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This article discusses the advantages and pitfalls of testing neuroprotective treatment strategies in patients suffering from optic neuritis.Spectral domain optical coherence tomography now permits for automated segmentation of individual retinal layers. The peripapillary retinal nerve fibre layer (pRNFL) has been used in 13 of the 15 trials reviewed. Twelve trials also made use of electrophysiology. Overestimation of good visual recovery in the past has recently been recognized. Assessment of low contrast visual acuity and colour vision are now mainstream.The availability of highly accurate and robust trial outcome measures has facilitated research on this topic. A single long-term structural outcome measurement of the pRNFL is sufficient. For shorter term, assessments of the ganglion cell/inner plexiform layer and axonal birefringence are promising. Longitudinal blood levels of neurofilament proteins permit to recognize axonal loss at presentation and monitor changes longitudinally. Inner nuclear layer volume changes relate to inflammatory disease activity.Pitfalls are related to the timing of events. Hyperacute recruitment is needed for future trials. The onset of demyelination is not known, which complicates timing of electrophysiological recordings. Optic disc oedema precludes the use of the pRNFL from the affected eye as a baseline variable. The concomitant use of corticosteroids complicates interpretation of trial data.