Removing mains interference from the mfERG by applying a post-processing digital notch filter: for the good or the bad?

Purpose Ideally, the multifocal electroretinogram (mfERG) is recorded without noticeable intrusion of mains interference. However, sometimes contamination is difficult to avoid. A post-processing digital notch filter can help to recover the retinal response even in severe cases of mains interference. While a digital filter can be designed to have little to no impact on peak times, filtering out mains interference also removes the retinal signal content of the same frequency, which may result in a change of amplitude. The present study addressed this issue in the standard first order kernel mfERG. Methods In 24 recordings from routine exams with no perceivable mains interference, the effects of 50-Hz and 60-Hz non-causal digital notch filters on amplitude and peak time were assessed. Furthermore, the effect of filtering on contaminated traces was demonstrated and simulated mains interference was used to provide an example of nonlinear superposition of retinal signal and mains interference. Results mfERG amplitudes were reduced by 0%–15% (median 6%) with the 50-Hz filter and remained virtually unaffected with the 60-Hz filter. Simulations illustrate that spurious high-frequency components can occur in the filtered signal if a strongly contaminated signal is clipped due to a limited input range of the analog-to-digital converter. Conclusion The application of a 50-Hz digital notch filter to mfERG traces causes a mild amplitude reduction which will not normally affect the clinical interpretation of the data. The situation is even more favorable with a 60-Hz digital notch filter. Caution is necessary if the assumption of linear additivity of retinal signal and mains interference is violated.

Electroretinogram responses in myopia: a review

The stretching of a myopic eye is associated with several structural and functional changes in the retina and posterior segment of the eye. Recent research highlights the role of retinal signaling in ocular growth. Evidence from studies conducted on animal models and humans suggests that visual mechanisms regulating refractive development are primarily localized at the retina and that the visual signals from the retinal periphery are also critical for visually guided eye growth. Therefore, it is important to study the structural and functional changes in the retina in relation to refractive errors. This review will specifically focus on electroretinogram (ERG) changes in myopia and their implications in understanding the nature of retinal functioning in myopic eyes. Based on the available literature, we will discuss the fundamentals of retinal neurophysiology in the regulation of vision-dependent ocular growth, findings from various studies that investigated global and localized retinal functions in myopia using various types of ERGs.

A novel 5-ring multifocal electroretinography stimulus for detecting hydroxychloroquine retinal toxicity

Purpose Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity. Methods Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study. Patients with amblyopia, high refractive error (more than 8 diopters), other retinal diseases precluding appropriate evaluation or history of retinal surgery were excluded. The data were collected from patients undergoing HCQ screening at a single center from July 2019 to March 2020. Patients were tested with the new concentric 5-ring mfERG stimulus, standard 61-hexagon mfERG stimulus, spectral domain optical coherence tomography and automated 10-2 visual fields. For the main outcome, the 5-ring mfERG was compared to 61-hexagon stimulus to determine the time-to-test completion and assess the association between ring (R1–R5) amplitude and ring ratio compared against cumulative dose, dose by real body weight and duration of therapy using Pearson correlation. Results In total, 52 patients (104 eyes; 5 males and 47 females) were recruited with a mean age of 59 years (range 23–85 years). The 5-ring protocol was markedly quicker to perform (1.3 ± 0.2 min; mean (SD)) compared to the 61-hexagon protocol (5.2 ± 0.6 min), p < 0.0001; n = 10 patients. The new R2/R5 ring ratio showed a moderate correlation with daily dose (r = − 0.640), cumulative dose (r = − 0.581) and duration of therapy (r = − 0.417). Similar correlations were observed with the new R2/R4 ring ratio which were not significantly different from the new R2/R5 correlation coefficients. The new R2/R5 ring ratio demonstrated a stronger correlation with daily (p = 0.002) and cumulative dose (p = 0.0001) compared to the 61-hexagon stimulus. Conclusions In this exploratory study, our novel 5-ring mfERG protocol significantly shortened data acquisition time while providing comparable results to the standard 61-hexagon stimulus for detecting HCQ-induced electrophysiological changes that are correlated with HCQ dosages and treatment duration. Our protocol has the potential to be more clinically practical by simplifying routine screening.

A three-year longitudinal study of retinal function and structure in patients with multiple sclerosis

Background Researchers have in recent years begun to investigate ophthalmological manifestations of multiple sclerosis (MS) other than optic neuritis (ON), and it is now clear that changes to retinal function (measured using the electroretinogram, ERG) and structure (measured using optical coherence tomography, OCT) are found in MS patients irrespective of prior ON episodes. ERG results are consistent with dysfunctional bipolar cells, as in other autoimmune diseases. To date, studies have presented only cross-sectional data regarding ERG and OCT. We, therefore, studied the longitudinal course of ERG and OCT in patients with MS, as well as the effect of disability changes and non-ON clinical relapses on these functional and structural measures. Methods MS patients (n = 23) participating in an ongoing longitudinal observational study were invited to take part in a 3-year ophthalmological substudy. ERG and OCT were performed, and measures of MS-related disability and relapse history were obtained. Study visits were repeated annually. ERG peak times, rod b-wave amplitude, mixed rod/cone and cone b-/a-wave amplitude ratios, thickness of the peripapillary retinal nerve fibre layer, and volumes of the segmented retinal layers/complexes were analysed. Using generalised estimating equation models adjusted for age, ON, and MS treatment status, we assessed changes to ERG and OCT over the study duration, the effect of changes in disability and recent non-ON MS relapses on ERG and OCT, and the effect of selected OCT parameters on corresponding ERG parameters. Results At the group level, small fluctuations of several ERG peak times were recorded, with OCT values remaining stable. Increased disability between visits was associated with significant prolongation of mixed rod-cone ERG b-wave peak times. No evidence of associations between OCT and ERG parameters was observed. Conclusions Retinal bipolar cell function may be affected by changes in disability in patients with MS; however, recent non-ON MS clinical relapses appear not to affect ERG or OCT results. As ERG changes in MS patients over 3 years are likely to be small and of uncertain clinical relevance, longitudinal studies of retinal function in MS should be planned over an extended period.

Monitoring for glaucoma progression with SAP, electroretinography (PERG and PhNR) and OCT

Purpose To investigate the value of pattern electroretinography (PERG) and photopic negative response (PhNR) in monitoring glaucoma compared to standard clinical tests (standard automated perimetry (SAP) and clinical optic disc assessment) and structural measurements using spectral-domain OCT. Methods A prospective study included 32 subjects (32 eyes) with ocular hypertension, suspect or early glaucoma monitored for progression with clinical examination, SAP, PERG, PhNR and OCT for at least 4 years. Progression was defined clinically by the documented change of the optic disc and/or significant visual field progression (EyeSuite™ trend analysis). One eye per patient was included in the analysis. Results During the follow-up, 13 eyes (40.6%) showed progression, whereas 19 remained stable. In the progressing group, all parameters showed significant worsening over time, except for the PhNR, whereas in the stable group only the OCT parameters showed a significant decrease at the last visit. The trend of change over time using linear regression was steepest for the OCT parameters. At baseline, only the ganglion cell complex (GCC) and peripapillary retinal nerve fibre (pRNFL) thicknesses significantly discriminated between the stable and progressing eyes with the area under the ROC curve of 0.72 and 0.71, respectively. The inter-session variability for the first two visits in the stable group was lower for OCT (% limits of agreement within ± 17.4% of the mean for pRNFL and ± 3.6% for the GCC thicknesses) than for ERG measures (within ± 35.9% of the mean for PERG N95 and ± 59.9% for PhNR). The coefficient of variation for repeated measurements in the stable group was 11.9% for PERG N95 and 23.6% for the PhNR, while it was considerably lower for all OCT measures (5.6% for pRNFL and 1.7% for GCC thicknesses). Conclusions Although PERG and PhNR are sensitive for early detection of glaucomatous damage, they have limited usefulness in monitoring glaucoma progression in clinical practice, mainly due to high inter-session variability. On the contrary, OCT measures show low inter-session variability and might have a predicting value for early discrimination of progressing cases.

Effects of fixed cutoff filtering on dark- and light-adapted ERG components and the application of variable cutoff filter

Purpose Human oscillatory potentials (OPs) are derived from dark-adapted (DA) electroretinograms (ERGs) with fixed frequency cutoff filters while light-adapted (LA) OPs are generally not isolated from ERGs. Our purpose was to analyze the effect of cutoff frequencies on DA and LA ERG components using a series of fixed and variable filters. Methods DA and LA ERGs were recorded from 10 healthy eyes of 10 subjects (mean age = 20.5 ± 6.7 years) following ISCEV standards. Each signal was filtered in the Fourier domain to acquire slow (a- and b-waves; below cutoff frequency) and fast (OPs; above cutoff frequency) components. Fixed cutoff frequencies ranged from 60 to 105 Hz and a variable cutoff frequency was calculated. Results were analyzed with statistical tests and specific models. Results DA ERG components were slightly influenced by the filter cutoff frequency. In contrast, fixed and variable filters significantly changed LA components: the lower the cutoff frequency the smaller the b-wave and OP3 and the higher the OP2/OP4 amplitudes. Analyzing the filter frequency limits a transition range between 68.9 Hz and 83.9 Hz was observed where amplitudes vary. Conclusions The present report shows that DA OPs may be isolated from ERGs using filtering procedures with high-pass cutoff frequency at about 75 Hz as recommended by ISCEV. On the other hand, the spectral distribution of low-frequency and high-frequency LA ERG components may overlap. Accordingly, filtering the signal using different cutoff frequencies is not necessarily separating b-wave and OPs.