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.

Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials

“…The anti-inflammatory agent EGCG has shown neuroprotective effects in animal models of MS [ 145 ], and, therefore, it has also evaluated as a potential therapeutic molecule for MS treatment. Currently, there are seven registered clinical trials to assess the effect of EGCG or EGCG-containing extracts in MS patients.…”

Estimation and Testing of Wilcoxon–Mann–Whitney Effects in Factorial Clustered Data Designs

“…In order to motivate the development of methods for factorial repeated measures data with a clustered structure, we consider the secondary/exploratory outcome analysis of retinal thickness in the 'Sunphenon in progressive forms of multiple sclerosis' (SUPREMES) trial by Klumbies et al [19], which was a relatively small clinical trial in progressive multiple sclerosis (MS) patients. MS is the most common autoimmune disorder of the central nervous system, affecting approximately 2.8 million people worldwide [20].…”

“…In animal models of MS, epigallocatechin gallate (EGCG), which is an anti-inflammatory agent, indicated neuroprotective properties. The recent paper of Klumbies et al [19] investigated the effect of EGCG on retinal thickness as an indicator for treatment response in progressive MS. For this motivating example, only the parameter peripapillary retinal nerve fiber layer (pRNFL) will be investigated.…”

Retinal imaging with optical coherence tomography in multiple sclerosis: novel aspects

“…OCT lately became of increased relevance as an additional outcome marker for neuroprotective or remyelinating therapies. For example, epigallocatechin gallate, phenytoin, and clemastine showed no significant change of OCT parameters compared to controls [ 80 – 82 ]. Ibudilast, on the other hand, showed a decreased pRNFL and macula volume thinning and reduced brain atrophy [ 83 ].…”