Non-invasive patterned electrical neurostimulation of the retina

Project Information

Outer-Ret

Grant agreement ID: 101053186

DOI

10.3030/101053186

EC signature date 16 November 2022

Start date 1 April 2023

End date 31 March 2028

Funded under

• European Research Council (ERC)

Total cost

€ 2 500 000,00

EU contribution

€ 2 500 000,00

Coordinated by

TEL AVIV UNIVERSITY
Israel

Periodic Reporting for period 1 - Outer-Ret (Non-invasive patterned electrical neurostimulation of the retina)

Reporting period: 2023-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

Vision loss affects millions globally, significantly leading to dependence and reduced quality of life. Many forms of vision impairment, such as those resulting from retinal degeneration, have limited treatment options. Current approaches, like retinal implants, are invasive, expensive, and require complex surgical procedures with so far very modest impact on patient well-being. The ERC OuterRetina project aims to address these challenges by developing non-invasive, flexible bioelectronic interfaces for vision restoration.
The project’s core objective is to create soft, wearable electrode systems that can stimulate the retina and elicit visual perception. We further aim to study how to optimize the stimulation to achieve rudimentary level of visual acuity. The wearable systems we develop leverage advanced materials, innovative electrode designs, and real-time biofeedback technologies to create simple solution to generate artificial functional vision. By integrating expertise in neuroscience, materials science, and electrical engineering, the project aims to overcome the technical and biological barriers that have historically limited non-invasive retinal stimulation.
Expected impact includes improved quality of life for individuals with retinal diseases, reduced healthcare costs, and expanded access to artificial vision technologies globally. The project also aims to advance the broader field of bioelectronics, opening new pathways for treating neurological disorders through non-invasive stimulation methods.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Over the course of the project, significant progress was made across all planned activities, including the development of novel dry and printed electrode systems, the refinement of stimulation protocols, and the validation of wearable technologies in both preclinical and human studies.
• We developed and tested soft, flexible electrode arrays capable of simultaneous stimulation and recording from intact retina. Each probe features 32 active channels (50 µm diameter) arranged in a compact, stacking design, achieving a total thickness of just 120 µm. These probes demonstrated mechanical stability over months of testing. Ongoing work aims to scale this design to 128 channels, significantly enhancing resolution and functionality. Designed custom setups to study the spontaneous activity and evoked responses of both intact and ex vivo retina, enabled critical insights guiding the refinement of stimulation protocols. Moreover, advanced data processing pipelines are being developed to handle high-volume, multi-channel data efficiently, supporting future clinical applications.
• We developed and tested flexible, skin-conformal electrodes for non-invasive human retina stimulation, eliminating the need for traditional gel-based systems. Human studies with both commercial gel electrodes and custom soft skin electrodes demonstrated successful phosphene induction, confirming the feasibility of trans-ocular stimulation for vision restoration. Current work focuses on optimizing electrode designs and stimulation waveforms for precise, localized phosphene perception, supported by parallel ex vivo studies to map activation zones and optimize response dynamics.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The ERC Outer Retina project has produced several breakthroughs advancing the state of the art in soft bioelectronics:
• High-density bi-directional soft neural interface: We developed, for the first time, soft, multi-channel probes for simultaneous recording and stimulation of intact retinas. These probes represent a significant step forward in neural interfacing technology, enabling precise, high-resolution data collection in intact neural systems. With these electrodes we can, for the first time, perform bi-direction stimulation and recording from the intact retina, to better understand the response of the retina to electrical stimulation under relatively natural conditions.
• Non-Invasive visual perception: Initial human studies confirmed the feasibility of using wearable, non-invasive interfaces to elicit visual perception, addressing a critical gap in current retinal prosthetic technology. These systems provide a first critical step towards practical, patient-friendly approach to vision restoration, reducing the need for invasive approaches.
• Real-Time biofeedback: Facial EMG systems with machine learning and AI-driven biofeedback was demonstrated for real-time expression decoding. This technology is designed to assist the development of vision restoration by providing objective reporting of human physiology including affect, cognitive load and more. These strategies have far reaching implications far beyond the field of detecting visual perception, including neurorehabilitation and human-computer interaction.
• Knowledge transfer and clinical Impact: Protocols and systems developed in the project are already being used in clinical studies at two leading medical centers, supporting translational research in vision restoration and neurorehabilitation. These efforts have also generated industry interest in the realm of human machine interfacing, laying the groundwork for future commercialization.

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