Ocular direct current stimulation affects retinal ganglion cells.

Ocular current stimulation (oCS) with weak current intensities (a few mA) has shown positive effects on retinal nerve cells, which indicates that neurodegenerative ocular diseases could be treated with current stimulation of the eye. During oCS, a significant polarity-independent reduction in the characteristic P50 amplitude of a pattern-reversal electroretinogram was found, while no current stimulation effect was found for a full field electroretinogram (ffERG). The ffERG data indicated a trend for a polarity-dependent influence during oCS on the photopic negative response (PhNR) wave, which represents the sum activity of the retinal ganglion cells. Therefore, an ffERG with adjusted parameters for the standardized measurement of the PhNR wave was combined with simultaneous oCS to study the potential effects of direct oCS on cumulative ganglion cell activity. Compared with that measured before oCS, the PhNR amplitude in the cathodal group increased significantly during current stimulation, while in the anodal and sham groups, no effect was visible (α = 0.05, pcathodal = 0.006*). Furthermore, repeated-measures ANOVA revealed a significant difference in PhNR amplitude between the anodal and cathodal groups as well as between the cathodal and sham groups (p* ≤ 0.0167, pcathodal - anodal = 0.002*, pcathodal - sham = 0.011*).

Effects of Ocular Direct Current Stimulation on Full Field Electroretinogram.

Studies on weak current stimulation (1-2 mA) examine effects on neuronal cells for the treatment of neurological diseases, like depression. Ocular current stimulation showed positive effects on retinal nerve cells which indicate that neurodegenerative ocular diseases, e.g., glaucoma, can be treated with current stimulation of the eye. However, up to now it remains unclear which exact retinal cells can be influenced. During an ocular direct current stimulation, a significant reduction of the characteristic P50 amplitude of a pattern-reversal electroretinogram (PERG) was found for an anodal and a cathodal stimulation. This current stimulation effect could originate from the modulation of pre-ganglion cell activity or by changes in local ON and OFF responses of ganglion cells. For clarification, we investigate acute direct current stimulation effects on a full field electroretinogram (ERG), which represents the activity of pre-ganglion cells (specifically cones and bipolar cells). The ERG from 15 subjects was evaluated before (ERG 1) and during (ERG 2) an ocular direct current stimulation with 800 µA over 5 min. The current was applied through a ring rubber electrode placed around the eye and a 25 cm2 rubber electrode placed at the ipsilateral temple. For ERG measurements, sintered Ag/AgCl skin-electrodes were positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). The volunteers were stimulated in three independent sessions, each with a different current application (randomized order): cathodal polarity, anodal polarity (referred to the electrode around the eye), or sham stimulation. The changes between the two ERG measurements of the characteristic full field ERG amplitudes, a-wave, b-wave, and b'-wave (b-wave measured from zero line) were tested with the Wilcoxon signed-rank test (α = 0.05). Comparing before to during the current stimulation for all applications, the ERG waves showed no effects on amplitudes or latencies. Furthermore, no significant difference between the cathodal, anodal, and sham stimulation could be found by a Friedman test. These results indicate an unlikely contribution of pre-ganglion cells to the previously reported stimulation effect on PERG signals.

The Influence of the Stimulus Design on the Harmonic Components of the Steady-State Visual Evoked Potential.

Steady-state visual evoked potentials (ssVEPs) are commonly used for functional objective diagnostics. In general, the main response at the stimulation frequency is used. However, some studies reported the main response at the second harmonic of the stimulation frequency. The aim of our study was to analyze the influence of the stimulus design on the harmonic components of ssVEPs. We studied 22 subjects (8 males, mean age ± SD = 27 ± 4.8 years) using a circular layout (r 1 = 0-1.6°, r 2 = 1.6-3.5°, r 3 = 3.5-6.4°, r 4 = 6.4-10.9°, and r 5 = 10.9-18°). At a given eccentricity, the stimulus was presented according to a 7.5 Hz square wave with 50% duty cycle. To analyze the influence of the stimulus eccentricity, a background luminance of 30 cd/m2 was added to suppress foveal stray light effects; to analyze the influence of simultaneous foveal and peripheral stimulations, stimulations are performed without stray light suppression. For statistical analysis, medians M of the amplitude ratios for amplitudes at the second harmonic to the first harmonic and the probability of the occurrence of the main response at the second harmonic P(MCSH) are calculated. For stimulations with foveal stray light suppression, the medians were M 0 -1.6^ ∘ = 0.45, M 1.6 -3.5^ ∘ = 0.45, M 3.5 -6.4^ ∘ = 0.76, M 6.4 -10.9^ ∘ = 0.72, and M 10.9 -18^ ∘ = 0.48, and the probabilities were P 0-1.6^ ∘ (MCSH) = 0.05, P 1.6 -3.5^ ∘ (MCSH) = 0.05, P 3.5 -6.4^ ∘ (MCSH) = 0.32, P 6.4 -10.9^ ∘ (MCSH) = 0.29, and P 10.9 -18^ ∘ (MCSH) = 0.30. For stimulations without foveal stray light suppression, the medians M were M 0 -1.6^ ∘ = 0.29, M 1.6 -3.5^ ∘ = 0.37, M 3.5 -6.4^ ∘ = 0.98, M 6.4 -10.9 ^^ ∘ = 1.08, and M 10.9 -18^ ∘ = 1.24, and the probabilities were P 0-1.6^ ∘ (MCSH) = 0.09, P 1.6 -3.5^ ∘ (MCSH) = 0.05, P 3.5 -6.4^ ∘ (MCSH) = 0.50, P 6.4 -10.9^ ∘ (MCSH) = 0.55, and P 10.9 -18^ ∘ (MCSH) = 0.55. In conclusion, the stimulus design has an influence on the harmonic components of ssVEPs. An increase in stimulation eccentricity during extrafoveal stimulation leads to a transition of the main response to the second harmonic. The effect is enhanced by a simultaneous foveal stimulation.

Corrigendum: The Influence of the Stimulus Design on the Harmonic Components of the Steady-State Visual Evoked Potential.

[This corrects the article DOI: 10.3389/fnhum.2020.00343.].

The Effects of an Ocular Direct Electrical Stimulation on Pattern-Reversal Electroretinogram.

Studies on transcranial current stimulation have shown that a direct current stimulation of the occipital cortex can influence the amplitude size of a visual evoked potential (VEP). The current direction (cathodal or anodal) determines whether the VEP amplitudes increase or decrease. The aim of this study was to design a new experimental setup that will enable a simultaneous ocular direct current stimulation and electroretinogram (ERG) recording which will broaden our understanding of current stimulation effects on the visual system. Furthermore, we examined whether a direct current stimulation on the eye has a similar effect on an ERG as on a VEP. The pattern-reversal ERG was measured with sintered Ag/AgCl skin-electrodes, positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). Direct current was applied through a ring rubber electrode placed around the eye and a 5 cm × 5 cm rubber electrode placed at the ipsilateral temple with a current strength of 500 µA and a duration time of 5 min. Fifty-seven healthy volunteers were divided into three groups depending on the current direction (cathodal, anodal, and sham stimulation, n = 19 each). One ERG measurement (ERG 1) was performed before and another (ERG 2) during the direct current stimulation. The difference between ERG 1 and ERG 2 measurements for the characteristic P50, N95 and N95' (N95 minimum measured from zero line) amplitudes were evaluated by both confidence interval analysis and t-test for related samples (α = 0.05, after Bonferroni correction p ∗ = 0.0055). The P50 amplitude was significantly decreased for ERG 2 measurement in the cathodal and anodal stimulation group (cathodal p = 0.001, anodal p = 0.000). No significant changes could be found in the N95 and N95' amplitudes as well as in the sham-stimulation group. Additionally, the latencies did not undergo any significant changes. In conclusion, the newly designed experimental setup enables simultaneous current stimulation and ERG recording. The current influenced P50 amplitude although not the N95 and N95' amplitudes. Furthermore, the amplitude size decreased for both current directions and did not lead to contrary effects as expected.

Objective measurement of forward-scattered light in the human eye: An electrophysiological approach.

PURPOSE: Psychophysical measurements are used to examine the perception of ocular stray light, for example, with C-Quant. These measurements are subjective due to their principles. This work aims to determine ocular stray light objectively; thus, a psychophysical method is transferred into an electrophysiological setup. METHODS: Stray light perception was measured using steady-state visual evoked potentials (VEPs) in 10 healthy subjects (7 males, 3 females, mean age ± SD: 29.6 ± 4.1 years). Stray light emulating filters (Tiffen Black Pro Mist 2) were used for simulating the effect of cataracts to validate the results for increased scattered light conditions. Based on the direct compensation method, the stimulus consisted of a central test field (radius = 2°) with a luminance adjustable compensation light and surrounding ring-shaped stray light source (radius = 5 to 10°). Both flickered in the counter phase at a frequency of 7.5 Hz. The stimuli were presented for 15 luminance levels of the compensation light. The recorded steady-state VEPs at Oz channel were transformed by means of Fourier analysis. The magnitudes at the evoked frequency were plotted against the measured brightness levels of the compensation light. By fitting two linear functions to the resulting data points, a robust minimum log(Leq) was determined, which was correlated with the amount of stray light perception. We measured the stray light parameter log(sc) using C-Quant. For comparison, our results were converted into the C-Quant equivalent parameter log(sepm) and paired t-tests were performed for normal distributed results. RESULTS: A significant difference is observed between log(sepm) (without filter) and log(sepm) (with BPM 2 Filter) (p>0.05). No significant difference is observed between log(sepm) (without filter) and log(sc) (without filter) (p > 0.05) and between log(sepm) (with BPM 2 filter) and log(sc) (with BPM 2 filter) (p > 0.05). CONCLUSION: The electrophysiological approach offers the ability to measure stray light perception in an objective manner.