Photovoltaic retinal prosthesis restores high-resolution responses to single-pixel stimulation in blind retinas

Chenais, Naïg Aurélia Lüdmilla; Leccardi, Marta Jole Ildelfonsa Airaghi; Ghezzi, Diego

doi:10.1038/s43246-021-00133-2

Cited by 80 publications

(98 citation statements)

References 89 publications

(110 reference statements)

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“…Overall, the OPTO-EPIRET restores a theoretical visual angle of approximately 30° in a normal-sized human eye [14,33], resulting in safely navigating through an observed environment [12,34]. Nevertheless, the theoretical visual angle of VLARS or POLYRETINA comprises a larger visual angle, 37.6° and 43°, respectively [12,13,35].…”

Section: Discussionmentioning

confidence: 95%

“…This flexible, foldable and self-opening array with an hemispherical shape mounts 2215 photovoltaic stimulating pixels and can be implanted via a 6.5-mm large scleral incision. Just recently, the photovoltaic pixel number was enlarged to 10,498 pixels [35]. POLYRETINA overcomes most of the abovementioned challenges of OPTO-EPIRET, combines an increased size of the array and a huge number of stimulation pixels to increase both visual acuity and visual field size.…”

Section: Discussionmentioning

confidence: 99%

“…POLYRETINA overcomes most of the abovementioned challenges of OPTO-EPIRET, combines an increased size of the array and a huge number of stimulation pixels to increase both visual acuity and visual field size. But, so far, the auspicious in vitro and ex vivo results still have to be transferred and approved in an in vivo study [13,35].…”

Section: Discussionmentioning

confidence: 99%

“…When comparing the epiretinal with the subretinal photovoltaic approach, e.g., alpha AMS, PRIMA, the epiretinal one shows the advantage of good fixation of wide-field implants, whereas large subretinal approaches can encounter difficulties in the surgical subretinal placement and, hence, representing a higher risk of retinal detachment [8,10,35].…”

Section: Discussionmentioning

confidence: 99%

“…8). Thus, the OPTO-EPIRET covers approximately 64 mm 2 of the retinal surface, which represents a visual angle of approximately 30° [14,35]. In the middle and on each wing of the array, there are apertures to fixate the implant on the retinal surface with a retinal tack (Geuder AG, Heidelberg, Germany).…”

Section: Concept/fabricating Of the Structuresmentioning

confidence: 99%

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New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo

et al. 2021

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Background Retinal degenerative diseases, e.g., retinitis pigmentosa, cause a severe decline of the visual function up to blindness. Treatment still remains difficult; however, implantation of retinal prostheses can help restoring vision. In this study, the biocompatibility and surgical feasibility of a newly developed epiretinal stimulator (OPTO-EPIRET) was investigated. The previously developed implant was extended by an integrated circuit-based optical capturing, which will enable the immediate conversion of the visual field into stimulation patterns to stimulate retinal ganglion cells. Results The biocompatibility of the OPTO-EPIRET was investigated in vitro using the two different cell lines L-929 and R28. Direct and indirect contact were analyzed in terms of cell proliferation, cell viability, and gene expression. The surgical feasibility was initially tested by implanting the OPTO-EPIRET in cadaveric rabbit eyes. Afterwards, inactive devices were implanted in six rabbits for feasibility and biocompatibility testings in vivo. In follow-up controls (1–12 weeks post-surgery), the eyes were examined using fundoscopy and optical coherence tomography. After finalization, histological examination was performed to analyze the retinal structure. Regarding the in vitro biocompatibility, no significant influence on cell viability was detected (L929: < 1.3% dead cells; R-28: < 0.8% dead cells). The surgery, which comprised phacoemulsification, vitrectomy, and implantation of the OPTO-EPIRET through a 9–10 mm corneal incision, was successfully established. The implant was fixated with a retinal tack. Vitreal hemorrhage or retinal tearing occurred as main adverse effects. Transitional corneal edema caused difficulties in post-surgical imaging. Conclusions The OPTO-EPIRET stimulator showed a good biocompatibility profile in vitro. Furthermore, the implantation surgery was shown to be feasible. However, further design optimization steps are necessary to avoid intra- and postoperative complications. Overall, the OPTO-EPIRET will allow for a wide visual field and good visual acuity due to a high density of electrodes in the central retina.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Concept/fabricating Of the Structuresmentioning

confidence: 99%

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New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo

et al. 2021

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Engineering Materials for Neurotechnology

Ghezzi

2023

Adv Eng Mater

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A crucial issue for a neural interface is the chronic foreign body reaction (FBR) upon implantation. [1][2][3] Avoiding the FBR, or at least reducing its severity, is necessary to preserve the long-term functioning of neural interfaces. [4][5][6] Yet, this is still an open research question. The FBR is traditionally described as a passive barrier encapsulating the device, altering the neural interface, and impairing implant-to-cell communication. [2,7,8] Besides acting as a passive insulating barrier, soluble factors released during the inflammatory and fibrotic process can accelerate device degradation and electrode corrosion. [9] The FBR is inevitable whenever any material becomes in contact with body fluids. [10] In contrast, materials engineering and advanced fabrication processes can minimize its severity, for example, by improving the mechanical compliance of the implant, decreasing the device size, and reducing implantation and chronic trauma. [3] One of the most common limitations of neural interfaces is the mechanical mismatch between the stiff neural implant and the soft neural tissue. This mismatch intensifies the neural damage and FBR caused by insertion, compression, and motion. [11] The neural tissue is curved, soft, dynamic, and subject to deformations caused, for example, by blood pulsation, respiratory pressure, and natural body movements. [11,12] By contrast, most neural interfaces are static and struggle to conform to neural tissue in static and dynamic conditions. A large body of research in neural interfaces addresses this issue using flexible, conformable, or stretchable neural interfaces (Figure 1).Polyimide (PI), parylene-C, and SU-8 are widely used materials in flexible neural interfaces. [13][14][15][16][17][18][19][20][21][22] The advantages of these materials are their biochemical and thermal stability, and their compatibility with clean-room microfabrication processes. [23][24][25] However, they exhibit high Young's modulus (GPa range) and limited elastic deformation (<3%). [26] Ultra-thin neural interfaces made of these materials still reach low bending stiffness if sufficiently thin (<15 μm) despite the high Young's modulus. [27] They can conform to a cylindrical body such as a nerve or a smooth brain surface (Figure 1a), thus reducing the FBR severity. [23] Moreover, ultra-thin neural interfaces with a small cross-sectional area also can minimize tissue damage during penetration (Figure 1b). [22,24,28] Conformability to cylindrical or smooth surfaces is sufficient in rodents, but more is needed for large and complex surfaces with gyri, like in primates, where spherical conformability is required. Because of the limited elastic deformation, conformability to convoluted surfaces is difficult to achieve with these materials. Compliance with neural macro-and micro-movements is also reduced. [26] Elastomers exhibit a lower Young's modulus of at least three orders of magnitude (MPa range) and a much broader elastic regime under strain (>20%). Bending stiffness is influenced by both thick...

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Adaptive Interfacial Materials and Implants for Visual Restoration

Zhu,

Wang,

Zhao

et al. 2024

Adv Funct Materials

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Blindness is a globally critical challenge for public health, affecting more than 43 million individuals worldwide. Retinal degenerative diseases including retinitis pigmentosa and age‐related macular degeneration, involving degeneration of retinal pigment epithelium (RPE) and thereby the dysfunction of retina, are primary causes of blindness. For treating these retinal degeneration diseases, emerging interfacial materials and implants that can adapt to nerve tissues and stimulate residual neurons within the visual pathway have shown particular promise, where some issued products are approved for commercialization. Given the attractive opportunities and challenges of the interfacial materials and implants for visual restoration, a comprehensive and state‐of‐the‐art review that provides insight into their design principle and biological performances will be urgently required yet missing. In this review, the latest progress of these adaptive interfacial materials and implants for visual restoration will be summarized, and their challenges and opportunities for clinical use will be further discussed.

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Photovoltaic retinal prosthesis restores high-resolution responses to single-pixel stimulation in blind retinas

Cited by 80 publications

References 89 publications

New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo

New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo

Engineering Materials for Neurotechnology

Adaptive Interfacial Materials and Implants for Visual Restoration

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