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Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis
Marta Pengo1, Silvia Miante1, Silvia Franciotta1
1From the Multiple Sclerosis Centre (M. Pengo, S.M., S.F., M.S., M.M., P.G., M. Puthenparampil), Neurology Clinic, Department of Neuroscience, Università degli Studi di Padova; Department of Health Sciences (M. Ponzano, F.B., M.P.S.), Section of Biostatistics, University of Genova; Ophthalmology Clinic (T.T., E.P., E.M.), Department of Neuroscience, Università degli Studi di Padova, Italy; Fellow of the European Board of Ophthalmology (T.T., E.P., E.M.), London, United Kingdom; Multiple Sclerosis Centre (F.R., P.P.), Neurology Clinic, Azienda Ospedaliera di Padova; and Department of Information Engineering (DEI) (A.B.), University of Padova, Italy.
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.
Insights
Retinal microglia clusters (hyperreflecting foci or HRF) are elevated in early multiple sclerosis (MS) patients. Higher HRF counts correlate with disease activity, suggesting HRF as a potential prognostic biomarker for MS.
Area of Science:
- Neuroimmunology
- Ophthalmology
- Radiology
Background:
- Microglia, the brain's immune cells, are activated in multiple sclerosis (MS).
- Retinal microglia activation, visualized as hyperreflecting foci (HRF), is widespread in MS.
- The association between HRF and clinical/radiological parameters in early relapsing-remitting MS (RRMS) requires evaluation.
Purpose of the Study:
- To assess the presence and number of retinal HRF in patients with early RRMS.
- To investigate the correlation between HRF and clinical/radiological disease parameters.
- To explore HRF as a potential prognostic biomarker in RRMS.
Main Methods:
- 80 RRMS patients underwent optical coherence tomography (OCT) and 3T-MRI near disease onset.
- Patients were followed for 43 months, assessing no evidence of disease activity (NEDA) status.
- Exclusion criteria included a history of optic neuritis (ON) or suggestive MRI/OCT findings.
Main Results:
- HRF counts were significantly higher in the inner nuclear layer (INL) of RRMS patients compared to controls.
- HRF count correlated with INL volume and gray matter (GM) lesion volume.
- Higher INL HRF counts were associated with both clinical (cNEDA) and radiological (rNEDA) disease activity.
Conclusions:
- A strong association exists between retinal microglial proliferation (HRF) and cortical pathology in RRMS.
- Microglial activation at baseline, indicated by HRF, may predict future inflammatory events.
- HRF shows promise as a prognostic biomarker for MS, warranting further investigation.
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