ARVO 2026 presentation: Deep learning-based OCT profiling and functional assessment of fingolimod treatment in experimental autoimmune encephalomyelitis (EAE)

Methods

EAE was induced in C57BL/6JRj female mice using MOG formulated in Complete Freund’s adjuvant followed by pertussis toxin. Fingolimod hydrochloride (n=14) or vehicle (n=14) was administered by oral gavage every other day from day 2. Naïve mice served as controls (n=11). Disease progression was assessed by clinical scoring, in vivo imaging, and functional evaluation of vision. The thickness of retinal layers and the number and area of vitreous inflammatory cells were quantified from spectral-domain OCT scans at day 42 using a pipeline based on U-Net model. Functional assessment was performed using flash electroretinography (ERG) and visual evoked potentials (VEP). On day 42, tissues were collected. Optic nerves and cervical segments of spinal cord, were stained for myelin basic protein (MBP) to assess demyelination.

Results

Fingolimod treatment significantly reduced clinical scores. In the vehicle-treated group, the inner retinal layers were thinner as compared to naïve (P<0.01) and fingolimod (P<0.001) groups. Conversely, deep learning-based quantification of hyperreflective foci (presumably inflammatory cells) revealed no significant differences in cell number, area, or median size between groups. ERG showed impairment of photoreceptor and ON-bipolar cell function in the vehicle group, which was significantly alleviated by fingolimod. EAE also reduced oscillatory potential amplitudes and increased latencies. Fingolimod provided partial protection against these deficits. VEP N1 latency was significantly delayed in vehicle-treated animals as compared to the fingolimod group. Immunohistochemical analysis confirmed morphological protection, showing rescue of MBP area in optic nerves in fingolimod-treated mice when compared to vehicle (P<0.01). Similar but non-significant trend was observed in spinal cord.

Conclusions

Fingolimod effectively mitigates neurodegeneration of vision in EAE mice. Automated OCT segmentation results suggest that fingolimod’s beneficial effect acts on multiple retinal layers simultaneously.

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Authors

Maria Vähätupa, Anni Tenhunen, Leena Tähtivaara, Xavier Ekolle, Hajnalka Nádai, Niina Jääskeläinen, Simas Bijeikis, Olga Vergun, Anne Mari Haapaniemi, Sanni Varis, Anna Mari Koponen, Päivi Partanen, and Giedrius Kalesnykas