Neurol Neuroimmunol Neuroinflamm. 2018 Mar 13;5(3):e449. doi: 10.1212/NXI.0000000000000449.

by Oberwahrenbrock T, Traber GL, Lukas S, Gabilondo I, Nolan R, Songster C, Balk L, Petzold A, Paul F, Villoslada P, Brandt AU, Green AJ, Schippling S

Objective: To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans.
Methods: Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps.
Results: Agreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC >0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers.
Conclusions: Automated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL.

JAMA Neurol. 2018 Mar 1;75(3):296-303

by Finke C, Zimmermann H, Pache F, Oertel FC, Chavarro VS, Kramarenko Y, Bellmann-Strobl J, Ruprecht K, Brandt AU, Paul F

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.

JAMA Neurol. 2018 Mar 1;75(3):287-295

by Backner Y, Kuchling J, Massarwa S, Oberwahrenbrock T, Finke C, Bellmann-Strobl J, Ruprecht K, Brandt AU, Zimmermann H, Raz N, Paul F, Levin N

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 < .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 < .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.