Effects of Ocular Direct Current Stimulation on Full Field Electroretinogram

Abstract

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.

Keywords: direct current stimulation; electroretinogram; full field ERG; non-invasive brain stimulation; ocular electrical stimulation; transorbital electrical stimulation.

FIGURE 1

(A) Measurement setup which consists of (1) a visual stimulator system (RETI-port/scan 21 Q4; Roland Consult Stasche & Finger GmbH, Brandenburg a.d. Havel, Germany), (2) the current stimulator system (MC-stimulator DC; neuroCare Group GmbH, Munich, Germany), and (3) the amplifier system (Cubias-M; neuroCare Group GmbH, Munich, Germany). (B) Measurement timeline.

FIGURE 2

Grand mean signals for every stimulation group (i.e., cathodal polarity, anodal polarity, and sham stimulation; n = 15 for each curve) for the different ERG measurements. ERG 1 (blue curve) was done before and ERG 2 (orange curve) during the current stimulation. No effects are visible on the a, b′, or b-wave amplitudes or latencies comparing before and during current stimulation. Due to latency time differences between the subjects, different amplitudes could have occurred in the grand mean diagrams. Therefore, the grand mean signals show only a trend for the amplitude changes.

FIGURE 3

Data distribution of (A) amplitude and (B) latency differences between the ERG 1 and ERG 2 measurement for the ERG components (i.e., a-wave, b′-wave, and b-wave) and current stimulation groups (blue: cathodal polarity; red: anodal polarity; green: sham stimulation). The color-coded violin plots include data representations (colored dots) and the box-and-whisker plot (25 and 75% quartiles represented by the gray boxes and whiskers by the gray lines). Small changes are visible for the amplitudes of the cathodal and sham stimulation group while no changes can be seen for all latencies. Neither the Wilcoxon signed-rank test (α = 0.05, after Bonferroni correction p* ≤ 0.0056) comparing ERG 1 with ERG 2 measurement for the different amplitudes nor the Friedman test (α = 0.05, after Bonferroni correction p* ≤ 0.016) for the comparison between the current stimulation groups could find a significant current effect.