PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.

PURPOSE: To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. METHODS: Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. RESULTS: The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. CONCLUSIONS: We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials.

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.

Behavioural responses to a photovoltaic subretinal prosthesis implanted in non-human primates.

Retinal dystrophies and age-related macular degeneration related to photoreceptor degeneration can cause blindness. In blind patients, although the electrical activation of the residual retinal circuit can provide useful artificial visual perception, the resolutions of current retinal prostheses have been limited either by large electrodes or small numbers of pixels. Here we report the evaluation, in three awake non-human primates, of a previously reported near-infrared-light-sensitive photovoltaic subretinal prosthesis. We show that multipixel stimulation of the prosthesis within radiation safety limits enabled eye tracking in the animals, that they responded to stimulations directed at the implant with repeated saccades and that the implant-induced responses were present two years after device implantation. Our findings pave the way for the clinical evaluation of the prosthesis in patients affected by dry atrophic age-related macular degeneration.

A test method for quantification of stimulus-induced depression effects on perceptual threshold in epiretinal prosthesis.

PURPOSE: As part of a clinical trial, an investigational epiretinal implant (IMI Intelligent Medical Implant) was implanted in a retinitis pigmentosa patient. The prosthesis was wirelessly controlled by a visual interface containing a microcamera, providing wireless data and energy transmission. Forty-nine (49) electrodes were used for pattern recognition. This study examined the changes of perceptual thresholds over time and its relation to long-term stimulation. The goal of the study was to introduce stimulus-related depression of perceptual threshold (StirDepth) measurements as a method to gain further insight into the safety profile of electrical stimulation. METHODS: The perceptual threshold was defined as the level of stimulation intensity at which a phosphene perception with a probability of 50% was detected using the Best-PEST method. StirDepth was measured by comparing the threshold changes immediately before and after a stimulation session of using three active electrodes and one passive electrode, which served as control. RESULTS: The initial threshold of the day remained stable over the observed period. In StirDepth measurement all thresholds raised significantly after the stimulation sessions. The threshold increase of the active electrodes never exceeded that of the inactive control electrode. CONCLUSIONS: StirDepth measurement is feasible in epiretinal implants. The prolonged stimulation raised no safety concerns in the patient. The threshold increase of both the active electrodes and the control electrode leads one to hypothesise that cognitive or neurophysiological effects are the cause rather than the desensitizing of the retinal network or incipient retinal damage.

Acute electrical stimulation of the human retina with an epiretinal electrode array.

PURPOSE: To determine the threshold charges needed for eliciting visual perceptions through acute electrical stimulation of the human retina in patients suffering from retinitis pigmentosa, using an epiretinal microelectrode array. METHODS: In a multicentre study, 20 patients (average age 55 years) with visual acuities ranging from 4/200 to no light perception were included. The stimulation procedure was performed during a pars plana vitrectomy, for a maximum of 45 min, by using a microcontact film with IrO(x) electrodes connected by cable to a current generator. After repeated stimulation and threshold charge determination, the microelectrode array was removed. RESULTS: Nineteen of 20 patients stated in the postoperative interviews that they experienced one or more visual perceptions with close time correlation to single stimulation events. Minimum threshold charges needed to generate visual perceptions could be measured and verified in 15 patients. The charge level ranged from 20 to 768 nC with single or multiple electrodes. One patient suffered a retinal detachment during the procedure; this patient's retina was successfully reattached. There were no further adverse reactions observed during the 3-month follow-up. CONCLUSION: Acute epiretinal stimulation of the human retina, using a microelectrode array, can elicit visual perceptions in blind patients with retinitis pigmentosa.

Progress in the development of vision prostheses.

Degenerative retinal diseases like retinitis pigmentosa and age-related macular degeneration are among the most common causes of blindness worldwide. Electronic visual prostheses represent a potential therapeutic option of increasing importance in otherwise incurably impaired patients. Based on extensive animal experiments, several devices are now being tested in clinical trials. According to the placement of the electrodes, possible stimulation sites are located subretinally, epiretinally, along the optic nerve or cortically. Anatomical, physiological and pathophysiological aspects must be considered in development and clinical application. To provide an appropriate retinal substitute, the optimal integration and adaptation of the prosthesis into the highly complex system of the visual pathway is important. This article aims to summarize the relevant studies and provides an overview of the current status of developments and challenges that still need to be mastered.

A method and technical equipment for an acute human trial to evaluate retinal implant technology.

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 microm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.