Retinal Prosthesis Research Articles

Nanoparticle-based optical interfaces for retinal neuromodulation: a review.

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.

Explainable machine learning predictions of perceptual sensitivity for retinal prostheses

Objective. Retinal prostheses evoke visual precepts by electrically stimulating functioning cells in the retina. Despite high variance in perceptual thresholds across subjects, among electrodes within a subject, and over time, retinal prosthesis users must undergo ‘system fitting’, a process performed to calibrate stimulation parameters according to the subject’s perceptual thresholds. Although previous work has identified electrode-retina distance and impedance as key factors affecting thresholds, an accurate predictive model is still lacking. Approach. To address these challenges, we (1) fitted machine learning models to a large longitudinal dataset with the goal of predicting individual electrode thresholds and deactivation as a function of stimulus, electrode, and clinical parameters (‘predictors’) and (2) leveraged explainable artificial intelligence (XAI) to reveal which of these predictors were most important. Main results. Our models accounted for up to 76% of the perceptual threshold response variance and enabled predictions of whether an electrode was deactivated in a given trial with F1 and area under the ROC curve scores of up to 0.732 and 0.911, respectively. Our models identified novel predictors of perceptual sensitivity, including subject age, time since blindness onset, and electrode-fovea distance. Significance. Our results demonstrate that routinely collected clinical measures and a single session of system fitting might be sufficient to inform an XAI-based threshold prediction strategy, which has the potential to transform clinical practice in predicting visual outcomes.

Femtosecond Laser Microfabrication of Artificial Compound Eyes

Over millions of years of evolution, arthropods have intricately developed and fine-tuned their highly sophisticated compound eye visual systems, serving as a valuable source of inspiration for human emulation and tracking. Femtosecond laser processing technology has attracted attention for its excellent precision, programmable design capabilities, and advanced three-dimensional processing characteristics, especially in the production of artificial bionic compound eye structures, showing unparalleled advantages. This comprehensive review initiates with a succinct introduction to the operational principles of biological compound eyes, providing essential context for the design of biomimetic counterparts. It subsequently offers a concise overview of crucial manufacturing methods for biomimetic compound eye structures. In addition, the application of femtosecond laser technology in the production of biomimetic compound eyes is also briefly introduced. The review concludes by highlighting the current challenges and presenting a forward-looking perspective on the future of this evolving field.

Prosthetic Visual Acuity with the PRIMA Subretinal Microchip in Patients with Atrophic Age-Related Macular Degeneration at 4 Years Follow-up

ObjectiveTo assess the efficacy and safety of the PRIMA neurostimulation system with a subretinal microchip for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months post-implantation. DesignFirst-in-human clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.gov NCT03333954). SubjectsFive patients with GA, no foveal light perception and VA of logMAR 1.3 to 1.7 (20/400-20/1000) in their worse-seeing “study” eye. MethodsIn patients subretinally implanted with a photovoltaic neurostimulation array containing 378 pixels of 100 μm in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 meter. The system’s external components, augmented reality glasses and pocket computer, provide image processing capabilities, including zoom. Main Outcome MeasuresVA using ETDRS charts with and without the system, as well as light sensitivity in the central visual field, measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and optical coherence tomography up to 48-months post-implantation. ResultsAll five subjects met the primary endpoint of light perception elicited by the implant in the scotoma area. In one patient the implant was incorrectly inserted into the choroid. One subject died 18-months post-implantation due to study-unrelated reason. ETDRS VA results for the remaining three subjects are reported herein. Without zoom, VA closely matched the pixel size of the implant: 1.17 ± 0.13 pixels, corresponding to mean logMAR 1.39, or Snellen 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (SE 5.1) 95% CI[13.4,49.9], p<0.0001. Natural peripheral visual function in the treated eye did not decline after surgery, nor during the 48 months follow-up period (p=0.08). ConclusionsSubretinal implantation of PRIMA in subjects with GA suffering from profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48-months. Prosthetic central vision provided by photovoltaic neurostimulation enabled patients to reliably recognize letters and sequences of letters, and with zoom it improved VA of up to eight ETDRS lines.

Artificial Retina Based on Organic Heterojunction Transistors for Mobile Recognition.

The flicker frequency of incident light constitutes a critical determinant in biology. Nevertheless, the exploration of methods to simulate external light stimuli with varying frequencies and develop artificial retinal neurons capable of responsive behavior remains an open question. This study presents an artificial neuron comprising organic phototransistors. The triggering properties of neurons are modulated by optical input, enabling them to execute rudimentary synaptic functions, emulating the biological characteristics of retinal neurons. The artificial retinal neuron exhibits varying responses to incoming light frequencies, allowing it to replicate the persistent visual behavior of the human eye and facilitating image discrimination. Additionally, through seamless integration with circuitry, it can execute motion recognition on a machine cart, preventing collisions with high-speed obstacles. The artificial retinal neuron offers a cost-effective and energy-efficient route for future mobile robot processors.

Towards biologically plausible phosphene simulation for the differentiable optimization of visual cortical prostheses.

Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or 'phosphenes') has limited resolution, and a great portion of the field's research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator's suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.

Demonstration of multi-point stimulation with AC-driven CMOS chips for retinal prosthesis

We demonstrated a multi-point stimulation system using CMOS chips designed for distributed implantable retinal prostheses. The CMOS chip integrates current sources and electrode selection circuits. This integration enables stimulation current control from multiple electrodes with minimal wires. In this study, we constructed a validation system with 49 electrodes capable of visually observing stimulation current outputs. The validation results show that it is possible to configure stimulation conditions in approximately 9.3 μs per electrode, and we demonstrated the ability to complete one frame, including the stimulation time, within approximately 11 ms. We also demonstrated parallel current stimulation from multiple electrodes using an in vitro experiment.

Cooperative correction method for distortion and dispersion of deflected field of view in Risley-prism bionic-human-eye imaging systems.

The Risley-prism imaging system (RPIS) is a powerful way to achieve bionic human eye imaging with great advantages on large field of view (FOV) and variable resolution imaging owing to the autonomous controlled deflection of light. But the imaging dispersion originating from nonlinear and uneven light deflection results in limited imaging wavelength that seriously hinders its application. The existing solutions for imaging dispersion mainly rely on the hardware, which generally has bulky structure and limited improvement on image. Besides, the existing image evaluation methods for dispersion are not suitable for RPIS due to inhomogeneous dispersion. Herein, this paper systematically analyzes the mechanism and characteristics of dispersion in the RPIS, and proposes a cooperative correction method for image distortion and dispersion of multiple-color imaging, achieving the elimination of distortion and dispersion simultaneously without changing the optical structure. A dispersion evaluation index based on Pearson's correlation coefficient (PCC) is also established, and the objectivity and validity of the index are proved by experiments. Furthermore, a kind of compact RPIS based on an RGB camera is built, and both indoor and outdoor experiments are conducted. The experimental results demonstrate that proposed algorithm has strong universality and robustness for various scenes and targets.

An actor-model framework for visual sensory encoding

A fundamental challenge in neuroengineering is determining a proper artificial input to a sensory system that yields the desired perception. In neuroprosthetics, this process is known as artificial sensory encoding, and it holds a crucial role in prosthetic devices restoring sensory perception in individuals with disabilities. For example, in visual prostheses, one key aspect of artificial image encoding is to downsample images captured by a camera to a size matching the number of inputs and resolution of the prosthesis. Here, we show that downsampling an image using the inherent computation of the retinal network yields better performance compared to learning-free downsampling methods. We have validated a learning-based approach (actor-model framework) that exploits the signal transformation from photoreceptors to retinal ganglion cells measured in explanted mouse retinas. The actor-model framework generates downsampled images eliciting a neuronal response in-silico and ex-vivo with higher neuronal reliability than the one produced by a learning-free approach. During the learning process, the actor network learns to optimize contrast and the kernel’s weights. This methodological approach might guide future artificial image encoding strategies for visual prostheses. Ultimately, this framework could be applicable for encoding strategies in other sensory prostheses such as cochlear or limb.

Ultrananocrystalline diamond (UNCD™) coating for new-generation implantable medical devices/prostheses

Ultrananocrystalline diamond (UNCD™) coating for new-generation implantable medical devices/prostheses In this materials science piece, Orlando Auciello, describes the development of a unique multifunctional/best biocompatible ultrananocrystalline diamond (UNCDTM) coating for new-generation implantable medical devices and prostheses. Materials’ surfaces of vital medical devices, such as silicon (Si) microchip (artificial retina) implanted on human retina, restoring partial vision to people blinded by genetically induced photoreceptors degeneration, and metallic dental implants, are attacked chemically by eyes’ fluids or oral fluids respectively. Metallic stents/artificial heart valves, inside human blood vessels, activate blood enzymes, inducing coagulation, and fibrinolytic, leading to thrombus formation (i.e., blood clot in blood vessels, obstructing blood flow or loosed clot getting stuck in arteries/veins’ walls, causing life-threatening stroke/heart attack.

Geometric Shape Recognition with an Ultra-High Density Perovskite Nanowire Array-Based Artificial Vision System.

Artificial vision systems (AVS) have potential applications in visual prosthetics and artificially intelligent robotics, and they require a preprocessor and a processor to mimic human vision. Halide perovskite (HP) is a promising preprocessor and processor due to its excellent photoresponse, ubiquitous charge migration pathways, and innate hysteresis. However, the material instability associated with HP thin films hinders their utilization in physical AVSs. Herein, we have developed ultrahigh-density arrays of robust HP nanowires (NWs) rooted in a porous alumina membrane (PAM) as the active layer for an AVS. The NW devices exhibit gradual photocurrent change, responding to changes in light pulse duration, intensity, and number, and allow contrast enhancement of visual inputs with a device lifetime of over 5 months. The NW-based processor possesses temporally stable conductance states with retention >105 s and jitter <10%. The physical AVS demonstrated 100% accuracy in recognizing different shapes, establishing HP as a reliable material for neuromorphic vision systems.

Benefits of thermal and distance-filtered imaging for wayfinding with prosthetic vision

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% (p<0.01\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p<0.01$$\\end{document}). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% (p<0.01\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p<0.01$$\\end{document}). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants’ success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 μm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium–indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm−2) to elicit neural responses in the retina. Their low Young’s modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Neuro Receptor Signal Detecting and Monitoring Smart Devices for Biological Changes in Cognitive Health Conditions.

Currently, wearable sensors significantly impact health care through continuous monitoring and event prediction. The types and clinical applications of wearable technology for the prevention of mental illnesses, as well as associated health authority rules, are covered in the current review. The technologies behind wearable ECG monitors, biosensors, electronic skin patches, neural interfaces, retinal prosthesis, and smart contact lenses were discussed. We described how sensors will examine neuronal impulses using verified machine-learning algorithms running in real-time. These sensors will closely monitor body signals and demonstrate continuous sensing with wireless functionality. The wearable applications in the following medical fields were covered in our review: sleep, neurology, mental health, anxiety, depression, Parkinson's disease, epilepsy, seizures, and schizophrenia. These mental health conditions can cause serious issues, even death. Inflammation brought on by mental health problems can worsen hypothalamic-pituitary-adrenal axis dysfunction and interfere with certain neuroregulatory systems such as the neural peptide Y, serotonergic, and cholinergic systems. Severe depressive disorder symptoms are correlated with elevated Interleukin (IL-6) levels. On the basis of previous and present data collected utilizing a variety of sensory modalities, researchers are currently investigating ways to identify or detect the current mental state. This review explores the potential of various mental health monitoring technologies. The types and clinical uses of wearable technology, such as ECG monitors, biosensors, electronic skin patches, brain interfaces, retinal prostheses, and smart contact lenses, were covered in the current review will be beneficial for patients with mental health problems like Alzheimer, epilepsy, dementia. The sensors will closely monitor bodily signals with wireless functionality while using machine learning algorithms to analyse neural impulses in real time.

An Average Amplitude Regulation Scheme for Ambient Illuminance Adaptation in Retinal Prosthesis

An Average Amplitude Regulation Scheme for Ambient Illuminance Adaptation in Retinal Prosthesis

Investigating Different Paradigms of Electrical Stimulation for Retinal Prosthesis

Background and Aims: Retinal prostheses have been suggested to restore vision for those with retinal diseases. This study aimed to identify the most effective stimulation approaches for retinal prostheses. Methods: This study examined various return electrode configurations on a realistic retinal ganglion cell model. Two return electrode configurations, monopolar and hexapolar, were implanted on epiretinal side. There were four waveforms used to send electrical current through the active electrode. The study also compared two stimulation methods: single stimulation and concurrent (parallel) stimulation. Results: Directly placing the retinal ganglion cell beneath the active electrode resulted in no significant difference in the required current for stimulating retinal ganglion cells between monopolar and hexapolar return electrodes, regardless of the stimulation waveform. For retinal ganglion cells located away from the active electrode, differences in the required current were noted between the two return electrode configurations. The study discovered that parallel stimulation with two or three active elec¬trodes lowered current requirements by up to 70% compared to single stimulation. Monophasic anod¬ic stimulation yielded the most effective pulse waveform, regardless of the configuration (monopolar or hexapolar) or stimulation mode (single or parallel). Moreover, monophasic cathodic stimulation usually targets retinal ganglion cells around the active electrode. Conclusions: These results illuminate the best stimulation strategies for enhancing the efficacy of retinal prosthe¬sis. The study highlights the importance of electrode arrangement, waveform selection, and single or concurrent stimulation for improving retinal ganglion cell activation.

Design and Implementation of a Highly Compact Intraocular Antenna With Enhanced Bandwidth for Wireless Data Telemetry in Retinal Prosthesis

Design and Implementation of a Highly Compact Intraocular Antenna With Enhanced Bandwidth for Wireless Data Telemetry in Retinal Prosthesis

High-performance photodetector based on quasi-two-dimensional Ruddlesden–Popper perovskite PEA2FA2Pb3Br10 film

For next-generation Internet-of-Everything applications, such as artificial neural-network image sensors, artificial retina, visible light communication, flexible devices, and so on, the photodetectors with excellent properties are urgently demanded. In recent years, two-dimensional (2D) material-based photodetectors have been developed and certified for remarkable performances. Nonetheless, it cannot meet the need of wide linear dynamic range, ultralow dark current, and large on/off ratio, which are critical factors for commercial applications. Recently, quasi-2D Ruddlesden–Popper (RP) perovskites are explored and developed as well-known photovoltaic and optoelectronic materials. Herein, an excellent photodetector based on quasi-2D RP layered perovskite PEA2FA2Pb3Br10 film was fabricated. The photodetector displays an ultralow dark current of 4.08 × 10−11 A, high specific detectivity of 1.69 × 1010 Jones, high on/off ratio of 7.33 × 103, and fast rise/fall times of 32/38 ms, attributed to its multiple quantum wells in PEA2FA2Pb3Br10. Therefore, the photodetectors based on quasi-2D RP perovskite PEA2FA2Pb3Br10 have immense potentials in the field of optoelectronics.

A simple method for preservation of embryonic rat brain tissue for primary neuron culture

Aims/Purpose: In this study we aim to investigate the effect of short‐term storage of embryonic rat brain tissue in Hibernate‐E medium to be used in the isolation of primary neurons for in vitro biocompatibility and electrophysiology tests of retinal and optic nerve prosthesis. Functionally viable neuron cells will be an alternative method for regular dissection from tissue for further experiments.Methods: Hippocampal tissues from E15‐E17 embryos of Wistar Albino rat were dissecting for primary neuron culture. Half of the tissues were isolated on the same day and used as a control group for further experiments. The test group was stored in a Hibernate‐E medium for 1 week and the same isolation method was performed for the test group. For tissue preservation, half medium replacement with fresh Hibernate‐E medium on the 4th day was enhanced cell viability. Morphology, characterization and synapse formation were determined with immunoflorescence staining.Results: Comparison of neuronal survival between cultures prepared from stored hippocampi and freshly isolated hippocampi resulted in similar neuronal survival rates in both preparations with cell viability assays. Cell viability rate of hippocampus tissue isolated from rat embryo brain was demonstrated as 96% and cell viability rate of preserved tissue in Hibernate‐E Medium for 7 days was revealed as 90.22% by trypan blue cell viability test (n = 4). Morphological and immunocytochemical characterizations of stored and fresh hippocampal cultures were similar by observing beta‐III Tubulin neuron cytoskeleton biomarker.Conclusions: As a conclusion, our method has the potential to increase repeatability of primary neuron cultures within 1 week and reduce the number of isolation steps in research. In addition, it will provide a great convenience in the experimental timelines of the researchers and contribute to the reduction of the workload despite any obstacles during primary neuron culture.

Velocity measurement technology of curved bionic compound eye

Velocity measurement technology of curved bionic compound eye