Hyperreflective Foci in the Inner Nuclear Layer: Proof-of-Concept for an Optical Coherence Tomography Derived Microglia-Related Marker in Multiple Sclerosis

The role of microglia has emerged as a critical driver of disease progression in multiple sclerosis (MS), but we lack broadly applicable monitoring tools. Here, we investigated whether hyperreflective foci (HRF), as detected by optical coherence tomography (OCT) within the inner nuclear layer (INL) of the retina, can be used as a marker for microglial pathology. We demonstrate that HRF counts are increased in persons with relapsing and progressive MS and correlate with global white and gray matter, as well as deep gray matter [18F]GE-180 uptake. [Color figure can be viewed at www.annalsofneurology.org] ANN NEUROL 2026;99:1480-1485.