Biology subjects

Palanker, D.

Publications and source records attributed to Palanker, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Retinal Resistivity Mapped by Electrical Resistance Tomography

Retinal resistivity is a key parameter for modeling both the electric field in tissue and the resulting neural response - a crucial step in designing retinal prostheses, especially since both depend on resistivity nonlinearly. Previous studies using penetrating microelectrodes reported vastly different values, varying by as much as two orders of magnitude, likely due to parasitic capacitance in microelectrodes, compression of tissue and its rupture by the inserted probe, allowing the conductive medium to seep in and alter the measurement. To measure retinal resistivity without compression or rupture, we applied electrical resistance tomography using a planar multielectrode array with a 30 m pitch. Voltage waveforms generated in response to current injected from one electrode were measured on other electrodes in the array, at distances ranging from 30 to 600 m. Data from wild-type and degenerated rat retinas were analyzed using two methods: a commercial inversion software, Res2DInv, and a custom machine learning-based decoder, with healthy retina approximated as a 4-layer structure and degenerated retina - as a 3-layer one.

biophysics↗

bioRxiv2026

Biomimetic scaffolds mimic human subretinal debris for preclinical testing of prosthetic vision

Photovoltaic subretinal prostheses replace the lost photoreceptors in patients blinded by atrophic age-related macular degeneration (AMD) and provide central vision by electrically stimulating the inner retinal neurons. Subretinal debris in geographic atrophy separate the inner nuclear layer from the implant by tens of micrometers, increasing the stimulation threshold and reducing the pattern contrast. Absence of this separating layer in animal models diminishes the accuracy of preclinical testing of the next-generation implants, especially with smaller pixels. We developed three-dimensional biomimetic scaffolds nanoprinted onto photovoltaic arrays to provide a precisely controlled separation between the implants and target neurons in animal models of retinal degeneration. Gap sizes of the scaffolds were adjusted to meet the following requirements: they should allow light penetration to the implant, provide unobstructed flow of electric current, but preclude migration of cells into their 3-D structure. Gaps of 3 m were found to be optimal as they restricted cellular migration and maintained the inner nuclear layer above both planar and pillar electrode arrays. Scaffolds did not measurably alter the photovoltaic response and accurately reproduced the distance dependence of stimulation threshold. Following implantation, the initially fluid-filled intra-scaffold space was progressively filled by cellular matter matching the density of the subretinal debris. This transition is expected to increase resistivity of the scaffold to that of tissue, which was evidenced by concurrently improved grating acuity. These results establish a model of the controlled separation between the implant and the target neurons reproducing the features of subretinal debris in geographic atrophy of human patients, thereby providing a platform for accurate preclinical evaluation of the subretinal implants.

bioengineering↗

bioRxiv2026

Electrodeposited Biocompatible Coatings for 3D Electrodes on Retinal Prostheses

Photovoltaic subretinal prosthesis, PRIMA, provides central vision to patients blinded by age-related macular degeneration, with acuity matching the 100 m pixel size. Further miniaturization requires pillar electrodes to position the stimulating surfaces closer to the inner retinal neurons. While such structures can be electroplated in gold and coated on their tops with SIROF, the exposed gold sidewalls are not biocompatible. Sputtering or atomic layer deposition of protective coatings are unsuitable for selectively passivating the pillar structures without also coating the photosensitive regions and return electrodes of the implant. Here, we present a strategy for biocompatible coating of pillar sidewalls while preserving surrounding implant functionality. The approach combines non-critical photoresist lithography to protect planar return electrodes with electrodeposition of TiO2; or Pt onto gold pillar sidewalls. In-vivo studies demonstrated that both TiO2 and Pt coatings are biocompatible and prevent adverse reactions of the retinal tissue to gold. Since specific capacitance of electroplated TiO2 (25 F/cm2) is much lower than that of Pt (240 F/cm2), the former better limits the current from the side walls and ensures that charge injection occurs predominantly through the pillar tops coated with SIROF (~6 mF/cm2). Electrodeposition, combined with noncritical photolithography provides a scalable wafer-level solution for fabrication of biocompatible three-dimensional electro-neural interfaces, addressing a critical bottleneck in bioelectronics.

bioengineering↗

bioRxiv2026

Eye-tracked Maxwellian illumination system for power-efficient retinal stimulation

Augmented reality glasses typically have poor optical efficiency (<1%), which is detrimental for high power applications, such as prosthetic vision. Maxwellian view optics are a candidate for increasing efficiency, but suffer from a very limited exit pupil and thus field of view. Many approaches to extend the eyebox inherently decrease the optical power. We present a design that uses a high-density VCSEL array and eye tracking to create an extended eyebox without sacrificing the advantages of a Maxwellian view display. Our system achieves a 20 degree field of view, a resolution 48.8 LP/mm (10 m), and an end-to-end optical efficiency of 83%

bioengineering↗

bioRxiv2026

Titanium and platinum coatings reduce inflammation induced by gold on subretinal prosthesis

Subretinal photovoltaic implants provide central vision to patients blinded by atrophic age-related macular degeneration, with acuity limited by their 100-{micro}m pixels. Higher resolution requires smaller pixels incorporating three-dimensional electrodes, which can be fabricated by gold electroplating. However, the retinal response to exposed gold remains poorly characterized. Here, we evaluated gold biocompatibility on subretinal implants in Royal College of Surgeons rats and compared it with platinum- and titanium-coated surfaces. Although in-vivo optical coherence tomography revealed no overt structural disruption, gold implants induced cellular-scale anomalies, including abnormal morphology of rod bipolar cells, microglial accumulation near the implant, and increased cell death within days after implantation. These effects occurred across flat, pillar, and honeycomb geometries, indicating a material-rather than geometry-dependent response. By contrast, platinum- and titanium-coated implants showed substantially lower loss and morphological disruption of rod bipolar cells, together with markedly reduced microglial activation. These findings indicate that exposed gold surfaces can induce acute retinal inflammation and neuronal loss, whereas conformal platinum or titanium coatings substantially improve biocompatibility. Such coatings enable the development of three-dimensional subretinal prostheses with smaller pixels for improved visual resolution.

bioengineering↗

bioRxiv2026

Identification of Direct and Network-Mediated Activation of Retinal Ganglion Cells from Visually Evoked Potentials Using Machine Learning

ObjectiveTo preserve the encoding of visual information in prosthetic vision as close to natural as possible, subretinal photovoltaic implants, which replace the lost photoreceptors, strive to stimulate the second-order retinal neurons, the bipolar cells, while avoiding direct activation of the downstream retinal ganglion cells. To assess the range of such selective subretinal activation, we implanted the devices in rodent models of retinal degeneration and measured the stimulation thresholds based on the visually evoked potentials. After assessment of the bipolar cell-mediated thresholds, direct activation of retinal ganglion cells was measured following intraocular injection of synaptic blockers. Since these chemicals are toxic to the retina, this procedure can only be done once in each animal. ApproachWe developed a machine-learning model that identifies the stimulation pathway directly from the recorded visually evoked potentials, eliminating the need for synaptic blockers. The model was trained on recordings from rats implanted with PRIMA subretinal arrays and evaluated on two additional implant architectures, a second rat species, and a different anesthesia protocol. Main ResultsThe classifier achieved a balanced accuracy of 92% in cross-validation on the training data. Generalization to all unseen experimental conditions yielded an average balanced accuracy of 91%. Integrated Gradients analysis showed that combined bipolar and ganglion cell responses were driven by the early P1 component, while bipolar cell responses relied on later waveform components, consistent with thalamocortical processing dynamics. SignificanceThe described computational alternative to pharmacological blockers should improve the experimental throughput, allow multiple recordings over the lifetime of the same animal, and might be applicable to optimization of the stimulation settings in patients.

bioengineering↗

bioRxiv2025

Residual photoreceptors affect the response of a degenerate retina to electrical stimulation

Patients with age-related macular degeneration (AMD) implanted with the PRIMA photovoltaic subretinal prosthesis demonstrated letter acuity closely matching the devices 100 {micro}m pixel size. Improving visual acuity requires smaller pixels, which, in turn, require relaxation of electric field confinement to maintain effective stimulation of bipolar cells. Eliminating local return electrodes broadens the electric field but may inadvertently engage residual photoreceptors adjacent to the implant, thereby altering electrically evoked visual percepts. Here we quantify the contribution of residual photoreceptors to electrically evoked retinal responses across various implant configurations. Monopolar photovoltaic arrays with 20 {micro}m pixels and bipolar arrays with 100 {micro}m pixels were implanted subretinally in Long Evans rats, resulting in local degeneration of photoreceptors directly above the device. Responses were compared with those obtained in RCS rats, which lack functional photoreceptors. Implants were activated by patterns of 880 nm laser at pulse durations varying from 0.5 to 10 ms. Visually evoked potentials were measured in scotopic and photopic conditions, with and without the intravitreal application of mGluR6 agonist L-AP4 to block photoreceptor-driven ON pathways. Experimental thresholds were interpreted using a computational model of retinal network activation in distinct electric field geometries. In locally degenerate retina stimulated with monopolar arrays, blocking photoreceptor input yielded a rheobase (0.06 mW/mm{superscript 2}) and chronaxie ([~]3 ms) of the stimulation threshold, matching that measured in fully degenerate RCS retina, indicating direct activation of bipolar cells. In contrast, when photoreceptor input was intact, stimulation thresholds decreased significantly, and dark adaptation further modulated the threshold in a pulse-duration dependent manner. Bipolar arrays provided identical thresholds in locally degenerate and fully degenerate retina (0.2 mW/mm{superscript 2}) when stimulation was confined to the implant center; however, shifting stimulation to the implants edge lowered the thresholds, revealing a contribution from adjacent photoreceptors. These findings demonstrate that residual photoreceptors can substantially influence responses evoked by subretinal prostheses in a degenerate retina, with direct consequences for perceptual uniformity in patients, such as edge brightening. These results provide guidance for design of the next-generation higher-resolution implants, supporting the use of local return electrodes to maximize resolution while minimizing the effect of photoreceptors in clinical applications.

neuroscience↗

bioRxiv2025

Amorphous silicon resistors enable smaller pixels in photovoltaic retinal prosthesis

ObjectiveClinical trials of the photovoltaic subretinal prosthesis PRIMA demonstrated feasibility of prosthetic central vision with resolution matching its 100{micro}m pixel size. To improve prosthetic acuity further, pixel size should be decreased. However, there are multiple challenges, one of which is related to accommodating a compact shunt resistor within each pixel that discharges the electrodes between stimulation pulses and helps increase the contrast of the electric field pattern. Unfortunately, standard materials used in integrated circuit resistors do not match the resistivity required for small photovoltaic pixels. Therefore, we used a novel material - doped amorphous silicon (a-Si) and integrated it into photovoltaic arrays with pixel sizes down to 20{micro}m. ApproachTo fit within a few {micro}m2 area of the pixels and provide resistance in the M{Omega} range, the material should have sheet resistance of a few hundred k{Omega}/sq, which translates to resistivity of a few {Omega}*cm. The a-Si layer was deposited by low-pressure chemical vapor deposition (LPCVD) and its resistivity was adjusted by PH3 doping before encapsulating the resistors between SiO2 and SiC for stability in-vivo. Main ResultsHigh-resolution retinal implants with integrated shunt resistors were fabricated with values ranging from 0.75 to 4 M{Omega} on top of the photovoltaic pixels of 55, 40, 30 and 20 {micro}m in size. Photoresponsivity with all pixel sizes was approximately 0.53 A/W, as high as in the arrays with no shunt resistor. The shunts shortened electrodes discharge time, with the average electric potential in electrolyte decreasing by only 21-31% when repetition rate increased from 2 to 30 Hz, as opposed to a 54-55% decrease without a shunt. Similarly, contrast of a Landolt C pattern increased from 16-22% with no shunt to 22-34% with a shunt. Further improvement in contrast is expected with pillar electrodes and local returns within each pixel. SignificanceMiniature shunt resistors in a MOhm range can be fabricated from doped a-Si in a process compatible with manufacturing of photovoltaic arrays. The shunt resistors improved current injection and spatial contrast at video frame rates, without compromising the photoresponsivity. These advances are critical for scaling pixel sizes below 100 {micro}m to improve visual acuity of prosthetic vision.

neuroscience↗

bioRxiv2025

Label-free Imaging of the Reversible Rhodopsin Dynamics in a Living Eye

Vision begins with photoisomerization of a retinal, triggering further conformational changes, followed by a phototransduction cascade in photoreceptors. Microelectrode recordings revealed an early receptor potential (ERP) signal accompanying these conformational transitions. Such techniques are invasive, obscured by multiple electrical processes in the retina, and in rods, they are limited to the contribution of a small fraction of rhodopsin embedded in the nascent disc membrane and plasma membrane. Recent advances in phase-sensitive OCT (Optoretinography, ORG) enable detection of nanoscale deformations of retinal cells associated with physiological processes. However, in previous ORG studies, focused primarily on cones, cell deformation related to ERP was largely obscured by osmotic swelling and long stimuli did not resolve the isomerization dynamics of photopigments. Here, we demonstrate a very robust electromechanical signature of photoisomerization in rods at microsecond-scale temporal resolution. Green flash induces sub-millisecond-fast contraction of the outer segments by hundreds of nanometers, while subsequent UV flash reverts the activated molecules, producing an opposite response of a similar magnitude. This approach surpasses the sensitivity of electrical methods by integrating the response across all the discs in rod outer segments. Noninvasive and label-free imaging of the rhodopsin dynamics in a living eye opens the door to fundamental studies of visual transduction and to differential diagnosis of the photoreceptors dysfunction.

bioengineering↗

bioRxiv2025

Maximizing the fidelity of a photovoltaic subretinal prosthesis for human patients

ObjectivePRIMA subretinal implants provide prosthetic vision to patients blinded by age-related macular degeneration, with acuity closely matching the sampling limit of the pixel pitch: a single 100{micro}m pixel per line of a letter corresponds to 20/420 acuity. Decreasing the pixel size in the same flat geometry is difficult due to the constrained electric field, especially considering a 40{micro}m thick debris layer separating the implant from the target neurons. Here we optimize the electrode design to help overcome such limitations. ApproachAn end-to-end modeling pipeline combines the retinal photovoltaic implant simulator (RPSim) based on the Xyce circuit simulator with an interface to COMSOL Multiphysics for electric field modelling. It was used to generate and characterize implants in an open-loop sampling-based optimization. Implant performance was evaluated with respect to voltage drop across bipolar cells (representing the stimulation strength), pattern contrast, and neural selectivity. Main ResultsThe highest selectivity in stimulation of bipolar cells was achieved with arrays having active electrodes on pillars and return electrodes connected in a mesh surrounding the photovoltaic pixels in the array. Such a design, even with pixels down to 20{micro}m, provides stimulation strength exceeding, and contrast similar to that of flat 100{micro}m PRIMA pixels. SignificanceUsing a novel 3-D electrode design, the pitch of the photovoltaic array can be decreased to 20{micro}m, while providing performance that exceeds the flat 100{micro}m PRIMA pixels. In humans, 20{micro}m resolution on the retina corresponds to a visual acuity of 20/80 - a five times improvement compared to the current clinical device.

bioengineering↗

bioRxiv2024

Retinal thermometry in-vivo using phase-sensitive optical coherence tomography

Controlling the tissue temperature rise during retinal laser therapy is essential for predictable outcomes, especially at non-damaging settings. We demonstrate a method for determining the temperature rise in the retina using phase-resolved optical coherence tomography (pOCT) in vivo. Measurements based on the thermally induced optical path length changes ({Delta}OPL) in the retina during a 10-ms laser pulse allow detection of the temperature rise with a precision less than 1 {degrees}C, which is sufficient for calibration of the laser power for patient-specific non-damaging therapy. We observed a significant difference in confinement of the retinal deformations between the normal and the degenerate retina: in wild-type rats, thermal deformations are localized between the retinal pigment epithelium (RPE) and the photoreceptors inner segments (IS), as opposed to a deep penetration of the deformations into the inner retinal layers in the degenerate retina. This implies the presence of a structural component within healthy photoreceptors that dampens the tissue expansion induced by the laser heating of the RPE and pigmented choroid. We hypothesize that the thin and soft cilium connecting the inner and outer segments (IS, OS) of photoreceptors may absorb the deformations of the OS and thereby preclude the tissue expansion further inward. Striking difference in the confinement of the retinal deformations induced by a laser pulse in healthy and degenerate retina may be used as a biomechanical diagnostic tool for the characterization of photoreceptor degeneration.

bioengineering↗

bioRxiv2024

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

ObjectiveModeling of Multi-Electrode Arrays used in neural stimulation can be computationally challenging since it may involve incredibly dense circuits with millions of intercon-nected 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 with minimal error by using a sparse plus low-rank approximation of the resistance matrix. MethodsWe prove that thresholding of the resistance matrix elements enables its sparsification with minimized error. This is accomplished with a sorting algorithm, implying efficient O (N log (N)) complexity. The eigenvalue-based low-rank compensation then helps achieve greater accuracy without significantly increasing the problem size. Results: Utilizing these matrix techniques, we reduced the computation time of the simulation of multi-electrode arrays by about 10-fold, while maintaining an average error of less than 0.3% in the current injected from each electrode. We also show a case where acceleration reaches at least 133 times with additional error in the range of 4%, demonstrating the ability of this algorithm to perform under extreme conditions. ConclusionCritical improvements in the efficiency of simulations of the electric field generated by multi-electrode arrays presented here enable the computational modeling of high-fidelity neural implants with thousands of pixels, previously impossible. Significance: Computational acceleration techniques described in this manuscript were developed for simulation of high-resolution photovoltaic retinal prostheses, but they are also immediately applicable to any circuits involving dense connections between nodes, and, with modifications, more generally to any systems involving non-sparse matrices.

bioengineering↗

bioRxiv2024

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 100m 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. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22m pixels increased the grating acuity from the 100m capability of PRIMA implants to 28m, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.

neuroscience↗

bioRxiv2023

Three-dimensional electro-neural interfaces electroplated on subretinal prostheses

ObjectiveHigh-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. We investigate 3-dimensional structures on top of the photovoltaic arrays for enhanced penetration of electric field to permit higher-resolution implants. ApproachWe developed 3D COMSOL models of subretinal photovoltaic arrays that accurately quantify the device electrodynamics during stimulation and verified it experimentally through comparison with the standard (flat) photovoltaic arrays. The models were then applied to optimise the design of 3D electrode structures (pillars and honeycombs) to efficiently stimulate the inner retinal neurons. The return electrodes elevated on top of the honeycomb walls surrounding each pixel orient the electric field inside the cavities vertically, aligning it with bipolar cells for optimal stimulation. Alternatively, pillars elevate the active electrode into the inner nuclear layer, improving proximity to the target neurons. Modelling results informed a microfabrication process of electroplating the 3D electrode structures on top of the existing flat subretinal prosthesis. Main resultsSimulations demonstrate that despite the conductive sidewalls of the 3D electrodes being exposed to electrolyte, most of the charge flows via the high-capacitance sputtered Iridium Oxide film that caps the top of the 3D structures. The 24 {micro}m height of the electroplated honeycomb structures was optimised for integration with the inner nuclear layer cells in rat retina, while 35 {micro}m height of the pillars was optimized for penetrating the debris layer in human patients. Release from the wafer and implantation of the 3D arrays demonstrated that they are mechanically robust to withstand the associated forces. Histology demonstrated successful integration of the 3D structures with the rat retina in-vivo. SignificanceElectroplated 3D honeycomb structures produce a vertically oriented electric field that offers low stimulation threshold, high spatial resolution and high contrast for the retinal implants with pixel sizes down to 20{micro}m in width. Pillar electrodes offer an alternative configuration for extending the stimulation past the debris layers. Electroplating of the 3D structures is compatible with the fabrication process of the flat photovoltaic arrays, thereby enabling much more efficient stimulation than in their original flat configuration.

neuroscience↗

bioRxiv2023

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 m pixel size. Since decreasing the pixel size below 75 m 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. With both flat and 3D implants, VEP amplitude decreased after the day of implantation by more than 3-fold, and gradually recovered over about 3 months. With 25 m high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the second-order neurons. Retinal thickness and full-field stimulation threshold with 40 m-wide honeycomb pixels were comparable to those with planar devices - 0.05 mW/mm2 with 10ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 m-wide wells, and stimulation threshold increased over 5 months, before stabilizing at about 0.08 mW/mm2. Such threshold is significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.

neuroscience↗

bioRxiv2022

Cellular integration with a subretinal honeycomb-shaped prosthesis

In patients blinded by geographic atrophy, subretinal photovoltaic implant with 100{micro}m pixels provided visual acuity closely matching the pixel pitch. However, such flat bipolar pixels cannot be scaled below 75{micro}m, limiting the attainable visual acuity. This limitation can be overcome by shaping the electric field with 3-dimensional electrodes. In particular, elevating the return electrode on top of honeycomb-shaped vertical walls surrounding each pixel extends the electric field vertically and decouples its penetration into tissue from the pixel width. This approach relies on migration of the retinal cells into the honeycomb wells. Here, we demonstrate that the majority of the inner retinal neurons migrate into 25{micro}m deep wells, leaving the third-order neurons, such as amacrine and ganglion cells, outside. This is important for selective stimulation of the second-order neurons to preserve the retinal signal processing in prosthetic vision. Comparable glial response to that with flat implants suggests that migration and separation of the retinal cells by the walls does not cause additional stress. Furthermore, retinal migration into the honeycombs does not negatively affect its electrical excitability.

neuroscience↗

bioRxiv2022

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

ObjectiveRetinal 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 100m-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which necessitates more intense stimulation. ApproachHere, we examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, as well as using a preclinical animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials were measured in RCS rats with photovoltaic implants of 100 and 75m pixels and compared to clinical thresholds with 100 m pixels. Electrical stimulation model calibrated by these clinical and rodent data was used to predict the performance of the implant with smaller pixels. Main ResultsWe found that PRIMA implants with 75m pixels under the maximum safe near-infrared (880nm) illumination of 8 mW/mm2 with 30% duty cycle (10ms pulses at 30Hz) should provide a similar perceptual brightness as with 100 m pixels under 3 mW/mm2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75m pixels is also similar under such illumination to that with 100m pixels in clinical settings, increasing the maximum acuity from 20/420 to 20/300. SignificanceComputational model of the photovoltaic subretinal prosthesis defines the minimum pixel size of the PRIMA implants as 75m. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75m will nearly quadrupole the number of pixels and thereby should significantly improve the visual performance. 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.

bioengineering↗

bioRxiv2022

Photovoltaic Implant Simulator Reveals the Resolution Limits in Subretinal Prosthesis

ObjectiveThe photovoltaic subretinal prosthesis, PRIMA, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100 {micro}m 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, giving low contrast stimulation patterns. We study approaches to shaping the electric field in the retina for prosthetic vision with higher resolution and improved contrast. ApproachWe present a new computational framework, RPSim, that efficiently computes the electric field in the retina generated by a photovoltaic implant with thousands of electrodes. Leveraging the PRIMA clinical results as a benchmark, we use RPSim to predict the stimulus strength and contrast of the electric field in the retina with various pixel designs and stimulation patterns. Main resultsWe demonstrate that by utilizing monopolar pixels as both, anodes and cathodes to suppress crosstalk, most patients may achieve resolution no worse than 48 {micro}m. Closer proximity between the electrodes and the INL, achieved with pillar electrodes, enhances the stimulus strength and contrast and may enable 24 {micro}m resolution with 20 {micro}m pixels, at least in some patients. SignificanceA resolution of 24 {micro}m on the retina corresponds to a visual acuity of 20/100, which is over 4 times higher than the current best prosthetic acuity of 20/438, promising a significant improvement of central vision for many AMD patients.

bioengineering↗