Corneal epithelial dendritic cells in patients with multiple sclerosis: An in vivo confocal microscopy study (original) (raw)
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Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
Scientific Reports
Axonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) [(clinically isolated syndrome (n = 9); relapsing–remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21)] underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm2, 95% CI − 18.24 to − 11.59, P
Anatomical and functional retinal changes in multiple sclerosis
Eye, 2015
Aims The aims of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with multiple sclerosis (MS). We also investigated the correlation between anatomical and functional changes in terms of visual acuity and macular sensitivity investigated and visual fields. Methods Prospective comparative study included 105 eyes of 53 consecutive patients. The patients were divided into two groups: group A included 56 eyes of 28 patients with diagnosis of MS; group B involved 49 eyes of 25 healthy patients. The examination included Goldmann tonometry, biomicroscopic and fundus oculi examination, retinography, GCC examination, circumpapillary RNFL (cpRNFL), and macular volume. The functional test included measurement of best-corrected visual acuity (BCVA), visual field, and MP. Results MS group showed a significant reduced GCC, cpRNFL, macular volume, BCVA, visual field, and macular sensitivity compared with the control group (Po0.001). This reduction was more representative (Po0.001) in patients with MS complicated by optic neuritis (ON). We found in the MS group a strong correlation between GCC thickness and macular volume (r 2 = 0.59, Po0.001) and also between GCC and RNFL thickness (r 2 = 0.48, Po0.001). There was also a correlation between macular sensitivity and macular volume reduction (r 2 = 0.25, Po0.001) and also between RNFL and macular volume (r 2 = 0.43, Po0.001). Conclusions The significant statistical evidence and the strong correlation between anatomical and functional parameters support the use of OCT and MP in the evaluation, treatment, and follow-up of patients diagnosed with MS.
Neurology Research International
Background. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and demyelination of the central nervous system which often involves the optic nerve even though only 20% of the patients experience optic neuritis (ON). Objective. This study aims to compare the retinal structure and optic nerve function between patients with MS and healthy controls (HCs), evaluate optic nerve alterations in MS over 1-year follow-up, and analyze its correlations with disease duration, number of relapses, degree of disability, and different subtypes. Methods. This is a prospective cohort study involving 58 eyes of MS patients. Optic nerve function was evaluated with best-corrected visual acuity (BCVA), contrast sensitivity, and P100 latency, while the retinal structure was evaluated from the GCIPL and RNFL thickness measured with optical coherence tomography (OCT) and fundus photography. Results. The MS group had lower BCVA ( p = 0.001 ), contrast sensitivity ( p < 0.001 ),...
Association of Retinal Architecture, Intrathecal Immunity, and Clinical Course in Multiple Sclerosis
JAMA Neurology, 2017
IMPORTANCE Biomarkers to estimate long-term outcomes in patients with multiple sclerosis (MS) and to assign patients to individual treatment regimens are urgently needed. OBJECTIVE To assess whether retinal layer volumes are correlated with immune cell subsets and immunoglobulin indices in the cerebrospinal fluid and whether retinal layer volumes alone or in combination with intrathecal variables are associated with worsening of disease in patients with relapsing-remitting MS. DESIGN, SETTING, AND PARTICIPANTS This observational cohort study included 312 patients with relapsing-remitting MS in 2 independent cohorts (72 patients with short disease duration [cohort 1] and 240 patients with longer disease duration [cohort 2]) treated at a single German university hospital from April 15, 2013, through November 11, 2015. MAIN OUTCOMES AND MEASURES The common ganglion cell and inner plexiform layer (GCIPL) and inner nuclear layer (INL) volumes were tested for association with the immunoglobulin indices and the frequencies of immune cells in the cerebrospinal fluid (including B cells, T cells, and natural killer cells) (cohort 1). Volumes of GCIPL alone (cohorts 1 and 2) or GCIPL corrected for intrathecal B-cell frequencies (cohort 1) were tested for their association with worsening disability. RESULTS A total of 312 patients (212 women [67.9%] and 100 men [32.1%]; median age, 34.0 years [interquartile range (IQR), 28.0-42.0 years]) were available for analysis. In cohort 1 (50 women [69.4%] and 22 men [30.6%]; median age, 31.0 years [IQR, 26.3-38.3 years]), with short disease durations (median, 1.0 months [IQR, 1.0-2.0 months]), low GCIPL volumes were associated with increased intrathecal B-cell frequencies (median, 1.96% [IQR, 1.45%-4.20%]) and intrathecal IgG synthesis (median cerebrospinal fluid/serum IgG index, 0.78 [IQR, 0.53-1.07]). The INL volumes correlated with the frequencies of intrathecal CD56 bright natural killer cells (r = 0.28; P = .007). Individuals with low GCIPL volumes (<1.99 mm 3) had a 6.4-fold risk for worsening disability during follow-up compared with patients with higher GCIPL values (95% CI, 1.7-24.2; P = .007). This finding was reproduced in cohort 2 (162 women [67.5%] and 78 men [32.5%]; median age, 34.0 years [IQR, 29.0-42.0 years]) consisting of patients with longer disease durations (median, 36.0 months [IQR, 21.0-60.0 months]) (hazard ratio, 2.4; 95% CI, 1.2-4.8; P = .02). In both cohorts, INL volumes correlated with the prospective increase in T2 lesion load and the number of gadolinium-enhancing lesions. CONCLUSIONS AND RELEVANCE Retinal layers reflect different aspects of disease activity during MS. Loss of GCIPL is associated with intrathecal B-cell immunity and constitutes an independent risk factor for worsening disability, whereas high INL volumes are associated with activity on magnetic resonance imaging in the brain parenchyma. Thus, retinal optical coherence tomography might be a means to support stratification of patients with MS for different therapeutic regimens.
The Lancet Neurology, 2016
Background: Most of Multiple Sclerosis (MS) patients without previous optic neuritis (ON) show thinner retinal measurements compared to healthy controls. We aimed to evaluate the role of peripapillary retinal nerve fiber layer (pRNFL) thickness or macular volume (MV) in non-ON eyes as a biomarker of disability worsening in a cohort of MS patients with at least one non-ON eye available. Methods: In this multicenter longitudinal study, we enrolled 879 patients (739 relapsing-remitting and 141 progressive patients). Disability worsening was assessed using the expanded disability status scale (EDSS). pRNFL thickness and MV were assessed by optical coherence tomography (OCT) and calculated as the mean value of both non-ON eyes for patients without previous ON or the fellow eye's value for those with previous unilateral ON. We estimated the association between pRNFL thickness and MV in non-ON eyes, and the risk of disability worsening using proportional hazards models including OCT metrics and age, disease duration, disability, presence of previous unilateral ON and use of disease modifying therapies as covariates. Findings: Disability worsening was noted in 252 out of 879 (29%) patients after a mean follow-up of 2.32 years of follow-up. MS patients with a pRNFL≤92-93μm in non-ON eyes were associated with a 58% increased risk of disability worsening as compared to patients with pRNFL>92-93μm, at any time after the first year of ascertainment in this cohort [HR=1.58 95% CI (1.13-2.21); p=0.007]. Further, a pRNFL ≤87-88μm doubled the risk of disability worsening at any time during the second and third year of follow-up [HR=2.06 95%CI (1.36-3.11); p=0.001], and increased the risk by four-fold after 4-5 years of follow-up [HR=3.81 95% CI (1.63-8.91) p=0.002]. We did not identify meaningful associations for disability worsening with MV. Interpretation: Our results provide compelling evidence of the utility of monitoring pRNFL thickness by OCT for predicting the likelihood of disability worsening in MS patients over time.
Using retinal architecture to help characterize multiple sclerosis patients
Canadian Journal of Ophthalmology / Journal Canadien d'Ophtalmologie, 2010
N RÉ SUMÉ Objective: We compared retinal nerve fibre layer (RNFL) thickness and visual function in a heterogeneous multiple sclerosis (MS) cohort to determine whether optical coherence tomography (OCT) may complement the existing methods used to characterize MS patients. Design: Cross-sectional cohort study. Participants: One hundred and ninety-three patients with optic neuritis (ON) as a clinically isolated syndrome (CIS) (n 5 63), relapsing-remitting MS (RRMS) (n 5 108), secondary progressive MS (SPMS) (n 5 13), and primary progressive MS (PPMS) (n 5 9). Methods: All patients underwent standardized ophthalmic, neurological, and OCT testing at a single academic institution. Results: RNFL values were reduced in PPMS (94.3 mm), RRMS (99.6 mm), and SPMS eyes (84.7 mm) relative to CIS eyes (105.7 mm) (p , 0.0001). RNFL values were lower in eyes with recurrent ON (64.2 mm) relative to eyes affected by a single ON event (86.3 mm) (p , 0.0001). The strongest correlation between RNFL thickness and neurological disability occurred in RRMS patients (r 5 20.51, p , 0.0001). RNFL thickness correlated with visual field sensitivity for CIS (r 5 0.23, p , 0.01) and RRMS (r 5 0.22, p , 0.01) patients. Simple linear regression showed that every 10 mm decrease in RNFL correlated with a 5.8 decibel decrease in visual field sensitivity (adjusted R 2 5 0.35, p , 0.0001) for RNFL values less than 75 mm. Conclusions: There were robust correlations between RNFL thickness and visual function, particularly in ON eyes.