# The clinical relevance of hyper-reflective foci in the inner retina at the diagnosis of multiple sclerosis

**Authors:** Marco Puthenparampil, Alessandro Miscioscia, Elisa Basili, Valentina Annamaria Mauceri, Marta Pengo, Tommaso Torresin, Federica De Napoli, Elisabetta Pilotto, Francesca Rinaldi, Paola Perini, Edoardo Midena, Paolo Gallo

PMC · DOI: 10.1186/s42466-025-00447-3 · Neurological Research and Practice · 2025-11-14

## TL;DR

This study shows that higher numbers of hyper-reflective foci in the inner retina at MS diagnosis are linked to a greater risk of treatment failure.

## Contribution

The study identifies hyper-reflective foci in the inner retina as a potential biomarker for predicting treatment efficacy in multiple sclerosis.

## Key findings

- Patients with higher HRF counts in the inner nuclear layer had a significantly increased risk of therapeutic switch.
- HRF counts were significantly higher in patients who switched therapies compared to those who did not.
- HRF may help neurologists make better treatment decisions for MS patients.

## Abstract

Hyper-Reflective foci (HRF) increased in the inner retina (IR) of patients with Multiple Sclerosis (pwMS).

To evaluate the risk of therapeutic failure, based on HRF count at baseline.

Fifty-seven pwMS were included in this retrospective, cohort, single-centre study. All patients were enrolled at clinical onset and were treatment-naive, with no evidence of optic nerve involvement. Patient were divided at baseline based on the MS treatment in platform-therapy pwMS (PTpwMS) and as High efficacy therapy pwMS (HETpwMS). Then, all PTpwMS were followed up (87.6±31.2 months) to evaluate the time to therapeutic switch for lack of efficacy on outcomes. HRF count was expressed as the sum of both eyes in Ganglion Cell-Inner Plexiform Layer (GCIP), Inner Nuclear Layer (INL) and Inner Retina (IR, GCIP + INL).

Survival analysis confirmed an increased risk of therapeutic switch in those patients with a higher HRF-INL count (Log-Rank p < 0.0001, H.R. 7.9, 95%CI 2.6–24.5). PTpwMS switching during the follow up had significantly higher HRF count in INL compared to not-switching (45.80 ± 10.32vs 31.75 ± 6.27, p < 0.05).

HRF might be a useful marker to predict the risk of acute demyelination in MS and might give help Neurologist in therapeutic decision.

The online version contains supplementary material available at 10.1186/s42466-025-00447-3.

## Linked entities

- **Diseases:** Multiple Sclerosis (MONDO:0005301)

## Full-text entities

- **Diseases:** MS (MESH:D009103), HRF (MESH:C565785), demyelination (MESH:D003711)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

12 references — full list in the complete paper: https://tomesphere.com/paper/PMC12619398/full.md

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Source: https://tomesphere.com/paper/PMC12619398