Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Association between functional network connectivity, retina structure and microvasculature, and visual performance in patients after thalamic stroke: An exploratory multi-modality study.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmologic symptoms and retinal changes have been increasingly observed following thalamic stroke, and there is mounting evidence indicating distinct alterations occurring in the vision-related functional network. However, the intrinsic correlations between these changes are not yet fully understood. Our objective was to explore the altered patterns of functional network connectivity and retina parameters, and their correlations with visual performance in patients with thalamic stroke. METHODS: We utilized resting-state functional MRI to obtain multi-modular functional connectivity (FC), and optical coherence tomography-angiography to measure various retina parameters, such as the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), superficial vascular complex (SVC), and deep vascular complex. Visual acuity (VA) was used as a metric for visual performance. RESULTS: We included 46 patients with first-ever unilateral thalamic stroke (mean age 59.74 ± 10.02 years, 33 males). Significant associations were found between FC of attention-to-default mode and SVC, RNFL, and GCIPL, as well as between FC of attention-to-visual and RNFL (p < .05). Both RNFL and GCIPL exhibited significant associations with FC of visual-to-visual (p < .05). Only GCIPL showed an association with VA (p = .038). Stratified analysis based on a disease duration of 6 months revealed distinct and significant linking patterns in multi-modular FC and specific retina parameters, with varying correlations with VA in each subgroup. CONCLUSION: These findings provide valuable insight into the neural basis of the associations between brain network dysfunction and impaired visual performance in patients with thalamic stroke. Our novel findings have the potential to inform future targeted and individualized therapies. However, further comprehensive studies are necessary to validate our results.

Correlation between serum biomarkers, brain volume, and retinal neuronal loss in early-onset Alzheimer's disease.

PURPOSE: To compare the peripapillary retinal nerve fiber layer (pRNFL), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) thickness measurement in early-onset Alzheimer's disease (EOAD) and controls using spectral domain optical coherence tomography (SD-OCT). We also assessed the relationship between SD-OCT measurements and cognitive measures, serum biomarkers for Alzheimer's disease (AD), and cerebral microstructural volume. METHODS: pRNFL, RNFL, and GCC thicknesses were measured in 43 EOAD and 42 controls using SD-OCT. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status, magnetic resonance imaging (MRI) tool was used to quantify cerebral microstructural volume, and serum biomarkers were quantified from peripheral blood. RESULTS: EOAD patients had thinner pRNFL (P < 0.001), RNFL (P = 0.008), and GCC (P = 0.018) thicknesses compared to controls after adjusting for multiple factors. pRNFL thickness correlated (P = 0.016) with serum t-tau level. Serum Aß42 (P < 0.05) concentration correlated with RNFL thickness. Importantly, occipital lobe volume (P = 0.010) correlated with GCC thicknesses in EOAD patients. CONCLUSION: Our findings suggest that retinal thickness may be useful markers for assessing neurodegenerative process in EOAD.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Characterization of retinal microvasculature and structure in atrial fibrillation.

Background and objective: Quantitative changes in retinal microvasculature are associated with subclinical cardiac alterations and clinical cardiovascular diseases (i.e., heart failure and coronary artery disease). Nonetheless, very little is known about the retinal vascular and structural changes in patients with atrial fibrillation (AF). Our study aims to characterize the microvasculature and structure of the retina in AF patients and explore their differences in different types of AF (paroxysmal and sustained AF). Methods: This cross-sectional study was conducted at the Departments of Neurology and Cardiology in West China Hospital, Chengdu, China. Individuals aged 40 years or older with a diagnosis of AF were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 40 years or older and without a history of AF, ocular abnormalities/disease, or any significant systemic illness were recruited. The retinal vascular and structural parameters were assessed using swept-source optical coherence tomography (SS-OCT)/SS-OCT angiography. Echocardiographic data of left atrium (LA) diameter were collected in patients with AF at the time of inclusion. Results: A total of 242 eyes of 125 participants [71 men (56.8%); mean (SD) age, 61.98 (8.73) years] with AF and 219 eyes of 111 control participants [53 men (47.7%); mean (SD) age, 62.31 (6.47) years] were analyzed. In our AF cohort, 71 patients with paroxysmal AF and 54 patients with sustained AF (i.e., persistent/permanent AF) were included. Decreased retinal microvascular perfusion (ß coefficient = -0.08; 95% CI, -0.14 to -0.03) and densities (ß coefficient = -1.86; 95% CI, -3.11 to -0.60) in superficial vascular plexus (SVC) were found in the eyes of the participants with AF. In regard to retinal structures, thinner ganglion cell-inner plexiform layer (GCIPL; ß coefficient = -2.34; 95% CI, -4.32 to -0.36) and retinal nerve fiber layer (RNFL) thicknesses (ß coefficient = -0.63; 95% CI, -2.09 to -0.18) were observed in the eyes of the participants with AF. The retinal parameters did not significantly differ between paroxysmal and sustained AF (all P > 0.05). However, significant interactions were observed between LA diameter and AF subtypes with the perfusion and densities in SVC (P < 0.05). Conclusion: This study found that individuals with AF had decreased retinal vascular densities and perfusion in SVC, as well as thinner GCIPL and RNFL thickness compared with age- and sex-matched control participants. The differences of the retinal microvasculature in SVC between paroxysmal and sustained AF depend on the LA diameter. Given our findings, further longitudinal studies with our participants are of interest to investigate the natural history of retinal microvascular and structural changes in individuals across the clinical process of AF and AF subtypes.

The Association of Retinal Microvasculature With Gray Matter Changes and Structural Covariance Network: A Voxel-Based Morphometry Study.

Purpose: Increasing evidence suggests that retinal microvasculature may reflect global cerebral atrophy. However, little is known about the relation of retinal microvasculature with specific brain regions and brain networks. Therefore, we aimed to unravel the association of retinal microvasculature with gray matter changes and structural covariance network using a voxel-based morphometry (VBM) analysis. Methods: One hundred and forty-four volunteers without previously known neurological diseases were recruited from West China Hospital, Sichuan University between April 1, 2021, and December 31, 2021. Retinal microvasculature of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were measured by optical coherence tomography angiography using an automatic segmentation. The VBM and structural covariance network analyses were applied to process brain magnetic resonance imaging (MRI) images. The associations of retinal microvasculature with voxel-wise gray matter volumes and structural covariance network were assessed by linear regression models. Results: In the study, 137 participants (mean age = 59.72 years, 37.2% men) were included for the final analysis. Reduced perfusion in SVP was significantly associated with reduced voxel-wise gray matter volumes of the brain regions including the insula, putamen, occipital, frontal, and temporal lobes, all of which were located in the anterior part of the brain supplied by internal carotid artery, except the occipital lobe. In addition, these regions were also involved in visual processing and cognitive impairment (such as left inferior occipital gyrus, left lingual gyrus, and right parahippocampal gyrus). In regard to the structural covariance, the perfusions in SVP were positively related to the structural covariance of the left lingual gyrus seed with the left middle occipital gyrus, the right middle occipital gyrus, and the left middle frontal gyrus. Conclusions: Poor perfusion in SVP was correlated with reduced voxel-wise gray matter volumes and structural covariance networks in regions related to visual processing and cognitive impairment. It suggests that retinal microvasculature may offer a window to identify aging related cerebral alterations.

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults.

Purpose: We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort. Methods: This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (µm) were measured on the OCT tool. Results: Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults. Conclusion: Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.

Optic Nerve Head Changes Measured by Swept Source Optical Coherence Tomography and Angiography in Patients with Intracranial Hypertension.

INTRODUCTION: This study explored the structural and microvascular changes in the optic nerve head (ONH) of patients with intracranial hypertension (IH) by using swept-source optical coherence tomography (SS-OCT)/OCT angiography (OCTA) and evaluated their association with clinical features. METHODS: The optic disc morphology, peripapillary retinal nerve fiber layer (pRNFL), ganglion cell-inner plexiform layer (GCIPL), and microvascular densities of the nerve fiber layer plexus (NFLP), superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were measured by the SS-OCT/OCTA tool. Frisen score, visual acuity, and intracranial pressure were assessed and recorded in patients with IH. RESULTS: Sixty-one patients with IH and 65 controls were included in this study. Patients with IH showed thicker pRNFL and GCIPL thickness with larger ONH rim area when compared to controls (P < 0.001). Microvascular densities were increased in NFLP while densities were reduced in SVP, ICP, and DCP when compared to controls (P < 0.001). Structural thickness and microvascular densities were significantly correlated with Frisen scores (P < 0.05) and intracranial pressure (P < 0.05) in patients with IH. CONCLUSION: Structural and microvasculature variations of the ONH were found in patients with IH compared to controls. Importantly, we showed that structural and microvascular changes in the ONH were correlated with their Frisen score and intracranial pressure in patients with IH.

Automated evaluation of retinal hyperreflective foci changes in diabetic macular edema patients before and after intravitreal injection.

Purpose: Fast and automated reconstruction of retinal hyperreflective foci (HRF) is of great importance for many eye-related disease understanding. In this paper, we introduced a new automated framework, driven by recent advances in deep learning to automatically extract 12 three-dimensional parameters from the segmented hyperreflective foci in optical coherence tomography (OCT). Methods: Unlike traditional convolutional neural networks, which struggle with long-range feature correlations, we introduce a spatial and channel attention module within the bottleneck layer, integrated into the nnU-Net architecture. Spatial Attention Block aggregates features across spatial locations to capture related features, while Channel Attention Block heightens channel feature contrasts. The proposed model was trained and tested on 162 retinal OCT volumes of patients with diabetic macular edema (DME), yielding robust segmentation outcomes. We further investigate HRF's potential as a biomarker of DME. Results: Results unveil notable discrepancies in the amount and volume of HRF subtypes. In the whole retinal layer (WR), the mean distance from HRF to the retinal pigmented epithelium was significantly reduced after treatment. In WR, the improvement in central macular thickness resulting from intravitreal injection treatment was positively correlated with the mean distance from HRF subtypes to the fovea. Conclusion: Our study demonstrates the applicability of OCT for automated quantification of retinal HRF in DME patients, offering an objective, quantitative approach for clinical and research applications.

APOE ε4 Gene Carriers Demonstrate Reduced Retinal Capillary Densities in Asymptomatic Older Adults.

Early identification of Apolipoprotein E (APOE)-related microvascular pathology will help to study the microangiopathic contribution to Alzheimer's disease and provide a therapeutic target for early intervention. To evaluate the differences in retinal microvasculature parameters between APOE ε4 carriers and non-carriers, asymptomatic older adults aged ≥ 55 years underwent APOE ε4 genotype analysis, neuropsychological examination, and optical coherence tomography angiography (OCTA) imaging. One hundred sixty-three older adults were included in the data analysis. Participants were also defined as cognitively impaired (CI) and non-cognitively impaired (NCI) according to their MoCA scores and educational years. APOE ε4 carriers demonstrated reduced SVC (p = 0.023) compared to APOE ε4 non-carriers. Compared to NCI, CI participants showed reduced SVC density (p = 0.006). In the NCI group, no significant differences (p > 0.05) were observed in the microvascular densities between APOE ε4 carriers and non-carriers. In the CI group, APOE ε4 carriers displayed reduced microvascular densities compared to non-carriers (SVC, p = 0.006; DVC, p = 0.048). We showed that CI and APOE ε4 affect retinal microvasculature in older adults. Quantitative measures of the retinal microvasculature could serve as surrogates for brain microcirculation, providing an opportunity to study microvascular contributions to AD.

Length of Carotid Plaque Impacts Retinal Microvascular Densities of Carotid Artery Stenosis Patients.

Purpose: We explored the retinal microvascular changes in carotid artery stenosis (CAS) and their relationship with carotid plaque morphology. Methods: All participants were diagnosed with carotid artery stenosis by a neurologist. Participants underwent digital subtraction angiography (DSA) and optical coherence tomography angiography (OCTA) imaging. The degree and length of carotid plaque were obtained from the DSA tool. OCTA tool measured the densities in the superficial vascular complex (SVC) and deep vascular complex (DVC). Results: One hundred seventeen patients with CAS patients were included in our data analysis. Eyes with ipsilateral stenosis had reduced retinal microvascular densities when compared to contralateral eyes in patients with CAS (P = 0.016 for SVC, and P = 0.004 for DVC). Microvascular densities correlated with the length of carotid plaque (P = 0.015 for SVC, and P = 0.022 for DVC) in our CAS cohort, although they did not correlate with the degree of carotid plaque (P = 0.264 for SVC, and P = 0.298 for DVC). However, when stratified into moderate and severe subgroups, the degree of carotid plaque correlated with microvascular densities in patients with severe stenosis (P = 0.045 for SVC, and P = 0.038 for DVC). Conclusions: Our study suggests that OCTA can noninvasively detect retinal microvascular changes in patients with CAS and that these changes correlated with the length of the stenosis, but future studies are required to confirm these findings. Translational Relevance: Noninvasive and rapid acquisition of the OCTA image might have the potential to be used as a screening tool to detect microvascular changes in carotid artery stenosis.

Retinal microvascular and structural changes in intracranial hypertension patients correlate with intracranial pressure.

AIMS: We aimed to evaluate the retinal microvascular and structural changes in intracranial hypertension (IH) patients compared with an age- and sex-matched control group. We also investigated the association between clinical parameters and retinal changes in IH patients. METHODS: Intracranial hypertension patients were divided into eyes with papilledema (IH-P) and eyes without papilledema (IH-WP). IH patients underwent lumbar puncture to measure intracranial pressure (ICP); visual acuity was performed using the Snellen chart. Optical coherence tomography (OCT) was used to image and measure the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) while OCT angiography was used to image and measure the superficial vascular complex (SVC) and deep vascular complex (DVC). RESULTS: Intracranial hypertension patients showed reduced microvascular densities and thinner retinal thicknesses compared with the control group (all p < 0.001). Compared with the control group, IH-P showed reduced microvascular densities and thinner retinal thicknesses (all p < 0.001). IH-P showed reduced SVC density and thinner retinal thicknesses when compared with IH-WP (p = 0.008 for SVC, p = 0.025 for RNFL, and p = 0.018 for GCIPL). ICP correlated with the microvascular densities and GCIPL thickness in IH patients (p = 0.025 for GCIPL, p = 0.004 for SVC, and p = 0.002 for DVC). A significant association of ICP with SVC (p = 0.010) and DVC (p = 0.005) densities were also found in IH-P. CONCLUSIONS: Given the observed differences in these noninvasive retinal imaging markers, further research into their clinical utility in IH is needed.

Retinal structural and microvascular changes in myelin oligodendrocyte glycoprotein antibody disease and neuromyelitis optica spectrum disorder: An OCT/OCTA study.

Purpose: To compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Methods: Twenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients. Results: Compared with NMOSD patients, MOGAD patients showed significantly reduced SVP density (P = 0.023). No significant difference (P > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated (P < 0.05) with SVP and ICP densities; in MOGAD patients, SVP correlated with EDSS, duration, reduced visual acuity, and frequency of ON (P < 0.05), while DCP density correlated with disease duration, visual acuity, and frequency of ON. Conclusions: Distinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging via the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.

Association of retinal thickness and microvasculature with cognitive performance and brain volumes in elderly adults.

Background: Retinal structural and microvascular changes can be visualized and have been linked with cognitive decline and brain changes in cerebral age-related disorders. We investigated the association between retinal structural and microvascular changes with cognitive performance and brain volumes in elderly adults. Materials and methods: All participants underwent magnetic resonance imaging (MRI), and a battery of neuropsychological examinations. Macula retinal thicknesses (retinal nerve fiber layer, mRNFL, and ganglion cell-inner plexiform layer, GCIPL) were imaged and measured with swept-source optical coherence tomography (SS-OCT) while Optical Coherence Tomography Angiography (OCTA) imaged and measured the superficial vascular complex (SVC) and deep vascular complex (DVC) of the retina. Results: Out of the 135 participants, 91 (67.41%) were females and none had dementia. After adjusting for risk factors, Shape Trail Test (STT)-A correlated with SVC (P < 0.001), DVC (P = 0.015) and mRNFL (P = 0.013) while STT-B correlated with SVC (P = 0.020) and GCIPL (P = 0.015). mRNFL thickness correlated with Montreal Cognitive Assessment (MoCA) (P = 0.007) and Stroop A (P = 0.030). After adjusting for risk factors and total intracranial volume, SVC correlated with hippocampal volume (P < 0.001). Hippocampal volume correlated (P < 0.05) with most cognitive measures. Stroop B (P < 0.001) and Stroop C (P = 0.020) correlated with white matter volume while Stroop measures and STT-A correlated with gray matter volume (P < 0.05). Conclusion: Our findings suggest that the retinal structure and microvasculature can be useful pointers for cognitive performance, giving a choice for early discovery of decline in cognition and potential early treatment.

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

PURPOSE: To investigate the relationship between retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery (ICA) stenosis. METHODS: Patients with unilateral moderate or severe ICA stenosis(≥50%) from West China hospital, Sichuan university were consecutively and prospectively recruited enrolled in the current study. En face angiograms of the superficial vascular complex (SVC), deep vascular complex (DVC), superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were generated by automatic segmentation using swept-source optical coherence tomography angiography (SS-OCTA) to assess the retinal microvascular perfusion. The cerebral blood flow perfusion on bilateral middle cerebral artery territories measured at the basal ganglia level was assessed by brain computed tomography perfusion (CTP). CTP data were postprocessed to generate maps of different perfusion parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and permeability surface(PS). Relative perfusion parameters (rPS, rCBF, etc.) were calculated as the ratio of the value on the contralateral side to that on the ipsilateral side. RESULTS: In the final analysis, 31 patients were included, of whom 11 patients had a moderate ICA stenosis (50-69%) and 20 with a severe ICA stenosis(≥70%). A total of 55 eyes were analyzed in the study, 27 eyes from the ipsilateral side (ie, side with stenosis) and 28 eyes from the contralateral side. In the patients with ICA stenosis, there was a strong correlation between the retinal microvascular perfusion of SVC with rCBV(B = 0.45, p = 0.03), rCBF(B = 0.26, p = 0.02) and rPS(B = 0.45, p < 0.001) after adjustment for age, sex and vascular risk factors. Similar correlations were also found between microvasculature in SVP and cerebral perfusion changes. There were no any significant associations of microvascular perfusion in both DVC and DCP with CTP parameters(all p > 0.05). CONCLUSIONS: Retinal perfusion changes in superficial vascular layer (SVC and SVP) were correlated with brain hemodynamic compromise in patients with unilateral moderate or severe ICA stenosis(≥50%). Given the limited size of our study, future studies with larger sample size are needed to confirm our findings.

Microvascular Changes in the Retina Correlate with MRI Markers in Patients with Early-Onset Dementia.

Background and Aims: Recent reports suggest that results from imaging retinal microvascular changes with optical coherence tomography angiography (OCTA) in dementia patients reflect cerebral microcirculation changes that occur during dementia. Macula microvascular impairment has been shown in dementia patients compared to controls, but very little is known about its correlation with radiological visual rating scores associated with dementia. We aimed to explore the association between retinal microvasculature and radiological visual rating in early-onset dementia (EOD) patients. Methods: Swept-source OCTA (SS-OCTA) was used to image the retinal microvasculature of all EOD patients. Automated software in the OCTA tool segmented and measured the densities in the superficial vascular plexus (SVC) and deep vascular plexus (DVC) and foveal avascular zone (FAZ) areas. Radiological visual rating scores were evaluated on all MR images. Results: Medial temporal lobe atrophy (MTA) scores significantly correlated with FAZ area (p = 0.031) in EOD patients after adjusting for risk factors. PWMH correlated with SVC (p = 0.032) while DWMH significantly correlated with SVC (p = 0.007), DVC (p = 0.018) and FAZ (p = 0.001) in EOD patients. Discussion: FAZ changes correlated with MTA scores in EOD patients, while retinal microvasculature correlated with white matter hyperintensity. Our report suggests that microvascular changes in the retina may reflect cortical changes in the brain of EOD patients.

Retinal microvasculature and imaging markers of brain frailty in normal aging adults.

Background: The retina and brain share a similar embryologic origin, blood barriers, and microvasculature features. Thus, retinal imaging has been of interest in the aging population to help in the early detection of brain disorders. Imaging evaluation of brain frailty, including brain atrophy and markers of cerebral small vessel disease (CSVD), could reflect brain health in normal aging, but is costly and time-consuming. In this study, we aimed to evaluate the retinal microvasculature and its association with radiological indicators of brain frailty in normal aging adults. Methods: Swept-source optical coherence tomography angiography (SS-OCTA) and 3T-MRI brain scanning were performed on normal aging adults (aged ≥ 50 years). Using a deep learning algorithm, microvascular tortuosity (VT) and fractal dimension parameter (Dbox) were used to evaluate the superficial vascular complex (SVC) and deep vascular complex (DVC) of the retina. MRI markers of brain frailty include brain volumetric measures and CSVD markers that were assessed. Results: Of the 139 normal aging individuals included, the mean age was 59.43 ± 7.31 years, and 64.0% (n = 89) of the participants were females. After adjustment of age, sex, and vascular risk factors, Dbox in the DVC showed a significant association with the presence of lacunes (ß = 0.58, p = 0.007), while VT in the SVC significantly correlated with the score of cerebral deep white matter hyperintensity (ß = 0.31, p = 0.027). No correlations were found between brain volumes and retinal microvasculature changes (P > 0.05). Conclusion: Our report suggests that imaging of the retinal microvasculature may give clues to brain frailty in the aging population.

Alterations of optic tract and retinal structure in patients after thalamic stroke.

Objectives: To investigate the association between degeneration of retinal structure and shrinkage of the optic tract in patients after thalamic stroke. Materials and methods: Patients with unilateral thalamic stroke were included. Structural magnetic resonance imaging (MRI) and optical coherence tomography (OCT) were performed to obtain parameters of optic tract shrinkage (lateral index) and retina structural thickness (retinal nerve fiber layer, RNFL; peripapillary retinal nerve fiber layer, pRNFL; ganglion cell-inner plexiform layer, GCIP), respectively. Visual acuity (VA) examination under illumination was conducted using Snellen charts and then converted to the logarithm of the minimum angle of resolution (LogMAR). We investigated the association between LI and OCT parameters and their relationships with VA. Results: A total of 33 patients and 23 age-sex matched stroke-free healthy controls were enrolled. Patients with thalamic stroke showed altered LI compared with control participants (P = 0.011) and a significantly increased value of LI in the subgroup of disease duration more than 6 months (P = 0.004). In these patients, LI were significantly associated with pRNFL thickness (ß = 0.349, 95% confidence interval [CI]: 0.134-0.564, P = 0.002) after adjusting for confounders (age, sex, hypertension, diabetes, dyslipidemia, and lesion volume). LI and pRNFL were both significantly associated with VA in all patients (LI: ß = -0.275, 95% CI: -0.539 to -0.011, P = 0.041; pRNFL: ß = -0.023, 95% CI: -0.046 to -0.001, P = 0.040) and in subgroup of disease duration more than 6 months (LI: ß = -0.290, 95% CI: -0.469 to -0.111, P = 0.002; pRNFL: ß = -0.041, 95% CI: -0.065 to -0.017, P = 0.003). Conclusion: Shrinkage of the optic tract can be detected in patients with thalamic stroke, especially after 6 months of stroke onset. In these patients, the extent of optic tract atrophy is associated with pRNFL thickness, and they are both related to visual acuity changes.

Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts.

BACKGROUND: As currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes. METHODS: In a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS). RESULTS: In a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21-6.84), multiple lacunes (aOR 3.5, CI 1.29-9.48) and higher total SVD burden (aOR 1.68, CI 1.11-2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up. CONCLUSIONS: Patients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation.

Retinal Thickness Correlates with Cerebral Hemodynamic Changes in Patients with Carotid Artery Stenosis.

Background: We aimed to assess the retinal structural and choroidal changes in carotid artery stenosis (CAS) patients and their association with cerebral hemodynamic changes. Asymptomatic and symptomatic patients with unilateral CAS were enrolled in our study. Material and methods: Swept-source optical coherence tomography (SS-OCT) was used to image the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), while SS-OCT angiography (SS-OCTA) was used to image and measure the choroidal vascular volume (CVV) and choroidal vascular index (CVI). Computed Tomography Perfusion (CTP) was used to assess the cerebral perfusion parameters; relative perfusion (r) was calculated as the ratio of the value on the contralateral side to that on the ipsilateral side. Results: Compared with contralateral eyes, ipsilateral eyes showed significantly thinner RNFL (p < 0.001), GCIPL (p = 0.013) and CVV (p = 0.001). Relative cerebral blood volume (rCBV) showed a significant correlation with RNFL (p < 0.001), GCIPL (p < 0.001) and CVI (p = 0.027), while the relative permeability surface (rPS) correlated with RNFL (p < 0.001) and GCIPL (p < 0.001). Conclusions: Our report suggests that retinal and choroidal changes have the potential to detect hemodynamic changes in CAS patients and could predict the risk of stroke.