Eye movements and the perceived location of phosphenes generated by intracranial primary visual cortex stimulation in the blind.

BACKGROUND: Restoring sight for the blind using electrical stimulation of the visual pathways is feasible but demands an understanding of the spatial mapping of the visual world at the site of targeted stimulation, whether in the retina, thalamus, or cortex. While a visual cortex stimulator can bypass the eye and create visual percepts, there is an inherent dissociation between this stimulation and eye movements. It is unknown whether and how robustly the brain maintains the oculomotor circuitry in patients with bare- or no-light perception. OBJECTIVE: To critically and quantitatively evaluate the effect of eye movements have on phosphene locations elicited by cortical stimulation that bypasses the eyes in order to restore sight in blind subjects. METHODS: The NeuroPace Responsive Neurostimulator (RNS) and the Orion visual cortical prosthesis devices were used to electrically stimulate the visual cortex of blind subjects with bare or no light perception. Eye positions were recorded synchronized with stimulation and the location of the percepts were measured using a handheld marker. RESULTS: The locations of cortical stimulation-evoked percepts are shifted based on the eye position at the time of stimulation. Measured responses can be remapped based on measured eye positions to determine the retinotopic locations associated with the implanted electrodes, with remapped responses having variance limited by pointing error. CONCLUSIONS: Eye movements dominate the perceived location of cortical stimulation-evoked phosphenes, even after years of blindness. By accounting for eye positions, we can mimic retinal mapping as in natural sight.

Electronic retinal prosthesis for severe loss of vision in geographic atrophy in age-related macular degeneration: First-in-human use.

BACKGROUND: To date there are yet no available approved therapies for Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD). METHODS: Single site, non-randomized safety and efficacy study presenting the preliminary results in a cohort of five late stage AMD (GA) patients successfully implanted with the Argus II Retinal Prosthesis System (Second Sight Medical Products Inc., Sylmar, CA, USA). Extensive fundus imaging including retinal photographs from which the GA area was measured. A combination of custom and traditional tests designed for very low vision subjects assessed visual function in study subjects. A Functional Low-Vision Observer Rated Assessment was carried out to evaluate the impact of the system on the subject's daily life. In addition, a study to evaluate structural characteristics of the visual cortex of the brain was performed in one subject using magnetic resonance imaging. RESULTS: Seven device-related adverse events were reported, four of which were classed as serious adverse events. Retinal detachment was reported in three patients and was successfully treated within 12 months of onset. Testing showed an improvement in visual function in three of five patients with the system turned on. Magnetic resonance imaging assessed in one patient after implantation indicates a selective increase in cortical myelin and thickness in visual brain regions 1 year post implantation. CONCLUSIONS: Epiretinal prostheses can successfully be implanted in those affected by GA secondary to late-stage AMD and can elicit visual percepts by electrical stimulation of residual neuroretinal elements and improve basic visual function in those affected.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Phosphene perceptions and safety of chronic visual cortex stimulation in a blind subject.

Stimulation of primary visual cortices has the potential to restore some degree of vision to blind individuals. Developing safe and reliable visual cortical prostheses requires assessment of the long-term stability, feasibility, and safety of generating stimulation-evoked perceptions.A NeuroPace responsive neurostimulation system was implanted in a blind individual with an 8-year history of bare light perception, and stimulation-evoked phosphenes were evaluated over 19 months (41 test sessions). Electrical stimulation was delivered via two four-contact subdural electrode strips implanted over the right medial occipital cortex. Current and charge thresholds for eliciting visual perception (phosphenes) were measured, as were the shape, size, location, and intensity of the phosphenes. Adverse events were also assessed.Stimulation of all contacts resulted in phosphene perception. Phosphenes appeared completely or partially in the left hemifield. Stimulation of the electrodes below the calcarine sulcus elicited phosphenes in the superior hemifield and vice versa. Changing the stimulation parameters of frequency, pulse width, and burst duration affected current thresholds for eliciting phosphenes, and increasing the amplitude or frequency of stimulation resulted in brighter perceptions. While stimulation thresholds decreased between an average of 5% and 12% after 19 months, spatial mapping of phosphenes remained consistent over time. Although no serious adverse events were observed, the subject experienced mild headaches and dizziness in three instances, symptoms that did not persist for more than a few hours and for which no clinical intervention was required.Using an off-the-shelf neurostimulator, the authors were able to reliably generate phosphenes in different areas of the visual field over 19 months with no serious adverse events, providing preliminary proof of feasibility and safety to proceed with visual epicortical prosthetic clinical trials. Moreover, they systematically explored the relationship between stimulation parameters and phosphene thresholds and discovered the direct relation of perception thresholds based on primary visual cortex (V1) neuronal population excitation thresholds.

One-Year Safety and Performance Assessment of the Argus II Retinal Prosthesis: A Postapproval Study.

IMPORTANCE: The Argus II Retinal Prosthesis System is indicated for patients with vision loss due to severe to profound outer retinal degeneration, a group with few treatment options. OBJECTIVES: To collect postapproval safety and visual function data for the Argus II. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, postapproval clinical trial conducted at 9 sites in Germany and Italy. Data were collected from December 2, 2011, to September 30, 2017, and patients were followed-up for 12 months or longer. Patients were 25 years or older with severe to profound outer retinal degeneration, some residual light perception or the ability of the retina to respond to electrical stimulation, and a history of useful form vision and were already planning to undergo Argus II implantation. MAIN OUTCOMES AND MEASURES: The primary end point of this study was the nature and rate of adverse events. Secondary end points included 3 visual function tests: square localization (SL), direction of motion, and grating visual acuity (GVA). RESULTS: Forty-seven patients were followed for 12 months or longer after implant. Mean (SD) age was 56 (12) years, 37 (79%) had retinitis pigmentosa, and 27 (57%) were male. Through the first 12 months postimplantation, 23 patients (49%) experienced 51 nonserious adverse events and 12 (26%) experienced 13 serious adverse events (SAEs), 9 of which were judged to be related to the Argus II, and 4 of which were judged to be related to the procedure. The most common SAE was conjunctival erosion, reported in 4 patients. No significance testing was done for group analysis for the SL or direction-of-motion tests. When averaged across the group, patients' accuracy on the SL test, but not on the direction-of-motion test, appeared better when the Argus II was on than when it was switched off. For GVA, more patients at each point in time achieved the 2.9 GVA cutoff in the implanted eye when the Argus II was on compared with it switched off. CONCLUSIONS AND RELEVANCE: Safety and visual function outcomes in this clinical practice setting cohort of patients with Argus II implants were consistent with previously reported results. Longer follow-up of these patients and data from additional patients are required to better outline the risks and benefits of this approach to addressing blindness secondary to severe-to-profound outer retinal degeneration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01490827.

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.

Retinotopic to Spatiotopic Mapping in Blind Patients Implanted With the Argus II Retinal Prosthesis.

Purpose: To quantify the precision of mapping from retinotopic (retina-centered) to spatiotopic (world-centered) coordinates in blind humans implanted with a retinal prosthesis device. Additionally, to demonstrate that an eye tracker can be calibrated on sightless patients based on the percept from a visual implant. Methods: We directly activated epiretinal electrodes to create retinotopic stimuli and recorded the location of the percept at world-based coordinates. In contrast to normal Argus II use where stimulation is a function of the captured scene's image, in this research we directly controlled the waveform in each electrode and measured the percept's location using a trackable handheld marker. For eye tracking, pupil images were recorded with a timestamp synchronized to the stimulation and marker positions. Results: Remapping of the measured world locations to the position of the electrodes on the retina is feasible by accounting for eye orientation at the onset of stimulation. Transformation of pupil images to the eye's orientation (i.e., eye tracker calibration) can be done by solving for the variables that minimize the spread of the remapped retinal electrode locations. After mapping to retinal coordinates based on eye positions, the measured precision of pointing was 2° to 3°, which is comparable to open-loop pointing in sighted individuals. Conclusions: The brain accurately maps the artificial vision induced by a retinal prosthesis based on instantaneous gaze position. Remapping based on eye position is feasible and will increase visual stability in prosthetic vision.

Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis.

BACKGROUND: The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end-stage retinitis pigmentosa. METHODS: The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30-patient single-arm clinical study. VisQoL is a multi-attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub-group between baseline and the combined follow-up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow-up periods. RESULTS: Overall, 80 per cent of the patients reported difficulty in one or more dimensions pre-implant. Composite VisQoL utility scores at follow-up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. CONCLUSION: Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36-month follow-up, suggesting a long-term, durable improvement.

Performance of real-world functional vision tasks by blind subjects improves after implantation with the Argus® II retinal prosthesis system.

BACKGROUND: The main objective of this study was to test Argus II subjects on three real-world functional vision tasks. DESIGN: The study was designed to be randomized and prospective. Testing was conducted in a hospital/research laboratory setting at the various participating centres. PARTICIPANTS: Twenty eight Argus II subjects, all profoundly blind, participated in this study. METHODS: Subjects were tested on the three real-world functional vision tasks: Sock Sorting, Sidewalk Tracking and Walking Direction Discrimination task MAIN OUTCOME MEASURES: For the Sock Sorting task, percentage correct was computed based on how accurately subjects sorted the piles on a cloth-covered table and on a bare table. In the Sidewalk Tracking task, an 'out of bounds' count was recorded, signifying how often the subject veered away from the test course. During the Walking Direction Discrimination task, subjects were tested on the number of times they correctly identified the direction of testers walking across their field of view. RESULTS: The mean percentage correct OFF versus ON for the Sock Sorting task was found to be significantly different for both testing conditions (t-test, P < 0.01). On the Sidewalk Tracking task, subjects performed significantly better with the system ON than they did with the system OFF (t-test, P < 0.05). Eighteen (18) of 27 subjects (67%) performed above chance with the system ON, and 6 (22%) did so with system OFF on the Walking Direction Discrimination task. CONCLUSIONS: Argus II subjects performed better on all three tasks with their systems ON than they did with their systems OFF.

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

PURPOSE: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN: Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. PARTICIPANTS: Thirty participants in 10 centers in the United States and Europe. METHODS: The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS: Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS: The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

An analysis of observer-rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years.

OBJECTIVE: The purpose of this analysis was to compare observer-rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. METHODS: The Functional Low-Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow-up of 36 months. FLORA is a multi-component instrument that consists in part of observer-rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four-point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including 'Visual orientation', 'Visual mobility', 'Daily life and 'Interaction with others'. RESULTS: Twenty-six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients' performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. CONCLUSION: Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision-related tasks with the device ON versus OFF.

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration.

Retinal prosthetic implants are the only approved treatment for retinitis pigmentosa, a disease of the eye that causes blindness through gradual degeneration of photoreceptors. An array of microelectrodes triggered by input from a camera stimulates surviving retinal neurons, with each electrode acting as a pixel. Unintended stimulation of retinal ganglion cell axons causes patients to see large oblong shapes of light, rather than focal spots, making it difficult to perceive forms. To address this problem, we performed calcium imaging in isolated retinas and mapped the patterns of cells activated by different electrical stimulation protocols. We found that pulse durations two orders of magnitude longer than those typically used in existing implants stimulated inner retinal neurons while avoiding activation of ganglion cell axons, thus confining retinal responses to the site of the electrode. Multielectrode stimulation with 25-ms pulses can pattern letters on the retina corresponding to a Snellen acuity of 20/312. We validated our findings in a patient with an implanted epiretinal prosthesis by demonstrating that 25-ms pulses evoke focal spots of light.

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.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind.

PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

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 Detection of Motion by Blind Subjects With the Epiretinal 60-Electrode (Argus II) Retinal Prosthesis.

OBJECTIVE: To investigate the ability of 28 blind subjects implanted with a 60-electrode Argus II (Second Sight Medical Products Inc) retinal prosthesis system to detect the direction of a moving object. METHODS: Blind subjects (bare light perception or worse in both eyes) with retinitis pigmentosa were implanted with the Argus II prosthesis as part of a phase 1/2 feasibility study at multiple clinical sites worldwide. The experiment measured their ability to detect the direction of motion of a high-contrast moving bar on a flatscreen monitor in 3 conditions: with the prosthesis system on and a 1-to-1 mapping of spatial information, with the system off, and with the system on but with randomly scrambled spatial information. RESULTS: Fifteen subjects (54%) were able to perform the task significantly better with their prosthesis system than they were with their residual vision, 2 subjects had significantly better performance with their residual vision, and no difference was found for 11 subjects. Of the 15 better-performing subjects, 11 were available for follow-up testing, and 10 of them had significantly better performance with normal rather than with scrambled spatial information. CONCLUSIONS: This work demonstrates that blind subjects implanted with the Argus II retinal prosthesis were able to perform a motion detection task they could not do with their native vision, confirming that electrical stimulation of the retina provides spatial information from synchronized activation of multiple electrodes. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00407602

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.