Visually Evoked Potential as Prognostic Biomarker for Neuroaxonal Damage in Multiple Sclerosis From a Multicenter Longitudinal Cohort
Frederike Cosima Oertel, Julia Krämer, Seyedamirhosein Motamedi, Azeen Keihani, Hanna Zimmermann, Nikolaos G. Dimitriou, Shivany Condor Montes, Charlotte Bereuter, Christian Cordano, Ahmed Abdelhak, Anand Trip, Orhan Aktaş, Sven G. Meuth, Heinz Wiendl, Klemens Ruprecht, Judith Bellmann–Strobl, Friedemann Paul, Axel Petzold, Alexander U. Brandt, Philipp Albrecht, Ari Green
Abstract
<h3>Background and Objectives</h3> With the increasing use of visually evoked potentials (VEPs) as quantitative outcome parameters for myelin in clinical trials, an in-depth understanding of longitudinal VEP latency changes and their prognostic potential for subsequent neuronal loss will be required. In this longitudinal multicenter study, we evaluated the association and prognostic potential of VEP latency for retinal neurodegeneration, measured by optical coherence tomography (OCT), in relapsing-remitting MS (RRMS). <h3>Methods</h3> We included 293 eyes of 147 patients with RRMS (age [years, median ± SD] 36 ± 10, male sex 35%, F/U [years, median {IQR} 2.1 {1.5–3.9}]): 41 eyes had a history of optic neuritis (ON) ≥6 months before baseline (CHRONIC-ON), and 252 eyes had no history of ON (CHRONIC-NON). P100 latency (VEP), macular combined ganglion cell and inner plexiform layer volume (GCIPL), and peripapillary retinal nerve fiber layer thickness (pRNFL) (OCT) were quantified. <h3>Results</h3> P100 latency change over the first year predicted subsequent GCIPL loss (36 months) across the entire chronic cohort (<i>p</i> = 0.001) and in (and driven by) the CHRONIC-NON subset (<i>p</i> = 0.019) but not in the CHRONIC-ON subset (<i>p</i> = 0.680). P100 latency and pRNFL were correlated at baseline (CHRONIC-NON <i>p</i> = 0.004, CHRONIC-ON <i>p</i> < 0.001), but change in P100 latency and pRNFL were not correlated. P100 latency did not differ longitudinally between protocols or centers. <h3>Discussion</h3> VEP in non-ON eyes seems to be a promising marker of demyelination in RRMS and of potential prognostic value for subsequent retinal ganglion cell loss. This study also provides evidence that VEP may be a useful and reliable biomarker for multicenter studies.