scholarly journals Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (4) ◽  
pp. 1127-1142 ◽  
Author(s):  
Michael Dietrich ◽  
Valeria Koska ◽  
Christina Hecker ◽  
Peter Göttle ◽  
Alexander M Hilla ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optical Coherence Tomography ◽  
Optic Neuritis ◽  
Visual Function ◽  
Mode Of Action ◽  
Nuclear Translocation ◽  
Prospective Clinical Study ◽  
Symptomatic Therapy ◽  
Optical Coherence ◽  
Retinal Neurodegeneration

Abstract Chronic disability in multiple sclerosis is linked to neuroaxonal degeneration. 4-aminopyridine (4-AP) is used and licensed as a symptomatic treatment to ameliorate ambulatory disability in multiple sclerosis. The presumed mode of action is via blockade of axonal voltage gated potassium channels, thereby enhancing conduction in demyelinated axons. In this study, we provide evidence that in addition to those symptomatic effects, 4-AP can prevent neuroaxonal loss in the CNS. Using in vivo optical coherence tomography imaging, visual function testing and histologic assessment, we observed a reduction in retinal neurodegeneration with 4-AP in models of experimental optic neuritis and optic nerve crush. These effects were not related to an anti-inflammatory mode of action or a direct impact on retinal ganglion cells. Rather, histology and in vitro experiments indicated 4-AP stabilization of myelin and oligodendrocyte precursor cells associated with increased nuclear translocation of the nuclear factor of activated T cells. In experimental optic neuritis, 4-AP potentiated the effects of immunomodulatory treatment with fingolimod. As extended release 4-AP is already licensed for symptomatic multiple sclerosis treatment, we performed a retrospective, multicentre optical coherence tomography study to longitudinally compare retinal neurodegeneration between 52 patients on continuous 4-AP therapy and 51 matched controls. In line with the experimental data, during concurrent 4-AP therapy, degeneration of the macular retinal nerve fibre layer was reduced over 2 years. These results indicate disease-modifying effects of 4-AP beyond symptomatic therapy and provide support for the design of a prospective clinical study using visual function and retinal structure as outcome parameters.

scholarly journals Optical Coherence Tomography and Optical Coherence Tomography Angiography Findings After Optic Neuritis in Multiple Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Olwen C. Murphy ◽  
Grigorios Kalaitzidis ◽  
Eleni Vasileiou ◽  
Angeliki G. Filippatou ◽  
Jeffrey Lambe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optical Coherence Tomography ◽  
Optic Neuritis ◽  
Visual Function ◽  
Inner Plexiform Layer ◽  
Optical Coherence ◽  
Cross Sectional ◽  
Mixed Effect ◽  
Retinal Microvasculature ◽  
History Of

Background: In people with multiple sclerosis (MS), optic neuritis (ON) results in inner retinal layer thinning, and reduced density of the retinal microvasculature.Objective: To compare inter-eye differences (IEDs) in macular optical coherence tomography (OCT) and OCT angiography (OCTA) measures in MS patients with a history of unilateral ON (MS ON) vs. MS patients with no history of ON (MS non-ON), and to assess how these measures correlate with visual function outcomes after ON.Methods: In this cross-sectional study, people with MS underwent OCT and OCTA. Superficial vascular plexus (SVP) density of each eye was quantified using a deep neural network. IEDs were calculated with respect to the ON eye in MS ON patients, and with respect to the right eye in MS non-ON patients. Statistical analyses used mixed-effect regression models accounting for intra-subject correlations.Results: We included 43 MS ON patients (with 92 discrete OCT/OCTA visits) and 14 MS non-ON patients (with 24 OCT/OCTA visits). Across the cohorts, mean IED in SVP density was −2.69% (SD 3.23) in MS ON patients, as compared to 0.17% (SD 2.39) in MS non-ON patients (p = 0.002). When the MS ON patients were further stratified according to time from ON and compared to MS non-ON patients with multiple cross-sectional analyses, we identified that IED in SVP density was significantly increased in MS ON patients at 1–3 years (p = < 0.001) and >3 years post-ON (p < 0.001), but not at <3 months (p = 0.21) or 3–12 months post-ON (p = 0.07), while IED in ganglion cell + inner plexiform layer (GCIPL) thickness was significantly increased in MS ON patients at all time points post-ON (p ≦ 0.01 for all). IED in SVP density and IED in GCIPL thickness demonstrated significant relationships with IEDs in 100% contrast, 2.5% contrast, and 1.25% contrast letter acuity in MS ON patients (p < 0.001 for all).Conclusions: Our findings suggest that increased IED in SVP density can be detected after ON in MS using OCTA, and detectable changes in SVP density after ON may occur after changes in GCIPL thickness. IED in SVP density and IED in GCIPL thickness correlate well with visual function outcomes in MS ON patients.

scholarly journals Campimetry changes, optical coherence tomography and visual function changes in patients with multiple sclerosis

2017 ◽  
Vol 76 (3) ◽  
Author(s):  
Régia Bentes de Souza ◽  
Juliana Tessari Dias Rohr ◽  
Ronaldo Maciel Dias ◽  
Milena Magalhães Lima
Keyword(s):  
Multiple Sclerosis ◽  
Optical Coherence Tomography ◽  
Visual Function ◽  
Optical Coherence

scholarly journals Optical coherence tomography angiography indicates subclinical retinal disease in neuromyelitis optica spectrum disorders

2021 ◽  
pp. 135245852110288
Author(s):  
Lilian Aly ◽  
Eva-Maria Strauß ◽  
Nikolaus Feucht ◽  
Isabella Weiß ◽  
Achim Berthele ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optical Coherence Tomography ◽  
Optic Neuritis ◽  
Disease Activity ◽  
Optical Coherence Tomography Angiography ◽  
Visual Performance ◽  
Healthy Controls ◽  
Optical Coherence ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Spectrum Disorders

Background: Neuromyelitis optica spectrum disorders (NMOSD) are neuroinflammatory diseases of the central nervous system. Patients suffer from recurring relapses and it is unclear whether relapse-independent disease activity occurs and whether this is of clinical relevance. Objective: To detect disease-specific alterations of the retinal vasculature that reflect disease activity during NMOSD. Methods: Cross-sectional analysis of 16 patients with NMOSD, 21 patients with relapsing-remitting multiple sclerosis, and 21 healthy controls using retinal optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), measurement of glial fibrillary acidic protein (GFAP) serum levels, and assessment of visual acuity. Results: Patients with NMOSD but not multiple sclerosis revealed lower foveal thickness (FT) ( p = 0.02) measures and an increase of the foveal avascular zone (FAZ) ( p = 0.02) compared to healthy controls independent to optic neuritis. Reduced FT ( p = 0.01), enlarged FAZ areas ( p = 0.0001), and vessel loss of the superficial vascular complex ( p = 0.01) were linked to higher serum GFAP levels and superficial vessel loss was associated with worse visual performance in patients with NMOSD irrespective of optic neuritis. Conclusion: Subclinical parafoveal retinal vessel loss might occur during NMOSD and might be linked to astrocyte damage and poor visual performance. OCT-A may be a tool to study subclinical disease activity during NMOSD.

scholarly journals Retinal Oxygen Metabolism and Haemodynamics in Patients With Multiple Sclerosis and History of Optic Neuritis

2021 ◽  
Vol 15 ◽  
Author(s):  
Martin Kallab ◽  
Nikolaus Hommer ◽  
Andreas Schlatter ◽  
Gabriel Bsteh ◽  
Patrick Altmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optical Coherence Tomography ◽  
Optic Neuritis ◽  
Layer Thickness ◽  
Oxygen Metabolism ◽  
Retinal Blood Flow ◽  
Oxygen Extraction ◽  
Inner Plexiform Layer ◽  
Optical Coherence ◽  
History Of

Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O2 saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O2/min), higher in MS-ON (2.1 ± 0.5 μl O2/min, p = 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O2/min, p = 0.002 vs. MS, ANOVA p = 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min, p = 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min, p = 0.014 vs. MS+ON, ANOVA p = 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation.Clinical Trial Registration:ClinicalTrials.gov registry, NCT03401879.

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