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Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

ABSTRACT: Background and purpose: Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers.

Methods: Twenty-one D-CAA mutation carriers (n = 8 presymptomatic, n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of ?1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age.

Results: The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) µm vs. 99 (87-108) µm; P = 0.006]. Both presymptomatic [111 (93-122) µm vs. 131 (123-143) µm; P < 0.001] and symptomatic carriers [119 (95-128) µm vs. 131 (123-143) µm; P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls.

Conclusions: Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression.

SUBMITTER: van Etten ES

PROVIDER: S-EPMC7702135 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

van Etten E S ES de Boer I I Steenmeijer S R SR Al-Nofal M M Wermer M J H MJH Notting I C IC Terwindt G M GM

European journal of neurology 20201005 12

<h4>Background and purpose</h4>Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers.<h4>Methods</h4>Twenty ...[more]

PMID: 32894579

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Project description: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.

Project description:Background and Purpose- Magnetic resonance imaging visible perivascular spaces in the centrum semiovale (CSO-PVS) have been associated with cerebral amyloid angiopathy (CAA).We aimed to further confirm this link by evaluating CSO-PVS volume in pathologically-demonstrated sporadic and genetically-demonstrated hereditary forms of the disease. Methods- We studied a retrospective hospital-based cohort consisting of 63 individuals aged >55 having brain magnetic resonance imaging and pathological assessment of CAA (mean age, 73.6±8.5; 46% female), and a separate cohort consisting of 26 carriers, and 28 noncarriers of the hereditary cerebral hemorrhage with amyloidosis-Dutch type (mean age, 46.7±12.8; 61.1% female). CSO-PVS volume was quantified on a single magnetic resonance imaging slice using a computer-assisted segmentation method and expressed as the relative volume of the intracranial volume in that particular slice (CSO-PVS relative volume). We compared CSO-PVS relative volume (1) between subjects with and without the disease in both cohorts; (2) between non-CAA, CAA without hemorrhage, and CAA with hemorrhage cases in the sporadic CAA cohort. All variables reaching P<0.1 in bivariate analyses were entered in logistic regression models. Results- In both sporadic and Dutch cohorts, cases with CAA had significantly higher CSO-PVS relative volume than cases without (median [IQR]: 3.7% [2.5-5.3] versus 1.8% [1.2-2.4], P<0.0001; 3.8% [0.6-6.2] versus 0.7% [0.4-1.6], P=0.007; respectively). In linear regression models, sporadic CAA was associated with higher CSO-PVS relative volume ( P=0.008). In the sporadic CAA cohort, compared with non-CAA cases, CSO-PVS relative volume was higher in both CAA with hemorrhage and without hemorrhage (4.4% [2.6-6.1] and 3% [2.4-3.6] versus 1.8% [1.2-2.4], P<0.001 and P=0.005, respectively). Higher CSO-PVS relative volume was associated with CAA in regression models, both when hemorrhage was present (odds ratio, 2.63; [95% confidence interval, 1.33-5.18]; P=0.005) and absent (odds ratio, 4.55; [95% confidence interval, 0.98-21.04]; P=0.05). Conclusions- Increased CSO-PVS volume is a consistent magnetic resonance imaging marker of cerebrovascular amyloid deposition and a promising diagnostic tool for sporadic CAA without hemorrhagic manifestations.

Project description:BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2?months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.

Dataset Information

Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

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Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

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