Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning – an ultrahigh-field MR pilot study

Sinnecker, Tim; Oberwahrenbrock, Timm; Metz, Imke; Zimmermann, Hanna; Pfueller, Caspar F.; Harms, Lutz; Ruprecht, Klemens; Ramien, Caren; Hahn, Katrin; Brück, Wolfgang; Niendorf, Thoralf; Paul, Friedemann; Brandt, Alexander U.; Dörr, Jan; Wuerfel, Jens

doi:10.1007/s00330-014-3358-8

Cited by 88 publications

(83 citation statements)

References 43 publications

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“…Similar associations were seen in a study looking at focal atrophy in the optic radiations and RNFL thinning in early MS [78]. Whilst initial studies observed this relationship in patients with or without a history of ON [47,77], more recent studies [60,78] found that this relationship was significant only in MS patients without previous ON. Additionally, another study found no correlation between DTI measures in the optic radiations and RNFL thickness in a cohort of RRMS patients with a history of ON [49].…”

Section: Optic Radiationsupporting

confidence: 75%

“…Peripapillary RNFL thickness and macular volume was associated with lesion volume, NAWM and abnormal DTI measurements in the optic radiations of MS patients [47,60,72,77]. Similar associations were seen in a study looking at focal atrophy in the optic radiations and RNFL thinning in early MS [78]. Whilst initial studies observed this relationship in patients with or without a history of ON [47,77], more recent studies [60,78] found that this relationship was significant only in MS patients without previous ON.…”

Section: Optic Radiationmentioning

confidence: 55%

“…Another study found a positive relationship between retinal OCT parameters (peripapillary RNFL thickness, GCL, IPL, and TMV, although not INL) and MWI of the optic radiations in a cohort including healthy controls, MS and NMOSD patients [79]. The authors did not find any relationship between OCT measures and lesion volume in the optic radiations, unlike in previous work [60,78], but this may have been due to the small sample size of the study [79]. The relationship between retinal and optic radiation degeneration most likely involves both subclinical disease activity and possibly a common, as yet unknown, disease process affecting both the anterior and posterior visual pathway.…”

Section: Optic Radiationmentioning

confidence: 80%

“…Additionally, another study found no correlation between DTI measures in the optic radiations and RNFL thickness in a cohort of RRMS patients with a history of ON [49]. The significance of the relationship to RNFL in MS patients with a history of ON may be masked by severe damage in the retina post-ON [60,78]. Likewise, the ganglion cell complex (GCC) thickness, which includes the RNFL, GCL and IPL, was also significantly associated with abnormal DTI and increased lesion volume in the optic radiations of MS patients without a history of ON [60].…”

Section: Optic Radiationmentioning

confidence: 99%

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Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Manogaran

Hanson

Olbert

et al. 2016

IJMS

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Irreversible disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is largely attributed to neuronal and axonal degeneration, which, along with inflammation, is one of the major pathological hallmarks of these diseases. Optical coherence tomography (OCT) is a non-invasive imaging tool that has been used in MS, NMOSD, and other diseases to quantify damage to the retina, including the ganglion cells and their axons. The fact that these are the only unmyelinated axons within the central nervous system (CNS) renders the afferent visual pathway an ideal model for studying axonal and neuronal degeneration in neurodegenerative diseases. Structural magnetic resonance imaging (MRI) can be used to obtain anatomical information about the CNS and to quantify evolving pathology in MS and NMOSD, both globally and in specific regions of the visual pathway including the optic nerve, optic radiations and visual cortex. Therefore, correlations between brain or optic nerve abnormalities on MRI, and retinal pathology using OCT, may shed light on how damage to one part of the CNS can affect others. In addition, these imaging techniques can help identify important differences between MS and NMOSD such as disease-specific damage to the visual pathway, trans-synaptic degeneration, or pathological changes independent of the underlying disease process. This review focuses on the current knowledge of the role of the visual pathway using OCT and MRI in patients with MS and NMOSD. Emphasis is placed on studies that employ both MRI and OCT to investigate damage to the visual system in these diseases.

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Section: Optic Radiationsupporting

confidence: 75%

Section: Optic Radiationmentioning

confidence: 55%

Section: Optic Radiationmentioning

confidence: 80%

Section: Optic Radiationmentioning

confidence: 99%

See 2 more Smart Citations

Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Manogaran

Hanson

Olbert

et al. 2016

IJMS

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“…Wallerian degeneration (anterograde axonal degeneration) and retrograde axonal degeneration (Bdying-back^degeneration) have been suggested to occur as mid-to long-term damage after acute inflammatory changes [22], e.g., due to ON or after lesional development within the OR. Beyond focal axonal damage and its direct mid-term consequences, the question has emerged as to whether trans-synaptic degeneration may play an additional significant role in chronic disease development and neurodegeneration [23].…”

Section: Ms Visual Pathway White Matter Damage Patternsmentioning

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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Association of Retinal Ganglion Cell Layer Thickness With Future Disease Activity in Patients With Clinically Isolated Syndrome

et al. 2018

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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 < .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 < .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.

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Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning – an ultrahigh-field MR pilot study

Cited by 88 publications

References 43 publications

Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

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

Association of Retinal Ganglion Cell Layer Thickness With Future Disease Activity in Patients With Clinically Isolated Syndrome

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