Highest reported visual acuity after electronic retinal implantation

Cehajic-Kapetanovic, Jasmina; Troelenberg, Nicole; Edwards, Thomas; Ramsden, James D.; Stett, Alfred; Zrenner, Eberhart; MacLaren, Robert E.

doi:10.1111/aos.14443

Cited by 25 publications

(11 citation statements)

References 9 publications

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“…The PRIMA subretinal photovoltaic implants electrically stimulate the second-order retinal neurons, primarily the bipolar cells, to elicit visual perception, thereby enabling restoration of sight [15]. Subretinal photovoltaic pixels activated by light [14], [16] act as an optoelectronic substitute for the lost photoreceptors.…”

Section: Photovoltaic Subretinal Prosthesis Designmentioning

confidence: 99%

Pixel size limit of the PRIMA implants: from humans to rodents and back

et al. 2022

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Objective: Retinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic Age-related Macular Degeneration (AMD) using the PRIMA subretinal implant, a 2x2 mm array of 100µm-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which, with the current bipolar design, necessitates more intense stimulation. Approach: We examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, and using animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials measured in RCS rats with photovoltaic implants composed of 100µm and 75µm pixels were compared to clinical thresholds with 100µm pixels. Electrical stimulation model calibrated by the clinical and rodent data was used to predict the performance of the implant with smaller pixels. Main Results: PRIMA implants with 75µm bipolar pixels under the maximum safe near-infrared (880nm) illumination of 8mW/mm2 with 30% duty cycle (10ms pulses at 30Hz) should provide a similar perceptual brightness as with 100µm pixels under 3mW/mm2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75µm pixels is also similar under such illumination to that with 100µm pixels, increasing the maximum acuity from 20/420 to 20/315. Significance: Computational modelling defines the minimum pixel size of the PRIMA implants as 75µm. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75µm will nearly quadrupole the number of pixels, which should be very beneficial for patients. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.

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Section: Photovoltaic Subretinal Prosthesis Designmentioning

confidence: 99%

Pixel size limit of the PRIMA implants: from humans to rodents and back

et al. 2022

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“…Selective expression of opsins in ONbipolar cells is considered important to avoid interfering with the complex interconnected signaling pathways of the remaining neural retina. Making both ON-and OFF-bipolar cells respond to light in the same way could result in ambiguous signals, although cortical plasticity could play a role in filtering out the noise, as seen with subretinal implants (Cehajic-Kapetanovic et al, 2020a). A combination of effective AAV transduction and promoter for selective expression of opsins in ON-bipolar cells are therefore highly desirable features of optogenetic therapies.…”

Section: Transgene Considerationsmentioning

confidence: 99%

Optogenetic Gene Therapy for the Degenerate Retina: Recent Advances

et al. 2020

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The degeneration of light-detecting rod and cone photoreceptors in the human retina leads to severe visual impairment and ultimately legal blindness in millions of people worldwide. Multiple therapeutic options at different stages of degeneration are being explored but the majority of ongoing clinical trials involve adeno-associated viral (AAV) vector-based gene supplementation strategies for select forms of inherited retinal disease. Over 300 genes are associated with inherited retinal degenerations and only a small proportion of these will be suitable for gene replacement therapy. However, while the origins of disease may vary, there are considerable similarities in the physiological changes that occur in the retina. When early therapeutic intervention is not possible and patients suffer loss of photoreceptor cells but maintain remaining layers of cells in the neural retina, there is an opportunity for a universal gene therapy approach that can be applied regardless of the genetic origin of disease. Optogenetic therapy offers such a strategy by aiming to restore vision though the provision of light-sensitive molecules to surviving cell types of the retina that enable light perception through the residual neurons. Here we review the recent progress in attempts to restore visual function to the degenerate retina using optogenetic therapy. We focus on multiple pre-clinical models used in optogenetic strategies, discuss their strengths and limitations, and highlight considerations including vector and transgene designs that have advanced the field into two ongoing clinical trials.

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“…(13) This Conformité Européenne (CE)marked medical device has been used for several years in clinical studies (14,15) and in every day life. (16) Starting with microelectrode arrays (MEAs) for developing the sputter process and investigating the electrochemical and morphological properties, the process is implemented into the fabrication routine of the retinal prosthesis. This work describes the full experimental examination of the electrode material by means of cyclic voltammetry (CV), electrochemical (32) gray platinum, (33) impedance spectroscopy (EIS), and voltage transient measurements to estimate CIC.…”

Section: Introductionmentioning

confidence: 99%

Sputtered Iridium Oxide as Electrode Material for Subretinal Stimulation

Haas¹,

Rudorf²,

Becker³

et al. 2020

Sensors and Materials

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The efficiency and safety of neuronal stimulation with implants strongly depend on the electrode material. Microelectrodes composed of iridium oxide are becoming increasingly important as they exhibit excellent charge injection capacity (CIC) as well as charge storage capacity (CSC). We present the development of a robust process for the fabrication of sputtered iridium oxide films (SIROF). This process has been used for the "RETINA IMPLANT Alpha AMS" for several years of subretinal stimulation. In this paper, we describe the full experimental investigation of the electrode material. The electrochemical and morphological properties were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), voltage transient measurements, and focused ion beam-scanning electron microscopy (FIB-SEM). The implementation on the CMOS chip of the retinal prosthesis is presented. The deposition process window was investigated extensively. Major changes in process parameters lead to a difference in impedance of only 10% of the mean. Accelerated aging tests revealed a long-term stability of the electrodes of at least 10 years under conditions of use. The SIROF electrodes (diameter 30 µm) show low impedance (15.9 kΩ), excellent CSC (50.9 mC/cm 2), and high CIC (4.2 mC/cm 2). In summary, the robustness of the presented deposition process and the large process window enable the integration of high-quality SIROF microelectrodes in active implants and thus long-term stability in a wide range of safe electrical stimulation.

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Highest reported visual acuity after electronic retinal implantation

Cited by 25 publications

References 9 publications

Pixel size limit of the PRIMA implants: from humans to rodents and back

Pixel size limit of the PRIMA implants: from humans to rodents and back

Optogenetic Gene Therapy for the Degenerate Retina: Recent Advances

Sputtered Iridium Oxide as Electrode Material for Subretinal Stimulation

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