Optical Coherence Tomography in Alzheimer’s Disease and Other Neurodegenerative Diseases

Abstract

Over the past decade, a surge of evidence has documented various pathological processes in the retina of patients suffering from mild cognitive impairment, Alzheimer’s disease (AD), Parkinson’s disease (PD), and other neurodegenerative diseases. Numerous studies have shown that the retina, a central nervous system tissue formed as a developmental outgrowth of the brain, is profoundly affected by AD. Harboring the earliest detectable disease-specific signs, amyloid β-protein (Aβ) plaques, the retina of AD patients undergoes substantial ganglion cell degeneration, thinning of the retinal nerve fiber layer, and loss of axonal projections in the optic nerve, among other abnormalities. More recent investigations described Aβ plaques in the retina located within sites of neuronal degeneration and occurring in clusters in the mid- and far-periphery of the superior and inferior quadrants, regions that had been previously overlooked. Diverse structural and/or disease-specific changes were also identified in the retina of PD, Huntington’s disease, and multiple sclerosis patients. The pathological relationship between the retina and brain prompted the development of imaging tools designed to noninvasively detect and monitor these signs in living patients. One such tool is optical coherence tomography (OCT), uniquely providing high-resolution two-dimensional cross-sectional imaging and three-dimensional volumetric measurements. As such, OCT emerged as a prominent approach for assessing retinal abnormalities in vivo, and indeed provided multiple parameters that allowed for the distinction between normal aged individuals and patients with neurodegenerative diseases. Beyond the use of retinal optical fundus imaging, which recently allowed for the detection and quantification of amyloid plaques in living AD patients via a wide-field view of the peripheral retina, a major advantage of OCT has been the ability to measure the volumetric changes in specified retinal layers. OCT has proven to be particularly useful in analyzing retinal structural abnormalities consistent with disease pathogenesis. In this review, we provide a summary of OCT findings in the retina of patients with AD and other neurodegenerative diseases. Future studies should explore the combination of imaging early hallmark signs together with structural–functional biomarkers in the accessible retina as a practical means of assessing risk, disease progression, and therapeutic efficacy in these patients.

Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases

“…Furthermore, to emphasize the clinical relevance of this technique, it was designed to be used with widely available clinical imaging devices (Ehler et al, 2015). It has recently been proposed that OCT may be used in various neurodegenerative diseases, due to its capability in measuring volumetric changes of the retina (Doustar et al, 2017). However, given the nature of neurodegenerative diseases, it is paramount that the diagnosis is established at the earliest possible time-point to provide the best prognosis to the patient.…”

Reduced Retinal Thickness Predicts Age-Related Changes in Cognitive Function

“…Prominent visual deficits including contrast sensitivity and poor visual memory performance have been reported in AD patients years before clinical diagnosis, with increasing evidence of pathology at several levels of the visual pathway (Gao et al, 2015). Optical coherence tomography (OCT) has emerged as a non-invasive and readily available approach to observe changes in retinal structure, providing high-resolution cross-sectional images of the macula, and retinal nerve fiber layer (RNFL) (Cheung et al, 2017;Doustar et al, 2017). The RNFL is formed by retinal ganglion cells axons and represents the innermost layer of the retina.…”

Deep Brain Stimulation in Non-motor Symptoms of Neurodegenerative Diseases

“…Recent neuroimaging studies reveal a decreased volume in the olfactory regions of the brain, while neuropathological studies found a high accumulation of α-synuclein, αβ amyloid, and Tau proteins in the olfactory bulb during the early stages of neurodegenerative diseases [47,48]. Something similar can be seen in the optical pathways as well, as there is an increase of visual hallucinations, reduced color recognition, visual acuity problems, and double vision as neurodegeneration progresses [49]. Pain syndromes are frequent as well and are more likely of neuropathic origin.…”