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Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness z Scores.
Lin, Ting-Yi; Motamedi, Seyedamirhosein; Asseyer, Susanna; Chien, Claudia; Saidha, Shiv; Calabresi, Peter A; Fitzgerald, Kathryn C; Samadzadeh, Sara; Villoslada, Pablo; Llufriu, Sara; Green, Ari J; Preiningerova, Jana Lizrova; Petzold, Axel; Leocani, Letizia; Garcia-Martin, Elena; Oreja-Guevara, Celia; Outteryck, Olivier; Vermersch, Patrick; Balcer, Laura J; Kenney, Rachel; Albrecht, Philipp; Aktas, Orhan; Costello, Fiona; Frederiksen, Jette; Uccelli, Antonio; Cellerino, Maria; Frohman, Elliot M; Frohman, Teresa C; Bellmann-Strobl, Judith; Schmitz-Hübsch, Tanja; Ruprecht, Klemens; Brandt, Alexander U; Zimmermann, Hanna G; Paul, Friedemann.
Afiliación
  • Lin TY; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Motamedi S; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Asseyer S; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Chien C; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Saidha S; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Calabresi PA; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Fitzgerald KC; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Samadzadeh S; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Villoslada P; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Llufriu S; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Green AJ; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Preiningerova JL; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Petzold A; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Leocani L; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Garcia-Martin E; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Oreja-Guevara C; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Outteryck O; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Vermersch P; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Balcer LJ; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Kenney R; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Albrecht P; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Aktas O; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Costello F; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Frederiksen J; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Uccelli A; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Cellerino M; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Frohman EM; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Frohman TC; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Bellmann-Strobl J; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Schmitz-Hübsch T; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Ruprecht K; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Brandt AU; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Zimmermann HG; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
  • Paul F; From the Charité - Universitätsmedizin Berlin (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.); Experimental and Clinical Research Center (T.-Y.L., S.M., S.A., C.C., S. Samadzadeh, J.B.-S., T.S.-H., A.U.B., H.G.Z., F.P.), a cooperation between the Max Delbrück Cente
Neurol Neuroimmunol Neuroinflamm ; 11(5): e200269, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38941572
ABSTRACT
BACKGROUND AND

OBJECTIVES:

Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted z scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS).

METHODS:

We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted z scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests.

RESULTS:

In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], p = 3.82e-5). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], p = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], p = 0.04). Compared with raw values with arbitrary cutoffs, applying the z score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score).

DISCUSSION:

In conclusion, our work demonstrated reference cohort-based z scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Progresión de la Enfermedad / Tomografía de Coherencia Óptica / Esclerosis Múltiple Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Progresión de la Enfermedad / Tomografía de Coherencia Óptica / Esclerosis Múltiple Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Año: 2024 Tipo del documento: Article