Evaluation of Retinal Layer Thickness Parameters as Biomarkers in a Real-World Multiple Sclerosis Cohort

Natascha Schurz,1,* Lydia Sariaslani,1,* Patrick Altmann,1 Fritz Leutmezer,1 Christoph Mitsch,2 Berthold Pemp,2 Paulus Rommer,1 Tobias Zrzavy,1 Thomas Berger,1 Gabriel Bsteh1 1Department of Neurology, Medical University of Vienna, Vienna, Austria; 2Department of Ophthalmology, Medical University of Vienna, Vienna, Austria*These authors contributed equally to this workCorrespondence: Gabriel BstehMedical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, AustriaTel +43 1 40400 31450Email gabriel.bsteh@meduniwien.ac.atPurpose: Retinal layer thickness parameters measured by optical coherence tomography (OCT) are emerging biomarkers of neuroaxonal degeneration and inflammation in multiple sclerosis (MS). We aimed to evaluate the value of retinal layer thickness for prediction of disability worsening and relapse in a real-world MS cohort.Patients and Methods: For this longitudinal observational study, we included MS patients with spectral-domain OCT scans available and ≥ 1 year of clinical follow-up. The value of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and inner nuclear layer (INL) thickness for prediction of disability worsening and relapse during the observation period was tested by multivariate models.Results: We analyzed 60 MS patients during a mean observation period of 2.9 years (SD 1.8). Lower baseline thickness of GCIPL (cut-off < 77μm; HR 4.1, p=0.001) and pRNFL (cut-off ≤ 88μm; HR 3.1, p=0.019) were associated with an increased risk of disability worsening. Longitudinally, mean thinning rates were − 0.8μm/year (SD 1.6) for GCIPL, − 0.6μm/year (SD 3.5) for pRNFL. GCIPL thinning ≥ 1.0μm/year and pRNFL > 1.5μm/year is associated with higher likelihood of disability worsening (HR 5.7, p=0.009 and HR 6.8, p=0.003, respectively). INL thickened in patients with relapse by a mean 0.9μm while thinning by 0.3μm in patients without relapse (p=0.04). In multivariate analyses, INL thickening was associated with an increased probability of relapse (OR 17.8, p=0.023).Conclusion: Cross-sectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Change of INL thickness is a promising marker of relapse, i.e. inflammatory activity.Keywords: multiple sclerosis, biomarker, optical coherence tomography, retinal thinning, progression, relapse