Inner nuclear layer and olfactory threshold are interlinked and reflect inflammatory activity in multiple sclerosis

Background Retinal inner nuclear layer (INL) and olfactory threshold (OT) are associated with inflammatory activity in multiple sclerosis (MS). Objective The study aims to investigate (a) whether there is an association of INL and OT in MS and (b) if changes in INL and OT follow a time pattern in relation to MS relapse. Methods We assessed INL by optical coherence tomography and OT by Sniffin’ Sticks in three different cohorts: a cross-sectional MS cohort ( n = 260), a longitudinal, 3-year cohort of MS ( n = 141) and healthy controls ( n = 30), and a longitudinal, 24-weeks cohort with acute MS relapse ( n = 28) and stable MS controls ( n = 27). Results Cross-sectionally, INL and OT were strongly correlated with number but not localization of relapse in the previous 12 months and INL correlated with OT. Longitudinally, INL was thicker and OT score was lower short term in times of relapse activity, but not long term and independent of relapse localization. In acute MS relapse, INL and OT were altered compared with stable MS, again, independent of relapse localization resolving over 12–24 weeks with faster approximation to stable MS after escalation of disease-modifying treatment. Conclusions INL and OT are interlinked markers of short-term inflammatory activity, following a nearly congruent time pattern and independent of relapse localization, possibly reflecting a proinflammatory state within the central nervous system.