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

Abstract

BackgroundOptical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course.Material and methodsThis study includes two different patient cohorts recruited at a tertiary German academic multiple sclerosis center between 2018 and 2020 and a cohort of 40 healthy controls. A total of 90 patients with RRMS undergoing lumbar puncture and OCT-A analysis were enrolled into a cross-sectional cohort study to search for associations between the retinal vasculature and the intrathecal immune compartment. We recruited another 86 RRMS patients into a prospective observational cohort study who underwent clinical examination, OCT-A and cerebral magnetic resonance imaging at baseline and during annual follow-up visits to clarify whether alterations of the retinal vessels are linked to RRMS disease activity. Eyes with a history of optic neuritis were excluded from the analysis.ResultsRarefication of the superficial vascular complex occured during RRMS and was linked to higher frequencies of activated B cells and higher levels of the pro-inflammatory cytokines interferon-γ, tumor necrosis factor α and interleukin-17 in the cerebrospinal fluid. During a median follow-up of 23 (interquartile range 14 - 25) months, vessel loss within the superficial (hazard ratio [HR] 1.6 for a 1%-point decrease in vessel density, p=0.01) and deep vascular complex (HR 1.6 for a 1%-point decrease, p=0.05) was associated with future disability worsening.DiscussionOptic neuritis independent rarefication of the retinal vasculature might be linked to neuroinflammatory processes during RRMS and might predict a worse disease course. Thus, OCT-A might be a novel biomarker to monitor disease activity and predict future disability.

Prognostic role of plasma IL-17a expression and neoadjuvant therapy efficacy in breast cancer

“…Overall, IL-17a directly promotes tumor growth, invasion, and metastasis. Additionally, there is more evidence that IL-17a negatively regulates the immune response in cancer patients by recruiting myeloid suppressor cells (MDSCs) [34]. Moreover, an increase in IL-17a is associated with neutrophil-tolymphocyte ratio (NLR) and stimulation of programmed death ligand 1 (PD-1), which are positively related to immune escape [35].…”

Association of retinal vessel pathology and brain atrophy in relapsing-remitting multiple sclerosis

“…We acquired OCTA examinations on both eyes of each patient under low-lighting conditions (Heidelberg Spectralis OCT 2 with angiography module, Heidelberg Engineering) by experienced operators as described elsewhere ( 10 , 11 ). In brief, en face images were recorded (2.9 × 2.9 mm scanning area) manually centred on the fovea centralis and with active eye tracking.…”

“…Superficial retinal vessel loss is evident during the first 90 days after acute optic neuritis (ON) and linked to a poor visual acuity ( 8 – 10 ). We could recently show that narrowing of superficial retinal vessels also occurs in eyes without a history of ON, might be associated with a pro-inflammatory intrathecal immunity, and might predict a worse disease course in patients with early relapsing-remitting MS (RRMS) ( 11 ). These data suggest that the retinal vasculature might be involved in CNS autoimmunity.…”

Literature Commentary

“…Although these alterations might also be secondary to background attrition of inner retinal layers brought about by chronic RRMS, primary vascular damage by inflammatory mediators may also play a role. In a recent article in Frontiers Immunology, Noll and colleagues used OCT-A to study the relationship of RRMS-associated retinal vessel loss with markers of humoral and cellular immunity in the cerebrospinal fluid (CSF) and further examined the ability of such changes to predict clinical outcomes such as disability (3).…”