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PurposeRetinal implants use electrical stimulation to elicit perceived flashes of light ("phosphenes"). Single-electrode phosphene shape has been shown to vary systematically with stimulus parameters and the retinal location of the stimulating electrode, due to incidental activation of passing nerve fiber bundles. However, this knowledge has yet to be extended to paired-electrode stimulation.MethodsWe retrospectively analyzed 3548 phosphene drawings made by three blind participants implanted with an Argus II Retinal Prosthesis. Phosphene shape (characterized by area, perimeter, major and minor axis length) and number of perceived phosphenes were averaged across trials and correlated with the corresponding single-electrode parameters. In addition, the number of phosphenes was correlated with stimulus amplitude and neuroanatomical parameters: electrode-retina and electrode-fovea distance as well as the electrode-electrode distance to ("between-axon") and along axon bundles ("along-axon"). Statistical analyses were conducted using linear regression and partial correlation analysis.ResultsSimple regression revealed that each paired-electrode shape descriptor could be predicted by the sum of the two corresponding single-electrode shape descriptors (p

Background: Retinal prostheses offer hope for individuals with degenerative retinal diseases by stimulating the remaining retinal cells to partially restore their vision. This review delves into the current advancements in retinal prosthesis technology, with a special emphasis on the pivotal role that image processing and machine learning techniques play in this evolution. Methods: We provide a comprehensive analysis of the existing implantable devices and optogenetic strategies, delineating their advantages, limitations, and challenges in addressing complex visual tasks. The review extends to various image processing algorithms and deep learning architectures that have been implemented to enhance the functionality of retinal prosthetic devices. We also illustrate the testing results by demonstrating the clinical trials or using Simulated Prosthetic Vision (SPV) through phosphene simulations, which is a critical aspect of simulating visual perception for retinal prosthesis users. Results: Our review highlights the significant progress in retinal prosthesis technology, particularly its capacity to augment visual perception among the visually impaired. It discusses the integration between image processing and deep learning, illustrating their impact on individual interactions and navigations within the environment through applying clinical trials and also illustrating the limitations of some techniques to be used with current devices, as some approaches only use simulation even on sighted‐normal individuals or rely on qualitative analysis, where some consider realistic perception models and others do not. Conclusion: This interdisciplinary field holds promise for the future of retinal prostheses, with the potential to significantly enhance the quality of life for individuals with retinal prostheses. Future research directions should pivot towards optimizing phosphene simulations for SPV approaches, considering the distorted and confusing nature of phosphene perception, thereby enriching the visual perception provided by these prosthetic devices. This endeavor will not only improve navigational independence but also facilitate a more immersive interaction with the environment. [ABSTRACT FROM AUTHOR]

This article presents two miniaturized antennas designed for retinal prosthesis devices, aimed at enhancing vision for blind individuals with functional optic nerves. The implantable antenna is 2.2 mm wide, 2.15 mm tall, and 0.78 mm thick. It works in the ISM bands but is small because it uses slot incorporation and high-permittivity substrates. High-frequency structure simulator (HFSS) electromagnetic simulations show great performance, with a 16.66% impedance bandwidth at 2.4 GHz and a 10.34% bandwidth at 5.8 GHz. The peak gain values are -27.76 dB at 2.4 GHz and -16.40 dB at 5.8 GHz. We have also developed an extraocular antenna for telemetry and energy transfer, with dimensions of 36x36x1.6 mm³. Validation through CST calculation software confirms the efficacy of both antenna designs. Implantable antennas hold significant promise in biomedical antenna research, demonstrating capabilities conducive to retinal implantation and offering potential advancements in vision restoration technology. [ABSTRACT FROM AUTHOR]

The goal of this study was to examine the characteristics of electrically induced retinal damage. A retinal prosthesis must be both effective and safe, but most research related to electrical stimulation of the retina has involved measures of efficacy (for example, stimulus threshold), while relatively little research has investigated the safety of electrical stimulation. In this study, a single platinum microelectrode was inserted into the vitreous cavity of normally-sighted adult Long Evans pigmented rats. In one group of animals, no contact was made between the electrode and the retina and current pulses of 0.05 (n = 3) and 0.2 (n = 6) μC/phase were applied. In a second group, visible contact (slight dimpling of the retina) was made between the electrode and the retina and current pulses of 0.09 (n = 4) μC/phase were applied. In both cases, stimulus pulses (biphasic, cathodic first, 1 ms/phase) were applied for 1 h at 100 Hz. Also, control experiments were run with no electrical stimulation with retina contact (n = 4) and with no retinal contact (n = 3). After stimulation, the animal was survived for 2 weeks with ocular photography and electroretinography (ERG) to document changes. During the follow-up period, retinal changes were observed only when the electrode contacted the retina, with or without electrical stimulation. No difference was noted in ERG amplitude or latency comparing the test eye to the stimulated eye. Histological analysis was performed after sacrifice at 2 weeks. A semi-quantitative method for grading 18 features of retina/RPE/choroidal appearance was established and integer grades applied to both test and control eyes. Using this method and comparing the most severely affected area (highest grade), significant differences ( p < 0.05) were noted between experiments with retinal contact and without retinal contact in all features except inner nuclear layer thickness. No difference was noted within a group based on the intensity of electrical stimulus applied. The size of the affected area was significantly larger with both retinal contact and electrical stimulation compared to withretinal contact alone. We conclude that mechanical pressure alone and mechanical pressure with excessive electrical stimulation causes damageto the retina but that electrical stimulation coupled with mechanical pressure increases the area of the damage.

With electrical stimulation, retinal prostheses bypass dysfunctional photoreceptors and activate the surviving bipolar or retinal ganglion cells (RGCs). Therefore, the effective modulation of RGCs is crucial for developing retinal prostheses. Substantial research has been performed on the ability of an electrical stimulus to generate a reliable RGC response. However, different experimental conditions show varying levels of how well the electrical stimulation evokes RGC spikes. Therefore, in this study, we attempted to extract an indicator to understand how the electrical stimulation effectively evokes RGC spikes. Six cynomolgus monkeys were used: three as controls and three as an N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model. The retinal recordings were performed using 8 x 8 multi-electrode arrays (MEAs). Electrical stimulation consisted of symmetrical biphasic pulses of varying amplitudes and durations. The number of stimulation conditions that resulted in significantly higher post-stimulation firing rates than pre-stimulus firing rates was defined as the modulation efficiency ratio (MER). The MER was significantly lower in degenerated retinas than in normal retinas. We investigated the relationship between the variables and the MER in normal and degenerated primate RGCs. External variables, such as duration and inter-electrode distance, and internal variables, such as average firing rates and statistics (mean, standard deviation, and coefficient of variation [CV]) of inter-spike intervals (ISIs) of spontaneous spikes, were used. External variables had similar effects on MER in normal and degenerated RGCs. In contrast, internal variables affected MER differently in normal and degenerated RGCs. While in normal RGCs, they were not related to MER, in degenerated RGCs, the mean ISIs were positively correlated with MER, and the CV of ISIs was negatively correlated with MER. The most important variable affecting MER was the mean ISI. A shorter ISI indicates hyperactive firing in the degenerated retina, which prevents electrical stimulation from evoking more RGCs. We believe that this hyperactivity in degenerated retinas results in a lower MER than that in the normal retina. Our findings can be used to optimize the selection of stimulation channels for in vitro MEA experiments and practical calibration methods to achieve higher efficiency when testing retinal prostheses. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To develop and evaluate a photovoltaic, wireless wide‐field epiretinal prosthesis for the treatment of retinitis pigmentosa.A mosaic array of thinned silicon‐based photodiodes with integrated thin‐film stimulation electrodes was fabricated with a flexible polyimide substrate film to form a film‐based miniaturized electronic system with wireless optical power and signal transmission and integrated electrostimulation. Manufactured implants were characterized with respect to their optoelectronic performance and biocompatibility following DIN EN ISO 10993.A 14 mm diameter prosthesis containing 1276 pixels with a maximum sensitivity at a near infrared wavelength of 905 nm and maximized stimulation current density 30–50 μm below the electrodes was developed for direct activation of retinal ganglion cells during epiretinal stimulation. Fabricated prostheses demonstrated mucosal tolerance and the preservation of both metabolic activity, proliferation and membrane integrity of human fibroblasts as well as the retinal functions of bovine retinas. Illumination of the prosthesis, which was placed epiretinally on an isolated perfused bovine retina, with infrared light resulted in electrophysiological recordings reminiscent of an a‐wave (hyperpolarization) and b‐wave (depolarization).A photovoltaic, wireless wide‐field epiretinal prosthesis for the treatment of retinitis pigmentosa using near infrared light for signal transmission was designed, manufactured and its biocompatibility and functionality demonstrated in vitro and ex vivo. [ABSTRACT FROM AUTHOR]

Introduction: Organic interfaces have recently emerged as a breakthrough trend in biomedical applications, demonstrating exceptional performance in stimulating retinal neuronal cells owing to their high flexibility and compatibility with tissues. However, the primary challenge associated with organic photovoltaics is their low efficiency compared to that of their inorganic counterparts. Among different approaches, embedding plasmonic metal nanoparticles (NPs) in active or buffer layers can efficiently improve photovoltaic cell performance. Methods: A cathode decorated with silver nanoparticles is introduced to increase the absorption Phenomenon and improve the interface performance as a computational study. In addition to embedding spherical silver nanoparticles in the active layer (A-AgNPs), a monolayer array of spherical AgNPs in the cathode electrode (K-AgNPs) is incorporated. In this configuration, the large K-AgNPs play dual roles: acting as cathode electrode and serving as plasmonic centers to increase light trapping and absorption. The bulk heterojunction PCPDTBT:PCBM is chosen as the active layer due to its favorable electronic properties. Results: Our computational analysis demonstrates a notable 10% enhancement in the photovoltaic cell current density for the developed structure with K-AgNPs in contrast to without them. Additionally, the simulation results reveal that the modeled device achieves a two-fold efficiency of the bare photovoltaic cell (without A-AgNPs and K-AgNPs), which is particularly evident at a low intensity of 0.26 mW/mm2. Discussion: This study aims to propose an efficient epiretinal prosthesis structure using a different strategy for plasmonic effects rather than conventional methods, such as incorporating NPs into the active or buffer layer. This structure can prevent the harmful side effects of using large metal NPs (r > 10 nm) in the active layer during exciton quenching, charge trapping, and recombination, which deteriorate the power conversion efficiency (PCE). [ABSTRACT FROM AUTHOR]

Photovoltaic retinal implants are emerging as a promising technological solution for restoring vision for patients suffering from retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. These prostheses contain arrays of miniaturized solar cells converting light into electrical output signals, which subsequently are employed for local activation of the intact neuroretina via microelectrodes. Leveraging cutting-edge microfabrication techniques, photovoltaic retinal implants are compact and provide a high density of solar cell pixels. This potentially increases the resolution of the artificial vision and the field of view and lowers the threshold for stimulation of retinal neurons. The introduction of flexible substrates and the integration of 3D electrodes has greatly improved the connection with retinal neurons, optimizing the spatial resolution and potentially lowering the stimulation threshold. This review explores the latest developments in photovoltaic retinal prostheses, highlighting key aspects of their design, fabrication and performance. This field of research is still in its early stage and particular emphasis is laid on promising future research directions including miniaturization of pixels, incorporation of organic flexible semiconductors and first studies considering 3D stimulating electrode structures. Despite the significant progress made, there are still substantial challenges to overcome, such as ensuring long-term biocompatibility and validation of the novel concepts in clinical trials. Ongoing interdisciplinary research and development are essential for moving these promising technologies from the lab to real-world clinical applications, ultimately enhancing vision restoration. This review aims to provide a comprehensive overview of the current state of photovoltaic retinal implants and pinpoints critical areas for future research to further advance this transformative technology.

Background: Microelectronic prostheses for artificial vision stimulate neurons surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the quality of prosthetic vision substantially varies across subjects, maybe due to different levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes are remarkably diverse, prosthetic studies have primarily used retinal degeneration (rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model which has Crb1 mutation. Methods: We first investigated age-dependent histological changes of wild-type (wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch clamping to record spiking responses of ON, OFF and direction selective (DS) types of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were analyzed in comparison with those of wt RGCs in terms of individual RGC spiking patterns, populational characteristics, and spiking consistency across trials. Results: In the histological examination, the rd8 mice showed partial retinal foldings, but the outer nuclear layer thicknesses remained comparable to those of the wt mice, indicating the early-stage of RP. Although spiking patterns of each RGC type seemed similar to those of the wt retinas, correlation levels between electric vs. light response features were different across the two mouse models. For example, in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of the rd8 mice showed the same/opposite correlation polarity with those of wt mice, respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas showed a positive correlation with their direction selectivity indices (r = 0.40), while those of the wt retinas were negatively correlated (r = -0.90). Lastly, the spiking timing consistencies of late responses were largely decreased in both ON and OFF RGCs in the rd8 than the wt retinas, whereas no significant difference was found across DS RGCs of the two models. Conclusion: Our results indicate the electric response features are altered depending on RGC types even from the early-stage RP caused by Crb1 mutation. Given the various degeneration patterns depending on mutation genes, our study suggests the importance of both genotype- and RGC type-dependent analyses for retinal prosthetic research. [ABSTRACT FROM AUTHOR]

Degeneration of photoreceptors in the retina is a leading cause of blindness, but commonly leaves the retinal ganglion cells (RGCs) and/or bipolar cells extant. Consequently, these cells are an attractive target for the invasive electrical implants colloquially known as "bionic eyes." However, after more than two decades of concerted effort, interfaces based on conventional electrical stimulation approaches have delivered limited efficacy, primarily due to the current spread in retinal tissue, which precludes high-acuity vision. The ideal prosthetic solution would be less invasive, provide single-cell resolution and an ability to differentiate between different cell types. Nanoparticlemediated approaches can address some of these requirements, with particular attention being directed at light-sensitive nanoparticles that can be accessed via the intrinsic optics of the eye. Here we survey the available known nanoparticle-based optical transduction mechanisms that can be exploited for neuromodulation. We review the rapid progress in the field, together with outstanding challenges that must be addressed to translate these techniques to clinical practice. In particular, successful translation will likely require efficient delivery of nanoparticles to stable and precisely defined locations in the retinal tissues. Therefore, we also emphasize the current literature relating to the pharmacokinetics of nanoparticles in the eye. While considerable challenges remain to be overcome, progress to date shows great potential for nanoparticlebased interfaces to revolutionize the field of visual prostheses. [ABSTRACT FROM AUTHOR]

Subretinal prostheses have been developed to stimulate survived retinal ganglion cells (RGCs), indirectly following the physiological visual pathways. However, current spreading from the prosthesis electrode causes the activation of unintended RGCs, thereby limiting the spatial resolution of artificial vision. This study proposes a strategy for focal stimulation of RGCs using a subretinal electrode array, in which six hexagonally arranged peripheral electrodes surround a stimulating electrode. RGCs in an in-vitro condition were subretinally stimulated using a fabricated electrode array coated with iridium oxide, following the three different stimulation configurations (with no peripheral, six electrodes of opposite current, and six ground). In-vitro experiments showed that the stimulation with six electrodes of opposite current was most effective in controlling RGC responses with a high spatial resolution. The results suggest that the effective utilization of return electrodes, such as by applying an opposite current to them, could help reduce current spreading beyond the local area targeted for stimulation and elicit RGC responses only in the vicinity of the stimulating electrode. [ABSTRACT FROM AUTHOR]

In this paper, a biologically-informed computational framework is developed to model the efficacy and to optimize the implementation of an implantable epi-retinal prosthesis that performs optogenetic stimulation through a $\mu $ LED array. The developed model is capable of translating visual stimulus inputs into corresponding signals evoked in the transfected retinal cells through optogenetic stimulation, calculating the subsequent neuronal activities of the following retinal layers, and estimating the resulted brain’s visual perception. As such, it can model and quantitatively analyze the impact of optical stimulation parameters (intensity, frequency, directivity, wavelength, etc.) and the $\mu $ LED array’s physical specifications (array size, density, pitch, implantation location, etc.) on the efficacy of the stimulation. Using this model, we compared optical and electrical stimulations in terms of the structural similarity between their induced visual perception in the brain and the visual stimulus input. We showed that thanks to the cell-type specificity of optogenetic stimulation, it can induce more relevant visual perception qualities than electrical stimulation. We also showed that its resulted visual perception substantially improves with scaling the stimulator’s array size. The model was also used to qualitatively and quantitatively analyze the impact of parameters such as implantation location, light intensity, single- and dual-wavelength stimulation, and illumination divergence angle on the quality of the optical-stimulation-induced visual perception. In each case, the simulation results were followed by our interpretation from a biological point of view. More importantly, in each case, we discussed how the results could be used for optimizing different parameters of an implantable optogenetic stimulator to achieve maximum efficacy and energy efficiency.

Ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, toxicity, invasiveness, and delivery range. While gene, cell, and antibody therapy and nanoparticle delivery directly treat regions that have been damaged by disease, they can be limited in the duration of the therapeutic delivery and have a focal effect. In contrast, contact lenses and ocular implants can more effectively achieve sustained and widespread delivery of therapies; however, they can increase dilution of therapeutics, which may result in reduced effectiveness. Current therapies either offer a sustained release or a broad therapeutic effect, and future directions should aim toward achieving both. This review discusses current ocular therapy delivery systems and their applications, mechanisms for delivering therapeutic products to ocular tissues, advantages and challenges associated with each delivery system, current approved therapies, and clinical trials. Future directions for the improvement in existing ocular therapies include combination therapies, such as combined cell and gene therapies, as well as AI-driven devices, such as cortical implants that directly transmit visual information to the cortex. [ABSTRACT FROM AUTHOR]

IntroductionOrganic interfaces have recently emerged as a breakthrough trend in biomedical applications, demonstrating exceptional performance in stimulating retinal neuronal cells owing to their high flexibility and compatibility with tissues. However, the primary challenge associated with organic photovoltaics is their low efficiency compared to that of their inorganic counterparts. Among different approaches, embedding plasmonic metal nanoparticles (NPs) in active or buffer layers can efficiently improve photovoltaic cell performance.MethodsA cathode decorated with silver nanoparticles is introduced to increase the absorption Phenomenon and improve the interface performance as a computational study. In addition to embedding spherical silver nanoparticles in the active layer (A-AgNPs), a monolayer array of spherical AgNPs in the cathode electrode (K-AgNPs) is incorporated. In this configuration, the large K-AgNPs play dual roles: acting as cathode electrode and serving as plasmonic centers to increase light trapping and absorption. The bulk heterojunction PCPDTBT:PCBM is chosen as the active layer due to its favorable electronic properties.ResultsOur computational analysis demonstrates a notable 10% enhancement in the photovoltaic cell current density for the developed structure with K-AgNPs in contrast to without them. Additionally, the simulation results reveal that the modeled device achieves a two-fold efficiency of the bare photovoltaic cell (without A-AgNPs and K-AgNPs), which is particularly evident at a low intensity of 0.26 mW/mm2.DiscussionThis study aims to propose an efficient epiretinal prosthesis structure using a different strategy for plasmonic effects rather than conventional methods, such as incorporating NPs into the active or buffer layer. This structure can prevent the harmful side effects of using large metal NPs (r > 10 nm) in the active layer during exciton quenching, charge trapping, and recombination, which deteriorate the power conversion efficiency (PCE).

Degeneration of photoreceptors in the retina is a leading cause of blindness, but commonly leaves the retinal ganglion cells (RGCs) and/or bipolar cells extant. Consequently, these cells are an attractive target for the invasive electrical implants colloquially known as “bionic eyes.” However, after more than two decades of concerted effort, interfaces based on conventional electrical stimulation approaches have delivered limited efficacy, primarily due to the current spread in retinal tissue, which precludes high-acuity vision. The ideal prosthetic solution would be less invasive, provide single-cell resolution and an ability to differentiate between different cell types. Nanoparticle-mediated approaches can address some of these requirements, with particular attention being directed at light-sensitive nanoparticles that can be accessed via the intrinsic optics of the eye. Here we survey the available known nanoparticle-based optical transduction mechanisms that can be exploited for neuromodulation. We review the rapid progress in the field, together with outstanding challenges that must be addressed to translate these techniques to clinical practice. In particular, successful translation will likely require efficient delivery of nanoparticles to stable and precisely defined locations in the retinal tissues. Therefore, we also emphasize the current literature relating to the pharmacokinetics of nanoparticles in the eye. While considerable challenges remain to be overcome, progress to date shows great potential for nanoparticle-based interfaces to revolutionize the field of visual prostheses.

Abstract Microelectronic retinal implants can restore a useful level of artificial vision in photoreceptor-damaged retina. Previously commercialized retinal prostheses require transocular connection lines to an external power supply and/or for data transmission, which are unwieldy and may cause unwanted side effects, such as infections. A recently reported wireless device used a rigid silicon substrate. However, it had the potential for a long-term mechanical mismatch with soft retinal tissue. In this work, we used organic photovoltaic materials which can be fabricated on flexible substrates as well as be operated without any physical connection to the external world. The present study employed PCE10 as an active layer for retinal prosthetic application for the first time. Compared to previously studied organic photovoltaic materials used in retinal prosthesis research (such as P3HT), our PCE10 devices showed higher efficiency, providing a huge advantage in this field. When the PCE10 was blended with other non-fullerene acceptors achieving a ternary organic photovoltaic layer (PCE10:ITIC:Y6 blend), it showed lower reduction of photocurrent under same irradiation frequency condition. The fabrication method for our organic photovoltaic device was simple and easy to control its thickness. The fabricated devices showed adequate photocurrent to stimulate the retinal neurons with a smaller reduction in generated photocurrent during repeating stimuli compared to P3HT or PCE10 alone.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author: Given name [Jae Young] Last name [Kim]. Author: Given name [Byung Chul] Last name [Lee].Yes, they are correct.

Two of the main obstacles to the development of epiretinal prosthesis technology are electrodes that require current amplitudes above safety limits to reliably elicit percepts, and a failure to consistently elicit pattern vision. Here, we explored the causes of high current amplitude thresholds and poor spatial resolution within the Argus II epiretinal implant. We measured current amplitude thresholds and two-point discrimination (the ability to determine whether one or two electrodes had been stimulated) in 3 blind participants implanted with Argus II devices. Our data and simulations show that axonal stimulation, lift and retinal damage all play a role in reducing performance in the Argus 2, by either limiting sensitivity and/or reducing spatial resolution. Understanding the relative role of these various factors will be critical for developing and surgically implanting devices that can successfully subserve pattern vision.

Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins (Clinical Identifiers: NCT02556736, NCT03326336, NCT04945772, and NCT04278131). Here we present preclinical efficacy and safety data for the NCT04278131 trial, which uses an AAV2 vector and Chronos as the optogenetic protein. Efficacy was assessed in mice in a dose-dependent manner using electroretinograms (ERGs). Safety was assessed in rats, nonhuman primates, and mice, using several tests, including immunohistochemical analyses and cell counts (rats), electroretinograms (nonhuman primates), and ocular toxicology assays (mice). The results showed that Chronos-expressing vectors were efficacious over a broad range of vector doses and stimulating light intensities, and were well tolerated: no test article-related findings were observed in the anatomical and electrophysiological assays performed.

Retinal prostheses have shown some clinical success in restoring vision in patients with retinitis pigmentosa. However, the post-implantation visual acuity does not exceed that of legal blindness. The reason for the poor visual acuity might be that (1) degenerate retinal ganglion cells (RGCs) are less responsive to electrical stimulation than normal RGCs, and (2) electrically-evoked RGC spikes show a more widespread not focal response. The single-biphasic pulse electrical stimulation, commonly used in artificial vision, has limitations in addressing these issues. In this study, we propose the benefit of multiple consecutive-biphasic pulse stimulation. We used C57BL/6J mice and C3H/HeJ (rd1) mice for the normal retina and retinal degeneration model. An 8 x 8 multi-electrode array was used to record electrically-evoked RGC spikes. We compared RGC responses when increasing the amplitude of a single biphasic pulse versus increasing the number of consecutive biphasic pulses at the same stimulus charge. Increasing the amplitude of a single biphasic pulse induced more RGC spike firing while the spatial resolution of RGC populations decreased. For multiple consecutive-biphasic pulse stimulation, RGC firing increased as the number of pulses increased, and the spatial resolution of RGC populations was well preserved even up to 5 pulses. Multiple consecutive-biphasic pulse stimulation using two or three pulses in degenerate retinas induced as much RGC spike firing as in normal retinas. These findings suggest that the newly proposed multiple consecutive-biphasic pulse stimulation can improve the visual acuity in prosthesis-implanted patients. [ABSTRACT FROM AUTHOR]

A high-performance porous stimulation electrode [femtosecond laser-induced porosity (FLiP) electrode] was designed for the safe and effective delivery of high stimulation currents. Herein, we evaluated the electrochemical properties of the FLiP electrode interface under prolonged in vivo stimulation. The FLiP electrodes were surgically implanted in rabbits and subjected to stimulation currents over a six-month period. The impedance of these electrodes was examined through equivalent circuit analysis, specifically employing the Randles circuit model. Comparative analysis with the results of previous in vitro/in vivo studies was conducted. Electrical stimulation served to purify the electrode interface, enhancing mass diffusion and promoting charge-transfer reactions at the electrode interface. As a result, the electric doublelayer capacitance (Cdl) could be enhanced by adjusting the ionic concentration at the electrode. The high charge injection capacity of the FLiP electrode is facilitated by not only capacitive currents resulting from Cdl but also pseudocapacitive currents stemming from the reversible redox reaction of H2 molecules. Our findings suggest that the initial evaluation outcomes can extrapolate the electrode properties during long-term stimulation, and the combined method of electrochemical impedance spectroscopy and equivalent circuit analysis clarifies intricate in vivo interactions, allowing accurate analysis of the properties of implantable electrodes over extended periods. [ABSTRACT FROM AUTHOR]

This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 μA and 500 to 4000 μs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm2 vs. 1.06 ± 0.09 mC/cm2, p < 0.05) at a 500 μs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm2, mouse; 1.04 ± 0.09 mC/cm2, and rat; 1.16 ± 0.16 mC/cm2, p < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics. [ABSTRACT FROM AUTHOR]

Microelectronic retinal implants can restore a useful level of artificial vision in photoreceptor-damaged retina. Previously commercialized retinal prostheses require transocular connection lines to an external power supply and/or for data transmission, which are unwieldy and may cause unwanted side effects, such as infections. A recently reported wireless device used a rigid silicon substrate. However, it had the potential for a long-term mechanical mismatch with soft retinal tissue. In this work, we used organic photovoltaic materials which can be fabricated on flexible substrates as well as be operated without any physical connection to the external world. The present study employed PCE10 as an active layer for retinal prosthetic application for the first time. Compared to previously studied organic photovoltaic materials used in retinal prosthesis research (such as P3HT), our PCE10 devices showed higher efficiency, providing a huge advantage in this field. When the PCE10 was blended with other non-fullerene acceptors achieving a ternary organic photovoltaic layer (PCE10:ITIC:Y6 blend), it showed lower reduction of photocurrent under same irradiation frequency condition. The fabrication method for our organic photovoltaic device was simple and easy to control its thickness. The fabricated devices showed adequate photocurrent to stimulate the retinal neurons with a smaller reduction in generated photocurrent during repeating stimuli compared to P3HT or PCE10 alone.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author: Given name [Jae Young] Last name [Kim]. Author: Given name [Byung Chul] Last name [Lee].Yes, they are correct. [ABSTRACT FROM AUTHOR]

Retinal prosthesis requires a microhermetic package with long-term reliability for the intraocular implantation of devices. The evaluation of the hermetic package generally involves leak testing, but it is challenging to detect micropackages by leak tests owing to their small volume. Therefore, a sensor that can sense the environment inside the package is necessary. However, conventional sensors are too large to be mounted inside a micropackage. To address this issue, we fabricated a humidity microsensor that is compatible with a microhermetic package and evaluated its performance. The humidity microsensor was fabricated by layering a sensitive film on glass using a simple photolithography technique. The humidity microsensor exhibited a linear response to changes in relative humidity in a 25 ° environment with a capacitance change of 0.059 pF. By using the humidity microsensor, we successfully detected device failure in the microhermetic package. Moreover, the fabricated humidity microsensor operated stably for >14 days under transient thermal stress at 200 ° during hermetic sealing and under continuous thermal stress during accelerated testing at 87 °. These results demonstrate that the fabricated humidity microsensor is useful for evaluating the long-term reliability of microhermetic packages. [ABSTRACT FROM AUTHOR]

The goal of this study was to examine the characteristics of electrically induced retinal damage. A retinal prosthesis must be both effective and safe, but most research related to electrical stimulation of the retina has involved measures of efficacy (for example, stimulus threshold), while relatively little research has investigated the safety of electrical stimulation. In this study, a single platinum microelectrode was inserted into the vitreous cavity of normally-sighted adult Long Evans pigmented rats. In one group of animals, no contact was made between the electrode and the retina and current pulses of 0.05 (n = 3) and 0.2 (n = 6) μC/phase were applied. In a second group, visible contact (slight dimpling of the retina) was made between the electrode and the retina and current pulses of 0.09 (n = 4) μC/phase were applied. In both cases, stimulus pulses (biphasic, cathodic first, 1 ms/phase) were applied for 1 h at 100 Hz. Also, control experiments were run with no electrical stimulation with retina contact (n = 4) and with no retinal contact (n = 3). After stimulation, the animal was survived for 2 weeks with ocular photography and electroretinography (ERG) to document changes. During the follow-up period, retinal changes were observed only when the electrode contacted the retina, with or without electrical stimulation. No difference was noted in ERG amplitude or latency comparing the test eye to the stimulated eye. Histological analysis was performed after sacrifice at 2 weeks. A semi-quantitative method for grading 18 features of retina/RPE/choroidal appearance was established and integer grades applied to both test and control eyes. Using this method and comparing the most severely affected area (highest grade), significant differences ( p < 0.05) were noted between experiments with retinal contact and without retinal contact in all features except inner nuclear layer thickness. No difference was noted within a group based on the intensity of electrical stimulus applied. The size of the affected area was significantly larger with both retinal contact and electrical stimulation compared to withretinal contact alone. We conclude that mechanical pressure alone and mechanical pressure with excessive electrical stimulation causes damageto the retina but that electrical stimulation coupled with mechanical pressure increases the area of the damage.

Age-related macular degeneration is one of the leading causes of irreversible vision loss in ageing populations worldwide. The PRIMA bionic vision system is a photovoltaic substitute for lost photoreceptors that is designed for patients with atrophic dry age-related macular degeneration. The subretinal implant, activated by near-infrared light from augmented-reality glasses, provides central prosthetic vision, perceived simultaneously with peripheral natural vision. This editorial reviews PRIMA’s mode of action, clinical trial data and potential impact on clinical practice. [ABSTRACT FROM AUTHOR]

Patients with inherited retinal diseases (IRDs) utilize various adaptive techniques and devices designed to assist them with activities of daily living (ADLs). The purpose of this study was to assess the assistive devices used by patients with IRDs, the difficulties they face despite these devices, and their recommendations for a future visual prosthesis. In collaboration with blind patients, an online survey was developed and administered to adults with IRDs and visual acuities of 20/400 to no light perception in the better-seeing eye. We analyzed data from 121 survey respondents (aged 18 to >80 years). Five respondents were Argus II prosthesis recipients. The most commonly used aids were cellular phones/tablets for reading (63.6%) as well as a sighted guide (75.0%) and a cane (71.4%) for mobility. Despite current assistive devices, participants reported continued difficulty with ADLs. Improved navigation, reading, and facial recognition were ranked the most desirable features for future visual prostheses. Argus II recipients suggested technology with improved ability to recognize objects and obstacles, detect movement, and cut out busy backgrounds. These insights are valuable in shaping the design of future prosthetic devices tailored to the needs of IRD patients. [ABSTRACT FROM AUTHOR]

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode–retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

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.

Retinal implants have been developed and implanted to restore vision from outer retinal degeneration, but their performance is still limited due to the poor spatial resolution. To improve the localization of stimulation, microelectrodes in various three-dimensional (3D) shapes have been investigated. In particular, computational simulation is crucial for optimizing the performance of a novel microelectrode design before actual fabrication. However, most previous studies have assumed a uniform conductivity for the entire retina without testing the effect of electrodes placement in different layers. In this study, we used the finite element method to simulate electric fields created by 3D microelectrodes of three different designs in a retina model with a stratified conductivity profile. The three electrode designs included two conventional shapes - a conical electrode (CE) and a pillar electrode (PE); we also proposed a novel structure of pillar electrode with an insulating wall (PEIW). A quantitative comparison of these designs shows the PEIW generates a stronger and more confined electric field with the same current injection, which is preferred for high-resolution retinal prostheses. Moreover, our results demonstrate both the magnitude and the shape of potential distribution generated by a penetrating electrode depend not only on the geometry, but also substantially on the insertion depth of the electrode. Although epiretinal insertions are mainly discussed, we also compared results for subretinal insertions. The results provide valuable insights for improving the spatial resolution of retinal implants using 3D penetrating microelectrodes and highlight the importance of considering the heterogeneity of conductivities in the retina.

Retinal pigmentosa (RP) patients lose vision due to the loss of photoreceptors. Retinal prostheses bypass the dead photoreceptors by electrically stimulating surviving retinal neurons, such as bipolar cells or retinal ganglion cells (RGCs). In previous studies, stimulus charge has been mainly optimized to maximize the RGC response to electrical stimulation. This study aimed to investigate the effect of amplitude and duration even under the same charge condition on eliciting RGC spikes in the wild-type and degenerate retinas. Wild-type (WT) Sprague–Dawley rats were used as the normal retinal model, and Pde6b knockout rats were used as a retinal degeneration (RD) model. Electrically-evoked RGC spikes were recorded from isolated rat retinas using an 8 × 8 multielectrode array. The same charge was maintained (10 or 20 nC), and electrical stimulation was applied to WT and RD retinas, adjusting the amplitude and duration of the 1st phase of biphasic pulses. In the pulse modulation of the 1st phase, high amplitude (short duration) pulses induced more RGC spikes than low amplitude (long duration) pulses. Both WT and RD retinas showed a significant reduction in the number of RGC spikes upon stimulation with lower amplitude (longer duration) pulses. In clinical trials where stimulus charges are delivered to the degenerate retina of blind patients, high amplitude (short duration) pulses would help elicit more RGC spikes. [ABSTRACT FROM AUTHOR]

Ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, toxicity, invasiveness, and delivery range. While gene, cell, and antibody therapy and nanoparticle delivery directly treat regions that have been damaged by disease, they can be limited in the duration of the therapeutic delivery and have a focal effect. In contrast, contact lenses and ocular implants can more effectively achieve sustained and widespread delivery of therapies; however, they can increase dilution of therapeutics, which may result in reduced effectiveness. Current therapies either offer a sustained release or a broad therapeutic effect, and future directions should aim toward achieving both. This review discusses current ocular therapy delivery systems and their applications, mechanisms for delivering therapeutic products to ocular tissues, advantages and challenges associated with each delivery system, current approved therapies, and clinical trials. Future directions for the improvement in existing ocular therapies include combination therapies, such as combined cell and gene therapies, as well as AI-driven devices, such as cortical implants that directly transmit visual information to the cortex.

PurposeSubretinal prostheses are a novel technology for restoring useful vision in patients with retinitis pigmentosa or age-related macular degeneration. We characterize the surgical implantation technique and functional time window of an acute rabbit eye model for testing of human subretinal prostheses.MethodsRetinal prostheses were implanted subretinally in 26 rabbits using a two-step technique. Fundus imaging, fluorescein fundus angiography, and optical coherence topography (OCT) were conducted postoperatively from days 1 to 21 to monitor prosthesis positioning and retinal anatomic changes.ResultsSuccessful implantation and excellent retina apposition were achieved in 84.6% of the rabbits. OCTs showed the overlying retina at full thickness for the first 2 days after implantation. Histology confirmed intact inner layers of the overlying retina until day 3. Progressive atrophy of the overlying retina was revealed by repeated OCTs; approximately 40% of the retina thickness remained on postoperative days 5 and 6.ConclusionsThe two-step implantation technique works well for the rabbit eye model with human prostheses. Rabbit retina may be used for acute electrophysiologic testing of a retinal prosthesis, but is unsuitable for chronic studies due to the merangiotic retina and its limited time window of validity.Translational relevanceThe improved efficacy in prosthesis surgery using this technique will circumvent the challenges in animal models that provide human-like features critical for the transition into human clinical trials.

PurposeFor more than 20 years, there has been an international, multidisciplinary effort to develop retinal prostheses to restore functional vision to patients blinded by retinal degeneration. We developed a novel subretinal prosthesis with 1512 optically addressed silicon nanowire photodiodes, which transduce incident light into an electrical stimulation of the remaining retinal circuitry. This study was conducted to evaluate the efficacy of optically driving the subretinal prosthesis to produce visual cortex activation via electrical stimulation of the retina.MethodsWe measured electrically evoked potential responses (EEPs) in rabbit visual cortex in response to illumination of the subretinal nanowire prosthesis with pulsed 852-nm infrared (IR) light. We compared the EEP responses to visually evoked potential responses (VEPs) to pulsed 532-nm visible light (positive control) and pulsed 852-nm IR light (negative control).ResultsActivating the devices with IR light produced EEP responses with a significantly higher trough-to-peak amplitude (54.17 ± 33.4 μV) than IR light alone (24.07 ± 22.1 μV) or background cortical activity (23.22 ± 17.2 μV). EEP latencies were significantly faster than focal VEP latencies. Focal VEPs produced significantly higher amplitudes (94.88 ± 43.3 μV) than EEPs. We also demonstrated how an electrode placed on the cornea can be used as a noninvasive method to monitor the function of the implant.ConclusionsThese results show that subretinal electrical stimulation with nanowire electrodes can elicit EEPs in the visual cortex, providing evidence for the viability of a subretinal nanowire prosthetic approach for vision restoration.

Background: Microelectronic prostheses for artificial vision stimulate neurons surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the quality of prosthetic vision substantially varies across subjects, maybe due to different levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes are remarkably diverse, prosthetic studies have primarily used retinal degeneration (rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model which has Crb1 mutation. Methods: We first investigated age-dependent histological changes of wild-type (wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch clamping to record spiking responses of ON, OFF and direction selective (DS) types of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were analyzed in comparison with those of wt RGCs in terms of individual RGC spiking patterns, populational characteristics, and spiking consistency across trials. Results: In the histological examination, the rd8 mice showed partial retinal foldings, but the outer nuclear layer thicknesses remained comparable to those of the wt mice, indicating the early-stage of RP. Although spiking patterns of each RGC type seemed similar to those of the wt retinas, correlation levels between electric vs. light response features were different across the two mouse models. For example, in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of the rd8 mice showed the same/opposite correlation polarity with those of wt mice, respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas showed a positive correlation with their direction selectivity indices (r = 0.40), while those of the wt retinas were negatively correlated (r = -0.90). Lastly, the spiking timing consistencies of late responses were largely decreased in both ON and OFF RGCs in the rd8 than the wt retinas, whereas no significant difference was found across DS RGCs of the two models. Conclusion: Our results indicate the electric response features are altered depending on RGC types even from the early-stage RP caused by Crb1 mutation. Given the various degeneration patterns depending on mutation genes, our study suggests the importance of both genotype- and RGC type-dependent analyses for retinal prosthetic research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A recent wave of pharmacologic and technologic innovations has revolutionized our management of retinal diseases. Many of these advancements have demonstrated efficacy and can increase the quality of life while potentially reducing complications and decreasing the burden of care for patients. Some advances, such as longer-acting anti-vascular endothelial growth factor agents, port delivery systems, gene therapy, and retinal prosthetics have been approved by the US Food and Drug Administration, and are available for clinical use. Countless other therapeutics are in various stages of development, promising a bright future for further improvements in the management of the retinal disease. Herein, we have highlighted several important novel therapies and therapeutic approaches and examine the opportunities and limitations offered by these innovations at the new frontier. Numerous pharmacologic and technologic advancements have been emerging, providing a higher treatment efficacy while decreasing the burden and associated side effects. Anti-vascular endothelial growth factor (anti-VEGF) and its longer-acting agents have dramatically improved visual outcomes and have become a mainstay treatment in various retinal diseases. Gene therapy and retinal prosthesis implantation in the treatment of congenital retinal dystrophy can accomplish the partial restoration of vision and improved daily function in patients with blindness, an unprecedented success in the field of retina. [ABSTRACT FROM AUTHOR]

This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 μA and 500 to 4000 μs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm2 vs. 1.06 ± 0.09 mC/cm2, p < 0.05) at a 500 μs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm2, mouse; 1.04 ± 0.09 mC/cm2, and rat; 1.16 ± 0.16 mC/cm2, p < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics.

Background: Most existing retinal prostheses contain a built‐in visible‐light camera module that captures images of the surrounding environment. Thus, in case of insufficient or lack of visible light, the camera fails to work, and the retinal prostheses enter a dormant or "OFF" state. A simple and effective solution is replacing the visible‐light camera with a dual‐mode camera. The present research aimed to achieve two main purposes: (1) to explore whether the dual‐mode camera in prosthesis recipients works under no visible‐light conditions and (2) to assess its performance. Methods: To accomplish these aims, we enrolled subjects in a psychophysical experiment under simulated prosthetic vision conditions. We found that the subjects could complete some simple visual tasks, but the recognition performance under the infrared mode was significantly inferior to that under the visible‐light mode. These results inspired us to develop and propose a feasible infrared image‐enhancement processing algorithm. Another psychophysical experiment was performed to verify the feasibility of the algorithm. Results: The obtained results showed that the average efficiency of the subjects completing visual tasks using our enhancement algorithm (0.014 ± 0.001) was significantly higher (p < 0.001) than that of subjects using direct pixelization (0.007 ± 0.001). Conclusions: We concluded that a dual‐mode camera could be a feasible solution to improving the performance of retinal prostheses as the camera adapted better to the specific existing ambient light conditions. Dual‐mode cameras combined with this infrared image‐enhancement algorithm could provide a promising direction for the design of future retinal prostheses. [ABSTRACT FROM AUTHOR]

The retinal structural changes after subretinal implantation of threedimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-µm-high 3D electrodes on a 200-µm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-µm-thick sloped PDMS substrate without electrodes (group 2); and a 140-µm-thick sloped PDMS substrate with 20-µm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain–optical coherence tomography (SD–OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-µm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD–OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-µm-high electrodes showed better structural compatibility than the 75-µm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-µm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue. [ABSTRACT FROM AUTHOR]

Resting-state functional connectivity (rsFC) has been used to assess the effect of vision loss on brain plasticity. With the emergence of vision restoration therapies, rsFC analysis provides a means to assess the functional changes following sight restoration. Our study demonstrates a partial reversal of blindness-induced rsFC changes in Argus II retinal prosthesis patients compared to those with severe retinitis pigmentosa (RP). For 10 healthy control (HC), 10 RP, and 7 Argus II subjects, four runs of resting-state functional magnetic resonance imaging (fMRI) per subject were included in our study. rsFC maps were created with the primary visual cortex (V1) as the seed. The rsFC group contrast maps for RP > HC, Argus II > RP, and Argus II > HC revealed regions in the post-central gyrus (PostCG) with significant reduction, significant enhancement, and no significant changes in rsFC to V1 for the three contrasts, respectively. These findings were also confirmed by the respective V1-PostCG ROI-ROI analyses between test groups. Finally, the extent of significant rsFC to V1 in the PostCG region was 5,961 in HC, 0 in RP, and 842 mm³ in Argus II groups. Our results showed a reduction of visual-somatosensory rsFC following blindness, consistent with previous findings. This connectivity was enhanced following sight recovery with Argus II, representing a reversal of changes in cross-modal functional plasticity as manifested during rest, despite the rudimentary vision obtained by Argus II patients. Future investigation with a larger number of test subjects into this rare condition can further unveil the profound ability of our brain to reorganize in response to vision restoration. [ABSTRACT FROM AUTHOR]

Argus II retinal prosthesis is the US Food and Drug Administration (FDA) approved medical device intended to restore sight to a patient's blind secondary to retinal degeneration (i.e., retinitis pigmentosa). However, Argus II and most reported retinal prostheses require invasive surgery to implant electrodes in the eye. Recent studies have shown that focused ultrasound can be developed into a non-invasive retinal prosthesis technology. Ultrasound energy focused on retinal neurons can trigger the activities of retinal neurons with high spatial-temporal resolution. This paper introduces a novel design and simulation of a ring array transducer that could be used as non-invasive ultrasonic retinal stimulation. The array transducer is designed in the shape of a racing ring with a hemisphere surface that mimics a contact lens to acoustically couple with the eye via the tear film and directs the ultrasound to avoid the high acoustic absorption from the crystalline lens. We will describe the design methods and simulation of the two-dimensional pattern stimulation. Finally, compared with other existing retinal prostheses, we show that the ultrasound ring array is practical and safe and could be potentially used as a non-invasive retinal prosthesis. [ABSTRACT FROM AUTHOR]