Retinal hyper-reflective foci link retinal and cortical pathology in paediatric multiple sclerosis

Area of Science:

• Ophthalmology
• Neurology
• Biomarkers

Background:

• Pediatric-onset multiple sclerosis (MS) exhibits high early inflammatory activity.
• Sensitive biomarkers for early pediatric MS pathology are limited.
• Hyper-reflective foci (HRF) on optical coherence tomography (OCT) are potential inflammation markers in adult MS, but their role in pediatric MS is unclear.

Purpose of the Study:

• To identify and quantify retinal layer-specific HRF burden in children with pediatric-onset MS.
• To evaluate the association between HRF burden and MRI markers of disease severity in pediatric MS.
• To assess HRF as a potential non-invasive biomarker for pediatric MS.

Main Methods:

• Cross-sectional study of 53 children with pediatric-onset MS and 36 healthy controls.
• Spectral-domain OCT and brain MRI (3D T1-weighted, FLAIR) were performed near disease onset.
• HRF were quantified in the ganglion cell-inner plexiform layer (GCIPL) and inner nuclear layer (INL); MRI data underwent parcellation and lesion segmentation.

Main Results:

• HRF counts and normalized indices were significantly higher in pediatric MS patients compared to controls in both retinal layers.
• Higher GCIPL HRF index correlated with greater white matter lesion volume and lower thalamic volume.
• Adjusted models showed independent associations between MS and increased HRF in GCIPL and INL, with HRF also linked to retinal nerve fiber layer thinning and brain atrophy.

Conclusions:

• Children with pediatric-onset MS show increased retinal HRF burden early in the disease course, even without optic neuritis.
• HRF burden, particularly in the GCIPL, is associated with both inflammatory (lesion volume) and neurodegenerative (thalamic and cortical atrophy) aspects of MS.
• HRF represent a promising non-invasive biomarker for assessing disease severity in pediatric-onset MS.