Association of Cerebrospinal Fluid Parameters and Neurofilament Light Chain With Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis

Abstract

IntroductionMultiple sclerosis (MS) pathophysiology comprises both inflammatory and neurodegenerative characteristics. Cerebrospinal fluid (CSF) analysis allows for assessment of inflammation while neurofilament light chain can indicate neuroaxonal damage. Retinal thinning is a robust prognostic biomarker for neurodegeneration in MS. To date, an association between CSF parameters upon MS diagnosis and retinal thinning has not been investigated.Aims and ObjectivesWe aimed to determine whether CSF parameters are associated with the evolution of retinal layer thinning in people with MS (pwMS).MethodsFor this longitudinal observational study, we investigated pwMS from the Vienna MS database (VMSD), who had undergone (1) a diagnostic lumbar puncture (LP) between 2015 and 2020, and (2) simultaneous optical coherence tomography (OCT) and/or (3) a follow-up OCT scan. Linear stepwise regression models were calculated with OCT parameters (peripapillary retinal nerve fiber layer [pRNFL] thickness at LP and at follow-up, annualized loss of pRNFL thickness [aLpRNFL]) as a dependent variable, and CSF parameters (white blood cell [WBC] count, total protein [CSFTP], CSF/serum albumin ratio [Qalb], intrathecal synthesis of immunoglobulins, neurofilament light chain [NfL] in both CSF and serum [CSFNfL/sNfL]) as independent variables adjusted for age, sex, and disease duration.ResultsWe analyzed 61 pwMS (median age 30.0 years [interquartile range 25.5–35.0], 57.4% female, median disease duration 1.0 month [IQR 0–2.0] before LP, median follow-up 1.9 years [IQR 1.1–3.5]). CSFNfL and sNfL measurements were available in 26 and 31 pwMS, respectively. pRNFL thickness at LP was inversely associated with the CSF WBC count (β = −0.36; 95% CI −0.51, −0.08; p = 0.008). We did not find any association between other CSF parameters, including CSFNfL, sNfL, and aLpRNFL.ConclusionsIncreased WBC count as an indicator of acute inflammation and blood-brain-barrier breakdown seems to be associated with the amount of retinal thickness already lost at the time of LP. However, neither routine CSF parameters nor a singular NfL measurement allows the prediction of future retinal thinning.

Association of the retinal vasculature, intrathecal immunity, and disability in multiple sclerosis

“…These findings are in line with the literature. We could show in the past that ganglion cell loss during multiple sclerosis might be linked to a pronounced humoral immune response within the CSF (3) and a recent publication suggested that CSF pleocytosis is associated with retinal axonal loss (25). Moreover, there is first evidence that retinal OCT might also allow to monitor microglia function and immunity during MS. Retinal hyperreflective foci, which are mainly found within the inner nuclear layer and are considered as clustered retinal microglia, have been linked to elevated levels of several pro-inflammatory cytokines within the CSF (26).…”

Optical Coherence Tomography Angiography: Revolutionizing Clinical Diagnostics and Treatment in Central Nervous System Disease

“…A previous study by Knier et al using OCT showed that loss of GC-IPL is associated with intrathecal B-cell immunity and constitutes an independent risk factor for worsening disability, whereas high INL volumes are associated with activity on MRI in the brain parenchyma [135]. Another study by Krajnc et al using OCT showed that increased leukocyte counts in CSF appeared to be associated with loss of RNFL thickness [136].…”