Showing papers by "Mark S. Humayun published in 2011"

Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task

Abstract: Background/aims To determine to what extent subjects implanted with the Argus II retinal prosthesis can improve performance compared with residual native vision in a spatial-motor task. Methods High-contrast square stimuli (5.85 cm sides) were displayed in random locations on a 19 99 (48.3 cm) touch screen monitor located 12 99 (30.5 cm) in front of the subject. Subjects were instructed to locate and touch the square centre with the system on and then off (40 trials each). The coordinates of the square centre and location touched were recorded. Results Ninety-six percent (26/27) of subjects showed a significant improvement in accuracy and 93% (25/27) show a significant improvement in repeatability with the system on compared with off (p<0.05, Student t test). A group of five subjects that had both accuracy and repeatability values <250 pixels (7.4 cm) with the system off (ie, using only their residual vision) was significantly more accurate and repeatable than the remainder of the cohort (p<0.01). Of this group, four subjects showed a significant improvement in both accuracy and repeatability with the system on. Conclusion In a study on the largest cohort of visual prosthesis recipients to date, we found that artificial vision augments information from existing vision in a spatial-motor task. Clinical trials registry no NCT00407602.

Resolution of the Epiretinal Prosthesis is not Limited by Electrode Size

Abstract: Epiretinal prostheses for the blind bypass diseased photosensitive cells in the retina, directly stimulating retinal neurons electrically and evoking signals that are relayed to the brain. Current clinical implants have few electrodes and provide limited visual acuity. Acuity may be improved by identifying electrode array design features and operational details that enhance or interfere with visual percept formation. We labeled all retinal ganglion cells in whole mount retina with a calcium reporter and then measured the number and pattern of cells responding, over a range of electrode diameters and stimulus durations. Span of the response scaled with electrode diameter for electrodes 60 μm and larger. Short stimulation pulse widths selectively activated cells nearest the electrode. Our measurements in the salamander retina suggest that the spatial resolution is 150 μm, which on a human retina is equivalent to 0.55° of human visual field and corresponding Snellen acuity of 20/660. Reading large print could be possible with such a prosthesis.

Combined spectral and polarimetry imaging and diagnostics

Abstract: Combined spectral and polarimetry imaging and diagnostic techniques are disclosed, including an imaging system that simultaneously records spatially co- registered spectral and polarization information from an image of a target scene such as an ocular structure or material or device in an around the eye. Image acquisition and image calibration by such an imaging system or an imaging spectrometer or polarimeter are also disclosed. Methods of data storage and image display relevant to medical practice in general and ophthalmology practice specifically are further disclosed.

Parylene-based integrated wireless single-channel neurostimulator

Abstract: This paper presents the design, fabrication, and functional testing of a fully implantable, flexible, Parylene-enable neurostimulator that features single-channel wireless stimulation capability [1]. This system comprises a fold-and-bond microelectromechanical systems (MEMS) coil for wireless power and data transmission, a BION 1-3 CMOS stimulator chip, discrete capacitors, as well as a carrier substrate with two platinum stimulating electrodes and interconnections for system assembly. The physical geometries of the devices are designed for use in retinal implantation with the specifications determined from the implantation results in canine eyes. The coil and carrier substrate are separately fabricated using a Parylene–metal skin technology. The unique properties of Parylene C allow these MEMS devices to be flexible and biocompatible, facilitating surgical procedure. The system assembly is achieved by interconnecting individual components together on the carrier substrate with a biocompatible silver epoxy. A 10 μm layer of Parylene C is selectively deposited on the integrated system to protect it from corrosive eye environment. The system functionality is verified using a telemetry link setup, and single-phase pulses with amplitudes ranging from 7 to 8.5 V are detected.

Optical coherence tomography with multiple sample arms

Abstract: A multiplexed OCT imaging system includes a plurality of sample arms, an imaging engine, and an optical controller. The sample arms are optically coupled to the imaging engine via the optical controller; the optical controller multiplexes optical signals from the sample arms to permit some of the sample arms to operate sequentially or simultaneously.

Both electrical stimulation thresholds and SMI-32-immunoreactive retinal ganglion cell density correlate with age in S334ter line 3 rat retina.

Abstract: Electrical stimulation threshold and retinal ganglion cell density were measured in a rat model of retinal degeneration. We performed in vivo electrophysiology and morphometric analysis on normal a...

Electrolytically driven drug pump devices

Abstract: Electrolytically driven drug pump devices may be configured so as to ensure sustained contact of the electrolysis electrodes with the electrolyte, thereby improving the reliability and/or pump capacity of the devices. In piston-pump drug-delivery devices, changes in friction between the piston and vial in which it moves may be reduced and/or compensated for by suitable surface coatings and/or feedback control. These and other drug pump devices may be remotely controlled and/or reprogrammed by a smartphone or other wireless handheld device. The filling status of a drug reservoir in the drug pump devices may be determined with mechanical and/or magnetic position sensor associated with a reservoir boundary.

Hyperspectral Computed Tomographic Imaging Spectroscopy of Vascular Oxygen Gradients in the Rabbit Retina In Vivo

Abstract: Diagnosis of retinal vascular diseases depends on ophthalmoscopic findings that most often occur after severe visual loss (as in vein occlusions) or chronic changes that are irreversible (as in diabetic retinopathy). Despite recent advances, diagnostic imaging currently reveals very little about the vascular function and local oxygen delivery. One potentially useful measure of vascular function is measurement of hemoglobin oxygen content. In this paper, we demonstrate a novel method of accurately, rapidly and easily measuring oxygen saturation within retinal vessels using in vivo imaging spectroscopy. This method uses a commercially available fundus camera coupled to two-dimensional diffracting optics that scatter the incident light onto a focal plane array in a calibrated pattern. Computed tomographic algorithms are used to reconstruct the diffracted spectral patterns into wavelength components of the original image. In this paper the spectral components of oxy- and deoxyhemoglobin are analyzed from the vessels within the image. Up to 76 spectral measurements can be made in only a few milliseconds and used to quantify the oxygen saturation within the retinal vessels over a 10–15 degree field. The method described here can acquire 10-fold more spectral data in much less time than conventional oximetry systems (while utilizing the commonly accepted fundus camera platform). Application of this method to animal models of retinal vascular disease and clinical subjects will provide useful and novel information about retinal vascular disease and physiology.

Modeling and percept of transcorneal electrical stimulation in humans

Abstract: Retinal activation via transcorneal electrical stimulation (TcES) in normal humans was investigated by comparing subject perception, model predictions, and brain activation patterns. The preferential location of retinal stimulation was predicted from 3-D admittance modeling. Visual cortex activation was measured using positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG). Two different corneal electrodes were investigated: DTL-Plus and ERG-Jet. Modeling results predicted preferential stimulation of the peripheral, inferior, nasal retina during right eye TcES using DTL-Plus, but more extensive activation of peripheral, nasal hemiretina using ERG-Jet. The results from human FDG PET study using both corneal electrodes showed areas of visual cortex activation that consistently corresponded with the reported phosphene percept and modeling predictions. ERG-Jet was able to generate brighter phosphene percept than DTL-Plus and elicited retinotopically mapped primary visual cortex activation. This study demonstrates that admittance modeling and PET imaging consistently predict the perceived location of electrically elicited phosphenes produced during TcES.

Impedance as a Method to Sense Proximity at the Electrode-Retina Interface

Abstract: Precise positioning of a stimulating electrode in the eye is not possible by simple visualization. However, reliable measurement of responses to retinal stimulation requires consistent positioning. The present study focuses on impedance measurement techniques to sense the proximity of the electrode to the retina. A platinum-iridium stimulation electrode was placed inside the rat eye and impedance was recorded at different positions of the stimulating electrode relative to the retina. The presence of robust electrically evoked response in the superior colliculus indicates that the electrode may not have to be in absolute contact in order to elicit a neural response. Optical coherence tomography imaging confirmed the distance-impedance relationship.

Biocompatible substrate for facilitating interconnections between stem cells and target tissues and methods for implanting same

Abstract: Disclosed herein are substrates for cell delivery to target tissues requiring treatment for various diseases that induce cell death, damage or loss of function The substrates are configured to provide seeded cells, including stem cells, with a structural support that allows interconnection with and transmission of biological signals between the cells and the target tissue

Vitreal oxygenation in retinal ischemia reperfusion.

Abstract: Several ocular and systemic diseases (e.g., central retinal artery occlusion, carotid artery disease, diabetic retinopathy, and possibly glaucoma) are accompanied by retinal ischemia, which is a common cause of visual impairment and blindness.1 Retinal ischemia results in neuronal cell degeneration and activation of glial cells. Neuronal cell degeneration is caused by oxygen and substrate deprivation during ischemia and by reperfusion injury.1,2 Apoptosis (programmed cell death without necrosis) has been cited as a potential pathway of retinal ganglion cell death in both human glaucoma and experimental primate glaucoma associated with elevated IOP.2–4 In the eye, growth factor deprivation of retinal ganglion cells results from the blockade of retrograde transport at the lamina cribrosa, preventing growth factors from reaching their site of action in the cell body.5,6 When the IOP is elevated, the choroidal blood flow decreases, leading to a reduction in approximately 0.5 mm Hg choroidal partial oxygen pressure/1 mm Hg perfusion pressure.7–10 This reduction leads to a reduction in photoreceptor oxygen availability and consumption.10 Similarly, anything that decreases choroidal blood flow would be expected to have a negative impact on retinal oxygenation and on photoreceptor function. Experimental glaucoma has been shown to affect photoreceptors,11 possibly because of a reduction in the photoreceptor oxygen supply. There is also direct evidence of retinal damage by reduced choroidal blood flow in birds.12 Several studies have shown that retinal oxygenation can be partially or completely restored during arterial occlusion by making the animal hyperoxic.13–16 Studies using models of total ischemia have corroborated the importance of oxygen as the limiting factor during occlusion. Anderson and Saltzman17 have shown that if human subjects breathed oxygen before IOP elevation, their vision was sustained longer than if they breathed room air. Blair et al.18 have shown that perfusing the vitreous with an oxygenated solution after total occlusion can maintain the structural and electrophysiological integrity of the retina. Despite these positive experimental data, the clinical experience with hyperoxia has been mixed, with only few studies recommending hyperoxia as a treatment for vascular occlusion.19 In the present study, we present a novel system for vitreal oxygenation using electrolysis of the water content of the vitreous gel. Specifically, our aim was to evaluate the potential role of anterior vitreal oxygenation, by oxygen-generating electrodes, for reversing ischemic insult in a rabbit model with ischemia reperfusion.

Morphometric Analysis of Optic Nerves and Retina from an End-Stage Retinitis Pigmentosa Patient with an Implanted Active Epiretinal Array

Abstract: Microelectronic retinal implants have shown great promise in restoring useful vision in patients with outer retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration.1–3 Our research group and several others have been investigating epiretinal arrays4–8 that electrically stimulate the remaining inner retinal neurons. These arrays generate multiple spots of light described as phosphenes, which when viewed in a specific pattern, allow patients to regain some visual function.9,10 Six patients have undergone monocular implantation with an epiretinal array (Argus I; Second Sight Medical Products, Sylmar, CA) of 5.5 × 6-mm silicone-platinum electrodes connected to an implanted neural stimulator. We present data from the first patient in this group of six, who had the 16-electrode epiretinal array implanted and has since died. This patient had shown an ability to use the epiretinal prosthesis for simple visual tasks.11 In the present study, we morphometrically analyzed the patient's optic nerves and retina. This study represents the very first opportunity to histologically characterize changes in a patient with an epiretinal prosthesis implanted with subsequent electrical stimulation. Comparison with appropriate controls yielded valuable information regarding the effects of end-stage RP and long-term epiretinal array implantation and stimulation on both the optic nerve and retina. We anticipated that the retina would show the direct effects of RP and long-term implantation and stimulation, whereas the optic nerve, representing the final common pathway for information processing, would demonstrate more global and indirect effects.

Combined endoscopic surgical tools

Abstract: A probe assembly includes a forward-imaging optical coherence tomography (OCT) probe having a field of view and an instrument, adjacent to the probe, for performing manipulations at least within the OCT field of view.

Interphase gap decreases electrical stimulation threshold of retinal ganglion cells

Abstract: The most common electrical stimulation pulse used in retinal implants is a symmetric biphasic current pulse. Prior electrophysiological studies in peripheral nerve have shown that adding an interphase gap (IPG) between the two phases makes stimulation more efficient. We investigated the effect of IPG duration on retinal ganglion cell (RGC) electrical threshold. We used calcium imaging to measure the activity of RGCs in isolated retina in response to electrical stimulation. By varying IPG duration, we were able to examine the effect of duration on threshold. We further studied this effect by simulating RGC behavior with a Hodgkin-Huxley-type model. Our results indicate that the threshold for electrical activation of RGCs can be reduced by increasing the length of the IPG.

Continuous electrical stimulation decreases retinal excitability but does not alter retinal morphology.

Abstract: Retinal prostheses aim to provide visual perception through electrical stimulation of the retina. Hence they have to operate between threshold charge density and maximum safe charge density. To date most studies in the retina have concentrated on understanding the threshold, while stimulation safety has predominantly been studied in structures other than the retina. Toward this end, the present study focuses on determining the effect of continuous electrical stimulation of the retina both on retinal morphology and on the electrically evoked responses in the superior colliculus in a rodent model. The results demonstrate that the retina is able to tolerate 1 h long stimulation with only minor changes evident in retinal histology when examined three to 14 days later, even at charge densities (0.68 mC cm−2) above the safe limit of platinum delivered at high stimulus frequency (300 Hz). However, this continuous electrical stimulation causes an elevation in the threshold of the electrically evoked response in the superior colliculus, indicating some form of adaptation to continuous stimulation.

Semipermeable parylene membrane as an artificial Bruch's membrane

Abstract: This paper investigates the feasibility of a mesh-supported submicron-thick semipermeable parylene-C membrane as an artificial Bruch's membrane for the treatment of age-related macular degeneration (AMD). First, the permeabilities of parylene-C membranes with different thickness were measured and the results showed that as-deposited 0.30µm-thick parylene-C, which has a similar permeability to biological Bruch's membrane, is a good candidate to replace the diseased Bruch's membrane. This was further validated by perfusion cell culture experiments, in which nutrients were supplied to the cultured cells only by permeation through the submicron membrane. It was also found that retinal pigment epithelial (RPE) cells could grow and well-polarize with normal morphology on the membrane Finally, the implantation of the submicron-thick membrane (with in vitro cultured RPE cells) into rat's retina was successfully done with the help of a parylene-C/SU-8 microsurgical tool, and the following histological study of the retina showed that the reported thin parylene-C membrane could be a promissing RPE substrate candidate for further study.

Performance analysis of millennium vitreous enhancer™ system

Abstract: BACKGROUND AND OBJECTIVE This study evaluates water and porcine vitreous flow rates and duty cycle using the Millennium Vitrectomy Enhancer (MVE) system (Bausch & Lomb, St. Louis, MO). MATERIALS AND METHODS A precision balance measured mass of water or vitreous removed from a vial within a certain time by 20-, 23-, and 25-gauge MVE cutters at 800, 1,000, 1,500, 2,000, and 2,500 cuts per minute (CPM) with various aspiration levels was studied. Frame-by-frame analysis of high-speed video was used to determine duty cycle. RESULTS Larger cutter and higher aspiration levels produced greater flow rates. Water flow rate showed a parabolic trend peaking at 1,500 CPM and dropping moderately and vitreous flow rate increased moderately with cut-rate increased. The MVE system maintained a high flow rate and high duty cycle even at high cut-rates. CONCLUSION Flow rates for the MVE system are stable and predictable for all cutter gauges, which should aid the surgeon to select the optimal parameters for vitrectomy.

Optical coherence tomography with multiple imaging instruments

Abstract: A combination includes an OCT system, an optical instrument, optics defining an optical path from the optical instrument to a target, and secondary optics for coupling the OCT system to the optical path. This combination permits simultaneous operation of the OCT system and the optical instrument.

Encoding of Size and Brightness of Percepts in a Visual Prosthesis

Abstract: Methods of electrically stimulating percepts in a patient with a visual prosthesis are discussed. Changes in amplitude of stimulation increase both the perceived brightness and the perceived size of the precept. Changes in frequency of stimulation change the perceived brightness without altering the perceived size of the percept. Hence, a source image may be mapped to a combination of amplitude and frequency that best induces the desired image.

Piston-driven drug pump devices

Abstract: In piston-pump drug-delivery devices, changes in friction between the piston and vial in which it moves may be reduced and/or compensated for by suitable surface coatings and/or feedback control.

Retinal prosthesis with separate electrode array and return electrodes

Abstract: The artificial percept of light may be created by electrically stimulating the neurons of the retina. While a photolithographed array internal to the retina provides superior resolution, an array external to the retina provides easier implantation and improved manufacturability. Therefore it is advantageous to supply a high-resolution electrode array internal to the sclera, near the fovea and a lower-resolution electrode array external to the sclera near the periphery of the retina. It is advantageous to encourage current to flow through the retina by providing a physically separate and distinct electrode array and return electrode. The high-resolution electrode array and lower-resolution electrode array may be return electrodes for the other, or completely separate return electrodes may be provided.

Multiplexed oct imaging; combined oct and visual imanging; combined oct imaging and neural signaling

Abstract: A multiplexed OCT imaging system includes a plurality of sample arms (410), an imaging engine (420), and an optical controller (425). The sample arms are optically coupled to the imaging engine via the optical controller; the optical controller multiplexes optical signals from the sample arms to permit some of the sample arms to operate sequentially or simultaneously. A combination includes an OCT system (750), an optical instrument (780), optics defining an optical path (755) from the optical instrument to a target, and secondary optics (770) for coupling the OCT system to the optical path. This combination permits simultaneous operation of the OCT system and the optical instrument. An electrode carrier (1410) includes multiple electrodes, each electrode having a contact (1470) located at a different position along a distal end of the carrier, and multiple optical fibers (1460), each associated with one of the electrodes and having an end face proximate to the contact of the associated electrode. Each optical fiber end face may capture optical information from tissue adjacent to the associated contact. The electrode carrier may be used for interfacing with an OCT system and a neural signal system.

Optical coherence tomography for neural-signal applications

Abstract: An electrode carrier includes multiple electrodes, each electrode having a contact located at a different position along a distal end of the carrier, and multiple optical fibers, each associated with one of the electrodes and having an end face proximate to the contact of the associated electrode. Each optical fiber end face may capture optical information from tissue adjacent to the associated contact. The electrode carrier may be used for interfacing with an OCT system and a neural signal system.