The effect of waveform asymmetry on perception with epiretinal prostheses.

Objective: Retinal prosthetic implants have helped improve vision in patients blinded by photoreceptor degeneration. Retinal implant users report improvements in light perception and performing visual tasks, but their ability to perceive shapes and letters is limited due to the low precision of retinal activation, which is exacerbated by axonal stimulation and high perceptual thresholds. A previous in vitro study in our lab used calcium imaging to measure the spatial activity of mouse retinal ganglion cells (RGCs) in response to electrical stimulation. Based on this study, symmetric anodic-first (SA) stimulation effectively avoided axonal activation and asymmetric anodic-first stimulation (AA) with duration ratios (ratio of the anodic to cathodic phase) greater than 10 reduced RGC activation thresholds significantly. Applying these novel stimulation strategies in clinic may increase perception precision and improve the overall patient outcomes. Approach: We combined human subject testing and computational modeling to further examine the effect of SA and AA stimuli on perception shapes and thresholds for epiretinal stimulation of RGCs. Main results: Threshold measurement in three Argus II participants indicated that AA stimulation could increase perception probabilities compared to a standard symmetric cathodic-first (SC) pulse, and this effect can be intensified by addition of an interphae gap (IPG). Our in silico RGC model predicts lower thresholds with AA and asymmetric cathodic-first (AC) stimuli compared to a SC pulse. This effect was more pronounced at shorter pulse widths. The most effective pulse for threshold reduction with short pulse durations (≤0.12 ms) was AA stimulation with small duration ratios (≤5) and long IPGs (≥2 ms). For the 0.5 ms pulse duration, SC stimulation with IPGs longer than 0.5 ms, or asymmetric stimuli with large duration ratios (≥20) were most effective in threshold reduction. Phosphene shape analysis did not reveal a significant change in percept elongation with SA stimulation. However, there was a significant increase in percept size (P < 0.01) with AA stimulation compared to the standard pulse in one participant. Significane: Including asymmetric waveform capability will provide more flexible options for optimization and personalized fitting of retinal implants.

Retina-electrode interface properties and vision restoration by two generations of retinal prostheses in one patient-one in each eye.

OBJECTIVE: The Argus I implant is a first-generation epiretinal prosthesis approved for an investigational clinical trial in the U.S. Its successor, the Argus II implant, has a higher electrode density for increased spatial resolution and covers a larger retinal area to accommodate a wider visual angle. Both generations of Argus restored some vision to end-stage RP patients, but it remains unclear how the increased electrode count affected the visual percepts. Here we report a study of the first person on earth with two 'bionic eyes', with an Argus I implanted in one eye and Argus II in the other, to compare the retina-electrode interface and the visual outcome of the two devices. APPROACH: The retina-electrode interface was examined by electrode impedance, perceptual threshold, and ophthalmic images such as ocular coherence tomography data and fundus imaging. The subject's visual outcomes were evaluated by computer-based visual function tests and subjective feedback. MAIN RESULTS: The electrode impedance of both Argus I and II slowly decreased overtime after implantation, accompanied by a gradual increase in the perceptual threshold. A quantitative analysis of the impedance and retina-electrode distance revealed somewhat different causes of impedance change in Argus I vs. II. Evaluation of the visual functions restored and feedback from the subject suggest that the Argus II device enables improved spatial visual ability over Argus I, but adaptation to prosthetic vision did not lead to a measurable performance improvement in the standard visual function tests. SIGNIFICANCE: This study of Argus I and II in the same subject directly compares for the first time the interface properties and prosthetic vision in two eyes that share the same disease mechanism and converged visual pathway in higher visual centers, offering exciting new insights into the influence of the electrode parameters and layout to prosthetic vision. TRIAL REGISTRATION: Data collected within clinical trials registered at NIH (NCT00279500 & NCT01860092).

Eye Movement Control in the Argus II Retinal-Prosthesis Enables Reduced Head Movement and Better Localization Precision.

Purpose: Visual scanning by sighted individuals is done using eye and head movements. In contrast, scanning using the Argus II is solely done by head movement, since eye movements can introduce localization errors. Here, we tested if a scanning mode utilizing eye movements increases visual stability and reduces head movements in Argus II users. Methods: Eye positions were measured in real-time and were used to shift the region of interest (ROI) that is sent to the implant within the wide field of view (FOV) of the scene camera. Participants were able to use combined eye-head scanning: shifting the camera by moving their head and shifting the ROI within the FOV by eye movement. Eight blind individuals implanted with the Argus II retinal prosthesis participated in the study. A white target appeared on a touchscreen monitor and the participants were instructed to report the location of the target by touching the monitor. We compared the spread of the responses, the time to complete the task, and the amount of head movements between combined eye-head and head-only scanning. Results: All participants benefited from the combined eye-head scanning mode. Better precision (i.e., narrower spread of the perceived location) was observed in six out of eight participants. Seven of eight participants were able to adopt a scanning strategy that enabled them to perform the task with significantly less head movement. Conclusions: Integrating an eye tracker into the Argus II is feasible, reduces head movements in a seated localization task, and improves pointing precision.

Ten-Year Follow-up of a Blind Patient Chronically Implanted with Epiretinal Prosthesis Argus I.

PURPOSE: The Argus I implant is the first-generation epiretinal prosthesis approved for an investigational clinical trial by the United States Food and Drug Administration. Herein we report testing results obtained from a 10-year follow-up to study the physiologic effects of the bioelectronic visual implant after prolonged chronic electrical stimulation. DESIGN: Case report. PARTICIPANT: One man, 55 years of age when enrolled in the study, underwent surgical implantation of the Argus I in June 2004, followed by periodic tests from July 2004 through June 2014, spanning a total of 10 years. METHODS: The decade-long follow-up consisted of implant system performance tests, subject visual function evaluation, and implant-retina interface analysis. MAIN OUTCOME MEASURES: Changes in electrode impedance and perceptual threshold over the time course; subject's performance on visual function task, orientation, and mobility tests; and optical coherence tomography data, fundus imaging, and fluorescein angiography results for the assessment of subject's implant-retina physical interface. RESULTS: Electrically elicited phosphenes were present 10 years after implantation of an epiretinal stimulator. The test subject not only was able to perceive phosphenes, but also could perform visual tasks at rates well above chance. CONCLUSIONS: This decade-long follow-up report provides further support for the use of retinal prostheses as a long-lasting treatment for some types of blindness.

Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses.

OBJECTIVE: Epiretinal prostheses are designed to restore functional vision to the blind by electrically stimulating surviving retinal neurons. These devices have classically employed symmetric biphasic current pulses in order to maintain a balance of charge. Prior electrophysiological and psychophysical studies in peripheral nerve show that adding an interphase gap (IPG) between the two phases makes stimulation more efficient than pulses with no gap. This led us to investigate the effect of IPG duration on retinal stimulation thresholds. APPROACH: We measured retinal ganglion cell (RGC) electrical thresholds in salamander retina and phosphene perceptual thresholds in epiretinal prosthesis patients during stimulation with different IPG lengths. We also built Hodgkin-Huxley-type models of RGCs to further study how IPG affects thresholds. MAIN RESULTS: In general, there was a negative exponential correlation between threshold and IPG duration. Durations greater than or equal to ~0.5 ms reduced salamander RGC thresholds by 20-25%. Psychophysical testing in five retinal prosthesis patients indicated that stimulating with IPGs can decrease perceptual thresholds by 10-15%. Results from computational models of RGCs corroborated the observed behavior. SIGNIFICANCE: Incorporating interphase gaps can reduce the power consumption of epiretinal prostheses and increase the available dynamic range of phosphene size and brightness.

The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss.

BACKGROUND: Retinal prosthesis systems (RPS) are a novel treatment for profound vision loss in outer retinal dystrophies. Ideal prostheses would offer stable, long-term retinal stimulation and reproducible spatial resolution in a portable form appropriate for daily life. METHODS: We report a prospective, internally controlled, multicentre trial of the Argus II system. Twenty-eight subjects with light perception vision received a retinal implant. Controlled, closed-group, forced-choice letter identification, and, open-choice two-, three- and four-letter word identification tests were carried out. RESULTS: The mean±SD percentage correct letter identification for 21 subjects tested were: letters L, T, E, J, F, H, I, U, 72.3±24.6% system on and 17.7±12.9% system off; letters A, Z, Q, V, N, W, O, C, D, M, 55.0±27.4% system on and 11.8%±10.7% system off, and letters K, R, G, X, B, Y, S, P, 51.7±28.9% system on and 15.3±7.4% system off. (p<0.001 for all groups). A subgroup of six subjects was able to consistently read letters of reduced size, the smallest measuring 0.9 cm (1.7°) at 30 cm, and four subjects correctly identify unrehearsed two-, three- and four-letter words. Average implant duration was 19.9 months. CONCLUSIONS: Multiple blind subjects fitted with the Argus II system consistently identified letters and words using the device, indicating reproducible spatial resolution. This, in combination with stable, long-term function, represents significant progress in the evolution of artificial sight.