Biomarkers In Multiple Sclerosis Research Articles

The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis.

High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease. Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue. Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map. HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons. HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.

A comment on the paper ‘Biomarkers in Multiple Sclerosis’ by Sapko et al.

A comment on the paper ‘Biomarkers in Multiple Sclerosis’ by Sapko et al.

A comment on the paper 'Biomarkers in Multiple Sclerosis: a review of diagnostic and prognostic factors' by Sapko et al.

A comment on the paper 'Biomarkers in Multiple Sclerosis: a review of diagnostic and prognostic factors' by Sapko et al.

Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss

Background: The research is focused on sensitive biomarkers in multiple sclerosis (MS). Objective: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA (no evident disease activity), including brain volumetry, in a cohort of MS patients treated with disease-modifying treatment (DMT). Methods: Levels of pNfL (Single Molecule Array (SIMOA) technology) were examined in 95 RRMS (relapsing-remitting multiple sclerosis) patients and analyzed in relationship to NEDA-3 status and NEDA-BVL (brain volume loss; NEDA-3 extended by brain volumetry) during the last 12 months. The statistical model was developed using logistic regression analysis, including the independent variables: demographic, clinical, and magnetic resonance imaging (MRI) data. Dependent variables were NEDA-3 and NEDA-BVL status. Results: The mean age of the study participants (n = 95, 62% females) was 37.85 years (standard deviation (SD) = 9.62) and the median disability score was 3.5 (2.5–4.1). Receiver operating characteristics (ROC) analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 92% and 78%, respectively, p < 0.001) and NEDA-BVL status (the sensitivity and specificity were 80% and 65%, respectively, p < 0.001). Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-BVL status, including brain MRI-volumetry in patients with RRMS.

A pharmacokinetic and biomarker study of delayed-release dimethyl fumarate in subjects with secondary progressive multiple sclerosis: evaluation of cerebrospinal fluid penetration and the effects on exploratory biomarkers

BackgroundBiomarkers are a useful and reliable measure of disease activity in many fields of medicine. Axonal and glial biomarkers in multiple sclerosis (MS) are being applied more often as technology is improving and becoming increasingly reliable. Nonclinical studies have shown dimethyl fumarate (DMF) to have cytoprotective and anti-inflammatory effects. The purpose of this study is to explore the pharmacokinetics (PK) of DMF (by measuring MMF, the active compound) in serum and cerebrospinal fluid (CSF) as well as relevant biomarker data for patients with secondary progressive MS (pwSPMS) and whether there is objective evidence for neuroprotection in pwSPMS treated with DMF. MethodsSixteen pwSPMS had serum and cerebrospinal fluid (CSF) evaluation for PK studies levels of MMF at various time points after ingestion of DMF. The CSF biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxyo-terminal hydrolase isozyme L1 (UCH-L1) and total tau (T-tau) were measured at baseline, week 6 and week 28 after initiating DMF with a starting dose of 120 mg twice daily for 4 weeks, followed by a maintenance dose of 240 mg twice daily. Clinical correlation of these patients with EDSS and MRI at these same time periods were made with the biomarkers. Four normal human volunteers had CSF studies for biomarkers at baseline. ResultsPK data showed CSF MMF concentration 11% of plasma with Tmax of plasma at 5 hr and Tmax of CSF at 7 hr. Biomarker data showed that CS NfL and to a lesser extent, GFAP, but not UCH-L1 nor T-tau showed relevant changes with clinical data. Some pwSPMS receiving DMF showed clinical improvements in Expanded Disability Status Scale (EDSS). Biomarker changes, but not MRI, correlated with clinical measures in this group of pwSPMS over the observation period. ConclusionsPK data showed that the Tmax of CSF MMF peaked only 2 hours later than that of plasma with 11% measured in the CSF so that MMF readily crossed the blood brain barrier allowing potential direct penetration into the brain. NfL CSF levels, and to a lesser extent, GFAP CSF levels, showed correlation to disease activity in pwSPMS . These data suggest that DMF may have some benefit in reducing disease activity in pwSPMS if studied for a longer duration and larger well-controlled studies are warranted. DMF was reasonably well tolerated but 3 of the 16 patients did discontinue DMF at 6 weeks due to persistent side effects. NfL appeared to be more clinically relevant biomarker than brain MRI in this this group during the 28-week study period.

Neuronal and glial CSF biomarkers in multiple sclerosis: a systematic review and meta-analysis.

Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.

Neutrophil-to-lymphocyte ratio and CRP as biomarkers in multiple sclerosis: A systematic review.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, which causes demyelination and neuroaxonal damage. Low-grade systemic inflammation has been suggested to contribute to the pathogenesis due to amplification of pathogenic immune activation. However, there is a lack of reliable biomarkers of systemic inflammation predicting disease activity and progression in MS. The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) have been identified as biomarkers of severity and disease activity in various disorders. In September 2020, we conducted a systematic literature search on multiple databases on studies reporting NLR values or CRP levels in MS. The aim of this systematic review was to highlight the current knowledge about the potential of NLR and CRP as biomarkers in MS. A total of nineteen articles qualified for inclusion. Data on CRP were included in fourteen studies and NLR in nine studies. The results regarding CRP were inconsistent, and present literature does not support the use of CRP as a diagnostic or prognostic biomarker in MS. In contrast, NLR values were increased in MS patients compared with healthy controls in all case-control studies. Furthermore, NLR was associated with disease activity in untreated patients. Our systematic review therefore indicates that NLR might serve as a potential biomarker of disease activity. Given that the results of NLR are mainly drawn from retrospective case-control or cross-sectional studies, future prospective studies with long-term follow-up are required to accurately determine optimal timing and cutoff values that may be used in the clinical setting.

Deep Learning Corpus Callosum Segmentation as a Neurodegenerative Marker in Multiple Sclerosis.

Corpus callosum atrophy is a sensitive biomarker of multiple sclerosis (MS) neurodegeneration but typically requires manual 2D or volumetric 3D-based segmentations. We developed a supervised machine learning algorithm, DeepnCCA, for corpus callosum segmentation and relate callosal morphology to clinical disability using conventional MRI scans collected in clinical routine. In a prospective study of 553 MS patients with 704 acquisitions, 200 unique 2D T2 -weighted MRI scans were delineated to develop, train, and validate DeepnCCA. Comparative FreeSurfer segmentations were obtained in 504 3D T1 -weighted scans. Both FreeSurfer and DeepnCCA outputs were correlated with clinical disability. Using principal component analysis of the DeepnCCA output, the morphological changes were explored in relation to clinical disease burden. DeepnCCA and manual segmentations had high similarity (Dice coefficients 98.1 .11%, 89.3 .76%, for intracranial and corpus callosum area, respectively through 10-fold cross-validation). DeepnCCA had numerically stronger correlations with cognitive and physical disability as compared to FreeSurfer: Expanded disability status scale (EDSS) ±6 months (r = -.22 P = .002; r = -.17, P = .013), future EDSS (r = -.26, P<.001; r = -.17, P = .012), and future symbol digit modalities test (r = .26, P = .001; r = .24, P = .003). The corpus callosum became thinner with increasing cognitive and physical disability. Increasing physical disability, additionally, significantly correlated with a more angled corpus callosum. DeepnCCA (https://github.com/plattenmichael/DeepnCCA/) is an openly available tool that can provide fast and accurate corpus callosum measurements applicable to large MS cohorts, potentially suitable for monitoring disease progression and therapy response.

Serum neurofilament levels and patient-reported outcomes in multiple sclerosis.

ObjectiveSerum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients.MethodsMS patients with serum samples and health‐outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log‐transformed sNfL values.ResultsA total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23–78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow‐up sNfL correlated with MSQoL physical‐role limitations (mean = 48.9 (10.8), P = 0.043) and social‐functioning (mean = 52.3 (7), P = 0.034) at 24‐month follow‐up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24‐month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053).ConclusionSerum NfL is a patient‐centric biomarker that correlated with MS patient health‐outcomes and healthcare utilization measures in a real‐world cohort.

KIF5A and the contribution of susceptibility genotypes as a predictive biomarker for multiple sclerosis

There is increasing interest in the development of multiple sclerosis (MS) biomarkers that reflect central nervous system tissue injury to determine prognosis. We aimed to assess the prognostic value of kinesin superfamily motor protein KIF5A in MS by measuring levels of KIF5A in cerebrospinal fluid (CSF) combined with analysis of single nucleotide polymorphisms (SNPs; rs12368653 and rs703842) located within a MS susceptibility gene locus at chromosome 12q13–14 region. Enzyme-linked immunosorbent assay was used to measure KIF5A in CSF obtained from two independent biobanks comprising non-inflammatory neurological disease controls (NINDC), clinically isolated syndrome (CIS) and MS cases. CSF KIF5A expression was significantly elevated in progressive MS cases compared with NINDCs, CIS and relapsing–remitting MS (RRMS). In addition, levels of KIF5A positively correlated with change in MS disease severity scores (EDSS, MSSS and ARMSSS), in RRMS patients who had documented disease progression at 2-year clinical follow-up. Copies of adenine risk alleles (AG/AA; rs12368653 and rs703842) corresponded with a higher proportion of individuals in relapse at the time of lumbar puncture (LP), higher use of disease-modifying therapies post LP and shorter MS duration. Our study suggests that CSF KIF5A has potential as a predictive biomarker in MS and further studies into the potential prognostic value of analysing MS susceptibility SNPs should be considered.

ELTD1 as a biomarker for multiple sclerosis: Pre-clinical molecular-targeted studies in a mouse experimental autoimmune encephalomyelitis model

Multiple sclerosis (MS) and glioblastoma (GBM) are two distinct diseases that affect the central nervous system (CNS). However, perturbation in CNS vasculature are hallmarks of both diseases. ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain containing protein 1 on chromosome 1) is associated with vascular development, and has been linked with tumor angiogenesis. In glioblastomas, we detected over-expression of ELTD1, and found that an antibody targeting ELTD1 could increase animal survival and decrease tumor volumes in a xenograft GBM model. RNA-seq analysis of the preclinical data in the model for GBM identified that some of the molecular pathways affected by the anti-ELTD1 antibody therapy are also found to be associated with MS. In this study, we used molecular-targeted (mt) MR imaging and immunohistochemistry to assess ELTD1 levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Specifically, we found that ELTD1 is readily detected in the brains of mice with EAE and is predominantly found in the corpus callosum. In addition, we found that the blood-brain barrier (BBB) was compromised in the brains of EAE mice using contrast-enhanced MRI (CE-MRI), as well as altered relative cerebral blood flow (rCBF) in the brains and cervical spinal cords of these mice using perfusion imaging, compared to controls. These findings indicate that ELTD1 may be a promising biomarker for CNS-inflammation in MS.

Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. “Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)” is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the North American Imaging in MS Cooperative (NAIMS) to evaluate CVS as a diagnostic biomarker for immediate translation into clinical care. Study objectives include determining the concordance of CVS and McDonald Criteria to diagnose MS, the sensitivity of CVS to detect MS in those with typical presentations, and the specificity of CVS among those with atypical presentations. The study will recruit a total of 400 participants (200 with typical and 200 with atypical presentations) across 11 sites. T2*-weighted, high-isotropic-resolution, segmented echo-planar MRI will be acquired at baseline and 24 months on 3-tesla scanners, and FLAIR* images (combination of FLAIR and T2*) will be generated for evaluating CVS. Data will be processed on a cloud-based platform that contains clinical and CVS rating modules. Imaging quality control will be conducted by automated methods and neuroradiologist review. CVS will be determined by Select6* and Select3* lesion methods following published criteria at each site and by central readers, including neurologists and neuroradiologists. Automated CVS detection and algorithms for incorporation of CVS into McDonald Criteria will be tested. Diagnosis will be adjudicated by three neurologists who served on the 2017 International Panel on the Diagnosis of MS. The CAVS-MS study aims to definitively establish CVS as a diagnostic biomarker that can be applied broadly to individuals presenting for evaluation of the diagnosis of MS.

Minimum detectable spinal cord atrophy with automatic segmentation: Investigations using an open-access dataset of healthy participants

Spinal cord atrophy is a well-known biomarker in multiple sclerosis (MS) and other diseases. It is measured by segmenting the spinal cord on an MRI image and computing the average cross-sectional area (CSA) over a few slices. Introduced about 25 years ago, this procedure is highly sensitive to the quality of the segmentation and is prone to rater-bias. Recently, fully-automated spinal cord segmentation methods, which remove the rater-bias and enable the automated analysis of large populations, have been introduced. A lingering question related to these automated methods is: How reliable are they at detecting atrophy? In this study, we evaluated the precision and accuracy of automated atrophy measurements by simulating scan-rescan experiments.Spinal cord MRI data from the open-access spine-generic project were used. The dataset aggregates 42 sites worldwide and consists of 260 healthy subjects and includes T1w and T2w contrasts. To simulate atrophy, each volume was globally rescaled at various scaling factors. Moreover, to simulate patient repositioning, random rigid transformations were applied. Using the DeepSeg algorithm from the Spinal Cord Toolbox, the spinal cord was segmented and vertebral levels were identified. Then, the average CSA between C3-C5 vertebral levels was computed for each Monte Carlo sample, allowing us to derive measures of atrophy, intra/inter-subject variability, and sample-size calculations.The minimum sample size required to detect an atrophy of 2% between unpaired study arms, commonly seen in MS studies, was 467 +/− 13.9 using T1w and 467 +/− 3.2 using T2w images. The minimum sample size to detect a longitudinal atrophy (between paired study arms) of 0.8% was 60 +/− 25.1 using T1w and 10 +/− 1.2 using T2w images. At the intra-subject level, the estimated CSA, observed in this study, showed good precision compared to other studies with COVs (across Monte Carlo transformations) of 0.8% for T1w and 0.6% for T2w images.While these sample sizes seem small, we would like to stress that these results correspond to a “best case” scenario, in that the dataset used here was of particularly good quality and the model for simulating atrophy does not encompass all the variability met in real-life datasets. The simulated atrophy and scan-rescan variability may over-simplify the biological reality. The proposed framework is open-source and available at https://csa-atrophy.readthedocs.io/.

Serum and Saliva Myelin Basic Protein as Multiple Sclerosis Biomarker.

Introduction:Multiple Sclerosis (MS) is presented with motor and sensory function loss. It is caused by demyelination and following axonal lesion. As Myelin Basic Protein (MBP) is one of the key elements of the myelin cover, we examined the level of MBP in serum, stimulated, and unstimulated saliva as a suitable biomarker for detecting MS.Methods:A case-control study was performed in 29 healthy women and 32 definitive relapsing-remitting MS patients hospitalized in Imam Reza hospital, Tehran, Iran. MBP level was assayed in serum and stimulated and unstimulated whole saliva.Results:MBP was expressed at a lower level in serum and stimulated saliva of MS patients compared to the control group. The serum MBP level had a considerable correlation with its stimulated saliva level. The receiver operating characteristic analysis showed significant diagnostic ability for MBP to discriminate MS patients with serum and stimulated saliva from controls.Conclusion:Serum and saliva level of MBP is lower in MS, so it may be considered a potential biomarker in MS.

Update on promising biomarkers for multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease, in which there is chronic inflammation leading to neurodegeneration and demyelination. To detect MS at an early stage is impossible as it includes environmental factors and genetic factors as it varies from person to person. There are various methodologies that have been developed for the treatment of this disease; however, several complications as well as obstacles have been seen which are yet to be resolved. This review describes the biomarker for MS including microRNA and vaccine as a biomarker. Some of the drugs which are under phase II clinical trials are also discussed here. Testing and continuous validation is required for improvement where MS biomarkers are brought into clinical settings.

Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches.

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.

Brain Homogenate Decoys for Antigen-Specific Cell Amplification.

Multiple sclerosis is complex and heterogeneous. Better tools are needed to be able to monitor this disease among individuals, but blood-based biomarkers are often too rare to profile. In this work, we developed antigen-specific biomaterials to replicate the central nervous system niche where multiple sclerosis biomarkers are amplified. We incorporated mouse brain homogenate into a microporous gelatin methacrylate network. Homogenate-containing biomaterials differentially stimulated cells and led to the marked amplification of disease-relevant, antigen-specific B cells. These results demonstrate that biomaterials containing primary tissue homogenate retain antigen specificity and may be a useful tool for decoding human autoimmunity.

Chitinase 3-like 1 is not a target antigen in patients with multiple sclerosis

Autoimmunity to chitinase 3-like 1 (CHI3L1) has recently been reported in hepatic and bowel inflammatory conditions. Considering that CHI3L1 plays a role as prognostic biomarker in multiple sclerosis (MS), here we investigated CHI3L1 as potential autoantigenic target in the disease. We determined serum CHI3L1 autoantibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 60 untreated MS patients with different clinical forms of the disease and 20 healthy controls (HC). IgG levels to CHI3L1 were similar between patients with relapsing-remitting MS, primary and secondary progressive MS, and HC. These findings do not support a role for CHI3L1 autoantibodies in MS pathogenesis.

Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage. Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing–remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years. Regression models explored how sNfL data predicted 4-year values of brain volume, expanded disability status scale score, and T2 lesions. sNfL levels were assessed in those receiving placebo, peginterferon beta-1a, and those with disease activity. Results: Baseline sNfL was a predictor of 4-year brain atrophy and development of new T2 lesions. Clinical (p = 0.02) and magnetic resonance imaging (MRI) (p < 0.01) outcomes improved in those receiving peginterferon beta-1a whose sNfL decreased to <16 pg/mL after 12 months versus those whose sNfL remained ⩾16 pg/mL. Mean sNfL levels decreased in peginterferon beta-1a-treated patients and increased in placebo-treated patients (–9.5% vs. 6.8%; p < 0.01). sNfL was higher and more variable in patients with evidence of active MS. Conclusion: These data support sNfL as a prognostic and disease-monitoring biomarker for RRMS.

Angiography with optical coherence tomography as a biomarker in multiple sclerosis

To investigate superficial retinal microvascular plexuses detected by optical coherence tomography angiography (OCT-A) in multiple sclerosis (MS) subjects and compare them with healthy controls. A total of 92 eyes from 92 patients with relapsing-remitting MS and 149 control eyes were included in this prospective observational study. OCT-A imaging was performed using Triton Swept-Source OCT (Topcon Corporation, Japan). The vessel density (VD) percentage in the superficial retinal plexus and optic disc area (6 x 6 mm grid) was measured and compared between groups. MS patients showed a significant decrease VD in the superior (p = 0.005), nasal (p = 0.029) and inferior (p = 0.040) parafoveal retina compared with healthy subjects. Patients with disease durations of more than 5 years presented lower VD in the superior (p = 0.002), nasal (p = 0.017) and inferior (p = 0.022) parafoveal areas compared with healthy subjects. Patients with past optic neuritis episodes did not show retinal microvasculature alterations, but patients with an EDSS score of less than 3 showed a significant decrease in nasal (p = 0.024) and superior (p = 0.006) perifoveal VD when compared with healthy subjects. MS produces a decrease in retinal vascularization density in the superficial plexus of the parafoveal retina. Alterations in retinal vascularization observed in MS patients are independent of the presence of optic nerve inflammation. OCT-A has the ability to detect subclinical vascular changes and is a potential biomarker for diagnosing the presence and progression of MS.