Association of Visual Impairment in Neuromyelitis Optica Spectrum Disorder With Visual Network Reorganization

Abstract

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.

Figure 1.. Primary and Secondary Visual Networks

The primary (A) and secondary (B) visual networks were identified using independent component analysis.

Figure 2.. Visual Network Connectivity in Neuromyelitis Optica Spectrum Disorder (NMOSD)

A, Patients with NMOSD had substantially increased functional connectivity within the entire primary visual network bilaterally (calcarine sulcus, lingual gyrus, and cuneus) and regions outside the primary visual network, including the lateral occipital cortex, occipital fusiform gyrus, and middle temporal gyrus (P < .05, familywise error corrected). Coronal and axial sections are shown in the lower panel and regression coefficients extracted from regions with significant group differences on the right. B, Secondary visual network functional connectivity was increased in the occipital pole bilaterally. Coronal and axial sections are shown in the lower panel and extracted regression coefficients on the right. Error bars indicate SD. ^aP < .05.

Figure 3.. Correlation of Visual Network Connectivity With Visual Function and Retinal Damage

A and B, Correlation analyses using generalized estimating equation models revealed that impaired high-contrast visual acuity and impaired low-contrast sensitivity were associated with increased primary visual network connectivity regression coefficients. C, Reduced ganglion cell–inner plexiform layers (GCIPLs) of the retina (ie, retinal damage) were likewise associated with increased primary visual network connectivity. AUC indicates area under the curve.

Figure 4.. Visual Network Connectivity in Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD) With and Without a History of Optic Neuritis (ON)

A, In the primary visual network, patients with NMOSD and previous ON had significantly higher functional connectivity compared with patients with NMOSD without prior ON. B, In the secondary visual network, no connectivity differences were observed between patients with NMOSD with and without ON. Error bars indicate SD. ^aP < .05.