End-stage Retinitis Pigmentosa Research Articles

Evaluation of the Long-Term Clinical Results of 3 Patients Implanted with the Argus II Retinal Prosthesis.

This study presents the long-term clinical results of Argus II retinal prosthesis implantation in eyes with light perception and projection in 3 patients with end-stage retinitis pigmentosa. No conjunctival erosion, hypotony, or implant displacement was observed during postoperative follow-up. The electrical threshold values were lower in the macular region and higher close to the tack fixation region and peripherally. Optical coherence tomography scans showed fibrosis and retinoschisis formation at the retina-implant interface in two cases. This was attributed to mechanical and electrical effects on the tissue due to the active daily use of the system and the electrodes' proximity to the retina. The patients were able to integrate the system into their daily lives and perform activities that they could not do before. Studies on retinal prostheses for the rehabilitation of hereditary retinal diseases are ongoing, so both social and clinical observations and experiences related to the implant are valuable.

A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Long-Term Observation of the Electrode-Tissue Interface.

PurposeTo report the long-term observations of the electrode–tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant.MethodsFour subjects (S1–4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode–retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase.ResultsElectrode impedances were stable longitudinally. The electrode–retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode–retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode–retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02).ConclusionsChronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode–retina distances after a period of settling after surgery.Translational RelevanceChronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.

First Human Results With the 256 Channel Intelligent Micro Implant Eye (IMIE 256).

PurposeTo report on the safety and efficacy of the 256-channel Intelligent Micro Implant Eye epiretinal prosthesis system (IMIE 256).MethodsThe IMIE 256 implants were implanted in the right eyes of five subjects with end-stage retinitis pigmentosa. Following implantation, the subjects underwent visual rehabilitation training for 90 days, and their visual performance was evaluated using the grating visual acuity test, Tumbling E visual acuity test, direction of motion, square localization, and orientation and mobility test. To evaluate the safety of the IMIE 256, all adverse events were recorded.ResultsSubjects performed significantly better on all evaluations with the IMIE 256 system on as compared with the performance at baseline or with the system off. There was a steady improvement in performance at each observation interval, indicating that the training and/or practice helped the subjects use the IMIE 256. There were two serious adverse events—electrode array movement and low intraocular pressure in one subject, which resolved with surgery. There were no other adverse events observed except those expected in the course of postoperative healing.ConclusionsThese results show an improved safety and efficacy profile compared with that of the Argus II implant. Further clinical trials are needed to confirm these results in a larger number of subjects and over longer durations.Translational RelevanceTo our knowledge, this study reports the first in-human data from a high-density (256 electrodes) epiretinal implant to restore sight to a subset of blind patients.

Effects of the Argus II Retinal Prosthesis System on the Quality of Life of Patients With Ultra-Low Vision Due to Retinitis Pigmentosa: Protocol for a Single-Arm, Mixed Methods Study.

BackgroundRetinitis pigmentosa is an incurable, degenerative retinal condition causing progressive sight loss, significantly affecting patients’ quality of life. The Argus II Retinal Prosthesis is a surgically implanted medical device that delivers electrical stimulation to the retina. It is intended to produce a form of artificial vision for blind people with severe-to-profound retinitis pigmentosa by stimulating the remaining viable retinal cells to induce visual perception. This study has been initiated by National Health Service England’s Commissioning through Evaluation program and funded through the National Institute of Health Research of the United Kingdom.ObjectiveThe aim of this study was to assess the effect of the Argus II device on patient’s daily activities and quality of life.MethodsThis protocol is a prospective, single-arm, open-label, mixed methods study on 10 consecutive participants receiving the Argus II device. The patient representatives played an integral role in the design of this study. Eligibility criteria include ultra-low vision in both eyes as a result of end-stage retinitis pigmentosa and a willingness and capacity to complete the postimplantation rehabilitation program. Participants will be interviewed by independent researchers at baseline and 12 months later by using a semistructured, in-depth approach, alongside validated questionnaires (Impact of Vision Impairment-Very Low Vision, 5-level EuroQoL-5 dimensions scale, EuroQoL-visual analog scale, and Hospital Anxiety and Depression Scale) and a bespoke device-related questionnaire, which includes questions about users’ experiences with the procedure, the device, and rehabilitation. The effect of the device on patients’ functional vision and activities of daily living will be assessed by vision rehabilitation specialists using a set of tests measured on an ordinal scale (eg, ability to locate objects and avoid obstacles). Clinical outcomes include full-field stimulus light threshold, square localization, direction of motion, grating visual acuity, Landolt-C, procedural success, and adverse events. Qualitative and quantitative outcomes will be linked in a single database to enable individual participant measures to be considered in toto, comparing baseline to the final review.ResultsThis study was approved by the local ethics committee on April 24, 2019 (London-Camberwell St. Giles Research Ethics Committee, reference 19/LO/0429). It has also been approved by the Health Research Authority and Health and Care Research Wales. At the time of protocol writing, Argus II was available for use in the United Kingdom; however, the manufacturer recently withdrew the Argus II device from sale in the United Kingdom. Therefore, the study is not going ahead at this time.ConclusionsThe mixed methods approach provides a rich and in-depth assessment of the effect of the device on participants’ quality of life. Despite the work not going ahead, the publication of this publicly funded protocol is important for researchers planning similar work.International Registered Report Identifier (IRRID)PRR1-10.2196/17436

Improved performance and safety from Argus II retinal prosthesis post-approval study in France.

To evaluate the post-approval long-term outcomes of the Argus II Retinal Prosthesis, with a specific focus on its functional visual benefit in patients' daily activities. Eighteen patients with bare light perception due to end-stage retinitis pigmentosa were included in a French prospective, multicentre, single-arm study and followed for 2years. Visual benefit in patients' daily activities was monitored through the use of the Functional Low-vision Observer Rated Assessment (FLORA), and the final score at 2years was the primary effectiveness outcome. Standardized visual assessments were also performed. Device- or procedure-related adverse events were recorded. Seventeen subjects completed the study. Positive impacts of the Argus II system on functional vision and well-being were demonstrated for over 70% of subjects on the FLORA. Among the daily activities/tasks tested, finding doorways was one of the most statistically significantly improved tasks (p<0.001), along with estimating the size of an obstacle (p<0.001), visually locating a place setting on a dining table (p<0.001) and visually locating people in a non-crowded setting (p<0.001). Visual function was improved on most standardized tests. Only two device- or procedure-related serious adverse events were observed (one vitreous haemorrhage and one endophthalmitis, both resolved with treatment). No explantation was required. This first report of a completed post-approval study of Argus II with a two-year follow-up demonstrates the safety and effectiveness of the Argus II System in a real-world cohort of patients and further highlights its real functional benefit in implanted patients' daily activities.

One-Year Anatomical and Functional Outcomes of the Argus II Implantation in Korean Patients with Late-Stage Retinitis Pigmentosa: A Prospective Case Series Study

Purpose: To report the anatomical and functional outcomes of Argus II retinal prosthesis implantation in Korean patients. Methods: We included 5 consecutive patients with end-stage retinitis pigmentosa (RP) who underwent Argus II retinal prosthesis implantation and were followed for at least 12 months. The transcorneal electrical evoked response was utilized for patient selection. We used intraoperative optical coherence tomography (OCT) for optimal placement of the array and provided specialized vision rehabilitation training. A morphological evaluation using SD-OCT and a functional evaluation using computer-based visual function tests, a letter-reading ability test, and the Functional Low-Vision Observer Rated Assessment (FLORA) were conducted. Results: Postoperatively, the array was completely apposed to the retinal surface in all eyes, except for one eye which had a preexisting macular concavity. Fibrosis-like tissues of ≥50-μm thickness developed at the interface in 2 eyes. All of the patients showed improvement in computer-based visual function tests and could read ETDRS letters at a distance of 50 cm. Three patients could read Korean words. FLORA was improved in all patients, mainly in tasks of visual mobility, daily activities, and social interactions. Conclusions: Along with good anatomical outcomes and specialized rehabilitation practices, recipients of the Argus II implant showed profound improvements in functional vision and mobility.

Restoring Color Perception to the Blind: An Electrical Stimulation Strategy of Retina in Patients with End-stage Retinitis Pigmentosa

Bioelectronic retinal prostheses that stimulate the remaining inner retinal neurons, bypassing degenerated photoreceptors, have been demonstrated to restore some vision in patients blinded by retinitis pigmentosa (RP). These implants encode luminance of the visual scene into electrical stimulation, however, leaving out chromatic information. Yet color plays an important role in visual processing when it comes to recognizing objects and orienting to the environment, especially at low spatial resolution as generated by current retinal prostheses. In this study, we tested the feasibility of partially restoring color perception in blind RP patients, with the aim to provide chromatic information as an extra visual cue. Case series. Seven subjects blinded by advanced RP and monocularly fitted with an epiretinal prosthesis. Frequency-modulated electrical stimulation of retina was tested. Phosphene brightness was controlled by amplitude tuning, and color perception was acquired using the Red, Yellow, Green, and Blue (RYGB) hue and saturation scaling model. Brightness and color of the electrically elicited visual perception reported by the subjects. Within the tested parameter space, 5 of 7 subjects perceived chromatic colors along or nearby the blue-yellow axis in color space. Aggregate data obtained from 20 electrodes of the 5 subjects show that an increase of the stimulation frequency from 6 to 120 Hz shifted color perception toward blue/purple despite a significant inter-subject variation in the transition frequency. The correlation between frequency and blue-yellow perception exhibited a good level of consistency over time and spatially matched multi-color perception was possible with simultaneous stimulation of paired electrodes. No obvious correlation was found between blue sensations and array placement or status of visual impairment. These findings present a strategy for the generation and control of color perception along the blue-yellow axis in blind patients with RP by electrically stimulating the retina. It could transform the current prosthetic vision landscape by leading in a new direction beyond the efforts to improve the visual acuity. This study also offers new insights into the response of our visual system to electrical stimuli in the photoreceptor-less retina that warrant further mechanistic investigation.

PP-13 - A case report of carfilzomib-induced hepatotoxicity

To report clinical and genetic features of a Japanese patient with end-stage retinitis pigmentosa (RP) caused by a homozygous PDE6A variant.We performed comprehensive ophthalmic examinations. Whole exome sequencing analysis was used to investigate the RP patient with parental consanguinity. The pedigree included 4 RP patients in the two generations, which suggests presumed pseudo-autosomal dominant inheritance.A PDE6A variant (p.R653X) was identified to be homozygous and disease-causing in the patient. Homozygosity mapping revealed the homozygous region including the variant and confirmation of autosomal recessive inheritance. The patient reported night blindness at 4 years of age and exhibited typical RP fundus appearance with macula involvement during the follow-up period from at the age of 52–69 years. At the age of 52, the patient exhibited a loss of visual acuity and had severely constricted visual fields, with a further gradual deterioration of her vision until she was 69 years old. At the age of 69, funduscopy showed severe chorioretinal degeneration in the area from the posterior pole to the peripheral retina.This is the first report that the PDE6A variant (p.R653X) has been identified as one of the causes of autosomal recessive RP in the Japanese population. Longitudinal natural history/end-stage findings demonstrated early-onset and a severe RP phenotype with macula involvement when the patient was in her 50s and severe chorioretinal degenerations in her late 60s.

Trade-Off Between Field-of-View and Resolution in the Thermal-Integrated Argus II System.

PurposeTo investigate the effect of a wider field-of-view (FOV) of a retinal prosthesis on the users' performance in locating objects.MethodsOne female and four male subjects who were blind due to end-stage retinitis pigmentosa and had been implanted with the Argus II retinal prosthesis participated (aged 63.4 ± 15.4). Thermal imaging was captured by an external sensor and converted to electrical stimulation to the retina. Subjects were asked to localize and to reach for heat-emitting objects using two different FOV mappings: a normal 1:1 mapping (no zoom) that provided 18° × 11° FOV and a 3:1 mapping (zoom out) that provided 49° × 35° FOV. Their accuracy and response time were recorded.ResultsSubjects were less accurate and took longer to complete the tasks with zoom out compared to no zoom. Localization accuracy decreased from 83% (95% confidence interval, 75%, 90%) with no zoom to 76% (67%, 83%) with zoom out (P = 0.07). Reaching accuracy differed between the two mappings only in one subject. Response time increased by 43% for the localization task (24%, 66%; P < 0.001) and by 20% for the reaching task (0%, 45%; P = 0.055).ConclusionsArgus II wearers can efficiently find heat-emitting objects with the default 18° × 11° FOV of the current Argus II. For spatial localization, a higher spatial resolution may be preferred over a wider FOV.Translational RelevanceUnderstanding the trade-off between FOV and spatial resolution in retinal prosthesis users can guide device optimization.

A bionic eye: performance of the Argus II retinal prosthesis in low-vision and social rehabilitation of patients with end-stage retinitis pigmentosa

The death of outer retinal layers occurring in retinitis pigmentosa causes severe visual impairment and often leads to total blindness. Inner retinal layers are spared, though, which provides a possibility of inducing visual perception by direct electrical stimulation of intact retinal cells. This article presents clinical outcomes of two patients who were the first in Russia to have received the Argus II Retinal Prosthesis System. Both implantations were successful. No complications were reported throughout the entire follow-up period. Upon completing 3 rehabilitation sessions, the patients were able to navigate indoors and outdoors, locate small high-contrast objects, discern contours of large objects and people’s silhouettes.

Histopathologic Assessment of Optic Nerves and Retina From a Patient With Chronically Implanted Argus II Retinal Prosthesis System.

PurposeTo characterize histologic changes in the optic nerve and the retina of an end-stage retinitis pigmentosa (RP) patient after long-term implantation with the Argus II retinal prosthesis system.MethodsSerial cross sections from the patient's both eyes were collected postmortem 6 years after implantation. Optic nerve from both eyes were morphometrically analyzed and compared. Retina underneath and outside the array was analyzed and compared with corresponding regions in the fellow eye.ResultsAlthough the optic nerve of the implant eye demonstrated significantly more overall atrophy than the fellow eye (P < 0.01), the temporal quadrant that retinotopically corresponded to the location of the array did not show additional damage. The total neuron count of the macular area was not significantly different between the two eyes, but the tack locations and their adjacent areas showed significantly fewer neurons than other perimacular areas. There was an increased expression of glial fibrillary acidic protein (GFAP) throughout the retina in the implant eye versus the fellow eye, but there was no significant difference in the cellular retinaldehyde-binding protein (CRALBP) expression. Except for the revision tack site, no significant increase of inflammatory reaction was detected in the implant eye.ConclusionLong-term implantation and electrical stimulation with an Argus II retinal prosthesis system did not result in significant tissue damage that could be detected by a morphometric analysis.Translational RelevanceThis study supports the long-term safety of the Argus II device and encourages further development of bioelectronics devices at the retina-machine interface.

Influence of optic media of the human eye on the imaging of Argus® II retinal prosthesis with intraoperative spectral-domain optical coherence tomography

This study aimed to evaluate the influence of the optic media of the human eye on intraoperative spectral-domain optical coherence tomography (iSD-OCT) of an Argus® II retinal prosthesis (AIIRP) during its implantation. One AIIRP was implanted in a human eye with end-stage retinitis pigmentosa and another one in a test eye. Intraoperative imaging was performed using the Rescan™ 700, a microscope-integrated iSD-OCT system. The feasibility of iSD-OCT imaging for AIIRP implantation was assessed during different surgical steps. Data were post-processed postoperatively using the ImageJ graphic software. The quality of imaging of the AIIRP during its implantation was good and almost the same in the human eye and in the training eye. The histograms showed that the optic media had no impact on the quality of iSD-OCT scans, as the difference between the pixel values was not statistically significant. Additionally, the quality of iSD-OCT imaging of the retina under the AIIRP array was not decreased by the array itself. The iSD-OCT-assisted surgical approach facilitates imaging of the AIIRP during its implantation. Uncompromised human optic media do not reduce the quality of AIIRP array imaging throughout all the surgical steps. The influence of the opaque cornea in long-lasting surgeries on the iSD-OCT scan quality during AIIRP implantation has to be investigated.

Clinical findings of end-stage retinitis pigmentosa with a homozygous PDE6A variant (p.R653X)

PurposeTo report clinical and genetic features of a Japanese patient with end-stage retinitis pigmentosa (RP) caused by a homozygous PDE6A variant. MethodsWe performed comprehensive ophthalmic examinations. Whole exome sequencing analysis was used to investigate the RP patient with parental consanguinity. The pedigree included 4 RP patients in the two generations, which suggests presumed pseudo-autosomal dominant inheritance. ResultsA PDE6A variant (p.R653X) was identified to be homozygous and disease-causing in the patient. Homozygosity mapping revealed the homozygous region including the variant and confirmation of autosomal recessive inheritance. The patient reported night blindness at 4 years of age and exhibited typical RP fundus appearance with macula involvement during the follow-up period from at the age of 52–69 years. At the age of 52, the patient exhibited a loss of visual acuity and had severely constricted visual fields, with a further gradual deterioration of her vision until she was 69 years old. At the age of 69, funduscopy showed severe chorioretinal degeneration in the area from the posterior pole to the peripheral retina. Conclusions and ImportanceThis is the first report that the PDE6A variant (p.R653X) has been identified as one of the causes of autosomal recessive RP in the Japanese population. Longitudinal natural history/end-stage findings demonstrated early-onset and a severe RP phenotype with macula involvement when the patient was in her 50s and severe chorioretinal degenerations in her late 60s.

Assessment of the Electronic Retinal Implant Alpha AMS in Restoring Vision to Blind Patients with End-Stage Retinitis Pigmentosa

PurposeTo report the initial efficacy results of the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for partial restoration of vision in end-stage retinitis pigmentosa (RP).DesignProspective, single-arm, investigator-sponsored interventional clinical trial. Within-participant control comprising residual vision with the retinal implant switched ON versus OFF in the implanted eye.ParticipantsThe Retina Implant Alpha AMS was implanted into the worse-seeing eye of 6 participants with end-stage RP and no useful perception of light vision. Eligibility criteria included previous normal vision for ≥12 years and no significant ocular or systemic comorbidity.MethodsVision assessments were scheduled at 1, 2, 3, 6, 9, and 12 months postimplantation. They comprised tabletop object recognition tasks, a self-assessment mobility questionnaire, and screen-based tests including Basic Light and Motion (BaLM), grating acuity, and greyscale contrast discrimination. A full-field stimulus test (FST) was also performed.Main Outcome MeasuresImprovement in activities of daily living, recognition tasks, and assessments of light perception with the implant ON compared with OFF.ResultsAll 6 participants underwent successful implantation. Light perception and temporal resolution with the implant ON were achieved in all participants. Light localization was achieved with the implant ON in all but 1 participant (P4) in whom the chip was not functioning optimally because of a combination of iatrogenic intraoperative implant damage and incorrect implantation. Implant ON correct grating detections (which were at chance level with implant OFF) were recorded in the other 5 participants, ranging from 0.1 to 3.33 cycles/degree on 1 occasion. The ability to locate high-contrast tabletop objects not seen with the implant OFF was partially restored with the implant ON in all but 1 participant (P4). There were 2 incidents of conjunctival erosion and 1 inferotemporal macula-on retinal detachment, which were successfully repaired, and 2 incidents of inadvertent damage to the implant during surgery (P3 and P4).ConclusionsThe Alpha AMS subretinal implant improved visual performance in 5 of 6 participants and has exhibited ongoing function for up to 24 months. Although implantation surgery remains challenging, new developments such as OCT microscope guidance added refinements to the surgical technique.

Adapted Surgical Procedure for Argus II Retinal Implantation: Feasibility, Safety, Efficiency, and Postoperative Anatomic Findings

To evaluate the feasibility, safety, and efficiency of an adapted surgical procedure used for postmarket Argus II implantations, so as to lower risks of postoperative hypotony or conjunctivoscleral erosion, and to describe the observed anatomic characteristics of the positioning of the implanted array. Single-arm prospective multicenter clinical trial. Eighteen consecutive patients with end-stage retinitis pigmentosa. To protect the site of insertion of the cable of the device, a scleral flap was systematically added to the standardized implantation procedure. It was associated with temporalis fascia autograft, so as to cover the episcleral-fixed electronics case. Intraoperative and postoperative data at day 1, weeks 1 and 2, and months 1, 3, and 6 were collected. Postoperative distance between electrode-array and retina was measured on spectral-domain optical coherence tomography images. Position of the array was evaluated on fundus images between months 1 and6. Feasibility of the modified surgical technique (time constraints, intraoperative complications), variations of intraocular pressure over time, postoperative ocular findings and adverse events, postoperative distance between the array and the retina, and rotation of the array between months 1 and 6 after implantation. The adapted surgical technique was performed easily without associated specific complications. No cases of chronic hypotony or conjunctivoscleral erosion were reported. One serious device/procedure-related adverse event was recorded (sterile posterior uveitis), which resolved after vitrectomy. Postoperative distance between array and retina was variable: full apposition was achieved in 4 patients (22.22%), partial apposition observed in 9 patients (50.00%), and absence of strict apposition noted in 5 patients (27.78%, 4 of whom had posterior staphyloma). A statistically significant slight rotation of the array was observed between months 1 and 6 (P < 0.0001), occurring downwardly in 68.75% of cases. The combined use of scleral flap and temporalis fascia autograft was easily achieved and effective in preventing hypotony and conjunctival erosion in our study. Postoperative distance between semirigid array and retinal surface was variable, and increased in the case of preoperative staphyloma. A slight rotation of the device occurred over time. Further studies based on larger samples are needed to confirm our findings and determine their functional consequences.

Optical coherence tomography imaging in the management of the Argus II retinal prosthesis system.

To report a real-life experience with the Argus II retinal prosthesis system in blind patients with end-stage retinitis pigmentosa (RP) or choroideremia (CHM), focusing on the pivotal role of optical coherence tomography (OCT) in both preoperative and postoperative management. This hospital-based case series included 3 blind patients who were uneventfully implanted with Argus II epiretinal device. These patients (2 with RP and 1 with CHM) were selected during the Argus™ II Retinal Prosthesis System PostMarket Surveillance Study Protocol. Complete screening procedures had involved 66 eyes of 33 patients afferent to the Center for Retinitis Pigmentosa of the Veneto Region. Preoperative OCT examination resulted in the exclusion of 8 eyes in 4 patients with bilateral posterior staphyloma diagnosing unexpected staphylomatous macular patterns in 2 patients with RP and no sign of pathologic myopia. Postoperative OCT study of Argus II proximity to retinal surface indicated a plausible correlation between electrode-retina distance and perceptual threshold in 2 of our 3 patients. In particular, during the first 6 months of follow-up, the patient with the closest contact between device and macula showed a continuous vision-related improvement in the performance of several real-life tasks. The present findings illustrate the modalities by which each different OCT examination is an essential tool to optimize safety and efficacy profiles during Argus II protocol. Optical coherence tomography will be crucial for future investigative approaches on patient selection criteria and next-generation implant design.

Hand-Camera Coordination Varies over Time in Users of the Argus(®) II Retinal Prosthesis System.

Introduction: Most visual neuroprostheses use an external camera for image acquisition. This adds two complications to phosphene perception: (1) stimulation locus will not change with eye movements; and (2) external cameras can be aimed in directions different from the user’s intended direction of gaze. Little is known about the stability of where users perceive light sources to be or whether they will adapt to changes in camera orientation.Methods: Three end-stage retinitis pigmentosa patients implanted with the Argus II participated in this study. This prosthesis stimulated the retina based on an 18° × 11° area selected within the camera’s 66° × 49° field of view. The center of the electrode array’s field of view mapped within the camera’s field of view is the camera alignment position (CAP). Proper camera alignments minimize errors in localizing visual percepts in space. Subjects touched single white squares in random locations on a darkened touchscreen 40 or more times. To study adaptation, subjects were given intentional CAP misalignments of 15–40° for 5–6 months. Subjects performed this test with auditory feedback during (bi-)weekly lab sessions. Misaligned CAPs were maintained for another 5–6 months without auditory feedback. Touch alignment was tracked to detect any adaptation. To estimate localization stability, data for when CAPs were set to minimize errors were tracked. The same localization test as above was used. Localization errors were tracked every 1–2 weeks for up to 40 months.Results: Two of three subjects used auditory feedback to improve accuracy with misaligned CAPs at an average rate of 0.02°/day (p < 0.05, bootstrap analysis of linear regression). The rates observed here were ~4000 times slower than those seen in normally-sighted subjects adapting to prism glasses. Removal of auditory feedback precipitated error increases for all subjects. Optimal CAPs varied significantly across test sessions (p < 10−4, bootstrap multivariate analysis of variance (MANOVA)), up to 21–29° within subjects over the observed period. Across subjects, optimal CAPs showed an average rate of change of 0.39°/day (SD 0.36°/day).Conclusions: Optimal CAPs varied dramatically over time for all subjects. Subjects displayed no adaptation to misaligned CAPs without feedback. Regular recalibration of CAPs may be required to maintain hand-camera coordination.

Assistive peripheral phosphene arrays deliver advantages in obstacle avoidance in simulated end-stage retinitis pigmentosa: a virtual-reality study

Objective. The prospective efficacy of peripheral retinal prostheses for guiding orientation and mobility in the absence of residual vision, as compared to an implant for the central visual field (VF), was evaluated using simulated prosthetic vision (SPV). Approach. Sighted volunteers wearing a head-mounted display performed an obstacle circumvention task under SPV. Mobility and orientation performance with three layouts of prosthetic vision were compared: peripheral prosthetic vision of higher visual acuity (VA) but limited VF, of wider VF but limited VA, as well as centrally restricted prosthetic vision. Learning curves using these layouts were compared fitting an exponential model to the mobility and orientation measures. Main results. Using peripheral layouts, performance was superior to the central layout. Walking speed with both higher-acuity and wider-angle layouts was 5.6% higher, and mobility errors reduced by 46.4% and 48.6%, respectively, as compared to the central layout. The wider-angle layout yielded the least number of collisions, 63% less than the higher-acuity and 73% less than the central layout. Using peripheral layouts, the number of visual-scanning related head movements was 54.3% (higher-acuity) and 60.7% (wider-angle) lower, as compared to the central layout, and the ratio of time standing versus time walking was 51.9% and 61.5% lower, respectively. Learning curves did not differ between layouts, except for time standing versus time walking, where both peripheral layouts achieved significantly lower asymptotic values compared to the central layout. Significance. Beyond complementing residual vision for an improved performance, peripheral prosthetic vision can effectively guide mobility in the later stages of retinitis pigmentosa (RP) without residual vision. Further, the temporal dynamics of learning peripheral and central prosthetic vision are similar. Therefore, development of a peripheral retinal prosthesis and early implantation to alleviate VF constriction in RP should be considered to extend the target group and the time of benefit for potential retinal prosthesis implantees.

Electrically evoked electroretinograms and pupil responses in Argus II retinal implant wearers.

We have recorded the electrically evoked electroretinogram (eERG) and flash ERG in Argus II retinal prosthesis wearers with end-stage retinitis pigmentosa to estimate response properties of the degenerated inner retina to local electrical stimulation. In addition, we have recorded pupil diameters during electrical stimulation. Raw corneal eERGs were recorded at multiple stimulus levels in three subjects. eERG signals were heavily contaminated with various artifacts, including switching artifacts generated by the implant electronics, stimulus, blink, and eye-movement artifacts. Pupil responses were recorded in one subject using a pupil tracker. eERGs were decontaminated by a variety of techniques, including wavelet transformation and response averaging. The dominant component was a negative wave peaking at approximately 200 ms. eERG amplitudes correlated significantly with stimulus level, but peak latencies did not correlate with stimulus level. Pupil constriction correlated significantly with stimulus level and pupil responses could be accurately used to estimate subjective threshold. eERG recordings hold the potential to be developed further for use as a diagnostic tool for retinal implants. A straightforward approach to increase eERG amplitudes would be the development of intraocular recording methods based on reverse telemetry. The robust pupil response to electrical stimulation in one subject indicates that pupillography can be exploited to assess implant functionality, but reliable pupil recordings could not be obtained in all subjects.

Restoring Visual Function to Blind Mice with a Photoswitch that Exploits Electrophysiological Remodeling of Retinal Ganglion Cells

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. Here, we report a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight. A single intraocular injection of DENAQ photosensitizes the blind retina for days, restoring electrophysiological and behavioral responses with no toxicity. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated photoreceptors. DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.