Accelerated Simulation of Multi-Electrode Arrays Using Sparse and Low-Rank Matrix Techniques.

Modeling of Multi-Electrode Arrays used in neural stimulation can be computationally challenging since it may involve incredibly dense circuits with millions of interconnected resistors, representing current pathways in an electrolyte (resistance matrix), coupled to nonlinear circuits of the stimulating pixels themselves. Here, we present a method for accelerating the modeling of such circuits while minimizing the error of a simplified simulation by using a sparse plus low-rank approximation of the resistance matrix. Specifically, we prove that thresholding of the resistance matrix elements enables its sparsification with minimized error.

Light-evoked deformations in rod photoreceptors, pigment epithelium and subretinal space revealed by prolonged and multilayered optoretinography.

Phototransduction involves changes in concentration of ions and other solutes within photoreceptors and in subretinal space, which affect osmotic pressure and the associated water flow. Corresponding expansion and contraction of cellular layers can be imaged using optoretinography (ORG), based on phase-resolved optical coherence tomography (OCT). Until now, ORG could reliably detect only photoisomerization and phototransduction in photoreceptors, primarily in cones under bright stimuli.

3D electronic implants in subretinal space: Long-term follow-up in rodents.

Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 μm pixel size. Since scaling the pixels below 75 μm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime - up to 32-36 weeks post-implantation in aged rats.

Prosthetic Visual Acuity with the PRIMA Subretinal Microchip in Patients with Atrophic Age-Related Macular Degeneration at 4 Years Follow-up.

Objective: To assess the efficacy and safety of the PRIMA neurostimulation system with a subretinal microchip for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months postimplantation.

Design: Feasibility clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.govNCT03333954).

Enhancing Prosthetic Vision by Upgrade of a Subretinal Photovoltaic Implant in situ.

In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100μm pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo.

Three-dimensional electro-neural interfaces electroplated on subretinal prostheses.

Retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables increasing prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue.

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

Objective: To assess the efficacy and safety of the PRIMA subretinal neurostimulation system 48-months post-implantation for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months post-implantation.

Design: First-in-human clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.gov NCT03333954).

Three-dimensional electro-neural interfaces electroplated on subretinal prostheses.

Objective: High-resolution retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables an increase in prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue.

Cellular migration into a subretinal honeycomb-shaped prosthesis for high-resolution prosthetic vision.

In patients blinded by geographic atrophy, a subretinal photovoltaic implant with 100 µm pixels provided visual acuity closely matching the pixel pitch. However, such flat bipolar pixels cannot be scaled below 75 µm, limiting the attainable visual acuity. This limitation can be overcome by shaping the electric field with 3-dimensional (3-D) electrodes.

3D electronic implants in subretinal space: long-term follow-up in rodents.

Photovoltaic subretinal prosthesis (PRIMA) enables restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution limited by the 100 μm pixel size. Since decreasing the pixel size below 75 μm in the current bipolar geometry is impossible, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime - up to 9 months post-implantation in aged rats.

Electronic Retinal Prostheses.

Retinal prostheses are a promising means for restoring sight to patients blinded by photoreceptor atrophy. They introduce visual information by electrical stimulation of the surviving inner retinal neurons. Subretinal implants target the graded-response secondary neurons, primarily the bipolar cells, which then transfer the information to the ganglion cells via the retinal neural network.

Interferometric thermometry of ocular tissues for retinal laser therapy.

Controlling the tissue temperature rise during retinal laser therapy is highly desirable for predictable and reproducible outcomes of the procedure, especially with non-damaging settings. In this work, we demonstrate a method for determining the optical absorption, the thermal conductivity, and the thermal expansion coefficients of RPE and choroid using phase-resolved optical coherence tomography (pOCT). These parameters are extracted from the measured changes in the optical path length (Δ) using an axisymmetric thermo-mechanical model.

Electronic photoreceptors enable prosthetic visual acuity matching the natural resolution in rats.

Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal crosstalk from the neighboring electrodes. Local return electrodes within each pixel limit the crosstalk, but they over-constrain the electric field, thus precluding the efficient stimulation with subretinal pixels smaller than 55 μm. Here we demonstrate a high-resolution prosthetic vision based on a novel design of a photovoltaic array, where field confinement is achieved dynamically, leveraging the adjustable conductivity of the diodes under forward bias to turn the designated pixels into transient returns.

Photovoltaic implant simulator reveals resolution limits in subretinal prosthesis.

PRIMA, the photovoltaic subretinal prosthesis, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100m pixel size of the implant. Improvement in resolution requires smaller pixels, but the resultant electric field may not provide sufficient stimulation strength in the inner nuclear layer (INL) or may lead to excessive crosstalk between neighboring electrodes, resulting in low contrast stimulation patterns. We study the approaches to electric field shaping in the retina for prosthetic vision with higher resolution and improved contrast.

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

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 using the PRIMA subretinal implant, a 2 × 2 mm array of 100m-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.

Interferometric imaging of thermal expansion for temperature control in retinal laser therapy.

Precise control of the temperature rise is a prerequisite for proper photothermal therapy. In retinal laser therapy, the heat deposition is primarily governed by the melanin concentration, which can significantly vary across the retina and from patient to patient. In this work, we present a method for determining the optical and thermal properties of layered materials, directly applicable to the retina, using low-energy laser heating and phase-resolved optical coherence tomography (pOCT).

A Smartphone-Based Near-Vision Testing System: Design, Accuracy, and Reproducibility Compared With Standard Clinical Measures.

Background And Objective: Ophthalmologic telemedicine has emerged during the COVID-19 pandemic. The objective of this study is to assess the accuracy and reproducibility of a smartphone-based home vision monitoring system (Sightbook) and to compare it with existing clinical standards.

Patients And Methods: Near Snellen visual acuity (VA) was measured with Sightbook and compared with conventional measurements for distance and near VA at an academic medical center ophthalmology clinic in 200 patients with a variety of different specified preexisting ocular conditions.

Simultaneous perception of prosthetic and natural vision in AMD patients.

Loss of photoreceptors in atrophic age-related macular degeneration (AMD) results in severe visual impairment. Since the low-resolution peripheral vision is retained in such conditions, restoration of central vision should not jeopardize the surrounding healthy retina and allow for simultaneous use of the natural and prosthetic sight. This interim report, prespecified in the study protocol, presents the first clinical results with a photovoltaic substitute of the photoreceptors providing simultaneous use of the central prosthetic and peripheral natural vision in atrophic AMD.

Vertical-junction photodiodes for smaller pixels in retinal prostheses.

To restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100m pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient.

FUNCTIONAL AND STRUCTURAL EFFECTS OF NONDAMAGING RETINAL LASER THERAPY FOR MACULAR TELANGIECTASIA TYPE 2: A Randomized Sham-Controlled Clinical Trial.

Purpose: Macular telangiectasia (MacTel) Type 2 is a progressing neurovascular disease of the macula, currently lacking effective treatment. This study assessed the effect of nondamaging retinal laser therapy (NRT) compared with sham.

Methods: Twelve MacTel patients were enrolled in this double-masked, controlled, randomized clinical trial.

Decoding network-mediated retinal response to electrical stimulation: implications for fidelity of prosthetic vision.

. Patients with photovoltaic subretinal implant PRIMA demonstrated letter acuity ∼0.1 logMAR worse than sampling limit for 100m pixels (1.

Mechanisms of Light-Induced Deformations in Photoreceptors.

Biological cells deform on a nanometer scale when their transmembrane voltage changes, an effect that has been visualized during the action potential using quantitative phase imaging. Similar changes in the optical path length have been observed in photoreceptor outer segments after a flash stimulus via phase-resolved optical coherence tomography. These optoretinograms reveal a fast, millisecond-scale contraction of the outer segments by tens of nanometers, followed by a slow (hundreds of milliseconds) elongation reaching hundreds of nanometers.

The optoretinogram reveals the primary steps of phototransduction in the living human eye.

Photoreceptors initiate vision by converting photons to electrical activity. The onset of the phototransduction cascade is marked by the isomerization of photopigments upon light capture. We revealed that the onset of phototransduction is accompanied by a rapid (<5 ms), nanometer-scale electromechanical deformation in individual human cone photoreceptors.