Suprachoroidal Electrode Array Research Articles

Safety Studies for a 44-Channel Suprachoroidal Retinal Prosthesis: A Chronic Passive Study.

Following successful clinical outcomes of the prototype suprachoroidal retinal prosthesis, Bionic Vision Australia has developed an upgraded 44-channel suprachoroidal retinal prosthesis to provide a wider field of view and more phosphenes. The aim was to evaluate the preclinical passive safety characteristics of the upgraded electrode array. Ten normal-sighted felines were unilaterally implanted with an array containing platinum electrodes (44 stimulating and 2 returns) on a silicone carrier near the area centralis. Clinical assessments (color fundus photos, optical coherence tomography, full-field electroretinography, intraocular pressure) were performed under anesthesia prior to surgery, and longitudinally for up to 20 weeks. Histopathology grading of fibrosis and inflammation was performed in two animals at 13 to 15 weeks. Eight animals showed safe electrode array insertion (good retinal health) and good conformability of the array to the retinal curvature. Eight animals demonstrated good mechanical stability of the array with only minor (<2 disc diameters) lateral movement. Four cases of surgical or stability complications occurred due to (1) bulged choroid during surgery, (2) hemorrhage from a systemic bleeding disorder, (3) infection, and (4) partial erosion of thin posterior sclera. There was no change in retinal structure or function (other than that seen at surgery) at endpoint. Histopathology showed a mild foreign body response. Electrodes were intact on electrode array removal. The 44-channel suprachoroidal electrode array has an acceptable passive safety profile to proceed to clinical trial. The safety profile is expected to improve in human studies, as the complications seen are specific to limitations (anatomic differences) with the feline model.

Implantation of multiple suprachoroidal electrode arrays in rabbits

PurposeEpiretinal and subretinal prosthesis have been shown to be a valid way to provide some vision to patients with advanced outer retinal degeneration and profound vision loss. However, the field of vision for these patients is markedly limited by the area occupied by the electrode array. In this study, we aimed to evaluate the feasibility of implantation of multiple suprachoroidal electrode arrays in a single eye in order to increase the field of vision in patients implanted with retinal prosthesis. MethodsThe right eye of seventeen Dutch rabbits (age range, 5–6 months) was used for the study. Multiple inactive custom-made electrode arrays were inserted into the suprachoroidal space (SCS) and animals were followed up for up to 6 months using fundus photography, optical coherence tomography (OCT), and fluorescein angiography (FA). ResultsIt was possible to surgically implant up to 8 electrode arrays in a single eye. None of the rabbits showed any major complications. The electrodes were well tolerated and remained in position in all rabbits. There was no evidence of retinal damage on follow-up exams and FA throughout the study. ConclusionMultiple suprachoroidal electrode array implantation is feasible and may provide a novel approach to increase the field of vision in subjects implanted with retinal prosthesis.

Identification of Characters and Localization of Images Using Direct Multiple-Electrode Stimulation With a Suprachoroidal Retinal Prosthesis.

Retinal prostheses provide vision to blind patients by eliciting phosphenes through electrical stimulation. This study explored whether character identification and image localization could be achieved through direct multiple-electrode stimulation with a suprachoroidal retinal prosthesis. Two of three retinitis pigmentosa patients implanted with a suprachoroidal electrode array were tested on three psychophysical tasks. Electrode patterns were stimulated to elicit perception of simple characters, following which percept localization was tested using either static or dynamic images. Eye tracking was used to assess the association between accuracy and eye movements. In the character identification task, accuracy ranged from 2.7% to 93.3%, depending on the patient and character. In the static image localization task, accuracy decreased from near perfect to <20% with decreasing contrast (patient 1). Patient 2 scored up to 70% at 100% contrast. In the dynamic image localization task, patient 1 recognized the trajectory of the image up to speeds of 64 deg/s, whereas patient 2 scored just above chance. The degree of eye movement in both patients was related to accuracy and, to some extent, stimulus direction. The ability to identify characters and localize percepts demonstrates the capacity of the suprachoroidal device to provide meaningful information to blind patients. The variation in scores across all tasks highlights the importance of using spatial cues from phosphenes, which becomes more difficult at low contrast. The use of spatial information from multiple electrodes and eye-movement compensation is expected to improve performance outcomes during real-world prosthesis use in a camera-based system. (ClinicalTrials.gov number, NCT01603576.).

Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration.

Retinal prostheses have emerged as a promising technology to restore vision in patients with severe photoreceptor degeneration. To better understand how neural degeneration affects the efficacy of electronic implants, we investigated the function of a suprachoroidal retinal implant in a feline model. Unilateral retinal degeneration was induced in four adult felines by intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post injection, animals received suprachoroidal electrode array implants in each eye, and responses to electrical stimulation were obtained using multiunit recordings from the visual cortex. Histologic measurements of neural and glial changes in the retina at the implant site were correlated with cortical thresholds from individual stimulating electrodes. Adenosine triphosphate-injected eyes displayed changes consistent with mid-to-late stage retinal degeneration and remodeling. A significant increase in electrical charge was required to induce a cortical response from stimulation of the degenerated retina compared to that in the fellow control eye. Spatial and temporal characteristics of the electrically evoked cortical responses were no different between eyes. Individual electrode thresholds varied in both the control and the ATP-injected eyes and were correlated with ganglion cell density. In ATP-injected eyes, cortical threshold was also independently correlated with an increase in the extent of retinal gliosis. These data suggest that even when ganglion cell density remains unaffected, glial changes in the retina following degeneration can influence the efficacy of suprachoroidal electrical stimulation. A better understanding of how glial change impacts retinal prosthesis function may help to further the optimization of retinal implants.

The Appearance of Phosphenes Elicited Using a Suprachoroidal Retinal Prosthesis.

Phosphenes are the fundamental building blocks for presenting meaningful visual information to the visually impaired using a bionic eye device. The aim of this study was to characterize the size, shape, and location of phosphenes elicited using a suprachoroidal retinal prosthesis. Three patients with profound vision loss due to retinitis pigmentosa were implanted with a suprachoroidal electrode array, which was used to deliver charge-balanced biphasic constant-current pulses at various rates, amplitudes, and durations to produce phosphenes. Tasks assessing phosphene appearance, location, overlap, and the patients' ability to recognize phosphenes were performed using a custom psychophysics setup. Phosphenes were reliably elicited in all three patients, with marked differences in the reported appearances between patients and between electrodes. Phosphene shapes ranged from simple blobs to complex forms with multiple components in both space and time. Phosphene locations within the visual field generally corresponded to the retinotopic position of the stimulating electrodes. Overlap between phosphenes elicited from adjacent electrodes was observed with one patient, which reduced with increasing electrode separation. In a randomized recognition task, two patients correctly identified the electrode being stimulated for 57.2% and 23% of trials, respectively. Phosphenes of varying complexity were successfully elicited in all three patients, indicating that the suprachoroidal space is an efficacious site for electrically stimulating the retina. The recognition scores obtained with two patients suggest that a suprachoroidal implant can elicit phosphenes containing unique information. This information may be useful when combining phosphenes into more complex and meaningful images that provide functional vision.

Spatial Restriction of Neural Activation Using Focused Multipolar Stimulation With a Retinal Prosthesis.

The resolution provided by present state-of-the-art retinal prostheses is severely limiting for recipients, partly due to the broad spread of activation in the retina in response to monopolar (MP) electrical stimulation. Focused multipolar (FMP) stimulation has been shown to restrict neural activation in the cochlea compared to MP stimulation. We extended the FMP stimulation technique to a two-dimensional electrode array and compared its efficacy to MP and hexapolar (HP) stimulation in the retina. Normally-sighted cats (n = 6) were implanted with a suprachoroidal electrode array containing 42 electrodes. Multichannel multiunit spiking activity was recorded from the visual cortex in response to MP, HP, and FMP retinal stimulation. When inferring retinal spread using voltage recordings off the stimulating array, FMP stimulation showed significantly reduced voltages in regions surrounding the primary stimulating electrode. When measuring the retinal and cortical selectivity of neural responses, FMP and HP stimulation showed significantly higher selectivity compared to MP stimulation (separate 2-way ANOVAs, P < 0.05). However, the lowest cortical thresholds for each stimulating electrode were higher for FMP and HP compared to MP stimulation (1-way ANOVA, P < 0.001). No significant differences were observed between FMP and HP stimulation in any measures. Focused multipolar and HP stimulation using a two-dimensional array are promising techniques to reduce the spread of activation for a retinal prosthesis. Clinical application would be expected to result in smaller phosphenes; thus, reducing phosphene overlap between electrodes and increasing the resolution at the expense of higher thresholds for activation.

Spatiotemporal interactions in the visual cortex following paired electrical stimulation of the retina.

Retinal prostheses use spatiotemporal patterns of electrical stimulation across multiple electrodes to provide visual percepts to blind patients. It is generally assumed that percepts produced by individual electrodes are independent of one another, which may not be the case. In this study, we aimed to quantify interactions between pairs of electrical stimuli delivered to the retina. Normally sighted cats were implanted with a suprachoroidal electrode array. The retina was stimulated with a paired-pulse paradigm that consisted of a conditioning stimulus followed by a test stimulus, while recording multiunit activity in the visual cortex. Conditioning current, and spatial and temporal separation between the conditioning and test stimuli were varied. Cortical interactions were quantified by changes in multiunit activity elicited by stimulation with the paired-pulse paradigm, compared to stimulation of the test stimulus alone (control). Interactions varied as a function of conditioning current and temporal separation between the two stimulating pulses. Cortical activity increased compared to the control condition at an interstimulus delay of 1.025 ms and was significantly suppressed for delays between 20 and 90 ms, returning to near control levels for longer delays. The level of interactions increased when the conditioning current was increased. Interactions were found to be similar for electrode separations up to 3 mm. Interactions between sequential stimulation of pairs of electrodes in a suprachoroidal retinal prosthesis occur for delays up to 100 ms and electrode separations of several millimeters. Knowledge of these spatiotemporal interactions is essential for developing effective patterns of stimulation for retinal prostheses.

Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis

Objective. The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. Approach. A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. Main results. The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm−2). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. Significance. Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.

Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study.

PurposeTo assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.MethodsSeven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.ResultsAll subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.ConclusionsChronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.

A Wide-Field Suprachoroidal Retinal Prosthesis Is Stable and Well Tolerated Following Chronic Implantation

The safety of chronic implantation of a retinal prosthesis in the suprachoroidal space has not been established. This study aimed to determine the safety of a wide-field suprachoroidal electrode array following chronic implantation using histopathologic techniques and electroretinography. A platinum electrode array in a wide silicone substrate was implanted unilaterally in the suprachoroidal space in adult cats (n = 7). The lead and connector were tunneled out of the orbit and positioned subcutaneously. Postsurgical recovery was assessed using fundus photography and electroretinography (ERG). Following 3 months of passive implantation, the animals were terminated and the eyes assessed for the pathologic response to implantation. The implant was mechanically stable in the suprachoroidal space during the course of the study. The implanted eye showed a transient increase in ERG response amplitude at 2 weeks, which returned to normal by 3 months. Pigmentary changes were observed at the distal end of the implant, near the optic disc. Histopathologic assessment revealed a largely intact retina and a thin fibrous capsule around the suprachoroidal implant cavity. The foreign body response was minimal, with sporadic presence of macrophages and no active inflammation. All implanted eyes were negative for bacterial or fungal infections. A midgrade granuloma and thick fibrous buildup surrounded the extraocular cable. Scleral closure was maintained in six of seven eyes. There were no staphylomas or choroidal incarceration. A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe.

Evaluation of stimulus parameters and electrode geometry for an effective suprachoroidal retinal prosthesis

Several approaches have been proposed for placement of retinal prostheses: epiretinal, subretinal and suprachoroidal. We aimed to systematically evaluate the effectiveness of varying a range of stimulus parameters and electrode geometry for a suprachoroidal electrode array, using cortical evoked responses to monopolar electrical stimulation in cats. Our results indicate that charge thresholds were not dependent on electrode size, pulse widths or position of the return electrode tested, but were dependent on the number of sites stimulated in parallel. Further, we found that the combination of monopolar stimulation with large diameter electrodes, wide pulse widths and parallel stimulation minimized the voltage requirements for stimulation. These results provide useful insights for the design specifications of a low voltage suprachoroidal stimulator.