A model of ganglion axon pathways accounts for percepts elicited by retinal implants.

Degenerative retinal diseases such as retinitis pigmentosa and macular degeneration cause irreversible vision loss in more than 10 million people worldwide. Retinal prostheses, now implanted in over 250 patients worldwide, electrically stimulate surviving cells in order to evoke neuronal responses that are interpreted by the brain as visual percepts ('phosphenes'). However, instead of seeing focal spots of light, current implant users perceive highly distorted phosphenes that vary in shape both across subjects and electrodes. We characterized these distortions by asking users of the Argus retinal prosthesis system (Second Sight Medical Products Inc.) to draw electrically elicited percepts on a touchscreen. Using ophthalmic fundus imaging and computational modeling, we show that elicited percepts can be accurately predicted by the topographic organization of optic nerve fiber bundles in each subject's retina, successfully replicating visual percepts ranging from 'blobs' to oriented 'streaks' and 'wedges' depending on the retinal location of the stimulating electrode. This provides the first evidence that activation of passing axon fibers accounts for the rich repertoire of phosphene shape commonly reported in psychophysical experiments, which can severely distort the quality of the generated visual experience. Overall our findings argue for more detailed modeling of biological detail across neural engineering applications

Data analysis of retinal recordings from multi-electrode arrays under in situ electrical stimulation

The development of retinal implants has become an important field of study in recent years, with increasing numbers of people falling victim to legal or physical blindness as a result of retinal damage. Important weaknesses in current retinal implants include a lack of the resolution necessary to give a patient a viable level of visual acuity, question marks over the amount of power and energy required to deliver adequate stimulation, and the removal of eye movements from the analysis of the visual scene. This thesis documents investigations by the author into a new CMOS stimulation and imaging chip with the potential to overcome these difficulties. An overview is given of the testing and characterisation of the componments incorporated in the device to mimic the normal functioning of the human retina. Its application to in situ experimental studies of frog retina is also described, as well as how the data gathered from these experiments enables the optimisation of the geometry of the electrode array through which the device will interface with the retina. Such optimisation is important as the deposit of excess electrical charge and energy can lead to detrimental medical side effects. Avoidance of such side effects is crucial to the realisation of the next generation of retinal implants

Non-viral delivery and optimized optogenetic stimulation of retinal ganglion cells led to behavioral restoration of vision

Stimulation of retinal neurons using optogenetics via use of chanelrhodopsin-2 (ChR2) has opened up a new direction for restoration of vision for treatment of retinitis pigmentosa (RP). Here, we report non-viral in-vivo electroporation of degenerated retina of adult RP-mice with ChR2-plasmids and subsequent in-vivo imaging of retina to confirm expression. Further, we demonstrate that in addition to efficient non-viral delivery of ChR2 to a specific retinal layer, threshold level of stimulation light needs to be delivered onto the retina for achieving successful behavioral outcome. Measurement of intensity of light reaching the retina of RP-mouse models along with geometrical optics simulation of light propagation in the eye is reported in order to determine the stimulating source position for optimal light delivery to the retina. The light-guided navigation of mice with ChR2 expressing retinal ganglion cells was found to be significantly improved over a long distance in correlation with stimulation intensity

New Technologies in Eye Surgery — A Challenge for Clinical, Therapeutic, and Eye Surgeons

Eye surgery is always progresses as the same way that the science advances. New emerging technologies such as bio-printing in 3D, developments and mathematical modeling in prototyping lab- on- a chip, visual implants, new biopolymers started to use in eye enucleation, detection of eye biomarkers at the cellular level, bio-sensors and new diagnostic tests should be considered to improve the quality of life of patients after surgery. This chapter provides a review of new and emerging technologies which are already working on global research centers. Emerging and converging technologies are terms used interchangeably to indicate the emergence and convergence of new technologies with demonstrated potential as disruptive technologies. Among them are: nanotechnology, biotechnology, information technology and communication, cognitive science, robotics, and artificial intelligence that have been launched as innovative products that promise to improve the quality of life and vision of patients with ocular compromised or low vision impairment. Some acronyms for these are: NBIC: Nanotechnology, Biotechnology, Information technology and Cognitive science. GNR: Genetics, Nanotechnology and Robotics. GRIN: Genetic, Robotic, Information, and Nanotechnology. BANG: Bits, Atoms, Neurons and Genes. Otherwise, to training ophthalmologist on news techniques, sophisticated simulation machines has been developing around the world

Novel graphene electrode for retinal implants : an in vivo biocompatibility study

Altres ajuts: this work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MICINN and the ICTS 'NANBIOSIS'.Evaluating biocompatibility is a core essential step to introducing a new material as a candidate for brain-machine interfaces. Foreign body reactions often result in glial scars that can impede the performance of the interface. Having a high conductivity and large electrochemical window, graphene is a candidate material for electrical stimulation with retinal prosthesis. In this study, non-functional devices consisting of chemical vapor deposition (CVD) graphene embedded onto polyimide/SU-8 substrates were fabricated for a biocompatibility study. The devices were implanted beneath the retina of blind P23H rats. Implants were monitored by optical coherence tomography (OCT) and eye fundus which indicated a high stability in vivo up to 3 months before histology studies were done. Microglial reconstruction through confocal imaging illustrates that the presence of graphene on polyimide reduced the number of microglial cells in the retina compared to polyimide alone, thereby indicating a high biocompatibility. This study highlights an interesting approach to assess material biocompatibility in a tissue model of central nervous system, the retina, which is easily accessed optically and surgically

Future of smart cardiovascular implants

Cardiovascular disease remains the leading cause of death in Western society. Recent technological advances have opened the opportunity of developing new and innovative smart stent devices that have advanced electrical properties that can improve diagnosis and even treatment of previously intractable conditions, such as central line access failure, atherosclerosis and reporting on vascular grafts for renal dialysis. Here we review the latest advances in the field of cardiovascular medical implants, providing a broad overview of the application of their use in the context of cardiovascular disease rather than an in-depth analysis of the current state of the art. We cover their powering, communication and the challenges faced in their fabrication. We focus specifically on those devices required to maintain vascular access such as ones used to treat arterial disease, a major source of heart attacks and strokes. We look forward to advances in these technologies in the future and their implementation to improve the human condition

An update on retinal prostheses

Retinal prostheses are designed to restore a basic sense of sight to people with profound vision loss. They require a relatively intact posterior visual pathway (optic nerve, lateral geniculate nucleus and visual cortex). Retinal implants are options for people with severe stages of retinal degenerative disease such as retinitis pigmentosa and age-related macular degeneration. There have now been three regulatory-approved retinal prostheses. Over five hundred patients have been implanted globally over the past 15 years. Devices generally provide an improved ability to localize high-contrast objects, navigate, and perform basic orientation tasks. Adverse events have included conjunctival erosion, retinal detachment, loss of light perception, and the need for revision surgery, but are rare. There are also specific device risks, including overstimulation (which could cause damage to the retina) or delamination of implanted components, but these are very unlikely. Current challenges include how to improve visual acuity, enlarge the field-of-view, and reduce a complex visual scene to its most salient components through image processing. This review encompasses the work of over 40 individual research groups who have built devices, developed stimulation strategies, or investigated the basic physiology underpinning retinal prostheses. Current technologies are summarized, along with future challenges that face the field

Characterization of Retinal Ganglion Cell Responses to Electrical Stimulation Using White Noise

Retinitis pigmentosa and age-related macular degeneration are two leading causes of degenerative blindness. While there is still not a definitive course of treatment for either of these diseases, there is currently the world over, many different treatment strategies being explored. Of these various strategies, one of the most successful has been retinal implants. Retinal implants are microelectrode or photodiode arrays, that are implanted in the eye of a patient, to electrically stimulate the degenerating retina. Clinical trials have shown that many patients implanted with such a device, are able to regain a certain degree of functional vision. However, while the results of these ongoing clinical trials have been promising, there are still many technical challenges that need to be overcome. One of the biggest challenges facing present implants is the inability to preferentially stimulate different retinal pathways. This is because retinal implants use large-amplitude current or voltage pulses. This in turn leads to the indiscriminate activation of multiple classes of retinal ganglion cells (RGCs), and therefore, an overall reduction in the restored visual acuity. To tackle this issue, we decided to explore a novel stimulus paradigm, in which we present to the retina, a stream of smaller-amplitude subthreshold voltage pulses. By then correlating the retinal spikes to the stimuli preceding them, we calculate temporal input filters for various classes of RGCs, using a technique called spike-triggered averaging (STA). In doing this, we found that ON and OFF RGCs have electrical filters, which are very distinct from each other. This finding creates the possibility for the selective activation of the retina through the use of STA-based waveforms. Finally, using statistical models, we verify how well these temporal filters can predict RGC responses to novel electrical stimuli. In a broad sense, our work represents the successful application of systems engineering tools to retinal prosthetics, in an attempt to answer one of the field’s most difficult questions, namely selective stimulation of the retina