Imaging retinal microvascular manifestations of carotid artery disease in older adults: from diagnosis of ocular complications to understanding microvascular contributions to cognitive impairment

Abstract

Carotid artery stenosis (CAS) is a consequence of systemic atherosclerotic disease affecting the aging populations of the Western world. CAS is frequently associated with cognitive impairment. However, the mechanisms contributing to the development of vascular cognitive impairment (VCI) associated with CAS are multifaceted and not fully understood. In addition to embolization and decreased blood flow due to the atherosclerotic lesion in the carotid artery, microcirculatory dysfunction in the cerebral circulation also plays a critical role in CAS-related VCI. To better understand the microvascular contributions to cognitive decline associated with CAS and evaluate microvascular protective effects of therapeutic interventions, it is essential to examine the structural and functional changes of the microvessels in the central nervous system (CNS). However, there are some limitations of in vivo brain vascular imaging modalities. The retinal microvasculature provides a unique opportunity to study pathogenesis of cerebral small vessel disease and VCI, because the cerebral circulation and the retinal circulation share similar anatomy, physiology and embryology. Similar microvascular pathologies may manifest in the brain and the retina, thus ocular examination can be used as a noninvasive screening tool to investigate pathological changes in the CNS associated with CAS. In this review, ocular signs of CAS and the retinal manifestations of CAS-associated microvascular dysfunction are discussed. The advantages and limitation of methods that are capable of imaging the ocular circulation (including funduscopy, fluorescein angiography, Doppler sonography, optical coherence tomography [OCT] and optical coherence tomography angiography [OCTA]) are discussed. The potential use of dynamic retinal vessel analysis (DVA), which allows for direct visualization of neurovascular coupling responses in the CNS, for understanding microvascular contributions to cognitive decline in CAS patients is also considered.

Retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery stenosis

“…Given the homology between the retinal and cerebral microvasculature, concomitant cerebral hemodynamic changes in ICA stenosis might extend to the retina, causing changes in the microvascular network. Similarly, reports using different OCTA machines showed patients with ICA stenosis have significantly decreased superficial vasculature densities compared with controls [25,24]. It suggested the superficial vessels of the retina are sensitive to ischemic injury [24], which are the main blood flow channel and responsible for the arterial circulation of the retina [26][27][28].…”

Increased Susceptibility to Cerebral Microhemorrhages Is Associated With Imaging Signs of Microvascular Degeneration in the Retina in an Insulin-Like Growth Factor 1 Deficient Mouse Model of Accelerated Aging

“…Here we confirm that the effects of adult-onset circulating IGF-1 deficiency phenocopy important aspects of cerebrovascular aging ( Toth et al, 2015b ; Tarantini et al, 2017c ) and demonstrate that increased susceptibility to CMHs in IGF-1 deficient mice is associated with imaging signs of vascular defects in the retina. There has been significant research interest in using the eye to model or predict disease in the brain, and several neurodegenerative or cerebrovascular diseases have measurable ocular manifestations ( Czako et al, 2020 ; Istvan et al, 2021 ). Previous human studies also provide prima facie evidence that retinal microvascular changes (microaneurysms and retinal hemorrhage) together with other imaging and histological signs [Müller cell gliosis, retinal nerve fiber layer (RNFL) thinning] predict a higher risk of subsequent stroke in humans ( Wong et al, 2001a , b ; London et al, 2013 ; Zhao et al, 2020 ).…”

Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases

“…Strokes due to atherosclerosis of a larger artery account for approximately one third of all stroke cases [ 116 ]. For instance, carotid artery atherosclerosis [ 117 , 118 , 119 ] may lead to ischemia, as a result of distal embolization or due to the hypoperfusion of brain tissue supplied by a severely narrowed or occluded vessel [ 116 ]. Strong epidemiological evidence link VDD to the increased risk of cerebrovascular diseases, including ischemic stroke [ 13 , 120 , 121 , 122 , 123 , 124 ].…”