Low-contrast visual acuity test is associated with central inflammation and predicts disability development in newly diagnosed multiple sclerosis patients

Ettore Dolcetti; Fabio Buttari; Antonio Bruno; Federica Azzolini; Luana Gilio; Veronica Di Caprio; Gianluca Lauritano; Angela Borrelli; Giovanni Galifi; Roberto Furlan; Annamaria Finardi; Alessandra Musella; Livia Guadalupi; Georgia Mandolesi; Valentina Rovella; Diego Centonze; Mario Stampanoni Bassi

doi:10.3389/fneur.2024.1326506

Low-contrast visual acuity test is associated with central inflammation and predicts disability development in newly diagnosed multiple sclerosis patients

Front Neurol. 2024 Feb 23:15:1326506. doi: 10.3389/fneur.2024.1326506. eCollection 2024.

Authors

Ettore Dolcetti^#¹, Fabio Buttari^#^{1

2}, Antonio Bruno¹, Federica Azzolini¹, Luana Gilio^{1

3}, Veronica Di Caprio¹, Gianluca Lauritano¹, Angela Borrelli¹, Giovanni Galifi¹, Roberto Furlan⁴, Annamaria Finardi⁴, Alessandra Musella^{5

6}, Livia Guadalupi^{2

5}, Georgia Mandolesi^{5

6}, Valentina Rovella², Diego Centonze^{1

2}, Mario Stampanoni Bassi¹

Affiliations

¹ Neurology Unit, IRCSS Neuromed, Pozzilli, Italy.
² Department of Systems Medicine, Tor Vergata University, Rome, Italy.
³ Faculty of Psychology, Uninettuno Telematic International University, Rome, Italy.
⁴ Clinical Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
⁵ Synaptic Immunopathology Lab, IRCCS San Raffaele Roma, Rome, Italy.
⁶ Department of Human Sciences and Quality of Life Promotion, University of Rome San Raffaele, Rome, Italy.

^# Contributed equally.

Abstract

Introduction: The visual system is a prominent site of damage in MS since the earliest phases of the disease. Altered low-contrast visual acuity (LCVA) test has been associated with visual impairment and retinal degeneration, predicting medium- and long-term disability. However, it is unclear whether LCVA may also represent a reliable measure of neuroinflammation and a predictor of disease evolution in the very early stages of MS.

Methods: We explored in a group of 76 consecutive newly diagnosed relapsing-remitting MS (RR-MS) patients without visual impairment or altered visual evoked potentials, the association between LCVA scores at 2.5% and 1.25% and clinical characteristics, including prospective disability evaluated after 1- and 2 years of follow-up. Associations between LCVA and the CSF levels of IL-10 at diagnosis were also analyzed.

Results: A negative correlation was found between LCVA at 2.5% and Expanded Disability Status Scale (EDSS) evaluated at first (Spearman's Rho = -0.349, p = 0.005, n = 62) and second year (Spearman's Rho = -0.418, p < 0.001, n = 62) of follow-up, and negative correlations were found with Multiple Sclerosis Severity Score (MSSS) at first (Spearman's Rho = -0.359, p = 0.004, n = 62) and second year (Spearman's Rho = -0.472, p < 0.001, n = 62). All the data were confirmed by a mixed effect model, considering other clinical variables. A positive correlation was found between the CSF concentrations of IL-10 and LCVA at 2.5% (Spearman's Rho = 0.272, p = 0.020, n = 76), and 1.25% (Spearman's Rho, = 0.276, p = 0.018, n = 76), also evidenced in a linear regression.

Discussion: In MS patients at diagnosis, altered LCVA may be associated with CSF inflammation and represent a useful parameter to identify patients with worse disease course.

Keywords: EDSS; IL-10; LCVA; MSSS; disability; multiple sclerosis; neuroinflammation.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The study was supported by: Ministero della Salute (Ministry of Health, Italy): DC and GM RF-2018-12366144; Ministero della Salute (Ministry of Health, Italy): FB GR-2018-12366154; Ministero della Salute (Ministry of Health, Italy): Progetto Ricerca Corrente to IRCCS Neuromed; Ministero della Salute (Ministry of Health, Italy): Progetto Ricerca Corrente to IRCCS San Raffaele: GM; Fondazione Italiana Sclerosi Multipla (FISM): DG cod. 2019/S/1 and financed or co-financed with the “5 per mille” public funding; Fondazione Italiana Sclerosi Multipla (FISM): MS cod. 2020/R-Multi/018 and financed or co-financed with the “5 per mille” public funding; Project “Nuovi Biomarker Diagnostici e Terapeutici delle Malattie Neurodegenerative”—ADOPT co-funded by FOE 2020—funding from CNR to DC.