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Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis
BACKGROUND AND OBJECTIVES: Microglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activ...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128002/ https://www.ncbi.nlm.nih.gov/pubmed/35606113 http://dx.doi.org/10.1212/NXI.0000000000001180 |
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author | Pengo, Marta Miante, Silvia Franciotta, Silvia Ponzano, Marta Torresin, Tommaso Bovis, Francesca Rinaldi, Francesca Perini, Paola Saiani, Martina Margoni, Monica Bertoldo, Alessandra Sormani, Maria Pia Pilotto, Elisabetta Midena, Edoardo Gallo, Paolo Puthenparampil, Marco |
author_facet | Pengo, Marta Miante, Silvia Franciotta, Silvia Ponzano, Marta Torresin, Tommaso Bovis, Francesca Rinaldi, Francesca Perini, Paola Saiani, Martina Margoni, Monica Bertoldo, Alessandra Sormani, Maria Pia Pilotto, Elisabetta Midena, Edoardo Gallo, Paolo Puthenparampil, Marco |
author_sort | Pengo, Marta |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Microglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS). METHODS: At baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study. RESULTS: Compared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (β: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002). DISCUSSION: We found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA. |
format | Online Article Text |
id | pubmed-9128002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-91280022022-08-03 Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis Pengo, Marta Miante, Silvia Franciotta, Silvia Ponzano, Marta Torresin, Tommaso Bovis, Francesca Rinaldi, Francesca Perini, Paola Saiani, Martina Margoni, Monica Bertoldo, Alessandra Sormani, Maria Pia Pilotto, Elisabetta Midena, Edoardo Gallo, Paolo Puthenparampil, Marco Neurol Neuroimmunol Neuroinflamm Research Article BACKGROUND AND OBJECTIVES: Microglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS). METHODS: At baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study. RESULTS: Compared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (β: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002). DISCUSSION: We found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA. Lippincott Williams & Wilkins 2022-05-23 /pmc/articles/PMC9128002/ /pubmed/35606113 http://dx.doi.org/10.1212/NXI.0000000000001180 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Research Article Pengo, Marta Miante, Silvia Franciotta, Silvia Ponzano, Marta Torresin, Tommaso Bovis, Francesca Rinaldi, Francesca Perini, Paola Saiani, Martina Margoni, Monica Bertoldo, Alessandra Sormani, Maria Pia Pilotto, Elisabetta Midena, Edoardo Gallo, Paolo Puthenparampil, Marco Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis |
title | Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis |
title_full | Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis |
title_fullStr | Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis |
title_full_unstemmed | Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis |
title_short | Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis |
title_sort | retinal hyperreflecting foci associate with cortical pathology in multiple sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128002/ https://www.ncbi.nlm.nih.gov/pubmed/35606113 http://dx.doi.org/10.1212/NXI.0000000000001180 |
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