Outer Retinal Dysfunction on Multifocal Electroretinography May Help Differentiating Multiple Sclerosis From Neuromyelitis Optica Spectrum Disorder

Abstract

Purpose: To evaluate the intermediate and outer retina of patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using OCT and multifocal electroretinography (mf-ERG). Methods: Patients with MS ( n = 30), NMOSD ( n = 30), and healthy controls ( n = 29) underwent visual field (VF), OCT, and mf-ERG testing. The eyes were distributed into 5 groups: MS with or without history of ON (MS+ON, MS–ON), NMOSD with or without ON (NMOSD+ON, NMOSD–ON), and controls. The thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was measured. mf-ERG P1 and N1 responses were registered and grouped in 3 sets of rings. The groups were compared using GEE models, and effect size (ES) calculated. Results: Compared to controls, GCL and IPL thickness was significantly smaller in MS+ON (both p < 0.01), MS–ON ( p < 0.01 and p = 0.015, respectively), NMOSD+ON (both p < 0.01) and NMOSD–ON ( p = 0.03 and p = 0.018, respectively). ES was >0.80. mRNFL was smaller in three of the above groups ( p < 0.01, p < 0.001, and p = 0.028; ES > 0.80) but not in MS–ON eyes ( p = 0.18). No significant difference was observed for the remaining layers. Compared to controls, P1 and N1 peak times were shorter in MS ( p -values in the range 0.049–0.002, ES < 0.50; and 0.049–0.010; ES < 0.50, respectively) but not in NMOSD. These abnormalities were strongly correlated with intermediate and outer retinal layer thickness. Conclusions: mf-ERG data suggest outer retinal abnormalities in MS, but not in NMOSD. Our results may help understand how the two conditions differ regarding retinal damage.

Commentary: Outer Retinal Dysfunction on Multifocal Electroretinography May Help Differentiating Multiple Sclerosis From Neuromyelitis Optica Spectrum Disorder

“…How, then, can we interpret the findings of Filgueiras et al (1) suggesting supernormal bipolar function in MS patients in the light of this pre-existing literature, and are there any factors which may account for this apparent discrepancy? In attempting to reconcile their findings with previous work from our group (8), Filgueiras suggested that our findings may be less reliable due to the use of manufacturers' normative databases from our electrophysiology device for comparison, rather than control data acquired on-site using the same conditions as for our patient cohort.…”

“…These differences included the MF-ERG waveform components and retinal areas analyzed. The exclusion of R5 from analysis by Filgueiras et al (1), in order to facilitate comparison with perimetric data, may be particularly relevant given that we recorded R5 P1 peak times which were significantly delayed in MS patients relative to normative data (8). The analysis of different retinal areas makes it challenging to compare the results of the two studies directly.…”

“…We read with interest the recent manuscript by Filgueiras et al (1), which presented data collected using multifocal electroretinography (MF-ERG) in patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and control subjects. Given that MF-ERG peak times were slightly shorter (i.e., supernormal) in MS patients relative to both NMOSD patients and controls, the authors interpreted their findings as evidence of excitatory outer retinal dysfunction in MS (1). Whilst this is a potentially exciting conclusion, a degree of caution appropriate to the novelty of the findings is warranted when attempting to interpret these data.…”

“…Whilst this is a potentially exciting conclusion, a degree of caution appropriate to the novelty of the findings is warranted when attempting to interpret these data. In this commentary, we highlight a number of factors which may influence the conclusions drawn from the work of Filgueiras (1).…”

Empirical Mode Decomposition-Based Filter Applied to Multifocal Electroretinograms in Multiple Sclerosis Diagnosis

“…However, the few papers that have investigated the potential of mfERG analysis for diagnosing MS are based on traditional analysis of amplitudes and latencies and have produced conflicting findings [7,[15][16][17][18][19][20], perhaps because of the heterogeneity of the subjects analyzed (different types of MS and presence/absence of ON) and the use of different mfERG technologies.…”