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

Abstract

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

A thin-film optogenetic visual prosthesis

“…The FlexLED device described in this study has 8,192 pixels at up to 90 FPS at 8-bit global intensity levels. In comparison, no previous retinal stimulation device of which we are aware has achieved this pixel density 20,22 (1250 px/mm 2 ). This version of the FlexLED uses a passive driver, which limits frame rates when taken in conjunction with the minimum times required to reliably elicit optogenetically-evoked action potentials at safe light levels.…”

“…As expected, high contrast full-field visual stimuli from a computer monitor failed to evoke significant responses (Figure 4f-g). In contrast, full-field excitation using a 530 nm LED light elicited responses across the ECoG grid (Figure 4b-e), with a median of 16 channels (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) interquartile range) displaying significant responses (Figure 4b). This wide-spread activation of visual cortex is distinct from ECoG activation patterns generated by visual-evoked experiments (Figure 3d), and likely reflects activation of opsin-expressing RGCs distributed widely in the retina.…”

“…A promising electrical stimulation approach is to implant photovoltaic electrodes in the subretinal space that simulate bipolar cells, which normally receive direct input from photoreceptors 21 . The use of photovoltaic pixels elegantly eliminates the requirement for a through-sclera via, but implanting a device between the retina and choroid requires creating a retinal detachment, which limits the area of the visual field that can be safely accessed 22 . This approach is also more susceptible to the substantial structural reorganization present in most retinal degenerative diseases 23, 24 .…”

Structural changes in the retina after implantation of subretinal three-dimensional implants in mini pigs

“…They reported that such surgically induced retinal detachments resolved within 1 week, and that the retinal vasculature overlying the implant appeared normal on fluorescein angiography. Muqit et al (2020) also reported adverse effects of retinal detachment 6 weeks after surgery in one eye in a study evaluating surgical techniques for subretinal implantation of PRIMA microchips of two sizes in two different (feline and non-human primate) animal models. They indicated that retinal detachment is a recognized risk in vitreoretinal surgery, and that retinal detachment in similar subretinal surgery models occurs at a rate of 6-9% (Guthoff and Schrader, 2004;Muqit et al, 2020).…”

Prosthetic Visual Acuity with the PRIMA System in Patients with Atrophic Age-related Macular Degeneration at 4 years follow-up

“…The first clinical version of this implant (PRIMA, Pixium Vision, Paris, France) is 2 mm wide (corresponding to about 7° of the visual angle in a human eye) and 30 μm thick, containing 378 pixels of 100 µm in width ( Figure 1 ). Images captured by the camera mounted on agmented-reality glasses are processed and projected onto the retina and implant using near-infrared (880 nm) light to avoid photophobic and phototoxic effects of bright illumination 24 ( Figures 2 ). Current flowing through the retina between the active and return electrodes in front of the pixels stimulates the nearby inner retinal neurons 12 , which then pass the responses to ganglion cells, thereby harnessing residual retinal signal processing 9,13,14 .…”