• Sina C Rosenkranz, Lilija Gutmann, Arzu Ceylan Has Silemek, Michael Dorr, Vivien Häußler, Margareta Lüpke, Andrea Mönch, Stefanie Reinhardt, Jens Kuhle, Penelope Tilsley, Christoph Heesen, Manuel A Friese, Alexander Brandt, Friedemann Paul, Hanna Zimmermann, and Jan-Patrick Stellmann.
• Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany.
• J. Neurol. Neurosurg. Psychiatr. 2023 Nov 1; 94 (11): 924933924-933.

BackgroundNeurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood.MethodsWe assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNfL) levels in a prospective PPMS cohort and matched healthy controls. We investigated the changes over time, correlations between outcomes and with loss of visual function.ResultsWe followed 81 patients with PPMS (mean disease duration 5.9 years) over 2.7 years on average. Retinal nerve fibre layer thickness (RNFL) was reduced in comparison with controls (90.1 vs 97.8 µm; p<0.001). Visual function quantified by the area under the log contrast sensitivity function (AULCSF) remained stable over a continuous loss of RNFL (0.46 µm/year, 95% CI 0.10 to 0.82; p=0.015) up until a mean turning point of 91 µm from which the AULCSF deteriorated. Intereye RNFL asymmetry above 6 µm, suggestive of subclinical optic neuritis, occurred in 15 patients and was related to lower AULCSF but occurred also in 5 out of 44 controls. Patients with an AULCSF progression had a faster increase in Expanded Disability Status Scale (beta=0.17/year, p=0.043). sNfL levels were elevated in patients (12.2 pg/mL vs 8.0 pg/mL, p<0.001), but remained stable during follow-up (beta=-0.14 pg/mL/year, p=0.291) and were not associated with other outcomes.ConclusionWhereas neurodegeneration in the anterior visual system is already present at onset, visual function is not impaired until a certain turning point. sNfL is not correlated with structural or functional impairment in the visual system.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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