Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions

Klistorner, Alexander; Sriram, Prema; Vootakuru, Nikitha; Wang, Chenyu; Barnett, Michael; Garrick, R.; Parratt, John; Levin, Netta; Raz, Noa; Walt, Anneke van der; Masters, Lynette; Graham, Stuart L.; Yiannikas, Con

doi:10.1212/wnl.0000000000000522

Cited by 99 publications

(95 citation statements)

References 40 publications

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“…Data were from 2367 eyes from 18 studies In MSNON eyes, the ONPL was minimally thinner compared to con-17 trol eyes ( Figure 5E, p=0.14). Data were based on 954 eyes from five studies 20,37,53,54,57 .…”

Section: Resultsmentioning

confidence: 99%

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis

Imsvisual

2017

The Lancet Neurology

429

413

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Section: Resultsmentioning

confidence: 99%

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis

Imsvisual

2017

The Lancet Neurology

429

413

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“…In comparison with the macular RNFL (mRNFL) thickness, combined ganglion cell layer and inner plexiform layers (GCIPL) thickness appear to have a better but still only moderate correlation with gray matter volume which is linked to disability in MS (Balcer et al., 2015). Moreover, OCT and MRI are promising tools to detect anterograde neurodegeneration after acute optic neuritis as well as retrograde neurodegeneration due to MS lesions in the posterior visual pathway (Gabilondo et al., 2014; Klistorner et al., 2014). How other functional networks aside from the primary visual system might be associated with neuronal loss within the anterior visual system has not been analyzed in depth (Saidha et al., 2013).…”

Section: Introductionmentioning

confidence: 99%

Pattern of gray matter volumes related to retinal thickness and its association with cognitive function in relapsing–remitting MS

et al. 2016

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BackgroundNeurodegeneration in multiple sclerosis (MS) may be investigated in the visual system as optical coherence tomography (OCT) and magnetic resonance imaging (MRI) allows examining structural integrity in detail. The association between thickness of retinal layers and focal cortical volumes beyond the primary visual system has not been thoroughly investigated.ObjectiveTo investigate the association between focal cortical volume and thickness of retinal layers.MethodsFifty‐four patients (relapsing–remitting MS, mean age 40.5 years, mean disease duration 7.6 years, median EDSS 2) underwent OCT and MRI. The association between focal cortical volume and OCT measurements was investigated with voxel‐based morphometry (VBM). Patterns of association were determined with Yeo's functional network atlas and the Harvard‐Oxford cortical atlas. We used GEE models with cortical volumes from the FreeSurfer parcellation to confirm VBM results. Post hoc, we analyzed the association between OCT, focal cortical volumes, and an extended neuropsychological assessment in a subgroup of 14 patients.ResultsMacular retinal nerve fiber layer (mRNFL) and ganglion cell /inner plexiform layer (GCIPL) showed a robust association with mainly the insular cortex and the cingulate cortex. VBM findings were confirmed with FreeSurfer volumes. The post hoc analysis detected significant correlations between both OCT outcomes and cognition.ConclusionBesides the primary visual system, OCT outcomes show a correlation pattern with cortical regions that are known to be important for cognitive performance, predominantly the insula in both hemispheres. Thus, OCT should be further investigated as a marker for neurodegeneration in MS.

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“…By contrast, this correlation was absent in fellow eyes of MS-ON patients [92]. A further study detected associations between high OR T2 lesion volume and OCT RNFL thinning as well as between increased OR T2 lesion volume and low LCVA scores [90]. These findings indicate functional impairment within the entire visual pathway caused by T2 lesions within the OR.…”

Section: Optic Radiation Dtimentioning

confidence: 86%

“…Analysis of optic tract asymmetry demonstrated significant associations with left/ right asymmetry of the OR lesion volume (r = −0.42, p = 0.001). This is possibly occurring due to retrograde trans-neuronal degeneration of optic tract fibers caused by OR lesions [90].…”

Section: Lesional Posterior Visual Pathway Damage In Msmentioning

confidence: 99%

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

et al. 2017

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The afferent visual pathway represents the most frequently affected white matter pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt brain tissue damage and quantify pathological processes. DTI facilitates the reconstruction of major white matter fiber tracts allowing for the assessment of structure-function and damage-dysfunction relationships. In this review, we outline DTI studies investigating the afferent visual pathway in idiopathic optic neuritis (ON), NMOSD, and MS. Since MS damage patterns are believed to depend on multiple factors, i.e., ON (anterior visual pathway damage), inflammatory lesions (posterior visual pathway damage), and global diffuse inflammatory and neurodegenerative processes, comprehensive knowledge on different contributing factors using DTI in vivo may advance our understanding of MS disease pathology. Combination of DTI measures and visual outcome parameters yields the potential to improve routine clinical diagnostic procedures and may further the accuracy of individual prognosis with regard to visual function and personalized disease outcome. However, due to the inherent limitations of DTI acquisition and post-processing techniques and the so far heterogeneous and equivocal data of previous studies, evaluation of the true potential of DTI as a possible biomarker for afferent visual pathway dysfunction is still substantially limited. Further research efforts with larger longitudinal studies and standardized DTI acquisition and post-processing validation criteria are needed to overcome current DTI limitations. DTI evaluation at different levels of the visual pathway has the potential to provide markers for individual damage evaluation in the future. As an imaging biomarker, DTI may support individual outcome prediction during personalized treatment algorithms in MS and other neuroinflammatory diseases, hereby leveraging the concept of predictive, preventive, and personalized medicine in the field of clinical neuroimmunology.

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Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions

Abstract: The results demonstrate a strong tract-specific association between loss of tRNFL fibers and MS-related inflammation within OR.

Cited by 99 publications

References 40 publications

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis

Pattern of gray matter volumes related to retinal thickness and its association with cognitive function in relapsing–remitting MS

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

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