Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of retinal atrophy in progressive MS are less clear. We investigated retinal layer thickness changes in RRMS, primary and secondary progressive MS (PPMS, SPMS), and their prognostic value for disease activity. Here, we analyzed 2651 OCT measurements of 195 RRMS, 87 SPMS, 125 PPMS patients, and 98 controls from five German MS centers after quality control. Peripapillary and macular retinal nerve fiber layer (pRNFL, mRNFL) thickness predicted future relapses in all MS and RRMS patients while mRNFL and ganglion cell-inner plexiform layer (GCIPL) thickness predicted future MRI activity in RRMS (mRNFL, GCIPL) and PPMS (GCIPL). mRNFL thickness predicted future disability progression in PPMS. However, thickness change rates were subject to considerable amounts of measurement variability. In conclusion, retinal degeneration, most pronounced of pRNFL and GCIPL, occurs in all subtypes. Using the current state of technology, longitudinal assessments of retinal thickness may not be suitable on a single patient level.

Aix Marseille University CNRS CRMBM UMR 7339 Marseille France

APHM La Timone CEMEREM Marseille France

Biomedical Center Faculty of Medicine Ludwig Maximilians University München München Germany

Brain and Mind Center University of Sydney Sydney NSW Australia

Department of Neurology Center for Neurology and Neuropsychiatry LVR Klinikum Heinrich Heine University Düsseldorf Düsseldorf Germany

Department of Neurology Kliniken Maria Hilf Mönchengladbach Germany

Department of Neurology Medical Faculty and University Hospital Düsseldorf Heinrich Heine University Düsseldorf Düsseldorf Germany

Department of Neurology Palacky University Olomouc Olomouc Czech Republic

Department of Neurology University Medical Centre Hamburg Eppendorf Hamburg Germany

Department of Neurology with Institute of Translational Neurology University Hospital Münster Münster Germany

Experimental and Clinical Research Center Max Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Berlin Germany

Hanseatic Statistics Hamburg Germany

Institute of Clinical Neuroimmunology LMU Hospital Ludwig Maximilians University München München Germany

Institute of Neuroimmunology and Multiple Sclerosis University Hospital Hamburg Eppendorf Hamburg Germany

Munich Cluster for Systems Neurology Munich Germany

Zobrazit více v PubMed

Saidha S, et al. Optical coherence tomography reflects brain atrophy in multiple sclerosis: a four-year study. Ann. Neurol. 2015;78:801–813. doi: 10.1002/ana.24487. PubMed DOI PMC

Sotirchos ES, Saidha S. OCT is an alternative to MRI for monitoring MS - YES. Mult. Scler. 2018;24:701–703. doi: 10.1177/1352458517753722. PubMed DOI

Albrecht P, et al. Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography. Mult. Scler. 2012;18:1422–1429. doi: 10.1177/1352458512439237. PubMed DOI

Lambe, J. et al. Association of spectral-domain OCT with long-term disability worsening in multiple sclerosis. Neurology96, e2058–e2069 (2021). PubMed PMC

Martinez-Lapiscina EH, et al. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurol. 2016;15:574–584. doi: 10.1016/S1474-4422(16)00068-5. PubMed DOI

Albrecht P, Frohlich R, Hartung HP, Kieseier BC, Methner A. Optical coherence tomography measures axonal loss in multiple sclerosis independently of optic neuritis. J. Neurol. 2007;254:1595–1596. doi: 10.1007/s00415-007-0538-3. PubMed DOI

Baetge SJ, et al. Association of retinal layer thickness with cognition in patients with multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2021;8:e1018. doi: 10.1212/NXI.0000000000001018. PubMed DOI PMC

Bsteh G, et al. Macular ganglion cell-inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis. Mult. Scler. 2021;27:684–694. doi: 10.1177/1352458520935724. PubMed DOI

Bsteh G, et al. Retinal layer thinning predicts treatment failure in relapsing multiple sclerosis. Eur. J. Neurol. 2021;28:2037–2045. doi: 10.1111/ene.14829. PubMed DOI PMC

Bsteh G, et al. Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis. Mult. Scler. J. Exp. Transl. Clin. 2020;6:2055217320966344. PubMed PMC

Bsteh G, et al. Peripapillary retinal nerve fibre layer as measured by optical coherence tomography is a prognostic biomarker not only for physical but also for cognitive disability progression in multiple sclerosis. Mult. Scler. 2019;25:196–203. doi: 10.1177/1352458517740216. PubMed DOI

Bsteh G, et al. Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing-remitting multiple sclerosis. Eur. J. Neurol. 2019;26:865–871. doi: 10.1111/ene.13897. PubMed DOI

Schurz N, et al. Evaluation of retinal layer thickness parameters as biomarkers in a real-world multiple sclerosis cohort. Eye Brain. 2021;13:59–69. doi: 10.2147/EB.S295610. PubMed DOI PMC

Pisa M, et al. No evidence of disease activity is associated with reduced rate of axonal retinal atrophy in MS. Neurology. 2017;89:2469–2475. doi: 10.1212/WNL.0000000000004736. PubMed DOI

Knier B, et al. Retinal inner nuclear layer volume reflects response to immunotherapy in multiple sclerosis. Brain J. Neurol. 2016;139:2855–2863. doi: 10.1093/brain/aww219. PubMed DOI

Rothman A, et al. Retinal measurements predict 10-year disability in multiple sclerosis. Ann. Clin. Transl. Neurol. 2019;6:222–232. doi: 10.1002/acn3.674. PubMed DOI PMC

Cordano C, et al. pRNFL as a marker of disability worsening in the medium/long term in patients with MS. Neurol. Neuroimmunol. Neuroinflamm. 2019;6:e533. doi: 10.1212/NXI.0000000000000533. PubMed DOI PMC

Lin TY, et al. Increased serum neurofilament light and thin ganglion cell-inner plexiform layer are additive risk factors for disease activity in early multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2021;8:e1051. doi: 10.1212/NXI.0000000000001051. PubMed DOI PMC

Zimmermann HG, et al. Association of retinal ganglion cell layer thickness with future disease activity in patients with clinically isolated syndrome. JAMA Neurol. 2018;75:1071–1079. doi: 10.1001/jamaneurol.2018.1011. PubMed DOI PMC

Graves JS, et al. Leveraging visual outcome measures to advance therapy development in neuroimmunologic disorders. Neurol. Neuroimmunol. Neuroinflamm. 2022;9:e1126. doi: 10.1212/NXI.0000000000001126. PubMed DOI PMC

Lambe J, Murphy OC, Saidha S. Can optical coherence tomography be used to guide treatment decisions in adult or pediatric multiple sclerosis? Curr. Treat. Options Neurol. 2018;20:9. doi: 10.1007/s11940-018-0493-6. PubMed DOI

Bsteh, G. et al. Retinal layer thinning for monitoring disease-modifying treatment in relapsing multiple sclerosis—evidence for applying a rebaselining concept (P6-6.005). Neurology102, 1253 (2024).

Balk LJ, et al. Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study. J. Neurol. 2016;263:1323–1331. doi: 10.1007/s00415-016-8127-y. PubMed DOI PMC

Sotirchos ES, et al. Progressive multiple sclerosis is associated with faster and specific retinal layer atrophy. Ann. Neurol. 2020;87:885–896. doi: 10.1002/ana.25738. PubMed DOI PMC

Henderson AP, et al. A preliminary longitudinal study of the retinal nerve fiber layer in progressive multiple sclerosis. J. Neurol. 2010;257:1083–1091. doi: 10.1007/s00415-010-5467-x. PubMed DOI

Behbehani R, Adnan H, Al-Hassan AA, Al-Salahat A, Alroughani R. Predictors of retinal atrophy in multiple sclerosis: a longitudinal study using spectral domain optical coherence tomography with segmentation analysis. Mult. Scler. Relat. Disord. 2018;21:56–62. doi: 10.1016/j.msard.2018.02.010. PubMed DOI

Klumbies K, et al. Retinal thickness analysis in progressive multiple sclerosis patients treated with epigallocatechin gallate: optical coherence tomography results from the SUPREMES study. Front. Neurol. 2021;12:615790. doi: 10.3389/fneur.2021.615790. PubMed DOI PMC

Barro C, et al. Fluid biomarker and electrophysiological outcome measures for progressive MS trials. Mult. Scler. 2017;23:1600–1613. doi: 10.1177/1352458517732844. PubMed DOI

Hardmeier M, Leocani L, Fuhr P. A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS. Mult. Scler. 2017;23:1309–1319. doi: 10.1177/1352458517707265. PubMed DOI PMC

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) Neurology. 1983;33:1444–1452. doi: 10.1212/WNL.33.11.1444. PubMed DOI

Paul F, et al. Optical coherence tomography in multiple sclerosis: a 3-year prospective multicenter study. Ann. Clin. Transl. Neurol. 2021;8:2235–2251. doi: 10.1002/acn3.51473. PubMed DOI PMC

Saidha S, et al. Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study. Lancet Neurol. 2012;11:963–972. doi: 10.1016/S1474-4422(12)70213-2. PubMed DOI PMC

Balk LJ, et al. Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study. Mult. Scler. J. Exp. Transl. Clin. 2019;5:2055217319871582. PubMed PMC

Cellerino M, et al. Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS. Neurol. Neuroimmunol. Neuroinflamm. 2019;6:e596. doi: 10.1212/NXI.0000000000000596. PubMed DOI PMC

Green AJ, McQuaid S, Hauser SL, Allen IV, Lyness R. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain J. Neurol. 2010;133:1591–1601. doi: 10.1093/brain/awq080. PubMed DOI PMC

Panda-Jonas S, Jonas JB, Jakobczyk-Zmija M. Retinal photoreceptor density decreases with age. Ophthalmology. 1995;102:1853–1859. doi: 10.1016/S0161-6420(95)30784-1. PubMed DOI

Balcer LJ, et al. Contrast letter acuity as a visual component for the Multiple Sclerosis Functional Composite. Neurology. 2003;61:1367–1373. doi: 10.1212/01.WNL.0000094315.19931.90. PubMed DOI

Balcer LJ, et al. Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis. Mult. Scler. 2017;23:734–747. doi: 10.1177/1352458517690822. PubMed DOI PMC

Villoslada P, Cuneo A, Gelfand J, Hauser SL, Green A. Color vision is strongly associated with retinal thinning in multiple sclerosis. Mult. Scler. 2012;18:991–999. doi: 10.1177/1352458511431972. PubMed DOI

Pueyo V, et al. Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis. Mult. Scler. 2008;14:609–614. doi: 10.1177/1352458507087326. PubMed DOI

Klistorner A, et al. Long-term effect of permanent demyelination on axonal survival in multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2022;9:e1155. doi: 10.1212/NXI.0000000000001155. PubMed DOI PMC

Berek K, et al. Retinal layer thinning as a biomarker of long-term disability progression in multiple sclerosis. Mult. Scler. 2022;28:1871–1880. doi: 10.1177/13524585221097566. PubMed DOI

Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162–173. doi: 10.1016/S1474-4422(17)30470-2. PubMed DOI

Schippling S, et al. Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria. Mult. Scler. 2015;21:163–170. doi: 10.1177/1352458514538110. PubMed DOI

Tewarie P, et al. The OSCAR-IB consensus criteria for retinal OCT quality assessment. PloS One. 2012;7:e34823. doi: 10.1371/journal.pone.0034823. PubMed DOI PMC

Petzold A, et al. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2010;9:921–932. doi: 10.1016/S1474-4422(10)70168-X. PubMed DOI

Nolan-Kenney RC, et al. Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: an international study. Ann. Neurol. 2019;85:618–629. doi: 10.1002/ana.25462. PubMed DOI

Odom JV, et al. ISCEV standard for clinical visual evoked potentials: (2016 update) Doc. Ophthalmol. Adv. Ophthalmol. 2016;133:1–9. doi: 10.1007/s10633-016-9553-y. PubMed DOI

Aytulun, A., et al. The APOSTEL 2.0 recommendations for reporting quantitative optical coherence tomography studies. Neurology97, 68–79 (2021). PubMed PMC

Cruz-Herranz A, et al. The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology. 2016;86:2303–2309. doi: 10.1212/WNL.0000000000002774. PubMed DOI PMC

Krämer, J., et al. Evolution of retinal degeneration and prediction of disease activity in relapsing and progressive multiple sclerosis; (1.0.0) [Data set]. Zenodo. 10.5281/zenodo.11106449 (2024). PubMed PMC

Hartmann, A., et al. Evolution of retinal degeneration and prediction of disease activity in relapsing and progressive multiple sclerosis; (1.0). Zenodo. 10.5281/zenodo.11096799 PubMed PMC

Evolution of retinal degeneration and prediction of disease activity in relapsing and progressive multiple sclerosis