In individuals with multiple sclerosis (MS), abnormal thinning of the retinal layers has been observed, which is linked to clinical disability and brain atrophy. This thinning could serve as a potential surrogate marker for neurodegeneration and the effects of treatment. In an exploratory substudy, thinning was noted across all retinal layers and time points in the placebo group.
Siponimod, however, significantly reduced the thinning of the ganglion cell-inner plexiform layer (GCIPL) compared to placebo at month 24 (adjusted mean [SE] [µm]: −0.47 [0.81] vs. −4.29 [1.23]; p = 0.01). Moreover, overall retinal thinning at months 12 and 24 was also reduced with siponimod. At month 12, the adjusted mean retinal thinning was +0.66 [0.54] in the siponimod group versus −1.86 [0.75] in the placebo group (p = 0.006), and at month 24, it was −0.05 [0.59] versus −2.30 [0.88] (p = 0.033), respectively. Although not statistically significant, the results for the peripapillary retinal nerve fiber layer (pRNFL) followed similar trends.
These findings suggest that optical coherence tomography (OCT) measurement of retinal atrophy may serve as a non-invasive biomarker for monitoring the effects of treatment on neurodegeneration in secondary progressive multiple sclerosis (SPMS). Further investigation is warranted to validate this approach.