Search

BackgroundNeurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood.MethodsWe assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNfL) levels in a prospective PPMS cohort and matched healthy controls. We investigated the changes over time, correlations between outcomes and with loss of visual function.ResultsWe followed 81 patients with PPMS (mean disease duration 5.9 years) over 2.7 years on average. Retinal nerve fibre layer thickness (RNFL) was reduced in comparison with controls (90.1 vs 97.8 µm; p<0.001). Visual function quantified by the area under the log contrast sensitivity function (AULCSF) remained stable over a continuous loss of RNFL (0.46 µm/year, 95% CI 0.10 to 0.82; p=0.015) up until a mean turning point of 91 µm from which the AULCSF deteriorated. Intereye RNFL asymmetry above 6 µm, suggestive of subclinical optic neuritis, occurred in 15 patients and was related to lower AULCSF but occurred also in 5 out of 44 controls. Patients with an AULCSF progression had a faster increase in Expanded Disability Status Scale (beta=0.17/year, p=0.043). sNfL levels were elevated in patients (12.2 pg/mL vs 8.0 pg/mL, p<0.001), but remained stable during follow-up (beta=–0.14 pg/mL/year, p=0.291) and were not associated with other outcomes.ConclusionWhereas neurodegeneration in the anterior visual system is already present at onset, visual function is not impaired until a certain turning point. sNfL is not correlated with structural or functional impairment in the visual system.

BackgroundThe novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagnostic accuracy of intereye absolute (IEAD) and percentage difference (IEPD) in AQP4+NMOSD after unilateral ON >6 months before OCT as compared with healthy controls (HC).MethodsTwenty-eight AQP4+NMOSD after unilateral ON (NMOSD-ON), 62 HC and 45 AQP4+NMOSD without ON history (NMOSD-NON) were recruited by 13 centres as part of the international Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica study. Mean thickness of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) were quantified by Spectralis spectral domain OCT. Threshold values of the ON diagnostic criteria (pRNFL: IEAD 5 µm, IEPD 5%; GCIPL: IEAD: 4 µm, IEPD: 4%) were evaluated using receiver operating characteristics and area under the curve (AUC) metrics.ResultsThe discriminative power was high for NMOSD-ON versus HC for IEAD (pRNFL: AUC 0.95, specificity 82%, sensitivity 86%; GCIPL: AUC 0.93, specificity 98%, sensitivity 75%) and IEPD (pRNFL: AUC 0.96, specificity 87%, sensitivity 89%; GCIPL: AUC 0.94, specificity 96%, sensitivity 82%). The discriminative power was high/moderate for NMOSD-ON versus NMOSD-NON for IEAD (pRNFL: AUC 0.92, specificity 77%, sensitivity 86%; GCIP: AUC 0.87, specificity 85%, sensitivity 75%) and for IEPD (pRNFL: AUC 0.94, specificity 82%, sensitivity 89%; GCIP: AUC 0.88, specificity 82%, sensitivity 82%).ConclusionsResults support the validation of the IED metrics as OCT parameters of the novel diagnostic ON criteria in AQP4+NMOSD.

Large, international, real-world MRI assessments showed high heterogeneity in the data collected from patients with aquaporin-4 immunoglobulin G–seropositive neuromyelitis optica spectrum disorder and frequent cerebral and lower spinal cord abnormalities.

Supplemental Digital Content is Available in the Text.

BackgroundPatients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort.Method197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site.ResultsNo significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere.ConclusionThe results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

IMPORTANCE: N-glycan branching modulates cell surface receptor availability, and its deficiency in mice promotes inflammatory demyelination, reduced myelination, and neurodegeneration. N-acetylglucosamine (GlcNAc) is a rate-limiting substrate for N-glycan branching, but, to our knowledge, endogenous serum levels in patients with multiple sclerosis (MS) are unknown. OBJECTIVE: To investigate a marker of endogenous serum GlcNAc levels in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional discovery study and cross-sectional confirmatory study were conducted at 2 academic MS centers in the US and Germany. The discovery study recruited 54 patients with MS from an outpatient clinic as well as 66 healthy controls between April 20, 2010, and June 21, 2013. The confirmatory study recruited 180 patients with MS from screening visits at an academic MS study center between April 9, 2007, and February 29, 2016. Serum samples were analyzed from December 2, 2013, to March 2, 2015. Statistical analysis was performed from February 23, 2020, to March 18, 2021. MAIN OUTCOMES AND MEASURES: Serum levels of GlcNAc plus its stereoisomers, termed N-acetylhexosamine (HexNAc), were assessed using targeted tandem mass spectroscopy. Secondary outcomes (confirmatory study) comprised imaging and clinical disease markers. RESULTS: The discovery cohort included 66 healthy controls (38 women; mean [SD] age, 42 [20] years), 33 patients with relapsing-remitting MS (RRMS; 25 women; mean [SD] age, 50 [11] years), and 21 patients with progressive MS (PMS; 14 women; mean [SD] age, 55 [7] years). The confirmatory cohort included 125 patients with RRMS (83 women; mean [SD] age, 40 [9] years) and 55 patients with PMS (22 women; mean [SD] age, 49 [80] years). In the discovery cohort, the mean (SD) serum level of GlcNAc plus its stereoisomers (HexNAc) was 710 (174) nM in healthy controls and marginally reduced in patients with RRMS (mean [SD] level, 682 [173] nM; P = .04), whereas patients with PMS displayed markedly reduced levels compared with healthy controls (mean [SD] level, 548 [101] nM; P = 9.55 × 10−9) and patients with RRMS (P = 1.83 × 10−4). The difference between patients with RRMS (mean [SD] level, 709 [193] nM) and those with PMS (mean [SD] level, 405 [161] nM; P = 7.6 × 10−18) was confirmed in the independent confirmatory cohort. Lower HexNAc serum levels correlated with worse expanded disability status scale scores (ρ = –0.485; P = 4.73 × 10−12), lower thalamic volume (t = 1.7; P = .04), and thinner retinal nerve fiber layer (B = 0.012 [SE = 7.5 × 10−11]; P = .008). Low baseline serum HexNAc levels correlated with a greater percentage of brain volume loss at 18 months (t = 1.8; P = .04). CONCLUSIONS AND RELEVANCE: This study suggests that deficiency of GlcNAc plus its stereoisomers (HexNAc) may be a biomarker for PMS. Previous preclinical, human genetic, and ex vivo human mechanistic studies revealed that N-glycan branching and/or GlcNAc may reduce proinflammatory responses, promote myelin repair, and decrease neurodegeneration. Combined, the data suggest that GlcNAc deficiency may be associated with progressive disease and neurodegeneration in patients with MS.

BackgroundNeurological disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been increasingly recognised as a new type of neuroinflammatory disorder.ObjectiveThe study aimed to identify regional and ethnic differences in clinical profiles of MOG-IgG–associated disorders between East Asian (Japanese) and Caucasian (German) patients.MethodsDemographic, clinical and therapeutic data from 68 MOG-IgG–positive adults were collected (Japanese, n=44; German, n=24).ResultsAge and sex were similar between cohorts, with optic neuritis occurring most frequently at onset (Japanese: 61%; German: 58%). However, Japanese patients had a lower annualised relapse rate (0.4 vs 0.8, p=0.019; no relapse, 64% vs 25%, p=0.002) and lower Expanded Disability Status Scale score at the last visit (1.0 vs 2.0; p=0.008), despite similar follow-up periods (mean, 73.9 months vs 73.4 months), than those of German patients, respectively. Cerebral syndromes were more common (27% vs 4%; p=0.021) and myelitis less common (21% vs 50%; p=0.012) in Japanese than in German patients, respectively. Japanese patients were more commonly treated with long-term corticosteroids (73%), whereas German patients were more commonly treated with rituximab or other immunosuppressants (63%).ConclusionsAmong patients with MOG-IgG, Japanese tended to have a monophasic milder disease, whereas the majority of German patients had a relapsing course and more frequent myelitis, findings compatible with neuromyelitis optica spectrum disorder. Although the attack-prevention treatment regimens were considerably different, genetic and environmental factors may be important to determine clinical phenotypes and disease activity.

•Decision-making (DM) in well-studied DM domains is impaired in persons with MS.•Impaired DM is assumed to worsen the quality of life and neuropsychiatric symptoms.•Using a novel DM paradigm, we found that also perceptual DM is impaired in MS.•Neural mechanisms of perceptual DM are linked to depression and fatigue.•Neurobehavioral deficits in perceptual DM appear to be clinically relevant for MS.

ObjectivesIn neuromyelitis optica spectrum disorders (NMOSD) thalamic damage is controversial, but thalamic nuclei were never studied separately. We aimed at assessing volume loss of thalamic nuclei in NMOSD. We hypothesised that only specific nuclei are damaged, by attacks affecting structures from which they receive afferences: the lateral geniculate nucleus (LGN), due to optic neuritis (ON) and the ventral posterior nucleus (VPN), due to myelitis.MethodsThirty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 50.1±14.1 years, 36 women, 25 with prior ON, 36 with prior myelitis) and 37 healthy controls (age: 47.8 ± 12.5 years, 32 women) were included in this cross-sectional study. Thalamic nuclei were assessed in magnetic resonance images, using a multi-atlas-based approach of automated segmentation. Retinal optical coherence tomography was also performed.ResultsPatients with ON showed smaller LGN volumes (181.6±44.2 mm3) compared with controls (198.3±49.4 mm3; B=−16.97, p=0.004) and to patients without ON (206.1±50 mm3; B=−23.74, p=0.001). LGN volume was associated with number of ON episodes (Rho=−0.536, p<0.001), peripapillary retinal nerve fibre layer thickness (B=0.70, p<0.001) and visual function (B=−0.01, p=0.002). Although VPN was not smaller in patients with myelitis (674.3±67.5 mm3) than controls (679.7±68.33; B=−7.36, p=0.594), we found reduced volumes in five patients with combined myelitis and brainstem attacks (B=−76.18, p=0.017). Volumes of entire thalamus and other nuclei were not smaller in patients than controls.ConclusionThese findings suggest attack-related anterograde degeneration rather than diffuse thalamic damage in NMOSD. They also support a potential role of LGN volume as an imaging marker of structural brain damage in these patients.

The optic nerve head (ONH) is affected by many neurodegenerative and autoimmune inflammatory conditions. Optical coherence tomography can acquire high-resolution 3D ONH scans. However, the ONH’s complex anatomy and pathology make image segmentation challenging. This paper proposes a robust approach to segment the inner limiting membrane (ILM) in ONH volume scans based on an active contour method of Chan-Vese type, which can work in challenging topological structures. A local intensity fitting energy is added in order to handle very inhomogeneous image intensities. A suitable boundary potential is introduced to avoid structures belonging to outer retinal layers being detected as part of the segmentation. The average intensities in the inner and outer region are then rescaled locally to account for different brightness values occurring among the ONH center. The appropriate values for the parameters used in the complex computational model are found using an optimization based on the differential evolution algorithm. The evaluation of results showed that the proposed framework significantly improved segmentation results compared to the commercial solution.

IMPORTANCE: Clinically isolated syndrome (CIS) describes a first clinical incident suggestive of multiple sclerosis (MS). Identifying patients with CIS who have a high risk of future disease activity and subsequent MS diagnosis is crucial for patient monitoring and the initiation of disease-modifying therapy. OBJECTIVE: To investigate the association of retinal optical coherence tomography (OCT) results with future disease activity in patients with CIS. DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study took place between January 2011 and May 2017 at 2 German tertiary referral centers. A total of 179 patients with CIS were screened (80 in Berlin and 99 in Munich). Patients underwent neurological examination, magnetic resonance imaging (MRI), and OCT. Only eyes with no previous optic neuritis were considered for OCT analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was not meeting the no evidence of disease activity (NEDA-3) criteria; secondary outcomes were MS diagnosis (by the 2010 McDonald criteria) and worsening of disability. The primary measure was OCT-derived ganglion cell and inner plexiform layer thickness; the secondary measures included peripapillary retinal nerve fiber layer thickness, inner nuclear layer thickness, and MRI-derived T2-weighted lesions. RESULTS: A total of 97 of the 179 screened patients (54.2%) were enrolled in the study at a median of 93 (interquartile range [IQR], 62-161) days after a first demyelinating event. The median follow-up duration (Kaplan-Meier survival time) was 729 (IQR, 664-903) days. Of 97 patients with CIS (mean age 33.6 [7.9] years; 61 [62.9%] female), 58 (59%) did not meet NEDA-3 criteria during the follow-up period. A Kaplan-Meier analysis showed a significant probability difference in not meeting NEDA-3 criteria by ganglion cell and inner plexiform later thickness (thinnest vs thickest tertile: hazard ratio [HR], 3.33 [95% CI, 1.70-6.55; P &lt; .001; log-rank P = .001). A follow-up diagnosis of MS was more likely for patients with low ganglion cell and inner plexiform layer thickness (thinnest vs thickest tertile: HR, 4.05 [95% CI, 1.93-8.50]; P &lt; .001). Low peripapillary retinal nerve fiber layer thickness likewise indicated risk of not meeting NEDA-3 criteria (thinnest vs thickest tertile: HR, 2.46 [95% CI, 1.29-4.66]; P = .01; log-rank P = .02). Inner nuclear layer thickness and T2-weighted lesion count were not associated with not meeting NEDA-3 criteria. CONCLUSIONS AND RELEVANCE: Retinal ganglion cell and inner plexiform layer thickness might prove a valuable imaging marker for anticipating future disease activity and diagnosis of MS in patients with CIS, which can potentially support patient monitoring and initiation of disease-modifying therapy.

To identify the extent of ganglion cell damage after first-time optic neuritis (ON) using the inter-ocular difference between affected and fellow eyes, and whether this approach is able to detect more patients suffering from ganglion cell damage than using absolute values.

IMPORTANCE: Severe visual impairment is one of the major symptoms in neuromyelitis optica spectrum disorder (NMOSD), but functional network reorganization induced by the diminished sensory input has not been investigated thus far. OBJECTIVE: To examine adaptive visual network connectivity changes in NMOSD. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, data were collected from May 1, 2013, through February 31, 2016, from 31 patients with aquaporin-4 antibody–positive NMOSD and 31 age- and sex-matched healthy control individuals at the Department of Neurology and NeuroCure Clinical Research Center at Charité–Universitätsmedizin Berlin, Berlin, Germany. MAIN OUTCOMES AND MEASURES: Visual function (high-contrast visual acuity and contrast sensitivity), optical coherence tomography (peripapillary retinal nerve fiber layer and ganglion cell layer thickness), and resting-state functional magnetic resonance imaging (functional connectivity of large-scale brain networks). RESULTS: Thirty-one patients with NMOSD (mean [SD] age, 48.2 [13.9] years; 28 women and 3 men) and 31 healthy controls (mean [SD] age, 47.2 [15.3] years; 28 women and 3 men) participated in the study. Patients had a selective and pronounced increase of functional connectivity in the primary and secondary visual networks. Increased primary visual network connectivity correlated with reduced high-contrast visual acuity (r = −0.39, P = .006), reduced low-contrast sensitivity (r = −0.33, P = .03), and more severe retinal damage measured by optical coherence tomography (r = −0.4, P = .01). Furthermore, visual functional connectivity was significantly higher in patients with a history of optic neuritis compared with patients without optic neuritis (mean [SD] regression coefficients, 50.0 [4.3] vs 34.6 [5.6]; P = .04). CONCLUSIONS AND RELEVANCE: Impaired visual function and retinal damage are associated with selective reorganization of the visual network in NMOSD. These findings advance the understanding of visual system dysfunction in NMOSD and, more generally, provide insight into pathophysiologic responses of the visual system to impaired visual input.

IMPORTANCE: Clinical outcome in multiple sclerosis was suggested to be driven by not only remyelination but also adaptive reorganization. This mechanism needs to be further understood. OBJECTIVE: To explore anatomical and functional visual networks in patients with optic neuritis (ON) to assess the relative weight of each connectivity modality to expedite visual recovery. DESIGN, SETTING, AND PARTICIPANTS: Between March 11, 2011, and May 26, 2014, 39 patients with either clinically isolated syndrome (CIS) ON (n = 18) or other CIS (non-ON) (n = 21) were recruited 1 to 28 months following an initial clinical event. These patients enrolled in an ongoing prospective cohort study (107 participants at the time of this present study) about the disease course of CIS and multiple sclerosis. Inclusion criteria were an age of 18 to 65 years, the suggestive clinical and paraclinical diagnosis of CIS or multiple sclerosis after relevant differential diagnoses have been ruled out, the existence of complete imaging data, and no ocular comorbidities. Anatomical connectivity was evaluated by diffusion tensor imaging, and functional connectivity was evaluated by resting-state functional magnetic resonance imaging. The visual pathways, including optic tracts, optic radiations, and splenial fibers, were delineated, and the resting-state visual networks were detected. Data analysis took place from September 1, 2015, to December 1, 2015. MAIN OUTCOMES AND MEASURES: Connectivity changes were quantified and compared to determine the association of ON with the visual network. RESULTS: This study included 18 patients with CIS ON, 11 (61%) of whom were women with a mean (SD) age of 32.83 (8.53) years, and 21 patients with CIS non-ON (11 [52%] of whom were women with a mean [SD] age of 30.86 [7.54] years). With the use of diffusion tensor imaging, reduced diffusivity (mean [SD] fractional anisotropy, 0.35 [0.03] vs 0.38 [0.03]; P &lt; .01) was evident along the optic tracts of patients with ON, suggesting the extension of axonal injury from the damaged optic nerve. Neither the optic radiations nor the splenial fibers showed evidence of loss of integrity. Yet, in the presence of an intact postgeniculate anatomical network, the functional connectivity within the visual network was higher in the ON cohort. Functional connectivity observed in cortical motion–related areas was inversely correlated with the visual evoked potential–measured conduction velocity (r = −0.59; P &lt; .05). CONCLUSIONS AND RELEVANCE: In this cohort, local optic nerve demyelinating damage does not affect distant wiring, but even in the presence of an intact anatomical network, functional modification may occur. These functional network changes may be part of the recovery process, but further research is needed to elucidate this process.

ObjectivesNeuromyelitis optica spectrum disorders (NMOSD) are inflammatory conditions of the central nervous system and an important differential diagnosis of multiple sclerosis (MS). Unlike MS, the course is usually relapsing, and it is unclear, if progressive neurodegeneration contributes to disability. Therefore, we aimed to investigate if progressive retinal neuroaxonal damage occurs in aquaporin4-antibody-seropositive NMOSD.MethodsOut of 157 patients with NMOSD screened, 94 eyes of 51 patients without optic neuritis (ON) during follow-up (F/U) and 56 eyes of 28 age-matched and sex-matched healthy controls (HC) were included (median F/U 2.3 years). The NMOSD cohort included 60 eyes without (EyeON−) and 34 eyes with a history of ON prior to enrolment (EyeON+). Peripapillary retinal nerve fibre layer thickness (pRNFL), fovea thickness (FT), volumes of the combined ganglion cell and inner plexiform layer (GCIP) and the inner nuclear layer (INL) and total macular volume (TMV) were acquired by optical coherence tomography (OCT).ResultsAt baseline, GCIP, FT and TMV were reduced in EyeON+(GCIP p<2e−16; FT p=3.7e−4; TMV p=3.7e−12) and in EyeON− (GCIP p=0.002; FT p=0.040; TMV p=6.1e−6) compared with HC. Longitudinally, we observed GCIP thinning in EyeON−(p=0.044) but not in EyeON+. Seven patients had attacks during F/U; they presented pRNFL thickening compared with patients without attacks (p=0.003).ConclusionThis study clearly shows GCIP loss independent of ON attacks in aquaporin4-antibody-seropositive NMOSD. Potential explanations for progressive GCIP thinning include primary retinopathy, drug-induced neurodegeneration and retrograde neuroaxonal degeneration from lesions or optic neuropathy. pRNFL thickening in the patients presenting with attacks during F/U might be indicative of pRNFL susceptibility to inflammation.

Multiple sclerosis (MS) is one of the most prevalent chronic inflammatory diseases caused by demyelination and axonal damage in the central nervous system. Structural retinal imaging via optical coherence tomography (OCT) shows promise as a noninvasive biomarker for monitoring of MS. There are successful reports regarding the application of Artificial Intelligence (AI) in the analysis of cross-sectional OCTs in ophthalmologic diseases. However, the alteration of thicknesses of various retinal layers in MS is noticeably subtle compared to other ophthalmologic diseases. Therefore, raw cross-sectional OCTs are replaced with multilayer segmented OCTs for discrimination of MS and healthy controls (HCs).

Few studies have evaluated patient perspectives on neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD).

Optical coherence tomography (OCT) allows three-dimensional (3D) imaging of the retina, and is commonly used for assessing pathological changes of fovea and macula in many diseases. Many neuroinflammatory conditions are known to cause modifications to the fovea shape. In this paper, we propose a method for parametric modeling of the foveal shape. Our method exploits invariant features of the macula from OCT data and applies a cubic Bézier polynomial along with a least square optimization to produce a best fit parametric model of the fovea. Additionally, we provide several parameters of the foveal shape based on the proposed 3D parametric modeling. Our quantitative and visual results show that the proposed model is not only able to reconstruct important features from the foveal shape, but also produces less error compared to the state-of-the-art methods. Finally, we apply the model in a comparison of healthy control eyes and eyes from patients with neuroinflammatory central nervous system disorders and optic neuritis, and show that several derived model parameters show significant differences between the two groups.

Neuromyelitis optica spectrum disorders (NMOSD) are characterized by devastating optic neuritis attacks causing more structural damage and visual impairment than in multiple sclerosis (MS). The objective of this study was to compare vision-related quality of life in NMOSD and MS patients and correlate it to structural retinal damage and visual function.

Supplemental Digital Content is Available in the Text.This study describes the retinal lesion development in Susac syndrome during acute, postacute, and late phases of the disease using high-resolution optical coherence tomography, as well as identification and detailed description of four different lesion sections.

•Increased sGFAP levels are associated with neuro-axonal retinal layer thinning in clinically stable AQP4-IgG+NMOSD patients.•More profound functional visual impairment can be found in AQP4-IgG+NMOSD patients with higher sGFAP levels.•The absence of associations between sGFAP and retinal or functional visual alterations in MOGAD supports the specificity of sGFAP as a marker for subclinical chronic disease activity in AQP4-IgG+NMOSD.

To test the assumption of vitreous traction as a cause of macular microcysts in neuroinflammatory diseases and to establish a testable model to quantify vitreous traction changes.

Chronic inflammation in various organs, such as the brain, implies that different subpopulations of immune cells interact with the cells of the target organ. To monitor this cellular communication both morphologically and functionally, the ability to visualize more than two colors in deep tissue is indispensable. Here, we demonstrate the pronounced power of optical parametric oscillator (OPO)-based two-photon laser scanning microscopy for dynamic intravital imaging in hardly accessible organs of the central nervous and of the immune system, with particular relevance for long-term investigations of pathological mechanisms (e.g., chronic neuroinflammation) necessitating the use of fluorescent proteins. Expanding the wavelength excitation farther to the infrared overcomes the current limitations of standard Titanium:Sapphire laser excitation, leading to 1), simultaneous imaging of fluorophores with largely different excitation and emission spectra (e.g., GFP-derivatives and RFP-derivatives); and 2), higher penetration depths in tissue (up to 80%) at higher resolution and with reduced photobleaching and phototoxicity. This tool opens up new opportunities for deep-tissue imaging and will have a tremendous impact on the choice of protein fluorophores for intravital applications in bioscience and biomedicine, as we demonstrate in this work.

Schülerexperimente in außerschulischen Experimentierlabors sollen die Motivation von Schülern steigern, sich den naturwissenschaftlichen Unterrichtsfächern zuzuwenden. Mit der vorliegenden Fragebogenstudie wurde diese Annahme am Beispiel eines chemischen Experimentierlabors überprüft. Die Untersuchung erhob bei N= 272 Schülern der Sekundarstufe 1 motivationale Variablen vor und nach dem Laborbesuch, deren Angaben mit N= 222 Schülern einer Kontrollgruppe verglichen wurden. Die Ergebnisse zeigen, dass sich die Teilnahme am Experimentierangebot des außerschulischen Labors positiv auf motivationale Komponenten auswirkte. Das fachliche Selbstkonzept der Schüler wurde gesteigert, darüber hinaus verzögerte der Besuch des Chemielabors den in der Sekundarstufe 1 allgemein vorzufindenden Rückgang verschiedener Interessekomponenten. Bei einer Befragung vier Monate nach dem Laborbesuch waren allerdings keine positiven Effekte des Laborbesuchs mehr festzustellen.