Retinal Layer Thinning for Monitoring Disease-modifying Treatment in Relapsing Multiple Sclerosis—Evidence for Applying a Rebaselining Concept
Gabriel Bsteh1, Harald Hegen2, Nik Krajnc4, Patrick Altmann5, Michael Auer3, Klaus Berek3, Barbara Kornek5, Fritz Leutmezer5, Stefan Macher5, Tobias Monschein5, Markus Ponleitner5, Paulus Rommer5, Christiane Schmied5, Karin Zebenholzer5, Gudrun Zulehner5, Tobias Zrzavy5, Florian Deisenhammer3, Franziska Di Pauli3, Berthold Pemp5, Thomas Berger5
1Medical University Vienna, Department of Neurology, 2Neurology, Medical University of Innsbruck, 3Medical University of Innsbruck, 4Neurology, Medical University of Vienna, 5Medical University of Vienna
Objective:
To investigate whether rebaselining the longitudinal measurement of neuroaxonal damage improves sensitivity for detecting effects of disease-modifying treatment (DMT) in monitoring relapsing multiple sclerosis (RMS).
Background:
Retinal layer thinning measured by optical coherence tomography (OCT) is a promising biomarker for monitoring neuroaxonal degeneration in RMS. Noise by carry-over damage and delay of biological insertion of DMT effect may be reduced by rebaselining.
Design/Methods:
From an ongoing prospective observational study, we included patients with RMS newly initiated on a DMT and ≥12 months of observed clinical history before DMT start, who had OCT 1) at DMT start (baseline), 2) 6 to 12 months after DMT start (rebaseline), and 3) ≥1 follow-up OCT, and 4) adhered to the DMT during follow-up. Mean annualized thinning rates (µm/year) were calculated both from baseline and rebaseline for peripapillary retinal-nerve-fiber-layer (aLpRNFLbaseline/aLpRNFLrebaseline) and macular ganglion-cell-plus-inner-plexiform-layer (aLGCIPLbaseline/aLGCIPLrebaseline) by mixed-effects linear regression evaluating influence of relapses and EDSS (Expanded Disability Status Scale) worsening in the year before baseline as well as DMT class (moderate [M-DMT] vs. high efficacy [H-DMT]) with adjustment for age, sex, disease duration and relapses/EDSS worsening during follow-up.
Results:
We included 173 RMS patients (mean age 31.7 years [SD 8.8], 72.8% female, median disease duration 15 months [range: 12-94], median number of OCT scans 6 [range: 4-12], median baseline-to-last-follow-up-interval 37 months [range: 13-71], 56.6% M-DMT, 53.4% H-DMT).
Both mean aLpRNFLbaseline and aLGCIPLbaseline significantly increased with relapse (0.51and 0.31 per relapse, p<0.001 respectively) and EDSS worsening (1.13 and 0.78, p<0.001 respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFLrebaseline nor aLGCIPLrebaseline were dependent on relapse or EDSS worsening before baseline, while H-DMT significantly lowered aLpRNFLrebaseline (by 0.31, p<0.001) respectively) and aLGCIPLrebaseline (0.25, p<0.001) compared to M-DMT.
Conclusions:
Employing rebaselining significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.