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

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.

Conflict of interest statement

RR received speaking honoraria from Roche. JD reports research support by Bayer and Novartis, honoraria for lectures and advisory by Bayer, Novartis, Sanofi-Aventis, Merck-Serono, Biogen and Roche and travel support by Bayer, Novartis, Biogen, and Merck-Serono. FP reports non-financial support from Taiyo International, grants from TEVA GmbH, other from German Research Council (DFG), during the conduct of the study; He serves on scientific advisory boards of Novartis's OCTIMS study steering committee and MedImmune/Viela Bio steering committee. He received funding for travel or speaker honoraria from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, and Merck Serono, Alexion, Chugai, MedImmune, Shire, Roche, Actelion, Celgene and serves on editorial Boards at PLos ONE (academic editor) and Neurology Neuroimmunology and Neuroinflammation (Associate Editor). He provided consultancies for SanofiGenzyme, BiogenIdec, MedImmune, Shire, Alexion; He received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion and Merck Serono, German Research Council (DFG Exc 257), Werth Stiftung of the City of Cologne, German Ministry of Education and Research (BMBF Competence Network Multiple Sclerosis), Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program (combims.eu) Guthy Jackson Charitable Foundation, and National Multiple Sclerosis Society of the USA. JB-S has received travel grants and speaking honoraria from Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi Genzyme, Teva Pharmaceuticals, Roche, and Novartis all unrelated to this work. AB is cofounder and shareholder of technology startups Motognosis GmbH and Nocturne GmbH. He is named as inventor on several patent applications describing serum biomarkers for multiple sclerosis, perceptive computing for motor symptoms and retinal image analysis using optical coherence tomography. HZ received research grants from Novartis and speaking fees from Bayer, unrelated to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Klumbies, Rust, Dörr, Konietschke, Paul, Bellmann-Strobl, Brandt and Zimmermann.

Figures

Figure 1

CONSORT chart describing the enrolment process of OCT analysis and case numbers at each year of follow-up. PMS, progressive MS; OCT, Optical coherence tomography; pRNFL, peripapillary retinal nerve fiber layer; GCIP, ganglion cell and inner plexiform layer; INL, inner nuclear layer.

Figure 2

Longitudinal retinal layer changes in the EGCG treated and placebo group. Error bars indicate the standard error to the mean. EGCG, epigallocatechin-gallate; pRNFL, peripapillary retinal nerve fiber layer; GCIP, ganglion cell and inner plexiform layer; INL, inner nuclear layer.