Phosphene Thresholds Elicited by Transcorneal Electrical Stimulation in Healthy Subjects and Patients with Retinal Diseases

Naycheva, Lubka; Schatz, Andreas; Röck, Tobias; Willmann, Gabriel; Messias, André; Bartz‐Schmidt, Karl Ulrich; Zrenner, Eberhart; Gekeler, Florian

doi:10.1167/iovs.12-9612

Cited by 45 publications

(55 citation statements)

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“…7b) suggests that information from the ON system may somehow be more useful to downstream visual centers. This is consistent with preferential reporting of ON responses in human trials (Humayun et al 1996; Humayun et al 2003; Fujikado et al 2007; Naycheva et al 2012). In addition, the rates that maximize ON responses may be more preferable because electric responses of ON types have better levels of correlations to their light responses (Im and Fried, 2015).…”

Section: Discussionsupporting

confidence: 87%

Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

Im¹,

Fried

2016

J. Neural Eng.

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Objective To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. Approach We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10–1000 ms). Each stimulus was a 4-ms-long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. Main results ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported ‘reset’ behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4–7 Hz) that maximized the ratio of the responses arising in ON vs. OFF cells. Significance Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5–7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (> ~7 Hz) due to the reset while responses of OFF cells are strong at low rates (< ~4 Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried, 2015), our results offer a potential reason for the user preference of intermediate rates (5–7 Hz).

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Section: Discussionsupporting

confidence: 87%

Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

Im¹,

Fried

2016

J. Neural Eng.

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“…The specific stimulation parameter was chosen due to the fact that the lowest EPT was observed at 20 Hz. This trough for EPT at 20 Hz was also found in healthy subjects, and patients with other retinal diseases, such as RP, nonarteritic anterior ischemic optic neuropathy, Stargardt’s disease, and primary open-angle glaucoma [42]. …”

Section: Discussionmentioning

confidence: 73%

Transcorneal Electrical Stimulation in Patients with Retinal Artery Occlusion: A Prospective, Randomized, Sham-Controlled Pilot Study

et al. 2013

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IntroductionThe purpose of this study was to investigate the safety and efficacy of transcorneal electrical stimulation (TES) in patients suffering from retinal artery occlusion (RAO).MethodsTwelve patients with central and one patient with branch RAO (age 25–84 years, median 74 years) were enrolled in this prospective, randomized, sham-controlled study. RAO was diagnosed 10 days to 17 months prior to study participation. Patients were treated with TES (5 ms positive followed by 5 ms negative biphasic pulses at 20 Hz; applied with DTL electrodes) for 30 min once a week for 6 consecutive weeks. Patients were randomly assigned to TES with 0 mA (sham, n = 3), 66% (n = 5) or 150% (n = 5) of the patient’s individual electrical phosphene threshold (EPT) at 20 Hz. Best corrected visual acuity, ophthalmology examination and EPT (at 3, 6, 9, 20, 40, 60, and 80 Hz) were determined at baseline and at eight follow-up visits over 17 weeks. During four visits (week 1, 5, 9, and 17) kinetic and static visual fields as well as full-field and multifocal electroretinography were measured. The method of restricted maximum likelihood (P < 0.05, Tukey–Kramer) was used to estimate the development of parameters under treatment.ResultsTES was tolerated well; no ocular or systemic adverse events were observed except for foreign-body sensation after TES (n = 3). During the study period the slopes of the scotopic a-wave increased significantly (high-intensity flash white 10 cd.s/m2; P = 0.03) in the 150% treatment group. All other parameters in all other groups remained statistically unchanged.ConclusionsAlthough TES was tolerated well, statistically significant improvements were found only for specific a-wave slopes. This is in contradiction to previous smaller, uncontrolled reports. Further studies with larger sample sizes and longer duration might, however, show additional significant effects.

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“…In a recent study using TES, electrical phosphene threshold varied between disease groups. 42 Across all tested frequencies (3, 6, 9, 20, 40, and 80 Hz), electrical phosphene thresholds were significantly higher when compared with healthy subjects, except in Stargardt disease patients at 20 Hz. Improvements in visual acuity in a recent case report with best vitelliform macular dystrophy suggest that TES should also be investigated in other cases of retinal dystrophies.…”

Section: The Effects Of Tes In Clinical Studiesmentioning

confidence: 81%

Electrical Stimulation as a Means for Improving Vision

Sehic

Guo

Cho

et al. 2016

The American Journal of Pathology

138

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Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision. (Am J Pathol 2016 http://dx

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Phosphene Thresholds Elicited by Transcorneal Electrical Stimulation in Healthy Subjects and Patients with Retinal Diseases

Cited by 45 publications

References 50 publications

Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type

Transcorneal Electrical Stimulation in Patients with Retinal Artery Occlusion: A Prospective, Randomized, Sham-Controlled Pilot Study

Electrical Stimulation as a Means for Improving Vision

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