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1.
Nat Commun ; 15(1): 5243, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38897994

ABSTRACT

Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of retinal atrophy in progressive MS are less clear. We investigated retinal layer thickness changes in RRMS, primary and secondary progressive MS (PPMS, SPMS), and their prognostic value for disease activity. Here, we analyzed 2651 OCT measurements of 195 RRMS, 87 SPMS, 125 PPMS patients, and 98 controls from five German MS centers after quality control. Peripapillary and macular retinal nerve fiber layer (pRNFL, mRNFL) thickness predicted future relapses in all MS and RRMS patients while mRNFL and ganglion cell-inner plexiform layer (GCIPL) thickness predicted future MRI activity in RRMS (mRNFL, GCIPL) and PPMS (GCIPL). mRNFL thickness predicted future disability progression in PPMS. However, thickness change rates were subject to considerable amounts of measurement variability. In conclusion, retinal degeneration, most pronounced of pRNFL and GCIPL, occurs in all subtypes. Using the current state of technology, longitudinal assessments of retinal thickness may not be suitable on a single patient level.


Subject(s)
Disease Progression , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis, Relapsing-Remitting , Retina , Retinal Degeneration , Tomography, Optical Coherence , Humans , Retinal Degeneration/diagnostic imaging , Retinal Degeneration/pathology , Male , Female , Tomography, Optical Coherence/methods , Adult , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/pathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Retina/diagnostic imaging , Retina/pathology , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Multiple Sclerosis, Chronic Progressive/pathology , Multiple Sclerosis, Chronic Progressive/physiopathology , Magnetic Resonance Imaging/methods , Prognosis , Nerve Fibers/pathology , Retinal Ganglion Cells/pathology
2.
Article in English | MEDLINE | ID: mdl-34667130

ABSTRACT

BACKGROUND AND OBJECTIVES: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease primarily affecting the peripheral nervous system. However, several noncontrolled studies have suggested concomitant inflammatory CNS demyelination similar to multiple sclerosis. The aim of this study was to investigate an involvement of the visual pathway in patients with CIDP. METHODS: In this prospective cross-sectional study, we used high-resolution spectral-domain optical coherence tomography to compare the thickness of the peripapillary retinal nerve fiber layer and the deeper macular retinal layers as well as the total macular volume (TMV) in 22 patients with CIDP and 22 age-matched and sex-matched healthy control (HC) individuals. Retinal layers were semiautomatically segmented by the provided software and were correlated with clinical measures and nerve conduction studies. RESULTS: In patients with CIDP compared with healthy age-matched and sex-matched controls, we found slight but significant volume reductions of the ganglion cell/inner plexiform layer complex (CIDP 1.86 vs HC 1.95 mm3, p = 0.015), the retinal pigment epithelium (CIDP 0.38 vs HC 0.40 mm3, p = 0.02), and the TMV (CIDP 8.48 vs HC 8.75 mm3, p = 0.018). The ganglion cell layer volume and motor nerve conduction velocity were positively associated (B = 0.002, p = 0.02). DISCUSSION: Our data reveal subtle retinal neurodegeneration in patients with CIDP, providing evidence for visual pathway involvement, detectable by OCT. The results need corroboration in independent, larger cohorts.


Subject(s)
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology , Retina/pathology , Visual Pathways/pathology , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Neural Conduction/physiology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnostic imaging , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology , Prospective Studies , Retina/diagnostic imaging , Tomography, Optical Coherence , Visual Pathways/diagnostic imaging
3.
Article in English | MEDLINE | ID: mdl-34045307

ABSTRACT

OBJECTIVE: Retinal layer thickness (RLT) measured by optical coherence tomography (OCT) is considered a noninvasive, cost-efficient marker of neurodegeneration in multiple sclerosis (MS). We aimed to investigate associations of RLT with cognitive performance and its potential as indicator of cognitive status in patients with MS by performing generalized estimating equation (GEE) analyses. METHODS: In this cross-sectional study, patients with at least mild signs of cognitive impairment were examined by OCT as well as by the Brief International Cognitive Assessment for MS and tests assessing attention and executive functions (Trail Making Test [TMT] A and B). Associations of these factors were investigated using GEE models controlling for demographic and disease-related factors and correcting for multiple testing. RESULTS: A total of 64 patients entered the study. In the final sample (n = 50 [n = 14 excluded due to missing data or drop-outs]; n = 44 relapsing-remitting MS and n = 6 secondary progressive MS, mean Expanded Disability Status Scale score = 2.59 [SD = 1.17], disease duration [median] = 7.34 [interquartile range = 12.1]), 36.0% were cognitively impaired. RLT of the macular retinal nerve fiber layer was associated with performance in TMT-B (ß = -0.259). Analyses focusing on the upper and lower tertile of RLT additionally revealed associations between macular ganglion cell-inner plexiform layer and TMT-B and verbal short-term memory and learning, respectively. CONCLUSION: In patients with MS, at less advanced disease stages, RLT was especially associated with cognitive flexibility promoting OCT as a potential marker advocating further extensive neuropsychological examination.


Subject(s)
Cognitive Dysfunction , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis, Relapsing-Remitting , Retinal Neurons/pathology , Adolescent , Adult , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/complications , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Multiple Sclerosis, Chronic Progressive/pathology , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/pathology , Neuropsychological Tests , Tomography, Optical Coherence , Young Adult
4.
BMC Neurol ; 20(1): 333, 2020 Sep 03.
Article in English | MEDLINE | ID: mdl-32883246

ABSTRACT

BACKGROUND: It is unknown whether microangiopathic ischemic strokes outside the visual pathway go along with subclinical changes of the retinal structure or the visual system. The objectives of this prospective non-interventional case series were to investigate if spectral-domain optical coherence tomography (SD-OCT) or multifocal visual evoked potentials (mfVEPs) can detect structural retinal changes or functional impairment of the visual system in patients with microangiopathic ischemic stroke. METHODS: We used SD-OCT to cross-sectionally analyze the retinal morphology of 15 patients with microangiopathic ischemic stroke according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification not affecting the visual pathway. We employed semi-automated segmentation of macular volume scans to analyze the thickness of the macular retinal layers and peripapillary ring scans to investigate the retinal morphology in comparison to a control group without stroke. Visual function was assessed by the mfVEP technique in 13 microangiopathic ischemic stroke patients. RESULTS: First peak latency of mfVEPs was significantly delayed in the microangiopathic ischemic stroke group compared to the control patients. Neither the retinal layers nor the mfVEPs' amplitude differed between the microangiopathic ischemic stroke patients and the control group. CONCLUSIONS: In conclusion, microangiopathic ischemic stroke patients presented a delayed first peak latency in mfVEPs as a sign of subclinical functional impairment of the visual pathway. However, our case series suggests no influence on retinal structure resulting from microangiopathic ischemic stroke outside the visual system. Larger and longitudinal studies are needed to confirm these mfVEP findings.


Subject(s)
Brain Ischemia/physiopathology , Retina/diagnostic imaging , Stroke/physiopathology , Aged , Evoked Potentials, Visual , Female , Humans , Male , Middle Aged , Prospective Studies , Tomography, Optical Coherence/methods , Visual Field Tests , Visual Pathways/physiopathology
5.
Article in English | MEDLINE | ID: mdl-32576604

ABSTRACT

OBJECTIVE: To investigate disease-specific foveal shape changes in patients with neuromyelitis optica spectrum disorders (NMOSDs) using foveal morphometry. METHODS: This cross-sectional study included macular spectral domain optical coherence tomography scans of 52 eyes from 28 patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD, 116 eyes from 60 patients with MS, and 123 eyes from 62 healthy controls (HCs), retrospectively, and an independent confirmatory cohort comprised 33/33 patients with NMOSD/MS. The fovea was characterized using 3D foveal morphometry. We included peripapillary retinal nerve fiber layer (pRNFL) thickness and combined macular ganglion cell and inner plexiform layer (GCIPL) volume to account for optic neuritis (ON)-related neuroaxonal damage. RESULTS: Group comparison showed significant differences compared with HC in the majority of foveal shape parameters in NMOSD, but not MS. Pit flat disk area, average pit flat disk diameter, inner rim volume, and major slope disk length, as selected parameters, showed differences between NMOSD and MS (p value = 0.017, 0.002, 0.005, and 0.033, respectively). This effect was independent of ON. Area under the curve was between 0.7 and 0.8 (receiver operating characteristic curve) for discriminating between NMOSD and MS. Pit flat disk area and average pit flat disk diameter changes independent of ON were confirmed in an independent cohort. CONCLUSIONS: Foveal morphometry reveals a wider and flatter fovea in NMOSD in comparison to MS and HC. Comparison to MS and accounting for ON suggest this effect to be at least in part independent of ON. This supports a primary retinopathy in AQP4-IgG-seropositive NMOSD.


Subject(s)
Aquaporin 4/immunology , Fovea Centralis/pathology , Multiple Sclerosis/pathology , Neuromyelitis Optica/immunology , Neuromyelitis Optica/pathology , Adult , Cross-Sectional Studies , Female , Fovea Centralis/diagnostic imaging , Humans , Immunoglobulin G , Male , Middle Aged , Multiple Sclerosis/diagnostic imaging , Neuromyelitis Optica/diagnostic imaging , Retrospective Studies , Tomography, Optical Coherence
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