Optical coherence tomography-based assessment of retinal vascular pathology in cerebral small vessel disease

Abstract

Background 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. 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. Methods We 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. Results Among 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 (r s = − 0.5) and with CSF-levels of Chitinase 3 like 1 protein (r s = − 0.6), zona occludens 1 protein (r s = − 0.5) and GFAP (r s = − 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). Conclusions In 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.

Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review

“…The median number of CSVD patients per study was 262 (range 24–4395) and the median number of controls per study was 814 (range 20–10158). We identified 10 reports using fundus photography [ 21 – 30 ], one study using OCT [ 52 ], one using OCTA [ 59 ], and one combining OCT and OCTA [ 51 ]. We found no report leveraging VF assessment, FA or ERG to investigate sporadic CSVD.…”

“…A single large study [ 26 ] reported higher prevalence among CSVD patients (compared to healthy controls) of RNFL wedge-shaped defects on fundus photography, a semi-quantitative marker of focal nerve fiber damage [ 69 ]. Regarding OCT imaging, one study [ 51 ] reported no associations with retinal measurements, while another [ 52 ] reported increased arteriolar thickness, quantified as Mean Wall Thickness (MWT) or Wall-to-Lumen Ratio (WLR), among CSVD patients compared to controls. The latter report also identified an association between arteriolar WLR and WMH severity on MRI, as well as with select cerebrospinal fluid biomarkers.…”

Structural retinal changes in cerebral small vessel disease

“…The strengths of this study include the thorough screening for concurrent neurological or ocular comorbidities, the use of high-resolution MRI, a complete ophthalmic assessment, the use of state-of-the-art high-resolution SD-OCT imaging including novel read-outs corrected for ocular anatomy such as MRW and the use of standardized and published automated image analysis for both MRI and OCT. To date, this study is the first to investigate structural retinal changes considering all layers assessed by OCT in patients with CSVD after few studies assessed single-layer structural changes or structural and flow changes within the retinal vasculature 38 , 42 – 44 . The limitations of our study include foremost its relatively small sample size.…”

Changes of the retinal and choroidal vasculature in cerebral small vessel disease

“…Wang et al 25 recently reported a vessel density reduction in the superficial retinal capillary plexus in CSVD patients but did not consider any choroidal parameters either. Abdelhak et al 26 used structural OCT data to assess the retinal arterioles in individuals with stroke secondary to sporadic CSVD. They identified an increase in ratio between wall and lumen ratio in patients with CSVD, supporting that the retinal vasculature is altered www.nature.com/scientificreports/ in CSVD.…”