Retinal Function in Advanced Multiple Sclerosis

Abstract

Purpose: People with multiple sclerosis (pwMS) experience autoimmunity-mediated inflammation and neurodegeneration throughout the central nervous system. There remains a need for clinically accessible, reliable functional markers of neurodegeneration in MS. Previous research has described changes to electroretinography (ERG)-derived measures of retinal bipolar cell function in pwMS early in the disease course. We, therefore, investigated ERG as a potential outcome measure in individuals with more advanced disease.

Methods: This cross-sectional observational study included pwMS with Expanded Disability Status Scale (EDSS) scores of ≥3.0 and healthy control (HC) participants who underwent ERG, optical coherence tomography, high- and low-contrast visual acuity measurement, and an ophthalmological examination. ERG findings in MS eyes with and without previous optic neuritis (MS +ON; MS -ON) were compared with those in HC eyes. Effects of EDSS, disease duration, ON, and treatment status on selected ERG outcomes were measured. Additional exploratory analyses assessed potential influences of MS phenotype and disease status (clinically active, radiologically active, and disease progression).

Results: Delays to two ERG peak times (dark-adapted 3.0 b-wave; light-adapted flicker) were recorded in MS +ON and MS -ON eyes. No influences of EDSS score, disease duration, previous ON, or treatment status were observed. Exploratory analyses were consistent with no effects of MS phenotype or disease status.

Conclusions: ERG findings are abnormal in individuals with moderate-severe disability caused by MS; however, these findings are not distinct from those observed earlier in the disease course. Although bipolar dysfunction appears to be common in pwMS throughout the disease course, ERG is likely not useful in monitoring or prognostication of MS.

Figure 1.

(A–F) Boxplots showing ERG response amplitudes in eyes of people with multiple sclerosis both with (MS +ON) and without (MS −ON) previous ON with those of HC participants. Units on all y axes are microvolts. Median values and IQRs are indicated by horizontal lines and boxes, respectively; whiskers show the lowest and highest data points still within 1.5 IQR of the lower and upper quartiles. Individual outlying data points are represented by black dots. AMP, response amplitude; DA, dark adapted; LA, light adapted.

Figure 2.

(A–F) Boxplots showing ERG response peak times in eyes of people with multiple sclerosis both with (MS +ON) and without (MS −ON) previous ON with those of HC participants. Units on all y axes are milliseconds. Median values and IQRs are indicated by horizontal lines and boxes, respectively; whiskers show the lowest and highest data points still within 1.5 IQR of the lower and upper quartiles. Individual outlying data points are represented by black dots. DA, dark adapted; LA, light adapted; PEAK, response peak time.

Figure 3.

(A–H) ERG peak times plotted against EDSS (A, E), disease duration (B, F), history of ON (C, G), and binarized treatment status (D, h). Peak times selected for display and analysis were the dark (A–d) and light adapted (E–H) 3.0 single flash responses, as discussed in the Statistical Analysis subsection. On the scatterplots (A, B, E, F), data points from both eyes of individual participants are connected by a line; in the violin plots (C, D, G, H), individual data points have been horizontally jittered for clarity. DA, dark adapted; LA, light adapted.

Figure 4.

(A–H) ERG peak times plotted against multiple sclerosis subtype (A, e) And Disease activity (clinically active, radiologically active, with evidence of progression, B–D and F–H, respectively). Peak times selected for display and analysis were the dark (A–D) and light adapted (E–H) 3.0 single flash responses, as discussed in the Statistical Analysis subsection. Data points are horizontally jittered for clarity. DA, dark adapted; LA, light adapted.