Suprachoroidal-transretinal Stimulation Research Articles

A flexible retinal device with CMOS smart electrodes fabricated on parylene C thin-film and bioceramic substrate

We developed implementation technologies for artificial vision devices compatible with suprachoroidal transretinal stimulation. We aimed to develop a device that can be safely implanted in the sclera of the eye for a long period. Using parylene C and bioceramics as biocompatible base materials, we realized a device with high in vivo safety by making the device structure flexible and reducing the wires of control signals. We successfully created a prototype device that combines a flexible wire structure based on a parylene C thin film with a wire-saving CMOS smart electrode structure based on CMOS integrated circuits. We conducted in vitro and in vivo experiments to confirm their performances. The immersion test confirmed that the device could work normally for four days. Furthermore, in the in vivo experiments using rats, we successfully measured evoked potentials in the brain induced by the stimulation current using the device.

The influence of stimulating electrode conditions on electrically evoked potentials and resistance in suprachoroidal transretinal stimulation.

To determine the influence of stimulating electrode conditions on the amplitudes and latencies of electrically evoked potentials (EEPs) and the resistance at the electrode-tissue interface in the suprachoroidal transretinal stimulation (STS) system. Experimental study. A scleral pocket (3 × 5 mm) was created just over the visual streak in anesthetized pigmented rabbits (weight, 1.9-2.7 kg), and STS stimulating electrodes were implanted into the pocket. Measurements were obtained with stimulating electrodes of different lengths (0.3 or 0.5 mm) and different surface characteristics (smooth or porous). EEPs elicited with a fixed current under each set of electrode conditions were recorded; three measurement sessions were performed for each rabbit. The resistance at each electrode-tissue interface was measured. The latencies and amplitudes of the EEPs did not differ significantly with changes in the height and surface characteristics of the stimulating electrodes, but the resistances at the electrode-tissue interface differed significantly (P = 0.001; the resistance values for the 0.3-mm-long electrode with a porous surface was 5.24 ± 0.67 kΩ and with the 0.3- and 0.5-mm-long electrodes with smooth surfaces were 7.63 ± 0.12 kΩ and6.77 ± 0.20 kΩ). Being shorter did not affect the EEPs of the stimulating electrodes with a porous surface while decreasing the resistance at the electrode-tissue interface.

Spatial Resolution of Suprachoroidal-Transretinal Stimulation Estimated by Recording Single-Unit Activity From the Cat Lateral Geniculate Nucleus.

Retinal prostheses are devices used to restore visual sensation in patients suffering from photoreceptor degeneration, such as retinitis pigmentosa. Suprachoroidal–transretinal stimulation (STS) is a prosthesis with retinal electrodes located in the sclera. STS has the advantage that it is safer than epiretinal or subretinal prostheses, as the implant is not directly attached to the retinal tissue. We have previously reported feasibility of STS with animal experiments and clinical trials. However, functional evaluation with neurophysiological experiments is still largely missing. To estimate the spatial resolution of STS, single-unit activities in response to STS were recorded from relay cells in the dorsal lateral geniculate nucleus of cats, and the response probability of the units was analyzed in relation to the distance between the stimulus location and the receptive field of each recorded unit. A platinum electrode was attached to the sclera after lamellar resection, and the return electrode was placed in the vitreous. The stimulating current, which ranged from 50 to 500 μA, was applied between these electrodes, and the probability of spike responses occurring just after retinal stimulation was measured. The distance at half-maximum of response was determined from the collected response probabilities as a function of stimulus intensity for all units characterized by their distances from the receptive field center to the stimulation point. As the stimulation became weaker, this distance decreased to 1.8° at 150 and 100 μA. As another estimation, the radius of 25% response probability was 1.4° at 100 μA. The diameter of the stimulated cat retinal area, 3.6° or 2.8°, corresponds to human visual acuity of 0.005 or 0.007, or finger counting. Considering the lower hazard to the retina of STS and its potentially large visual field coverage, STS is an attractive method for retinal prosthetic device development.

Honeycomb-type retinal device using chemically derived iridium oxide biointerfaces

Long-term operational stability and high-efficiency neuron stimulation are key to the development of retinal prostheses. In this research, a retinal device with a chemically inert and flexible substrate is introduced, which satisfies these requirements. We have developed a honeycomb-type retinal device that has a high-performance electrode for suprachoroidal transretinal stimulation. The device structure, in which conjunctional bioceramic substrates are embedded with large numbers of stimulating electrodes, provides high-resolution electrical stimulation. The custom CMOS microchip precisely controls the stimulation delivery of the electrodes to initiate artificial vision, offering a partial remedy for retinal ophthalmic diseases. The CMOS chip design was optimized to drastically reduce the number of input wirings. A high-performance stimulating electrode based on iridium oxide was fabricated using a unique solution process called chemical bath deposition (CBD). The honeycomb-type retinal device, equipped with CBD-derived iridium oxide electrodes, was used to evaluate the electrodes’ and device’s performances in vitro.

Testing of Newly Developed Wide-Field Dual-Array Suprachoroidal-Transretinal Stimulation Prosthesis in Dogs.

PurposeThis study was conducted to investigate the feasibility of a newly developed wide-field dual-array suprachoroidal–transretinal stimulation (STS) prosthesis in dogs and to examine its biocompatibility and stability over a 4-month period.MethodsThree types of STS dual arrays were designed and tested. The STS dual-array was implanted into a scleral pocket of the left eye of six healthy beagle dogs. Ophthalmic examinations, fundus photography, fluorescein angiography (FA), electroretinography (ERG), and functional testing of this system were conducted postoperatively. The dogs were euthanatized at the end of the experiment, and their eyes were enucleated and histologically examined.ResultsAll prostheses were successfully implanted without complications, and no serious adverse event occurred during the postoperative period. Fundus photographs and FA showed no serious damage in the retina surrounding the arrays. The ERGs recorded from the implanted eyes showed no significant differences from those from control eyes. Histological evaluations demonstrated good preservation of the retina over the array. However, system failure occurred in 50% of the dogs owing to dog-specific habits.ConclusionsImplantation of this prosthesis system in dogs is feasible and can be performed without significant damage to the eye. The biocompatibility and stability of the array were good during the observation period, but the low durability of the system against dogs (not humans) is an issue to be resolved in the future.Translational RelevanceThis study suggests that this wide-field dual-array prosthesis might widen the visual field and might be useful for patients with retinitis pigmentosa.

The influence of visual field position induced by a retinal prosthesis simulator on mobility.

Our aim is to develop a new generation of suprachoroidal-transretinal stimulation (STS) retinal prosthesis using a dual-stimulating electrode array to enlarge the visual field. In the present study, we aimed to examine how position and size of the visual field-created by a retinal prosthesis simulator-influenced mobility. Twelve healthy subjects wore retinal prosthesis simulators. Images captured by a web camera attached to a head-mounted display (HMD) were processed by a computer and displayed on the HMD. Three types of artificial visual fields-designed to imitate phosphenes-obtained by a single (5 × 5 electrodes; visual angle, 15°) or dual (5 × 5 electrodes ×2; visual angle, 30°) electrode array were created. Visual field (VF)1 is an inferior visual field, which corresponds to a dual-electrode array implanted in the superior hemisphere. VF2 is a superior visual field, which corresponds to a single-electrode array implanted in the inferior hemisphere. VF3 is a superior visual field, which corresponds to a dual-electrode array implanted in the inferior hemisphere. In each type of artificial visual field, a natural circular visual field (visual angle, 5°) which imitated the vision of patients with advanced retinitis pigmentosa existed at the center. Subjects were instructed to walk along a black carpet (6m long × 2.2m wide) without stepping on attached white circular obstacles. Each obstacle was 20cm in diameter, and obstacles were installed at 40-cm intervals. We measured the number of footsteps on the obstacles, the time taken to complete the obstacle course, and the extent of head movement to scan the area (head-scanning). We then compared the results recorded from these 3 types of artificial visual field. The number of footsteps on obstacles was lowest in VF3 (One-way ANOVA; P = 0.028, Fisher's LSD; VF 1 versus 3 P = 0.039, 2 versus 3 P = 0.012). No significant difference was observed for the time to complete the obstacle course or the extent of head movement between the 3 visual fields. The superior and wide visual field (VF3) obtained by the retinal prosthesis simulator resulted in better mobility performance than the other visual fields.

Electrophysiological evaluation of a chronically implanted electrode for suprachoroidal transretinal stimulation in rabbit eyes.

In this study, we aimed to determine the electrophysiological efficacy, safety, and electrical stability of a chronically implanted electrode for suprachoroidal transretinal stimulation (STS) in rabbit eyes. A platinum microelectrode was implanted into the scleral pocket of rabbit eyes (n = 5) and followed-up for 6months. To evaluate the electrophysiological efficacy, electrically evoked potentials (EEPs) were measured every month after implantation. To evaluate safety, fundus examinations, fluorescein angiograms, electroretinograms (ERGs), and visually evoked potentials (VEPs) were measured before and every month after the implantation. At the end of the experiment, histological examination of retinal tissue beneath the site of the electrode was performed. To evaluate electrical stability, the resistance of the circuit was measured every month after implantation. EEPs could be elicited from the STS electrodes at all testing times. The mean threshold current to evoke EEPs was 186.4 ± 47.0µA at 6months after implantation. There was no significant change in the threshold over the follow-up period. The resistance of the circuit was significantly increased at 1months after implantation, with no further increase at 6months. There was no statistically significant change in the relative amplitudes and implicit times of a- and b-waves of ERGs and VEPs. No intraocular infection, inflammation, or vitreoretinal proliferation was observed in any eye. Histological examination revealed no retinal damage beneath the electrode. We conclude that chronically implanted electrodes for STS appear to be effective, safe, and electrically stable.

Correction to: Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

The original publication of this paper contain an error because of an incorrect captured corresponding author.

In Vitro and In Vivo Long-term Electrochemical Properties of Electrodes with Femtosecond-laser-induced Porosity for Visual Prostheses Based on Suprachoroidal Transretinal Stimulation

In Vitro and In Vivo Long-term Electrochemical Properties of Electrodes with Femtosecond-laser-induced Porosity for Visual Prostheses Based on Suprachoroidal Transretinal Stimulation

Safety and Efficacy of Semichronic Suprachoroidal Transretinal Stimulation with Femtosecond Laser-induced Porosity and Smooth-surface Electrodes

Safety and Efficacy of Semichronic Suprachoroidal Transretinal Stimulation with Femtosecond Laser-induced Porosity and Smooth-surface Electrodes

The relationship between retinal damage and current intensity in a pre-clinical suprachoroidal-transretinal stimulation model using a laser-formed microporous electrode

Objective. Suprachoroidal-transretinal stimulation (STS) is a stimulation method for retinal prostheses. For STS-type retinal prostheses, we developed a new type of stimulating electrode called a femtosecond laser-induced porous electrode (FLiP electrode). To verify the safety of the FLiP electrode for STS, we investigated the characteristics of STS-induced retinal injury. Approach. Sixteen eyes of pigmented rabbits were studied in this in vivo study. For each examined eye, we implanted a single-channel FLiP electrode (diameter, 0.5 mm; height, 0.3 mm; geometric surface area, 0.43 mm2) in a scleral pocket created at the posterior pole of the eye. A return electrode (diameter, 0.5 mm; length, 3 mm) was inserted into the vitreous cavity. The eyes were divided into five groups, and each group was stimulated with a different current intensity. The stimulus intensities and the number of eyes in each group were as follows: 1.0 mA (n = 2), 1.5 mA (n = 3), 2.0 mA (n = 3), 2.5 mA (n = 4), and 3.0 mA (n = 2). Continuous biphasic pulses (0.5 ms/phase) were applied under general anesthesia at a frequency of 20 Hz for 48 h. Fundus photography, fluorescein angiography (FA), and optical coherence tomography were performed before and after applying the electrical stimulation to evaluate the retinal injury. Main results. The 1.0 mA and 1.5 mA groups showed little or no retinal damage. Fluorescent dye leakage in FA and punctate pigmentation in the fundus were observed around the stimulation site with stimulation of 2.0 mA (1/3), 2.5 mA (1/4), and 3.0 mA (2/2). Significance. Our findings indicate that the threshold current for inducing retinal damage is greater than that for eliciting electrical phosphenes (<1 mA) with STS observed in human trials. Therefore, STS by the FLiP electrode is a safe and feasible stimulation method for retinal prostheses as long as it is used with these pulse parameters.

Initial Evaluation of the Safety and Durability of Retinal Prostheses Based on Suprachoroidal–transretinal Stimulation using Bullet-shaped Platinum Electrodes

Initial Evaluation of the Safety and Durability of Retinal Prostheses Based on Suprachoroidal–transretinal Stimulation using Bullet-shaped Platinum Electrodes

Effectiveness of triangular and saw-tooth pulses in a retinal prosthesis with suprachoroidal-transretinal stimulation (STS)

Effectiveness of triangular and saw-tooth pulses in a retinal prosthesis with suprachoroidal-transretinal stimulation (STS)

One-Year Outcome of 49-Channel Suprachoroidal-Transretinal Stimulation Prosthesis in Patients With Advanced Retinitis Pigmentosa.

To determine the feasibility of a 49-channel suprachoroidal-transretinal stimulation (STS) retinal prosthesis that was implanted for 1 year. Three patients with advanced retinitis pigmentosa (RP) and with less than or equal to hand motion (HM) vision were studied. A 49-channel STS system was implanted in a scleral pocket, and the stability of the prosthesis, adverse events, and its efficacy were investigated. The electrode array was implanted in a scleral pocket located under the parafoveal area through a scleral incision at 14 mm in patient (Pt) 1, 16 mm in Pt 2, and 18 mm in Pt 3 from the sclerocorneal limbus. No complications occurred during surgery in all cases. During the follow-up period, iridocyclitis developed in Pt 2 and Pt 3, which was successfully treated with topical medications. The implanted devices continued functioning and elicited phosphenes in all cases. The results of localization tests (P < 0.05) and table tests (P < 0.05) were significantly better with the prosthesis turned on than turned off in Pt 3. The deviations of the walking tests were smaller with the prosthesis turned on than off in Pt 2 and Pt 3 at multiple times after the implantation. The 49-channel STS retinal prosthesis was able to elicit phosphenes in all patients with advanced RP for the entire 1-year experimental period without major complications. Better results on visual tasks were found in the eyes in which the electrode array was implanted closer to the fovea centralis.

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

To investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle-sized animals. 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 14days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14days 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. 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 100μA for a chiasm response and 300μA for the retinal imaging. Implantation of a newly-developed dual-array STS prosthesis for 2weeks 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.

Spatial characteristics of evoked potentials elicited by a MEMS microelectrode array for suprachoroidal-transretinal stimulation in a rabbit

Suprachoroidal-transretinal stimulation (STS) can potentially restore vision. This study investigated the spatial characteristics of cortical electrical evoked potentials (EEPs) elicited by STS. A 4 × 4 thin-film platinum microelectrode stimulating array (200 μm electrode diameter and 400 μm center-to-center distance) was fabricated by a micro-electro-mechanical systems (MEMS) techniques and implanted into the suprachoroidal space of albino rabbits. The current threshold to elicit reliable EEPs by a single electrode was 41.6 ± 12.6 μA, corresponding to a 66.2 ± 20.1 μC · cm(-2) charge density per phase, which was lower than the reported safety limits. Spatially differentiated cortical responses could be evoked by STS through different rows or columns of electrical stimulation; furthermore, shifts in the location of the maximum cortical activities were consistent with cortical visuotopic maps; increasing the number of simultaneously stimulating electrodes increased the response amplitudes of EEPs and expanded the spatial spread as well. In addition, long-term implantation and electrical stimulation of the MEMS electrode array in suprachoroidal space are necessary to evaluate systematically the safety and biocompatibility of this approach. This study indicates that the STS approach by a MEMS-based platinum electrode array is a feasible alternative for visual restoration, and relatively high spatial discrimination may be achieved.

A Review in Innovation in Ocular Prostheses and Visual Implants: New Biomaterials and Neuro-Implants is the Challenge for the Visual Care

Objective: To update in new biopolymers and innovations for ocular prostheses and visual implants for visual care. Methodology: The systematic review about biomaterials for ocular prostheses and visual implants was consulted on the following Journals Databases: Investigative Ophthalmology and Visual Science, Nature Eye, Ophthalmology, Br. J. Ophthalmology, Ophthalmic plastic in reconstructive surgery for a total review of 67 articles and 8 e-books were consulted with the following keywords: ocular prostheses and biopolymers, visual and ocular implants, artificial eye. Inclusion criteria: “ocular prostheses”, retinal prostheses systems (RPS) and “visual implants”. Search resources: MEDLINE, PubMed, SciELO, Biblioteca virtual en salud (BVS). Results: The traditional concept of ocular prostheses (ocular, orbital, epithesis, maxillofacial) and visual implants (retinal, optic nerve, cortical, subretinal, epiretinal and cortical implants, artificial silicon retinas and suprachoroidal transretinal stimulation (STS)) among others are changing on now days due to the new advances in technologies and also to the developing of new biomaterials, new microelectrodes and neural devices of several types around the world. Now, real “artificial eyes” are not only the craniofacial, maxillofacial, ocular and orbital prostheses, that replaces an absent eye after an enucleation. But also, new materials such as cryolite glass, gel from cellulose produced by Zoogloea sp., glass, silicone and porous polyethylene, graphene, dental biopolymers among others are being implemented as a materials for heart, eye and other organs implants due to their characteristics to improve good biological compatibility, to be more resistant and to contribute to reduce allergies and improve durability. These implants are used for replacement of the orbital content of the anophthalmic cavities. In addition to this, the existing wearing protocols must be updated, as the three phases model of prosthetic eye wear: establishment of homeostasis deposits builds up, recovery from effects of handling the prosthesis, and the posterior homeostasis´s stabilization for mucus and deposits, must be reduced in a near future by means of surface nanofilm or the inclusion of new biopolymers for fabrication to prevent the adherences and anticipate to immune responses after the implantation of these foreign bodies. Conclusions: The new emerging sciences that are applied to visual sciences will be helpful for the ocular prostheses and visual implant´s users, involving a better performance for fabrication and implantation of these devices. New more biocompatible, resistant materials and the inclusion of microelectrodes for the fabrication of visual implants and also the implementation of the artificial intelligence for the eye have been developed by many researchers around world, because of emerging technologies which have been already patented and that are providing alternatives to patients who have lost their vision, and require visual rehabilitation and in a near future to recover their vision. Additional to the creation of new devices, there are some important processes that take a place such as: Complex biomathematical modeling, new surgical techniques, placement, trial In vivo animal experiments (multielectrode arrays) and In vitro animal experiments (patch clamping, extracellular recording, two-photon imaging) and in the same way, after patient´s process follow up: simulated human psychophysics and some advances have been developed in 3D printers.

Chronic Implantation of Newly Developed Suprachoroidal-Transretinal Stimulation Prosthesis in Dogs

To investigate the feasibility of implanting a newly developed suprachoroidal-transretinal stimulation (STS) prosthesis in dogs and to determine its biocompatibility and stability over a 3-month period. The STS prosthesis system consisted of an array of 49 electrodes (nine were active), an intravitreal return electrode, and an extraocular microstimulator. The 49-electrode array was implanted into a scleral pocket of each of three healthy beagle dogs. Color fundus photography, fluorescein angiography, electroretinography, and functional testing of the STS system were performed postoperatively. The dogs were euthanatized 3 months after the implantation, and the retinas were evaluated histologically. All the prostheses were successfully implanted without complications, and no serious complications occurred during the 3-month postoperative period. The fixation of the implant was stable throughout the experimental period. Fluorescein angiography showed that the entire retina, including the area on the electrode array, remained well perfused without intraocular inflammation. Electroretinograms recorded from the eyes with the prosthesis did not differ significantly from those recorded from control eyes. Functional testing of the STS system showed that this system performed well for the 3-month experimental period. Histologic evaluations showed good preservation of the retina over the electrode array. Implantation of a newly developed STS retinal prosthesis into a scleral pocket of beagle dogs is surgically feasible and can be performed without significant damage to the retina or the animal. The biocompatibility and stability of the system were good for the 3-month observation period.

Spatial profile of suprachoroidal-transretinal stimulation (STS) for retinal prosthesis evaluated by optical imaging

Spatial profile of suprachoroidal-transretinal stimulation (STS) for retinal prosthesis evaluated by optical imaging

Testing of Semichronically Implanted Retinal Prosthesis by Suprachoroidal-Transretinal Stimulation in Patients with Retinitis Pigmentosa

To examine the safety and effectiveness of a retinal prosthesis that is implanted semichronically in two patients with advanced retinitis pigmentosa (RP). Two eyes of two patients with advanced RP had a retinal prosthesis implanted in a sclera pocket of one eye. The visual acuity of both eyes before the implantation was bare light perception. Phosphenes were elicited by suprachoroidal-transretinal stimulation (STS). The internal devices of the STS were implanted under the skin on the temporal side of the head, and the 49 electrode-array was implanted in the scleral pocket of one eye. Biphasic electrical pulses (duration, 0.5 ms; frequency, 20 Hz) were delivered through nine active electrodes. The threshold current was determined by currents ≤1 mA. Behavioral tasks were used to determine the functioning of the prosthesis. The surgery was completed without a retinal detachment and retinal/vitreous hemorrhage. The implanted STS system remained functional for the 4-week test period. Phosphenes were elicited by currents delivered through six electrodes in Patient 1 and through four electrodes in Patient 2. The success of discriminating two bars was better than the chance level in both patients. In Patient 2, the success of a grasping task was better than the chance level, and the success rate of identifying a white bar on a touch panel increased with repeated testing. Semichronic implantation of a microelectrode-STS system showed that it was safe and remained functional for at least 4 weeks in two patients with advanced RP. (www.umin.ac.jp/ctr number, R000002690.).