Hyperreflective Foci in the Inner Nuclear Layer: Proof-of-Concept for an Optical Coherence Tomography Derived

Jonathan A Gernert1,2, Laura M Bartos1,3, Tara Christmann1

  • 1Institute of Clinical Neuroimmunology, LMU Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Annals of Neurology
|April 8, 2026
PubMed

Insights

Hyperreflective foci (HRF) in optical coherence tomography (OCT) scans may serve as a novel monitoring tool for microglial pathology in multiple sclerosis (MS). Increased HRF counts correlate with disease activity and microglial uptake of a PET tracer.

Area of Science:

  • Neuroimmunology
  • Ophthalmology
  • Neuroimaging

Background:

  • Microglia play a key role in multiple sclerosis (MS) pathogenesis.
  • Current monitoring tools for microglial pathology in MS are limited.
  • Hyperreflective foci (HRF) are detectable in the retina using optical coherence tomography (OCT).

Purpose of the Study:

  • To investigate if retinal hyperreflective foci (HRF) detected by optical coherence tomography (OCT) can serve as a marker for microglial pathology in multiple sclerosis (MS).

Main Methods:

  • Utilized optical coherence tomography (OCT) to detect hyperreflective foci (HRF) in the inner nuclear layer (INL) of the retina.
  • Quantified HRF counts in individuals with relapsing and progressive MS.
  • Correlated HRF counts with global white and gray matter volumes and [18F]GE-180 uptake in deep gray matter using positron emission tomography (PET).

Main Results:

  • HRF counts were significantly increased in patients with relapsing and progressive MS compared to controls.
  • A positive correlation was observed between HRF counts and [18F]GE-180 uptake, a marker of microglial activation, in deep gray matter.
  • HRF counts also correlated with global white and gray matter integrity.

Conclusions:

  • Retinal hyperreflective foci (HRF) detected by OCT show promise as a non-invasive imaging biomarker for microglial pathology in multiple sclerosis (MS).
  • HRF may reflect disease activity and microglial involvement in both white and gray matter lesions.
  • Further research is warranted to validate HRF as a reliable tool for monitoring MS progression and treatment response.