Daniel Palanker

Stanford University | SU · Department of Ophthalmology

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...

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...

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). U...

In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100 μm 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,...

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 atr...

Objective. High-resolution retinal prosthetics offer partial sight restoration to patients blinded by retinal degenerative diseases through electrical stimulation of remaining neurons. Decreasing pixel size enables increasing prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar...

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 p...

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...

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) electro...

Photovoltaic subretinal prosthesis (PRIMA) enables restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution limited by the 100 um pixel size. Since decreasing the pixel size below 75 um in the current bipolar geometry is impossible, we explore the possibility of using smaller pixels based on a novel...

The femtosecond laser has become an integral part of cataract and refractive surgery. In this chapter the basic physical principles are described and different laser system presented.KeywordsFemtosecond laserLaser system

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 gangl...

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

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...

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...

Objective: PRIMA, the photovoltaic subretinal prosthesis, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100μm pixel size of the implant. Improvement in resolution requires smaller pixels, but the resultant electric field may not provide sufficient stimulation...

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 prosthet...

Objective The photovoltaic subretinal prosthesis, PRIMA, restores central vision in patients blinded by atrophic age-related macular degeneration (AMD), with a resolution closely matching the 100 µm pixel size of the implant. Improvement in resolution requires smaller pixels, but the resultant electric field may not provide sufficient stimulation s...

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 2×2 mm array of 100μm-wide photovoltaic pixels, have demonstrated a prosthetic...

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 mea...

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...

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...

Retinal degenerative diseases lead to loss of photoreceptors, while neurons in the inner retinal layers are largely preserved. Retinal prostheses seek to restore sight by reintroducing visual information via electrical stimulation of the surviving neurons in the retina. Photovoltaic retinal prostheses consist of silicon photodiodes in each pixel of...

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...

Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal cross-talk from neighboring electrodes. Local return electrodes within each pixel can limit the crosstalk, but they over-constrain the electric field, thus precluding the efficient stimulation with subretinal pixels smaller than 50...

Objective.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 100 μm pixels, and hence...

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. We report the...

Current steering on a multi-electrode array is commonly used to shape the electric field in the neural tissue in order to improve selectivity and efficacy of stimulation. Previously, simulations of the electric field in tissue required separate computation for each set of the stimulation parameters. Not only is this approach to modeling time-consum...

Objective 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 of this technology demonstrated shaped vision with prosthetic acuity closely matching the sampling...

Objective: Patients with photovoltaic subretinal implant PRIMA demonstrated letter acuity ~0.1 logMAR worse than sampling limit for 100μm pixels (1.3 logMAR) and performed slower than healthy subjects tested with equivalently pixelated images. To explore the underlying differences between natural and prosthetic vision, we compare the fidelity of r...

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....

Current retinal prostheses provide electrical stimulation without feedback from the stimulated neurons. Incorporation of multichannel recording electronics would typically require trans-scleral cables for power supply and data transmission. In this work, we explore a wireless, optoelectronic, miniature, modular, and distributed electro-neural inter...

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 photorec...

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. For...

Objective Patients with the photovoltaic subretinal implant PRIMA demonstrated letter acuity by ~0.1 logMAR worse than the sampling limit for 100μm pixels (1.3 logMAR) and performed slower than healthy subjects, which exceeded the sampling limit at equivalently pixelated images by ~0.2 logMAR. To explore the underlying differences between the natur...

Objective: To restore sight in atrophic age-related macular degeneration, the lost photoreceptors can be replaced with electronic implants, which replicate their two major functions: (1) converting light into an electric signal, and (2) transferring visual information to the secondary neurons in the retinal neural network—the bipolar cells (BC). W...

Neurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear. Here we report full-field imaging of cellular defor...

Objective: Avoidance of the adverse electrochemical reactions at the electrode-electrolyte interface defines the voltage safety window and limits the charge injection capacity (CIC) of an electrode material. For an electrode that is not ideally capacitive, the CIC depends on the waveform of the stimulus. We study the modeling of the charge injecti...

Objective Loss of photoreceptors in atrophic age-related macular degeneration results in severe visual impairment, although some peripheral vision is retained. To restore central vision without compromising the residual peripheral field, we developed a wireless photovoltaic retinal implant (PRIMA), in which pixels convert images projected from vide...

Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo have restricted studies of their physiology to in-vitro preparations and animal models. Physiological changes underlying neural signaling are mediated by changes in electrical potential that alters the surface tension of the cell membrane. In addition, physiol...

Objective Avoidance of the adverse electrochemical reactions at the electrode-electrolyte interface defines the voltage safety window and limits the charge injection capacity (CIC) of an electrode material. For an electrode that is not ideally capacitive, the CIC depends on the waveform of the stimulus. We study the modeling of the charge injection...

Photoreceptors in the retina convert light into electrical signals through a phototransduction cycle that consists of multiple electrical and biochemical events. Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in the cone photoreceptor outer segments after a light stimulus (optoretinogram) rev...

The distribution of electric current on an electrode surface in an electrolyte varies with time due to charge accumulation at a capacitive interface, as well as due to the electrode kinetics and concentration polarization in the medium. Initially, the potential at the electrode-electrolyte interface is uniform, resulting in a nonuniform current dis...

Synopsis Electronic retinal prostheses are a promising means for restoring sight to patients blinded by the atrophy of photoreceptors in retinal degeneration. They introduce information into the visual system by electrical stimulation of either the second-order neurons, called bipolar cells, or the spiking output retinal layer – the ganglion cells....

Vision loss in age-related macular degeneration (AMD) stems from disruption of photoreceptor cells in the macula, the central retinal area required for high-acuity vision. Mice and rats have no macula, but surgical insertion of a subretinal implant can induce localized photoreceptor degeneration due to chronic separation from retinal pigment epithe...

Outer retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are among the leading causes of incurable blindness in the Western world [1]. Retinal prostheses have been shown to restore some useful vision by electrically stimulating the remaining retinal neurons [2]. In contrast to inherited reti...

Photovoltaic subretinal prosthesis is designed for restoration of central vision in patients with age-related macular degeneration (AMD). We investigated the utility of prosthetic central vision for complex visual tasks using augmented-reality (AR) glasses simulating reduced acuity, contrast, and visual field. AR glasses with blocked central 20° of...

Neurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear. We report full-field imaging of cellular deformatio...

Purpose: We investigated the effects of various retinal laser therapies on preservation of the photoreceptors in an animal model of Mer tyrosine kinase receptor (MERTK)-related retinitis pigmentosa (RP). These modalities included photocoagulation with various pattern densities, selective RPE therapy (SRT), and nondamaging retinal therapy (NRT). M...

Purpose: To evaluate and compare the effect of lacrimal nerve stimulation (LNS) and anterior ethmoid nerve stimulation (AENS) on aqueous tear secretion, and tissue condition following chronic implantation. Methods: A neurostimulator was implanted in rabbits adjacent to the (1) lacrimal nerve, and (2) anterior ethmoid nerve. Tear volume was measu...

Objective: Retinal prostheses aim to restore sight by electrically stimulating the surviving retinal neurons. In clinical trials of the current retinal implants, prosthetic visual acuity does not exceed 20/550. However, to provide meaningful restoration of central vision in patients blinded by age-related macular degeneration (AMD), prosthetic acu...

High-resolution visual prostheses require small, densely packed pixels, but limited penetration depth of the electric field formed by a planar electrode array constrains such miniaturization. We present a novel honeycomb configuration of an electrode array with vertically separated active and return electrodes designed to leverage migration of reti...

Purpose: Photovoltaic subretinal prosthesis is designed for restoration of central vision in patients with age-related macular degeneration (AMD). We investigated the utility of prosthetic central vision for complex visual tasks using augmented-reality (AR) glasses simulating reduced acuity, contrast and visual field. Methods: AR glasses with block...

The distribution of electric current on an electrode surface in electrolyte varies with time due to charge accumulation at a capacitive interface, as well as due to electrode kinetics and concentration polarization in the medium. Initially, the potential at the electrode-electrolyte interface is uniform, resulting in a non-uniform current distribut...

Purpose: To demonstrate survival and integration of mature photoreceptors transplanted with the retinal pigment epithelium (RPE). Methods: Full-thickness retina with attached RPE was harvested from healthy adult rats. Grafts were implanted into two rat models of retinal degeneration, Royal College of Surgeons (RCS) and S334ter-3. Survival of the h...

Purpose: To review and discuss current innovations and future implications of promising biotechnology and biomedical offerings in the field of retina. We focus on therapies that have already emerged as clinical offerings or are poised to do so. Methods: Literature review and commentary focusing on stem cell therapies, gene-based therapies, optog...

Despite many decades of research and development, corneal opacity remains a leading cause of reversible blindness worldwide. Corneal transplantation and keratoprosthesis can restore corneal clarity, but both have well-known limitations. High-resolution electronic microdisplays may offer an alternative to traditional methods of treating corneal dise...