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Published on: May 26, 2023
Hyperreflective dots in the avascular outer retina in relapsing-remitting multiple sclerosis.
Mathias Falck Schmidt1, Gorm Pihl-Jensen1, Marie Elise Wistrup Torm2
1Department of Neurology, Clinic of Optic Neuritis, The Danish Multiple Sclerosis Center (DMSC), Rigshospitalet and University of Copenhagen, Valdemar Hansens Vej 13, 2600, Glostrup, Denmark.
Optical coherence tomography (OCT) detected hyperreflective foci in the outer nuclear layer of the retina in most relapsing-remitting multiple sclerosis (RRMS) patients, but rarely in healthy individuals. This finding may offer a new non-invasive method for studying CNS inflammation in RRMS.
Area of Science:
- Ophthalmology
- Neuroscience
- Medical Imaging
Background:
- Hyperreflective foci in the retina, detected by optical coherence tomography (OCT), may indicate activated microglia.
- Their presence in the outer nuclear layer (ONL) of the retina, typically avascular and acellular in healthy individuals, has not been previously established.
- Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system (CNS).
Purpose of the Study:
- To investigate the presence and density of hyperreflective foci in the ONL of patients with relapsing-remitting multiple sclerosis (RRMS).
- To utilize high-resolution OCT for detecting these foci in the ONL.
- To explore potential associations between hyperreflective foci and other retinal parameters.
Main Methods:
- A cross-sectional study involving 44 RRMS patients and 53 healthy controls.
- Spectral domain OCT imaging was performed on all participants.
- High-resolution analysis of 23,200 B-scans per participant to quantify hyperreflective foci in the ONL within total scans and a 6-mm fovea-centered field.
Main Results:
- Hyperreflective foci were found in 70.5% of RRMS patients versus 1.8% of healthy subjects (p < 0.0001).
- The median number of foci in the ONL was significantly higher in RRMS patients (1) compared to controls (0) (p < 0.0001).
- No association was observed between hyperreflective foci and retinal nerve fiber layer or ganglion cell layer thickness.
Conclusions:
- Hyperreflective foci in the ONL are largely absent in healthy individuals but present in the majority of RRMS patients.
- OCT detection of these foci offers a novel, non-invasive method for investigating CNS inflammation in MS.
- This approach may open new avenues for studying infiltrating elements in the unmyelinated CNS.

