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

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.

Epigallocatechin Gallate in Progressive MS: A Randomized, Placebo-Controlled Trial.

OBJECTIVE: To examine whether treatment with epigallocatechin gallate (EGCG) influences progression of brain atrophy, reduces clinical and further radiologic disease activity markers, and is safe in patients with progressive multiple sclerosis (PMS). METHODS: We enrolled 61 patients with primary or secondary PMS in a randomized double-blind, parallel-group, phase II trial on oral EGCG (up to 1,200 mg daily) or placebo for 36 months with an optional open-label EGCG treatment extension (OE) of 12-month duration. The primary end point was the rate of brain atrophy, quantified as brain parenchymal fraction (BPF). The secondary end points were radiologic and clinical disease parameters and safety assessments. RESULTS: In our cohort, 30 patients were randomized to EGCG treatment and 31 to placebo. Thirty-eight patients (19 from each group) completed the study. The primary endpoint was not met, as in 36 months the rate of decrease in BPF was 0.0092 ± 0.0152 in the treatment group and -0.0078 ± 0.0159 in placebo-treated patients. None of the secondary MRI and clinical end points revealed group differences. Adverse events of EGCG were mostly mild and occurred with a similar incidence in the placebo group. One patient in the EGCG group had to stop treatment due to elevated aminotransferases (>3.5 times above normal limit). CONCLUSIONS: In a phase II trial including patients with multiple sclerosis (MS) with progressive disease course, we were unable to demonstrate a treatment effect of EGCG on the primary and secondary radiologic and clinical disease parameters while confirming on overall beneficial safety profile. CLINICALTRIALGOV IDENTIFIER: NCT00799890. CLASSIFICATION OF EVIDENCE: This phase II trial provides Class II evidence that for patients with PMS, EGCG was safe, well tolerated, and did not significantly reduce the rate of brain atrophy.

Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome.

BACKGROUND: Axonal and neuronal damage are widely accepted as key events in the disease course of multiple sclerosis. However, it has been unclear to date at which stage in disease evolution neurodegeneration begins and whether neuronal damage can occur even in the absence of acute inflammatory attacks. OBJECTIVE: To characterize inner retinal layer changes in patients with clinically isolated syndrome (CIS). METHOD: 45 patients with CIS and age- and sex-matched healthy controls were investigated using spectral domain optical coherence tomography. Patients' eyes were stratified into the following categories according to history of optic neuritis (ON): eyes with clinically-diagnosed ON (CIS-ON), eyes with suspected subclinical ON (CIS-SON) as indicated by a visual evoked potential latency of >115 ms and eyes unaffected by ON (CIS-NON). RESULTS: CIS-NON eyes showed significant reduction of ganglion cell- and inner plexiform layer and a topography similar to that of CIS-ON eyes. Seven eyes were characterized as CIS-SON and likewise showed significant retinal layer thinning. The most pronounced thinning was present in CIS-ON eyes. CONCLUSION: Our findings indicate that retinal pathology does occur already in CIS. Intraretinal layer segmentation may be an easily applicable, non-invasive method for early detection of retinal pathology in patients unaffected by ON.