Abstract
BackgroundCerebral small vessel disease (CSVD) is a disorder of brain vasculature that causes various structural changes in the brain parenchyma, and is associated with various clinical symptoms such as cognitive impairment and gait disorders. Structural changes of brain arterioles cannot be visualized with routine imaging techniques in vivo. However, optical coherence tomography (OCT) is thought to be a “window to the brain”. Thus, retinal vessel parameters may correlate with CSVD characteristic brain lesions and cerebrospinal fluid biomarkers (CSF) of the neuropathological processes in CSVD like endothelial damage, microglial activation and neuroaxonal damage.MethodsWe applied OCT-based assessment of retinal vessels, magnetic resonance imaging (MRI), and CSF biomarker analysis in a monocentric prospective cohort of 24 patients with sporadic CSVD related stroke and cognitive impairment. MRI lesions were defined according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Biomarkers were assessed using commercially available ELISA kits. Owing to the unavailability of an age-matched control-group lacking MRI-characteristics of CSVD, we compared the retinal vessel parameters in CSVD patients (73.8 ± 8.5 years) with a younger group of healthy controls (51.0 ± 16.0 years) by using an age- and sex-adjusted multiple linear regression analysis model.ResultsAmong the parameters measured with OCT, the Wall to Lumen Ratio (WLR) but not Mean Wall Thickness (MWT) of the superior branch of the retinal artery correlated significantly with the volume of white matter hyperintensities on MRI (rs = − 0.5) and with CSF-levels of Chitinase 3 like 1 protein (rs = − 0.6), zona occludens 1 protein (rs = − 0.5) and GFAP (rs = − 0.4). MWT and WLR were higher in CSVD than in controls (28.9 μm vs. 23.9 μm, p = 0.001 and 0.32 vs. 0.25, p = 0.001).ConclusionsIn this exploratory study, WLR correlated with the volume of white matter hyperintensities, and markers of vascular integrity, microglial activation, and neuroaxonal damage in CSVD. Further prospective studies should clarify whether retinal vessel parameters and CSF biomarkers may serve to monitor the natural course and treatment effects in clinical studies on CSVD.
Highlights
Cerebral small vessel disease (CSVD) is a common cause of stroke and dementia in elderly individuals with poorly managed cardiovascular risk factors [28]
We focused on 1) zonula occludens-1 (ZO-1), a novel marker of blood-brain barrier disruption that is often associated with glial pathology in CSVD (A [8, 29].), 2) glial fibrillary acidic protein (GFAP) as a marker of astrogliosis [37], 3) phosphorylated neurofilament heavy chain as a marker of neuroaxonal damage [36], and 4) chitinase-3-like-1 protein (CHI3L1, alias YKL40) that reflects microglial/ macrophage activation [3, 5, 21]
Clinical features Between 2015 and 2017, we included 104 patients with sporadic CSVD related stroke and cognitive impairment that presented to our outpatient clinic
Summary
Cerebral small vessel disease (CSVD) is a common cause of stroke and dementia in elderly individuals with poorly managed cardiovascular risk factors [28]. While magnetic resonance imaging (MRI) can capture the end results, such as white matter hyperintensities (WMH), the underlying pathophysiological mechanisms, and especially changes in small cerebral vessels, remain unexplored in in vivo studies [42, 43]. Similarities between the retinal vessels and small cerebral vessels are numerous and have been described extensively [24]. The employed retinal fundus imaging analysis may not have assessed all aspects of retinal vessel changes: the previous studies mainly assessed total vessel diameters and presented the arteriole to venule ratio, but did not report the thickness of the wall or the lumen diameter of the retinal arterioles [15, 44]. Cerebral small vessel disease (CSVD) is a disorder of brain vasculature that causes various structural changes in the brain parenchyma, and is associated with various clinical symptoms such as cognitive impairment and gait disorders. Retinal vessel parameters may correlate with CSVD characteristic brain lesions and cerebrospinal fluid biomarkers (CSF) of the neuropathological processes in CSVD like endothelial damage, microglial activation and neuroaxonal damage
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