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Hyper-reflective foci changes in RRMS under natalizumab therapy
Marco Puthenparampil1,2, Elisa Basili1,2, Marta Ponzano3
1Department of Neurosciences, University of Padua, Padua, Italy.
Introduction:
Microglia (MG) is suggested to play an immunopathological role of in Multiple Sclerosis (MS). Since hyper-reflective foci (HRF) might mark MG activation, in vivo analysis by Optic Coherence Tomography (OCT) in MS patients under disease modifying therapies may help to clarify MS immunopathology as well as drug's mechanism of intrathecal action.
Objective:
To analyze HRF in patients treated with Natalizumab (NTZ), a high efficacy therapy for MS.
Materials And Methods:
The effect of NTZ on the retina of 36 Relapsing-Remitting MS patients was investigated in a prospective, single-center study. OCT was performed immediately before the first infusion and then between infusion 3 and 4, infusion 6 and 7, infusion 11 and 13. Peripapillary and macular scans were acquired, evaluating peripapillary RNFL thickness, macular volumes (vertical scans), and HRF count (horizontal scan) in Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL) and Inner Nuclear Layer (INL). Clinical examination was performed every six months.
Results:
HRF count significantly increased under NTZ therapy (p<0.001) in both GCL (18.85 ± 6.93 at baseline, 28.24 ± 9.55 after 12 months) and IPL (25.73 ± 7.03 at baseline, 33.21 ± 8.50 after 12 months) but remained stable in INL (33.65 ± 7.76 at baseline, 36.06 ± 6.86 after 12 months, p=0.87), while no relevant modification of pRNFL and macular volumes were observed during the study. EDSS remained stable and no clinical relapse was observed between month 6 and 12.
Conclusion:
In RRMS NTZ affects HRF count in GCL and IPL, but not in INL, suggesting that NTZ does not impact on some aspects of MS immunopathology.
Insights
Natalizumab (NTZ) therapy for Multiple Sclerosis (MS) increases hyper-reflective foci (HRF) in the retinal ganglion cell layer and inner plexiform layer. This suggests NTZ may not impact all aspects of MS immunopathology.
Area of Science:
- Neuro-immunology
- Ophthalmology
- Neuroscience
Background:
- Microglia (MG) activation is implicated in Multiple Sclerosis (MS) immunopathology.
- Hyper-reflective foci (HRF) observed via Optical Coherence Tomography (OCT) may indicate MG activation.
- Understanding drug mechanisms in MS is crucial for treatment optimization.
Purpose of the Study:
- To investigate the effect of Natalizumab (NTZ) on HRF in MS patients.
- To clarify the impact of NTZ on retinal layers indicative of microglial activity.
- To explore NTZ's mechanism of intrathecal action in MS.
Main Methods:
- Prospective, single-center study of 36 Relapsing-Remitting MS (RRMS) patients treated with NTZ.
- OCT imaging (peripapillary and macular scans) performed at multiple time points during NTZ therapy.
- Analysis of peripapillary retinal nerve fiber layer (RNFL) thickness, macular volumes, and HRF count in specific retinal layers (GCL, IPL, INL).
Main Results:
- HRF count significantly increased in the Ganglion Cell Layer (GCL) and Inner Plexiform Layer (IPL) under NTZ therapy.
- No significant changes in HRF count were observed in the Inner Nuclear Layer (INL).
- No significant modifications in RNFL thickness or macular volumes were detected; clinical outcomes (EDSS, relapses) remained stable.
Conclusions:
- NTZ therapy influences HRF count in the GCL and IPL of RRMS patients.
- The observed changes suggest NTZ may not affect all microglial-related immunopathological processes in MS.
- Further research is needed to fully elucidate the impact of NTZ on MS immunopathology.

