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.

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.

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.

Interim results from the international trial of Second Sight's visual prosthesis.

PURPOSE: This study evaluated the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in blind subjects with severe outer retinal degeneration. DESIGN: Single-arm, prospective, multicenter clinical trial. PARTICIPANTS: Thirty subjects were enrolled in the United States and Europe between June 6, 2007, and August 11, 2009. All subjects were followed up for a minimum of 6 months and up to 2.7 years. METHODS: The electronic stimulator and antenna of the implant were sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed, and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array then was tacked to the epiretinal surface. MAIN OUTCOME MEASURES: The primary safety end points for the trial were the number, severity, and relation of adverse events. Principal performance end points were assessments of visual function as well as performance on orientation and mobility tasks. RESULTS: Subjects performed statistically better with the system on versus off in the following tasks: object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects' mean performance on orientation and mobility tasks was significantly better when the system was on versus off. Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was treated successfully in all subjects except in one, who required explantation of the device without further complications. CONCLUSIONS: The long-term safety results of Second Sight's retinal prosthesis system are acceptable, and most subjects with profound visual loss perform better on visual tasks with system than without it.

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.

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.

Factors affecting perceptual thresholds in epiretinal prostheses.

PURPOSE: The goal was to evaluate how perceptual thresholds are related to electrode impedance, electrode size, the distance of electrodes from the retinal surface, and retinal thickness in six subjects blind as a result of retinitis pigmentosa, who received epiretinal prostheses implanted monocularly as part of a U.S. Food and Drug Administration (FDA)-approved clinical trial. METHODS: The implant consisted of an extraocular unit containing electronics for wireless data, power recovery, and generation of stimulus current, and an intraocular unit containing 16 platinum stimulating electrodes (260- or 520-microm diameter) arranged in a 4 x 4 pattern. The electrode array was held onto the retina by a small tack. Stimulation was controlled by a computer-based external system that allowed independent control over each electrode. Perceptual thresholds (the current necessary to see a percept on 79% of trials) and impedance were measured for each electrode on a biweekly basis. The distance of electrodes from the retinal surface and retinal thickness were measured by optical coherence tomography on a less regular basis. RESULTS: Stimulation thresholds for detecting phosphenes correlated with the distance of the electrodes from the retinal surface, but not with electrode size, electrode impedance, or retinal thickness. CONCLUSIONS: Maintaining close proximity between the electrode array and the retinal surface is critical in developing a successful retinal implant. With the development of chronic electrode arrays that are stable and flush on the retinal surface, it is likely that the influence of other factors such as electrode size, retinal degeneration, and subject age will become more apparent. (ClinicalTrials.gov number, NCT00279500.).

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.

Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa.

PURPOSE: To assess visual task performance in three blind subjects implanted with epiretinal prostheses. DESIGN: Prospective, investigational device exemption trial. METHODS: Three subjects with light perception or no light perception vision were enrolled at a single center. All subjects had retinitis pigmentosa (RP). Main inclusion criteria: light perception or worse vision in one eye and some visual experience as an adult before blindness. Main exclusion criteria included other ophthalmic problems. A prototype retinal prosthesis was implanted in the eye with worse light sensitivity. The prosthesis had 4 x 4 array of platinum electrodes tacked to the epiretinal surface. The prosthesis was wirelessly controlled by a computer or by a head-worn video camera. Visual function testing was performed in single masked or double masked fashion. Scores from the visual task were compared to chance to determine statistical significance. RESULTS: The subjects performed significantly better than chance in 83% of the tests. Using the video camera, subjects scored as follows on simple visual tasks: locate and count objects (77% to 100%), differentiate three objects (63% to 73%), determine the orientation of a capital L (50% to 77%), and differentiate four directions of a moving object (40% to 90%). A subset of tests compared camera settings using multipixels vs single pixels. Using multipixel settings, subjects performed better (17%) or equivalent (83%) in accuracy and better (25%) or equivalent (75%) in reaction time. CONCLUSIONS: Three RP implant subjects used epiretinal prostheses to perform simple visual tasks. Multipixel settings proved slightly more effective than single pixel settings.

Electrical properties of retinal-electrode interface.

A critical element of a retinal prosthesis is the stimulating electrode array, which is placed in close proximity to the retina. It is via this retinal-electrode interface that a retinal prosthesis electrically stimulates nerve cells to produce the perception of light. The impedance load seen by the current driver consists of the tissue resistance and the complex electrode impedance. The results in this paper show that the tissue resistance of the retina is significantly greater than that of the vitreous humor in the eye. Circuit models of the electrode-retina interface are used to parameterize the different contributors to the overall impedance.

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.

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.

Microsensors and microbiosensors for retinal implants.

This paper concentrates on recent developments in microsensors and microbiosensors for the possible applications in visual prostheses, especially retinal prosthetic devices. A brief introduction on the developments of visual prosthesis will be presented. The importance for in-vivo pH measurements as well as the need for an implantable pH sensor will be demonstrated. Electrochemical biosensors developed for sensitive measurements of glucose and L-glutamate, a known neurotransmitter in the retina and brain will be reviewed. Novel electrode materials such as chemically modified thin-film diamond in applications for implantable biosensors will be shown. The challenges in the development of chronic implantable sensor systems, especially using MEMS technology for medical implants, will be discussed.