An RF-Ultrasound Relay for Adaptive Wireless Powering Across Tissue Interfaces.

Single modality wireless power transfer has limited depth for mm-sized implants across air / tissue or skull / tissue interfaces because they either suffer from high loss in tissue (RF, Optical) or high reflection at the medium interface (Ultrasound (US)). This paper proposes an RF-US relay chip at the media interface avoiding the reflection at the boundary, and enabling efficient wireless powering to mm-sized deep implants across multiple media. The relay chip rectifies the incoming RF power through an 85.5% efficient RF inductive link (across air) using a multi-output regulating rectifier (MORR) with 81% power conversion efficiency (PCE) at 186 mW load, and transmits ultrasound using adiabatic power amplifiers (PAs) to the implant in order to minimize cascaded power loss. To adapt the US focus to implant movement or placement, beamforming was implemented using 6 channels of US PAs with 2-bit phase control (0, 90, 180, and 270°) and 3 different amplitudes (6-29, 4.5, and 1.8 V) from the MORR. The adiabatic PA contributes a 30-40% increase in efficiency over class-D and beamforming increases the efficiency by 251% at 2.5 cm over fixed focusing. The proof-of-concept powering system for a retinal implant, from an external PA on a pair of glasses to a hydrophone with 1.2 cm (air) + 2.9 cm (agar eyeball phantom in mineral oil) separation distance, had a power delivered to the load (PDL) of 946 µW. The 2.3 × 2 mm2 relay chip was fabricated in a 180 nm high-voltage (HV) BCD process.

The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina.

BACKGROUND/AIMS: Retinal prostheses use electrical stimulation to restore functional vision to patients blinded by retinitis pigmentosa. A key detail is the spatial pattern of ganglion cells activated by stimulation. Therefore, we characterized the spatial extent of network-mediated electrical activation of retinal ganglion cells (RGCs) in the epiretinal monopolar electrode configuration. METHODS: Healthy mouse RGC activities were recorded with a micro-electrode array (MEA). The stimuli consisted of monophasic rectangular cathodic voltage pulses and cycling full-field light flashes. RESULTS: Voltage tuning curves exhibited significant hysteresis, reflecting adaptation to electrical stimulation on the time scale of seconds. Responses decreased from 0 to 300 µm, and were also dependent on the strength of stimulation. Applying the Rayleigh criterion to the half-width at half-maximum of the electrical point spread function suggests a visual acuity limit of no better than 20/946. Threshold voltage showed only a modest increase across these distances. CONCLUSION: The existence of significant hysteresis requires that future investigations of electrical retinal stimulation control for such long-memory adaptation. The spread of electrical activation beyond 200 µm suggests that neighbouring electrodes in epiretinal implants based on indirect stimulation of RGCs may be indiscriminable at interelectrode spacings as large as 400 µm.

Simplification of Visual Rendering in Simulated Prosthetic Vision Facilitates Navigation.

Visual neuroprostheses are still limited and simulated prosthetic vision (SPV) is used to evaluate potential and forthcoming functionality of these implants. SPV has been used to evaluate the minimum requirement on visual neuroprosthetic characteristics to restore various functions such as reading, objects and face recognition, object grasping, etc. Some of these studies focused on obstacle avoidance but only a few investigated orientation or navigation abilities with prosthetic vision. The resolution of current arrays of electrodes is not sufficient to allow navigation tasks without additional processing of the visual input. In this study, we simulated a low resolution array (15 × 18 electrodes, similar to a forthcoming generation of arrays) and evaluated the navigation abilities restored when visual information was processed with various computer vision algorithms to enhance the visual rendering. Three main visual rendering strategies were compared to a control rendering in a wayfinding task within an unknown environment. The control rendering corresponded to a resizing of the original image onto the electrode array size, according to the average brightness of the pixels. In the first rendering strategy, vision distance was limited to 3, 6, or 9 m, respectively. In the second strategy, the rendering was not based on the brightness of the image pixels, but on the distance between the user and the elements in the field of view. In the last rendering strategy, only the edges of the environments were displayed, similar to a wireframe rendering. All the tested renderings, except the 3 m limitation of the viewing distance, improved navigation performance and decreased cognitive load. Interestingly, the distance-based and wireframe renderings also improved the cognitive mapping of the unknown environment. These results show that low resolution implants are usable for wayfinding if specific computer vision algorithms are used to select and display appropriate information regarding the environment.

Amplitude Modulation-based Electrical Stimulation for Encoding Multipixel Spatiotemporal Visual Information in Retinal Neural Activities.

Retinal implants have been developed as a promising way to restore partial vision for the blind. The observation and analysis of neural activities can offer valuable insights for successful prosthetic electrical stimulation. Retinal ganglion cell (RGC) activities have been investigated to provide knowledge on the requirements for electrical stimulation, such as threshold current and the effect of stimulation waveforms. To develop a detailed 'stimulation strategy' for faithful delivery of spatiotemporal visual information to the brain, it is essential to examine both the temporal and spatial characteristics of RGC responses, whereas previous studies were mainly focused on one or the other. In this study, we investigate whether the spatiotemporal visual information can be decoded from the RGC network activity evoked by patterned electrical stimulation. Along with a thorough characterization of spatial spreading of stimulation current and temporal information encoding, we demonstrated that multipixel spatiotemporal visual information can be accurately decoded from the population activities of RGCs stimulated by amplitude-modulated pulse trains. We also found that the details of stimulation, such as pulse amplitude range and pulse rate, were crucial for accurate decoding. Overall, the results suggest that useful visual function may be restored by amplitude modulation-based retinal stimulation.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal-transretinal stimulation prosthesis in middle-sized animals.

PURPOSE: To investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle-sized animals. METHODS: The prosthesis consisted of two arrays with 50 to 74 electrodes. To test the feasibility of implanting the prosthesis and its efficacy, the prosthesis was implanted for 14 days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14 days after the implantation. Then the rabbits were euthanized, eyes were enucleated, and the posterior segment of the eye was examined histologically. In a second experiment, the arrays were implanted into two cats, and their ability to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina. RESULTS: All arrays were successfully implanted, and no major complications occurred during the surgery or during the 2-week postoperative period. Neither OCT nor ophthalmoscopy showed any major complications or instability of the arrays. Histological evaluations showed only mild cellular infiltration and overall good retinal preservation. Stimulation of the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging showed that the electrical pulses from the arrays altered the retinal images indicating an activation of retinal neurons. The thresholds were as low as 100 µA for a chiasm response and 300 µA for the retinal imaging. CONCLUSION: Implantation of a newly-developed dual-array STS prosthesis for 2 weeks in rabbits was feasible surgically, and safe. The results of retinal imaging showed that the dual-array system was able to activate retinal neurons. We conclude that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

Semiconductor nanorod-carbon nanotube biomimetic films for wire-free photostimulation of blind retinas.

We report the development of a semiconductor nanorod-carbon nanotube based platform for wire-free, light induced retina stimulation. A plasma polymerized acrylic acid midlayer was used to achieve covalent conjugation of semiconductor nanorods directly onto neuro-adhesive, three-dimensional carbon nanotube surfaces. Photocurrent, photovoltage, and fluorescence lifetime measurements validate efficient charge transfer between the nanorods and the carbon nanotube films. Successful stimulation of a light-insensitive chick retina suggests the potential use of this novel platform in future artificial retina applications.

Learning to see via epiretinal implant stimulationin silicowith model-based deep reinforcement learning.

OBJECTIVE: Diseases such as age-related macular degeneration and retinitis pigmentosa cause the degradation of the photoreceptor layer. One approach to restore vision is to electrically stimulate the surviving retinal ganglion cells with a microelectrode array such as epiretinal implants. Epiretinal implants are known to generate visible anisotropic shapes elongated along the axon fascicles of neighboring retinal ganglion cells. Recent work has demonstrated that to obtain isotropic pixel-like shapes, it is possible to map axon fascicles and avoid stimulating them by inactivating electrodes or lowering stimulation current levels. Avoiding axon fascicule stimulation aims to remove brushstroke-like shapes in favor of a more reduced set of pixel-like shapes. APPROACH: In this study, we propose the use of isotropic and anisotropic shapes to render intelligible images on the retina of a virtual patient in a reinforcement learning environment named rlretina. The environment formalizes the task as using brushstrokes in a stroke-based rendering task. MAIN RESULTS: We train a deep reinforcement learning agent that learns to assemble isotropic and anisotropic shapes to form an image. We investigate which error-based or perception-based metrics are adequate to reward the agent. The agent is trained in a model-based data generation fashion using the psychophysically validated axon map model to render images as perceived by different virtual patients. We show that the agent can generate more intelligible images compared to the naive method in different virtual patients. SIGNIFICANCE: This work shares a new way to address epiretinal stimulation that constitutes a first step towards improving visual acuity in artificially-restored vision using anisotropic phosphenes.

Chronic electrical stimulation with a peripheral suprachoroidal retinal implant: a preclinical safety study of neuroprotective stimulation.

Purpose: Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation. Methods: Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9-39 weeks. Charge balanced, biphasic, current pulses (100 µA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3-34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed. Results: All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. There was no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation. Conclusion: Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation.

Inferring light responses of primate retinal ganglion cells using intrinsic electrical signatures.

Objective. Retinal implants are designed to stimulate retinal ganglion cells (RGCs) in a way that restores sight to individuals blinded by photoreceptor degeneration. Reproducing high-acuity vision with these devices will likely require inferring the natural light responses of diverse RGC types in the implanted retina, without being able to measure them directly. Here we demonstrate an inference approach that exploits intrinsic electrophysiological features of primate RGCs.Approach.First, ON-parasol and OFF-parasol RGC types were identified using their intrinsic electrical features in large-scale multi-electrode recordings from macaque retina. Then, the electrically inferred somatic location, inferred cell type, and average linear-nonlinear-Poisson model parameters of each cell type were used to infer a light response model for each cell. The accuracy of the cell type classification and of reproducing measured light responses with the model were evaluated.Main results.A cell-type classifier trained on 246 large-scale multi-electrode recordings from 148 retinas achieved 95% mean accuracy on 29 test retinas. In five retinas tested, the inferred models achieved an average correlation with measured firing rates of 0.49 for white noise visual stimuli and 0.50 for natural scenes stimuli, compared to 0.65 and 0.58 respectively for models fitted to recorded light responses (an upper bound). Linear decoding of natural images from predicted RGC activity in one retina showed a mean correlation of 0.55 between decoded and true images, compared to an upper bound of 0.81 using models fitted to light response data.Significance.These results suggest that inference of RGC light response properties from intrinsic features of their electrical activity may be a useful approach for high-fidelity sight restoration. The overall strategy of first inferring cell type from electrical features and then exploiting cell type to help infer natural cell function may also prove broadly useful to neural interfaces.

Advanced Retina Implants.

PURPOSE: To discuss the role of advanced retinal implants in retinitis pigmentosa and age-related macular degeneration. DESIGN: Presented by Mark S. Humayun as the Charles Schepen's Lecture on the Retina Subspecialty Day of the American Academy of Ophthalmology in 2021. PARTICIPANTS: The details of subjects, participants, and controls are provided in the references pertaining to each study. METHODS: Review of published literature and clinical trials. MAIN OUTCOME MEASURES: Visual and anatomic outcomes from retinal implants. RESULTS: Retinal implants have been researched over the past few decades, and some have been advanced into the clinic. Two types of implants-bioelectronic and stem cell-based-have shown promising results in restoring some level of vision in patients with inherited retinal degeneration and geographic atrophy. These implants differ in their constructions, locations of implantation, and safety profiles. The results from some of these retinal implants have shown signs of efficacy, and 1 retinal implant, the Argus II, has been approved by the United States Food and Drug Administration. CONCLUSIONS: Careful consideration of the design of the implant and associated surgical techniques are necessary to obtain a stable and effective long-term interface between the implant and the retina.

Immersive Virtual Reality Simulations of Bionic Vision.

Bionic vision uses neuroprostheses to restore useful vision to people living with incurable blindness. However, a major outstanding challenge is predicting what people "see" when they use their devices. The limited field of view of current devices necessitates head movements to scan the scene, which is difficult to simulate on a computer screen. In addition, many computational models of bionic vision lack biological realism. To address these challenges, we present VR-SPV, an open-source virtual reality toolbox for simulated prosthetic vision that uses a psychophysically validated computational model to allow sighted participants to "see through the eyes" of a bionic eye user. To demonstrate its utility, we systematically evaluated how clinically reported visual distortions affect performance in a letter recognition and an immersive obstacle avoidance task. Our results highlight the importance of using an appropriate phosphene model when predicting visual outcomes for bionic vision.

Improving the spatial resolution of artificial vision using midget retinal ganglion cell populations modeled at the human fovea.

Objective. Retinal prostheses seek to create artificial vision by stimulating surviving retinal neurons of patients with profound vision impairment. Notwithstanding tremendous research efforts, the performance of all implants tested to date has remained rudimentary, incapable of overcoming the threshold for legal blindness. To maximize the perceptual efficacy of retinal prostheses, a device must be capable of controlling retinal neurons with greater spatiotemporal precision. Most studies of retinal stimulation were derived from either non-primate species or the peripheral primate retina. We investigated if artificial stimulation could leverage the high spatial resolution afforded by the neural substrates at the primate fovea and surrounding regions to achieve improved percept qualities.Approach.We began by developing a new computational model capable of generating anatomically accurate retinal ganglion cell (RGC) populations within the human central retina. Next, multiple RGC populations across the central retina were stimulatedin-silicoto compare clinical and recently proposed neurostimulation configurations based on their ability to improve perceptual efficacy and reduce activation thresholds.Main results.Our model uniquely upholds eccentricity-dependent characteristics such as RGC density and dendritic field diameter, whilst incorporating anatomically accurate features such as axon projection and three-dimensional (3D) RGC layering, features often forgone in favor of reduced computational complexity. Following epiretinal stimulation, the RGCs in our model produced response patterns in shapes akin to the complex and non-trivial percepts reported in clinical trials. Our results also demonstrated that even within the neuron-dense central retina, epiretinal stimulation using a multi-return hexapolar electrode arrangement could reliably achieve spatially focused RGC activation and could achieve single-cell excitation in 56% of all tested locations.Significance. This study establishes an anatomically accurate 3D model of RGC populations within the human central retina and demonstrates the potential for an epiretinal hexapolar configuration to achieve consistent, spatially confined retinal responses, even within the unique and neuron-dense foveal region. Our results and model promote the prospect and optimization of higher spatial resolution in future epiretinal implants.

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

PURPOSE: 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. METHODS: 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 2 years. 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 2 years was the primary effectiveness outcome. Standardized visual assessments were also performed. Device- or procedure-related adverse events were recorded. RESULTS: 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. CONCLUSION: 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.

Glow in the dark: Using a heat-sensitive camera for blind individuals with prosthetic vision.

To date, retinal implants are the only available treatment for blind individuals with retinal degenerations such as retinitis pigmentosa. Argus II is the only visual implant with FDA approval, with more than 300 users worldwide. Argus II stimulation is based on a grayscale image coming from a head-mounted visible-light camera. Normally, the 11°×19° field of view of the Argus II user is full of objects that may elicit similar phosphenes. The prosthesis cannot meaningfully convey so much visual information, and the percept is reduced to an ambiguous impression of light. This study is aimed at investigating the efficacy of simplifying the video input in real-time using a heat-sensitive camera. Data were acquired from four Argus II users in 5 stationary tasks with either hot objects or human targets as stimuli. All tasks were of m-alternative forced choice design where precisely one of the m≥2 response alternatives was defined to be "correct" by the experimenter. To compare performance with heat-sensitive and normal cameras across all tasks, regardless of m, we used an extension of signal detection theory to latent variables, estimating person ability and item difficulty in d' units. Results demonstrate that subject performance was significantly better across all tasks with the thermal camera compared to the regular Argus II camera. The future addition of thermal imaging to devices with very poor spatial resolution may have significant real-life benefits for orientation, personal safety, and social interactions, thereby improving quality of life.

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.

Highest reported visual acuity after electronic retinal implantation.

PURPOSE: To report the highest attained visual acuity with an electronic retinal implant for the treatment of advanced retinal degeneration following a novel intensive period of visual training. METHODS: A case study as part of the prospective, international, multi-centre, interventional clinical trial (ClinicalTrials.gov NCT02720640 and NCT01024803) of patients with the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for advanced retinal degeneration. A patient with subretinal device implanted into worse-seeing eye with no useful perception of light vision secondary to USH2A retinal degeneration underwent intensive period of visual training. RESULTS: The device remains functional with no safety concerns at 3 years postsurgical implantation, and following visual training, the patient achieved the highest visual acuity so far with an electronic retinal device, with real, digitally unenhanced, reading vision of 0.04 decimal (equivalent to 1.39 LogMAR and 20/500 or 6/150 Snellen). In addition, perception as well as partial identification of obstacles and evaluation of distances was possible in both daylight and night-time settings. CONCLUSIONS: Retinal implants are currently the only available therapy option for advanced retinal degeneration. Visual rehabilitation postimplantation has potential to maximize visual percepts. The novel concept of intensive visual training presented herein shows what is achievable with electronic retinal implants and has implications for other therapeutic options, such as optogenetics, that aim to stimulate remaining inner retinal cells in advanced retinal degeneration.

Implantation and Extraction of Penetrating Electrode Arrays in Minipig Retinas.

Purpose: This work was motivated by the goals of demonstrating methods to fabricate and implant large numbers of penetrating arrays into the retina and the feasibility of extraction. Methods: Arrays of inactive, three-dimensional (3D) SU-8 structures were microfabricated onto 13-µm polyimide substrates. Standard vitreoretinal surgical techniques were used with an ab externo approach for subretinal implantation of arrays in 12 mini-pigs. In the first three surgeries, different post-geometries were explored, while a preferred design (128-µm tall, 30-µm diameter, 200-µm spacing) was used for the remaining nine implantations. Two arrays were extracted. Funduscopy, optical coherence tomography (OCT) and immunohistochemistry of the retinae were performed. The unoperated eyes and tissue far from implantation served as controls. A thirteenth pig was implanted with a planar array. Results: Ten implant surgeries had no significant complication, and two arrays were successfully extracted. One retinal tear occurred after implantation due to too long posts in an early surgery. In "successful" cases, OCT showed close apposition of the arrays to the retina and integration of the posts, the tops of which were positioned at the junction of the inner plexiform and ganglion cells, without significant gliosis. Conclusions: These results provide a proof-of-concept that relatively large numbers of 3D posts can be implanted into, and extracted from, the retina of mini-pigs. Our surgical numbers were relatively small, especially for the extractions, and our conclusions must be viewed with that limitation. Our methods are applicable for human surgeries. Translational Relevance: This study provides results of implantation and extraction of relatively large numbers of 3D posts from the retina of minipig eyes. If similar technology were used in humans, a 3D array of this type should lower perceptual thresholds, provide safer long-term stimulation, and perhaps provide better perceptual outcomes.

Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement.

This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired dissipation of electric currents. Here, we applied the hexagonal arrangement to the microelectrode array for the localized activation of retinal cells and better visual acuity. To provide stimuli more efficiently to non-spiking neurons, a 3D structure was created through a customized pressing process, utilizing the elastic property of the materials used in the fabrication processes. The diameter and pitch of the Pt-coated electrodes were 150 µm and 350 µm, respectively, and the height of the protruded electrodes was around 20 µm. The array consisted of 98 hexagonally arranged electrodes, supported by a flexible and transparent polydimethylsiloxane (PDMS) base, with a thickness of 140 µm. Also, the array was coated with 2 µm-thick parylene-C, except the active electrode sites, for more focused stimulation. Finally, the electrochemical properties of the fabricated microelectrodes were characterized, resulting in the mean impedance of 384.87 kΩ at 1 kHz and the charge storage capacity (CSC) of 2.83 mC·cm-2. The fabricated microelectrodes are to be combined with an integrated circuit (IC) for additional in vitro and in vivo experiments.

Model-Based Recommendations for Optimal Surgical Placement of Epiretinal Implants.

A major limitation of current electronic retinal implants is that in addition to stimulating the intended retinal ganglion cells, they also stimulate passing axon fibers, producing perceptual 'streaks' that limit the quality of the generated visual experience. Recent evidence suggests a dependence between the shape of the elicited visual percept and the retinal location of the stimulating electrode. However, this knowledge has yet to be incorporated into the surgical placement of retinal implants. Here we systematically explored the space of possible implant configurations to make recommendations for optimal intraocular positioning of the electrode array. Using a psychophysically validated computational model, we demonstrate that better implant placement has the potential to reduce the spatial extent of axonal activation in existing implant users by up to ~55%. Importantly, the best implant location, as inferred from a population of simulated virtual patients, is both surgically feasible and is relatively stable across individuals. This study is a first step towards the use of computer simulations in patient-specific planning of retinal implant surgery.