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Background Researchers have in recent years begun to investigate ophthalmological manifestations of multiple sclerosis (MS) other than optic neuritis (ON), and it is now clear that changes to retinal function (measured using the electroretinogram, ERG) and structure (measured using optical coherence tomography, OCT) are found in MS patients irrespective of prior ON episodes. ERG results are consistent with dysfunctional bipolar cells, as in other autoimmune diseases. To date, studies have presented only cross-sectional data regarding ERG and OCT. We, therefore, studied the longitudinal course of ERG and OCT in patients with MS, as well as the effect of disability changes and non-ON clinical relapses on these functional and structural measures. Methods MS patients ( n  = 23) participating in an ongoing longitudinal observational study were invited to take part in a 3-year ophthalmological substudy. ERG and OCT were performed, and measures of MS-related disability and relapse history were obtained. Study visits were repeated annually. ERG peak times, rod b-wave amplitude, mixed rod/cone and cone b-/a-wave amplitude ratios, thickness of the peripapillary retinal nerve fibre layer, and volumes of the segmented retinal layers/complexes were analysed. Using generalised estimating equation models adjusted for age, ON, and MS treatment status, we assessed changes to ERG and OCT over the study duration, the effect of changes in disability and recent non-ON MS relapses on ERG and OCT, and the effect of selected OCT parameters on corresponding ERG parameters. Results At the group level, small fluctuations of several ERG peak times were recorded, with OCT values remaining stable. Increased disability between visits was associated with significant prolongation of mixed rod-cone ERG b-wave peak times. No evidence of associations between OCT and ERG parameters was observed. Conclusions Retinal bipolar cell function may be affected by changes in disability in patients with MS; however, recent non-ON MS clinical relapses appear not to affect ERG or OCT results. As ERG changes in MS patients over 3 years are likely to be small and of uncertain clinical relevance, longitudinal studies of retinal function in MS should be planned over an extended period.

A three-year longitudinal study of retinal function and structure in patients with multiple sclerosis