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

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.