wide‐field) OCT, fluorescent ligand eye‐scanning system, and fluorescence lifetime imaging ophthalmoscopy.…”

“…Indeed, besides more conclusive evidence for the use of OCT for early diagnosis, [231][232][233] several additional techniques to monitor ocular manifestations of Alzheimer's have been/are being developed; including assessing the neurovascular unit (oximetry, OCT-angiography, Doppler-OCT, dynamic retinal vessel analysis), 232 amyloid aggregation status and phosphorylated tau (hyperspectral imaging, confocal scanning laser ophthalmoscopy of autofluorescent or curcumin-labelled amyloid, fluorescent ligand eye-scanning system, fluorescence lifetime imaging ophthalmoscopy), and RGC apoptosis (DARC). [234][235][236][237][238][239][240][241] Furthermore, we have only just entered an era of groundbreaking imaging techniques, with novel developments such as (wide-field) OCT, fluorescent ligand eyescanning system, and fluorescence lifetime imaging ophthalmoscopy. More applications, for example, identifying specific cell types, are to be expected to further revolutionize research in neurodegenerative disease.…”

Visual Features in Alzheimer’s Disease: From Basic Mechanisms to Clinical Overview

“…Similarly, increased arterial tortuosity has been observed in clinical studies [ 133 ], with standard deviation of vessel width [ 136 ] and amplitude of arterial pulsation [ 126 , 133 , 136 , 137 ]. Moreover, these findings relate to cognitive impairment, disease progression, and reduction in NFL diameter in the superior quadrant [ 21 , 26 , 27 , 138 – 140 ]. Although other studies differ in these conclusions, no significant variations were shown for arteriolar–venular caliber, branching angle, or venular tortuosity in AD patients [ 133 ].…”

Systematic Review on Fractal Dimension of the Retinal Vasculature in Neurodegeneration and Stroke: Assessment of a Potential Biomarker

“…Hence, the retina can be approached as an integral part of the central nervous system. The occurrence of ocular manifestations in neurodegenerative and cerebrovascular pathologies, such as Alzheimer's disease (AD), Parkinson's disease (PD) and stroke, accentuates the strong relationship between the eye and the brain (Archibald et al, 2009;Armstrong, 2015;Lim et al, 2016;Cheung et al, 2017;Mahajan and Votruba, 2017). Retinal changes in particular can present a surrogate for cerebral changes in these disorders.…”