Background: Although the retina represents an unmyelinated central nervous system structure, almost all aspects of multiple sclerosis (MS) related pathology (except demyelination) may be observed in the retina. Moreover, the retina represents an opportune site to study neurodegeneration, since optic nerve affliction is virtually ubiquitous in MS. Optical coherence tomography (OCT) derived measures of retinal neurodegeneration have been shown to strongly reflect the global MS disease process, and may be ideal outcomes for assessing neuroprotection, and/or neurorestoration. Accordingly, OCT outcomes are being increasingly incorporated as primary or secondary outcomes in MS clinical trials.
Goals: To describe the effects of MS disease modifying therapies (DMTs) on OCT derived assessment of retinal atophy.
Methods: Discussion of the emerging role of OCT for monitoring MS, as well as the effects of high-potency (including natalizumab and rituximab), and low-potency (including interferons and glatiramer acetate) MS DMTs on rates of OCT derived measures of composite ganglion cell+inner plexiform layer (GCIPL), inner nuclear layer (INL), and outer nuclear layer (ONL) atrophy. Differences in the effects of DMTs on retinal atrophy according to MS subtype will be reviewed. Finally, the role of the international MS visual system (IMSVISUAL) consortium in large scale MS studies will be discussed.
Results: Congruent with the effects of DMTs on rates of brain atrophy, high potency DMTs are associated with slower rates of retinal atophy in relapsing remitting MS (RRMS), as compared to low potency DMTs. Therepeutic optimization of the effect of rituximab on retinal atrophy in MS may take up to 6-12 months in RRMS. INL and ONL atrophy appear to be relatively speficic to progressive MS (PMS; both primary and secondary PMS), as compared to RRMS, and in PMS, INL and ONL atrophy are accelerated, independent of age. Rates of GCIPL, INL and ONL atrophy do not differ significantly between untreated PMS patients, and PMS patients treated with either low or high potency DMTs. Large scale MS studies utilizing visual system outcomes are facilitated by IMSVISUAL.
Conclusions: Rates of GCIPL atrophy are slower in RRMS patients treated with high potency, as compared to low potency DMTs. INL and ONL atrophy measures appear to be relatively specific to PMS, and may be novel outcomes for assessing neuroprotection and/or neurorestoration in PMS. Current, conventional, and primarily anti-inflammatory DMTs (whether high or low potency) have not been shown to significantly reduce retinal atophy in PMS, unlike RRMS.