Multiple sclerosis disease-modifying treatments have reduced inflammatory activity but have limited impact on progressive neurodegeneration. In this context, remyelination and neuroprotection appear as key therapeutic goals. The visual pathway offers an attractive translational model, as optic neuritis recapitulates the demyelinating and neurodegenerative features of multiple sclerosis while providing accessible functional and structural readouts through visual evoked potentials and optical coherence tomography. Over the past two decades, several clinical trials have evaluated remyelinating and neuroprotective agents using optic neuritis as a model. However, so far, no phase 3 trial has met its primary endpoint for either indication. This review synthesises the preclinical rationale, clinical trial evidence, and methodological lessons from these studies. Key challenges include the timing of intervention, heterogeneity in baseline damage, variability of electrophysiological assessments, and uncertain clinical impact of surrogate markers. Addressing these limitations through refined trial design, outcome measure harmonisation, and combined therapeutic strategies will be essential for future translational success.