Retinal Thickness Analysis in Progressive Multiple Sclerosis Patients Treated With Epigallocatechin Gallate: Optical Coherence Tomography Results From the SUPREMES Study

Katharina Klumbies; Rebekka Rust; Jan Dörr; Frank Konietschke; Friedemann Paul; Judith Bellmann-Strobl; Alexander U Brandt; Hanna G Zimmermann

doi:10.3389/fneur.2021.615790

Retinal Thickness Analysis in Progressive Multiple Sclerosis Patients Treated With Epigallocatechin Gallate: Optical Coherence Tomography Results From the SUPREMES Study

Front Neurol. 2021 Apr 28:12:615790. doi: 10.3389/fneur.2021.615790. eCollection 2021.

Authors

Katharina Klumbies^{1

2}, Rebekka Rust^{1

2}, Jan Dörr^{1

2

3}, Frank Konietschke⁴, Friedemann Paul^{1

2

5}, Judith Bellmann-Strobl^{1

2}, Alexander U Brandt^{1

2

6}, Hanna G Zimmermann^{1

2}

Affiliations

¹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Neurology Department, Oberhavel Clinic, Hennigsdorf, Germany.
⁴ Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁶ Department of Neurology, University of California, Irvine, Irvine, CA, United States.

Abstract

Background: Epigallocatechin gallate (EGCG) is an anti-inflammatory agent and has proven neuroprotective properties in animal models of multiple sclerosis (MS). Optical coherence tomography (OCT) assessed retinal thickness analysis can reflect treatment responses in MS. Objective: To analyze the influence of EGCG treatment on retinal thickness analysis as secondary and exploratory outcomes of the randomized controlled Sunphenon in Progressive Forms of MS trial (SUPREMES, NCT00799890). Methods: SUPREMES patients underwent OCT with the Heidelberg Spectralis device at a subset of visits. We determined peripapillary retinal nerve fiber layer (pRNFL) thickness from a 12° ring scan around the optic nerve head and thickness of the ganglion cell/inner plexiform layer (GCIP) and inner nuclear layer (INL) within a 6 mm diameter grid centered on the fovea from a macular volume scan. Longitudinal OCT data were available for exploratory analysis from 31 SUPREMES participants (12/19 primary/secondary progressive MS (PPMS/SPMS); mean age 51 ± 7 years; 12 female; mean time since disease onset 16 ± 11 years). We tested the null hypothesis of no treatment^*time interaction using nonparametric analysis of longitudinal data in factorial experiments. Results: After 2 years, there were no significant differences in longitudinal retinal thickness changes between EGCG treated and placebo arms in any OCT parameter (Mean change [confidence interval] ECGC vs. Placebo: pRNFL: -0.83 [1.29] μm vs. -0.64 [1.56] μm, p = 0.156; GCIP: -0.67 [0.67] μm vs. -0.14 [0.47] μm, p = 0.476; INL: -0.06 [0.58] μm vs. 0.22 [0.41] μm, p = 0.455). Conclusion: Retinal thickness analysis did not reveal a neuroprotective effect of EGCG. While this is in line with the results of the main SUPREMES trial, our study was probably underpowered to detect an effect. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT00799890.

Keywords: epigallocatechin gallate; optical coherence tomography; progressive multiple sclerosis; retina; treatment response.

Associated data

ClinicalTrials.gov/NCT00799890