. 2020 Sep;30(9):5048-5058.

doi: 10.1007/s00330-020-06859-w. Epub 2020 Apr 26.

Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders

Valentin Juenger^{1

2

3}, Graham Cooper^{1

2

4

5}, Claudia Chien^{1

2}, Meera Chikermane^{1

2}, Frederike Cosima Oertel^{1

2

6}, Hanna Zimmermann^{1

2}, Klemens Ruprecht⁷, Sven Jarius⁸, Nadja Siebert², Joseph Kuchling^{2

7}, Athina Papadopoulou^{2

9}, Susanna Asseyer^{2

7}, Judith Bellmann-Strobl^{1

2}, Friedemann Paul^{10

11

12

13}, Alexander U Brandt^{2

14}, Michael Scheel^{2

3}

Affiliations

¹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
² NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
³ Department of Neuroradiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁴ Einstein Center for Neurosciences, Berlin, Germany.
⁵ Department of Experimental Neurology and Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁶ Multiple Sclerosis Center, Dept. of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁷ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁸ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
⁹ Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine University Hospital Basel, Basel, Switzerland.
¹⁰ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. friedemann.paul@charite.de.
¹¹ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. friedemann.paul@charite.de.
¹² Einstein Center for Neurosciences, Berlin, Germany. friedemann.paul@charite.de.
¹³ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. friedemann.paul@charite.de.
¹⁴ Department of Neurology, University of California, Irvine, CA, USA.

PMID: 32335748
PMCID: PMC7431438
DOI: 10.1007/s00330-020-06859-w

Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders

Valentin Juenger et al. Eur Radiol. 2020 Sep.

. 2020 Sep;30(9):5048-5058.

doi: 10.1007/s00330-020-06859-w. Epub 2020 Apr 26.

Authors

Affiliations

¹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
² NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
³ Department of Neuroradiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁴ Einstein Center for Neurosciences, Berlin, Germany.
⁵ Department of Experimental Neurology and Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁶ Multiple Sclerosis Center, Dept. of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁷ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
⁸ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
⁹ Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine University Hospital Basel, Basel, Switzerland.
¹⁰ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. friedemann.paul@charite.de.
¹¹ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. friedemann.paul@charite.de.
¹² Einstein Center for Neurosciences, Berlin, Germany. friedemann.paul@charite.de.
¹³ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. friedemann.paul@charite.de.
¹⁴ Department of Neurology, University of California, Irvine, CA, USA.

PMID: 32335748
PMCID: PMC7431438
DOI: 10.1007/s00330-020-06859-w

Abstract

Objectives: We aimed to evaluate optic chiasm (OC) measures as potential imaging marker for anterior optic pathway damage assessment in the context of neuromyelitis optica spectrum disorders (NMOSD).

Materials and method: This cross-sectional study included 39 patients exclusively with aquaporin 4-IgG seropositive NMOSD of which 25 patients had a history of optic neuritis (NMOSD-ON) and 37 age- and sex-matched healthy controls (HC). OC heights, width, and area were measured using standard 3D T1-weighted MRI. Sensitivity of these measures to detect neurodegeneration in the anterior optic pathway was assessed in receiver operating characteristics analyses. Correlation coefficients were used to assess associations with structural measures of the anterior optic pathway (optic nerve dimensions, retinal ganglion cell loss) and clinical measures (visual function and disease duration).

Results: OC heights and area were significantly smaller in NMOSD-ON compared to HC (NMOSD-ON vs. HC p < 0.0001). An OC area smaller than 22.5 mm² yielded a sensitivity of 0.92 and a specificity of 0.92 in separating chiasms of NMOSD-ON from HC. OC area correlated well with structural and clinical measures in NMOSD-ON: optic nerve diameter (r = 0.4, p = 0.047), peripapillary retinal nerve fiber layer thickness (r = 0.59, p = 0.003), global visual acuity (r = - 0.57, p = 0.013), and diseases duration (r = - 0.5, p = 0.012).

Conclusion: Our results suggest that OC measures are promising and easily accessible imaging markers for the assessment of anterior optic pathway damage.

Key points: • Optic chiasm dimensions were smaller in neuromyelitis optica spectrum disorder patients compared to healthy controls. • Optic chiasm dimensions are associated with retinal measures and visual dysfunction. • The optic chiasm might be used as an easily accessible imaging marker of neurodegeneration in the anterior optic pathway with potential functional relevance.

Keywords: Magnetic resonance imaging; Neuromyelitis optica; Optic chiasm; Optic neuritis.

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Conflict of interest statement

The authors of this manuscript declare relationships with the following companies:

NS has received travel grants from Biogen Idec and sanofi-aventis/Genzyme.

SA received travel grants from Celgene GmbH, unrelated to this project.

FCO was employed by Nocturne, unrelated to this project.

HZ received research grants from Novartis, unrelated to this project.

KR was supported by the German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis) and has received research support from Novartis and Merck Serono as well as speaking fees and travel grants from Guthy Jackson Charitable Foundation, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche, and Novartis.

JBS has received travel grants and speaking fees from Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, and Novartis.

FP declares that he has received research grants and speaker’s honoraria from Bayer Healthcare, Teva Pharmaceuticals, Genzyme, Merck and Co., Novartis, and MedImmune. He is also a member of the steering committee for the OCTIMS study (run by Novartis).

AUB is cofounder and shareholder of technology start-ups Motognosis and Nocturne. He is named as inventor on several patent applications describing MS serum biomarkers, perceptive visual computing for motor function assessment and retinal image analysis.

Figures

**Fig. 1**
Optic chiasm measurement. Panels a, b, and c illustrate how axes were adjusted perpendicularly to the orientation of the OC in the center point. Panel d shows a sample OC measurement (a = right, b = central, c = left height, d = area, e = width)

**Fig. 2**
Optic nerve measurement. Panels a, b, and c illustrate how axes were adjusted perpendicularly to the orientation of the optic nerve

**Fig. 3**
Difference in optic chiasm dimensions. Shown are OCs of NMOSD-ON (a, b), NMOSD-NON (c, d), and HC (e, f)

**Fig. 4**
Optic chiasm measures. Group differences in optic chiasm heights, width, and area between neuromyelitis optica spectrum disorders patients with optic neuritis (NMOSD-ON), without optic neuritis (NMOSD-NON), and healthy controls (HC). ns: p > 0.05, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, ****p ≤ 0.0001

**Fig. 5**
Receiver operating characteristic for optic chiasm measures. Each line represents one group differentiation: green lines HC vs. NMOSD-ON, red lines HC vs. NMOSD-NON, blue lines NMOSD-ON vs. NMOSD-NON; ON = optic neuritis

See this image and copyright information in PMC

References

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1. Waters P, Reindl M, Saiz A, et al. Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2016;87(9):1005–1015. - PMC - PubMed
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Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders

Affiliations

Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

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LinkOut - more resources

Full Text Sources

Miscellaneous