Design of a high-resolution optoelectronic retinal prosthesis.

PubMed

Palanker, Daniel; Vankov, Alexander; Huie, Phil; Baccus, Stephen

2005-03-01

It has been demonstrated that electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. However, current retinal implants provide very low resolution (just a few electrodes), whereas at least several thousand pixels would be required for functional restoration of sight. This paper presents the design of an optoelectronic retinal prosthetic system with a stimulating pixel density of up to 2500 pix mm(-2) (corresponding geometrically to a maximum visual acuity of 20/80). Requirements on proximity of neural cells to the stimulation electrodes are described as a function of the desired resolution. Two basic geometries of sub-retinal implants providing required proximity are presented: perforated membranes and protruding electrode arrays. To provide for natural eye scanning of the scene, rather than scanning with a head-mounted camera, the system operates similar to 'virtual reality' devices. An image from a video camera is projected by a goggle-mounted collimated infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. The goggles are transparent to visible light, thus allowing for the simultaneous use of remaining natural vision along with prosthetic stimulation. Optical delivery of visual information to the implant allows for real-time image processing adjustable to retinal architecture, as well as flexible control of image processing algorithms and stimulation parameters.

Design of a high-resolution optoelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Vankov, Alexander; Huie, Phil; Baccus, Stephen

2005-03-01

It has been demonstrated that electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa. However, current retinal implants provide very low resolution (just a few electrodes), whereas at least several thousand pixels would be required for functional restoration of sight. This paper presents the design of an optoelectronic retinal prosthetic system with a stimulating pixel density of up to 2500 pix mm-2 (corresponding geometrically to a maximum visual acuity of 20/80). Requirements on proximity of neural cells to the stimulation electrodes are described as a function of the desired resolution. Two basic geometries of sub-retinal implants providing required proximity are presented: perforated membranes and protruding electrode arrays. To provide for natural eye scanning of the scene, rather than scanning with a head-mounted camera, the system operates similar to 'virtual reality' devices. An image from a video camera is projected by a goggle-mounted collimated infrared LED-LCD display onto the retina, activating an array of powered photodiodes in the retinal implant. The goggles are transparent to visible light, thus allowing for the simultaneous use of remaining natural vision along with prosthetic stimulation. Optical delivery of visual information to the implant allows for real-time image processing adjustable to retinal architecture, as well as flexible control of image processing algorithms and stimulation parameters.

Implantable multilayer microstrip antenna for retinal prosthesis: antenna testing.

PubMed

Permana, Hans; Fang, Qiang; Rowe, Wayne S T

2012-01-01

Retinal prosthesis has come to a more mature stage and become a very strategic answer to Retinitis Pigmentosa (RP) and Age-related Macular Degeneration (AMD) diseases. In a retinal prosthesis system, wireless link holds a great importance for the continuity of the system. In this paper, an implantable multilayer microstrip antenna was proposed for the retinal prosthesis system. Simulations were performed in High Frequency Structure Simulator (HFSS) with the surrounding material of air and Vitreous Humor fluid. The fabricated antenna was measured for characteristic validation in free space. The results showed that the real antenna possessed similar return loss and radiation pattern, while there was discrepancy with the gain values.

Fluocinolone acetonide implant (Retisert) for chronic cystoid macular edema in two patients with AIDS and a history of cytomegalovirus retinitis.

PubMed

Hu, Jianmin; Coassin, Marco; Stewart, Jay M

2011-06-01

To report the authors' experience using fluocinolone acetonide (Retisert) to treat cystoid macular edema (CME) resulting from immune recovery uveitis (IRU) in 2 acquired immunodeficiency syndrome (AIDS) patients with a history of cytomegalovirus (CMV) retinitis. Interventional case series. Medical records were reviewed of 2 patients who received Retisert implantation in 3 eyes for IRU-associated inflammation and CME. Suppression of CMV disease was achieved with oral medication in one patient and with simultaneous implantation of a ganciclovir implant in the other patient. After Retisert implantation in 3 eyes in AIDS patients on HAART, improvement in CME was seen in 2 eyes. No CMV reactivation was detected during the several-month follow-up period. Retisert may be an effective treatment for CME in AIDS patients with IRU reactivation and a history of CMV retinitis.

Retinal prostheses: progress toward the next generation implants

PubMed Central

Ghezzi, Diego

2015-01-01

In the last decade, various clinical trials proved the capability of visual prostheses, in particular retinal implants, to restore a useful form of vision. These encouraging results promoted the emerging of several strategies for neuronal stimulation aiming at the restoration of sight. Besides the traditional approach based on electrical stimulation through metal electrodes in the different areas of the visual path (e.g., the visual cortex, the lateral geniculate nucleus, the optic nerve, and the retina), novel concepts for neuronal stimulation have been mostly exploited as building blocks of the next generation of retinal implants. This review is focused on critically discussing recent major advancements in the field of retinal stimulation with particular attention to the findings in the application of novel concepts and materials. Last, the major challenges in the field and their clinical implications will be outlined. PMID:26347602

Photovoltaic Retinal Prosthesis for Restoring Sight to Patients Blinded by Retinal Injury or Degeneration

DTIC Science & Technology

2016-02-01

are rapidly expanding [1][2]. Cochlear implants [3] have seen the most remarkable success in sensory neuroprosthetics, while retinal implants [4][5...intensities: Imax (bright pixels) and Imin (dark pixels). In the common return configurations (connected and monopolar), the current flowing through the...array forces the injected current to flow to the back side, which results in a potential build-up in front of the device. Near each pixel (within

Influence of solvent composition on the performance of carbodiimide cross-linked gelatin carriers for retinal sheet delivery.

PubMed

Lai, Jui-Yang

2013-09-01

Gelatin is a protein molecule that displays bioaffinity and provides a template to guide retinal pigment epithelial (RPE) cell organization and growth. We have recently demonstrated that the carbodiimide cross-linked gelatin membranes can be used as retinal sheet carriers. The purpose of this work was to further determine the role of solvent composition in the tissue delivery performance of chemically modified biopolymer matrices. The gelatin molecules were treated with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) in the presence of binary ethanol/water mixtures with varying ethanol concentrations (70-95 vol%) to obtain the carriers with different cross-linking efficiencies and mechanical properties. Results of melting point measurements and in vitro degradation tests showed that when the cross-linking index reached a high level of around 45 %, the EDC cross-linked gelatin materials have sufficient thermal stability and resistance to enzymatic degradation, indicating their suitability for the development of carriers for retinal sheet delivery. Irrespective of the solvent composition, the chemically modified gelatin samples are compatible toward human RPE cells without causing toxicity and inflammation. In particular, the membrane carriers prepared by the cross-linking in the presence of solvent mixtures containing 80-90 vol% of ethanol have no impact on the proliferative capacity of ARPE-19 cultures and possess good efficiency in transferring and encapsulating the retinal tissues. It is concluded that, except for cell viability and pro-inflammatory cytokine expression, the retinal sheet delivery performance strongly depends on the solvent composition for EDC cross-linking of gelatin molecules.

First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis

PubMed Central

Ayton, Lauren N.; Blamey, Peter J.; Guymer, Robyn H.; Luu, Chi D.; Nayagam, David A. X.; Sinclair, Nicholas C.; Shivdasani, Mohit N.; Yeoh, Jonathan; McCombe, Mark F.; Briggs, Robert J.; Opie, Nicholas L.; Villalobos, Joel; Dimitrov, Peter N.; Varsamidis, Mary; Petoe, Matthew A.; McCarthy, Chris D.; Walker, Janine G.; Barnes, Nick; Burkitt, Anthony N.; Williams, Chris E.; Shepherd, Robert K.; Allen, Penelope J.

2014-01-01

Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Trial Registration Clinicaltrials.gov NCT01603576 PMID:25521292

A method and technical equipment for an acute human trial to evaluate retinal implant technology

NASA Astrophysics Data System (ADS)

Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

2005-03-01

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 µm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

Optical coherence tomography-guided retinal prosthesis design: model of degenerated retinal curvature and thickness for patient-specific devices.

PubMed

Opie, Nicholas L; Ayton, Lauren N; Apollo, Nicholas V; Ganesan, Kumaravelu; Guymer, Robyn H; Luu, Chi D

2014-06-01

Retinitis pigmentosa affects over 1.5 million people worldwide and is a leading cause of vision loss and blindness. While retinal prostheses have shown some success in restoring basic levels of vision, only generic, "one-size-fits-all" devices are currently being implanted. In this study, we used optical coherence tomography scans of the degenerated retina from 88 patients with retinitis pigmentosa to generate models of retinal thickness and curvature for the design of customized implants. We found the average retinal thickness at the fovea to be 152.9 ± 61.3 μm, increasing to a maximum retinal thickness of 250.9 ± 57.5 μm at a nasal eccentricity of 5°. These measures could be used to assist the development of custom-made penetrating electrodes to enhance and optimize epiretinal prostheses. From the retinal thickness measurements, we determined that the optimal length of penetrating electrodes to selectively stimulate retinal ganglion cell bodies and interneuron axons in the ganglion cell layer should be 30-100 μm, and to preferentially stimulate interneurons in the inner nuclear layer, electrodes should be 100-200 μm long. Electrodes greater than 200 μm long had the potential to penetrate through the retina into the choroid, which could cause devastating complications to the eye and should be avoided. The two- and three-dimensional models of retinal thickness developed in this study can be used to design patient-specific epiretinal implants that will help with safety and to optimize the efficacy of neuronal stimulation, ensuring the best functional performance of the device for patients. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Misfolded opsin mutants display elevated β -sheet structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Lisa M.; Gragg, Megan; Kim, Tae Gyun

Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Förster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Also, both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated β-sheet and reduced α-helical content. The newly formed β-sheet structure may facilitate themore » aggregation of misfolded opsin mutants. In conclusion, the effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself.« less

Misfolded opsin mutants display elevated β -sheet structure

DOE PAGES

Miller, Lisa M.; Gragg, Megan; Kim, Tae Gyun; ...

2015-09-07

Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Förster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Also, both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated β-sheet and reduced α-helical content. The newly formed β-sheet structure may facilitate themore » aggregation of misfolded opsin mutants. In conclusion, the effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself.« less

Biocompatible implants and methods of making and attaching the same

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rowley, Adrian P; Laude, Lucien D; Humayun, Mark S

2014-10-07

The invention provides a biocompatible silicone implant that can be securely affixed to living tissue through interaction with integral membrane proteins (integrins). A silicone article containing a laser-activated surface is utilized to make the implant. One example is an implantable prosthesis to treat blindness caused by outer retinal degenerative diseases. The device bypasses damaged photoreceptors and electrically stimulates the undamaged neurons of the retina. Electrical stimulation is achieved using a silicone microelectrode array (MEA). A safe, protein adhesive is used in attaching the MEA to the retinal surface and assist in alleviating focal pressure effects. Methods of making and attachingmore » such implants are also provided.« less

In vivo performance of photovoltaic subretinal prosthesis

NASA Astrophysics Data System (ADS)

Mandel, Yossi; Goetz, George; Lavinsky, Daniel; Huie, Phil; Mathieson, Keith; Wang, Lele; Kamins, Theodore; Manivanh, Richard; Harris, James; Palanker, Daniel

2013-02-01

We have developed a photovoltaic retinal prosthesis, in which camera-captured images are projected onto the retina using pulsed near-IR light. Each pixel in the subretinal implant directly converts pulsed light into local electric current to stimulate the nearby inner retinal neurons. 30 μm-thick implants with pixel sizes of 280, 140 and 70 μm were successfully implanted in the subretinal space of wild type (WT, Long-Evans) and degenerate (Royal College of Surgeons, RCS) rats. Optical Coherence Tomography and fluorescein angiography demonstrated normal retinal thickness and healthy vasculature above the implants upon 6 months follow-up. Stimulation with NIR pulses over the implant elicited robust visual evoked potentials (VEP) at safe irradiance levels. Thresholds increased with decreasing pulse duration and pixel size: with 10 ms pulses it went from 0.5 mW/mm2 on 280 μm pixels to 1.1 mW/mm2 on 140 μm pixels, to 2.1 mW/mm2 on 70 μm pixels. Latency of the implant-evoked VEP was at least 30 ms shorter than in response evoked by the visible light, due to lack of phototransduction. Like with the visible light stimulation in normal sighted animals, amplitude of the implant-induced VEP increased logarithmically with peak irradiance and pulse duration. It decreased with increasing frequency similar to the visible light response in the range of 2 - 10 Hz, but decreased slower than the visible light response at 20 - 40 Hz. Modular design of the photovoltaic arrays allows scalability to a large number of pixels, and combined with the ease of implantation, offers a promising approach to restoration of sight in patients blinded by retinal degenerative diseases.

MEMS technologies for epiretinal stimulation of the retina

NASA Astrophysics Data System (ADS)

Mokwa, W.

2004-09-01

It has been shown that electrical stimulation of retinal ganglion cells yields visual sensations. Therefore, a retina implant for blind humans suffering from retinitis pigmentosa based on this concept seems to be feasible. In Germany, there are two projects funded by the government working on different approaches namely the subretinal and the epiretinal approaches. This paper describes the epiretinal approach for such a system. The extraocular part of this system records visual images. The images are transformed by a neural net into corresponding signals for stimulation of the retinal ganglion cells. These signals are transmitted to a receiver unit of an intraocular implant, the retina stimulator. Integrated circuitry of this unit decodes the signals and transfers the data to a stimulation circuitry that selects stimulation electrodes placed onto the retina and generates current pulses to the electrodes. By this, action potentials in retinal ganglion cells are evoked, causing a visual sensation. This paper concentrates on the MEMS part of this implant.

A Suprachoroidal Electrical Retinal Stimulator Design for Long-Term Animal Experiments and In Vivo Assessment of Its Feasibility and Biocompatibility in Rabbits

PubMed Central

Zhou, J. A.; Woo, S. J.; Park, S. I.; Kim, E. T.; Seo, J. M.; Chung, H.; Kim, S. J.

2008-01-01

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes. PMID:18317521

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

PubMed

Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P < 0.0001). By Month 6, mean central retinal thickness was 287.3 μm (P = 0.16). Eyes with only intraretinal fluid (13 eyes) achieved a fluid-free macula. Eyes with predominantly subretinal fluid (6 eyes) did not improve central retinal thickness and continued monthly ranibizumab. Mean baseline intraocular pressure was 13.2 mmHg, which peaked at 15.6 mmHg by Month 2 (P = 0.004). Intravitreal dexamethasone implant improved only macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Fighting blindness with microelectronics.

PubMed

Zrenner, Eberhart

2013-11-06

There is no approved cure for blindness caused by degeneration of the photoreceptor cells of the retina. However, there has been encouraging progress with attempts to restore vision using microelectronic retinal implant devices. Yet many questions remain to be addressed. Where is the best location to implant multielectrode arrays? How can spatial and temporal resolution be improved? What are the best ways to ensure the safety and longevity of these devices? Will color vision be possible? This Perspective discusses the current state of the art of retinal implants and attempts to address some of the outstanding questions.

Retinal Implants for Blind Patients

NASA Astrophysics Data System (ADS)

Rothermel, Albrecht

Recently, very promising results have been obtained in clinical trials with eye-prostheses for the blind. There is a chance that advances in surgical techniques, microelectronics design, and material science may lead to the first really useful applications of retinal implants in the near future. This chapter will focus on the actual status of subretinal surgery and implant technologies. Opportunities and limitations of the different technologies will be discussed in terms of patients benefit and technological challenges. Finally, a vision on how the devices may work and look like in the future will be given.

Enhanced osseointegration of titanium implants in a rat model of osteoporosis using multilayer bone mesenchymal stem cell sheets

PubMed Central

Duan, Yan; Ma, Wei; Li, Dehua; Wang, Tongfei; Liu, Baolin

2017-01-01

The present study aimed to investigate whether bone marrow-derived mesenchymal stem cell (BMSC) sheets combined with titanium implants enhanced implant osseointegration in an ovariectomized (OVX) rat model of osteoporosis. Sprague-Dawley rats were randomly assigned into a test group and control group. Allogenic BMSCs were collected from the rats, cultured and stored via cryopreservation. At 6 months post-ovariectomy, establishment of the OVX model was confirmed by micro-computed tomography (CT) measurements. BMSC sheets were subsequently layered and wrapped over titanium implants for implantation. Unmodified implants served as the control. At 8 weeks post-implantation, samples were observed by micro-CT reconstruction and histomorphometric evaluation. Micro-CT reconstruction identified a marked improvement in the surrounding bone volume following treatment, with data analyses indicating a significant increase in bone volume in the BMSC-implant group compared with the control implant group (P<0.05). In addition, histological staining identified new bone formation and an increased rate of bone-implant contact surrounding the BMSC-implant constructs. These results indicate that the use of BMSC sheets as a novel tissue engineering approach improves the osseointegration of titanium implants in an osteoporosis model. This method may expand the operative indications in patients with osteoporosis and improve the success rate of clinical dental implant treatments. PMID:29250137

High-Resolution Opto-Electronic Retinal Prosthesis: Physical Limitations and Design

NASA Astrophysics Data System (ADS)

Palanker, D.; Vankov, A.; Huie, P.; Butterwick, A.; Chan, I.; Marmor, M. F.; Blumenkranz, M. S.

Electrical stimulation of the retina can produce visual percepts in blind patients suffering from macular degeneration and retinitis pigmentosa (RP). However, current retinal implants provide very low resolution (just a few electrodes), whereas many more pixels would be required for a functional restoration of sight.

Use of a gentamicin-impregnated collagen sheet (Collatamp(®)) in the management of major soft tissue complications in pediatric cochlear implants.

PubMed

Benito-González, Fernando; Benito, Jose; Sánchez, Luis Alberto Guardado; Estevez Alonso, Santiago; Muñoz Herrera, Angel; Batuecas-Caletrio, Angel

2014-09-01

The objective was to report the effectiveness of salvage treatment in soft tissue infection around cochlear implants with an absorbable gentamicin collagen sheet and a periosteum and skin rotation flaps. Three patients with cochlear implant and persistent surrounding soft tissue infection are included. All of them underwent antibiotic treatment prior to surgery without any response. In this study preoperative and postoperative audiograms were practiced. Surgical excision of infectious skin and a periosteum and skin rotation flaps were performed. The cochlear implant was refixed in the temporal bone and a gentamicin-impregnated collagen sheet was located covering the cochlear implant. headings In all patients with soft tissue infection around the cochlear implant, infection was completely resolved. It was not necessary to remove the device in any case. The use of an absorbable gentamicin-impregnated collagen sheet is not described for the management of soft tissue complications in pediatric cochlear implant patients. The local application of high concentrations of antibiotic administered by this sheet may be effective against resistant bacteria and, in conjunction with surgery, may resolve this type of complications.

Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant.

PubMed

Winterhalter, Sibylle; Vom Brocke, Gerrit Alexander; Pilger, Daniel; Eckert, Annabelle; Schlomberg, Juliane; Rübsam, Anne; Klamann, Matthias Karl; Gundlach, Enken; Dietrich-Ntoukas, Tina; Joussen, Antonia Maria

2016-10-27

Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 μm (1 month; p = 0.003,) to 361 μm (2 months; p = 0,002) and to 415 μm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 μm (1 month; p < 0,001) and to 343 μm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity.

The potential of the second sight system bionic eye implant for partial sight restoration.

PubMed

Luo, Yvonne Hsu-Lin; Fukushige, Eka; Da Cruz, Lyndon

2016-07-01

Second Sight System bionic eye implant, a commercially available visual prosthesis developed by Second Sight Medical Products, has been implanted in over 125 patients with outer retinal dystrophies such as retinitis pigmentosa. The system has gained regulatory approval in both the USA and Europe, and aims to restore vision by electrical stimulation of the nerve cells of the inner retina. In this review, we present the safety profile of this implant from the international clinical trial and discuss the nature and levels of improvement in visual function achieved by patients implanted with the system. Expert commentary: Future developments for the system will be explored following the discussion of the current usefulness of the device, its limitation as and the areas in which further development is necessary.

21 CFR 886.3340 - Extraocular orbital implant.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES OPHTHALMIC DEVICES Prosthetic Devices § 886.3340 Extraocular orbital implant. (a) Identification. An extraocular orbital implant is a nonabsorbable device intended to be implanted during scleral surgery for buckling or building up the floor of the eye, usually in conjunction with retinal reattachment...

Artificial vision support system (AVS(2)) for improved prosthetic vision.

PubMed

Fink, Wolfgang; Tarbell, Mark A

2014-11-01

State-of-the-art and upcoming camera-driven, implanted artificial vision systems provide only tens to hundreds of electrodes, affording only limited visual perception for blind subjects. Therefore, real time image processing is crucial to enhance and optimize this limited perception. Since tens or hundreds of pixels/electrodes allow only for a very crude approximation of the typically megapixel optical resolution of the external camera image feed, the preservation and enhancement of contrast differences and transitions, such as edges, are especially important compared to picture details such as object texture. An Artificial Vision Support System (AVS(2)) is devised that displays the captured video stream in a pixelation conforming to the dimension of the epi-retinal implant electrode array. AVS(2), using efficient image processing modules, modifies the captured video stream in real time, enhancing 'present but hidden' objects to overcome inadequacies or extremes in the camera imagery. As a result, visual prosthesis carriers may now be able to discern such objects in their 'field-of-view', thus enabling mobility in environments that would otherwise be too hazardous to navigate. The image processing modules can be engaged repeatedly in a user-defined order, which is a unique capability. AVS(2) is directly applicable to any artificial vision system that is based on an imaging modality (video, infrared, sound, ultrasound, microwave, radar, etc.) as the first step in the stimulation/processing cascade, such as: retinal implants (i.e. epi-retinal, sub-retinal, suprachoroidal), optic nerve implants, cortical implants, electric tongue stimulators, or tactile stimulators.

Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion.

PubMed

Haller, Julia A; Bandello, Francesco; Belfort, Rubens; Blumenkranz, Mark S; Gillies, Mark; Heier, Jeffrey; Loewenstein, Anat; Yoon, Young-Hee; Jacques, Marie-Louise; Jiao, Jenny; Li, Xiao-Yan; Whitcup, Scott M

2010-06-01

To evaluate the safety and efficacy of dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, CA) compared with sham in eyes with vision loss due to macular edema (ME) associated with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Two identical, multicenter, masked, randomized, 6-month, sham-controlled clinical trials (each of which included patients with BRVO and patients with CRVO). A total of 1267 patients with vision loss due to ME associated with BRVO or CRVO. A single treatment with DEX implant 0.7 mg (n = 427), DEX implant 0.35 mg (n = 414), or sham (n = 426). The primary outcome measure for the pooled data from the 2 studies was time to achieve a > or =15-letter improvement in best-corrected visual acuity (BCVA). Secondary end points included BCVA, central retinal thickness, and safety. After a single administration, the time to achieve a > or =15-letter improvement in BCVA was significantly less in both DEX implant groups compared with sham (P<0.001). The percentage of eyes with a > or =15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (P<0.001). The percentage of eyes with a > or =15-letter loss in BCVA was significantly lower in the DEX implant 0.7-mg group compared with sham at all follow-up visits (P< or =0.036). Improvement in mean BCVA was greater in both DEX implant groups compared with sham at all follow-up visits (P< or =0.006). Improvements in BCVA with DEX implant were seen in patients with BRVO and patients with CRVO, although the patterns of response differed. The percentage of DEX implant-treated eyes with intraocular pressure (IOP) of > or =25 mmHg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. There was no significant between-group difference in the occurrence of cataract or cataract surgery. Dexamethasone intravitreal implant can both reduce the risk of vision loss and improve the speed and incidence of visual improvement in eyes with ME secondary to BRVO or CRVO and may be a useful therapeutic option for eyes with these conditions. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Retinal stimulation strategies to restore vision: Fundamentals and systems.

PubMed

Yue, Lan; Weiland, James D; Roska, Botond; Humayun, Mark S

2016-07-01

Retinal degeneration, a leading cause of blindness worldwide, is primarily characterized by the dysfunctional/degenerated photoreceptors that impair the ability of the retina to detect light. Our group and others have shown that bioelectronic retinal implants restore useful visual input to those who have been blind for decades. This unprecedented approach of restoring sight demonstrates that patients can adapt to new visual input, and thereby opens up opportunities to not only improve this technology but also develop alternative retinal stimulation approaches. These future improvements or new technologies could have the potential of selectively stimulating specific cell classes in the inner retina, leading to improved visual resolution and color vision. In this review we will detail the progress of bioelectronic retinal implants and future devices in this genre as well as discuss other technologies such as optogenetics, chemical photoswitches, and ultrasound stimulation. We will discuss the principles, biological aspects, technology development, current status, clinical outcomes/prospects, and challenges for each approach. The review will cover functional imaging documented cortical responses to retinal stimulation in blind patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

INTRAVITREAL DEXAMETHASONE IMPLANTATION IN PATIENTS WITH DIFFERENT MORPHOLOGICAL DIABETIC MACULAR EDEMA HAVING INSUFFICIENT RESPONSE TO RANIBIZUMAB.

PubMed

Kaldırım, Havva; Yazgan, Serpil; Atalay, Kursat; Gurez, Ceren; Savur, Fatma

2018-05-01

To evaluate the effectiveness of a single intravitreal injection of dexamethasone implant in resistant diabetic macular edema that have different morphological types. In this retrospective study, 31 patients (35 eyes) with persistent diabetic macular edema, who underwent a single injection of dexamethasone implant, were evaluated. Diabetic macular edema was classified into three types: diffuse retinal thickening (n = 10), cystoid macular edema (n = 13), and serous retinal detachment (n = 12). Primary outcome measures were best corrected visual acuity, and central macular thickness. The three subgroups were similar in terms of age and gender (P > 0.05). Total duration of diabetes was significantly less in the serous retinal detachment subgroup (P = 0.01). There were no differences in the best corrected visual acuity between the three subgroups until the sixth month. However, the best corrected visual acuity was significantly better in the diffuse retinal thickness subgroup at the sixth month (P = 0.008). Regarding the central macular thickness values, it was statistically better in serous retinal detachment than in diffuse retinal thickening and cystoid macular edema subgroups till the sixth month (P = 0.001). However, at the sixth month, there was not any statistical difference between subgroups regarding central macular thickness values. Antiglaucomatous agents were required in 4 (11.4%) patients throughout the study. Treatment algorithms should differ according to the morphology of diabetic macular edema; however, more data is needed to give specific recommendations.

Photovoltaic Retinal Prosthesis with High Pixel Density

PubMed Central

Mathieson, Keith; Loudin, James; Goetz, Georges; Huie, Philip; Wang, Lele; Kamins, Theodore I.; Galambos, Ludwig; Smith, Richard; Harris, James S.; Sher, Alexander; Palanker, Daniel

2012-01-01

Retinal degenerative diseases lead to blindness due to loss of the “image capturing” photoreceptors, while neurons in the “image processing” inner retinal layers are relatively well preserved. Electronic retinal prostheses seek to restore sight by electrically stimulating surviving neurons. Most implants are powered through inductive coils, requiring complex surgical methods to implant the coil-decoder-cable-array systems, which deliver energy to stimulating electrodes via intraocular cables. We present a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel receive power and data directly through pulsed near-infrared illumination and electrically stimulate neurons. Stimulation was produced in normal and degenerate rat retinas, with pulse durations from 0.5 to 4 ms, and threshold peak irradiances from 0.2 to 10 mW/mm2, two orders of magnitude below the ocular safety limit. Neural responses were elicited by illuminating a single 70 μm bipolar pixel, demonstrating the possibility of a fully-integrated photovoltaic retinal prosthesis with high pixel density. PMID:23049619

SiC Protective Coating for Photovoltaic Retinal Prostheses

PubMed Central

Lei, Xin; Kane, Sheryl; Cogan, Stuart; Lorach, Henri; Galambos, Ludwig; Huie, Philip; Mathieson, Keith; Kamins, Theodore; Harris, James; Palanker, Daniel

2016-01-01

Objective To evaluate PECVD SiC as a protective coating for retinal prostheses and other implantable devices, and to study their failure mechanisms in vivo. Approach Retinal prostheses were implanted in rats subretinally for up to 1 year. Degradation of implants was characterized by optical and scanning electron microscopy. Dissolution rates of SiC, SiNx and thermal SiO2 were measured in accelerated soaking tests in saline at 87°C. Defects in SiC films were revealed and analyzed by selectively removing the materials underneath those defects. Main results At 87°C SiNx dissolved at 18.3±0.3nm/day, while SiO2 grown at high temperature (1000°C) dissolved at 1.04±0.08A/day. SiC films demonstrated the best stability, with no quantifiable change after 112 days. Defects in thin SiC films appeared primarily over complicated topography and rough surfaces. Significance SiC coatings demonstrating no erosion in accelerated aging test for 112 days at 87°C, equivalent to about 10 years in vivo, can offer effective protection of the implants. Photovoltaic retinal prostheses with PECVD SiC coatings exhibited effective protection from erosion during the 4-month follow-up in vivo. The optimal thickness of SiC layers is about 560nm, as defined by anti-reflective properties and by sufficient coverage to eliminate defects. PMID:27323882

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats.

PubMed

Imai, Hisanori; Misra, Gauri P; Wu, Linfeng; Janagam, Dileep R; Gardner, Thomas W; Lowe, Tao L

2015-12-01

Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

PubMed Central

Imai, Hisanori; Misra, Gauri P.; Wu, Linfeng; Janagam, Dileep R.; Gardner, Thomas W.; Lowe, Tao L.

2015-01-01

Purpose Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. Methods The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. Results The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. Conclusions The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia. PMID:26658505

Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2016-08-01

Objective. The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. Approach. As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. Main results. We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. Significance. Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal ‘tickling’ has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.

Long-term follow-up of patients with retinitis pigmentosa (RP) receiving intraocular ciliary neurotrophic factor implants

PubMed Central

Birch, David G.; Bennett, Lea D.; Duncan, Jacque L.; Weleber, Richard G.; Pennesi, Mark E.

2016-01-01

Purpose To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Design Long-term follow up of a multicenter, sham-controlled study. Methods Thirty-six patients at three CNTF4 sites were randomly assigned to receive a high- or low- dose implant in one eye and sham surgery in the fellow eye. The primary endpoint (change in visual field sensitivity at 12 months) has been reported previously.1 Here we report long-term visual acuity, visual field and optical coherence tomography (OCT) outcomes in 24 patients either retaining or explanting the device at 24 months relative to sham-treated eyes. Results Eyes retaining the implant showed significantly greater visual field loss from baseline than either explanted eyes or sham eyes through 42 months. By 60 months and continuing through 96 months, visual field loss was comparable among sham-treated eyes, eyes retaining the implant and explanted eyes, as was visual acuity and OCT macular volume. Conclusions Over the short term, ciliary neurotrophic factor released continuously from an intra-vitreal implant lead to loss of total visual field sensitivity that was greater than the natural progression in the sham-treated eye. This additional loss of sensitivity related to the active implant was reversible when the implant was removed. Over the long term (60 – 96 months), there was no evidence of efficacy for visual acuity, visual field sensitivity or OCT measures of retinal structure. PMID:27457255

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

PubMed

Endo, Takao; Fujikado, Takashi; Hirota, Masakazu; Kanda, Hiroyuki; Morimoto, Takeshi; Nishida, Kohji

2018-04-20

To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p < 0.01). Performance of a reaching movement improved in a patient with an STS retinal prosthesis implanted in an eye with residual natural vision. Patients with a retinal prosthesis may be able to improve their visual performance by using both artificial vision and their residual natural vision. Beginning date of the trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

Five-year safety and performance results from the Argus II Retinal Prosthesis System clinical trial

PubMed Central

da Cruz, Lyndon; Dorn, Jessy D.; Humayun, Mark S.; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Ho, Allen C.; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V.; Arditi, Aries; Greenberg, Robert J.

2016-01-01

Purpose The Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) was developed to restore some vision to patients blind from retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception due to end-stage RP. Design The study is a prospective, multicenter, single-arm, clinical trial. Within-patient controls included the non-implanted fellow eye and patients' native residual vision compared to their vision when using the System. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II System. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Secondary measures included functional vision performance on objectively-scored real-world tasks. Results Twenty-four out of 30 patients remained implanted with functioning Argus II Systems at 5 years post-implant. Only one additional serious adverse event was experienced since the 3-year time point. Patients performed significantly better with the System ON than OFF on all visual function tests and functional vision tasks. Conclusions The five-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. PMID:27453256

Microfabrication of an Implantable silicone Microelectrode array for an epiretinal prosthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maghribi, Mariam Nader

2003-06-10

Millions of people suffering from diseases such as retinitis pigmentosa and macular degeneration are legally blind due to the loss of photoreceptor function. Fortunately a large percentage of the neural cells connected to the photoreceptors remain viable, and electrical stimulation of these cells has been shown to result in visual perception. These findings have generated worldwide efforts to develop a retinal prosthesis device, with the hope of restoring vision. Advances in microfabrication, integrated circuits, and wireless technologies provide the means to reach this challenging goal. This dissertation describes the development of innovative silicone-based microfabrication techniques for producing an implantable microelectrodemore » array. The microelectrode array is a component of an epiretinal prosthesis being developed by a multi-laboratory consortium. This array will serve as the interface between an electronic imaging system and the human eye, directly stimulating retinal neurons via thin film conducting traces. Because the array is intended as a long-term implant, vital biological and physical design requirements must be met. A retinal implant poses difficult engineering challenges due to the size of the intraocular cavity and the delicate retina. Not only does it have to be biocompatible in terms of cytotoxicity and degradation, but it also has to be structurally biocompatible, with regard to smooth edges and high conformability; basically mimicking the biological tissue. This is vital to minimize stress and prevent physical damage to the retina. Also, the device must be robust to withstand the forces imposed on it during fabrication and implantation. In order to meet these biocompatibility needs, the use of non-conventional microfabrication materials such as silicone is required. This mandates the enhancement of currently available polymer-based fabrication techniques and the development of new microfabrication methods. Through an iterative process, devices were designed, fabricated, tested and implanted into a canine eye. Metal traces were embedded within a thin substrate fabricated using poly (dimethyl siloxane) (PDMS), an inert biocompatible elastomeric material with high oxygen permeability and low water permeability. Due to its highly conformable nature, PDMS contacted the curved retinal surface uniformly. Fundamental material characteristics were examined to develop reliable and repeatable fabrication processes.« less

Deposition and Characterization of Hermetic, Biocompatible Thin Film Coatings for Implantable, Electrically Active Devices

NASA Astrophysics Data System (ADS)

Sweitzer, Robyn K.

Retinal prostheses may be used to support patients suffering from Age-related macular degeneration or retinitis pigmentosa. A hermetic encapsulation of the poly(imide )-based prosthesis is important in order to prevent the leakage of water and ions into the electric circuitry embedded in the poly(imide) matrix. The deposition of amorphous aluminum oxide (by sputtering) and diamond like carbon (by pulsed laser ablation and vacuum arc vapor deposition) were studied for the application in retinal prostheses. The resulting thin films were characterized for composition, thickness, adhesion and smoothness by scanning electron microscopy-energy dispersive spectroscopy, atomic force microscopy, profilometry and light microscopy. Electrical stability was evaluated and found to be good. The as-deposited films prevented incursion of salinated fluids into the implant over two (2) three month trials soaking in normal saline at body temperature, Biocompatibility was tested in vivo by implanting coated specimen subretinally in the eye of Yucatan pigs. While amorphous aluminum oxide is more readily deposited with sufficient adhesion quality, biocompatibility studies showed a superior behavior of diamond-like carbon. Amorphous aluminum oxide had more adverse effects and caused more severe damage to the retinal tissue.

Design and validation of a foldable and photovoltaic wide-field epiretinal prosthesis.

PubMed

Ferlauto, Laura; Airaghi Leccardi, Marta Jole Ildelfonsa; Chenais, Naïg Aurelia Ludmilla; Gilliéron, Samuel Charles Antoine; Vagni, Paola; Bevilacqua, Michele; Wolfensberger, Thomas J; Sivula, Kevin; Ghezzi, Diego

2018-03-08

Retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, few hundred patients have received a retinal implant. Inspired by intraocular lenses, we have designed a foldable and photovoltaic wide-field epiretinal prosthesis (named POLYRETINA) capable of stimulating wireless retinal ganglion cells. Here we show that within a visual angle of 46.3 degrees, POLYRETINA embeds 2215 stimulating pixels, of which 967 are in the central area of 5 mm, it is foldable to allow implantation through a small scleral incision, and it has a hemispherical shape to match the curvature of the eye. We demonstrate that it is not cytotoxic and respects optical and thermal safety standards; accelerated ageing shows a lifetime of at least 2 years. POLYRETINA represents significant progress towards the improvement of both visual acuity and visual field with the same device, a current challenging issue in the field.

Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo

NASA Astrophysics Data System (ADS)

Fransen, James W.; Pangeni, Gobinda; Pardue, Machelle T.; McCall, Maureen A.

2014-08-01

Objective. In clinical trials, retinitis pigmentosa patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). Approach. PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. Main results. When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (⩽7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells. The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. Significance. Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within the retina and is likely to produce higher spatial resolution in patients.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy

PubMed Central

Jabs, Douglas A.; Ahuja, Alka; Van Natta, Mark; Dunn, JP; Yeh, Steven

2012-01-01

Purpose To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Design Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. Participants 250 patients with CMV retinitis and CD4+ T cells <100 cells/µL (n=221) at enrollment or incident retinitis (n=29) during cohort follow-up. Methods The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Main Outcome Measures Mortality, CMV dissemination, retinitis progression, treatment side effects. Results Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR]=0.5; 95% confidence interval [CI] = 0.3, 0.7; P=0.006), 90% reduction in new visceral CMV disease (adjusted HR=0.1; 95% CI = 0.04, 0.4;P=0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR=0.2; 95% CI= 0.1, 0.5; P=0.0005) when compared to those using only intraocular therapy (implants or injections). Compared to systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR=3.4, P=0.004) and greater visual field loss (for loss of ½ of the normal field, adjusted HR=5.5, P<0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression =0.5, P=0.26, and for loss ½ visual field =0.5, P=0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis among those treated with intravitreal injections was 0.017/EY (95% CI =0.006, 0.05) and among those treated with an implant 0.01/EY (95% CI =0.002, 0.04). Conclusions In the HAART era, systemic anti-CMV therapy, while there is immune compromise, appears to provide benefits in terms of longer survival and decreased CMV dissemination. PMID:23419804

The electrical properties of 60 keV zinc ions implanted into semi-insulating gallium arsenide

NASA Technical Reports Server (NTRS)

Littlejohn, M. A.; Anikara, R.

1972-01-01

The electrical behavior of zinc ions implanted into chromium-doped semiinsulating gallium arsenide was investigated by measurements of the sheet resistivity and Hall effect. Room temperature implantations were performed using fluence values from 10 to the 12th to 10 to the 15th power/sq cm at 60 keV. The samples were annealed for 30 minutes in a nitrogen atmosphere up to 800 C in steps of 200 C and the effect of this annealing on the Hall effect and sheet resistivity was studied at room temperature using the Van der Pauw technique. The temperature dependence of sheet resistivity and mobility was measured from liquid nitrogen temperature to room temperature. Finally, a measurement of the implanted profile was obtained using a layer removal technique combined with the Hall effect and sheet resistivity measurements.

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.

PubMed

Liu, Xiangwei; Tan, Naiwen; Zhou, Yuchao; Wei, Hongbo; Ren, Shuai; Yu, Fan; Chen, Hui; Jia, Chengming; Yang, Guodong; Song, Yingliang

2017-01-01

Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.

Orbital cellulitis following silicone-sponge scleral buckles

PubMed Central

Nemet, Arie Y; Ferencz, Joseph R; Segal, Ori; Meshi, Amit

2013-01-01

Background Acute or chronic infection of the scleral explant is rare. We report seven cases of scleral explant infections that caused orbital cellulitis. Materials and methods This was a retrospective chart review of oculoplastics at oculoplastics and vitreo-retinal units in a secondary referral hospital. All subjects had orbital cellulitis secondary to scleral buckle in the range of January 1990 to March 2010. Demographics, imaging studies, and pathology specimens were reviewed. Results A total of 841 silicone-sponge scleral buckle implants for rhegmatogenous retinal detachment were performed. Forty were extracted (4.75%; annual rate of 1.9 cases). Seven (0.83%) had orbital cellulitis. The mean time from implantation to presentation was 5.7 years. There was bacterial growth in all specimens, with Staphylococcus aureus in four. Conclusions Patients who are operated on with silicone-sponge scleral buckling for rhegmatogenous retinal detachment sometimes require removal of the implant because of infection. However, the infection rate is low. Patients should be followed in the long term for possible complications. PMID:24204118

Subconjunctivally Implantable Hydrogels with Degradable and Thermoresponsive Properties for Sustained Release of Insulin to the Retina

PubMed Central

Misra, Gauri P.; Singh, Ravi S.J.; Aleman, Tomas S.; Jacobson, Samuel G.; Gardner, Thomas W.; Lowe, Tao L.

2009-01-01

The objective of this work is to develop subconjunctivally implantable, biodegradable hydrogels for sustained release of intact insulin to the retina to prevent and treat retinal neurovascular degeneration such as diabetic retinopathy. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-(2-hydroxyetheyl methacrylate) units (Dex-lactateHEMA) in 25:75 (v:v) ethanol:water mixture solvent. Insulin is loaded into the hydrogels during the synthesis process with loading efficiency up to 98%. The hydrogels can release biologically active insulin in vitro for at least one week and the release kinetics can be modulated by varying the ratio between NIPAAm and Dex-lactateHEMA and altering the physical size of the hydrogels. The hydrogels are not toxic to R28 retinal neuron cells in culture medium with 100% cell viability. The hydrogels can be implanted under the conjunctiva without causing adverse effects to the retina based on hematoxylin and eosin stain, immunostaining for microglial cell activation, and electroretinography. These subconjunctivally implantable hydrogels have potential for long-term periocular delivery of insulin or other drugs to treat diabetic retinopathy and other retinal diseases. PMID:19709741

An analysis of observer-rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years.

PubMed

Geruschat, Duane R; Richards, Thomas P; Arditi, Aries; da Cruz, Lyndon; Dagnelie, Gislin; Dorn, Jessy D; Duncan, Jacque L; Ho, Allen C; Olmos de Koo, Lisa C; Sahel, José-Alain; Stanga, Paulo E; Thumann, Gabriele; Wang, Vizhong; Greenberg, Robert J

2016-05-01

The purpose of this analysis was to compare observer-rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. The Functional Low-Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow-up of 36 months. FLORA is a multi-component instrument that consists in part of observer-rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four-point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including 'Visual orientation', 'Visual mobility', 'Daily life and 'Interaction with others'. Twenty-six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients' performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision-related tasks with the device ON versus OFF. © 2016 The Authors Clinical and Experimental Optometry published by John Wiley & Sons Australia, Ltd on behalf of Optometry Australia.

An analysis of observer‐rated functional vision in patients implanted with the Argus II Retinal Prosthesis System at three years

PubMed Central

Richards, Thomas P; Arditi, Aries; da Cruz, Lyndon; Dagnelie, Gislin; Dorn, Jessy D; Duncan, Jacque L; Ho, Allen C; Olmos de Koo, Lisa C; Sahel, José‐Alain; Stanga, Paulo E; Thumann, Gabriele; Wang, Vizhong; Greenberg, Robert J

2016-01-01

Abstract Objective The purpose of this analysis was to compare observer‐rated tasks in patients implanted with the Argus II Retinal Prosthesis System, when the device is ON versus OFF. Methods The Functional Low‐Vision Observer Rated Assessment (FLORA) instrument was administered to 26 blind patients implanted with the Argus II Retinal Prosthesis System at a mean follow‐up of 36 months. FLORA is a multi‐component instrument that consists in part of observer‐rated assessment of 35 tasks completed with the device ON versus OFF. The ease with which a patient completes a task is scored using a four‐point scale, ranging from easy (score of 1) to impossible (score of 4). The tasks are evaluated individually and organised into four discrete domains, including ‘Visual orientation’, ‘Visual mobility’, ‘Daily life and ‘Interaction with others’. Results Twenty‐six patients completed each of the 35 tasks. Overall, 24 out of 35 tasks (69 per cent) were statistically significantly easier to achieve with the device ON versus OFF. In each of the four domains, patients’ performances were significantly better (p < 0.05) with the device ON versus OFF, ranging from 19 to 38 per cent improvement. Conclusion Patients with an Argus II Retinal Prosthesis implanted for 18 to 44 months (mean 36 months), demonstrated significantly improved completion of vision‐related tasks with the device ON versus OFF. PMID:26804484

Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis

NASA Astrophysics Data System (ADS)

Villalobos, Joel; Fallon, James B.; Nayagam, David A. X.; Shivdasani, Mohit N.; Luu, Chi D.; Allen, Penelope J.; Shepherd, Robert K.; Williams, Chris E.

2014-08-01

Objective. The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. Approach. A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. Main results. The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm-2). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. Significance. Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.

An Intraocular Camera for Retinal Prostheses: Restoring Sight to the Blind

NASA Astrophysics Data System (ADS)

Stiles, Noelle R. B.; McIntosh, Benjamin P.; Nasiatka, Patrick J.; Hauer, Michelle C.; Weiland, James D.; Humayun, Mark S.; Tanguay, Armand R., Jr.

Implantation of an intraocular retinal prosthesis represents one possible approach to the restoration of sight in those with minimal light perception due to photoreceptor degenerating diseases such as retinitis pigmentosa and age-related macular degeneration. In such an intraocular retinal prosthesis, a microstimulator array attached to the retina is used to electrically stimulate still-viable retinal ganglion cells that transmit retinotopic image information to the visual cortex by means of the optic nerve, thereby creating an image percept. We describe herein an intraocular camera that is designed to be implanted in the crystalline lens sac and connected to the microstimulator array. Replacement of an extraocular (head-mounted) camera with the intraocular camera restores the natural coupling of head and eye motion associated with foveation, thereby enhancing visual acquisition, navigation, and mobility tasks. This research is in no small part inspired by the unique scientific style and research methodologies that many of us have learned from Prof. Richard K. Chang of Yale University, and is included herein as an example of the extent and breadth of his impact and legacy.

CHAPTER: In-Situ Characterization of Stimulating Microelectrode Arrays: Study of an Idealized Structure Based on Argus II Retinal implantsBOOK TITLE: Implantable Neural Prostheses 2: Techniques and Engineering Approaches, D.M. Zhou and E. Greenbaum, Eds., Springer, NY 2009

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenbaum, Elias; Sanders, Charlene A; Kandagor, Vincent

The development of a retinal prosthesis for artificial sight includes a study of the factors affecting the structural and functional stability of chronically implanted microelectrode arrays. Although neuron depolarization and propagation of electrical signals have been studied for nearly a century, the use of multielectrode stimulation as a proposed therapy to treat blindness is a frontier area of modern ophthalmology research. Mapping and characterizing the topographic information contained in the electric field potentials and understanding how this information is transmitted and interpreted in the visual cortex is still very much a work in progress. In order to characterize the electricalmore » field patterns generated by the device, an in vitro prototype that mimics several of the physical and chemical parameters of the in vivo visual implant device was fabricated. We carried out multiple electrical measurements in a model 'eye,' beginning with a single electrode, followed by a 9-electrode array structure, both idealized components based on the Argus II retinal implants. Correlating the information contained in the topographic features of the electric fields with psychophysical testing in patients may help reduce the time required for patients to convert the electrical patterns into graphic signals.« less

Wireless technologies for closed-loop retinal prostheses.

PubMed

Ng, David C; Bai, Shun; Yang, Jiawei; Tran, Nhan; Skafidas, Efstratios

2009-12-01

In this paper, we discuss various technologies needed to develop retinal prostheses with wireless power and data telemetry operation. In addition to the need to communicate with the implanted device, supply of power to the retinal prosthesis is especially difficult. This is because, in the implanted state, the device is not fixed in position due to constant motion of the eye. Furthermore, a retinal prosthesis incorporating a high density electrode array of more than 1000 electrodes is expected to consume approximately 45 mW of power and require 300 kbps of image and stimulation data. The front end of the wireless power and data transmission, the antenna, needs to be small compared to the size of the eye. Also, the wireless module is expected to operate in the reactive near-field region due to small separation between the transmit and receive antennas compared to their size and corresponding operating wavelength. An inductive link is studied as a means to transfer power and for data telemetry between the implant and external unit. In this work, the use of integrated circuit and microfabrication technologies for implementing inductive links is discussed. A closed-loop approach is taken to improve performance and reach optimum operation condition. Design and simulation data are presented as the basis for development of viable wireless module prototypes.

Wireless technologies for closed-loop retinal prostheses

NASA Astrophysics Data System (ADS)

Ng, David C.; Bai, Shun; Yang, Jiawei; Tran, Nhan; Skafidas, Efstratios

2009-12-01

In this paper, we discuss various technologies needed to develop retinal prostheses with wireless power and data telemetry operation. In addition to the need to communicate with the implanted device, supply of power to the retinal prosthesis is especially difficult. This is because, in the implanted state, the device is not fixed in position due to constant motion of the eye. Furthermore, a retinal prosthesis incorporating a high density electrode array of more than 1000 electrodes is expected to consume approximately 45 mW of power and require 300 kbps of image and stimulation data. The front end of the wireless power and data transmission, the antenna, needs to be small compared to the size of the eye. Also, the wireless module is expected to operate in the reactive near-field region due to small separation between the transmit and receive antennas compared to their size and corresponding operating wavelength. An inductive link is studied as a means to transfer power and for data telemetry between the implant and external unit. In this work, the use of integrated circuit and microfabrication technologies for implementing inductive links is discussed. A closed-loop approach is taken to improve performance and reach optimum operation condition. Design and simulation data are presented as the basis for development of viable wireless module prototypes.

Vision function testing for a suprachoroidal retinal prosthesis: effects of image filtering

NASA Astrophysics Data System (ADS)

Barnes, Nick; Scott, Adele F.; Lieby, Paulette; Petoe, Matthew A.; McCarthy, Chris; Stacey, Ashley; Ayton, Lauren N.; Sinclair, Nicholas C.; Shivdasani, Mohit N.; Lovell, Nigel H.; McDermott, Hugh J.; Walker, Janine G.; BVA Consortium,the

2016-06-01

Objective. One strategy to improve the effectiveness of prosthetic vision devices is to process incoming images to ensure that key information can be perceived by the user. This paper presents the first comprehensive results of vision function testing for a suprachoroidal retinal prosthetic device utilizing of 20 stimulating electrodes. Further, we investigate whether using image filtering can improve results on a light localization task for implanted participants compared to minimal vision processing. No controlled implanted participant studies have yet investigated whether vision processing methods that are not task-specific can lead to improved results. Approach. Three participants with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal retinal prosthesis. All three completed multiple trials of a light localization test, and one participant completed multiple trials of acuity tests. The visual representations used were: Lanczos2 (a high quality Nyquist bandlimited downsampling filter); minimal vision processing (MVP); wide view regional averaging filtering (WV); scrambled; and, system off. Main results. Using Lanczos2, all three participants successfully completed a light localization task and obtained a significantly higher percentage of correct responses than using MVP (p≤slant 0.025) or with system off (p\\lt 0.0001). Further, in a preliminary result using Lanczos2, one participant successfully completed grating acuity and Landolt C tasks, and showed significantly better performance (p=0.004) compared to WV, scrambled and system off on the grating acuity task. Significance. Participants successfully completed vision tasks using a 20 electrode suprachoroidal retinal prosthesis. Vision processing with a Nyquist bandlimited image filter has shown an advantage for a light localization task. This result suggests that this and targeted, more advanced vision processing schemes may become important components of retinal prostheses to enhance performance. ClinicalTrials.gov Identifier: NCT01603576.

Viral retinitis following intraocular or periocular corticosteroid administration: a case series and comprehensive review of the literature.

PubMed

Takakura, Ako; Tessler, Howard H; Goldstein, Debra A; Guex-Crosier, Yan; Chan, Chi-Chao; Brown, Diane M; Thorne, Jennifer E; Wang, Robert; Cunningham, Emmett T

2014-06-01

To describe viral retinitis following intravitreal and periocular corticosteroid administration. Retrospective case series and comprehensive literature review. We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.

Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature

PubMed Central

Takakura, Ako; Tessler, Howard H.; Goldstein, Debra A.; Guex-Crosier, Yan; Chan, Chi-Chao; Brown, Diane M.; Thorne, Jennifer E.; Wang, Robert; Cunningham, Emmett T.

2014-01-01

Purpose To describe viral retinitis following intravitreal and periocular corticosteroid administration. Methods Retrospective case series and comprehensive literature review. Results We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25–13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Conclusions Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy. PMID:24655372

A case of aminoglycosides induced retinal toxicity treated with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex(®)).

PubMed

Hernández Pardines, F; Tapia-Quijada, H; Hueso-Abancens, J R

2016-06-01

The case is described of a patient who had a sudden loss of vision in her right eye after glaucoma surgery. A diagnosis of retinal toxicity due to tobramycin (an aminoglycoside) was reached, which was characterised by retinal whitening with a red cherry stain, macular oedema, and vasculitis that progressed to papillary and macular atrophy with arteriolar sclerosis. Given the severity of symptoms an early attempt was made with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex®, Allergan S.A.), without response. Aminoglycoside toxicity is a rare, idiosyncratic, very serious complication for which there is no effective treatment. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Ranibizumab versus dexamethasone implant for central retinal vein occlusion: the RANIDEX study.

PubMed

Chatziralli, Irini; Theodossiadis, George; Kabanarou, Stamatina A; Parikakis, Efstratios; Xirou, Tina; Mitropoulos, Panagiotis; Theodossiadis, Panagiotis

2017-10-01

To compare intravitreal ranibizumab and dexamethasone implant in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). Participants were 42 treatment naive patients with ME due to CRVO, who received either intravitreal 0.5 mg ranibizumab (n = 25) or intravitreal 0.7 mg dexamethasone implant (n = 17). The main outcomes included the mean change in best corrected visual acuity (BCVA) and central subfield thickness (CST) at month 12 compared to baseline in the two groups. At month 12, there was no statistically significant difference in BCVA and CST change between the two groups. However, there was recurrence in ME at month 5 in the dexamethasone group. Both ranibizumab and dexamethasone implant were found to be safe and effective at the 12-month follow-up in patients with ME secondary to CRVO. Since there was a recurrence in ME at month 5 in the dexamethasone group, we suggested that intravitreal injection of dexamethasone implant should be potentially administered sooner than 6 months.

Suspected bacterial endophthalmitis following sustained-release dexamethasone intravitreal implant: a case report.

PubMed

Arıkan Yorgun, Mücella; Mutlu, Melek; Toklu, Yasin; Cakmak, Hasan Basri; Cağıl, Nurullah

2014-06-01

A 58-year-old man admitted to our opthalmology department with the complaint of branch retinal vein occlusion. He was treated with intravitreal Ozurdex in the right eye. Two days after the injection, the patient presented with ocular pain and the visual acuity was hand movement. A diagnosis of endophthalmitis was made. We performed emergent pars plana vitrectomy (PPV) and the implant was removed from the vitreous cavity using a retinal forceps. A combination of vancomycin 1.0 mg and amikacin 0.4 mg was injected intravitreally. However, because of the blurring in the vitreus one week after the procedure, phacoemulsification and a repeat PPV was performed. Five days after the last procedure the signs and symptoms of endophthalmitis were resolved. Our case demonstrated that endophthalmitis could develop after intravitreal implantation of Ozurdex. Surgical removal of the implant and immediate vitrectomy seems to be a useful treatment option in these cases.

Ring-shaped dysphotopsia associated with posterior chamber phakic implantable collamer lenses with a central hole.

PubMed

Eom, Youngsub; Kim, Dae Wook; Ryu, Dongok; Kim, Jun-Heon; Yang, Seul Ki; Song, Jong Suk; Kim, Sug-Whan; Kim, Hyo Myung

2017-05-01

To evaluate the incidence of central hole-induced ring-shaped dysphotopsia after posterior chamber phakic implantable collamer lens (ICL) with central hole (hole ICL) implantation and to investigate the causes of central hole-induced dysphotopsia. The clinical study enrolled 29 eyes of 15 consecutive myopic patients implanted with hole ICL. The incidence of ring-shaped dysphotopsia after hole ICL implantation was evaluated. In the experimental simulation study, non-sequential ray tracing was used to construct myopic human eye models with hole ICL and ICL without a central hole (conventional ICL). Simulated retinal images measured in log-scale irradiance were compared between the two ICLs for an extended Lambertian light-emitting disc object 20 cm in diameter placed 2 m from the corneal vertex. To investigate the causes of hole-induced dysphotopsia, a series of retinal images were simulated using point sources at infinity with well-defined field angles (0 to -20°) and multiple ICL models. Of 29 eyes, 15 experienced ring-shaped dysphotopsia after hole ICL implantation. The simulation study using an extended Lambertian source showed that hole ICL-evoked ring-shaped dysphotopsia was formed at a retinal field angle of ±40°. Component-level analysis using a well-defined off-axis point source from infinity revealed that ring-shaped dysphotopsia was generated by stray light refraction from the inner wall of the hole and the posterior ICL surface. Hole ICL-evoked ring-shaped dysphotopsia was related to light refraction at the central hole structure. Surgeons are advised to explain to patients the possibility of ring-shaped dysphotopsia after hole ICL implantation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

PubMed

Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark; Dunn, J P; Yeh, Steven

2013-06-01

To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Mortality, CMV dissemination, retinitis progression, and treatment side effects. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. Proprietary or commercial disclosure may be found after the references. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The Artificial Silicon Retina in Retinitis Pigmentosa Patients (An American Ophthalmological Association Thesis)

PubMed Central

Chow, Alan Y.; Bittner, Ava K.; Pardue, Machelle T.

2010-01-01

Purpose: In a published pilot study, a light-activated microphotodiode-array chip, the artificial silicon retina (ASR), was implanted subretinally in 6 retinitis pigmentosa (RP) patients for up to 18 months. The ASR electrically induced retinal neurotrophic rescue of visual acuity, contrast, and color perception and raised several questions: (1) Would neurotrophic effects develop and persist in additionally implanted RP patients? (2) Could vision in these patients be reliably assessed? (3) Would the ASR be tolerated and function for extended periods? Methods: Four additional RP patients were implanted and observed along with the 6 pilot patients. Of the 10 patients, 6 had vision levels that allowed for more standardized testing and were followed up for 7+ years utilizing ETDRS charts and a 4-alternative forced choice (AFC) Chow grating acuity test (CGAT). A 10-AFC Chow color test (CCT) extended the range of color vision testing. Histologic examination of the eyes of one patient, who died of an unrelated event, was performed. Results: The ASR was well tolerated, and improvement and/or slowing of vision loss occurred in all 6 patients. CGAT extended low vision acuity testing by logMAR 0.6. CCT expanded the range of color vision testing and correlated well with PV-16 (r = 0.77). An ASR recovered from a patient 5 years after implantation showed minor disruption and excellent electrical function. Conclusion: ASR-implanted RP patients experienced prolonged neurotrophic rescue of vision. CGAT and CCT extended the range of acuity and color vision testing in low vision patients. ASR implantation may improve and prolong vision in RP patients. PMID:21212852

In vivo operation of the Boston 15-channel wireless subretinal visual prosthesis

NASA Astrophysics Data System (ADS)

Shire, Douglas B.; Doyle, Patrick; Kelly, Shawn K.; Gingerich, Marcus D.; Chen, Jinghua; Cogan, Stuart F.; Drohan, William A.; Mendoza, Oscar; Theogarajan, Luke; Wyatt, John; Rizzo, Joseph F.

2010-02-01

This presentation concerns the engineering development of the Boston visual prosthesis for restoring useful vision to patients blind with degenerative retinal disease. A miniaturized, hermetically-encased, 15-channel wirelessly-operated retinal prosthetic was developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array having sputtered iridium oxide electrodes. This array is implanted into the subretinal space using a specially-designed ab externo surgical technique; the bulk of the prosthesis is on the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip; secondary power/data receiving coils surround the cornea. Long-term in vitro pulse testing was also performed on the electrodes to ensure their stability over years of operation. Assemblies were first tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a computer with a custom graphical user interface. Operation of the retinal implant was verified in vivo in 3 minipigs for more than three months by measuring stimulus artifacts on the eye surface using contact lens electrodes.

Evaluation of the ion implantation process for production of solar cells from silicon sheet materials

NASA Technical Reports Server (NTRS)

Spitzer, M. B.

1983-01-01

The objective of this program is the investigation and evaluation of the capabilities of the ion implantation process for the production of photovoltaic cells from a variety of present-day, state-of-the-art, low-cost silicon sheet materials. Task 1 of the program concerns application of ion implantation and furnace annealing to fabrication of cells made from dendritic web silicon. Task 2 comprises the application of ion implantation and pulsed electron beam annealing (PEBA) to cells made from SEMIX, SILSO, heat-exchanger-method (HEM), edge-defined film-fed growth (EFG) and Czochralski (CZ) silicon. The goals of Task 1 comprise an investigation of implantation and anneal processes applied to dendritic web. A further goal is the evaluation of surface passivation and back surface reflector formation. In this way, processes yielding the very highest efficiency can be evaluated. Task 2 seeks to evaluate the use of PEBA for various sheet materials. A comparison of PEBA to thermal annealing will be made for a variety of ion implantation processes.

Bilateral rhegmatogenous retinal detachment due to unusual retinal degeneration in Down syndrome: A case report.

PubMed

Yonemoto, Yumiko; Morishita, Seita; Fukumoto, Masanori; Mimura, Masashi; Sato, Takaki; Kida, Teruyo; Kojima, Shota; Oku, Hidehiro; Sugasawa, Jun; Ikeda, Tsunehiko

2018-06-01

The aim of this study was to report a case of Down syndrome (DS) complicated with bilateral retinal detachment (RD) due to unusual retinal degeneration. A 9-year-old girl complained of bilateral visual disturbance during a follow-up examination for myopia and strabismus. Slit-lamp examination revealed moderate posterior subcapsular cataract in both eyes. B-mode echography showed bilateral bullous RD; however, it was difficult to detect the causal retinal breaks due to poor mydriasis. For treatment, the patient underwent bilateral lensectomy, vitrectomy, and silicone oil tamponade. Intraoperative findings revealed symmetrical retinal breaks and unusual caterpillar-like retinal degeneration on the upper temporal side of both eyes. Three months later, the patient underwent bilateral silicone oil removal and intraocular lens implantation. In this case, the retinal degeneration was morphologically different from retinal lattice degeneration, thus suggesting that it might be involved in the onset of DS-related bilateral RD.

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

PubMed

da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

2016-10-01

The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Physiological Response in Ovis Aries Resulting from Electrical Stimuli Delivered by an Implantable Vision Prosthesis

DTIC Science & Technology

2001-10-25

inner retina. The device is intended as a treatment to blindness. Specifically, degenerative disorders of the retina such as retinitis pigmentosa ...Trullemans C., Chronic electrical stimulation of the optic nerve in a retinitis pigmentosa blind volunteer. Inv. Ophth. Vis. Sci., 1999, 40: S783...stimulation delivered to the retinal tissue is derived from two stimulation channels of the 100 channel neurostimulation electronics [9]. Power and

Pulse Mode Light Sensing Using Four-Layer Semiconductor Structures and Their Application in Neural Networks

DTIC Science & Technology

2008-12-01

However, the visual sensation was found to occur in retinal areas distant from the implant [10]. Since the current generated under normal light...electronics could limit the use of the microphotodetector array in retinal stimulation. Alternatively, a thin array, containing 64 electrodes...that passes through the skull and skin. Outside the skull, the device is similar to the retinal stimulators, with a television camera mounted on

Ophthalmologial Applications of Carbon Nanotube Nanotechology

NASA Technical Reports Server (NTRS)

Loftus, David; Girten, Beverly (Technical Monitor)

2002-01-01

The development of an implantable device consisting of an array of carbon nanotubes on a silicon chip for restoration of vision in patients with macular degeneration and other retinal disorders is presented. The use of carbon nanotube bucky paper for retinal cell transplantation is proposed. This paper is in viewgraph form.

Electric crosstalk impairs spatial resolution of multi-electrode arrays in retinal implants

NASA Astrophysics Data System (ADS)

Wilke, R. G. H.; Khalili Moghadam, G.; Lovell, N. H.; Suaning, G. J.; Dokos, S.

2011-08-01

Active multi-electrode arrays are used in vision prostheses, including optic nerve cuffs and cortical and retinal implants for stimulation of neural tissue. For retinal implants, arrays with up to 1500 electrodes are used in clinical trials. The ability to convey information with high spatial resolution is critical for these applications. To assess the extent to which spatial resolution is impaired by electric crosstalk, finite-element simulation of electric field distribution in a simplified passive tissue model of the retina is performed. The effects of electrode size, electrode spacing, distance to target cells, and electrode return configuration (monopolar, tripolar, hexagonal) on spatial resolution is investigated in the form of a mathematical model of electric field distribution. Results show that spatial resolution is impaired with increased distance from the electrode array to the target cells. This effect can be partly compensated by non-monopolar electrode configurations and larger electrode diameters, albeit at the expense of lower pixel densities due to larger covering areas by each stimulation electrode. In applications where multi-electrode arrays can be brought into close proximity to target cells, as presumably with epiretinal implants, smaller electrodes in monopolar configuration can provide the highest spatial resolution. However, if the implantation site is further from the target cells, as is the case in suprachoroidal approaches, hexagonally guarded electrode return configurations can convey higher spatial resolution. This paper was originally submitted for the special issue containing contributions from the Sixth Biennial Research Congress of The Eye and the Chip.

Establishing a Surgical Procedure for Rhesus Epiretinal Scaffold Implantation with HiPSC-Derived Retinal Progenitors

PubMed Central

Luo, Ziming; Li, Kang; Li, Kaijing; Xian, Bikun; Liu, Ying; Yang, Sijing; Xu, Chaochao; Lu, Shoutao; Zhang, Haijun

2018-01-01

Background To develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. Methods Retinal progenitors were seeded onto a poly(lactic-co-glycolic) acid (PLGA) scaffold. First, the cellular scaffolds were delivered by 18G catheter or retinal forceps into rabbit epiretinal space (n = 50). Then, the cell survival rate was evaluated by Cell Counting Kit-8 (CCK-8). Second, three methods of scaffold fixation, including adhesion after gas-liquid exchange (n = 1), tamponade by hydrogel (n = 1), and fixation by retinal tacks (n = 4), were performed in rhesus monkeys. After one month, fundus photography and SD-OCT were performed to assess the outcomes, and histological examination was performed to evaluate proliferation. Results The cell survival rate was significantly higher in the catheter group. Follow-up examination showed that retinal tack fixation was the only method to maintain the scaffolds attached to host retina for at least 3 weeks, which is the minimal time required for cell integration. Histological staining demonstrated slight glial fibrillary acidic protein (GFAP) accumulation in the retinal tack insertion area. Conclusions The established surgical procedure offers a new insight into research of epiretinal cell replacement therapy in rhesus eyes. The successful delivery and long-term fixation provide a prerequisite for cell migration and integration. PMID:29760741

Long-term results from an epiretinal prosthesis to restore sight to the blind

PubMed Central

Ho, Allen C.; Humayun, Mark S.; Dorn, Jessy D.; da Cruz, Lyndon; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Brown, Gary C.; Haller, Julia A.; Regillo, Carl D.; Del Priore, Lucian V.; Arditi, Aries; Geruschat, Duane R.; Greenberg, Robert J.

2015-01-01

Purpose Retinitis Pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. A rare disease, it affects about 100,000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in restoring some visual function to subjects completely blind from RP. Herein, we report clinical trial results at 1 and 3 years post-implant. Design The study is a multicenter, single-arm, prospective clinical trial. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Subjects served as their own controls – i.e., implanted eye vs. fellow eye, and System ON vs. System OFF (native residual vision). Methods The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Results Twenty-nine out of 30 subjects remained implanted with functioning Argus II Systems at 3 years post-implant. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the System ON than OFF on all visual function tests and functional vision assessments. Conclusions The three-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the FDA and a CE Mark in Europe. The Argus II System is the first and only retinal implant to have both approvals. PMID:26162233

Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye.

PubMed

Zhou, Chengxin; Robert, Marie-Claude; Kapoulea, Vassiliki; Lei, Fengyang; Stagner, Anna M; Jakobiec, Frederick A; Dohlman, Claes H; Paschalis, Eleftherios I

2017-01-01

Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS). The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months. After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation. This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation.

Combination therapy with dexamethasone intravitreal implant and macular grid laser in patients with branch retinal vein occlusion.

PubMed

Pichi, Francesco; Specchia, Claudia; Vitale, Lucia; Lembo, Andrea; Morara, Mariachiara; Veronese, Chiara; Ciardella, Antonio P; Nucci, Paolo

2014-03-01

To test a combination of dexamethasone intravitreal implant with macular grid laser for macular edema in patients with branch retinal vein occlusion (BRVO). Prospective interventional, randomized, multicenter study. Patients with macular edema secondary to BRVO underwent an Ozurdex intravitreal implant at baseline. After 1 month, patients were randomly assigned to 2 study groups. Patients in Group 1 were followed up monthly and retreated with Ozurdex implant whenever there was a recurrence of macular edema or a decrease in best-corrected visual acuity (BCVA). In Group 2 patients macular grid laser was performed between weeks 6 and 8. After that, patients were followed up and retreated as for Group 1. In Group 1 at 4 months, mean BCVA was 0.49 ± 0.35 logMAR and central retinal thickness (CRT) was 391 ± 172 μm; both improved significantly at 6 months, to 0.32 ± 0.29 logMAR and 322 ± 160 μm, respectively. In Group 2, CRT was reduced significantly to 291 ± 76 μm at 4 months, and BCVA improved to 0.25 ± 0.20 logMAR. At the final visit, BCVA was 0.18 ± 0.14 logMAR and mean CRT was 271 ± 44 μm. The number of Ozurdex implants at 4 months was 12 of 25 (48%) in Group 1 patients vs 3 of 25 (12%) in Group 2 patients (P = .012). At 6 months 3 of 25 patients (12%) in Group 1 vs 0 of 25 (0%) in Group 2 (P = .23) were retreated. The combination of Ozurdex implant and macular grid laser is synergistic in increasing BCVA and lengthening the time between injections. Copyright © 2014 Elsevier Inc. All rights reserved.

Cultured Human Retinal Pigment Epithelial (hRPE) Sheets: A Search for Suitable Storage Conditions.

PubMed

Khan, Ayyad Z; Utheim, Tor P; Reppe, Sjur; Sandvik, Leiv; Lyberg, Torstein; Roald, Borghild B-H; Ibrahim, Ibrahim B; Eidet, Jon R

2018-04-01

The advancement of human retinal pigment epithelial cell (hRPE) replacement therapy is partly dependent on optimization of cell culture, cell preservation, and storage medium. This study was undertaken to search for a suitable storage temperature and storage medium for hRPE. hRPE monolayer sheets were cultured under standard conditions at 37°C and then randomized for storage at six temperatures (4, 16, 20, 24, 28, and 37°C) for 7 days. After revealing a suitable storage temperature, hRPE sheets were subsequently stored with and without the silk protein sericin added to the storage medium. Live/dead assay, light microscopy, pH, and phenotypic expression of various proteins were used to assess cell cultures stored at different temperatures. After 7 days of storage, hRPE morphology was best preserved at 4°C. Addition of sericin to the storage medium maintained the characteristic morphology of the preserved cells, and improved pigmentation and levels of pigmentation-related proteins in the cultured hRPE sheets following a 7-day storage period at 4°C.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

NASA Astrophysics Data System (ADS)

Maya-Vetencourt, José Fernando; Ghezzi, Diego; Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; di Paolo, Mattia; di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-06-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

PubMed Central

Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; Di Paolo, Mattia; Di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-01-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of Retinitis pigmentosa. Electrophysiological and behavioral analyses reveal a prosthesis-dependent recovery of light-sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness. PMID:28250420

Wireless link and microelectronics design for retinal prostheses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wentai

2012-02-29

This project focuses on delivering power and data to the artificial retinal implant inside the eye and the implant microstimulator electronics which delivers the current pulses to stimulate the retinal layer to elicit visual perception. Since the use of invasive means such as tethering wires to transmit power and data results in discomfort to the patients which could eventually cause infection due to the abrasion caused by the wire and contact of the internals of the eye to the external environment, a completely wireless approach is used to transfer both power and data. Power is required inside the eye formore » the microelectronic implant which uses a dual voltage supply scheme (positive and negative) to deliver biphasic (anodic and cathodic) current pulses. Data in the form of digital bits from the data transmitter external to the eye, carries information about the amplitude, phase width, interphase delay, stimulation sequence for each implant electrode. The data receiver unit decodes the digital stream and the microstimulator unit generates the appropriate current stimuli. Since the external unit consisting of the power transmitter can experience coupling a variation with the power receiver due to the patient’s movements, a closed loop approach is used which varies the transmitted power dynamically to automatically compensate for such movements. This report presents the salient features of this research activities and results.« less

Evaluation of the True Wavefront Aberrations in Eyes Implanted With a Rotationally Asymmetric Multifocal Intraocular Lens.

PubMed

Akondi, Vyas; Pérez-Merino, Pablo; Martinez-Enriquez, Eduardo; Dorronsoro, Carlos; Alejandre, Nicolás; Jiménez-Alfaro, Ignacio; Marcos, Susana

2017-04-01

Standard evaluation of aberrations from wavefront slope measurements in patients implanted with a rotationally asymmetric multifocal intraocular lens (IOL), the Lentis Mplus (Oculentis GmbH, Berlin, Germany), results in large magnitude primary vertical coma, which is attributed to the intrinsic IOL design. The new proposed method analyzes aberrometry data, allowing disentangling the IOL power pupillary distribution from the true higher order aberrations of the eye. The new method of wavefront reconstruction uses retinal spots obtained at both the near and far foci. The method was tested using ray tracing optical simulations in a computer eye model virtually implanted with the Lentis Mplus IOL, with a generic cornea or with anterior segment geometry obtained from custom quantitative spectral-domain optical coherence tomography in a real patient. The method was applied to laser ray tracing aberrometry data at near and far fixation obtained in a patient implanted with the Lentis Mplus IOL. Higher order aberrations evaluated from simulated and real retinal spot diagrams following the new reconstruction approach matched the nominal aberrations (approximately 98%). Previously reported primary vertical coma in patients implanted with this IOL lost significance with the application of the proposed reconstruction. Custom analysis of ray tracing-based retinal spot diagrams allowed decoupling of the true higher order aberrations of the patient's eye from the power pupillary distribution of a rotationally asymmetric multifocal IOL, therefore providing the appropriate phase map to accurately evaluate through-focus optical quality. [J Refract Surg. 2017;33(4):257-265.]. Copyright 2017, SLACK Incorporated.

Implantation, removal and replacement of subretinal electronic implants for restoration of vision in patients with retinitis pigmentosa.

PubMed

Gekeler, Katrin; Bartz-Schmidt, Karl Ulrich; Sachs, Helmut; MacLaren, Robert E; Stingl, Katarina; Zrenner, Eberhart; Gekeler, Florian

2018-05-01

The purpose of this review is to provide an update on the efforts to restore vision through subretinal implants in patients with degenerative retinal diseases. In addition to the current technique and its latest improvements, it will focus on the surgical technique of implantation as well as explantation and reimplantation. The durability of the current subretinal implant RETINA IMPLANT Alpha AMS has increased substantially compared with the predecessor model RETINA IMPLANT Alpha IMS. According to validated examinations in the laboratory, a median lifetime of 4.7 years will be reached in clinical use; in similar examinations, the previous model has reached only 8 months. Visual function has slightly increased. The surgical technique for subretinal implants is complex and demanding for ophthalmic surgeons, as it is multifaceted and combines novel surgical steps in areas, which are not commonly entered such as the suprachoroidal and the subretinal space. The surgical approach for implantation has matured considerably and has led to successful implantation in 64 patient cases. Surgical challenges are now mainly encountered with the exact subfoveal positioning of the device. The explantation procedure is relatively straight-forward because the implant can be withdrawn in a reverse direction along the already existent subretinal path. Reimplantations, however, are more challenging because some degree of scar tissue may exist along the path of the chip and around the scleral trapdoor. Nevertheless, reimplantations have now been carried out successfully in four patients. The new RETINA IMPLANT Alpha AMS shows significantly improved durability compared with the predecessor model RETINA IMPLANT Alpha IMS. The subretinal implant offers excellent visual results but requires experienced surgeons. Explantation of devices is straight-forward, and reimplantations are challenging but have been successful in four patients.

Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results.

PubMed

Haller, Julia A; Bandello, Francesco; Belfort, Rubens; Blumenkranz, Mark S; Gillies, Mark; Heier, Jeffrey; Loewenstein, Anat; Yoon, Young Hee; Jiao, Jenny; Li, Xiao-Yan; Whitcup, Scott M; Li, Joanne

2011-12-01

To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO). Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension. We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO. At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm. The primary outcome for the open-label extension was safety; BCVA was also evaluated. At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively. Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

[To cognize retinitis pigmentosa with scientific view].

PubMed

Li, Gen-lin

2009-03-01

Retinitis pigmentosa (RP) is the most common inherited eye disease that usually leads into blind, and is high simplex and clinical heterogeneity. Recent years, some new hereditary forms have been found, such as digenic RP, mitochondrial RP, incomplete dominant inheritance RP. The phenotype of RP is multiplicity. Incompatible phenomenon between genotype and phenotypes was shown in some genes such as peripherin/RDS, RHO, RP2 and RP3. The complicated phenotype was shown in the rare RP forms, such as centricity RP, stemma RP, retinitis pigmentosa sine pigmento, and retinal degeneration slow. Retinal transplantation, retinal implantation, drug and neurotrophic factor therapy, and gene therapy have been well studied worldwide and presented some hopeful efficacy. Ophthalmologists and practitioners should cognize the new advance and new knowledge on RP therapy with a scientific view for better serving the RP patients.

Delayed onset porous polyethylene implant-related inflammation after orbital blowout fracture repair: four case reports.

PubMed

Aryasit, Orapan; Ng, Danny S; Goh, Alice S C; Woo, Kyung In; Kim, Yoon-Duck

2016-07-07

Porous polyethylene implants are commonly used in orbital blowout fracture repair because of purported biocompatibility, durability, and low frequency of complications. Delayed inflammation related to porous polyethylene sheet implants is very rare and no case series of this condition have been reported. This is a retrospective review of clinical presentations, radiographic findings, histopathological findings, treatments, and outcomes of patients who developed delayed complications in orbital blowout fracture repair using porous polyethylene sheets. Four male patients were included with a mean age of 49 years (range 35-69 years). Blowout fracture repair was complicated with implant-related inflammation 10 months, 2 years, 3 years, and 8 years after surgery. Chronic and subacute orbital inflammatory signs were noted in two patients and acute fulminant orbital inflammation was found in two patients. Three patients developed peri-implant abscesses and one patient had a soft tissue mass around the implant. All patients underwent implant removal and two of these patients with paranasal sinusitis had sinus surgery. Histopathological findings revealed chronic inflammatory changes with fibrosis, and one patient had foreign body granuloma with culture positive Staphylococcus aureus. Delayed complications with porous polyethylene sheets used in orbital blowout fracture repair may occur many years following the initial surgery in immunocompetent patients. Low-grade or fulminant inflammation could complicate blowout fracture repair related with the implant.

Quantification of fluid resorption from diabetic macular oedema with foveal serous detachment after dexamethasone intravitreal implant (Ozurdex® ) in a pregnant diabetic.

PubMed

Hodzic-Hadzibegovic, Delila; Ba-Ali, Shakoor; Valerius, Marianne; Lund-Andersen, Henrik

2017-05-01

To quantify the fluid resorption from the centre of the fovea in a pregnant woman with diabetic macular oedema by daily optical coherence tomography (OCT) measurements after the administration of intravitreal dexamethasone implant (Ozurdex ® ). A 36-year-old pregnant woman with type 1 diabetes for 33 years presented with diabetic macular oedema with foveal serous detachment and symptomatic vision loss at 16 gestational weeks. Best-corrected visual acuity (BCVA) in Snellen notation and central retinal volume assessed by optical coherence tomography (OCT, Topcon Corporation) were measured almost on a daily basis the first five weeks after implantation and then 2-3 times per month until childbirth. The pretreatment BCVA was 0.6/1.0, and pretreatment central retinal volume was 0.32 mm 3 . Near elimination of the oedema was achieved 3 days after treatment. One week after treatment, BCVA improved to preconception level, and full regression of the oedema was achieved. The rate of fluid resorption from the centre of the fovea was highest 3 days after treatment 0.00139 μL/hr and decreasing to 0.00065 μL/hr 1 week after treatment. Intravitreal dexamethasone implant Ozurdex reduces promptly central retinal volume in diabetic macular oedema involving the centre of the fovea in pregnancy with highest rate of fluid resorption 3 days after treatment initiation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Design and Simulations of an Energy Harvesting Capable CMOS Pixel for Implantable Retinal Prosthesis

NASA Astrophysics Data System (ADS)

Ansaripour, Iman; Karami, Mohammad Azim

2017-12-01

A new pixel is designed with the capability of imaging and energy harvesting for the retinal prosthesis implant in 0.18 µm standard Complementary Metal Oxide Semiconductor technology. The pixel conversion gain and dynamic range, are 2.05 \\upmu{{V}}/{{e}}^{ - } and 63.2 dB. The power consumption 53.12 pW per pixel while energy harvesting performance is 3.87 nW in 60 klx of illuminance per pixel. These results have been obtained using post layout simulation. In the proposed pixel structure, the high power production capability in energy harvesting mode covers the demanded energy by using all available p-n junction photo generated currents.

Optimization of pillar electrodes in subretinal prosthesis for enhanced proximity to target neurons

NASA Astrophysics Data System (ADS)

Flores, Thomas; Lei, Xin; Huang, Tiffany; Lorach, Henri; Dalal, Roopa; Galambos, Ludwig; Kamins, Theodore; Mathieson, Keith; Palanker, Daniel

2018-06-01

Objective. High-resolution prosthetic vision requires dense stimulating arrays with small electrodes. However, such miniaturization reduces electrode capacitance and penetration of electric field into tissue. We evaluate potential solutions to these problems with subretinal implants based on utilization of pillar electrodes. Approach. To study integration of three-dimensional (3D) implants with retinal tissue, we fabricated arrays with varying pillar diameter, pitch, and height, and implanted beneath the degenerate retina in rats (Royal College of Surgeons, RCS). Tissue integration was evaluated six weeks post-op using histology and whole-mount confocal fluorescence imaging. The electric field generated by various electrode configurations was calculated in COMSOL, and stimulation thresholds assessed using a model of network-mediated retinal response. Main results. Retinal tissue migrated into the space between pillars with no visible gliosis in 90% of implanted arrays. Pillars with 10 μm height reached the middle of the inner nuclear layer (INL), while 22 μm pillars reached the upper portion of the INL. Electroplated pillars with dome-shaped caps increase the active electrode surface area. Selective deposition of sputtered iridium oxide onto the cap ensures localization of the current injection to the pillar top, obviating the need to insulate the pillar sidewall. According to computational model, pillars having a cathodic return electrode above the INL and active anodic ring electrode at the surface of the implant would enable six times lower stimulation threshold, compared to planar arrays with circumferential return, but suffer from greater cross-talk between the neighboring pixels. Significance. 3D electrodes in subretinal prostheses help reduce electrode-tissue separation and decrease stimulation thresholds to enable smaller pixels, and thereby improve visual acuity of prosthetic vision.

Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients after Argus II Implantation: an International Study.

PubMed

Gregori, Ninel Z; Callaway, Natalia F; Hoeppner, Catherine; Yuan, Alex; Rachitskaya, Aleksandra; Feuer, William; Ameri, Hossein; Arevalo, J Fernando; Augustin, Albert J; Birch, David G; Dagnelie, Gislin; Grisanti, Salvatore; Davis, Janet L; Hahn, Paul; Handa, James T; Ho, Allen C; Huang, Suber S; Humayun, Mark S; Iezzi, Raymond; Jayasundera, K Thiran; Kokame, Gregg T; Lam, Byron L; Lim, Jennifer I; Mandava, Naresh; Montezuma, Sandra R; Olmos de Koo, Lisa; Szurman, Peter; Vajzovic, Lejla; Wiedemann, Peter; Weiland, James; Yan, Jiong; Zacks, David N

2018-06-22

To assess the retinal anatomy and array position in the Argus II Retinal Prosthesis recipients. Prospective, non-comparative cohort study METHODS: Setting: international multicenter study PATIENTS: Argus II recipients enrolled in the Post-Market Surveillance Studies. Spectral-domain Optical Coherence Tomography images collected for the Surveillance Studies (NCT01860092 and NCT01490827) were reviewed. Baseline and postoperative macular thickness, electrode-retina distance (gap), optic disc-array overlap, and preretinal membrane presence were recorded at 1, 3, 6, and 12 months. Axial retinal thickness and axial gap along the array's long axis (a line between the tack and handle), maximal retinal thickness and maximal gap along a B-scan near the tack, midline, and handle. Thirty-three patients from 16 surgical sites in the United States and Germany were included. Mean axial retinal thickness increased from month 1 through month 12 at each location, but reached statistical significance only at the array midline (p-value=0.007). The rate of maximal thickness increase was highest near the array midline (slope=6.02, p=0.004), compared to the tack (slope=3.60, p<0.001) or the handle (slope=1.93, p=0.368). The mean axial and maximal gaps decreased over the study period, and the mean maximal gap size decrease was significant at midline (p=0.032). Optic disc-array overlap was seen in the minority of patients. Preretinal membranes were common before and after implantation. Progressive macular thickening under the array was common and corresponded to decreased electrode-retina gap over time. By month 12, the array was completely apposed to the macula in approximately half of the eyes. Copyright © 2018. Published by Elsevier Inc.

Photovoltaic restoration of sight with high visual acuity

PubMed Central

Lorach, Henri; Goetz, Georges; Smith, Richard; Lei, Xin; Mandel, Yossi; Kamins, Theodore; Mathieson, Keith; Huie, Philip; Harris, James; Sher, Alexander; Palanker, Daniel

2015-01-01

Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight. PMID:25915832

Monitoring the evolution of boron doped porous diamond electrode on flexible retinal implant by OCT and in vivo impedance spectroscopy.

PubMed

Hébert, Clément; Cottance, Myline; Degardin, Julie; Scorsone, Emmanuel; Rousseau, Lionel; Lissorgues, Gaelle; Bergonzo, Philippe; Picaud, Serge

2016-12-01

Nanocrystalline Boron doped Diamond proved to be a very attractive material for neural interfacing, especially with the retina, where reduce glia growth is observed with respect to other materials, thus facilitating neuro-stimulation over long terms. In the present study, we integrated diamond microelectrodes on a polyimide substrate and investigated their performances for the development of neural prosthesis. A full description of the microfabrication of the implants is provided and their functionalities are assessed using cyclic voltammetry and electrochemical impedance spectroscopy. A porous structure of the electrode surface was thus revealed and showed promising properties for neural recording or stimulation. Using the flexible implant, we showed that is possible to follow in vivo the evolution of the electric contact between the diamond electrodes and the retina over 4months by using electrochemical impedance spectroscopy. The position of the implant was also monitored by optical coherence tomography to corroborate the information given by the impedance measurements. The results suggest that diamond microelectrodes are very good candidates for retinal prosthesis. Copyright © 2016. Published by Elsevier B.V.

Human eye-inspired soft optoelectronic device using high-density MoS2-graphene curved image sensor array.

PubMed

Choi, Changsoon; Choi, Moon Kee; Liu, Siyi; Kim, Min Sung; Park, Ok Kyu; Im, Changkyun; Kim, Jaemin; Qin, Xiaoliang; Lee, Gil Ju; Cho, Kyoung Won; Kim, Myungbin; Joh, Eehyung; Lee, Jongha; Son, Donghee; Kwon, Seung-Hae; Jeon, Noo Li; Song, Young Min; Lu, Nanshu; Kim, Dae-Hyeong

2017-11-21

Soft bioelectronic devices provide new opportunities for next-generation implantable devices owing to their soft mechanical nature that leads to minimal tissue damages and immune responses. However, a soft form of the implantable optoelectronic device for optical sensing and retinal stimulation has not been developed yet because of the bulkiness and rigidity of conventional imaging modules and their composing materials. Here, we describe a high-density and hemispherically curved image sensor array that leverages the atomically thin MoS 2 -graphene heterostructure and strain-releasing device designs. The hemispherically curved image sensor array exhibits infrared blindness and successfully acquires pixelated optical signals. We corroborate the validity of the proposed soft materials and ultrathin device designs through theoretical modeling and finite element analysis. Then, we propose the ultrathin hemispherically curved image sensor array as a promising imaging element in the soft retinal implant. The CurvIS array is applied as a human eye-inspired soft implantable optoelectronic device that can detect optical signals and apply programmed electrical stimulation to optic nerves with minimum mechanical side effects to the retina.

Optoelectronic retinal prosthesis: system design and performance

NASA Astrophysics Data System (ADS)

Loudin, J. D.; Simanovskii, D. M.; Vijayraghavan, K.; Sramek, C. K.; Butterwick, A. F.; Huie, P.; McLean, G. Y.; Palanker, D. V.

2007-03-01

The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10° visual field, with a full 30° field accessible via eye movements. Pixel sizes are scalable from 100 to 25 µm, corresponding to 640-10 000 pixels on an implant 3 mm in diameter.

Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.

PubMed

Gilger, B C; Wilkie, D A; Davidson, M G; Allen, J B

2001-12-01

To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. 16 horses with recurrent uveitis. Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis.

Investigation of thermal effects of infrared lasers on the rabbit retina: a study in the course of development of an active subretinal prosthesis.

PubMed

Sailer, Heiko; Shinoda, Kei; Blatsios, Georgios; Kohler, Konrad; Bondzio, Lars; Zrenner, Eberhart; Gekeler, Florian

2007-08-01

Retinal implants are intended to replace photoreceptors in patients suffering from degenerative retinal diseases such as retinitis pigmentosa. Data show that photodiodes in subretinal implants are not powerful enough to stimulate overlying retinal tissue by simply transforming light energy into electrical energy. Therefore, infrared (IR) irradiation has been envisioned to supply additional energy. While epiretinal implants mostly use induction coils for wireless energy transfer, IR irradiation seems to be an additional option. This study investigated the feasibility of an IR energy supply for an active subretinal implant by assessing thermal effects of IR irradiation onto the rabbit retina. Polyimide foil strips carrying an optical sensor as well as a thermal sensor were implanted into the subretinal space of the eyes of nine rabbits using a transchoroidal surgical approach. The area of the thermal sensor was irradiated by an IR laser (830 nm) focused on the device. The sensor provided simultaneous real-time measurements of absolute temperature and irradiation density, allowing direct correlation of the temperature increase to different intensities of IR irradiation. Possible IR-related damage to the retina was examined in histological sections. Temperature changes in living and dead animals were evaluated as a function of IR irradiation power of between 0.1 mW and 40 mW (0.03 mW/mm2-12.7 mW/mm2). We found an exponential relationship between IR irradiation power and temperature increase over the whole range (up to 12.7 mW/mm2) in the living animal. The maximum temperature increase caused by IR irradiation of 40 mW (12.7 mW/mm2) was 4.5 degrees C. The ratio of temperature increase to IR irradiation density postmortem (i.e., without ocular blood flow) was linear over the whole range, with 1.15 degrees C per 1 mW/mm2. Thus, the cooling effect of ocular blood flow varied depending on IR irradiance density. In histological sections, no IR-induced damage to the retina was detected. A temperature increase of 3.2 degrees C in the living rabbit eye is to be expected when powering a subretinal implant with 15 mW (4.8 mW/mm2) IR power, the wattage used in an external power supply for an active implant with 1,500 electrodes. This appears to be a tolerable increase for ocular tissue.

Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations

PubMed Central

Stingl, Katarina; Schippert, Ruth; Bartz-Schmidt, Karl U.; Besch, Dorothea; Cottriall, Charles L.; Edwards, Thomas L.; Gekeler, Florian; Greppmaier, Udo; Kiel, Katja; Koitschev, Assen; Kühlewein, Laura; MacLaren, Robert E.; Ramsden, James D.; Roider, Johann; Rothermel, Albrecht; Sachs, Helmut; Schröder, Greta S.; Tode, Jan; Troelenberg, Nicole; Zrenner, Eberhart

2017-01-01

Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy). Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks). Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs) were transient and mostly of mild to moderate intensity. Conclusions: Psychophysical and subjective data show that RETINA IMPLANT Alpha AMS is reliable, well tolerated and can restore limited visual functions in blind patients with degenerations of the outer retina. Compared with the previous implant Alpha IMS, longevity of the new implant Alpha AMS has been considerably improved. Alpha AMS has meanwhile been certified as a commercially available medical device, reimbursed in Germany by the public health system. PMID:28878616

Argus II retinal prosthesis system: a review of patient selection criteria, surgical considerations, and post-operative outcomes.

PubMed

Finn, Avni P; Grewal, Dilraj S; Vajzovic, Lejla

2018-01-01

Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal degenerative disorders characterized by progressive rod and cone dysfunction and ensuing photoreceptor loss. Many patients suffer from legal blindness by their 40s or 50s. Artificial vision is considered once patients have lost all vision to the point of bare light perception or no light perception. The Argus II retinal prosthesis system is one such artificial vision device approved for patients with RP. This review focuses on the factors important for patient selection. Careful pre-operative screening, counseling, and management of patient expectations are critical for the successful implantation and visual rehabilitation of patients with the Argus II device.

Bioelectronic retinal prosthesis

NASA Astrophysics Data System (ADS)

Weiland, James D.

2016-05-01

Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.

Photovoltaic restoration of sight in rodents with retinal degeneration (Conference Presentation)

NASA Astrophysics Data System (ADS)

Palanker, Daniel V.

2017-02-01

To restore vision in patients who lost their photoreceptors due to retinal degeneration, we developed a photovoltaic subretinal prosthesis which converts light into pulsed electric current, stimulating the nearby inner retinal neurons. Visual information is projected onto the retina by video goggles using pulsed near-infrared ( 900nm) light. This design avoids the use of bulky electronics and wiring, thereby greatly reducing the surgical complexity. Optical activation of the photovoltaic pixels allows scaling the implants to thousands of electrodes, and multiple modules can be tiled under the retina to expand the visual field. We found that similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies (>20Hz), adaptation to static images, and non-linear summation of subunits in the receptive fields. Photovoltaic arrays with 70um pixels restored visual acuity up to a single pixel pitch, which is only two times lower than natural acuity in rats. If these results translate to human retina, such implants could restore visual acuity up to 20/250. With eye scanning and perceptual learning, human patients might even cross the 20/200 threshold of legal blindness. In collaboration with Pixium Vision, we are preparing this system (PRIMA) for a clinical trial. To further improve visual acuity, we are developing smaller pixels - down to 40um, and on 3-D interface to improve proximity to the target neurons. Scalability, ease of implantation and tiling of these wireless modules to cover a large visual field, combined with high resolution opens the door to highly functional restoration of sight.

Restoration of vision in blind individuals using bionic devices: a review with a focus on cortical visual prostheses.

PubMed

Lewis, Philip M; Ackland, Helen M; Lowery, Arthur J; Rosenfeld, Jeffrey V

2015-01-21

The field of neurobionics offers hope to patients with sensory and motor impairment. Blindness is a common cause of major sensory loss, with an estimated 39 million people worldwide suffering from total blindness in 2010. Potential treatment options include bionic devices employing electrical stimulation of the visual pathways. Retinal stimulation can restore limited visual perception to patients with retinitis pigmentosa, however loss of retinal ganglion cells precludes this approach. The optic nerve, lateral geniculate nucleus and visual cortex provide alternative stimulation targets, with several research groups actively pursuing a cortically-based device capable of driving several hundred stimulating electrodes. While great progress has been made since the earliest works of Brindley and Dobelle in the 1960s and 1970s, significant clinical, surgical, psychophysical, neurophysiological, and engineering challenges remain to be overcome before a commercially-available cortical implant will be realized. Selection of candidate implant recipients will require assessment of their general, psychological and mental health, and likely responses to visual cortex stimulation. Implant functionality, longevity and safety may be enhanced by careful electrode insertion, optimization of electrical stimulation parameters and modification of immune responses to minimize or prevent the host response to the implanted electrodes. Psychophysical assessment will include mapping the positions of potentially several hundred phosphenes, which may require repetition if electrode performance deteriorates over time. Therefore, techniques for rapid psychophysical assessment are required, as are methods for objectively assessing the quality of life improvements obtained from the implant. These measures must take into account individual differences in image processing, phosphene distribution and rehabilitation programs that may be required to optimize implant functionality. In this review, we detail these and other challenges facing developers of cortical visual prostheses in addition to briefly outlining the epidemiology of blindness, and the history of cortical electrical stimulation in the context of visual prosthetics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Spatiotemporal characteristics of retinal response to network-mediated photovoltaic stimulation.

PubMed

Ho, Elton; Smith, Richard; Goetz, Georges; Lei, Xin; Galambos, Ludwig; Kamins, Theodore I; Harris, James; Mathieson, Keith; Palanker, Daniel; Sher, Alexander

2018-02-01

Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor degeneration using electrical activation of the surviving inner retinal neurons. Today, such implants deliver visual information with low-frequency stimulation, resulting in discontinuous visual percepts. We measured retinal responses to complex visual stimuli delivered at video rate via a photovoltaic subretinal implant and by visible light. Using a multielectrode array to record from retinal ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we estimated their spatiotemporal properties from the spike-triggered average responses to photovoltaic binary white noise stimulus with 70-μm pixel size at 20-Hz frame rate. The average photovoltaic receptive field size was 194 ± 3 μm (mean ± SE), similar to that of visual responses (221 ± 4 μm), but response latency was significantly shorter with photovoltaic stimulation. Both visual and photovoltaic receptive fields had an opposing center-surround structure. In the healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This reversal is consistent with depolarization of photoreceptors by electrical pulses, as opposed to their hyperpolarization under increasing light, although alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF photovoltaic responses were observed, but in the absence of visual responses, it is not clear what functional RGC types they correspond to. Degenerate retina maintained the antagonistic center-surround organization of receptive fields. These fast and spatially localized network-mediated ON and OFF responses to subretinal stimulation via photovoltaic pixels with local return electrodes raise confidence in the possibility of providing more functional prosthetic vision. NEW & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to deliver visual information at naturalistic frequencies, resulting in discontinuous percepts. We demonstrate modulation of the retinal ganglion cells (RGC) activity using complex spatiotemporal stimuli delivered via subretinal photovoltaic implant at 20 Hz in healthy and in degenerate retina. RGCs exhibit fast and localized ON and OFF network-mediated responses, with antagonistic center-surround organization of their receptive fields.

Electronic approaches to restoration of sight

NASA Astrophysics Data System (ADS)

Goetz, G. A.; Palanker, D. V.

2016-09-01

Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field.

Electronic Approaches to Restoration of Sight

PubMed Central

Goetz, G A; Palanker, D V

2016-01-01

Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex-vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field. PMID:27502748

Design and development of a ferroelectric micro photo detector for the bionic eye

NASA Astrophysics Data System (ADS)

Song, Yang

Driven by no effective therapy for Retinitis Pigmentosa and Age Related Macular Degeneration, artificial vision through the development of an artificial retina that can be implanted into the human eye, is being addressed by the Bionic Eye. This dissertation focuses on the study of a photoferroelectric micro photo detector as an implantable retinal prosthesis for vision restoration in patients with above disorders. This implant uses an electrical signal to trigger the appropriate ocular cells of the vision system without resorting to wiring or electrode implantation. The research work includes fabrication of photoferroelectric thin film micro detectors, characterization of these photoferroelectric micro devices as photovoltaic cells, and Finite Element Method (FEM) modeling of the photoferroelectrics and their device-neuron interface. A ferroelectric micro detector exhibiting the photovoltaic effect (PVE) directly adds electrical potential to the neuron membrane outer wall at the focal adhesion regions. The electrical potential then generates a retinal cell membrane potential deflection through a newly developed Direct-Electric-Field-Coupling (DEFC) model. This model is quite different from the traditional electric current model because instead of current directly working on the cell membrane, the PVE current is used to generate a localized high electric potential in the focal adhesion region by working together with the anisotropic high internal impedance of ferroelectric thin films. General electrodes and silicon photodetectors do not have such anisotropy and high impedance, and thus they cannot generate DEFC. This mechanism investigation is very valuable, because it clearly shows that our artificial retina works in a way that is totally different from the traditional current stimulation methods.

Release and velocity of micronized dexamethasone implants with an intravitreal drug delivery system: kinematic analysis with a high-speed camera.

PubMed

Meyer, Carsten H; Klein, Adrian; Alten, Florian; Liu, Zengping; Stanzel, Boris V; Helb, Hans M; Brinkmann, Christian K

2012-01-01

Ozurdex, a novel dexamethasone (DEX) implant, is released by a drug delivery system into the vitreous cavity. We analyzed the mechanical release aperture of the novel applicator, obtained real-time recordings using a high-speed camera system and performed kinematic analysis of the DEX application. Experimental study. : The application of intravitreal DEX implants (6 mm length, 0.46 mm diameter; 700 μg DEX mass, 0.0012 g total implant mass) was recorded by a high-speed camera (500 frames per second) in water (Group A: n = 7) or vitreous (Group B: n = 7) filled tanks. Kinematic analysis calculated the initial muzzle velocity as well as the impact on the retinal surface at approximately 15 mm of the injected drug delivery system implant in both groups. A series of drug delivery system implant positions was obtained and graphically plotted over time. High-speed real-time recordings revealed that the entire movement of the DEX implant lasted between 28 milliseconds and 55 milliseconds in Group A and 1 millisecond and 7 milliseconds in Group B. The implants moved with a mean muzzle velocity of 820 ± 350 mm/s (±SD, range, 326-1,349 mm/s) in Group A and 817 ± 307 mm/s (±SD, range, 373-1,185 mm/s) in Group B. In both groups, the implant gradually decelerated because of drag force. With greater distances, the velocity of the DEX implant decreased exponentially to a complete stop at 13.9 mm to 24.7 mm in Group A and at 6.4 mm to 8.0 mm in Group B. Five DEX implants in Group A reached a total distance of more than 15 mm, and their calculated mean velocity at a retinal impact of 15 mm was 408 ± 145 mm/s (±SD, range, 322-667 mm/s), and the consecutive normalized energy was 0.55 ± 0.44 J/m (±SD). In Group B, none of the DEX implants reached a total distance of 6 mm or more. An accidental application at an angle of 30 grade and consecutively reduced distance of approximately 6 mm may result in a mean velocity of 844 and mean normalized energy of 0.15 J/m (SD ± 0.47) in a water-filled eye. The muzzle velocity of DEX implants is approximately 0.8 m/s and decreases exponentially over distance. The drag over time in vitreous is faster than in water. The calculated retinal impact energy does not reach reported damage levels for direct foreign bodies or other projectiles.

Emotional wellbeing of blind patients in a pilot trial with subretinal implants.

PubMed

Peters, Tobias; Klingberg, Stefan; Zrenner, Eberhart; Wilhelm, Barbara

2013-06-01

Participation in first human applications of retinal neuroprosthesis may create psychological stress for blind retinitis pigmentosa patients. The aim of this study was to assess the emotional wellbeing of patients undergoing implantation of a subretinal implant. Nine blind patients participating in a pilot trial with subretinal implants were enlisted. The Brief Symptom Inventory (BSI), a short self-report scale of nine primary symptoms, was used to assess reaction to the psychological distress related to study participation. The number and the intensity of symptoms were analysed, and global scores for overall psychological distress (tGSI), severity of reported symptoms (tPDSI), and level number of self-reported symptoms (tPST) were calculated. The questionnaire was administered before implantation, 2-3 times during the trial and before explantation. There were no significant alterations during the trial for the average scores of the nine primary symptoms. One patient, however, showed values higher than the norm, for six subscores before implantation and for eight subscores before explantation. A significant improvement was found in both the overall psychological distress level (tGSI) and the severity of reported symptoms (tPDSI) at the final visit, compared to those at the study start. The number of self-reported symptoms (tPST) was not significantly altered. In the first ongoing pilot trial with an active, cable-bound subretinal implant, we found that trial participation and the implant procedure and subsequent testing did not have any adverse effects on the participants' emotional wellbeing. Their distress generally improved during study participation, rather than showing signs of decreased wellbeing.

Bilateral nanophthalmos and pigmentary retinal dystrophy--an unusual syndrome.

PubMed

Proença, Helena; Castanheira-Dinis, A; Monteiro-Grillo, M

2006-09-01

To report the clinical picture of the rare association of nanophthalmos and pigmentary retinal dystrophy and its cataract surgery outcome. We report a case of a 60-year-old female who presented with bilateral slowly progressive visual loss. The patient presented with bilateral light perception visual acuity, exotropia, brunescent cataract hindering fundus examination and hypodontia. Ultrasonography revealed bilateral nanophthalmos. A visual-evoked potential was also performed preoperatively. Cataract surgery with +40D IOL implantation was uneventful. Postoperative fundus examination revealed pigmentary retinal dystrophy, confirmed by electrophysiologic tests. Glycosaminoglycan urinary excretion was normal. Congenital bilateral nanophthalmos may rarely be associated with pigmentary retinal dystrophy. We suggest thorough preoperative evaluation in nanophthalmic eyes for the exclusion of significant features concerning visual prognosis.

The relationship between the retinal image quality and the refractive index of defects arising in IOL: numerical analysis

NASA Astrophysics Data System (ADS)

Geniusz, Malwina

2017-09-01

The best treatment for cataract patients, which allows to restore clear vision is implanting an artificial intraocular lens (IOL). The image quality of the lens has a significant impact on the quality of patient's vision. After a long exposure the implant to aqueous environment some defects appear in the artificial lenses. The defects generated in the IOL have different refractive indices. For example, glistening phenomenon is based on light scattering on the oval microvacuoles filled with an aqueous humor which refractive index value is about 1.34. Calcium deposits are another example of lens defects and they can be characterized by the refractive index 1.63. In the presented studies it was calculated how the difference between the refractive indices of the defect and the refractive index of the lens material affects the quality of image. The OpticStudio Professional program (from Radiant Zemax, LLC) was used for the construction of the numerical model of the eye with IOL and to calculate the characteristics of the retinal image. Retinal image quality was described in such characteristics as Point Spread Function (PSF) and the Optical Transfer Function with amplitude and phase. The results show a strong correlation between the refractive indices difference and retinal image quality.

Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.

PubMed

Chen, Lei; Xing, Qi; Zhai, Qiyi; Tahtinen, Mitchell; Zhou, Fei; Chen, Lili; Xu, Yingbin; Qi, Shaohai; Zhao, Feng

2017-01-01

Split thickness skin graft (STSG) implantation is one of the standard therapies for full thickness wound repair when full thickness autologous skin grafts (FTG) or skin flap transplants are inapplicable. Combined transplantation of STSG with dermal substitute could enhance its therapeutic effects but the results remain unsatisfactory due to insufficient blood supply at early stages, which causes graft necrosis and fibrosis. Human mesenchymal stem cell (hMSC) sheets are capable of accelerating the wound healing process. We hypothesized that pre-vascularized hMSC sheets would further improve regeneration by providing more versatile angiogenic factors and pre-formed microvessels. In this work, in vitro cultured hMSC cell sheets (HCS) and pre-vascularized hMSC cell sheets (PHCS) were implanted in a rat full thickness skin wound model covered with an autologous STSG. Results demonstrated that the HCS and the PHCS implantations significantly reduced skin contraction and improved cosmetic appearance relative to the STSG control group. The PHCS group experienced the least hemorrhage and necrosis, and lowest inflammatory cell infiltration. It also induced the highest neovascularization in early stages, which established a robust blood micro-circulation to support grafts survival and tissue regeneration. Moreover, the PHCS grafts preserved the largest amount of skin appendages, including hair follicles and sebaceous glands, and developed the smallest epidermal thickness. The superior therapeutic effects seen in PHCS groups were attributed to the elevated presence of growth factors and cytokines in the pre-vascularized cell sheet, which exerted a beneficial paracrine signaling during wound repair. Hence, the strategy of combining STSG with PHCS implantation appears to be a promising approach in regenerative treatment of full thickness skin wounds.

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

PubMed

Kent, Tiffany L; Glybina, Inna V; Abrams, Gary W; Iezzi, Raymond

2008-01-01

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

Transplanting Retinal Cells using Bucky Paper for Support

NASA Technical Reports Server (NTRS)

Loftus, David J.; Cinke, Martin; Meyyappan, Meyya; Fishman, Harvey; Leng, Ted; Huie, Philip; Bilbao, Kalayaan

2004-01-01

A novel treatment for retinal degenerative disorders involving transplantation of cells into the eye is currently under development at NASA Ames Research Center and Stanford University School of Medicine. The technique uses bucky paper as a support material for retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, and/or stem cells. This technology is envisioned as a treatment for age-related macular degeneration, which is the leading cause of blindness in persons over age 65 in Western nations. Additionally, patients with other retinal degenerative disorders, such as retinitis pigmentosa, may be treated by this strategy. Bucky paper is a mesh of carbon nanotubes (CNTs), as shown in Figure 1, that can be made from any of the commercial sources of CNTs. Bucky paper is biocompatible and capable of supporting the growth of biological cells. Because bucky paper is highly porous, nutrients, oxygen, carbon dioxide, and waste can readily diffuse through it. The thickness, density, and porosity of bucky paper can be tailored in manufacturing. For transplantation of cells into the retina, bucky paper serves simultaneously as a substrate for cell growth and as a barrier for new blood vessel formation, which can be a problem in the exudative type of macular degeneration. Bucky paper is easily handled during surgical implantation into the eye. Through appropriate choice of manufacturing processes, bucky paper can be made relatively rigid yet able to conform to the retina when the bucky paper is implanted. Bucky paper offers a distinct advantage over other materials that have been investigated for retinal cell transplantation - lens capsule and Descemet's membrane - which are difficult to handle during surgery because they are flimsy and do not stay flat.

Very low risk of light-induced retinal damage during Boston keratoprosthesis surgery: a rabbit study.

PubMed

Salvador-Culla, Borja; Behlau, Irmgard; Sayegh, Rony R; Stacy, Rebecca C; Dohlman, Claes H; Delori, François

2014-02-01

The aim of this study was to assess the possibility of light damage to the retina by a surgical microscope during implantation of a Boston Keratoprosthesis (B-KPro) in rabbits. The retinal irradiance from a Zeiss OPMI Lumera S7 operating microscope was measured at the working distance (16.5 cm). Light transmittance through an isolated B-KPro was measured. A B-KPro was implanted into 1 eye of 12 rabbits with the optic covered during the procedure. The operated eyes were then continuously exposed to a fixed light intensity under the microscope for 1 hour. Fluorescein angiography was carried out on days 2 and 9 postsurgery, after which the animals were euthanized. Further, we compared the potential of these retinal exposures to well-accepted light safety guidelines applicable to humans. Light transmittance of B-KPro revealed a blockage of short wavelengths (<390 nm) and of long wavelengths (1660-1750 nm) of light. In addition, the surgical microscope filtered a part of the blue, ultraviolet, and infrared wavelengths. Neither fluorescein angiography nor a histological examination showed any morphological retinal changes in our rabbits. Moreover, the retinal exposures were well below the safety limits. Modern surgical microscopes have filters incorporated in them that block the most damaging wavelengths of light. The B-KPro is made of 100% poly(methyl methacrylate), which makes it in itself a blocker of short wavelengths of light. No damage could be demonstrated in the animal study, and the retinal exposures were well below the safety limits. Together, these results suggest that light exposures during B-KPro surgery present a low risk of photochemical damage to the retina.

Inverted light-sheet microscope for imaging mouse pre-implantation development.

PubMed

Strnad, Petr; Gunther, Stefan; Reichmann, Judith; Krzic, Uros; Balazs, Balint; de Medeiros, Gustavo; Norlin, Nils; Hiiragi, Takashi; Hufnagel, Lars; Ellenberg, Jan

2016-02-01

Despite its importance for understanding human infertility and congenital diseases, early mammalian development has remained inaccessible to in toto imaging. We developed an inverted light-sheet microscope that enabled us to image mouse embryos from zygote to blastocyst, computationally track all cells and reconstruct a complete lineage tree of mouse pre-implantation development. We used this unique data set to show that the first cell fate specification occurs at the 16-cell stage.

A Hermetic Wireless Subretinal Neurostimulator for Vision Prostheses

PubMed Central

Shire, Douglas B.; Chen, Jinghua; Doyle, Patrick; Gingerich, Marcus D.; Cogan, Stuart F.; Drohan, William A.; Behan, Sonny; Theogarajan, Luke; Wyatt, John L.; Rizzo, Joseph F.

2016-01-01

A miniaturized, hermetically encased, wirelessly operated retinal prosthesis has been developed for preclinical studies in the Yucatan minipig, and includes several design improvements over our previously reported device. The prosthesis attaches conformally to the outside of the eye and electrically drives a microfabricated thin-film polyimide array of sputtered iridium oxide film electrodes. This array is implanted into the subretinal space using a customized ab externo surgical technique. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete circuit components. Feedthroughs in the case connect the stimulator chip to secondary power and data receiving coils on the eye and to the electrode array under the retina. Long-term in vitro pulse testing of the electrodes projected a lifetime consistent with typical devices in industry. The final assembly was tested in vitro to verify wireless operation of the system in physiological saline using a custom RF transmitter and primary coils. Stimulation pulse strength, duration, and frequency were programmed wirelessly from a Peripheral Component Interconnect eXtensions for Instrumentation (PXI) computer. Operation of the retinal implant has been verified in two pigs for up to five and a half months by detecting stimulus artifacts generated by the implanted device. PMID:21859595

Human RPE Stem Cells Grown into Polarized RPE Monolayers on a Polyester Matrix Are Maintained after Grafting into Rabbit Subretinal Space

PubMed Central

Stanzel, Boris V.; Liu, Zengping; Somboonthanakij, Sudawadee; Wongsawad, Warapat; Brinken, Ralf; Eter, Nicole; Corneo, Barbara; Holz, Frank G.; Temple, Sally; Stern, Jeffrey H.; Blenkinsop, Timothy A.

2014-01-01

Summary Transplantation of the retinal pigment epithelium (RPE) is being developed as a cell-replacement therapy for age-related macular degeneration. Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are currently translating toward clinic. We introduce the adult human RPE stem cell (hRPESC) as an alternative RPE source. Polarized monolayers of adult hRPESC-derived RPE grown on polyester (PET) membranes had near-native characteristics. Trephined pieces of RPE monolayers on PET were transplanted subretinally in the rabbit, a large-eyed animal model. After 4 days, retinal edema was observed above the implant, detected by spectral domain optical coherence tomography (SD-OCT) and fundoscopy. At 1 week, retinal atrophy overlying the fetal or adult transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. Taken together, the xeno-RPE survived with retained characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies. PMID:24511471

Intraocular and extraocular cameras for retinal prostheses: Effects of foveation by means of visual prosthesis simulation

NASA Astrophysics Data System (ADS)

McIntosh, Benjamin Patrick

Blindness due to Age-Related Macular Degeneration and Retinitis Pigmentosa is unfortunately both widespread and largely incurable. Advances in visual prostheses that can restore functional vision in those afflicted by these diseases have evolved rapidly from new areas of research in ophthalmology and biomedical engineering. This thesis is focused on further advancing the state-of-the-art of both visual prostheses and implantable biomedical devices. A novel real-time system with a high performance head-mounted display is described that enables enhanced realistic simulation of intraocular retinal prostheses. A set of visual psychophysics experiments is presented using the visual prosthesis simulator that quantify, in several ways, the benefit of foveation afforded by an eye-pointed camera (such as an eye-tracked extraocular camera or an implantable intraocular camera) as compared with a head-pointed camera. A visual search experiment demonstrates a significant improvement in the time to locate a target on a screen when using an eye-pointed camera. A reach and grasp experiment demonstrates a 20% to 70% improvement in time to grasp an object when using an eye-pointed camera, with the improvement maximized when the percept is blurred. A navigation and mobility experiment shows a 10% faster walking speed and a 50% better ability to avoid obstacles when using an eye-pointed camera. Improvements to implantable biomedical devices are also described, including the design and testing of VLSI-integrable positive mobile ion contamination sensors and humidity sensors that can validate the hermeticity of biomedical device packages encapsulated by hermetic coatings, and can provide early warning of leaks or contamination that may jeopardize the implant. The positive mobile ion contamination sensors are shown to be sensitive to externally applied contamination. A model is proposed to describe sensitivity as a function of device geometry, and verified experimentally. Guidelines are provided on the use of spare CMOS oxide and metal layers to maximize the hermeticity of an implantable microchip. In addition, results are presented on the design and testing of small form factor, very low power, integrated CMOS clock generation circuits that are stable enough to drive commercial image sensor arrays, and therefore can be incorporated in an intraocular camera for retinal prostheses.

Evaluation of the ion implantation process for production of solar cells from silicon sheet materials

NASA Technical Reports Server (NTRS)

Spitzer, M. B.

1983-01-01

For the ion implantation tooling was fabricated with which to hold dendritic web samples. This tooling permits the expeditious boron implantation of the back to form the back surface field (BSF). Baseline BSF web cells were fabricated.

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment

PubMed Central

Lee, Christine; Tu, Hong Anh; Weir, Mark; Holubowich, Corinne

2016-01-01

Background Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. Methods We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients’ lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. Results One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life-year. The 5-year budget impact of funding the Argus II system ranged from $800,404 to $837,596. Retinitis pigmentosa significantly affects people's ability to navigate physical and virtual environments. Argus II was described as enabling the fundamental elements of sight. As such, it had a positive impact on quality of life for people with retinitis pigmentosa. Conclusions Based on evidence of moderate quality, patients with advanced retinitis pigmentosa who were implanted with the Argus II retinal prosthesis system showed significant improvement in visual function, real-life functional outcomes, and quality of life, but there were complications associated with the surgery that could be managed through standard ophthalmologic treatments. The costs for the technology are high. PMID:27468325

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment.

PubMed

2016-01-01

Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients' lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life-year. The 5-year budget impact of funding the Argus II system ranged from $800,404 to $837,596. Retinitis pigmentosa significantly affects people's ability to navigate physical and virtual environments. Argus II was described as enabling the fundamental elements of sight. As such, it had a positive impact on quality of life for people with retinitis pigmentosa. Based on evidence of moderate quality, patients with advanced retinitis pigmentosa who were implanted with the Argus II retinal prosthesis system showed significant improvement in visual function, real-life functional outcomes, and quality of life, but there were complications associated with the surgery that could be managed through standard ophthalmologic treatments. The costs for the technology are high.

Function of Platelet-Induced Epithelial Attachment at Titanium Surfaces Inhibits Microbial Colonization.

PubMed

Maeno, M; Lee, C; Kim, D M; Da Silva, J; Nagai, S; Sugawara, S; Nara, Y; Kihara, H; Nagai, M

2017-06-01

The aim of this study was to evaluate the barrier function of platelet-induced epithelial sheets on titanium surfaces. The lack of functional peri-implant epithelial sealing with basal lamina (BL) attachment at the interface of the implant and the adjacent epithelium allows for bacterial invasion, which may lead to peri-implantitis. Although various approaches have been reported to combat bacterial infection by surface modifications to titanium, none of these have been successful in a clinical application. In our previous study, surface modification with protease-activated receptor 4-activating peptide (PAR4-AP), which induced platelet activation and aggregation, was successful in demonstrating epithelial attachment via BL and epithelial sheet formation on the titanium surface. We hypothesized that the platelet-induced epithelial sheet on PAR4-AP-modified titanium surfaces would reduce bacterial attachment, penetration, and invasion. Titanium surface was modified with PAR4-AP and incubated with platelet-rich plasma (PRP). The aggregated platelets released collagen IV, a critical BL component, onto the PAR4-AP-modified titanium surface. Then, human gingival epithelial cells were seeded on the modified titanium surface and formed epithelial sheets. Green fluorescent protein (GFP)-expressing Escherichia coli was cultured onto PAR4-AP-modified titanium with and without epithelial sheet formation. While Escherichia coli accumulated densely onto the PAR4-AP titanium lacking epithelial sheet, few Escherichia coli were observed on the epithelial sheet on the PAR4-AP surface. No bacterial invasion into the interface of the epithelial sheet and the titanium surface was observed. These in vitro results indicate the efficacy of a platelet-induced epithelial barrier that functions to prevent bacterial attachment, penetration, and invasion on PAR4-AP-modified titanium.

A biological study establishing the endotoxin limit of biomaterials for bone regeneration in cranial and femoral implantation of rats.

PubMed

Haishima, Yuji; Hasegawa, Chie; Todoki, Kazuo; Sasaki, Kazuo; Niimi, Shingo; Ozono, Satoru

2017-08-01

The purpose of this study was to accurately quantify the risk of endotoxin contamination in biomaterials for bone regeneration in order to establish the acceptable endotoxin limit. Collagen sheets containing varying amounts of purified endotoxin from Escherichia coli and dried, heat-killed E. coli or Staphylococcus aureus cells were implanted into cranial or femoral defects in rats. These defects were artificially prepared to a size of 5 × 5 mm or a diameter of 1 mm, respectively. The degree of osteoanagenesis was assessed by soft X-ray radiography and histopathology at 1 and 4 weeks after implantation. The collagen sheet containing the dried E. coli cells showed a dose-dependent delay in cranial and/or femoral osteoanagenesis at endotoxin activities of more than 33.6 EU/mg, at which no inflammatory response was observed. In contrast, no such observation occurred with the collagen sheet containing S. aureus cells. These results suggest that endotoxins may affect the process of osteoanagenesis. Additionally, the no-observed-adverse-effect level was 9.6 EU/mg, corresponding to 255 EU/kg body weight in rats. Interestingly, no delay in osteoanagenesis was induced by the implantation of collagen sheets containing purified endotoxin at any dose tested. This suggested that pure endotoxin implanted into tissues having poor circulation of bodily fluids without bleeding may not be recognized as a foreign substance and may not induce a significant biological response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1514-1524, 2017. © 2016 Wiley Periodicals, Inc.

Artificial Retina Project: Final Report for CRADA ORNL 01-0625

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenbaum, E; Little, J

The U.S. Department of Energy’s Artificial Retina Project is a collaborative, multi-institutional effort to develop an implantable microelectronic retinal prosthesis that restores useful vision to people blinded by retinal diseases. The ultimate goal of the project is to restore reading ability, facial recognition, and unaided mobility in people with retinitis pigmentosa and age-related macular degeneration. The project taps into the unique research technologies and resources developed at DOE national laboratories to surmount the many technical challenges involved with developing a safe, effective, and durable product. The research team includes six DOE national laboratories, four universities, and private industry.

Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

PubMed

Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

2018-03-01

Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals, Inc.

Use of the ex-press miniature glaucoma implant in a child with Sturge-Weber syndrome.

PubMed

Elgin, Ufuk; Simsek, Tulay; Batman, Aygen

2007-01-01

A two-stage antiglaucoma operation was planned for the left eye of an 11-year-old boy with bilateral Sturge-Weber syndrome to avoid intraoperative and postoperative choroidal and retinal effusion as with previous trabeculectomy. The Ex-Press miniature glaucoma implant was placed 10 days before trabeculectomy with mitomycin C. There were no complications with either procedure.

The Argus(®) II Retinal Prosthesis System.

PubMed

Luo, Yvonne Hsu-Lin; da Cruz, Lyndon

2016-01-01

The Argus(®) II Retinal Prosthesis System (Second Sight Medical Products) is the first prosthetic vision device to obtain regulatory approval in both Europe and the USA. As such it has entered the commercial market as a treatment for patients with profound vision loss from end-stage outer retinal disease, predominantly retinitis pigmentosa. To date, over 100 devices have been implanted worldwide, representing the largest group of patients currently treated with visual prostheses. The system works by direct stimulation of the relatively preserved inner retina via epiretinal microelectrodes, thereby replacing the function of the degenerated photoreceptors. Visual information from a glasses-mounted video camera is converted to a pixelated image by an external processor, before being transmitted to the microelectrode array at the macula. Elicited retinal responses are then relayed via the normal optic nerve to the cortex for interpretation. We reviewed the animal and human studies that led to the development of the Argus(®) II device. A sufficiently robust safety profile was demonstrated in the phase I/II clinical trial of 30 patients. Improvement of function in terms of orientation and mobility, target localisation, shape and object recognition, and reading of letters and short unrehearsed words have also been shown. There remains a wide variability in the functional outcomes amongst the patients and the factors contributing to these performance differences are still unclear. Future developments in terms of both software and hardware aimed at improving visual function have been proposed. Further experience in clinical outcomes is being acquired due to increasing implantation. Copyright © 2015. Published by Elsevier Ltd.

Analysis of the RPE sheet in the rd10 retinal degeneration model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Yi

2011-01-04

The normal RPE sheet in the C57Bl/6J mouse is subclassified into two major tiling patterns: A regular generally hexagonal array covering most of the surface and a 'soft network' near the ciliary body made of irregularly shaped cells. Physics models predict these two patterns based on contractility and elasticity of the RPE cell, and strength of cellular adhesion between cells. We hypothesized and identified major changes in RPE regular hexagonal tiling pattern in rdl0 compared to C57BL/6J mice. RPE sheet damage was extensive but occurred in rd10 later than expected, after most retinal degeneration. RPE sheet changes occur in zonesmore » with a bullseye pattern. In the posterior zone around the optic nerve RPE cells take on larger irregular and varied shapes to form an intact monolayer. In mid periphery, there is a higher than normal density of cells that progress into involuted layers of RPE under the retina. The periphery remains mostly normal until late stages of degeneration. The number of neighboring cells varies widely depending on zone and progression. RPE morphology continues to deteriorate long after the photoreceptors have degenerated. The RPE cells are bystanders to the rd10 degeneration within photo receptors, and the collateral damage to the RPE sheet resembles stimulation of migration or chemotaxis. Quantitative measures of the tiling patterns and histopathology detected here, scripted in a pipeline written in Perl and Cell Profiler (an open source Matlab plugin), are directly applicable to RPE sheet images from noninvasive fundus autofluorescence (FAF), adaptive optics confocal scanning laser ophthalmoscope (AO-cSLO), and spectral domain optical coherence tomography (SD-OCT) of patients with early stage AMD or RP.« less

Compact Radiative Control Structures for Millimeter Astronomy

NASA Technical Reports Server (NTRS)

Brown, Ari D.; Chuss, David T.; Chervenak, James A.; Henry, Ross M.; Moseley, s. Harvey; Wollack, Edward J.

2010-01-01

We have designed, fabricated, and tested compact radiative control structures, including antireflection coatings and resonant absorbers, for millimeter through submillimeter wave astronomy. The antireflection coatings consist of micromachined single crystal silicon dielectric sub-wavelength honeycombs. The effective dielectric constant of the structures is set by the honeycomb cell geometry. The resonant absorbers consist of pieces of solid single crystal silicon substrate and thin phosphorus implanted regions whose sheet resistance is tailored to maximize absorption by the structure. We present an implantation model that can be used to predict the ion energy and dose required for obtaining a target implant layer sheet resistance. A neutral density filter, a hybrid of a silicon dielectric honeycomb with an implanted region, has also been fabricated with this basic approach. These radiative control structures are scalable and compatible for use large focal plane detector arrays.

Science and Technology of Bio-Inert Thin Films as Hermetic-Encapsulating Coatings for Implantable Biomedical Devices: Application to Implantable Microchip in the Eye for the Artificial Retina

NASA Astrophysics Data System (ADS)

Auciello, Orlando; Shi, Bing

Extensive research has been devoted to the development of neuron prostheses and hybrid bionic systems to establish links between the nervous system and electronic or robotic prostheses with the main focus of restoring motor and sensory functions in blind patients. Artificial retinas, one type of neural prostheses we are currently working on, aim to restore some vision in blind patients caused by retinitis picmentosa or macular degeneration, and in the future to restore vision at the level of face recognition, if not more. Currently there is no hermetic microchip-size coating that provides a reliable, long-term (years) performance as encapsulating coating for the artificial retina Si microchip to be implanted inside the eye. This chapter focuses on the critical topics relevant to the development of a robust, long-term artificial retina device, namely the science and technology of hermetic bio-inert encapsulating coatings to protect a Si microchip implanted in the human eye from being attacked by chemicals existing in the eye's saline environment. The work discussed in this chapter is related to the development of a novel ultrananocrystalline diamond (UNCD) hermetic coating, which exhibited no degradation in rabbit eyes. The material synthesis, characterization, and electrochemical properties of these hermetic coatings are reviewed for application as encapsulating coating for the artificial retinal microchips implantable inside the human eye. Our work has shown that UNCD coatings may provide a reliable hermetic bio-inert coating technology for encapsulation of Si microchips implantable in the eye specifically and in the human body in general. Electrochemical tests of the UNCD films grown under CH4/Ar/H2 (1%) plasma exhibit the lowest leakage currents (˜7 × 10-7 A/cm2) in a saline solution simulating the eye environment. This leakage is incompatible with the functionality of the first-generation artificial retinal microchip. However, the growth of UNCD on top of the Si microchip passivated by a silicon nitride layer or the oxide layers is also under investigation in our group as introduced in this chapter. The electrochemically induced leakage will be reduced by at least one to three orders of magnitude to the range of 10-10 A/cm2, which is compatible with reliable, long-term implants.

Sheet of osteoblastic cells combined with platelet-rich fibrin improves the formation of bone in critical-size calvarial defects in rabbits.

PubMed

Wang, Zhifa; Hu, Hanqing; Li, Zhijin; Weng, Yanming; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

2016-04-01

Techniques that use sheets of cells have been successfully used in various types of tissue regeneration, and platelet-rich fibrin (PRF) can be used as a source of growth factors to promote angiogenesis. We have investigated the effects of the combination of PRF and sheets of mesenchymal stem cells (MSC) from bone marrow on the restoration of bone in critical-size calvarial defects in rabbits to find out whether the combination promotes bony healing. Sheets of MSC and PRF were prepared from the same donor. We then implanted the combined MSC and PRF in critical-size calvarial defects in rabbits and assessed bony restoration by microcomputed tomography (microCT) and histological analysis. The results showed that PRF significantly increased bony regeneration at 8 weeks after implantation of sheets of MSC and PRF compared with sheets of MSC alone (p=0.0048). Our results indicate that the combination of sheets of MSC and PRF increases bone regeneration in critical-size calvarial defects in rabbits, and provides a new way to improve skeletal healing. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Characteristics of the retinal images of the eye optical systems with implanted intraocular lenses

NASA Astrophysics Data System (ADS)

Siedlecki, Damian; Zając, Marek; Nowak, Jerzy

2007-04-01

Cataract, or opacity of crystalline lens in the human eye is one of the most frequent reasons of blindness nowadays. Removing the pathologically altered crystalline lens and replacing it with artificial implantable intraocular lens (IOL) is practically the only therapy in this illness. There exist a wide variety of artificial IOL types on the medical market, differing in their material and design (shape). In this paper six exemplary models of IOL's made of PMMA, acrylic and silicone are considered. The retinal image quality is analyzed numerically on the basis of Liou-Brennan eye model with these IOL's inserted. Chromatic aberration as well as polychromatic Point Spread Function and Modulation Transfer Function are calculated as most adequate image quality measures. The calculations made with Zemax TM software show the importance of chromatic aberration correction.

Pars plana vitrectomy for retinal detachment due to internal posterior ophthalmomyiasis after cataract extraction.

PubMed

Billi, B; Lesnoni, G; Audisio, P; Giuliano, M A; Rossi, T; Costi, E; Stirpe, M

1997-04-01

The authors report a case of posterior internal ophthalmomyiasis causing vitreous haemorrhage and retinal detachment after uncomplicated cataract extraction. The patient suffered an abrupt vitreous haemorrhage 9 days after ECCE and posterior chamber IOL implantation. After 2 months the haemorrhage did not clear up and a retinal detachment arose. The patient underwent encircling scleral buckle, pars plana vitrectomy and fluid-gas exchange. In course of intervention the surgeon removed from the vitreous chamber a 14-mm-long round worm subsequently identified as a dipterous larva of the Sarcophagidae family. The patient showed no sign of subretinal tracking or retinal breaks or holes. The sclerocorneal surgical wound seems the most likely site of entrance of the parasite, and this would then be the first reported case of myiasis with no RPE tracking.

Hollow fibers - Their applications to the study of mammalian cell function

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Angeline, M.; Harkness, J.; Chu, M.; Grindleland, R.

1984-01-01

The use of hollow fiber technology in cell culture and transplantation is examined. The morphologies of encapsulated pituitary cells before and after implantation into the rat are defined. Implantation experiments using hollow fibers to study mammalian cell functions are described. Consideration is given to examining somatotroph, prolactin, prostrate, fibroblast, and retinal cell functions. These experiments demonstrate that hollow fiber technology is applicable for studying mammalian cell functions.

A system verification platform for high-density epiretinal prostheses.

PubMed

Chen, Kuanfu; Lo, Yi-Kai; Yang, Zhi; Weiland, James D; Humayun, Mark S; Liu, Wentai

2013-06-01

Retinal prostheses have restored light perception to people worldwide who have poor or no vision as a consequence of retinal degeneration. To advance the quality of visual stimulation for retinal implant recipients, a higher number of stimulation channels is expected in the next generation retinal prostheses, which poses a great challenge to system design and verification. This paper presents a system verification platform dedicated to the development of retinal prostheses. The system includes primary processing, dual-band power and data telemetry, a high-density stimulator array, and two methods for output verification. End-to-end system validation and individual functional block characterization can be achieved with this platform through visual inspection and software analysis. Custom-built software running on the computers also provides a good way for testing new features before they are realized by the ICs. Real-time visual feedbacks through the video displays make it easy to monitor and debug the system. The characterization of the wireless telemetry and the demonstration of the visual display are reported in this paper using a 256-channel retinal prosthetic IC as an example.

Novel Strategies for the Improvement of Stem Cells' Transplantation in Degenerative Retinal Diseases

PubMed Central

Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga

2016-01-01

Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation. PMID:27293444

a Review of Retinal Prosthesis Approaches

NASA Astrophysics Data System (ADS)

Kien, Tran Trung; Maul, Tomas; Bargiela, Andrzej

Age-related macular degeneration and retinitis pigmentosa are two of the most common diseases that cause degeneration in the outer retina, which can lead to several visual impairments up to blindness. Vision restoration is an important goal for which several different research approaches are currently being pursued. We are concerned with restoration via retinal prosthetic devices. Prostheses can be implemented intraocularly and extraocularly, which leads to different categories of devices. Cortical Prostheses and Optic Nerve Prostheses are examples of extraocular solutions while Epiretinal Prostheses and Subretinal Prostheses are examples of intraocular solutions. Some of the prostheses that are successfully implanted and tested in animals as well as humans can restore basic visual functions but still have limitations. This paper will give an overview of the current state of art of Retinal Prostheses and compare the advantages and limitations of each type. The purpose of this review is thus to summarize the current technologies and approaches used in developing Retinal Prostheses and therefore to lay a foundation for future designs and research directions.

No efficacy for silicone gel sheeting in prevention of abnormal scar formation in children with cancer: a randomized controlled trial.

PubMed

Braam, Katja I; Kooijmans, Esmee C M; van Dulmen-den Broeder, Eline; Veening, Margreet A; Schouten-van Meeteren, Antoinette Y N; Verhaegen, Pauline D H M; Kaspers, Gertjan J L; Niessen, Frank B; Heij, Hugo A

2015-04-01

Placement of a totally implantable venous access device in children with cancer often leads to hypertrophic scars after its removal. This study investigates whether the use of silicone gel sheets has a beneficial effect on scar outcome in children with cancer. In a three-arm randomized controlled trial, the effects of use of silicone gel sheets for 2 and 6 months were assessed and compared with no intervention in children with cancer after removal of the totally implantable venous access device. Silicone gel sheets were first administered 14 days after surgery. The 1-year follow-up included measurements at seven time points. Next to scar size assessment, the modified Vancouver Scar Scale was used to assess scar outcome. Thirty-six children participated. For hypertrophy, no significant differences were found between the two intervention groups and the control group. However, at 1-year follow-up, the 2-month application group showed significantly smaller scars compared with the group receiving silicone gel sheet treatment for 6 months (p = 0.04), but not when compared with the control group (p = 0.22). Longitudinal multilevel analyses could not confirm these findings and showed no significant intervention effects on both outcomes. This study provides no strong evidence to support the use of silicone gel sheets after totally implantable venous access device removal in children with cancer. There seems to be a small benefit for scar width with application for 2 months. However, for hypertrophy, the scar outcome shows no significant difference between the control group and the 2-month and 6-month treatment groups.

Diabetic retinopathy and complexity of retinal surgery in a general hospital.

PubMed

Mijangos-Medina, Laura Fanny; Hurtado-Noriega, Blanca Esmeralda; Lima-Gómez, Virgilio

2012-01-01

Usual retinal surgery (vitrectomy or surgery for retinal detachment) may require additional procedures to deal with complex cases, which increase time and resource use and delay access to treatment. We undertook this study to identify the proportion of primary retinal surgeries that required complex procedures and the associated causes. We carried out an observational, descriptive, cross-sectional, retrospective study. Patients with primary retinal surgery were evaluated (January 2007-December 2010). The proportion and 95% confidence intervals (CI) of preoperative diagnosis and cause of the disease requiring retinal surgery as well as the causes for complex retinal surgery were identified. Complex retinal surgery was defined as that requiring lens extraction, intraocular lens implantation, heavy perfluorocarbon liquids, silicone oil tamponade or intravitreal drugs, in addition to the usual surgical retinal procedure. The proportion of complex retinal surgeries was compared among preoperative diagnoses and among causes (χ(2), odds ratio [OR]). We studied 338 eyes. Mean age of subjects was 53.7 years, and there were 49% females. The most common diagnoses were vitreous hemorrhage (27.2%) and rhegmatogenous retinal detachment (24.6%). The most common cause was diabetes (50.6%); 273 eyes required complex surgery (80.8%, 95% CI: 76.6-85). The proportion did not differ among diagnoses but was higher in diabetic retinopathy (89%, p <0.001, OR 3.04, 95% CI: 1.63-5.7). Of the total sample, 80.8% of eyes required complex surgical procedures; diabetic retinopathy increased by 3-fold the probability of requiring these complex procedures. Early treatment of diabetic retinopathy may reduce the proportion of complex retinal surgery by 56%.

Extracellular matrix proteins as temporary coating for thin-film neural implants

NASA Astrophysics Data System (ADS)

Ceyssens, Frederik; Deprez, Marjolijn; Turner, Neill; Kil, Dries; van Kuyck, Kris; Welkenhuysen, Marleen; Nuttin, Bart; Badylak, Stephen; Puers, Robert

2017-02-01

Objective. This study investigates the suitability of a thin sheet of extracellular matrix (ECM) proteins as a resorbable coating for temporarily reinforcing fragile or ultra-low stiffness thin-film neural implants to be placed on the brain, i.e. microelectrocorticographic (µECOG) implants. Approach. Thin-film polyimide-based electrode arrays were fabricated using lithographic methods. ECM was harvested from porcine tissue by a decellularization method and coated around the arrays. Mechanical tests and an in vivo experiment on rats were conducted, followed by a histological tissue study combined with a statistical equivalence test (confidence interval approach, 0.05 significance level) to compare the test group with an uncoated control group. Main results. After 3 months, no significant damage was found based on GFAP and NeuN staining of the relevant brain areas. Significance. The study shows that ECM sheets are a suitable temporary coating for thin µECOG neural implants.

Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet.

PubMed

Li, Dan; Zhu, Lian; Liu, Yu; Yin, Zongqi; Liu, Yi; Liu, Fangjun; He, Aijuan; Feng, Shaoqing; Zhang, Yixin; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

2017-05-01

In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells. In vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by high-density culture of chondrocytes in vitro could cearte a chondrogenic niche in subcutaneous environment and efficiently retain the chondrogenic phenotype of in vitro BMSC engineered cartilage (vitro-BEC). Furthermore, cell tracing results revealed that the regenerated cartilage mainly derived from the implanted vitro-BEC. The current study not only proposes a novel research model for microenvironment simulation but also provides a useful strategy for stable ectopic cartilage regeneration of stem cells. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biomimetic collagen/elastin meshes for ventral hernia repair in a rat model.

PubMed

Minardi, Silvia; Taraballi, Francesca; Wang, Xin; Cabrera, Fernando J; Van Eps, Jeffrey L; Robbins, Andrew B; Sandri, Monica; Moreno, Michael R; Weiner, Bradley K; Tasciotti, Ennio

2017-03-01

Ventral hernia repair remains a major clinical need. Herein, we formulated a type I collagen/elastin crosslinked blend (CollE) for the fabrication of biomimetic meshes for ventral hernia repair. To evaluate the effect of architecture on the performance of the implants, CollE was formulated both as flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The morphology, hydrophylicity and in vitro degradation were assessed by SEM, water contact angle and differential scanning calorimetry, respectively. The stiffness of the meshes was determined using a constant stretch rate uniaxial tensile test, and compared to that of native tissue. CollE Sheets and Scaffolds were tested in vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and finally implanted in a rat ventral hernia model. Neovascularization and tissue regeneration within the implants was evaluated at 6weeks, by histology, immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were not only biomechanically sturdy enough to provide immediate repair of the hernia defect, but also promoted tissue restoration in only 6weeks. In fact, the presence of elastin enhanced the neovascularization in both sheets and scaffolds. Overall, CollE Scaffolds displayed mechanical properties more closely resembling those of native tissue, and induced higher gene expression of the entire marker genes tested, associated with de novo matrix deposition, angiogenesis, adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this data suggests that the improved mechanical properties and bioactivity of CollE Sheets and Scaffolds make them valuable candidates for applications of ventral hernia repair. Due to the elevated annual number of ventral hernia repair in the US, the lack of successful grafts, the design of innovative biomimetic meshes has become a prime focus in tissue engineering, to promote the repair of the abdominal wall, avoid recurrence. Our meshes (CollE Sheets and Scaffolds) not only showed promising mechanical performance, but also allowed for an efficient neovascularization, resulting in new adipose and muscle tissue formation within the implant, in only 6weeks. In addition, our meshes allowed for the use of the same surgical procedure utilized in clinical practice, with the commercially available grafts. This study represents a significant step in the design of bioactive acellular off-the-shelf biomimetic meshes for ventral hernia repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Incidental retinal phototoxicity associated with ingestion of photosensitizing drugs.

PubMed

Mauget-Faÿsse, M; Quaranta, M; Francoz, N; BenEzra, D; Mauget-Fa, M

2001-07-01

to report on the possible correlation between incident retinal phototoxicity and the use of photosensitizing drugs. four patients were examined because of scotomas and visual loss after an incidental exposure to a strong light source. One patient (two eyes) was exposed to standard camera flash; one patient (one eye) had a brief exposure to welding light; one patient (two eyes) underwent uncomplicated phacoemulsifications with intraocular lens implantation. The fourth patient had a severe retinal phototoxicity following a secondary intraocular lens implantation. All four patients underwent a thorough assessment including history of systemic drug use. These patients had ophthalmologic evaluation including: best corrected visual acuity (ETDRS charts), fundus examination, fluorescein and indocyanine green angiographies and were followed for 1 year. on presentation, the mean visual acuity was 7.5/20 (range: 20/400-20/20). Fundus examination disclosed yellow-gray sub-retinal lesions in all affected eyes. Early phase fluorescein angiography showed one or multiple hypofluorescent spots surrounded by a halo of hyperfluorescent window defect. In the late phase, some of these spots leaked the fluorescein dye. Indocyanine green angiography demonstrated hypofluorescent spots throughout with ill-defined borders of hyperfluorescence observed during the late stages. The common finding in these four patients was the fact that they were all taking one or more photosensitizing drugs (hydrochlorothiazide, furosemide, allopurinol, and benzodiazepines). Three of the patients had a full visual recovery a few months after the phototoxicity. The fourth patient remained with a visual acuity of 20/60 12 months after the light exposure. Despite the visual recovery, non-homogeneous retinal pigment epithelial disturbances persisted in all affected eyes. phototoxicity following incidental light exposure may occur in patients taking drugs of photosensitizing potential. Therefore, the thorough history of systemic drug ingestion should be obtained if patients have exposure to strong light sources.

Complications and 2-year valve survival following Ahmed valve implantation during the first 2 years of life.

PubMed

Almobarak, F; Al-Mobarak, F; Khan, A O

2009-06-01

To report complications and 2-year valve survival following Ahmed valve implantation during the first 2 years of life. Retrospective institutional case series. Forty-two eyes of 36 patients with Ahmed valve implantation (without prior drainage device surgery) during the first 2 years of life and 2 years' postsurgical follow-up were identified. Most eyes had primary congenital glaucoma (28/42, 66.7%), aphakic glaucoma (5/42, 11.9%) or Peters anomaly (5/42, 11.9%). All but three eyes had prior ocular surgery. Surgery was at a mean age of 11.83 months (m) (SD 5.63). The most common significant postoperative complications were tube malpositioning requiring intervention (11/42, 26.2%), endophthalmitis (3/42, 7.1%; one with tube exposure) and retinal detachment (3/42, 7.1%). Thirty-six eyes (85.8%) required resumption of antiglaucoma medications to maintain intraocular pressure (IOP) < or =22 mm Hg a mean of 7.2 m (SD 6.8) postoperatively. Cumulative probabilities of valve survival (IOP< or =22 mm Hg with or without medication) by Kaplan-Meier analysis were 73.8% and 63.3% at 12 months and 24 months, respectively. Postoperative tube malpositioning that required surgical revision was common in this age group. Infectious endophthalmitis and retinal detachment are known potential complications following any incisional surgery for advanced buphthalmos; however, tube exposure is a unique potential problem following aqueous shunt implantation that can lead to intraocular infection. Cumulative valve survival 2 years following implantation was 63.3%.

An all-diamond, hermetic electrical feedthrough array for a retinal prosthesis.

PubMed

Ganesan, Kumaravelu; Garrett, David J; Ahnood, Arman; Shivdasani, Mohit N; Tong, Wei; Turnley, Ann M; Fox, Kate; Meffin, Hamish; Prawer, Steven

2014-01-01

The interface between medical implants and the human nervous system is rapidly becoming more and more complex. This rise in complexity is driving the need for increasing numbers of densely packed electrical feedthrough to carry signals to and from implanted devices. This is particularly crucial in the field of neural prosthesis where high resolution stimulating or recording arrays near peripheral nerves or in the brain could dramatically improve the performance of these devices. Here we describe a flexible strategy for implementing high density, high count arrays of hermetic electrical feedthroughs by forming conducting nitrogen doped nanocrystalline diamond channels within an insulating polycrystalline diamond substrate. A unique feature of these arrays is that the feedthroughs can themselves be used as stimulating electrodes for neural tissue. Our particular application is such a feedthrough, designed as a component of a retinal implant to restore vision to the blind. The hermeticity of the feedthroughs means that the array can also form part of an implantable capsule which can interface directly with internal electronic chips. The hermeticity of the array is demonstrated by helium leak tests and electrical and electrochemical characterisation of the feedthroughs is described. The nitrogen doped nanocrystalline diamond forming the electrical feedthroughs is shown to be non-cyctotoxic. New fabrication strategies, such as the one described here, combined with the exceptional biostability of diamond can be exploited to generate a range of biomedical implants that last for the lifetime of the user without fear of degradation.

Retinal complications after aqueous shunt surgical procedures for glaucoma.

PubMed

Law, S K; Kalenak, J W; Connor, T B; Pulido, J S; Han, D P; Mieler, W F

1996-12-01

To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

Development of a micromachined epiretinal vision prosthesis

NASA Astrophysics Data System (ADS)

Stieglitz, Thomas

2009-12-01

Microsystems engineering offers the tools to develop highly sophisticated miniaturized implants to interface with the nervous system. One challenging application field is the development of neural prostheses to restore vision in persons that have become blind by photoreceptor degeneration due to retinitis pigmentosa. The fundamental work that has been done in one approach is presented here. An epiretinal vision prosthesis has been developed that allows hybrid integration of electronics on one part of a thin and flexible substrate. Polyimide as a substrate material is proven to be non-cytotoxic. Non-hermetic encapsulation with parylene C was stable for at least 3 months in vivo. Chronic animal experiments proved spatially selective cortical activation after epiretinal stimulation with a 25-channel implant. Research results have been transferred successfully to companies that currently work on the medical device approval of these retinal vision prostheses in Europe and in the USA.

Nanowire arrays restore vision in blind mice.

PubMed

Tang, Jing; Qin, Nan; Chong, Yan; Diao, Yupu; Yiliguma; Wang, Zhexuan; Xue, Tian; Jiang, Min; Zhang, Jiayi; Zheng, Gengfeng

2018-03-06

The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.

Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons

PubMed Central

Apollo, Nicholas V.; Garrett, David J.

2018-01-01

Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell’s spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear. PMID:29432411

Full-Thickness Skin Wound Healing Using Human Placenta-Derived Extracellular Matrix Containing Bioactive Molecules

PubMed Central

Choi, Ji Suk; Kim, Jae Dong; Yoon, Hyun Soo

2013-01-01

The human placenta, a complex organ, which facilitates exchange between the fetus and the mother, contains abundant extracellular matrix (ECM) components and well-preserved endogenous growth factors. In this study, we designed a new dermal substitute from human placentas for full-thickness wound healing. Highly porous, decellularized ECM sheets were fabricated from human placentas via homogenization, centrifugation, chemical and enzymatic treatments, molding, and freeze-drying. The physical structure and biological composition of human placenta-derived ECM sheets dramatically supported the regeneration of full-thickness wound in vivo. At the early stage, the ECM sheet efficiently absorbed wound exudates and tightly attached to the wound surface. Four weeks after implantation, the wound was completely closed, epidermic cells were well arranged and the bilayer structure of the epidermis and dermis was restored. Moreover, hair follicles and microvessels were newly formed in the ECM sheet-implanted wounds. Overall, the ECM sheet produced a dermal substitute with similar cellular organization to that of normal skin. These results suggest that human placenta-derived ECM sheets provide a microenvironment favorable to the growth and differentiation of cells, and positive modulate the healing of full-thickness wounds. PMID:22891853

Safety of silastic sheet for orbital wall reconstruction.

PubMed

Moon, Seong June; Suh, Hyun Suk; Park, Bo Young; Kang, So Ra

2014-07-01

Many implants are being used for the reconstruction of orbital wall fractures. The effect of the choice of implant for the reconstruction of an orbital wall fracture on the surgical outcome is under debate. The purpose of this article is to compare the outcomes of orbital wall reconstruction of small orbital wall fractures on the basis of the implants used. The authors conducted a retrospective study using electronic databases. Between March 2001 and December 2012, 461 patients with orbital wall fractures were included in this study. Among them, 431 patients in whom the fracture size was less than 300 mm(2) were analyzed. The fracture size was calculated using computed tomography scans of the orbit in the sagittal and coronal images. Cases in which the fracture size was less than 300 mm(2) were included in this study. One hundred and twenty-nine patients were treated with silastic sheets; 238 patients were treated with titanium meshes; and absorbable meshes were used in the case of 64 patients. Overall, 13 patients required revision, and the revision rate was 3.0%. The revision rate of the silastic sheet group was 5.4%. In the multivariable analysis, the revision rate of the group reconstructed with silastic sheets was highly statistically significant (P=0.043, odds ratio=3.65). However, other factors such as age, sex, fracture type, and fracture size were not significant. Reconstruction of orbital wall fractures with silastic sheets may cause more complications than that with other materials such as titanium meshes and absorbable meshes.

Ultra-widefield retinal imaging through a black intraocular lens.

PubMed

Yusuf, Imran H; Fung, Timothy H M; Patel, Chetan K

2015-09-01

To evaluate the feasibility of ultra-widefield retinal imaging in patients with near infrared (IR)-transmitting black intraocular lenses (IOLs). Oxford Eye Hospital, Oxford, United Kingdom. Laboratory evaluation of a diagnostic technology with interventional case report. The field of retinal imaging through a Morcher poly(methyl methacrylate) (PMMA) black IOL was determined in a purpose-built adult schematic model eye with the HRA2 Spectralis confocal scanning laser ophthalmoscope using standard imaging, Staurenghi retina lens-assisted imaging, and ultra-widefield noncontact imaging. Retinal imaging using each modality was then performed on a patient implanted with another Morcher PMMA black IOL model. Ultra-widefield noncontact imaging and lens-assisted imaging captured up to 150 degrees of field (versus 40 degrees with a standard confocal scanning laser ophthalmoscope). Ultra-widefield retinal images were successfully acquired in a patient eye with a black IOL. This study has identified the first ultra-widefield retinal imaging modalities for patients with near IR-transmitting black IOLs. Should larger studies confirm this finding, noncontact ultra-widefield confocal scanning laser ophthalmoscopy might be considered the gold standard imaging technique for retinal surveillance in patients with near IR-transmitting black IOLs. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging.

PubMed

Kim, Hyuncheol; Lizak, Martin J; Tansey, Ginger; Csaky, Karl G; Robinson, Michael R; Yuan, Peng; Wang, Nam Sun; Lutz, Robert J

2005-02-01

Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty.

PubMed

Zafar, Andleeb; Aslanides, Ioannis M; Selimis, Vasileios; Tsoulnaras, Konstantinos I; Tabibian, David; Kymionis, George D

2018-01-01

We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye.

Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis.

PubMed

Chader, Gerald J; Weiland, James; Humayun, Mark S

2009-01-01

Hundreds of thousands around the world have poor vision or no vision at all due to inherited retinal degenerations (RDs) like retinitis pigmentosa (RP). Similarly, millions suffer from vision loss due to age-related macular degeneration (AMD). In both of these allied diseases, the primary target for pathology is the retinal photoreceptor cells that dysfunction and die. Secondary neurons though are relatively spared. To replace photoreceptor cell function, an electronic prosthetic device can be used such that retinal secondary neurons receive a signal that simulates an external visual image. The composite device has a miniature video camera mounted on the patient's eyeglasses, which captures images and passes them to a microprocessor that converts the data to an electronic signal. This signal, in turn, is transmitted to an array of electrodes placed on the retinal surface, which transmits the patterned signal to the remaining viable secondary neurons. These neurons (ganglion, bipolar cells, etc.) begin processing the signal and pass it down the optic nerve to the brain for final integration into a visual image. Many groups in different countries have different versions of the device, including brain implants and retinal implants, the latter having epiretinal or subretinal placement. The device furthest along in development is an epiretinal implant sponsored by Second Sight Medical Products (SSMP). Their first-generation device had 16 electrodes with human testing in a Phase 1 clinical trial beginning in 2002. The second-generation device has 60+ electrodes and is currently in Phase 2/3 clinical trial. Increased numbers of electrodes are planned for future versions of the device. Testing of the device's efficacy is a challenge since patients admitted into the trial have little or no vision. Thus, methods must be developed that accurately and reproducibly record small improvements in visual function after implantation. Standard tests such as visual acuity, visual field, electroretinography, or even contrast sensitivity may not adequately capture some aspects of improvement that relate to a better quality of life (QOL). Because of this, some tests are now relying more on "real-world functional capacity" that better assesses possible improvement in aspects of everyday living. Thus, a new battery of tests have been suggested that include (1) standard psychophysical testing, (2) performance in tasks that are used in real-life situations such as object discrimination, mobility, etc., and (3) well-crafted questionnaires that assess the patient's own feelings as to the usefulness of the device. In the Phase 1 trial of the SSMP 16-electrode device, six subjects with severe RP were implanted with ongoing, continuing testing since then. First, it was evident that even limited sight restoration is a slow, learning process that takes months for improvement to become evident. However, light perception was restored in all six patients. Moreover, all subjects ultimately saw discrete phosphenes and could perform simple visual spatial and motion tasks. As mentioned above, a Phase 2/3 trial is now ongoing with a 60+ device. A 250+ device is on the drawing board, and one with over 1000 electrodes is being planned. Each has the possibility of significantly improving a patient's vision and QOL, being smaller and safer in design and lasting for the lifetime of the patient. From theoretical modeling, it is estimated that a device with approximately 1000 electrodes could give good functional vision, i.e., face recognition and reading ability. This could be a reality within 5-10 years from now. In summary, no treatments are currently available for severely affected patients with RP and dry AMD. An electrical prosthetic device appears to offer hope in replacing the function of degenerating or dead photoreceptor neurons. Devices with new, sophisticated designs and increasing numbers of electrodes could allow for long-term restoration of functional sight in patients with improvement in object recognition, mobility, independent living, and general QOL.

Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy.

PubMed

Costa, Marina; Cerqueira, Mariana T; Santos, Tírcia C; Sampaio-Marques, Belém; Ludovico, Paula; Marques, Alexandra P; Pirraco, Rogério P; Reis, Rui L

2017-06-01

Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs. Neovascularization after implantation is a major obstacle for producing clinically viable cell sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic cell sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these cell sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb ischemia, the angiogenic cell sheets contributed to blood flux recovery. These cell sheets can therefore be used as a straightforward tool to increase the neovascularization of cell sheet-based thick constructs. Copyright © 2017. Published by Elsevier Ltd.

Antifibrotic effect of dexamethasone/alginate-coated silicone sheet in the abraded middle ear mucosa.

PubMed

Jang, Chul Ho; Ahn, Seung Hyun; Kim, Geun Hyung

2016-12-01

Silicone sheet is a material which is commonly used in middle ear surgery to prevent the formation of adhesions between the tympanic membrane and the medial bony wall of the middle ear cavity. However, silicone sheet can induce a tight and hard fibrous capsule in the region of the stapes, and this is particularly common in cases of eustachian tube dysfunction. As a result of the fibrous encapsulation around the silicone sheet, postoperative aeration of the stapes can be interrupted causing poor hearing gain. In this study, we performed an in vitro and in vivo evaluation of the antifibrotic effects of a dexamethasone and alginate (Dx/alginate) coating on silicone sheet. The Dx/alginate-coated silicone sheets were fabricated using a plasma-treatment and coating method. The Dx/alginate-coated silicone sheets effectively limited in vitro fibroblast attachment and proliferation due to the controlled release of Dx, which can be modified by manipulation of the alginate coating. For the in-vivo evaluation, guinea pigs (albino, male, weighing 250g) were divided into two groups, with the control group (n=5) implanted with silicone sheet and the test group (n=5) receiving Dx/alginate-coated silicone sheet. Animals were sacrificed 3 weeks after implantation, and histological analysis was performed using hematoxylin and eosin (H&E) and immunohistochemical staining techniques. Dx/alginate-coated silicone sheets showed marked inhibition of fibrosis in both the in vitro and in vivo studies. Silicone sheet that incorporates a Dx/alginate coating can release Dx and inhibit fibrosis in the middle ear. This material could be utilized in middle ear surgery as a means of preserving proper aeration and hearing gain following ossiculoplasty. Copyright © 2016 Elsevier B.V. All rights reserved.

Consecutive case series of 244 age-related macular degeneration patients undergoing implantation with an extended macular vision IOL.

PubMed

Qureshi, Muhammad A; Robbie, Scott J; Hengerer, Fritz H; Auffarth, Gerd U; Conrad-Hengerer, Ina; Artal, Pablo

2018-03-01

To determine safety and visual outcomes in eyes with age-related macular degeneration (AMD) implanted with a novel intraocular lens (IOL) that delivers an optimized retinal image to all macular areas within 10 degrees of retinal eccentricity. This was a consecutive case series of 244 eyes with dry/stable wet AMD and logMAR visual acuity ≥0.3 implanted with iolAMD Eyemax mono TM (London Eye Hospital Pharma), a single-piece, injectable, hydrophobic acrylic IOL sited in the capsular bag. Primary outcome was safety. Secondary outcomes were changes in corrected distance visual acuity (CDVA) and corrected near visual acuity (CNVA) (logMAR). Mean age at surgery was 80 years. Mean duration of follow-up was 3 months (range 1-16 months). No eyes had worsening of CDVA. Frequency of perioperative complications was equivalent to standard IOL implantation. Postoperative refractive outcomes were within ±1 D of the target refraction in 88% of cases. Mean preoperative CDVA improved from 1.06 to 0.71 postoperatively (mean of differences -0.35; 95% confidence interval [CI] -0.3886 to -0.3223; p<0.0001), equating to an approximate Early Treatment Diabetic Retinopathy Study gain of 18 letters. Mean preoperative CNVA (N-point; logMAR conversion) improved from 1.36 to 0.88 postoperatively (mean of differences -0.48; 95% CI -0.53 to -0.44; p<0.0001). This novel IOL appears safe in the short to medium term. Improvements in postoperative CDVA and CNVA exceed those observed with standard implants.

Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats.

PubMed

Zhang, Dan; Gao, Peng; Li, Qin; Li, Jinda; Li, Xiaojuan; Liu, Xiaoning; Kang, Yunqing; Ren, Liling

2017-06-05

There is a critical need for the management of large bone defects. The purpose of this study was to engineer a biomimetic periosteum and to combine this with a macroporous β-tricalcium phosphate (β-TCP) scaffold for bone tissue regeneration. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were harvested and cultured in different culture media to form undifferentiated rBMSC sheets (undifferentiated medium (UM)) and osteogenic cell sheets (osteogenic medium (OM)). Simultaneously, rBMSCs were differentiated to induced endothelial-like cells (iECs), and the iECs were further cultured on a UM to form a vascularized cell sheet. At the same time, flow cytometry was used to detect the conversion rates of rBMSCs to iECs. The pre-vascularized cell sheet (iECs/UM) and the osteogenic cell sheet (OM) were stacked together to form a biomimetic periosteum with two distinct layers, which mimicked the fibrous layer and cambium layer of native periosteum. The biomimetic periostea were wrapped onto porous β-TCP scaffolds (BP/β-TCP) and implanted in the calvarial bone defects of rats. As controls, autologous periostea with β-TCP (AP/β-TCP) and β-TCP alone were implanted in the calvarial defects of rats, with a no implantation group as another control. At 2, 4, and 8 weeks post-surgery, implants were retrieved and X-ray, microcomputed tomography (micro-CT), histology, and immunohistochemistry staining analyses were performed. Flow cytometry results showed that rBMSCs were partially differentiated into iECs with a 35.1% conversion rate in terms of CD31. There were still 20.97% rBMSCs expressing CD90. Scanning electron microscopy (SEM) results indicated that cells from the wrapped cell sheet on the β-TCP scaffold apparently migrated into the pores of the β-TCP scaffold. The histology and immunohistochemistry staining results from in vivo implantation indicated that the BP/β-TCP and AP/β-TCP groups promoted the formation of blood vessels and new bone tissues in the bone defects more than the other two control groups. In addition, micro-CT showed that more new bone tissue formed in the BP/β-TCP and AP/β-TCP groups than the other groups. Inducing rBMSCs to iECs could be a good strategy to obtain an endothelial cell source for prevascularization. Our findings indicate that the biomimetic periosteum with porous β-TCP scaffold has a similar ability to promote osteogenesis and angiogenesis in vivo compared to the autologous periosteum. This function could result from the double layers of biomimetic periosteum. The prevascularized cell sheet served a mimetic fibrous layer and the osteogenic cell sheet served a cambium layer of native periosteum. The biomimetic periosteum with a porous ceramic scaffold provides a new promising method for bone healing.

An optimized content-aware image retargeting method: toward expanding the perceived visual field of the high-density retinal prosthesis recipients

NASA Astrophysics Data System (ADS)

Li, Heng; Zeng, Yajie; Lu, Zhuofan; Cao, Xiaofei; Su, Xiaofan; Sui, Xiaohong; Wang, Jing; Chai, Xinyu

2018-04-01

Objective. Retinal prosthesis devices have shown great value in restoring some sight for individuals with profoundly impaired vision, but the visual acuity and visual field provided by prostheses greatly limit recipients’ visual experience. In this paper, we employ computer vision approaches to seek to expand the perceptible visual field in patients implanted potentially with a high-density retinal prosthesis while maintaining visual acuity as much as possible. Approach. We propose an optimized content-aware image retargeting method, by introducing salient object detection based on color and intensity-difference contrast, aiming to remap important information of a scene into a small visual field and preserve their original scale as much as possible. It may improve prosthetic recipients’ perceived visual field and aid in performing some visual tasks (e.g. object detection and object recognition). To verify our method, psychophysical experiments, detecting object number and recognizing objects, are conducted under simulated prosthetic vision. As control, we use three other image retargeting techniques, including Cropping, Scaling, and seam-assisted shrinkability. Main results. Results show that our method outperforms in preserving more key features and has significantly higher recognition accuracy in comparison with other three image retargeting methods under the condition of small visual field and low-resolution. Significance. The proposed method is beneficial to expand the perceived visual field of prosthesis recipients and improve their object detection and recognition performance. It suggests that our method may provide an effective option for image processing module in future high-density retinal implants.

Electrophysiological studies of the feasibility of suprachoroidal-transretinal stimulation for artificial vision in normal and RCS rats.

PubMed

Kanda, Hiroyuki; Morimoto, Takeshi; Fujikado, Takashi; Tano, Yasuo; Fukuda, Yutaka; Sawai, Hajime

2004-02-01

Assessment of a novel method of retinal stimulation, known as suprachoroidal-transretinal stimulation (STS), which was designed to minimize insult to the retina by implantation of stimulating electrodes for artificial vision. In 17 normal hooded rats and 12 Royal College of Surgeons (RCS) rats, a small area of the retina was focally stimulated with electric currents through an anode placed on the fenestrated sclera and a cathode inserted into the vitreous chamber. Evoked potentials (EPs) in response to STS were recorded from the surface of the superior colliculus (SC) with a silver-ball electrode, and their physiological properties and localization were studied. In both normal and RCS rats, STS elicited triphasic EPs that were vastly diminished by changing polarity of stimulating electrodes and abolished by transecting the optic nerve. The threshold intensity (C) of the EP response to STS was approximately 7.2 +/- 2.8 nC in normal and 12.9 +/- 7.7 nC in RCS rats. The responses to minimal STS were localized in an area on the SC surface measuring 0.12 +/- 0.07 mm(2) in normal rats and 0.24 +/- 0.12 mm(2) in RCS rats. The responsive area corresponded retinotopically to the retinal region immediately beneath the anodic stimulating electrode. STS is less invasive in the retina than stimulation through epiretinal or subretinal implants. STS can generate focal excitation in retinal ganglion cells in normal animals and in those with degenerated photoreceptors, which suggests that this method of retinal stimulation is suitable for artificial vision.

Transscleral implantation and neurophysiological testing of subretinal polyimide film electrodes in the domestic pig in visual prosthesis development

NASA Astrophysics Data System (ADS)

Sachs, Helmut G.; Schanze, Thomas; Brunner, Ursula; Sailer, Heiko; Wiesenack, Christoph

2005-03-01

Loss of photoreceptor function is responsible for a variety of blinding diseases, including retinitis pigmentosa. Advances in microtechnology have led to the development of electronic visual prostheses which are currently under investigation for the treatment of human blindness. The design of a subretinal prosthesis requires that the stimulation device should be implantable in the subretinal space of the eye. Current limitations in eye surgery have to be overcome to demonstrate the feasibility of this approach and to determine basic stimulation parameters. Therefore, polyimide film-bound electrodes were implanted in the subretinal space in anaesthetized domestic pigs as a prelude to electrical stimulation in acute experiments. Eight eyes underwent surgery to demonstrate the transscleral implantability of the device. Four of the eight eyes were stimulated electrically. In these four animals the cranium was prepared for epidural recording of evoked visual cortex responses, and stimulation was performed with sequences of current impulses. All eight subretinal implantation procedures were carried out successfully with polyimide film electrodes and each electrode was implanted beneath the outer retina of the posterior pole of the operated eyes. Four eyes were used for neurophysiological testing, involving recordings of epidural cortical responses to light and electrical stimulation. A light stimulus response, which occurred 40 ms after stimulation, proved the integrity of the operated eye. The electrical stimuli occurred about 20 ms after the onset of stimulation. The stimulation threshold was approximately 100 µA. Both the threshold and the cortical responses depended on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. The subretinal implantation of complex stimulation devices using the transscleral procedure with consecutive subretinal stimulation is feasible in acute experiments in an animal model approximating to the situation in humans. The domestic pig is an appropriate animal model for basic testing of subretinal implants. Animal experiments with chronically implanted devices and long-term stimulation are advisable to prepare the field for successful human experiments. The first two authors (H G Sachs and Th Schanze) contributed equally to this paper.

Rapid implantation of dissolving microneedles on an electrospun pillar array.

PubMed

Yang, Huisuk; Kim, Soyoung; Huh, Inyoung; Kim, Suyong; Lahiji, Shayan F; Kim, Miroo; Jung, Hyungil

2015-09-01

Dissolving microneedles (DMNs), designed to release drugs and dissolve after skin insertion, have been spotlighted as a novel transdermal delivery system due to their advantages such as minimal pain and tissue damage, ability to self-administer, and no associated hazardous residues. The drug delivery efficacy of DMNs, however, is limited by incomplete insertion and the extended period required for DMN dissolution. Here, we introduce a novel DMN delivery system, DMN on an electrospun pillar array (DEPA), which can rapidly implant DMNs into skin. DMNs were fabricated on a pillar array covered by a fibrous sheet produced by electrospinning PLGA solution (14%, w/v). DMNs were implanted into the skin by manual application (press and vibration for 10 s) by tearing of the fibers hung on the 300-μm pillars. Separation of DMNs from the fibrous sheet was dependent on both pillar height and the properties of the fibrous sheet. After evaluation of the implantation and dissolution of DMNs with diffusion of red dye by taking cross-sectional images of porcine skin, the hypoglycemic effect of insulin loaded DEPA was examined using a healthy mouse model. This DMN array overcomes critical issues associated with the low penetration efficiency of flat patch-based DMNs, and will allow realization of patient convenience with the desired drug efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of nanotopography on periodontal ligament stem cell functions and cell sheet based periodontal regeneration

PubMed Central

Gao, Hui; Li, Bei; Zhao, Lingzhou; Jin, Yan

2015-01-01

Periodontal regeneration is an important part of regenerative medicine, with great clinical significance; however, the effects of nanotopography on the functions of periodontal ligament (PDL) stem cells (PDLSCs) and on PDLSC sheet based periodontal regeneration have never been explored. Titania nanotubes (NTs) layered on titanium (Ti) provide a good platform to study this. In the current study, the influence of NTs of different tube size on the functions of PDLSCs was observed. Afterward, an ectopic implantation model using a Ti/cell sheets/hydroxyapatite (HA) complex was applied to study the effect of the NTs on cell sheet based periodontal regeneration. The NTs were able to enhance the initial PDLSC adhesion and spread, as well as collagen secretion. With the Ti/cell sheets/HA complex model, it was demonstrated that the PDLSC sheets were capable of regenerating the PDL tissue, when combined with bone marrow mesenchymal stem cell (BMSC) sheets and HA, without the need for extra soluble chemical cues. Simultaneously, the NTs improved the periodontal regeneration result of the ectopically implanted Ti/cell sheets/HA complex, giving rise to functionally aligned collagen fiber bundles. Specifically, much denser collagen fibers, with abundant blood vessels as well as cementum-like tissue on the Ti surface, which well-resembled the structure of natural PDL, were observed in the NT5 and NT10 sample groups. Our study provides the first evidence that the nanotopographical cues obviously influence the functions of PDLSCs and improve the PDLSC sheet based periodontal regeneration size dependently, which provides new insight to the periodontal regeneration. The Ti/cell sheets/HA complex may constitute a good model to predict the effect of biomaterials on periodontal regeneration. PMID:26150714

Influence of nanotopography on periodontal ligament stem cell functions and cell sheet based periodontal regeneration.

PubMed

Gao, Hui; Li, Bei; Zhao, Lingzhou; Jin, Yan

2015-01-01

Periodontal regeneration is an important part of regenerative medicine, with great clinical significance; however, the effects of nanotopography on the functions of periodontal ligament (PDL) stem cells (PDLSCs) and on PDLSC sheet based periodontal regeneration have never been explored. Titania nanotubes (NTs) layered on titanium (Ti) provide a good platform to study this. In the current study, the influence of NTs of different tube size on the functions of PDLSCs was observed. Afterward, an ectopic implantation model using a Ti/cell sheets/hydroxyapatite (HA) complex was applied to study the effect of the NTs on cell sheet based periodontal regeneration. The NTs were able to enhance the initial PDLSC adhesion and spread, as well as collagen secretion. With the Ti/cell sheets/HA complex model, it was demonstrated that the PDLSC sheets were capable of regenerating the PDL tissue, when combined with bone marrow mesenchymal stem cell (BMSC) sheets and HA, without the need for extra soluble chemical cues. Simultaneously, the NTs improved the periodontal regeneration result of the ectopically implanted Ti/cell sheets/HA complex, giving rise to functionally aligned collagen fiber bundles. Specifically, much denser collagen fibers, with abundant blood vessels as well as cementum-like tissue on the Ti surface, which well-resembled the structure of natural PDL, were observed in the NT5 and NT10 sample groups. Our study provides the first evidence that the nanotopographical cues obviously influence the functions of PDLSCs and improve the PDLSC sheet based periodontal regeneration size dependently, which provides new insight to the periodontal regeneration. The Ti/cell sheets/HA complex may constitute a good model to predict the effect of biomaterials on periodontal regeneration.

Respiratory epithelial ingrowth and hemorrhage as late complications of orbital floor fracture repair with silicone sheet implant.

PubMed

Jones, David F; Wilson, Matthew W

2008-01-01

The authors present a unique case of rapidly progressive proptosis in a woman 23 years after repair of an orbital floor fracture. Clinical studies, surgical exploration, and pathology revealed a hemorrhagic cyst lined with respiratory epithelium surrounding her previously placed silicone implant.

MEMS-based system and image processing strategy for epiretinal prosthesis.

PubMed

Xia, Peng; Hu, Jie; Qi, Jin; Gu, Chaochen; Peng, Yinghong

2015-01-01

Retinal prostheses have the potential to restore some level of visual function to the patients suffering from retinal degeneration. In this paper, an epiretinal approach with active stimulation devices is presented. The MEMS-based processing system consists of an external micro-camera, an information processor, an implanted electrical stimulator and a microelectrode array. The image processing strategy combining image clustering and enhancement techniques was proposed and evaluated by psychophysical experiments. The results indicated that the image processing strategy improved the visual performance compared with direct merging pixels to low resolution. The image processing methods assist epiretinal prosthesis for vision restoration.

Assistive peripheral phosphene arrays deliver advantages in obstacle avoidance in simulated end-stage retinitis pigmentosa: a virtual-reality study

NASA Astrophysics Data System (ADS)

Zapf, Marc Patrick H.; Boon, Mei-Ying; Lovell, Nigel H.; Suaning, Gregg J.

2016-04-01

Objective. The prospective efficacy of peripheral retinal prostheses for guiding orientation and mobility in the absence of residual vision, as compared to an implant for the central visual field (VF), was evaluated using simulated prosthetic vision (SPV). Approach. Sighted volunteers wearing a head-mounted display performed an obstacle circumvention task under SPV. Mobility and orientation performance with three layouts of prosthetic vision were compared: peripheral prosthetic vision of higher visual acuity (VA) but limited VF, of wider VF but limited VA, as well as centrally restricted prosthetic vision. Learning curves using these layouts were compared fitting an exponential model to the mobility and orientation measures. Main results. Using peripheral layouts, performance was superior to the central layout. Walking speed with both higher-acuity and wider-angle layouts was 5.6% higher, and mobility errors reduced by 46.4% and 48.6%, respectively, as compared to the central layout. The wider-angle layout yielded the least number of collisions, 63% less than the higher-acuity and 73% less than the central layout. Using peripheral layouts, the number of visual-scanning related head movements was 54.3% (higher-acuity) and 60.7% (wider-angle) lower, as compared to the central layout, and the ratio of time standing versus time walking was 51.9% and 61.5% lower, respectively. Learning curves did not differ between layouts, except for time standing versus time walking, where both peripheral layouts achieved significantly lower asymptotic values compared to the central layout. Significance. Beyond complementing residual vision for an improved performance, peripheral prosthetic vision can effectively guide mobility in the later stages of retinitis pigmentosa (RP) without residual vision. Further, the temporal dynamics of learning peripheral and central prosthetic vision are similar. Therefore, development of a peripheral retinal prosthesis and early implantation to alleviate VF constriction in RP should be considered to extend the target group and the time of benefit for potential retinal prosthesis implantees.

Accidental injections of dexamethasone intravitreal implant (Ozurdex) into the crystalline lens.

PubMed

Coca-Robinot, Javier; Casco-Silva, Bruno; Armadá-Maresca, Felix; García-Martínez, Jesús

2014-01-01

To describe the side effects and management after inadvertent injection of a dexamethasone implant (Ozurdex) into the crystalline lens. Two case reports. Two patients with macular edema due to unilateral retinal vein occlusion were scheduled for an intravitreal injection of Ozurdex. During the procedure, the implant was accidentally injected into the crystalline lens. Both patients developed cataracts during the course of several weeks and in both there was an intraocular pressure (IOP) increase, which required treatment with topical hypotensives. Macular edema improved only slightly. Cataract surgery with uneventful removal of the implant was performed 3 (case 1) and 6 months (case 2) after the injection. After inadvertent injection of Ozurdex into the crystalline lens, cataract surgery with removal of the implant should be performed as soon as possible in order to avoid IOP increase and so that the underlying condition may be treated adequately.

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty

PubMed Central

Zafar, Andleeb; Aslanides, Ioannis M.; Selimis, Vasileios; Tsoulnaras, Konstantinos I.; Tabibian, David; Kymionis, George D.

2018-01-01

Purpose We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. Methods The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Results Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. Conclusion A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye. PMID:29643797

Interaction of Extracellular Domain 2 of the Human Retina-specific ATP-binding Cassette Transporter (ABCA4) with All-trans-retinal*

PubMed Central

Biswas-Fiss, Esther E.; Kurpad, Deepa S.; Joshi, Kinjalben; Biswas, Subhasis B.

2010-01-01

The retina-specific ATP-binding cassette (ABC) transporter, ABCA4, is essential for transport of all-trans-retinal from the rod outer segment discs in the retina and is associated with a broad range of inherited retinal diseases, including Stargardt disease, autosomal recessive cone rod dystrophy, and fundus flavimaculatus. A unique feature of the ABCA subfamily of ABC transporters is the presence of highly conserved, long extracellular loops or domains (ECDs) with unknown function. The high degree of sequence conservation and mapped disease-associated mutations in these domains suggests an important physiological significance. Conformational analysis using CD spectroscopy of purified, recombinant ECD2 protein demonstrated that it has an ordered and stable structure composed of 27 ± 3% α-helix, 20 ± 3% β-pleated sheet, and 53 ± 3% coil. Significant conformational changes were observed in disease-associated mutant proteins. Using intrinsic tryptophan fluorescence emission spectrum of ECD2 polypeptide and fluorescence anisotropy, we have demonstrated that this domain specifically interacts with all-trans-retinal. Furthermore, the retinal interaction appeared preferential for the all-trans-isomer and was directly measurable through fluorescence anisotropy analysis. Our results demonstrate that the three macular degeneration-associated mutations lead to significant changes in the secondary structure of the ECD2 domain of ABCA4, as well as in its interaction with all-trans-retinal. PMID:20404325

Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate: An experimental study in sheep.

PubMed

Kira, Tsutomu; Akahane, Manabu; Omokawa, Shohei; Shimizu, Takamasa; Kawate, Kenji; Onishi, Tadanobu; Tanaka, Yasuhito

2017-10-18

To determine the effects of a cell sheet created from sheep bone marrow and tricalcium phosphate (TCP) on osteogenesis. Bone marrow cells were harvested from a sheep and cultured in a minimal essential medium (MEM) containing ascorbic acid phosphate (AscP) and dexamethasone (Dex). After 2 wk, the formed osteogenic matrix cell sheet was lifted from the culture dish using a scraper. Additionally, harvested bone marrow cells were cultured in MEM only as a negative control group, and in MEM with AscP, Dex, and β-glycerophosphate as a positive control group. For in vitro evaluation, we measured the alkaline phosphatase (ALP) activity and osteocalcin (OC) content in the media of the cultured cells from each group. For in vivo analysis, a porous TCP ceramic was used as a scaffold. We prepared an experimental group comprising TCP scaffolds wrapped with the osteogenic matrix cell sheets and a control group consisting of the TCP scaffold only. The constructs were implanted subcutaneously into athymic rats and the cell donor sheep, and bone formation was confirmed by histology after 4 wk. In the in vitro part, the mean ALP activity was 0.39 ± 0.03 mg/well in the negative control group, 0.67 ± 0.04 mg/well in the sheet group, and 0.65 ± 0.07 mg/well in the positive control group. The mean OC levels were 1.46 ± 0.33 ng/well in the negative control group, 3.92 ± 0.16 ng/well in the sheet group, and 4.4 ± 0.47 ng/well in the positive control group, respectively. The ALP activity and OC levels were significantly higher in the cell sheet and positive control groups than in the negative control group ( P < 0.05). There was no significant difference in ALP activity or OC levels between the cell sheet group and the positive control group ( P > 0.05). TCP constructs wrapped with cell sheets prior to implantation showed bone formation, in contrast to TCP scaffolds alone, which exhibited poor bone formation when implanted, in the subcutaneous layer both in athymic rats and in the sheep. This technique for preparing highly osteoinductive TCP may promote regeneration in large bone defects.

Microsystem technologies for ophtalmological implants

NASA Astrophysics Data System (ADS)

Mokwa, Wilfried

2003-01-01

Due to the low power consumption CMOS electronics is ideal for the use in implanted systems. This paper presents two projects working on ophthalmological implants. Both systems are powered by an external RF-field. One system has been developed to measure the intraocular pressure continuously which is important for the therapy of glaucoma patients. The system consists of a micro coil and an integrated pressure transponder chip built into an artificial soft lens. A second example is a very complex system for epiretinal stimulation of the nerve cells of the retina. With such a system it might be possible to give blind people that are suffering from retinitis pigmentosa some visual contact to their surrounding.

Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

PubMed Central

Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

2013-01-01

Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

Causes of Phakic Implantable Collamer Lens Explantation/Exchange at King Khaled Eye Specialist Hospital

PubMed Central

AlSabaani, Nasser A.; Behrens, Ashley; Jastanieah, Sabah; Al Malki, Salem; Al Jindan, Mohanna; Al Motowa, Saeed

2016-01-01

PURPOSE: The purpose of this study is to evaluate the causes of phakic implantable collamer lens (ICL) explantation/exchange at an eye hospital in Saudi Arabia. MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent ICL implantation from 2007 to March 2014 and data were collected on cases that underwent ICL explantation. RESULTS: Of the 787 ICL implants, 30 implants (3.8% [95% confidence interval 2.6%; 5.3%]) were explanted. The causes of explantation included incorrect lens size (22), cataract (4), high residual astigmatism (2), rhegmatogenous retinal detachment (1), and intolerable glare (1). Corrective measures mainly included an exchange with an appropriately sized lens (9), ICL explantation (11), with phacoemulsification and posterior chamber intraocular lens implantation (6), or replacement with an ICL of correct power (2). CONCLUSION: Incorrect ICL size was the most common cause of ICL explantation. More accurate sizing methods for ICL are required to reduce the explantation/exchange rate. PMID:27994391

Successful transplantation of in vitro expanded human cadaver corneal endothelial precursor cells on to a cadaver bovine's eye using a nanocomposite gel sheet.

PubMed

Parikumar, Periyasamy; Haraguchi, Kazutoshi; Ohbayashi, Akira; Senthilkumar, Rajappa; Abraham, Samuel J K

2014-05-01

In vitro expansion of human corneal endothelial precursor (HCEP) cells has been reported via production of cell aggregated spheres. However, to translate this procedure in human patients warrants maintaining the position of the eyeballs facing down for 36 h, which is not feasible. In this study, we report a method using a nanocomposite (NC) gel sheet to accomplish the integration of HCEP cells to the endothelium of cadaver bovine's eyes. HCEP cells were isolated from the corneal endothelium of a cadaver human eye and then expanded using a thermoreversible gelation polymer (TGP) as reported earlier. For the study, three cadaver bovine eyes were used. The NC gel sheets were inserted into the bovine eyes', aligned and suture-fixed in position under the host endothelium. HCEP cells previously expanded in the TGP were harvested and injected using a 26-gauge syringe between the endothelium and the NC gel sheet. The eyes were left undisturbed for three hours following which the NC gel sheets were gently removed. The corneas were harvested and subjected to histopathological studies. Histopathological studies showed that all the three corneas used for NC gel sheet implantation showed the presence of engrafted HCEP cells, seen as multi-layered cells over the native endothelium of the bovine cornea. Examination of the NC gel sheets used for implantation showed that only very few corneal endothelial cells remained on the sheets amounting to what could be considered negligible. The use of the NC gel sheet makes HCEP cell transplantation feasible for human patients. Further in vitro basic studies followed by translational studies are necessary to bring this method for clinical application in appropriate indications.

Implant Monitoring Measurements On Ultra Shallow Implants Before And After Anneal Using Photomodulated Reflection And Junction Photovoltage Measurement Techniques

NASA Astrophysics Data System (ADS)

Tallian, M.; Pap, A.; Mocsar, K.; Somogyi, A.; Nadudvari, Gy.; Kosztka, D.; Pavelka, T.

2011-01-01

Ultra shallow junctions are becoming widely used in the micro- and nanoelectronic devices, and novel measurement methods are needed to monitor the manufacturing processes. Photomodulated Reflection measurements before anneal and Junction Photovoltage-based sheet resistance measurements after anneal are non-contact, nondestructive techniques suitable for characterizing both the implantation and the annealing process. Tests verify that these methods are consistent with each other and by using them together, defects originating in the implantation and anneal steps can be separated.

ARM-based visual processing system for prosthetic vision.

PubMed

Matteucci, Paul B; Byrnes-Preston, Philip; Chen, Spencer C; Lovell, Nigel H; Suaning, Gregg J

2011-01-01

A growing number of prosthetic devices have been shown to provide visual perception to the profoundly blind through electrical neural stimulation. These first-generation devices offer promising outcomes to those affected by degenerative disorders such as retinitis pigmentosa. Although prosthetic approaches vary in their placement of the stimulating array (visual cortex, optic-nerve, epi-retinal surface, sub-retinal surface, supra-choroidal space, etc.), most of the solutions incorporate an externally-worn device to acquire and process video to provide the implant with instructions on how to deliver electrical stimulation to the patient, in order to elicit phosphenized vision. With the significant increase in availability and performance of low power-consumption smart phone and personal device processors, the authors investigated the use of a commercially available ARM (Advanced RISC Machine) device as an externally-worn processing unit for a prosthetic neural stimulator for the retina. A 400 MHz Samsung S3C2440A ARM920T single-board computer was programmed to extract 98 values from a 1.3 Megapixel OV9650 CMOS camera using impulse, regional averaging and Gaussian sampling algorithms. Power consumption and speed of video processing were compared to results obtained to similar reported devices. The results show that by using code optimization, the system is capable of driving a 98 channel implantable device for the restoration of visual percepts to the blind.

A low power MICS band phase-locked loop for high resolution retinal prosthesis.

PubMed

Yang, Jiawei; Skafidas, Efstratios

2013-08-01

Ultra low power dissipation is essential in retinal prosthesis and many other biomedical implants. Extensive research has been undertaken in designing low power biomedical transceivers, however to date, most effort has been focused on low frequency inductive links. For higher frequency, more robust and more complex applications, such as Medical Implant Communication Service (MICS) band multichannel transceivers, power consumption remains high. This paper explores the design of micro-power data links at 400 MHz for a high resolution retinal prosthesis. By taking advantage of advanced small geometry CMOS technology and precise transistor-level modeling, we successfully utilized subthreshold FET operation, which has been historically limited to low frequency circuits due to the inadequate transistor operating speed in and near weak inversion; we have implemented a low power MICS transceiver. Particularly, a low power, MICS band multichannel phase-locked loop (PLL) that employs a subthreshold voltage controlled oscillator (VCO) and digital synchronous dividers has been implemented on a 65-nm CMOS. A design methodology is presented in detail with the demonstration of EKV model parameters extraction. This PLL provides 600- mVpp quadrature oscillations and exhibits a phase noise of -102 dBc/Hz at 200-kHz offset, while only consuming 430- μW from a 1-V supply. The VCO has a gain (KVCO) of 12 MHz/V and is designed to operate in the near-weak inversion region and consumes 220- μA DC current. The designed PLL has a core area of 0.54 mm(2). It satisfies all specifications of MICS band operation with the advantage of significant reduction in power which is crucial for high resolution retinal prosthesis.

Experimental suprachoroidal plombage with a urethane based hydrophilic polymer.

PubMed Central

Foulds, W. S.; Aitken, D.; Lee, W. R.

1988-01-01

Small portions of dehydrated hydrophilic polymer (HPU 90, Smith and Nephew) have been inserted into the suprachoroidal space in rabbits to investigate the possible use of suprachoroidal plombage in retinal detachment surgery. As it hydrates, the material causes a pronounced elevation of choroid and retina, and the implants have been well tolerated for periods of up to one year in experimental animals. The implant slowly breaks down and stimulates a simple macrophagic reaction: fibrosis in the overlying choroid is associated with ischaemic gliosis and chorioretinal fusion. Images PMID:3378024

Suprachoroidal drainage with collagen sheet implant- a novel technique for non-penetrating glaucoma surgery.

PubMed

Szurman, Peter; Januschowski, Kai; Boden, Karl Thomas; Seuthe, Anna-Maria

2018-02-01

Our purpose was both to introduce the new technique of suprachoroidal drainage with collagen sheet implantation as a novel technique of non-penetrating glaucoma surgery and to present first results of a prospective pilot study. A superficial rectangular sclera flap of half-scleral thickness sized 4 × 4.5 mm is dissected anteriorly until clear cornea. Then, a second scleral flap is created underneath the first one sized 3.5x4mm and is cut down full-thickness to the choroid exposing the suprachoroidal space. The flap is then bluntly prepared until the scleral spur is reached. Sharp dissection above the sclera spur exposes Schlemm's canal, which is located directly anteriorly. Schlemm's canal is unroofed, juxtacanalicular meshwork is peeled and the deep flap is cut off at its base. An absorbable collagen sheet (Ologen®, Dahlhausen, Cologne, Germany) is placed into the suprachoroidal space at the level of the ciliary body, and the superficial sclera flap is sutured tightly to prevent leakage. We prospectively analyzed 65 eyes that underwent suprachoroidal drainage with collagen sheet implantation. Mean reduction of intraocular pressure after 3 months was 35.1% (from 21.0 ± 4.3 mmHg to 13.5 ± 3.4 mmHg)(p < 0.01) and after 12 months 35.6% (from 21.0 ± 4.3 mmHg to 13.5 ± 3.0  mmHg)(p < 0.01). The number of topical IOP-reducing medication decreased significantly from 3.5 ± 0.7 to 0.6 ± 0.9 and to 0.9 ± 1.1 after 3 and 12 months, respectively (p < 0.01). No serious complications occurred. Suprachoroidal drainage with collagen sheet implantation seems to be a safe and effective surgical technique for non-penetrating glaucoma surgery that yields the opportunity of a sufficient IOP reduction for eyes unsuitable for canaloplasty.

[Artificial sight: recent developments].

PubMed

Zeitz, O; Keserü, M; Hornig, R; Richard, G

2009-03-01

The implantation of electronic retina stimulators appears to be a future possibility to restore vision, at least partially in patients with retinal degeneration. The idea of such visual prostheses is not new but due to the general technical progress it has become more likely that a functioning implant will be on the market soon. Visual prosthesis may be integrated in the visual system in various places. Thus there are subretinal and epiretinal implants, as well as implants that are connected directly to the optic nerve or the visual cortex. The epiretinal approach is the most promising at the moment, but the problem of appropriate modulation of the image information is unsolved so far. This will be necessary to provide a interpretable visual information to the brain. The present article summarises the concepts and includes some latest information from recent conferences.

Retinal vein occlusion: current treatment.

PubMed

Lattanzio, Rosangela; Torres Gimeno, Ana; Battaglia Parodi, Maurizio; Bandello, Francesco

2011-01-01

Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management. Copyright © 2010 S. Karger AG, Basel.

Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities.

PubMed

Dohlman, Claes H; Cade, Fabiano; Regatieri, Caio V; Zhou, Chengxin; Lei, Fengyang; Crnej, Alja; Harissi-Dagher, Mona; Robert, Marie-Claude; Papaliodis, George N; Chen, Dongfeng; Aquavella, James V; Akpek, Esen K; Aldave, Anthony J; Sippel, Kimberly C; DʼAmico, Donald J; Dohlman, Jan G; Fagerholm, Per; Wang, Liqiang; Shen, Lucy Q; González-Andrades, Miguel; Chodosh, James; Kenyon, Kenneth R; Foster, C Stephen; Pineda, Roberto; Melki, Samir; Colby, Kathryn A; Ciolino, Joseph B; Vavvas, Demetrios G; Kinoshita, Shigeru; Dana, Reza; Paschalis, Eleftherios I

2018-02-01

To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases. Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed. Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells. Prompt anti-TNF-α treatment is markedly neuroprotective. Long term profound reduction of the intraocular pressure is also vital. A new regimen, in addition to standard treatment, for severe chemical burns is proposed. This involves tumor necrosis factor alpha (TNF-α) inhibition promptly after the accident (primarily for retinal neuroprotection), prophylactic maximal lowering of the intraocular pressure (starting immediately), and keratoprosthesis implantation in a later quiet state.

Variations in retinal nerve fiber layer measurements on optical coherence tomography after implantation of trifocal intraocular lens.

PubMed

García-Bella, Javier; Martínez de la Casa, José M; Talavero González, Paula; Fernández-Vigo, José I; Valcarce Rial, Laura; García-Feijóo, Julián

2018-01-01

To establish the changes produced after implantation of a trifocal intraocular lens (IOL) on retinal nerve fiber layer measurements performed with Fourier-domain optical coherence tomography (OCT). This prospective study included 100 eyes of 50 patients with bilateral cataract in surgical range, no other associated ocular involvement, refractive errors between +5 and -5 spherical diopters, and less than 1.5 D of corneal astigmatism. The eyes were operated by phacoemulsification with implantation of 2 different trifocal IOLs (FineVision and AT LISA tri 839MP) in randomized equal groups. Cirrus OCT and Spectralis OCT were performed before surgery and 3 months later. Both analyzed the thickness of the nerve fiber layer and thickness divided by quadrants (6 in case of Spectralis and 4 in case of Cirrus HD). The mean age of patients was 67.5 ± 5.8 years. The global nerve fiber layer thickness measured with Spectralis OCT was 96.77 μm before surgery and 99.55 μm after. With Cirrus OCT, the global thickness was 85.29 μm before surgery and 89.77 μm after. Statistically significant differences in global thickness measurements between preimplantation and postimplantation of the IOL were found with both OCT in the 2 groups. Statistically significant differences were also found in temporal and superior quadrants. The implantation of a diffractive trifocal IOL alters the results of the optic nerve fiber layer on Fourier-domain OCT in these patients, which should be taken into account in the posterior study of these patients.

Intravitreal steroids for the treatment of retinal diseases.

PubMed

Sarao, Valentina; Veritti, Daniele; Boscia, Francesco; Lanzetta, Paolo

2014-01-01

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Monitoring Ion Implantation Energy Using Non-contact Characterization Methods

NASA Astrophysics Data System (ADS)

Tallian, M.; Pap, A.; Mocsar, K.; Somogyi, A.; Nadudvari, Gy.; Kosztka, D.; Pavelka, T.

2011-01-01

State-of-the-art ultra-shallow junctions are produced using extremely low ion implant energies, down to the range of 1-3 keV. This can be achieved by a variety of production techniques; however there is a significant risk that the actual implantation energy differs from the desired value. To detect this, sensitive measurement methods need to be utilized. Experiments show that both Photomodulated Reflection measurements before anneal and Junction Photovoltage-based sheet resistance measurements after anneal are suitable for this purpose.

Evidence-based review of diabetic macular edema management: Consensus statement on Indian treatment guidelines

PubMed Central

Das, Taraprasad; Aurora, Ajay; Chhablani, Jay; Giridhar, Anantharaman; Kumar, Atul; Raman, Rajiv; Nagpal, Manish; Narayanan, Raja; Natarajan, Sundaram; Ramasamay, Kim; Tyagi, Mudit; Verma, Lalit

2016-01-01

The purpose of the study was to review the current evidence and design a diabetic macular edema (DME) management guideline specific for India. The published DME guidelines from different organizations and publications were weighed against the practice trends in India. This included the recently approved drugs. DME management consisted of control of diabetes and other associated systemic conditions, such as hypertension and hyperlipidemia, and specific therapy to reduce macular edema. Quantification of macular edema is precisely made with the optical coherence tomography and treatment options include retinal laser, intravitreal anti-vascular endothelial growth factors (VEGF), and implantable dexamethasone. Specific use of these modalities depends on the presenting vision and extent of macular involvement. Invariable eyes with center-involving macular edema benefit from intravitreal anti-VEGF or dexamethasone implant therapy, and eyes with macular edema not involving the macula center benefit from retinal laser. The results are illustrated with adequate case studies and frequently asked questions. This guideline prepared on the current published evidence is meant as a guideline for the treating physicians. PMID:26953019

Bilateral phacoemulsification and intraocular lens implantation in a great horned owl.

PubMed

Carter, Renee T; Murphy, Christopher J; Stuhr, Charles M; Diehl, Kathryn A

2007-02-15

A great horned owl of estimated age < 1 year that was captured by wildlife rehabilitators was evaluated because of suspected cataracts. Nuclear and incomplete cortical cataracts were evident in both eyes. Ocular ultrasonography revealed no evidence of retinal detachment, and electroretinography revealed normal retinal function. For visual rehabilitation, cataract surgery was planned and intraocular lens design was determined on the basis of values obtained from the schematic eye, which is a mathematical model representing a normal eye for a species. Cataract surgery and intraocular lens placement were performed in both eyes. After surgery, refraction was within -0.75 diopters in the right eye and -0.25 diopters in the left eye. Visual rehabilitation was evident on the basis of improved tracking and feeding behavior, and the owl was eventually released into the wild. In raptors with substantial visual compromise, euthanasia or placement in a teaching facility is a typical outcome because release of such a bird is unacceptable. Successful intraocular lens implantation for visual rehabilitation and successful release into the wild are achievable.

Optimal voltage stimulation parameters for network-mediated responses in wild type and rd10 mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Jalligampala, Archana; Sekhar, Sudarshan; Zrenner, Eberhart; Rathbun, Daniel L.

2017-04-01

To further improve the quality of visual percepts elicited by microelectronic retinal prosthetics, substantial efforts have been made to understand how retinal neurons respond to electrical stimulation. It is generally assumed that a sufficiently strong stimulus will recruit most retinal neurons. However, recent evidence has shown that the responses of some retinal neurons decrease with excessively strong stimuli (a non-monotonic response function). Therefore, it is necessary to identify stimuli that can be used to activate the majority of retinal neurons even when such non-monotonic cells are part of the neuronal population. Taking these non-monotonic responses into consideration, we establish the optimal voltage stimulation parameters (amplitude, duration, and polarity) for epiretinal stimulation of network-mediated (indirect) ganglion cell responses. We recorded responses from 3958 mouse retinal ganglion cells (RGCs) in both healthy (wild type, WT) and a degenerating (rd10) mouse model of retinitis pigmentosa—using flat-mounted retina on a microelectrode array. Rectangular monophasic voltage-controlled pulses were presented with varying voltage, duration, and polarity. We found that in 4-5 weeks old rd10 mice the RGC thresholds were comparable to those of WT. There was a marked response variability among mouse RGCs. To account for this variability, we interpolated the percentage of RGCs activated at each point in the voltage-polarity-duration stimulus space, thus identifying the optimal voltage-controlled pulse (-2.4 V, 0.88 ms). The identified optimal voltage pulse can activate at least 65% of potentially responsive RGCs in both mouse strains. Furthermore, this pulse is well within the range of stimuli demonstrated to be safe and effective for retinal implant patients. Such optimized stimuli and the underlying method used to identify them support a high yield of responsive RGCs and will serve as an effective guideline for future in vitro investigations of retinal electrostimulation by establishing standard stimuli for each unique experimental condition.

Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds.

PubMed

Kelbsch, Carina; Maeda, Fumiatsu; Lisowska, Jolanta; Lisowski, Lukasz; Strasser, Torsten; Stingl, Krunoslav; Wilhelm, Barbara; Wilhelm, Helmut; Peters, Tobias

2017-06-01

To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes. Chromatic pupillography was performed in 40 patients with advanced RP (visual acuity < 0.02 or visual field ≤5°, non-recordable ERGs) and 40 age-matched healthy subjects. Pupil responses to full-field red (605 nm) and blue (420 nm) stimuli of 28 lx corneal illumination were recorded and analysed for two stimulus durations (1 and 4 seconds). The perception threshold of phosphenes to transcorneal electrostimulation was ascertained and correlated to the pupil responses and visual acuity. Patients with RP showed significantly reduced pupil responses to red and blue stimuli compared with the controls. With red stimuli, pupillary escape could be observed; blue stimuli resulted in a well-preserved postillumination pupil response. Phosphene thresholds were significantly increased in patients with RP and correlated with the parameters of the pupil response if all subjects were considered. Within the RP group alone, this relationship was less pronounced and statistically not significant. Chromatic pupillography demonstrated a significant decrease in outer retinal photoreceptor responses but a persisting and disinhibited intrinsic photosensitive retinal ganglion cell function in advanced RP. These phenomena may be useful as an objective marker for the efficacy of any interventional treatment for hereditary retinal diseases as well as for the selection of suitable patients for an electronic retinal implant. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Surgical managment of retinal detachment].

PubMed

Haritoglou, C; Wolf, A

2015-05-01

The detachment of the neurosensory retina from the underlying retinal pigment epithelium can be related to breaks of the retina allowing vitreous fluid to gain access to the subretinal space, to exudative changes of the choroid such as tumours or inflammatory diseases or to excessive tractional forces exerted by interactions of the collagenous vitreous and the retina. Tractional retinal detachment is usually treated by vitrectomy and exudative detachment can be addressed by treatment of the underlying condition in many cases. In rhegmatogenous retinal detachment two different surgical procedures, vitrectomy and scleral buckling, can be applied for functional and anatomic rehabilitation of our patients. The choice of the surgical procedure is not really standardised and often depends on the experience of the surgeon and other more ocular factors including lens status, the number of retinal breaks, the extent of the detachment and the amount of preexisting PVR. Using both techniques, anatomic success rates of over 90 % can be achieved. Especially in young phakic patients scleral buckling offers the true advantage to prevent the progression of cataract formation requiring cataract extraction and intraocular lens implantation. Therefore, scleral buckling should be considered in selected cases as an alternative surgical option in spite of the very important technical refinements in modern vitrectomy techniques. Georg Thieme Verlag KG Stuttgart · New York.

Strategy for the Management of Macular Edema in Retinal Vein Occlusion: The European VitreoRetinal Society Macular Edema Study

PubMed Central

Adelman, Ron A.; Parnes, Aaron J.; Bopp, Silvia; Saad Othman, Ihab; Ducournau, Didier

2015-01-01

Objective. To compare the efficacy of different therapies in the treatment of macular edema associated with retinal vein occlusion (RVO). Design. This is a nonrandomized, multicenter collaborative study. Participants. 86 retina specialists from 29 countries provided clinical information, including choice of treatment and outcome, on 2,603 patients with macular edema including 738 cases of RVO. Methods. Reported data included the type and number of treatments performed, visual acuities, and other clinical and diagnostic findings. Main Outcome Measures. The mean increase in visual acuity and mean number of treatments performed. Results. 358 cases of central retinal vein occlusion (CRVO) and 380 cases of branch retinal vein occlusion (BRVO) were included in this investigation. Taking all RVO cases together, pars plana vitrectomy with internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than other therapies. Those treated with intravitreal antivascular endothelial growth factor (anti-VEGF) injection alone showed the second greatest improvement in vision. Dexamethasone intravitreal implant alone and intravitreal triamcinolone alone both resulted in modest visual gains. Conclusions. In the treatment of macular edema in RVO, vitrectomy with ILM peeling may achieve visual improvement and may be a good option for certain cases. Anti-VEGF injection is the most effective of the nonsurgical treatments. PMID:25705695

Strategy for the management of macular edema in retinal vein occlusion: the European VitreoRetinal Society macular edema study.

PubMed

Adelman, Ron A; Parnes, Aaron J; Bopp, Silvia; Saad Othman, Ihab; Ducournau, Didier

2015-01-01

To compare the efficacy of different therapies in the treatment of macular edema associated with retinal vein occlusion (RVO). This is a nonrandomized, multicenter collaborative study. 86 retina specialists from 29 countries provided clinical information, including choice of treatment and outcome, on 2,603 patients with macular edema including 738 cases of RVO. Reported data included the type and number of treatments performed, visual acuities, and other clinical and diagnostic findings. The mean increase in visual acuity and mean number of treatments performed. 358 cases of central retinal vein occlusion (CRVO) and 380 cases of branch retinal vein occlusion (BRVO) were included in this investigation. Taking all RVO cases together, pars plana vitrectomy with internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than other therapies. Those treated with intravitreal antivascular endothelial growth factor (anti-VEGF) injection alone showed the second greatest improvement in vision. Dexamethasone intravitreal implant alone and intravitreal triamcinolone alone both resulted in modest visual gains. In the treatment of macular edema in RVO, vitrectomy with ILM peeling may achieve visual improvement and may be a good option for certain cases. Anti-VEGF injection is the most effective of the nonsurgical treatments.

[The penis prolongation and augmentation combined with autologous granular fat injection and silicone implantation].

PubMed

Xie, Yang-chun; Zhang, Yang; Fan, Jin-cai; Liu, Yuan-bo; Liu, Li-qiang; Wang, Qian

2007-07-01

To prevent the retraction of the penis after prolongation and augmentation. After all the superficial and part of the deep suspensory ligament amputation, we implanted the silicon sheet (the length 2.3-3.6 cm, the width 1.5-2.5 cm, the thickness 2-3 mm) and injected autologous granular fat (30-48 ml) into penis. 16 patients (age 22-63 years, averagely 38 years) underwent this kind operation, the prolongation length is 1.8-5.1 cm, the average was 2.91 cm, the increased diameter of penis was 0.6-1 cm, the average is 0.85 cm, the following period is 3 months to 2 years. The results are satisfactory with the penis retraction less than 8%, and less than 10% decrease in diameter. This method is an ideal way of the penis prolongation and augmentation, the implantation of the silicon sheet is effective way to prevent the retraction of the penis.

Perspectives on human clinical trials of therapies using iPS cells in Japan: reaching the forefront of stem-cell therapies.

PubMed

Song, Peipei; Inagaki, Yoshinori; Sugawara, Yasuhiko; Kokudo, Norihiro

2013-06-01

A research project involving sheets of retinal pigment epithelium constructed from iPS cells derived from patients with age-related maculopathy is one step closer to being approved for clinical trials by the Japanese Government. Now is the time to make therapies using iPS cells clinically available.

Inflammatory nasal polyps: an unusual late complication of Silastic sheet repair of orbital floor fracture.

PubMed

Andrews, A E; Hicklin, L

2006-02-01

Silastic implants are very widely used in surgical practice and are considered to be relatively inert. They do however present with complications, including infection, local foreign body inflammatory response,calcification, migration and failure of repair of the defect, which sometimes may necessitate explantation. Head and neck implants do present a special case, as complications can cause obstruction and disruption of function in small cavities. A pertinent history, clinical review and computed tomography scan are usually invaluable in obtaining a diagnosis. We present a rare case of migrated Silastic orbital sheet, presenting as a nasal polyp and causing maxillary antral pain and infection. A detailed search of the medical literature revealed no other such case.

[Comparison of Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab as a First-Line Treatment of Macular Oedema due to Retinal Vein Occlusion].

PubMed

Mayer, W J; Hadjigoli, A; Wolf, A; Herold, T; Haritoglou, C

2015-11-01

The present study investigated the treatment effect of dexamethasone implant (Ozurdex®, group 1) and anti-VEGF injection (Lucentis®, group 2) in course of macular oedema due to retinal vein occlusion in a retrospective, non-randomised case series. Group 1 comprised 60 patients (31 with CRVO and 29 with BRVO) and group 2 included 52 patients, 27 with CRVO and 25 with BRVO) and both groups were further treated in case of recurrence. Preoperative and in monthly intervals best corrected visual acuity (BCVA), central retinal thickness using SD-OCT (Spectralis, Heidelberg Engineering), intraocular pressure, biomicroscopy status and a fundus photo documentation (Optomap) were evaluated. The primary clinical endpoint was visual acuity 12 months after the first intravitreal therapy, while secondary endpoints included the central retinal thickness change and safety of therapy. In group 1, an increase of BCVA (± standard deviation) of 8.4 (± 1.9) letters was observed in CRVO patients and a gain of 10.7 (± 3.8) letters in BRVO patients after 12 months, while in group 2, an increase of BCVA of 6.9 (± 1.9) letters (CRVO) compared to 12.5 (± 3.7) letters (BRVO) was observed after the same time span. In both groups a significant reduction in retinal thickness was achieved. An increase of intraocular pressure above 5 mmHg was observed in nearly half of the cases In group 1, but was well controlled by conservative antiglaucomatous therapy. We observed a progression of lens opacity in approximately 50 % of the cases in group 1. The treatment with Ozurdex compared to Lucentis appears to provide a trend towards a better although not significant visual acuity increase after 12 months in CRVO patients. A similar trend favouring anti-VEGF treatment with Lucentis was seen in patients with BRVO. However, the lens status and age of the patient should be taken into account when considering a treatment with Ozurdex. Georg Thieme Verlag KG Stuttgart · New York.

Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit

NASA Astrophysics Data System (ADS)

Yamauchi, Yasuyuki; Franco, Luisa M.; Jackson, Douglas J.; Naber, John F.; Ofer Ziv, R.; Rizzo, Joseph F., III; Kaplan, Henry J.; Enzmann, Volker

2005-03-01

The aim of the study was to directly compare the threshold electrical charge density of the retina (retinal threshold) in rabbits for the generation of electrical evoked potentials (EEP) by delivering electrical stimulation with a custom-made microelectrode array (MEA) implanted into either the subretinal or suprachoroidal space. Nine eyes of seven Dutch-belted rabbits were studied. The electroretinogram (ERG), visual evoked potentials (VEP) and EEP were recorded. Electrodes for the VEP and EEP were placed on the dura mater overlying the visual cortex. The EEP was recorded following electrical stimulation of the MEA placed either subretinally beneath the visual streak of the retina or in the suprachoroidal space in the rabbit eye. An ab externo approach was used for placement of the MEA. Liquid perfluorodecaline (PFCL; 0.4 ml) was placed within the vitreous cavity to flatten the neurosensory retina on the MEA after subretinal implantation. The retinal threshold for generation of an EEP was determined for each MEA placement by three consecutive measurements consisting of 100 computer-averaged recordings. Animals were sacrificed at the conclusion of the experiment and the eyes were enucleated for histological examination. The retinal threshold to generate an EEP was 9 ± 7 nC (0.023 ± 0.016 mC cm-2) within the subretinal space and 150 ± 122 nC (0.375 ± 0.306 mC cm-2) within the suprachoroidal space. Histology showed disruption of the outer retina with subretinal but not suprachoroidal placement. The retinal threshold to elicit an EEP is significantly lower with subretinal placement of the MEA compared to suprachoroidal placement (P < 0.05). The retinal threshold charge density with a subretinal MEA is well below the published charge limit of 1 mC cm-2, which is the level below which chronic stimulation of the retina is considered necessary to avoid tissue damage (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6). Supported in part by The Charles D Kelman, MD Postdoctoral Scholar Award 2003 (YY); Boston VA Hospital (V523P-7278); Research to Prevent Blindness, New York City, NY and Kentucky Research Challenge Trust Fund (HJK).

Cochlear implants: system design, integration, and evaluation.

PubMed

Zeng, Fan-Gang; Rebscher, Stephen; Harrison, William; Sun, Xiaoan; Feng, Haihong

2008-01-01

As the most successful neural prosthesis, cochlear implants have provided partial hearing to more than 120000 persons worldwide; half of which being pediatric users who are able to develop nearly normal language. Biomedical engineers have played a central role in the design, integration and evaluation of the cochlear implant system, but the overall success is a result of collaborative work with physiologists, psychologists, physicians, educators, and entrepreneurs. This review presents broad yet in-depth academic and industrial perspectives on the underlying research and ongoing development of cochlear implants. The introduction accounts for major events and advances in cochlear implants, including dynamic interplays among engineers, scientists, physicians, and policy makers. The review takes a system approach to address critical issues in cochlear implant research and development. First, the cochlear implant system design and specifications are laid out. Second, the design goals, principles, and methods of the subsystem components are identified from the external speech processor and radio frequency transmission link to the internal receiver, stimulator and electrode arrays. Third, system integration and functional evaluation are presented with respect to safety, reliability, and challenges facing the present and future cochlear implant designers and users. Finally, issues beyond cochlear implants are discussed to address treatment options for the entire spectrum of hearing impairment as well as to use the cochlear implant as a model to design and evaluate other similar neural prostheses such as vestibular and retinal implants.

New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

PubMed Central

Park, Young Gun; Roh, Young-Jung

2016-01-01

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results. PMID:26881240

Branch retinal artery occlusion post-penetrating globe injury with intraocular foreign body.

PubMed

Nagpal, Manish; Chaudhary, Pranita; Jain, Ashish

2018-01-01

Intraocular foreign body (IOFB) in cases of penetrating eye injury accounts for an important indication of vitreoretinal intervention following ocular trauma. Vascular occlusion as a complication of IOFB is rare. Here we present a case of a 34-year-old male with post-traumatic cataract and an intraocular metallic foreign body (IOFB) lodged in the superficial layers of the retina inferotemporal to the disc, causing an inferotemporal branch retinal artery occlusion. The case was managed by lensectomy with pars plana vitrectomy and IOFB removal followed by a second procedure of secondary IOL implantation. Final best-corrected visual acuity improved to 6/24. This case highlights an unusual sequelae following penetrating ocular trauma.

Design and assessment of a wrapped cylindrical Ca-P AZ31 Mg alloy for critical-size ulna defect repair.

PubMed

Smith, Montserrat Rabago; Atkinson, Patrick; White, Désirée; Piersma, Tyler; Gutierrez, Gloria; Rossini, Gianny; Desai, Sapna; Wellinghoff, Stephen; Yu, Hui; Cheng, Xingguo

2012-01-01

Recently, magnesium has been investigated as a promising bioresorbable orthopedic biomaterial. Its mechanical properties are very similar to natural bone, making it appropriate for load-bearing orthopedic fracture repair applications. However, significant hurdles remain regarding the design of practical implants and methods to control degradation and enhance biocompatibility. Although attempts have been made to hinder magnesium's rapid corrosion via alloying and coating, these studies have used solid monoliths. In an effort to reduce the amount of alloy used for implantation in a shape that mimics cortical bone shape, this study used a thin sheet of Mg AZ31 which was rolled into hollow cylindrical scaffolds. The scaffold was coated with different amounts of Ca-P; this implant demonstrated slowed corrosion in simulated body fluid (SBF) as well as enhanced biocompatibility for mesenchymal stem cells (MSC). In vivo implantation of magnesium alloy scaffold adjacent to the rat femur showed significant biointegration with further deposition of complex Mg-Ca phosphates/carbonates typical of natural bone. Finally, the implant was placed in a critical-size ulna defect in live rabbits, which lead to radiographic union and partial restoration of biomechanical strength in the defect. This study demonstrated that a thin sheet of coated Mg alloy that was spirally wrapped wound be a promising orthopedic biomaterial for bone repair. Copyright © 2011 Wiley Periodicals, Inc.

Iris-fixated phakic intraocular lens implantation after retinal detachment surgery: long-term clinical results.

PubMed

Chung, Jin Kwon; Kim, Jin Kook; Lee, Jae Bum; Lee, Sung Jin

2013-10-01

To assess the efficacy and safety of iris-fixated phakic intraocular lens (pIOL) implantation to correct myopia in eyes with previous retinal detachment (RD) surgery. Department of Ophthalmology, Soonchunhyang University College of Medicine, Seoul, South Korea. Retrospective case series. Patients having pIOL implantation in both eyes were enrolled. Eyes that had scleral buckling or encircling (RD group) and healthy fellow eyes (non-RD group) were evaluated over a 6-year follow-up. The corrected distance visual acuity (CDVA), endothelial cell density (ECD), intraoperative complications, and long-term complications were safety outcomes. Uncorrected distance visual acuity (UDVA), predictability, and stability of refraction were efficacy outcomes. The study comprised 34 eyes (17 patients). The mean postoperative CDVA and ECD were not significantly different between groups, and no patient lost CDVA. The rate of transient intraocular pressure spike was significantly higher in the RD group (P=.043). After 3 years and 6 years, the mean postoperative UDVA was 0.06 logMAR ± 0.09 (SD) and 0.08 ± 0.10 logMAR, respectively, in the RD group and 0.04 ± 0.08 logMAR and 0.04 ± 0.09 logMAR, respectively, in the non-RD group (P=.518 and P=.478, respectively). The rate of eyes within ±0.50 diopter of the desired refraction and the postoperative refraction was not significantly different between groups. No eye had vitreoretinal changes requiring secondary surgical intervention. Iris-fixated pIOL implantation corrected the myopic refractive error in patients who had scleral buckling or encircling surgery for RD with a high degree of efficacy, safety, and long-term stability. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Clinical effectiveness and safety of collagen sheet for dorsal augmentation in rhinoplasty.

PubMed

Chang, Chul; Kong, Won Kyoung

2014-09-01

In Asian rhinoplasty, dorsal augmentation often requires the use of alloplastic materials because sufficient amounts of autograft are difficult to harvest. Given considerations of aesthetics, costs, and the characteristics of the oriental nose, silicone or Gore-Tex is commonly used when augmenting the nasal dorsum to a great extent. Such materials can often result in postoperative complications and foreign-body sensations. Moreover, extrusion or visualization of the implant may occur because of thinning of the skin over time. Permacol collagen implants are specifically indicated for soft tissue reinforcement and repair of the head and face in plastic and reconstructive surgery. The handling versatility of the flexible collagen sheet allows it to be layered over itself until the requisite thickness and desired shape are obtained. A total of 50 patients who underwent nasal augmentation rhinoplasty between December 2007 and May 2011 were observed for at least 24 months. Depending on the nasal dorsum, we layered the collagen sheet up to a maximum of 4 times and we have not seen any case of severe resorption or overcorrection in the nasal configuration. Collagen implant material is safe for use in select rhinoplasty patients because of its low complication rate, as shown in our series. It could therefore be considered as a useful alternative when reconstruction is problematic because of the low quality or lack of available autologous grafts.

In vivo chromatic aberration in eyes implanted with intraocular lenses.

PubMed

Pérez-Merino, Pablo; Dorronsoro, Carlos; Llorente, Lourdes; Durán, Sonia; Jiménez-Alfaro, Ignacio; Marcos, Susana

2013-04-12

To measure in vivo and objectively the monochromatic aberrations at different wavelengths, and the chromatic difference of focus between green and infrared wavelengths in eyes implanted with two models of intraocular lenses (IOL). EIGHTEEN EYES PARTICIPATED IN THIS STUDY: nine implanted with Tecnis ZB99 1-Piece acrylic IOL and nine implanted with AcrySof SN60WF IOL. A custom-developed laser ray tracing (LRT) aberrometer was used to measure the optical aberrations, at 532 nm and 785 nm wavelengths. The monochromatic wave aberrations were described using a fifth-order Zernike polynomial expansion. The chromatic difference of focus was estimated as the difference between the equivalent spherical errors corresponding to each wavelength. Wave aberration measurements were highly reproducible. Except for the defocus term, no significant differences in high order aberrations (HOA) were found between wavelengths. The average chromatic difference of focus was 0.46 ± 0.15 diopters (D) in the Tecnis group, and 0.75 ± 0.12 D in the AcrySof group, and the difference was statistically significant (P < 0.05). Chromatic difference of focus in the AcrySof group was not statistically significantly different from the Longitudinal chromatic aberration (LCA) previously reported in a phakic population (0.78 ± 0.16 D). The impact of LCA on retinal image quality (measured in terms of Strehl ratio) was drastically reduced when considering HOA and astigmatism in comparison with a diffraction-limited eye, yielding the differences in retinal image quality between Tecnis and AcrySof IOLs not significant. LRT aberrometry at different wavelengths is a reproducible technique to evaluate the chromatic difference of focus objectively in eyes implanted with IOLs. Replacement of the crystalline lens by the IOL did not increase chromatic difference of focus above that of phakic eyes in any of the groups. The AcrySof group showed chromatic difference of focus values very similar to physiological values in young eyes.

[Early efficacy of dexamethasone implant (OZURDEX®) in diabetic macular edema: Real life study].

PubMed

Sarda, V; Fajnkuchen, F; Nghiem-Buffet, S; Grenet, T; Chaine, G; Giocanti-Auregan, A

2017-05-01

To assess early efficacy of dexamethasone intravitreal implant 0.7mg (OZURDEX ® ) at the time of peak efficacy (2 months after injection) in patients with decreased visual acuity secondary to diabetic macular edema (DME). Retrospective monocentric study. Inclusion criteria were best-corrected visual acuity (BCVA)≤70 letters (20/40) due to DME and central retinal thickness (CRT)≥300 microns (Cirrus 2, Carl Zeiss Meditec, Inc, Dublin). Enrolled patients could be treatment naive or not (after failure of laser photocoagulation and/or anti-VEGF therapy). Follow-up was at least 6 months. Our primary endpoint was BCVA gain at M2 after injection. Secondary endpoints were best-corrected visual acuity at 2 and 4 months, central retinal thickness at 2 and 4 months, mean interval between 2 injections, and adverse events. Nineteen eyes of 19 patients were included in this study. The mean age was 67.45 years, sex ratio was 2.17 men/women, and the patients were all type 2 diabetics. Three of 19 patients were treatment naive for anti-VEGF intravitreal injection, and 52.3% were pseudophakic (10/19 patients). The mean gain of BCVA at M2 was +7.7 letters. The mean BCVA was 51.1 ETDRS letters at baseline and 58.8 at M2. Mean CRT was 568.9μm at baseline and 291.2μm at M2. Treatment with dexamethasone implant was mainly a second-line treatment after failure of other treatments (macular laser photocoagulation and/or intravitreal injection of anti-VEGF). Three patients were naive of anti-VEGF treatment. Intraocular pressure≥25mmHg was found in 2 patients, and controlled medically. No glaucoma surgery was performed. The dexamethasone implant (OZURDEX ® ) allows an anatomical and functional improvement in patients suffering from vision loss due to DME. In this series, the implant was well tolerated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

21 CFR 874.3820 - Endolymphatic shunt.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Identification. An endolymphatic shunt is a device that consists of a tube or sheet intended to be implanted to... made of polytetrafluoroethylene or silicone elastomer. (b) Classification. Class II. ...

21 CFR 874.3820 - Endolymphatic shunt.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Identification. An endolymphatic shunt is a device that consists of a tube or sheet intended to be implanted to... made of polytetrafluoroethylene or silicone elastomer. (b) Classification. Class II. ...

21 CFR 874.3820 - Endolymphatic shunt.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Identification. An endolymphatic shunt is a device that consists of a tube or sheet intended to be implanted to... made of polytetrafluoroethylene or silicone elastomer. (b) Classification. Class II. ...

21 CFR 874.3820 - Endolymphatic shunt.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Identification. An endolymphatic shunt is a device that consists of a tube or sheet intended to be implanted to... made of polytetrafluoroethylene or silicone elastomer. (b) Classification. Class II. ...

21 CFR 874.3820 - Endolymphatic shunt.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Identification. An endolymphatic shunt is a device that consists of a tube or sheet intended to be implanted to... made of polytetrafluoroethylene or silicone elastomer. (b) Classification. Class II. ...

Cochlear Implants:System Design, Integration and Evaluation

PubMed Central

Rebscher, Stephen; Harrison, William V.; Sun, Xiaoan; Feng, Haihong

2009-01-01

As the most successful neural prosthesis, cochlear implants have provided partial hearing to more than 120,000 persons worldwide; half of which being pediatric users who are able to develop nearly normal language. Biomedical engineers have played a central role in the design, integration and evaluation of the cochlear implant system, but the overall success is a result of collaborative work with physiologists, psychologists, physicians, educators, and entrepreneurs. This review presents broad yet in-depth academic and industrial perspectives on the underlying research and ongoing development of cochlear implants. The introduction accounts for major events and advances in cochlear implants, including dynamic interplays among engineers, scientists, physicians, and policy makers. The review takes a system approach to address critical issues from design and specifications to integration and evaluation. First, the cochlear implant system design and specifications are laid out. Second, the design goals, principles, and methods of the subsystem components are identified from the external speech processor and radio frequency transmission link to the internal receiver, stimulator and electrode arrays. Third, system integration and functional evaluation are presented with respect to safety, reliability, and challenges facing the present and future cochlear implant designers and users. Finally, issues beyond cochlear implants are discussed to address treatment options for the entire spectrum of hearing impairment as well as to use the cochlear implant as a model to design and evaluate other similar neural prostheses such as vestibular and retinal implants. PMID:19946565

FTIR study of the photoreaction of bovine rhodopsin in the presence of hydroxylamine.

PubMed

Katayama, Kota; Furutani, Yuji; Kandori, Hideki

2010-07-15

In bovine rhodopsin, 11-cis-retinal forms a Schiff base linkage with Lys296. The Schiff base is not reactive to hydroxylamine in the dark, which is consistent with the well-protected retinal binding site. In contrast, under illumination it easily forms all-trans retinal oxime, resulting in the loss of color. This suggests that activation of rhodopsin creates a specific reaction channel for hydroxylamine or loosens the chromophore binding pocket. In the present study, to extract structural information on the Schiff base vicinity and to understand the changes upon activation of rhodopsin, we compared light-induced FTIR difference spectra of bovine rhodopsin in the presence and absence of hydroxylamine under physiological pH (approximately 7). Although the previous FTIR study did not observe the complex formation between rhodopsin and G-protein transducin in hydrated films, the present study clearly shows that hydrated films can be used for studies of the interaction between rhodopsin and hydroxylamine. Hydroxylamine does not react with the Schiff base of Meta-I intermediate trapped at 240 K, possibly because of decreased conformational motions under the frozen environment, while FTIR spectroscopy showed that hydroxylamine affects the hydrogen bonds of the Schiff base and water molecules in Meta-I. In contrast, formation of the retinal oxime was clearly observed at 280 K, the characteristic temperature of Meta-II accumulation in the absence of hydroxylamine, and time-dependent formation of retinal oxime was observed from Meta-II at 265 K as well. The obtained difference FTIR spectra of retinal oxime and opsin are different from that of Meta-II. It is likely that the antiparallel beta-sheet constituting a part of the retinal binding pocket at the extracellular surface is structurally disrupted in the presence of hydroxylamine, which allows the hydrolysis of the Schiff base into retinal oxime.

Intravitreal Steroids for the Treatment of Retinal Diseases

PubMed Central

Veritti, Daniele; Boscia, Francesco

2014-01-01

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologist's armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drug's half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events. PMID:24526927

Intraocular Pressure and Retinal Nerve Fibre Layer Thickness Changes After Carotid Artery Stenting.

PubMed

Biberoğlu, Esra; Eraslan, Muhsin; Baltacıoğlu, Feyyaz; Midi, İpek

2017-08-01

The aim of this study was to evaluate intraocular pressure (IOP) and retinal nerve fiber layer (RNFL) changes in patients with carotid artery stenosis (CAS) after carotid artery stenting. This study was conducted as a cross-sectional, non-randomised clinical case series. Fifteen male patients (mean age: 63.6±9.1) with CAS and more than 70% carotid artery narrowing were included. All of the patients were followed in the department of neurology and were operated in the interventional radiology division. Eighteen healthy male subjects (mean age: 63.7±5.3) were included in the control group. All of the healthy subjects had a detailed ophthalmological examination and subjects with any chronic eye disease were excluded from the study. All of the participants had a detailed ophthalmological examination including tonometry using Goldmann applanation tonometry and RNFL analysis using optical coherence tomography (RTVue-100 5.1). There were no ocular ischemic symptoms in any of the participants. The mean IOP value was 15.1±2.1 mmHg in the control group and 16.6±2.4 mmHg before stent implantation, 16.4±2.2 mmHg at 1 week after implantation, 16.6±2.5 mmHg at 1 month after implantation, and 16.7±2.9 mmHg at 3 months after implantation in the CAS group. Mean RNFL thickness was 105±6 µm in the control group; in the CAS group, mean RNFL thickness values were 98±27 µm before stent implantation and 103±11 µm, 101±10 µm, and 101±11 µm at 1 week, 1 month, and 3 months after stenting. There were no significant differences between the CAS group and control group regarding IOP and RNFL thickness values (p>0.05). IOP and RNFL thickness also did not show any statistically significant changes from preoperative measurements in 3 months postoperative follow-up in the CAS group (p>0.05). IOP and RNFL thickness remained unchanged after carotid stent implantation in carotid artery stenosis patients with no signs of ocular ischemic syndrome.

Intraocular Pressure and Retinal Nerve Fibre Layer Thickness Changes After Carotid Artery Stenting

PubMed Central

Biberoğlu, Esra; Eraslan, Muhsin; Baltacıoğlu, Feyyaz; Midi, İpek

2017-01-01

Objectives: The aim of this study was to evaluate intraocular pressure (IOP) and retinal nerve fiber layer (RNFL) changes in patients with carotid artery stenosis (CAS) after carotid artery stenting. Materials and Methods: This study was conducted as a cross-sectional, non-randomised clinical case series. Fifteen male patients (mean age: 63.6±9.1) with CAS and more than 70% carotid artery narrowing were included. All of the patients were followed in the department of neurology and were operated in the interventional radiology division. Eighteen healthy male subjects (mean age: 63.7±5.3) were included in the control group. All of the healthy subjects had a detailed ophthalmological examination and subjects with any chronic eye disease were excluded from the study. All of the participants had a detailed ophthalmological examination including tonometry using Goldmann applanation tonometry and RNFL analysis using optical coherence tomography (RTVue-100 5.1). Results: There were no ocular ischemic symptoms in any of the participants. The mean IOP value was 15.1±2.1 mmHg in the control group and 16.6±2.4 mmHg before stent implantation, 16.4±2.2 mmHg at 1 week after implantation, 16.6±2.5 mmHg at 1 month after implantation, and 16.7±2.9 mmHg at 3 months after implantation in the CAS group. Mean RNFL thickness was 105±6 µm in the control group; in the CAS group, mean RNFL thickness values were 98±27 µm before stent implantation and 103±11 µm, 101±10 µm, and 101±11 µm at 1 week, 1 month, and 3 months after stenting. There were no significant differences between the CAS group and control group regarding IOP and RNFL thickness values (p>0.05). IOP and RNFL thickness also did not show any statistically significant changes from preoperative measurements in 3 months postoperative follow-up in the CAS group (p>0.05). Conclusion: IOP and RNFL thickness remained unchanged after carotid stent implantation in carotid artery stenosis patients with no signs of ocular ischemic syndrome. PMID:28845322

The use of AlloDerm in postmastectomy alloplastic breast reconstruction: part II. A cost analysis.

PubMed

Jansen, Leigh A; Macadam, Sheina A

2011-06-01

Increasingly, AlloDerm is being used in alloplastic breast reconstruction, and has been the subject of a recent systematic review. The authors' objective was to perform a cost analysis comparing direct-to-implant with AlloDerm reconstruction to two-stage non-AlloDerm reconstruction. Seven clinically important health outcomes and their probabilities for both types of reconstruction were derived from the recent review. A decision analytic model from the Canadian provincial payer's perspective was constructed based on these health states. Direct medical costs were estimated from a university-based hospital, yielding expected costs for direct-to-implant reconstruction with AlloDerm and two-stage non-AlloDerm reconstruction. Sensitivity analyses were conducted. Baseline and expected costs were calculated for direct-to-implant AlloDerm and two-stage non-AlloDerm reconstruction. Direct-to-implant reconstruction with AlloDerm was found to be less expensive in the baseline ($10,240 versus $10,584) and expected cost ($10,734 versus $11,251) using a 6 × 16-cm AlloDerm sheet. With a 6 × 12-cm sheet, expected cost falls to $9673. By increasing direct-to-implant operative time from 2 hours to 2.5 hours, expected cost rises to $11,784. If capsular contracture rate requiring revision is set at 15 percent for both procedures, expected costs are $10,926 and $11,251 for direct-to-implant and two-stage procedures, respectively. If the capsular contracture rate is lowered for either procedure, this has minimal impact on expected cost. Although AlloDerm is expensive, it appears to be cost-effective if used for direct-to-implant breast reconstruction. The methods used here may be extrapolated to different centers incorporating local costs and complication rates. A formal randomized controlled trial, including costs, is recommended.

Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2017-08-01

Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on-off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off visual pathways.

Early light deprivation effects on human cone-driven retinal function.

PubMed

Esposito Veneruso, Paolo; Ziccardi, Lucia; Magli, Giulia; Parisi, Vincenzo; Falsini, Benedetto; Magli, Adriano

2017-03-01

To assess whether the early light deprivation induced by congenital cataract may influence the cone-driven retinal function in humans. Forty-one patients affected by congenital cataract (CC) who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity (BCVA) measurement; light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function respectively. Mean values of light-adapted ERG a- and b-wave and PhNR amplitude of CC eyes were significantly reduced and photopic ERG b-wave implicit time mean values were significantly delayed when compared to HS ones. When studying photopic ERG mean amplitudes at 5 ms, significant differences were found when comparing CC and control eyes. In CC eyes, statistically significant correlations were found between a- and b- wave amplitudes and PhNR amplitudes. No significant correlations were found between ERG parameters and BCVA, as well as between the age of CC patients at surgery and the time elapsed from lens extraction. No significant differences were found when functional parameters of bilateral and unilateral congenital cataract (uCC) eyes were compared, however uCC eyes showed significant differences when compared with contralateral healthy eyes. We found a significant impairment of cone-driven retinal responses in patients with a history of congenital cataract. These changes might result from the long-lasting effects of early light deprivation on the cone retinal pathways. Our findings support the relevance of retinal involvement in deficits induced by early light deprivation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Reading Visual Braille with a Retinal Prosthesis

PubMed Central

Lauritzen, Thomas Z.; Harris, Jordan; Mohand-Said, Saddek; Sahel, Jose A.; Dorn, Jessy D.; McClure, Kelly; Greenberg, Robert J.

2012-01-01

Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2–4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients. PMID:23189036

Reading visual braille with a retinal prosthesis.

PubMed

Lauritzen, Thomas Z; Harris, Jordan; Mohand-Said, Saddek; Sahel, Jose A; Dorn, Jessy D; McClure, Kelly; Greenberg, Robert J

2012-01-01

Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2-4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients.

Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.

PubMed

Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2013-11-15

To investigate the potential therapeutic benefit of intravitreally implanted dental pulp stem cells (DPSCs) on axotomized adult rat retinal ganglion cells (RGCs) using in vitro and in vivo neural injury models. Conditioned media collected from cultured rat DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were assayed for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) secretion using ELISA. DPSCs or BMSCs were cocultured with retinal cells, with or without Fc-TrK inhibitors, in a Transwell system, and the number of surviving βIII-tubulin⁺ retinal cells and length/number of βIII-tubulin⁺ neurites were quantified. For the in vivo study, DPSCs or BMSCs were transplanted into the vitreous body of the eye after a surgically induced optic nerve crush injury. At 7, 14, and 21 days postlesion (dpl), optical coherence tomography (OCT) was used to measure the retinal nerve fiber layer thickness as a measure of axonal atrophy. At 21 dpl, numbers of Brn-3a⁺ RGCs in parasagittal retinal sections and growth-associated protein-43⁺ axons in longitudinal optic nerve sections were quantified as measures of RGC survival and axon regeneration, respectively. Both DPSCs and BMSCs secreted NGF, BDNF, and NT-3, with DPSCs secreting significantly higher titers of NGF and BDNF than BMSCs. DPSCs, and to a lesser extent BMSCs, promoted statistically significant survival and neuritogenesis/axogenesis of βIII-tubulin⁺ retinal cells in vitro and in vivo where the effects were abolished after TrK receptor blockade. Intravitreal transplants of DPSCs promoted significant neurotrophin-mediated RGC survival and axon regeneration after optic nerve injury.

Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays

PubMed Central

Johnen, Sandra; Meißner, Frank; Krug, Mario; Baltz, Thomas; Endler, Ingolf; Mokwa, Wilfried; Walter, Peter

2016-01-01

Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue. PMID:27200182

Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays.

PubMed

Johnen, Sandra; Meißner, Frank; Krug, Mario; Baltz, Thomas; Endler, Ingolf; Mokwa, Wilfried; Walter, Peter

2016-01-01

Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue.

Probing the functional impact of sub-retinal prosthesis

PubMed Central

Roux, Sébastien; Matonti, Frédéric; Dupont, Florent; Hoffart, Louis; Takerkart, Sylvain; Picaud, Serge; Pham, Pascale; Chavane, Frédéric

2016-01-01

Retinal prostheses are promising tools for recovering visual functions in blind patients but, unfortunately, with still poor gains in visual acuity. Improving their resolution is thus a key challenge that warrants understanding its origin through appropriate animal models. Here, we provide a systematic comparison between visual and prosthetic activations of the rat primary visual cortex (V1). We established a precise V1 mapping as a functional benchmark to demonstrate that sub-retinal implants activate V1 at the appropriate position, scalable to a wide range of visual luminance, but with an aspect-ratio and an extent much larger than expected. Such distorted activation profile can be accounted for by the existence of two sources of diffusion, passive diffusion and activation of ganglion cells’ axons en passant. Reverse-engineered electrical pulses based on impedance spectroscopy is the only solution we tested that decreases the extent and aspect-ratio, providing a promising solution for clinical applications. DOI: http://dx.doi.org/10.7554/eLife.12687.001 PMID:27549126

Finite element simulation and Experimental verification of Incremental Sheet metal Forming

NASA Astrophysics Data System (ADS)

Kaushik Yanamundra, Krishna; Karthikeyan, R., Dr.; Naranje, Vishal, Dr

2018-04-01

Incremental sheet metal forming is now a proven manufacturing technique that can be employed to obtain application specific, customized, symmetric or asymmetric shapes that are required by automobile or biomedical industries for specific purposes like car body parts, dental implants or knee implants. Finite element simulation of metal forming process is being performed successfully using explicit dynamics analysis of commercial FE software. The simulation is mainly useful in optimization of the process as well design of the final product. This paper focuses on simulating the incremental sheet metal forming process in ABAQUS, and validating the results using experimental methods. The shapes generated for testing are of trapezoid, dome and elliptical shapes whose G codes are written and fed into the CNC milling machine with an attached forming tool with a hemispherical bottom. The same pre-generated coordinates are used to simulate a similar machining conditions in ABAQUS and the tool forces, stresses and strains in the workpiece while machining are obtained as the output data. The forces experimentally were recorded using a dynamometer. The experimental and simulated results were then compared and thus conclusions were drawn.

Wireless Power Transfer Strategies for Implantable Bioelectronics.

PubMed

Agarwal, Kush; Jegadeesan, Rangarajan; Guo, Yong-Xin; Thakor, Nitish V

2017-01-01

Neural implants have emerged over the last decade as highly effective solutions for the treatment of dysfunctions and disorders of the nervous system. These implants establish a direct, often bidirectional, interface to the nervous system, both sensing neural signals and providing therapeutic treatments. As a result of the technological progress and successful clinical demonstrations, completely implantable solutions have become a reality and are now commercially available for the treatment of various functional disorders. Central to this development is the wireless power transfer (WPT) that has enabled implantable medical devices (IMDs) to function for extended durations in mobile subjects. In this review, we present the theory, link design, and challenges, along with their probable solutions for the traditional near-field resonant inductively coupled WPT, capacitively coupled short-ranged WPT, and more recently developed ultrasonic, mid-field, and far-field coupled WPT technologies for implantable applications. A comparison of various power transfer methods based on their power budgets and WPT range follows. Power requirements of specific implants like cochlear, retinal, cortical, and peripheral are also considered and currently available IMD solutions are discussed. Patient's safety concerns with respect to electrical, biological, physical, electromagnetic interference, and cyber security from an implanted neurotech device are also explored in this review. Finally, we discuss and anticipate future developments that will enhance the capabilities of current-day wirelessly powered implants and make them more efficient and integrable with other electronic components in IMDs.

Interactions of Prosthetic and Natural Vision in Animals With Local Retinal Degeneration

PubMed Central

Lorach, Henri; Lei, Xin; Galambos, Ludwig; Kamins, Theodore; Mathieson, Keith; Dalal, Roopa; Huie, Philip; Harris, James; Palanker, Daniel

2015-01-01

Purpose Prosthetic restoration of partial sensory loss leads to interactions between artificial and natural inputs. Ideally, the rehabilitation should allow perceptual fusion of the two modalities. Here we studied the interactions between normal and prosthetic vision in a rodent model of local retinal degeneration. Methods Implantation of a photovoltaic array in the subretinal space of normally sighted rats induced local degeneration of the photoreceptors above the chip, and the inner retinal neurons in this area were electrically stimulated by the photovoltaic implant powered by near-infrared (NIR) light. We studied prosthetic and natural visually evoked potentials (VEP) in response to simultaneous stimulation by NIR and visible light patterns. Results We demonstrate that electrical and natural VEPs summed linearly in the visual cortex, and both responses decreased under brighter ambient light. Responses to visible light flashes increased over 3 orders of magnitude of contrast (flash/background), while for electrical stimulation the contrast range was limited to 1 order of magnitude. The maximum amplitude of the prosthetic VEP was three times lower than the maximum response to a visible flash over the same area on the retina. Conclusions Ambient light affects prosthetic responses, albeit much less than responses to visible stimuli. Prosthetic representation of contrast in the visual scene can be encoded, to a limited extent, by the appropriately calibrated stimulus intensity, which also depends on the ambient light conditions. Such calibration will be important for patients combining central prosthetic vision with natural peripheral sight, such as in age-related macular degeneration. PMID:26618643

Functional Tooth Restoration by Allogeneic Mesenchymal Stem Cell-Based Bio-Root Regeneration in Swine

PubMed Central

Wei, Fulan; Song, Tieli; Ding, Gang; Xu, Junji; Liu, Yi; Liu, Dayong; Fan, Zhipeng; Zhang, Chunmei

2013-01-01

Our previous proof-of-concept study showed the feasibility of regenerating the dental stem cell-based bioengineered tooth root (bio-root) structure in a large animal model. Here, we used allogeneic dental mesenchymal stem cells to regenerate bio-root, and then installed a crown on the bio-root to restore tooth function. A root shape hydroxyapatite tricalcium phosphate scaffold containing dental pulp stem cells was covered by a Vc-induced periodontal ligament stem cell sheet and implanted into a newly generated jaw bone implant socket. Six months after implantation, a prefabricated porcelain crown was cemented to the implant and subjected to tooth function. Clinical, radiological, histological, ultrastructural, systemic immunological evaluations and mechanical properties were analyzed for dynamic changes in the bio-root structure. The regenerated bio-root exhibited characteristics of a normal tooth after 6 months of use, including dentinal tubule-like and functional periodontal ligament-like structures. No immunological response to the bio-roots was observed. We developed a standard stem cell procedure for bio-root regeneration to restore adult tooth function. This study is the first to successfully regenerate a functional bio-root structure for artificial crown restoration by using allogeneic dental stem cells and Vc-induced cell sheet, and assess the recipient immune response in a preclinical model. PMID:23363023

Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: short-term results.

PubMed

Matsuda, Hidetoshi; Kitamura, Nobuto; Kurokawa, Takayuki; Arakaki, Kazunobu; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

2013-01-31

A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p<0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p<0.05) than that in Group IV. The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

Visual Prostheses: The Enabling Technology to Give Sight to the Blind

PubMed Central

Maghami, Mohammad Hossein; Sodagar, Amir Masoud; Lashay, Alireza; Riazi-Esfahani, Hamid; Riazi-Esfahani, Mohammad

2014-01-01

Millions of patients are either slowly losing their vision or are already blind due to retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) or because of accidents or injuries. Employment of artificial means to treat extreme vision impairment has come closer to reality during the past few decades. Currently, many research groups work towards effective solutions to restore a rudimentary sense of vision to the blind. Aside from the efforts being put on replacing damaged parts of the retina by engineered living tissues or microfabricated photoreceptor arrays, implantable electronic microsystems, referred to as visual prostheses, are also sought as promising solutions to restore vision. From a functional point of view, visual prostheses receive image information from the outside world and deliver them to the natural visual system, enabling the subject to receive a meaningful perception of the image. This paper provides an overview of technical design aspects and clinical test results of visual prostheses, highlights past and recent progress in realizing chronic high-resolution visual implants as well as some technical challenges confronted when trying to enhance the functional quality of such devices. PMID:25709777

Restoring visual perception using microsystem technologies: engineering and manufacturing perspectives.

PubMed

Krisch, I; Hosticka, B J

2007-01-01

Microsystem technologies offer significant advantages in the development of neural prostheses. In the last two decades, it has become feasible to develop intelligent prostheses that are fully implantable into the human body with respect to functionality, complexity, size, weight, and compactness. Design and development enforce collaboration of various disciplines including physicians, engineers, and scientists. The retina implant system can be taken as one sophisticated example of a prosthesis which bypasses neural defects and enables direct electrical stimulation of nerve cells. This micro implantable visual prosthesis assists blind patients to return to the normal course of life. The retina implant is intended for patients suffering from retinitis pigmentosa or macular degeneration. In this contribution, we focus on the epiretinal prosthesis and discuss topics like system design, data and power transfer, fabrication, packaging and testing. In detail, the system is based upon an implantable micro electro stimulator which is powered and controlled via a wireless inductive link. Microelectronic circuits for data encoding and stimulation are assembled on flexible substrates with an integrated electrode array. The implant system is encapsulated using parylene C and silicone rubber. Results extracted from experiments in vivo demonstrate the retinotopic activation of the visual cortex.

Corrosion testing using isotopes

DOEpatents

Hohorst, Frederick A.

1995-12-05

A method for determining the corrosion behavior of a material with respect to a medium in contact with the material by: implanting a substantially chemically inert gas in a matrix so that corrosion experienced by the material causes the inert gas to enter the medium; placing the medium in contact with the material; and measuring the amount of inert gas which enters the medium. A test sample of a material whose resistance to corrosion by a medium is to be tested, composed of: a body of the material, which body has a surface to be contacted by the medium; and a substantially chemically inert gas implanted into the body to a depth below the surface. A test sample of a material whose resistance to corrosion by a medium is to be tested, composed of: a substrate of material which is easily corroded by the medium, the substrate having a surface; a substantially chemically inert gas implanted into the substrate; and a sheet of the material whose resistance to corrosion is to be tested, the sheet being disposed against the surface of the substrate and having a defined thickness.

MRI

MedlinePlus

... the test, tell your provider if you have: Artificial heart valves Brain aneurysm clips Heart defibrillator or pacemaker Inner ear (cochlear) implants Kidney disease or dialysis (you may not ... artificial joints Vascular stents Worked with sheet metal in ...

Magnetic resonance angiography

MedlinePlus

... your provider if you have: Brain aneurysm clips Artificial heart valve Heart defibrillator or pacemaker Inner ear (cochlear) implants Insulin or chemotherapy port Intrauterine device (IUD) Kidney ... artificial joints Vascular stent Worked with sheet metal in ...

Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients.

PubMed

Besch, D; Sachs, H; Szurman, P; Gülicher, D; Wilke, R; Reinert, S; Zrenner, E; Bartz-Schmidt, K U; Gekeler, F

2008-10-01

Due to low energy levels in microphotodiode-based subretinal visual prostheses, an external power supply is mandatory. We report on the surgical feasibility and the functional outcome of the extraocular part of an approach to connect a subretinal prosthesis to an extracorporeal connector in the retro-auricular space via a trans-scleral, transchoroidal cable. Seven volunteers with retinitis pigmentosa received an active subretinal implant; energy was supplied by gold wires on a trans-sclerally, transchoroidally implanted polyimide foil leading to the lateral orbital rim where it was fixated and connected to a silicone cable. The cable was implanted subperiostally beneath the temporal muscle using a trocar to the retro-auricular space where it penetrated the skin for connection to a stimulator. To avoid subretinal movement of the implant, three tension relief points have been introduced. All implantations were performed as planned without complications, and no serious adverse events occurred in the postoperative period. Fixation of the implants was stable throughout the entire study duration of 4 weeks; permanent skin penetration proved to be uncomplicated. Motility was minimally restricted in downgaze and ab-/adduction. Explantation was uneventful. The above-described procedure provides a method for stable fixation of a subretinal device with a trans-scleral, transchoroidal cable connection to an extracorporeal connector.

Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet

PubMed Central

Kamei, Naosuke; Adachi, Nobuo; Hamanishi, Michio; Kamei, Goki; Mahmoud, Elhussein Elbadry; Nakano, Tomohiro; Iwata, Takanori; Yamato, Masayuki; Okano, Teruo; Ochi, Mitsuo

2015-01-01

Cell sheet engineering has developed as a remarkable method for cell transplantation. In the field of cartilage regeneration, several studies previously reported that cartilage defects could be regenerated by transplantation of a chondrocyte sheet using cell sheet engineering. However, it remains unclear how such a thin cell sheet could repair a deep cartilage defect. We, therefore, focused on the mechanism of cartilage repair using cell sheet engineering in this study. Chondrocyte sheets and synovial cell sheets were fabricated using cell sheet engineering, and these allogenic cell sheets were transplanted to cover an osteochondral defect in a rat model. Macroscopic and histological evaluation was performed at 4 and 12 weeks after transplantation. Analysis of the gene expression of each cell sheet and of the regenerated tissue at 1 week after transplantation was performed. In addition, green fluorescent protein (GFP) transgenic rats were used as donors (transplanted chondrocyte sheets) or recipients (osteochondral defect models) to identify the cell origin of regenerated cartilage. Cartilage repair was significantly better in the group implanted with a chondrocyte sheet than in that with a synovial cell sheet. The results of gene expression analysis suggest that the possible factor contributing to cartilage repair might be TGFβ1. Cell tracking experiments using GFP transgenic rats showed that the regenerated cartilage was largely composed of cells derived from the transplanted chondrocyte sheets. PMID:25396711

Characterization of PEEK, PET and PI implanted with Mn ions and sub-sequently annealed

NASA Astrophysics Data System (ADS)

Mackova, A.; Malinsky, P.; Miksova, R.; Pupikova, H.; Khaibullin, R. I.; Slepicka, P.; Gombitová, A.; Kovacik, L.; Svorcik, V.; Matousek, J.

2014-04-01

Polyimide (PI), polyetheretherketone (PEEK) and polyethylene terephthalate (PET) foils were implanted with 80 keV Mn+ ions at room temperature at fluencies of 1.0 × 1015-1.0 × 1016 cm-2. Mn depth profiles determined by RBS were compared to SRIM 2012 and TRIDYN simulations. The processes taking place in implanted polymers under the annealing procedure were followed. The measured projected ranges RP differ slightly from the SRIM and TRIDYN simulation and the depth profiles are significantly broader (up to 2.4 times) than those simulated by SRIM, while TRIDYN simulations were in a reasonable agreement up to the fluence 0.5 × 1016 in PEEK. Oxygen and hydrogen escape from the implanted layer was examined using RBS and ERDA techniques. PET, PEEK and PI polymers exhibit oxygen depletion up to about 40% of its content in virgin polymers. The compositional changes induced by implantation to particular ion fluence are similar for all polymers examined. After annealing no significant changes of Mn depth distribution was observed even the further oxygen and hydrogen desorption from modified layers appeared. The surface morphology of implanted polymers was characterized using AFM. The most significant change in the surface roughness was observed on PEEK. Implanted Mn atoms tend to dissipate in the polymer matrix, but the Mn nanoparticles are too small to be observed on TEM micrographs. The electrical, optical and structural properties of the implanted and sub-sequently annealed polymers were investigated by sheet resistance measurement and UV-Vis spectroscopy. With increasing ion fluence, the sheet resistance decreases and UV-Vis absorbance increases simultaneously with the decline of optical band gap Eg. The most pronounced change in the resistance was found on PEEK. XPS spectroscopy shows that Mn appears as a mixture of Mn oxides. Mn metal component is not present. All results were discussed in comparison with implantation experiment using the various ion species (Ni, Co) and energies used in our former experiments. Interesting differences were found in Mn concentration distribution, Mn nano-particle creation and structural changes comparing to Ni, Co ions implantation into the same polymers.

Characterizing the Material Properties of Polymer-Based Microelectrode Arrays for Retinal Prosthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Christina Soyeun

2003-06-01

The Retinal Prosthesis project is a three year project conducted in part at the Lawrence Livermore National Laboratory and funded by the Department of Energy to create an epiretinal microelectrode array for stimulating retinal cells. The implant must be flexible to conform to the retina, robust to sustain handling during fabrication and implantation, and biocompatible to withstand physiological conditions within the eye. Using poly(dimethyl siloxane) (PDMS), LLNL aims to use microfabrication techniques to increase the number of electrodes and integrate electronics. After the initial designs were fabricated and tested in acute implantation, it became obvious that there was a needmore » to characterize and understand the mechanical and electrical properties of these new structures. This knowledge would be imperative in gaining credibility for polymer microfabrication and optimizing the designs. Thin composite microfabricated devices are challenging to characterize because they are difficult to handle, and exhibit non-linear, viscoelastic, and anisotropic properties. The objective of this research is to device experiments and protocols, develop an analytical model to represent the composite behavior, design and fabricate test structures, and conduct experimental testing to determine the mechanical and electrical properties of PDMS-metal composites. Previous uniaxial stretch tests show an average of 7% strain before failure on resistive heaters of similar dimensions deposited on PDMS. Lack of background information and questionable human accuracy demands a more sophisticated and thorough testing method. An Instron tensile testing machine was set up to interface with a digital multiplexor and computer interface to simultaneously record and graph position, load, and resistance across devices. With a compliant load cell for testing polymers and electrical interconnect grips designed and fabricated to interface the sample to the electronics, real-time resistance measurements were taken. Wafers of test structures were fabricated with variables such as lead width, pad to lead interface shape, PDMS thickness, metal (Ti and Au) thickness, and lead shape. Results showed that the serpentine shaped leads were 70% more effective, and that thicker adhesion layers of Ti were too brittle for testing. The other variables did not produce significant results.« less

The effects of incomplete annealing on the temperature dependence of sheet resistance and gage factor in aluminum and phosphorus implanted silicon on sapphire

NASA Technical Reports Server (NTRS)

Pisciotta, B. P.; Gross, C.

1976-01-01

Partial annealing of damage to the crystal lattice during ion implantation reduces the temperature coefficient of resistivity of ion-implanted silicon, while facilitating controlled doping. Reliance on this method for temperature compensation of the resistivity and strain-gage factor is discussed. Implantation conditions and annealing conditions are detailed. The gage factor and its temperature variation are not drastically affected by crystal damage for some crystal orientations. A model is proposed to account for the effects of electron damage on the temperature dependence of resistivity and on silicon piezoresistance. The results are applicable to the design of silicon-on-sapphire strain gages with high gage factors.

Raman spectroscopy of few-layer graphene prepared by C2-C6 cluster ion implantation

NASA Astrophysics Data System (ADS)

Wang, Z. S.; Zhang, R.; Zhang, Z. D.; Huang, Z. H.; Liu, C. S.; Fu, D. J.; Liu, J. R.

2013-07-01

Few-layer graphene has been prepared on 300 nm-thick Ni films by C2-C6 cluster ion implantation at 20 keV/cluster. Raman spectroscopy reveals significant influence of the number of atoms in the cluster, the implantation dose, and thermal treatment on the structure of the graphene layers. In particular, the graphene samples exhibit a sharp G peak at 1584 cm-1 and 2D peaks at 2711-2717 cm-1. The IG/I2D ratios higher than 1.70 and IG/ID ratio as high as 1.95 confirm that graphene sheets with low density of defects have been synthesized with much improved quality by ion implantation with larger clusters of C4-C6.

The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering.

PubMed

Wang, Zhong-Shan; Feng, Zhi-Hong; Wu, Guo-Feng; Bai, Shi-Zhu; Dong, Yan; Chen, Fa-Ming; Zhao, Yi-Min

2016-06-21

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration.

RETINAL VEIN OCCLUSIONS, FROM BASICS TO THE LATEST TREATMENT.

PubMed

Ho, Mary; Liu, David T L; Lam, Dennis S C; Jonas, Jost B

2016-03-01

To review the pathophysiology, diagnosis, and updated treatments of retinal vein occlusions (RVOs). A review of the literature was performed, focusing on the epidemiology, pathophysiology, diagnosis, and treatments (including both medical and surgical treatments) of RVO. Based on this review, a comprehensive overview was provided regarding the topic of RVO and focused on recent treatment updates. Retinal vein occlusions have an age- and sex-standardized prevalence of 5.20 per 1,000 for any RVO, 4.42 per 1,000 for branch RVO, 0.80 per 1,000 for central RVO. Worldwide, an estimated 16.4 million adults are affected by RVOs, with 2.5 million affected by central RVO and 13.9 million affected by branch RVO. Retinal vein occlusion is recognized as an important cause of blindness and the diagnostic approaches and treatment options for RVO are reviewed and reported. The current treatment options including medical treatments (bevacizumab, ranibizumab, aflibercept, triamcinolone, and dexamethasone implants) and surgical alternatives were reviewed and reported with summaries on the corresponding strength of evidence. Despite the understanding of this disease entity, challenges persist in the long-term treatment of RVO-related complications and visual loss. This review provided a detailed summary on the rationality and efficacy of recently developed treatment regimes and evaluated the potential benefit of combination therapy.

Modeling and Simulation of Microelectrode-Retina Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beckerman, M

2002-11-30

The goal of the retinal prosthesis project is the development of an implantable microelectrode array that can be used to supply visually-driven electrical input to cells in the retina, bypassing nonfunctional rod and cone cells, thereby restoring vision to blind individuals. This goal will be achieved through the study of the fundamentals of electrical engineering, vision research, and biomedical engineering with the aim of acquiring the knowledge needed to engineer a high-density microelectrode-tissue hybrid sensor that will restore vision to millions of blind persons. The modeling and simulation task within this project is intended to address the question how bestmore » to stimulate, and communicate with, cells in the retina using implanted microelectrodes.« less

Iris-supported lens implantation v. simple cataract extraction. An analysis of data.

PubMed

Galin, M A; Obstbaum, S A; Boniuk, V; Galin, A; Silverstone, D

1977-04-01

In a study of a selected age (greater than 60) and ocularly matched population requiring cataract extraction, a perfectly executed intracapsular cataract extraction followed by the introduction of a Fyodorov Type II ("Sputnik") lens did not lead to irreversible anterior or posterior segment changes different from those seen in a group followed for from 5 to 9 years. It did lead to an incidence of implant support dislocation and to membrane formation in about 10% of cases, reducible to about 2% with correctly made lenses and the appropriate use of postoperative drugs. The incidence of corneal degeneration (0), retinal detachment (2%), and intraretinal cystic maculopathy (3%) was equal in each group. Visual acuity levels were also equal. In appropriate cases, if the surgery is carried out with sufficient skill, the reward to risk ratio of implantation not only justifies but indicates the use of such lenses.

Wireless power delivery for retinal prostheses.

PubMed

Ng, David C; Williams, Chris E; Allen, Penny J; Bai, Shun; Boyd, Clive S; Meffin, Hamish; Halpern, Mark E; Skafidas, Efstratios

2011-01-01

Delivering power to an implanted device located deep inside the body is not trivial. This problem is made more challenging if the implanted device is in constant motion. This paper describes two methods of transferring power wirelessly by means of magnetic induction coupling. In the first method, a pair of transmit and receive coils is used for power transfer over a large distance (compared to their diameter). In the second method, an intermediate pair of coils is inserted in between transmit and receive coils. Comparison between the power transfer efficiency with and without the intermediate coils shows power transfer efficiency to be 11.5 % and 8.8 %, respectively. The latter method is especially suitable for powering implanted devices in the eye due to immunity to movements of the eye and ease of surgery. Using this method, we have demonstrated wireless power delivery into an animal eye.

High performance 3-coil wireless power transfer system for the 512-electrode epiretinal prosthesis.

PubMed

Zhao, Yu; Nandra, Mandheerej; Yu, Chia-Chen; Tai, Yu-chong

2012-01-01

The next-generation retinal prostheses feature high image resolution and chronic implantation. These features demand the delivery of power as high as 100 mW to be wireless and efficient. A common solution is the 2-coil inductive power link, used by current retinal prostheses. This power link tends to include a larger-size extraocular receiver coil coupled to the external transmitter coil, and the receiver coil is connected to the intraocular electrodes through a trans-sclera trans-choroid cable. In the long-term implantation of the device, the cable may cause hypotony (low intraocular pressure) and infection. However, when a 2-coil system is constructed from a small-size intraocular receiver coil, the efficiency drops drastically which may induce over heat dissipation and electromagnetic field exposure. Our previous 2-coil system achieved only 7% power transfer. This paper presents a fully intraocular and highly efficient wireless power transfer system, by introducing another inductive coupling link to bypass the trans-sclera trans-choroid cable. With the specific equivalent load of our customized 512-electrode stimulator, the current 3-coil inductive link was measured to have the overall power transfer efficiency around 36%, with 1-inch separation in saline. The high efficiency will favorably reduce the heat dissipation and electromagnetic field exposure to surrounding human tissues. The effect of the eyeball rotation on the power transfer efficiency was investigated as well. The efficiency can still maintain 14.7% with left and right deflection of 30 degree during normal use. The surgical procedure for the coils' implantation into the porcine eye was also demonstrated.

3D Porous Graphene by Low-Temperature Plasma Welding for Bone Implants.

PubMed

Chakravarty, Dibyendu; Tiwary, Chandra Sekhar; Woellner, Cristano F; Radhakrishnan, Sruthi; Vinod, Soumya; Ozden, Sehmus; da Silva Autreto, Pedro Alves; Bhowmick, Sanjit; Asif, Syed; Mani, Sendurai A; Galvao, Douglas S; Ajayan, Pulickel M

2016-10-01

3D scaffolds of graphene, possessing ultra-low density, macroporous microstructure, and high yield strength and stiffness can be developed by a novel plasma welding process. The bonding between adjacent graphene sheets is investigated by molecular dynamics simulations. The high degree of biocompatibility along with high porosity and good mechanical properties makes graphene an ideal material for use as body implants. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flexible retinal electrode array

DOEpatents

Okandan, Murat [Albuquerque, NM; Wessendorf, Kurt O [Albuquerque, NM; Christenson, Todd R [Albuquerque, NM

2006-10-24

An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

Long-term results of the use of silicone sheets after diskectomy in the temporomandibular joint: clinical, radiographic and histopathologic findings.

PubMed

Schliephake, H; Schmelzeisen, R; Maschek, H; Haese, M

1999-10-01

The aim of the present study was to evaluate the long-term results of a group of patients who had the disk of the temporomandibular joint (TMJ) removed and permanently replaced by a silicone sheet. The study group comprised 48 patients, treated in the period from 1983 to 1993. In eight patients, the implants had to be removed after an average interval of 5.6 years and they were submitted for histopathological examination. Twenty-five of the 40 patients with silastic implants in place, and five of the 8 patients who had their implants removed, were available for long-term follow-up (mean interval of 7.0 years, SD 2.8 years). Clinical function was rated according to the Helkimo Dysfunction Index and compared to the preoperative findings. Results showed decreased tenderness of muscles and joints to palpation and increased mouth opening, but no statistically significant improvement in joint function. In 4 patients, a decrease in condylar width was found, while another 4 patients presented with thickening of the condyle by appositional bone formation. Histopathology of the failed implants showed scattered fragments of silastic material and dacron fibers with accumulation of histiocytes in immediate contact with the silicone particles and phagocytozed intracellular material. T-lymphocytes were also present in the vicinity of the silicone particles.

Electroretinogram assessment of children with sensorineural hearing loss: implications for screening.

PubMed

West, Stephanie K; Hindocha, Maya; Hogg, Chris R; Holder, Graham E; Moore, Anthony T; Reddy, M Ashwin

2015-10-01

The guidelines of the National Deaf Children's Society recommend that children with sensorineural hearing loss (SNHL) be routinely screened for ophthalmological problems and suggest electroretinography (ERG) to exclude Usher syndrome. The present study reports the nature and prevalence of abnormal ERG findings in a cohort of children with SNHL undergoing ERG with the aim of identifying risk factors for the diagnosis of Usher syndrome. The medical records of children (<18 years of age) with SNHL referred for ERG at Moorfields Eye Hospital, London, between January 2009 and December 2011 were retrospectively reviewed. Patients were included if they had been referred with SNHL by an audiological medicine consultant and the primary indication for electrodiagnostic testing was possible Usher syndrome. A total of 84 cases met inclusion criteria of which 13 (15%) had ERG findings showing rod-cone dysfunction consistent with a diagnosis of Usher syndrome. Two patients with retinal pigmentary changes had normal ERGs and were diagnosed with rubella retinopathy based on the clinical findings. Risk factor analysis showed that age of ≥8 years at the time of ERG, sex, and bilateral hearing loss were not predictive of a diagnosis of Usher syndrome. However, the presence of or referral for cochlear implants, having relevant symptoms and/or clinical signs consistent with a retinal dystrophy, and profound hearing loss were all highly predictive. ERG is a useful diagnostic tool in children with SNHL and should be performed in children with SNHL who have cochlear implants and/or have signs or symptoms of retinal dystrophy. A focused approach could have potential cost-saving benefit. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Non-ferromagnetic retinal tacks are a tolerable risk in magnetic resonance imaging.

PubMed

Kuethe, D O; Small, K W; Blinder, R A

1991-01-01

Should patients with cobalt alloy (ASTM F563) retinal tacks (Grieshaber cat. #611.95) in their eyes be subjected to the magnetic fields used in magnetic resonance imaging? Although the tacks are not ferromagnetic, they will experience a retarding torque when they are moved at the high angular velocities of human eye motion. Because retinal tacks are small (2.85 mm x 0.9 mm), the torque is difficult to measure. Rather, we measured the torque on a model 25.4 times larger and used a scaling law derived from Maxwell's equations to calculate the force on the tack. The scaling law states that the torque varies with the cube of the object's length. To mimic the motion, models of retinal tacks were attached to Plexiglas rods and the assemblies were swung as pendulums. The pendulums were oriented in the magnetic field of a 1.5 T imager to experience the greatest retardation. Retarding torques were estimated from the rate of decrease of the pendulum amplitude, both inside and outside the magnet. Even if the retinal tacks were as conductive as 6061T6 aluminum alloy (25 MS/m) and the velocity of the surface of the eye were 24 cm/s (angular vel. of 1130 deg/s), the retarding torque would be only 1.6 times the weight of the tack acting with a lever arm as long as the distance from its tip to its center of gravity. The maximum retarding torque on an implanted retinal tack in a 1.5 T magnet is similar to the torque produced by gravity alone acting on the tack and is a tolerable risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities

NASA Astrophysics Data System (ADS)

Samba, R.; Herrmann, T.; Zeck, G.

2015-02-01

Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

Assessment of the posterior segment of the cat eye by optical coherence tomography (OCT).

PubMed

Gekeler, Florian; Gmeiner, Helmut; Völker, Michael; Sachs, Helmut; Messias, Andre; Eule, Corinna; Bartz-Schmidt, Karl Ulrich; Zrenner, Eberhart; Shinoda, Kei

2007-01-01

To assess the feasibility of optical coherence tomography (OCT) for examining the cat ocular fundus, to provide normative data on retinal thickness in different fundus regions, and to demonstrate selected surgically induced vitreoretinal pathologies in the cat. Forty-five eyes of 28 healthy domestic cats and two eyes of domestic cats that had undergone subretinal implantation surgery for a visual prosthesis were examined. An optical coherence tomograph (Zeiss-Humphrey) was used to examine the anesthetized animals. At least five vertical and five horizontal scans in regular distribution were recorded for each cat including (1) the peripapillary region, (2) the area centralis, and (3) the peripheral retina. Thickness was measured manually at five locations in each scan. Retinal thickness was compared in the three above-mentioned fundus regions, between eyes and between vertical and horizontal scans. OCT was additionally performed in animals with retinal detachment and a subretinal visual prosthesis. OCT measurements required only minimal adjustments of human settings and yielded high quality images. In comparison to humans intraretinal layers were more difficult to differentiate. Retinal thickness was highest in the peripapillary region (245 +/- 21 microm), followed by the peripheral retina (204 +/- 11 microm) and the area centralis (182 +/- 11 microm; all P < 0.0001). There was no statistically significant difference between right and left eye or between vertical and horizontal scans. OCT demonstrated retinal detachment, an iatrogenic break and a subretinal prosthetic device in high detail. Retinal thickness was measurable with high precision; values compare well to older histologic studies. OCT bears significant advantages over histology in enabling one to repeat measurements in living animals and thus allowing longitudinal studies. Various vitreoretinal pathologies common in feline eyes are detectable and quantifiable by OCT.

Effect of Cell Sheet Manipulation Techniques on the Expression of Collagen Type II and Stress Fiber Formation in Human Chondrocyte Sheets.

PubMed

Wongin, Sopita; Waikakul, Saranatra; Chotiyarnwong, Pojchong; Siriwatwechakul, Wanwipa; Viravaidya-Pasuwat, Kwanchanok

2018-03-01

Cell sheet technology is applied to human articular chondrocytes to construct a tissue-like structure as an alternative treatment for cartilage defect. The effect of a gelatin manipulator, as a cell sheet transfer system, on the quality of the chondrocyte sheets was investigated. The changes of important chondrogenic markers and stress fibers, resulting from the cell sheet manipulation, were also studied. The chondrocyte cell sheets were constructed with patient-derived chondrocytes using a temperature-responsive polymer and a gelatin manipulator as a transfer carrier. The properties of the cell sheets, including sizes, expression levels of collagen type II and I, and the localization of the stress fibers, were assessed and compared with those of the cell sheets harvested without the gelatin manipulator. Using the gelatin manipulator, the original size of the chondrocyte cell sheets was retained with abundant stress fibers, but with a decrease in the expression of collagen type II. Without the gelatin manipulator, although the cell shrinkage occurred, the cell sheet with suppressed stress fiber formation showed significantly higher levels of collagen type II. These results support our observations that stress fiber formation in chondrocyte cell sheets affected the production of chondrogenic markers. These densely packed tissue-like structures possessed a good chondrogenic activity, indicating their potential for use in autologous chondrocyte implantation to treat cartilage defects.

Biodegradable near-infrared-photoresponsive shape memory implants based on black phosphorus nanofillers.

PubMed

Xie, Hanhan; Shao, Jundong; Ma, Yufei; Wang, Jiahong; Huang, Hao; Yang, Na; Wang, Huaiyu; Ruan, Changshun; Luo, Yanfeng; Wang, Qu-Quan; Chu, Paul K; Yu, Xue-Feng

2018-05-01

In this paper, we propose a new shape memory polymer (SMP) composite with excellent near-infrared (NIR)-photoresponsive shape memory performance and biodegradability. The composite is fabricated by using piperazine-based polyurethane (PU) as thermo-responsive SMP incorporated with black-phosphorus (BP) sheets as NIR photothermal nanofillers. Under 808 nm light irradiation, the incorporated BP sheets with concentration of only 0.08 wt% enable rapid temperature increase over the glass temperature of PU and trigger the shape change of the composite with shape recovery rate of ∼100%. The in vitro and in vivo toxicity examinations demonstrate the good biocompatibility of the PU/BP composite, and it degrades naturally into non-toxic carbon dioxide and water from PU and non-toxic phosphate from BP. By implanting PU/BP columns into back subcutis and vagina of mice, they exhibit excellent shape memory activity to change their shape quickly under moderate 808 nm light irradiaiton. Such SMP composite enable the development of intelligent implantable devices, which can be easily controlled by the remote NIR light and degrade gradually after performing the designed functions in the body. Copyright © 2018 Elsevier Ltd. All rights reserved.

Corrosion testing using isotopes

DOEpatents

Hohorst, F.A.

1995-12-05

A method is described for determining the corrosion behavior of a material with respect to a medium in contact with the material by: implanting a substantially chemically inert gas in a matrix so that corrosion experienced by the material causes the inert gas to enter the medium; placing the medium in contact with the material; and measuring the amount of inert gas which enters the medium. A test sample of a material whose resistance to corrosion by a medium is to be tested is described composed of: a body of the material, which body has a surface to be contacted by the medium; and a substantially chemically inert gas implanted into the body to a depth below the surface. A test sample of a material whose resistance to corrosion by a medium is to be tested is described composed of: a substrate of material which is easily corroded by the medium, the substrate having a surface; a substantially chemically inert gas implanted into the substrate; and a sheet of the material whose resistance to corrosion is to be tested, the sheet being disposed against the surface of the substrate and having a defined thickness. 3 figs.

[Postoperative evaluation of surgically treated cases with temporary silicone implant in temporomandibular joint].

PubMed

Aoyama, Shigeru; Kino, Koji; Shibuya, Toshihisa; Sato, Fumiaki; Kobayashi, Akiko; Yoshitake, Hiroyuki; Haketa, Tadasu; Amamori, Yoko; Ishikawa, Takayuki; Yoshida, Nahoko; Amagasa, Teruo

2003-09-01

We have carried out temporary silicone implants after diskectomies or arthroplasties in temporomandibular joint surgeries to avoid postoperative adhesion and to maintain articular space. We evaluated 19 joints in 15 patients who had received dacron-reinforced silicone implant after silicone sheet removal through follow-up for at least 6 months. The cases included temporomandibular joint disorder (10 joints in 9 patients), psoriatic arthritis (2 joints in 1 patient), ankylosis (4 joints in 3 patients) and synovial chondromatosis (2 joints in 2 patients). On the basis of the criteria of temporomandibular dysfunction for the results, they were classified as bad (4 patients). It is thought that factors other than the implant are related to the bad results in the postoperative evaluation. In this study, lymphadenopathy induced by exfoliated silicone debris could not be confirmed. The temporary silicone implant in the temporomandibular joint was thought to be useful.

Can interposition of a silicone implant after sapheno-femoral ligation prevent recurrent varicose veins?

PubMed

De Maeseneer, M G; Giuliani, D R; Van Schil, P E; De Hert, S G

2002-11-01

To investigate whether a silicone implant at the sapheno-femoral ligation site could prevent recurrent varicosities. Two non-randomised groups of patients were studied prospectively. In group A 173 patients and 212 limbs had sapheno-femoral ligation, while 172 patients and 210 limbs additionally had a piece (2x3cm) of silicone sheet sutured to the saphenous stump to cover the anterior half of the common femoral vein. The implant was fixed in apposition to the deep vein by carefully closing the cribriform fascia. Colour duplex scanning was performed after 2 and 12 months. In the no implant group neovascularisation was observed in 35 (17%) after 12 months, but only in 13 (6%) limbs treated with a silicone implant (p<0.05). Interposition of a partition of silicone implant seems to lower the incidence of neovascularisation one year after saphenofemoral ligation. This technique may constitute an efficient method to prevent recurrence at the correctly ligated saphenous stump.

Subretinal electrical stimulation preserves inner retinal function in RCS rat retina.

PubMed

Ciavatta, Vincent T; Mocko, Julie A; Kim, Moon K; Pardue, Machelle T

2013-01-01

Previously, studies showed that subretinal electrical stimulation (SES) from a microphotodiode array (MPA) preserves electroretinography (ERG) b-wave amplitude and regional retinal structure in the Royal College of Surgeons (RCS) rat and simultaneously upregulates Fgf2 expression. This preservation appears to be associated with the increased current produced when the MPA is exposed to ERG test flashes, as weekly ERG testing produces greater neuroprotection than biweekly or no testing. Using an infrared source to stimulate the MPA while avoiding potential confounding effects from exposing the RCS retina to high luminance white light, this study examined whether neuroprotective effects from SES increased with subretinal current in a dose-dependent manner. RCS rats (n=49) underwent subretinal implantation surgery at P21 with MPA devices in one randomly selected eye, and the other eye served as the control. Naïve RCS rats (n=25) were also studied. To increase SES current levels, implanted eyes were exposed to 15 min per session of flashing infrared light (IR) of defined intensity, frequency, and duty cycle. Rats were divided into four SES groups that received ERG testing only (MPA only), about 450 µA/cm2 once per week (Low 1X), about 450 µA/cm2 three times per week (Low 3X), and about 1350 µA/cm2 once per week (High 1X). One eye of the control animals was randomly chosen for IR exposure. All animals were followed for 4 weeks with weekly binocular ERGs. A subset of the eyes was used to measure retina Fgf2 expression with real-time reverse-transcription PCR. Eyes receiving SES showed significant preservation of b-wave amplitude, a- and b-wave implicit times, oscillatory potential amplitudes, and post-receptoral parameters (Vmax and log σ) compared to untreated eyes. All SES-treated eyes had similar preservation, regardless of increased SES from IR light exposure. SES-treated eyes tended to have greater retinal Fgf2 expression than untreated eyes, but Fgf2 expression did not increase with IR light. The larger post-receptoral responses (Vmax), greater post-receptoral sensitivity (logσ), and larger oscillatory potentials suggest SES-treated eyes maintained better inner retinal function than the opposite, untreated eyes. This suggests that in addition to preserving photoreceptors in RCS rats, SES may also promote more robust signal transmission through the retinal network compared to the control eyes. These studies suggest that the protective effects of SES on RCS retinal function cannot be improved with additional subretinal current induction from the MPA, or the charge injection provided by ERG Ganzfeld flashes was not adequately mimicked by the flashing IR light used in this study.

The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering

PubMed Central

Wang, Zhong-Shan; Feng, Zhi-Hong; Wu, Guo-Feng; Bai, Shi-Zhu; Dong, Yan; Chen, Fa-Ming; Zhao, Yi-Min

2016-01-01

Periodontal regeneration involves the restoration of at least three unique tissues: cementum, periodontal ligament tissue (PDL) and alveolar bone tissue. Here, we first isolated human PDL stem cells (PDLSCs) and jaw bone mesenchymal stem cells (JBMSCs). These cells were then induced to form cell sheets using an ascorbic acid-rich approach, and the cell sheet properties, including morphology, thickness and gene expression profile, were compared. Platelet-rich fibrin (PRF) derived from human venous blood was then fabricated into bioabsorbable fibrin scaffolds containing various growth factors. Finally, the in vivo potential of a cell-material construct based on PDLSC sheets, PRF scaffolds and JBMSC sheets to form periodontal tissue was assessed in a nude mouse model. In this model, PDLSC sheet/PRF/JBMSC sheet composites were placed in a simulated periodontal space comprising human treated dentin matrix (TDM) and hydroxyapatite (HA)/tricalcium phosphate (TCP) frameworks. Eight weeks after implantation, the PDLSC sheets tended to develop into PDL-like tissues, while the JBMSC sheets tended to produce predominantly bone-like tissues. In addition, the PDLSC sheet/PRF/JBMSC sheet composites generated periodontal tissue-like structures containing PDL- and bone-like tissues. Further improvements in this cell transplantation design may have the potential to provide an effective approach for future periodontal tissue regeneration. PMID:27324079

Clinical outcomes after combined Ahmed glaucoma valve implantation and penetrating keratoplasty or pars plana vitrectomy.

PubMed

Lee, Jin Young; Sung, Kyung Rim; Tchah, Hung Won; Yoon, Young Hee; Kim, June Gone; Kim, Myoung Joon; Kim, Jae Yong; Yun, Sung-Cheol; Lee, Joo Yong

2012-12-01

To evaluate whether a combination of penetrating keratoplasty (PKP) or pars plana vitrectomy (PPV) and Ahmed glaucoma valve (AGV) implantation affords a level of success similar to that of AGV implantation alone. Eighteen eyes underwent simultaneous PPV and AGV, 14 eyes with PKP and AGV and 30 eyes with AGV implantation alone were evaluated. Success was defined as attainment of an intraocular pressure (IOP) >5 and <22 mmHg, with or without use of anti-glaucoma medication. Kaplan-Meier survival analysis was performed to compare cumulative survival between the combined surgery groups and the AGV implantation-alone group. Cox proportional hazard regression analysis was conducted to identify factors predictive of success in each of the three groups. Mean (±standard deviation) preoperative IOP was 30.2 ± 10.2 mmHg in the PKP + AGV, 35.2 ± 9.8 mmHg in the PPV + AGV, and 36.2 ± 10.1 mmHg in the AGV implantation-alone group. The cumulative success rate at 18 months was 66.9%, 73.2%, and 70.8% in the three groups, respectively. Neither combined surgery group differed significantly in terms of cumulative success rate compared with the AGV implantation-alone group (p = 0.556, p = 0.487, respectively). The mean number of preoperative anti-glaucoma medications prescribed was significantly associated with success in the PKP + AGV implantation group (hazard ratio, 2.942; p = 0.024). Either PKP or PPV performed in conjunction with AGV implantation afforded similar success rates compared to patients treated with AGV implantation alone. Therefore, in patients with refractory glaucoma who have underlying corneal or retinal pathology requiring treatment with PKP or PPV, AGV implantation can be performed simultaneously.

Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

NASA Astrophysics Data System (ADS)

Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

2013-06-01

Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

Persistent photoconductivity in oxygen-ion implanted KNbO3 bulk single crystal

NASA Astrophysics Data System (ADS)

Tsuruoka, R.; Shinkawa, A.; Nishimura, T.; Tanuma, C.; Kuriyama, K.; Kushida, K.

2016-12-01

Persistent Photoconductivity (PPC) in oxygen-ion implanted KNbO3 ([001] oriented bulk single crystals; perovskite structure; ferroelectric with a band gap of 3.16 eV)　is studied in air at room temperature to prevent the degradation of its crystallinity caused by the phase transition. The residual hydrogens in un-implanted samples are estimated to be 5×1014 cm-2 from elastic recoil detection analysis (ERDA). A multiple-energy implantation of oxygen ions into KNbO3 is performed using energies of 200, 400, and 600 keV (each ion fluence:1.0×1014 cm-2). The sheet resistance varies from >108 Ω/□ for an un-implanted sample to 1.9×107 Ω/□ for as-implanted one, suggesting the formation of donors due to hydrogen interstitials and oxygen vacancies introduced by the ion implantation. The PPC is clearly observed with ultraviolet and blue LEDs illumination rather than green, red, and infrared, suggesting the release of electrons from the metastable conductive state below the conduction band relating to the charge states of the oxygen vacancy.

Axial length changes after retinal detachment surgery.

PubMed

Burton, T C; Herron, B E; Ossoinig, K C

1977-01-01

A-scan echography was an accurate method for detecting changes in the depth of the anterior chamber, lens thickness, and length of the vitreous cavity after retinal detachment surgery in 30 eyes. Approximately 60% of the eyes had significant alterations in axial lengths exceeding+/-0.36 mm in aphakic eyes and +/-0.54 mm in phakic eyes. However, the operation of scleral bucklingg with large segments of hard silicone rubber implants or explants supported by an encircling band failed to result in a significant predictable shift of axial change in phakic or aphakic eyes. A-scan echography showed significant shallowing of the anterior chamber, and scleral buckling significantly increases lens thickness for at least six weeks. This induced a minor myopic refractive change that may explain some of the difference in postoperative refracitons between phakic and aphakic eyes.

Effect of retinal detachment surgery on the course of preexisting open-angle glaucoma.

PubMed

Friedman, Z; Neumann, E

1975-10-01

In 11 of 12 eyes with chronic simple glaucoma after surgery for retinal detachment, intraocular pressures were decreased for one to 5 1/2 years without any antiglaucomatous treatment. No further deterioration in the state of the optic disks or the visual fields occurred in any of these eyes. In all 12 fellow eyes antiglaucomatous treatment is still being administered. The operation employed in nine of the 11 cases consisted of an encircling silicone rubber band shortened by 15 to 20% of its length when placed around the eyeball before tapping subretinal fluid. An episcleral silicone implant was placed under the encircling ban in seven of these eyes. Kinking and possibly narrowing of the long posterior ciliary arteries by the encircling silicone band probably caused the ciliary hyposecretion and the resultant hypotony.

Performance of photovoltaic arrays in-vivo and characteristics of prosthetic vision in animals with retinal degeneration

PubMed Central

Lorach, Henri; Goetz, Georges; Mandel, Yossi; Lei, Xin; Kamins, Theodore I.; Mathieson, Keith; Huie, Philip; Dalal, Roopa; Harris, James S.; Palanker, Daniel

2014-01-01

Summary Loss of photoreceptors during retinal degeneration leads to blindness, but information can be reintroduced into the visual system using electrical stimulation of the remaining retinal neurons. Subretinal photovoltaic arrays convert pulsed illumination into pulsed electric current to stimulate the inner retinal neurons. Since required irradiance exceeds the natural luminance levels, an invisible near-infrared (915nm) light is used to avoid photophobic effects. We characterized the thresholds and dynamic range of cortical responses to prosthetic stimulation with arrays of various pixel sizes and with different number of photodiodes. Stimulation thresholds for devices with 140µm pixels were approximately half those of 70µm pixels, and with both pixel sizes, thresholds were lower with 2 diodes than with 3 diodes per pixel. In all cases these thresholds were more than two orders of magnitude below the ocular safety limit. At high stimulation frequencies (>20Hz), the cortical response exhibited flicker fusion. Over one order of magnitude of dynamic range could be achieved by varying either pulse duration or irradiance. However, contrast sensitivity was very limited. Cortical responses could be detected even with only a few illuminated pixels. Finally, we demonstrate that recording of the corneal electric potential in response to patterned illumination of the subretinal arrays allows monitoring the current produced by each pixel, and thereby assessing the changes in the implant performance over time. PMID:25255990

Automatic Frequency Controller for Power Amplifiers Used in Bio-Implanted Applications: Issues and Challenges

PubMed Central

Hannan, Mahammad A.; Hussein, Hussein A.; Mutashar, Saad; Samad, Salina A.; Hussain, Aini

2014-01-01

With the development of communication technologies, the use of wireless systems in biomedical implanted devices has become very useful. Bio-implantable devices are electronic devices which are used for treatment and monitoring brain implants, pacemakers, cochlear implants, retinal implants and so on. The inductive coupling link is used to transmit power and data between the primary and secondary sides of the biomedical implanted system, in which efficient power amplifier is very much needed to ensure the best data transmission rates and low power losses. However, the efficiency of the implanted devices depends on the circuit design, controller, load variation, changes of radio frequency coil's mutual displacement and coupling coefficients. This paper provides a comprehensive survey on various power amplifier classes and their characteristics, efficiency and controller techniques that have been used in bio-implants. The automatic frequency controller used in biomedical implants such as gate drive switching control, closed loop power control, voltage controlled oscillator, capacitor control and microcontroller frequency control have been explained. Most of these techniques keep the resonance frequency stable in transcutaneous power transfer between the external coil and the coil implanted inside the body. Detailed information including carrier frequency, power efficiency, coils displacement, power consumption, supplied voltage and CMOS chip for the controllers techniques are investigated and summarized in the provided tables. From the rigorous review, it is observed that the existing automatic frequency controller technologies are more or less can capable of performing well in the implant devices; however, the systems are still not up to the mark. Accordingly, current challenges and problems of the typical automatic frequency controller techniques for power amplifiers are illustrated, with a brief suggestions and discussion section concerning the progress of implanted device research in the future. This review will hopefully lead to increasing efforts towards the development of low powered, highly efficient, high data rate and reliable automatic frequency controllers for implanted devices. PMID:25615728

Spectropathology-corroborated multimodal quantitative imaging biomarkers for neuroretinal degeneration in diabetic retinopathy

PubMed Central

Guha Mazumder, Arpan; Chatterjee, Swarnadip; Chatterjee, Saunak; Gonzalez, Juan Jose; Bag, Swarnendu; Ghosh, Sambuddha; Mukherjee, Anirban; Chatterjee, Jyotirmoy

2017-01-01

Introduction Image-based early detection for diabetic retinopathy (DR) needs value addition due to lack of well-defined disease-specific quantitative imaging biomarkers (QIBs) for neuroretinal degeneration and spectropathological information at the systemic level. Retinal neurodegeneration is an early event in the pathogenesis of DR. Therefore, development of an integrated assessment method for detecting neuroretinal degeneration using spectropathology and QIBs is necessary for the early diagnosis of DR. Methods The present work explored the efficacy of intensity and textural features extracted from optical coherence tomography (OCT) images after selecting a specific subset of features for the precise classification of retinal layers using variants of support vector machine (SVM). Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy were also performed to confirm the spectropathological attributes of serum for further value addition to the OCT, fundoscopy, and fluorescein angiography (FA) findings. The serum metabolomic findings were also incorporated for characterizing retinal layer thickness alterations and vascular asymmetries. Results Results suggested that OCT features could differentiate the retinal lesions indicating retinal neurodegeneration with high sensitivity and specificity. OCT, fundoscopy, and FA provided geometrical as well as optical features. NMR revealed elevated levels of ribitol, glycerophosphocholine, and uridine diphosphate N-acetyl glucosamine, while the FTIR of serum samples confirmed the higher expressions of lipids and β-sheet-containing proteins responsible for neoangiogenesis, vascular fragility, vascular asymmetry, and subsequent neuroretinal degeneration in DR. Conclusion Our data indicated that disease-specific spectropathological alterations could be the major phenomena behind the vascular attenuations observed through fundoscopy and FA, as well as the variations in the intensity and textural features observed in OCT images. Finally, we propose a model that uses spectropathology corroborated with specific QIBs for detecting neuroretinal degeneration in early diagnosis of DR. PMID:29200821

Induced Retro-Differentiation of Human Retinal Pigment Epithelial Cells on PolyHEMA.

PubMed

Nazemroaya, Fatemeh; Soheili, Zahra-Soheila; Samiei, Shahram; Deezagi, Abdolkhalegh; Ahmadieh, Hamid; Davari, Malihe; Heidari, Razeih; Bagheri, Abouzar; Darvishalipour-Astaneh, Shamila

2017-10-01

Retinal pigment epithelium (RPE) cells represent a great potential to rescue degenerated cells of the damaged retina. Activation of the virtually plastic properties of RPE cells may aid in recovery of retinal degenerative disorders without the need for entire RPE sheet transplantation. Poly (2-hydroxyethyl methacrylate)(PolyHEMA) is one of the most important hydrogels in the biomaterials world. This hydrophobic polymer does not normally support attachment of mammalian cells. In the current study we investigated the effect of PolyHEMA as a cell culture substrate on the growth, differentiation, and plasticity of hRPE cells. hRPE cells were isolated from neonatal human globes and cultured on PolyHEMA and polystyrene substrates (as controls) in 24-well culture plates. DMEM/F12 was supplemented with 10% fetal bovine serum (FBS) and/or 30% human amniotic fluid (HAF) for cultured cells on polystyrene and PolyHEMA coated vessels. Morphology, rate of cell proliferation and cell death, MTT assay, immunocytochemistry and Real-Time RT-PCR were performed to investigate the effects of PolyHEMA on the growth and differentiation of cultured hRPE cells. Proliferation rate of the cells that had been cultured on PolyHEMA was reduced; PolyHEMA did not induce cell death in the hRPE cultures. hRPE cells cultured on PolyHEMA formed many giant spheroid colonies. The giant colonies were re-cultured and the presence of retinal progenitor markers and markers of hRPE cells were detected in cell cultures on PolyHEMA. PolyHEMA seems to be promising for both maintenance and de-differentiation of hRPE cells and expansion of the retinal progenitor cells from the cultures that are originated from hRPE cells. J. Cell. Biochem. 118: 3080-3089, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Visual performance after bilateral implantation of 2 new presbyopia-correcting intraocular lenses: Trifocal versus extended range of vision.

PubMed

Monaco, Gaspare; Gari, Mariangela; Di Censo, Fabio; Poscia, Andrea; Ruggi, Giada; Scialdone, Antonio

2017-06-01

To compare the visual outcomes and quality of vision of 2 new diffractive multifocal intraocular lenses (IOLs) with those of a monofocal IOL. Fatebenefratelli e Oftalmico Hospital, Milan, Italy. Prospective case series. Patients had bilateral cataract surgery with implantation of a trifocal IOL (Panoptix), an extended-range-of-vision IOL (Symfony), or a monofocal IOL (SN60WF). Postoperative examinations included assessing distance, intermediate, and near visual acuity; binocular defocus; intraocular and total aberrations; point-spread function (PSF); modulation transfer function (MTF); retinal straylight; and quality-of-vision (QoV) and spectacle-dependence questionnaires. Seventy-six patients (152 eyes) were assessed for study eligibility. Twenty patients (40 eyes) in each arm of the study (60 patients, 120 eyes) completed the outcome assessment. At the 4-month follow-up, the trifocal group had significantly better near visual acuity than the extended-range-of-vision group (P = .005). The defocus curve showed the trifocal IOL had better intermediate/near performance than the extended-range-of-vision IOL and both multifocal IOLs performed better than the monofocal IOL. Intragroup comparison of the total higher-order aberrations, PSF, MTF, and retinal straylight were not statistically different. The QoV questionnaire results showed no differences in dysphotopsia between the multifocal IOL groups; however, the results were significantly higher than in the monofocal IOL group. Both multifocal IOLs seemed to be good options for patients with intermediate-vision requirements, whereas the trifocal IOL might be better for patients with near-vision requirements. The significant perception of visual side effects indicates that patients still must be counseled about these effects before a multifocal IOL is implanted. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Variable phenotypic expressivity in inbred retinal degeneration mouse lines: A comparative study of C3H/HeOu and FVB/N rd1 mice.

PubMed

van Wyk, Michiel; Schneider, Sabine; Kleinlogel, Sonja

2015-01-01

Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6b(rd1)) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well-known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. We followed retinal degeneration over 24 weeks in FVB/N, C3H/HeOu, and congenic Pde6b(+) seeing mouse lines, using a range of experimental techniques including extracellular recordings from retinal ganglion cells, PCR quantification of cone opsin and Pde6b transcripts, in vivo flash electroretinogram (ERG), and behavioral optokinetic reflex (OKR) recordings. We demonstrated a substantial difference in the speed of retinal degeneration and accompanying loss of visual function between the two rd1 lines. Photoreceptor degeneration and loss of vision were faster with an earlier onset in the FVB/N mice compared to C3H/HeOu mice, whereas the performance of the Pde6b(+) mice did not differ significantly in any of the tests. By postnatal week 4, the FVB/N mice expressed significantly less cone opsin and Pde6b mRNA and had neither ERG nor OKR responses. At 12 weeks of age, the retinal ganglion cells of the FVB/N mice had lost all light responses. In contrast, 4-week-old C3H/HeOu mice still had ERG and OKR responses, and we still recorded light responses from C3H/HeOu retinal ganglion cells until the age of 24 weeks. These results show that genetic background plays an important role in the rd1 mouse pathology. Analogous to human RP, the mouse genetic background strongly influences the rd1 phenotype. Thus, different rd1 mouse lines may follow different timelines of retinal degeneration, making exact knowledge of genetic background imperative in all studies that use rd1 models.

Reliability of spring interconnects for high channel-count polyimide electrode arrays

NASA Astrophysics Data System (ADS)

Khan, Sharif; Ordonez, Juan Sebastian; Stieglitz, Thomas

2018-05-01

Active neural implants with a high channel-count need robust and reliable operational assembly for the targeted environment in order to be classified as viable fully implantable systems. The discrete functionality of the electrode array and the implant electronics is vital for intact assembly. A critical interface exists at the interconnection sites between the electrode array and the implant electronics, especially in hybrid assemblies (e.g. retinal implants) where electrodes and electronics are not on the same substrate. Since the interconnects in such assemblies cannot be hermetically sealed, reliable protection against the physiological environment is essential for delivering high insulation resistance and low defusibility of salt ions, which are limited in complexity by current assembly techniques. This work reports on a combination of spring-type interconnects on a polyimide array with silicone rubber gasket insulation for chronically active implantable systems. The spring design of the interconnects on the backend of the electrode array compensates for the uniform thickness of the sandwiched gasket during bonding in assembly and relieves the propagation of extrinsic stresses to the bulk polyimide substrate. The contact resistance of the microflex-bonded spring interconnects with the underlying metallized ceramic test vehicles and insulation through the gasket between adjacent contacts was investigated against the MIL883 standard. The contact and insulation resistances remained stable in the exhausting environmental conditions.

Speech recognition and communication outcomes with cochlear implantation in Usher syndrome type 3.

PubMed

Pietola, Laura; Aarnisalo, Antti A; Abdel-Rahman, Akram; Västinsalo, Hanna; Isosomppi, Juha; Löppönen, Heikki; Kentala, Erna; Johansson, Reijo; Valtonen, Hannu; Vasama, Juha-Pekka; Sankila, Eeva-Marja; Jero, Jussi

2012-01-01

Usher syndrome Type 3 (USH3) is an autosomal recessive disorder characterized by variable type and degree of progressive sensorineural hearing loss and retinitis pigmentosa. Cochlear implants are widely used among these patients. To evaluate the results and benefits of cochlear implantation in patients with USH3. A nationwide multicenter retrospective review. During the years 1995-2005, in 5 Finnish university hospitals, 19 patients with USH3 received a cochlear implant. Saliva samples were collected to verify the USH3 genotype. Patients answered to 3 questionnaires: Glasgow Benefit Inventory, Glasgow Health Status Inventory, and a self-made questionnaire. Audiological data were collected from patient records. All the patients with USH3 in the study were homozygous for the Finnish major mutation (p.Y176X). Either they had severe sensorineural hearing loss or they were profoundly deaf. The mean preoperative hearing level (pure-tone average, 0.5-4 kHz) was 110 ± 8 dB hearing loss (HL) and the mean aided hearing level was 58 ± 11 dB HL. The postoperative hearing level (34 ± 9 dB HL) and word recognition scores were significantly better than before surgery. According to the Glasgow Benefit Inventory scores and Glasgow Health Status Inventory data related to hearing, the cochlear implantation was beneficial to patients with USH3. Cochlear implantation is beneficial to patients with USH3, and patients learn to use the implant without assistance.

Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery.

PubMed

McAvoy, Kathryn; Jones, David; Thakur, Raghu Raj Singh

2018-01-16

To investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents. Triamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin. Regardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period. Photocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.

Implantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats.

PubMed

Charng, Jason; He, Zheng; Bui, Bang; Vingrys, Algis; Ivarsson, Magnus; Fish, Rebecca; Gurrell, Rachel; Nguyen, Christine

2016-06-29

The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub-conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data.

A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering.

PubMed

Backman, Daniel E; LeSavage, Bauer L; Shah, Shivem B; Wong, Joyce Y

2017-06-01

In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm-PDMS substrates optimal for VSMC attachment. To allow long-term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm-PDMS surfaces were further modified with 3-aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single-layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single-layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visual Prosthesis: Interfacing Stimulating Electrodes with Retinal Neurons to Restore Vision

PubMed Central

Barriga-Rivera, Alejandro; Bareket, Lilach; Goding, Josef; Aregueta-Robles, Ulises A.; Suaning, Gregg J.

2017-01-01

The bypassing of degenerated photoreceptors using retinal neurostimulators is helping the blind to recover functional vision. Researchers are investigating new ways to improve visual percepts elicited by these means as the vision produced by these early devices remain rudimentary. However, several factors are hampering the progression of bionic technologies: the charge injection limits of metallic electrodes, the mechanical mismatch between excitable tissue and the stimulating elements, neural and electric crosstalk, the physical size of the implanted devices, and the inability to selectively activate different types of retinal neurons. Electrochemical and mechanical limitations are being addressed by the application of electromaterials such as conducting polymers, carbon nanotubes and nanocrystalline diamonds, among other biomaterials, to electrical neuromodulation. In addition, the use of synthetic hydrogels and cell-laden biomaterials is promising better interfaces, as it opens a door to establishing synaptic connections between the electrode material and the excitable cells. Finally, new electrostimulation approaches relying on the use of high-frequency stimulation and field overlapping techniques are being developed to better replicate the neural code of the retina. All these elements combined will bring bionic vision beyond its present state and into the realm of a viable, mainstream therapy for vision loss. PMID:29184478

Management of diabetic macular edema with intravitreal dexamethasone implants: Expert recommendations using a Delphi-based approach.

PubMed

Giovannini, Alfonso; Parravano, Mariacristina; Ricci, Federico; Bandello, Francesco

2018-06-01

Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema. A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy. Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti-vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti-vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti-vascular endothelial growth factor therapy. While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.

Periprosthetic bleeding 18 years post-silicone reconstruction of the orbital floor.

PubMed

Ilie, Vlad Ionut; Ilie, Victor George; Quarmby, Craig; Lefter, Mihaela

2011-10-01

Periprosthetic orbital haemorrhage is an uncommon complication of the alloplastic implants used in post-traumatic orbital floor repair. The small case series or individual reports provide no definite causative explanation for this delayed bleeding around silicone implants. It is likely that it is related to the disruption of fine capillaries within the pseudocapsule surrounding the implant, since the material does cause low-grade irritation with evidence of chronic inflammation. We report the case of a patient who developed a spontaneous periprosthetic bleeding 18 years' post-silicone sheet reconstruction of the orbital floor. Urgent removal of the implant insured prompt resolution of all symptoms and no further problem during the 2-year follow-up. This report emphasizes that periprosthetic orbital haemorrhage can occur years after the initial repair. Awareness of this rare complication allows for prompt diagnosis, decreasing the possibility of permanent damage of the orbital content. The removal of implant is necessary to relieve the symptoms and prevent potential infective complications.

Microcomputer-based artificial vision support system for real-time image processing for camera-driven visual prostheses

NASA Astrophysics Data System (ADS)

Fink, Wolfgang; You, Cindy X.; Tarbell, Mark A.

2010-01-01

It is difficult to predict exactly what blind subjects with camera-driven visual prostheses (e.g., retinal implants) can perceive. Thus, it is prudent to offer them a wide variety of image processing filters and the capability to engage these filters repeatedly in any user-defined order to enhance their visual perception. To attain true portability, we employ a commercial off-the-shelf battery-powered general purpose Linux microprocessor platform to create the microcomputer-based artificial vision support system (μAVS2) for real-time image processing. Truly standalone, μAVS2 is smaller than a deck of playing cards, lightweight, fast, and equipped with USB, RS-232 and Ethernet interfaces. Image processing filters on μAVS2 operate in a user-defined linear sequential-loop fashion, resulting in vastly reduced memory and CPU requirements during execution. μAVS2 imports raw video frames from a USB or IP camera, performs image processing, and issues the processed data over an outbound Internet TCP/IP or RS-232 connection to the visual prosthesis system. Hence, μAVS2 affords users of current and future visual prostheses independent mobility and the capability to customize the visual perception generated. Additionally, μAVS2 can easily be reconfigured for other prosthetic systems. Testing of μAVS2 with actual retinal implant carriers is envisioned in the near future.

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

PubMed Central

Ahuja, A K; Dorn, J D; Caspi, A; McMahon, M J; Dagnelie, G; daCruz, L; Stanga, P; Humayun, M S; Greenberg, R J

2012-01-01

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″ (48.3 cm) touch screen monitor located 12″ (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. PMID:20881025

Microcomputer-based artificial vision support system for real-time image processing for camera-driven visual prostheses.

PubMed

Fink, Wolfgang; You, Cindy X; Tarbell, Mark A

2010-01-01

It is difficult to predict exactly what blind subjects with camera-driven visual prostheses (e.g., retinal implants) can perceive. Thus, it is prudent to offer them a wide variety of image processing filters and the capability to engage these filters repeatedly in any user-defined order to enhance their visual perception. To attain true portability, we employ a commercial off-the-shelf battery-powered general purpose Linux microprocessor platform to create the microcomputer-based artificial vision support system (microAVS(2)) for real-time image processing. Truly standalone, microAVS(2) is smaller than a deck of playing cards, lightweight, fast, and equipped with USB, RS-232 and Ethernet interfaces. Image processing filters on microAVS(2) operate in a user-defined linear sequential-loop fashion, resulting in vastly reduced memory and CPU requirements during execution. MiccroAVS(2) imports raw video frames from a USB or IP camera, performs image processing, and issues the processed data over an outbound Internet TCP/IP or RS-232 connection to the visual prosthesis system. Hence, microAVS(2) affords users of current and future visual prostheses independent mobility and the capability to customize the visual perception generated. Additionally, microAVS(2) can easily be reconfigured for other prosthetic systems. Testing of microAVS(2) with actual retinal implant carriers is envisioned in the near future.

Topographic prominence discriminator for the detection of short-latency spikes of retinal ganglion cells

NASA Astrophysics Data System (ADS)

Choi, Myoung-Hwan; Ahn, Jungryul; Park, Dae Jin; Lee, Sang Min; Kim, Kwangsoo; Cho, Dong-il Dan; Senok, Solomon S.; Koo, Kyo-in; Goo, Yong Sook

2017-02-01

Objective. Direct stimulation of retinal ganglion cells in degenerate retinas by implanting epi-retinal prostheses is a recognized strategy for restoration of visual perception in patients with retinitis pigmentosa or age-related macular degeneration. Elucidating the best stimulus-response paradigms in the laboratory using multielectrode arrays (MEA) is complicated by the fact that the short-latency spikes (within 10 ms) elicited by direct retinal ganglion cell (RGC) stimulation are obscured by the stimulus artifact which is generated by the electrical stimulator. Approach. We developed an artifact subtraction algorithm based on topographic prominence discrimination, wherein the duration of prominences within the stimulus artifact is used as a strategy for identifying the artifact for subtraction and clarifying the obfuscated spikes which are then quantified using standard thresholding. Main results. We found that the prominence discrimination based filters perform creditably in simulation conditions by successfully isolating randomly inserted spikes in the presence of simple and even complex residual artifacts. We also show that the algorithm successfully isolated short-latency spikes in an MEA-based recording from degenerate mouse retinas, where the amplitude and frequency characteristics of the stimulus artifact vary according to the distance of the recording electrode from the stimulating electrode. By ROC analysis of false positive and false negative first spike detection rates in a dataset of one hundred and eight RGCs from four retinal patches, we found that the performance of our algorithm is comparable to that of a generally-used artifact subtraction filter algorithm which uses a strategy of local polynomial approximation (SALPA). Significance. We conclude that the application of topographic prominence discrimination is a valid and useful method for subtraction of stimulation artifacts with variable amplitudes and shapes. We propose that our algorithm may be used as stand-alone or supplementary to other artifact subtraction algorithms like SALPA.

Retinal Prosthetics, Optogenetics, and Chemical Photoswitches

PubMed Central

2015-01-01

Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream implementations. Even so, given the high density of human foveal ganglion cells, the ultimate chemical photoswitch treatment could deliver cost-effective, high-resolution vision for the blind. PMID:25089879

Effects of Subretinal Electrical Stimulation in Mer-KO Mice

PubMed Central

Mocko, Julie A.; Kim, Moon; Faulkner, Amanda E.; Cao, Yang; Ciavatta, Vincent T.

2011-01-01

Purpose. Subretinal electrical stimulation (SES) from microphotodiode arrays protects photoreceptors in the RCS rat model of retinitis pigmentosa. The authors examined whether merkd mice, which share a Mertk mutation with RCS rats, showed similar neuroprotective effects from SES. Methods. Merkd mice were implanted with a microphotodiode array at postnatal day (P) 14. Weekly electroretinograms (ERGs) followed by retinal histology at week 4 were compared with those of age-matched controls. RT-PCR for fibroblast growth factor beta (Fgf2), ciliary nerve trophic factor (Cntf), glial-derived neurotrophic factor (Gdnf), insulin growth factor 1 (Igf1), and glial fibrillary acidic protein (Gfap) was performed on retinas at 1 week after surgery. Rates of degeneration using ERG parameters were compared between merkd mice and RCS rats from P28 to P42. Results. SES-treated merkd mice showed no differences in ERG a- and b-wave amplitudes or photoreceptor numbers compared with controls. However, the expression of Fgf2 and Cntf was greater (6.5 ± 1.9- and 2.5 ± 0.5-fold, respectively; P < 0.02) in SES-treated merkd retinas. Rates of degeneration were faster for dark-adapted maximal b-wave, log σ, and oscillatory potentials in merkd mice than in RCS rats. Conclusions. Although SES upregulated Fgf2 in merkd retinas, as reported previously for RCS retinas, this was not accompanied by neuroprotection of photoreceptors. Comparisons of ERG responses from merkd mice and RCS rats across different ages showed inner retinal dysfunction in merkd mice but not in RCS rats. This inner retinal dysfunction and the faster rate of degeneration in merkd mice may produce a retinal environment that is not responsive to neuroprotection from SES. PMID:21467171

The functional performance of the Argus II retinal prosthesis

PubMed Central

Stronks, H Christiaan; Dagnelie, Gislin

2014-01-01

Summary Visual prostheses are devices to treat profound vision loss by stimulating secondary nerve cells anywhere along the visual pathway, typically with electrical pulses. The Argus® II implant, developed by Second Sight Medical Products (SSMP, Sylmar, CA, USA), targets the retina and features 60 electrodes that electrically stimulate the surviving retinal neurons. Of the approximately 20 research groups that are actively developing visual prostheses, SSMP has the longest track record. The Argus II was the first visual prosthesis to become commercially available: It received the CE mark in Europe in 2011 and FDA approval was granted in early 2013 for humanitarian use in the USA. Meanwhile, the Argus II safety/benefit study has been extended for research purposes, and is ongoing. In this review we will discuss the performance of the Argus II in restoring sight to the blind, and we will shed light on its expected developments in the coming years. PMID:24308734

Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia.

PubMed

Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

2015-01-01

The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering.

Chip-scale hermetic feedthroughs for implantable bionics.

PubMed

Guenther, Thomas; Dodds, Christopher W D; Lovell, Nigel H; Suaning, Gregg J

2011-01-01

Most implantable medical devices such as cochlear implants and visual prostheses require protection of the stimulating electronics. This is achieved by way of a hermetic feedthrough system which typically features three important attributes: biocompatibility with the human body, device hermeticity and density of feedthrough conductors. On the quest for building a visual neuroprosthesis, a high number of stimulating channels is required. This has encouraged new technologies with higher rates of production yield and further miniaturization. An Al(2)O(3) based feedthrough system has been developed comprising up to 20 platinum feedthroughs per square millimeter. Ceramics substrates are shown to have leak rates below 1 × 10(-12) atm × cc/s, thus exceeding the resolution limits of most commercially available leak detectors. A sheet resistance of 0.05 Ω can be achieved. This paper describes the design, fabrication process and hermeticity testing of high density feedthroughs for use in neuroprosthetic implants.

Transparency to Reduce Surgical Implant Waste.

PubMed

Pfefferle, Kiel J; Dilisio, Matthew F; Patti, Brianna; Fening, Stephen D; Junko, Jeffrey T

2015-06-01

Rising health care costs and emphasis on value have placed the onus of reducing healthcare costs on the surgeon. Financial data from 3,973 hip, knee, and shoulder arthroplasties performed at a physician owned orthopedic hospital was retrospectively reviewed over a two-year period. A wasted implant financial report was posted starting the second year of the study. Each surgeon's performance could be identified by his peers. After posting of the financial report, 1.11% of all hip and knee arthroplasty cases had a waste event compared to 1.50% during the control year. Shoulder arthroplasty waste events occurred twice as often than that observed in hip and knee arthroplasty during the study period. A decrease in waste events was observed but was not statistically significant (p = 0.30). Posting a non-blinded wasted implant data sheet was associated with a reduction in the number of wasted orthopedic surgical implants in this series, although the reduction was not statistically significant.

An implantation of multifocal lenses LS-313 MF30, Mplus and MplusX models, during and after posterior vitrectomy in patients treated for various diseases of the retina.

PubMed

Cywinski, Adam; Piwonska-Lobermajer, Anna; Penter, Sandra

2016-08-01

A retrospective analysis of visual function and postoperative complaints in patients after posterior vitrectomy and multifocal Mplus or MplusX intraocular lens implantation. 14 patients (14 eyes) were enrolled in the study. All patients underwent posterior vitrectomy due to underlying retinal pathologies. A combined procedure of phacovitrectomy was performed in some patients, whereas others underwent a separate cataract extraction as a second stage of treatment. The Mplus or MplusX intraocular lenses were implanted in all cases and the postoperative visual function and patient complaints were analysed. Multifocal lens explantation was not necessary in any case. Good uncorrected distance and near visual acuity was achieved in most cases. When implanted prior to vitrectomy, the intraocular lenses did not limit the view into the posterior segment, so precise manipulations within the macula and peripheral retina were feasible. The right choice between Mplus and MplusX minimises the rate of postoperative complaints. Conslusions: The multifocal Mplus and MplusX intraocular lenses offer a good alternative for patients who need posterior vitrectomy and still want to achieve good uncorrected distance and near visual acuity.

Iris-Claw Intraocular Lens and Scleral-Fixated Posterior Chamber Intraocular Lens Implantations in Correcting Aphakia: A Meta-Analysis.

PubMed

Jing, Wu; Guanlu, Liang; Qianyin, Zheng; Shuyi, Li; Fengying, He; Jian, Liu; Wen, Xu

2017-07-01

A meta-analysis to compare iris-claw intraocular lens (IC-IOL) and scleral-fixated posterior chamber intraocular lens (SF-PCIOL) implantations in correcting aphakia without sufficient capsular support. Eligible studies were collected through PubMed, Web of Science, Embase, and the Cochrane library. The pooled relative risks (RR), pooled standardized mean difference (SMD), and their 95% confidence interval of the eligible studies were then calculated. Seven studies met our inclusion criteria, involving 232 and 158 eyes in IC-IOL and SF-PCIOL groups, respectively. The pooled SMD of the mean postoperative corrected distance visual acuity (CDVA) (logMAR) was -0.25. The pooled RR of the eyes achieving 20/40 or better postoperatively was 1.16. The pooled SMD of the surgical time was -2.97. The pooled RR of the surgical complications was 0.86. The pooled RR of IOL dislocation, retinal detachment (RD), and cystoid macular edema (CME) between the two groups were 0.22, 0.63, and 0.64. Implantation of IC-IOL has a more simple procedure and shorter learning curve than SF-PCIOL implantation in correcting aphakia without sufficient capsular support.

Reduction of eddy current losses in inductive transmission systems with ferrite sheets.

PubMed

Maaß, Matthias; Griessner, Andreas; Steixner, Viktor; Zierhofer, Clemens

2017-01-05

Improvements in eddy current suppression are necessary to meet the demand for increasing miniaturization of inductively driven transmission systems in industrial and biomedical applications. The high magnetic permeability and the simultaneously low electrical conductivity of ferrite materials make them ideal candidates for shielding metallic surfaces. For systems like cochlear implants the transmission of data as well as energy over an inductive link is conducted within a well-defined parameter set. For these systems, the shielding can be of particular importance if the properties of the link can be preserved. In this work, we investigate the effect of single and double-layered substrates consisting of ferrite and/or copper on the inductance and coupling of planar spiral coils. The examined link systems represent realistic configurations for active implantable systems such as cochlear implants. Experimental measurements are complemented with analytical calculations and finite element simulations, which are in good agreement for all measured parameters. The results are then used to study the transfer efficiency of an inductive link in a series-parallel resonant topology as a function of substrate size, the number of coil turns and coil separation. We find that ferrite sheets can be used to shield the system from unwanted metallic surfaces and to retain the inductive link parameters of the unperturbed system, particularly its transfer efficiency. The required size of the ferrite plates is comparable to the size of the coils, which makes the setup suitable for practical implementations. Since the sizes and geometries chosen for the studied inductive links are comparable to those of cochlear implants, our conclusions apply in particular to these systems.

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study

PubMed Central

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-01-01

Background The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. Results 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Methods Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (μm) and group B with RTA equal to or more than 250 μm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Conclusions The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID:27391437

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study.

PubMed

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-07-26

The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (µm) and group B with RTA equal to or more than 250 µm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity.

The relationship between retinal damage and current intensity in a pre-clinical suprachoroidal-transretinal stimulation model using a laser-formed microporous electrode

NASA Astrophysics Data System (ADS)

Kanda, Hiroyuki; Nakano, Yukari; Terasawa, Yasuo; Morimoto, Takeshi; Fujikado, Takashi

2017-10-01

Objective. Suprachoroidal-transretinal stimulation (STS) is a stimulation method for retinal prostheses. For STS-type retinal prostheses, we developed a new type of stimulating electrode called a femtosecond laser-induced porous electrode (FLiP electrode). To verify the safety of the FLiP electrode for STS, we investigated the characteristics of STS-induced retinal injury. Approach. Sixteen eyes of pigmented rabbits were studied in this in vivo study. For each examined eye, we implanted a single-channel FLiP electrode (diameter, 0.5 mm height, 0.3 mm geometric surface area, 0.43 mm2) in a scleral pocket created at the posterior pole of the eye. A return electrode (diameter, 0.5 mm length, 3 mm) was inserted into the vitreous cavity. The eyes were divided into five groups, and each group was stimulated with a different current intensity. The stimulus intensities and the number of eyes in each group were as follows: 1.0 mA (n  =  2), 1.5 mA (n  =  3), 2.0 mA (n  =  3), 2.5 mA (n  =  4), and 3.0 mA (n  =  2). Continuous biphasic pulses (0.5 ms/phase) were applied under general anesthesia at a frequency of 20 Hz for 48 h. Fundus photography, fluorescein angiography (FA), and optical coherence tomography were performed before and after applying the electrical stimulation to evaluate the retinal injury. Main results. The 1.0 mA and 1.5 mA groups showed little or no retinal damage. Fluorescent dye leakage in FA and punctate pigmentation in the fundus were observed around the stimulation site with stimulation of 2.0 mA (1/3), 2.5 mA (1/4), and 3.0 mA (2/2). Significance. Our findings indicate that the threshold current for inducing retinal damage is greater than that for eliciting electrical phosphenes (<1 mA) with STS observed in human trials. Therefore, STS by the FLiP electrode is a safe and feasible stimulation method for retinal prostheses as long as it is used with these pulse parameters.

The double capsules in macro-textured breast implants.

PubMed

Giot, Jean-Philippe; Paek, Laurence S; Nizard, Nathanael; El-Diwany, Mostafa; Gaboury, Louis A; Nelea, Monica; Bou-Merhi, Joseph S; Harris, Patrick G; Danino, Michel A

2015-10-01

Breast implants are amongst the most widely used types of permanent implants in modern medicine and have both aesthetic and reconstructive applications with excellent biocompatibility. The double capsule is a complication associated with textured prostheses that leads to implant displacement; however, its etiology has yet to be elucidated. In this study, 10 double capsules were sampled from breast expander implants for in-depth analysis; histologically, the inner capsular layer demonstrated highly organized collagen in sheets with delamination of fibers. At the prosthesis interface (PI) where the implant shell contacts the inner capsular layer, scanning electron microscopy (SEM) revealed a thin layer which mirrored the three-dimensional characteristics of the implant texture; the external surface of the inner capsular layer facing the intercapsular space (ICS) was flat. SEM examination of the inner capsule layer revealed both a large bacterial presence as well as biofilm deposition at the PI; a significantly lower quantity of bacteria and biofilm were found at the ICS interface. These findings suggest that the double capsule phenomenon's etiopathogenesis is of mechanical origin. Delamination of the periprosthetic capsule leads to the creation of the ICS; the maintained separation of the 2 layers subsequently alters the biostability of the macro-textured breast implant. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improvements in vision‐related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis

PubMed Central

Duncan, Jacque L; Arditi, Aries; da Cruz, Lyndon; Dagnelie, Gislin; Dorn, Jessy D; Ho, Allen C; Olmos de Koo, Lisa C; Barale, Pierre‐Olivier; Stanga, Paulo E; Thumann, Gabriele; Wang, Yizhong; Greenberg, Robert J

2016-01-01

Background The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end‐stage retinitis pigmentosa. Methods The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30‐patient single‐arm clinical study. VisQoL is a multi‐attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub‐group between baseline and the combined follow‐up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow‐up periods. Results Overall, 80 per cent of the patients reported difficulty in one or more dimensions pre‐implant. Composite VisQoL utility scores at follow‐up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. Conclusion Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36‐month follow‐up, suggesting a long‐term, durable improvement. PMID:27558213

Hermetic diamond capsules for biomedical implants enabled by gold active braze alloys.

PubMed

Lichter, Samantha G; Escudié, Mathilde C; Stacey, Alastair D; Ganesan, Kumaravelu; Fox, Kate; Ahnood, Arman; Apollo, Nicholas V; Kua, Dunstan C; Lee, Aaron Z; McGowan, Ceara; Saunders, Alexia L; Burns, Owen; Nayagam, David A X; Williams, Richard A; Garrett, David J; Meffin, Hamish; Prawer, Steven

2015-01-01

As the field of biomedical implants matures the functionality of implants is rapidly increasing. In the field of neural prostheses this is particularly apparent as researchers strive to build devices that interact with highly complex neural systems such as vision, hearing, touch and movement. A retinal implant, for example, is a highly complex device and the surgery, training and rehabilitation requirements involved in deploying such devices are extensive. Ideally, such devices will be implanted only once and will continue to function effectively for the lifetime of the patient. The first and most pivotal factor that determines device longevity is the encapsulation that separates the sensitive electronics of the device from the biological environment. This paper describes the realisation of a free standing device encapsulation made from diamond, the most impervious, long lasting and biochemically inert material known. A process of laser micro-machining and brazing is described detailing the fabrication of hermetic electrical feedthroughs and laser weldable seams using a 96.4% gold active braze alloy, another material renowned for biochemical longevity. Accelerated ageing of the braze alloy, feedthroughs and hermetic capsules yielded no evidence of corrosion and no loss of hermeticity. Samples of the gold braze implanted for 15 weeks, in vivo, caused minimal histopathological reaction and results were comparable to those obtained from medical grade silicone controls. The work described represents a first account of a free standing, fully functional hermetic diamond encapsulation for biomedical implants, enabled by gold active alloy brazing and laser micro-machining. Copyright © 2015 Elsevier Ltd. All rights reserved.

Progress in the clinical development and utilization of vision prostheses: an update

PubMed Central

Brandli, Alice; Luu, Chi D; Guymer, Robyn H; Ayton, Lauren N

2016-01-01

Vision prostheses, or “bionic eyes”, are implantable medical bionic devices with the potential to restore rudimentary sight to people with profound vision loss or blindness. In the past two decades, this field has rapidly progressed, and there are now two commercially available retinal prostheses in the US and Europe, and a number of next-generation devices in development. This review provides an update on the development of these devices and a discussion on the future directions for the field. PMID:28539798

Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury

PubMed Central

van der Merwe, Yolandi

2015-01-01

Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910

Changes in blood pressure and sleep duration in patients with blue light-blocking/yellow-tinted intraocular lens (CHUKYO study).

PubMed

Ichikawa, Kazuo

2014-07-01

Blood pressure and sleep duration may be influenced by retinal light exposure. Cataracts may exert such an influence by decreasing the transparency of the crystalline lens. A large-scale clinical study was conducted to examine changes in blood pressure and sleep duration after intraocular lens (IOL) implantation during cataract surgery and to investigate how different types of IOL influence the degree of these effects. Using a questionnaire, we collected information, including blood pressure measurement and sleep duration, from 1367 patients (1367 eyes) before IOL implantation, 1 week after IOL implantation and 1 month after IOL implantation. Systolic and diastolic blood pressures were significantly decreased in the total patient group after implantation. The decrease in systolic blood pressure 1 month after implantation was significantly more in patients who received a yellow-tinted IOL than it was in those who received an ultraviolet (UV) light-filtering IOL. The post-implantation sleep duration, including naps, became shorter in patients who had slept too much and became longer in those who had slept too little before IOL implantation. Our observations suggest that a yellow-tinted IOL is better for patients with high blood pressure than a UV light-filtering IOL. Furthermore, the yellow-tinted IOL is as good as the UV light-filtering IOL for improving sleep duration. A pale yellow-tinted IOL is likely to be superior to a moderate yellow-tinted IOL in terms of allowing patients to discriminate different colors. Thus, the pale yellow-tinted IOL appears to be better for patients than the UV light-filtering IOL and the moderate yellow-tinted IOL.

Reduction in mean deviation values in automated perimetry in eyes with multifocal compared to monofocal intraocular lens implants.

PubMed

Farid, Marjan; Chak, Garrick; Garg, Sumit; Steinert, Roger F

2014-08-01

To evaluate differences in mean deviation values in automated perimetry in healthy eyes with multifocal compared to monofocal intraocular lens (IOL) implants. Prospective, age-matched, comparative analysis. Single-center, tertiary referral academic practice. A total of 37 healthy eyes in 37 patients with bilateral multifocal (n=22) or monofocal (n=15) IOL implants were studied. INTERVENTION/OBSERVATION PROCEDURE: Humphrey Visual Field 10-2 testing was performed on all patients. Mean deviation (MD) and pattern standard deviation (PSD) numerical values were evaluated and compared between groups. The average MD was -2.84 dB (SD 2.32) for the multifocal IOL group and -0.97 dB (SD 1.58) for the monofocal IOL group (P=.006). There was no significant difference in PSD between the 2 groups (P=.99). Eyes that had the visual field 10-2 testing≥6 months from time of IOL placement showed no improvement in MD when compared to eyes that were tested within 6 months from IOL placement. Multifocal IOL implants cause significant nonspecific reduction in MD values on Humphrey Visual Field 10-2 testing that does not improve with time or neuroadaptation. Multifocal IOL implants may be inadvisable in patients where central visual field reduction may not be tolerated, such as macular degeneration, retinal pigment epithelium changes, and glaucoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of Optical Quality: Ocular Scattering and Aberrations in Eyes Implanted with Diffractive Multifocal or Monofocal Intraocular Lenses.

PubMed

Liao, Xuan; Lin, Jia; Tian, Jing; Wen, BaiWei; Tan, QingQing; Lan, ChangJun

2018-06-01

To compare objective optical quality, ocular scattering and aberrations of eyes implanted with an aspheric monofocal intraocular lens (IOL) or an aspheric apodized diffractive multifocal IOL three months after surgery. Prospective consecutive nonrandomized comparative cohort study. A total of 80 eyes from 57 cataract patients were bilaterally or unilaterally implanted with monofocal (AcrySof IQ SN60WF) or multifocal (AcrySof IQ ReSTOR SN6AD1) IOLs. Respectively, 40 eyes of 27 patients were implanted with monofocal IOLs, and 40 eyes of 30 patients were implanted with multifocal IOLs. Ocular high-order aberration (HOA) values were obtained using Hartmann-Shack aberrometer; objective scatter index (OSI), modulation transfer function (MTF) cutoff, Strehl ratio (SR), and contrast visual acuity OV at 100%, 20%, and 9% were measured using Objective Quality Analysis System II (OQAS II). Ocular aberrations performed similar in both groups (p > 0.05). However, significantly higher values of OSI and lower values of MTF cutoff, SR and OV were found in the SN6AD1 group (p < 0.05). Both ocular scattering and wave-front aberrations play essential role in retinal image quality, which may be overestimated when only aberrations were taken into account. Combining the effect of ocular scattering with HOA will result in a more accurate assessment of the visual and optical quality.

PFC knee replacement: osteolytic failures from extreme polyethylene degradation.

PubMed

Casey, David; Cottrell, Jocelyn; DiCarlo, Edward; Windsor, Russell; Wright, Timothy

2007-11-01

Despite the long-term success of press-fit condylar (PFC) knee prostheses, premature failures caused by aggressive rapid osteolysis have been reported. To investigate why patients experience such failures, we reviewed 48 retrieved implants and surrounding tissues together with demographic and radiographic data. Polyethylene degradation was determined from density profiles taken through the retrieved inserts. We compared the histology of tissues around PFC implants with that from around failed implants of similar designs from patients matched to length of implantation, body mass index, and age. The pathologic response in PFC patients showed more widespread, dense, sheet-like cellular infiltrate, whereas in the matched patients, the infiltrate was generally scattered discontinuously. The dominant wear mode of the PFC inserts was severe delamination on the articular surfaces. Wear damage was worse with increased length of implantation and was correlated with oxidative degradation and osteolysis. Degradation and osteolysis were more severe with inserts stored longer and sterilized by gamma radiation in air. These results underscore that degradation and increased shelf life lead to osteolysis and loosening. However, they raise questions concerning the cellular reaction to the debris from PFC implants that could lead to a better general understanding of osteolysis.

Congenital cheek teratoma with temporo-mandibular joint ankylosis managed with ultra-thin silicone sheet interpositional arthroplasty.

PubMed

Bhatnagar, Ankur; Verma, Vinay Kumar; Purohit, Vishal

2013-01-01

Primary cheek teratomas are rare with < 5 reported cases. None had associated temporo mandibular joint ankylosis (TMJA). The fundamental aim in the treatment of TMJA is the successful surgical resection of ankylotic bone, prevention of recurrence, and aesthetic improvement by ensuring functional occlusion. Early treatment is necessary to promote proper growth and function of mandible and to facilitate the positive psychological development of child. Inter-positional arthroplasty with ultra-thin silicone sheet was performed. Advantages include short operative time, less foreign material in the joint space leading to negligible foreign body reactions and least chances of implant extrusion. Instead of excising a large bony segment, a thin silicone sheet was interposed and then sutured ensuring preservation of mandibular height. Aggressive post-operative physiotherapy with custom made dynamic jaw exerciser was used to prevent recurrence.

Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice

PubMed Central

Chi, Zai-Long; Yasumoto, Fumie; Sergeev, Yuri; Minami, Masayoshi; Obazawa, Minoru; Kimura, Itaru; Takada, Yuichiro; Iwata, Takeshi

2010-01-01

Primary open-angle glaucoma (POAG) is one of the three principal subtypes of glaucoma and among the leading cause of blindness worldwide. POAG is defined by cell death of the retinal ganglion cells (RGCs) and surrounding neuronal cells at higher or normal intraocular pressure (IOP). Coded by one of the three genes responsible for POAG, WD repeat-containing protein 36 (WDR36) has two domains with a similar folding. To address whether WDR36 is functionally important in the retina, we developed four transgenic mice strains overexpressing a wild-type (Wt) and three mutant variants of D606G, deletion of amino acids at positions 605–607 (Del605–607) and at 601–640 (Del601–640) equivalent to the location of the D658G mutation observed in POAG patients. A triple amino acid deletion of mouse Wdr36 at positions 605–607 corresponding to the deletion at positions 657–659 in humans developed progressive retinal degeneration at the peripheral retina with normal IOP. RGCs and connecting amacrine cell synapses were affected at the peripheral retina. Axon outgrowth rate of cultured RGC directly isolated from transgenic animal was significantly reduced by the Wdr36 mutation compared with Wt. Molecular modeling of wild and mutant mouse Wdr36 revealed that deletion at positions 605–607 removed three residues and a hydrogen bond, required to stabilize anti-parallel β-sheet of the 6th β-propeller in the second domain. We concluded that WDR36 plays an important functional role in the retina homeostasis and mutation to this gene can cause devastating retinal damage. These data will improve understanding of the functional property of WDR36 in the retina and provide a new animal model for glaucoma therapeutics. PMID:20631153

Neuroprotective Dose Response in RCS Rats Implanted with Microphotodiode Arrays

PubMed Central

Pardue, Machelle T.; Kim, Moon K.; Walker, Tiffany A.; Faulkner, Amanda E.; Chow, Alan Y.; Ciavatta, Vincent T.

2012-01-01

Purpose Neuropreservation of retinal function and structure in RCS rats following implantation of a microphotodiode array (MPA) has been shown in previous studies(Pardue et al. 2005a; Pardue et al. 2005b). Since microphotodiodes produce electrical currents in proportion to the intensity of incident light, increased light exposure may result in greater neuroprotective effects. Our previous studies suggested that the frequency of light exposure to electroretinogram (ERG) flash stimuli might provide increased neuroprotection. Thus, in this study, we examined the dose response of subretinal electrical stimulation by exposing RCS rats implanted with MPAs to variable durations and combinations of two different lighting regimens: pulsing incandescent bulbs and xenon stimuli from an ERG Ganzfeld. While incandescent light regimens did not produce any significant differences in ERG function, we found significantly greater dark-adapted ERG b-wave amplitudes in RCS rats that received weekly versus biweekly ERGs over the course of 8 weeks of follow-up. These results suggest that subretinal electrical stimulation may be optimized to produce greater neuroprotective effects by dosing with periodic higher current. PMID:22183323

A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina

PubMed Central

Maturana, Matias I.; Apollo, Nicholas V.; Hadjinicolaou, Alex E.; Garrett, David J.; Cloherty, Shaun L.; Kameneva, Tatiana; Grayden, David B.; Ibbotson, Michael R.; Meffin, Hamish

2016-01-01

Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron’s electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy. PMID:27035143

Integration of an Axcelis Optima HD Single Wafer High Current Implanter for p- and n-S/D Implants in an Existing Batch Implanter Production Line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmeide, Matthias; Kontratenko, Serguei; Krimbacher, Bernhard

2008-11-03

This paper is focused on the integration and qualification of an Axcelis Optima HD single wafer high current spot beam implanter in an existing 200 mm production line with different types of Axcelis batch implanters for high current applications. Both the design of the beamline and the beam shape are comparable between single wafer and batch high current spot beam implanters. In contrast to the single wafer high current ribbon beam implanter, energy contamination is not a concern for the considered spot beam tool because the drift mode can be used down to energies in the 2 keV region. Themore » most important difference between single wafer and batch high current implanters is the significantly higher dose rate and, therefore, the higher damage rate for the single wafer tool due to the different scanning architecture. The results of the integration of high dose implantations, mainly for p- and n-S/D formation, for DRAM 110 nm without pre-amorphization implantation (PAI), CMOS Logic from around 250 nm down to 90 nm without and with PAI, are presented and discussed. Dopant concentration profile analysis using SIMS was performed for different technologies and implantation conditions. The impurity activation was measured using sheet resistance and in some cases spreading resistance technique was applied. The amorphous layer thickness was measured using TEM. Finally, device data are presented in combination with dose, energy and beam current variations. The results have shown that the integration of implantation processes into crystalline structure without PAI is more complex and time consuming than implantations into amorphous layer where the damage difference due to the different dose rates is negligible.« less

An image-processing strategy to extract important information suitable for a low-size stimulus pattern in a retinal prosthesis.

PubMed

Chen, Yili; Fu, Jixiang; Chu, Dawei; Li, Rongmao; Xie, Yaoqin

2017-11-27

A retinal prosthesis is designed to help the blind to obtain some sight. It consists of an external part and an internal part. The external part is made up of a camera, an image processor and an RF transmitter. The internal part is made up of an RF receiver, implant chip and microelectrode. Currently, the number of microelectrodes is in the hundreds, and we do not know the mechanism for using an electrode to stimulate the optic nerve. A simple hypothesis is that the pixels in an image correspond to the electrode. The images captured by the camera should be processed by suitable strategies to correspond to stimulation from the electrode. Thus, it is a question of how to obtain the important information from the image captured in the picture. Here, we use the region of interest (ROI), a useful algorithm for extracting the ROI, to retain the important information, and to remove the redundant information. This paper explains the details of the principles and functions of the ROI. Because we are investigating a real-time system, we need a fast processing ROI as a useful algorithm to extract the ROI. Thus, we simplified the ROI algorithm and used it in an outside image-processing digital signal processing (DSP) system of the retinal prosthesis. The results show that our image-processing strategies are suitable for a real-time retinal prosthesis and can eliminate redundant information and provide useful information for expression in a low-size image.

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology

PubMed Central

Ouchi, M; Kinoshita, S

2015-01-01

Purpose To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. Methods LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Results Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. Conclusion With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies. PMID:25744442

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology.

PubMed

Ouchi, M; Kinoshita, S

2015-05-01

To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies.

Chronic Electrical Stimulation with a Suprachoroidal Retinal Prosthesis: A Preclinical Safety and Efficacy Study

PubMed Central

Nayagam, David A. X.; Williams, Richard A.; Allen, Penelope J.; Shivdasani, Mohit N.; Luu, Chi D.; Salinas-LaRosa, Cesar M.; Finch, Sue; Ayton, Lauren N.; Saunders, Alexia L.; McPhedran, Michelle; McGowan, Ceara; Villalobos, Joel; Fallon, James B.; Wise, Andrew K.; Yeoh, Jonathan; Xu, Jin; Feng, Helen; Millard, Rodney; McWade, Melanie; Thien, Patrick C.; Williams, Chris E.; Shepherd, Robert K.

2014-01-01

Purpose To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis. Methods Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue. Results All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses. Conclusions Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents. PMID:24853376

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

Full wafer size investigation of N+ and P+ co-implanted layers in 4H-SiC

NASA Astrophysics Data System (ADS)

Blanqué, S.; Lyonnet, J.; Pérez, R.; Terziyska, P.; Contreras, S.; Godignon, P.; Mestres, N.; Pascual, J.; Camassel, J.

2005-03-01

We report a full wafer size investigation of the homogeneity of electrical properties in the case of co-implanted nitrogen and phosphorus ions in 4H-SiC semi-insulating wafers. To match standard industrial requirements, implantation was done at room temperature. To achieve a detailed electrical knowledge, we worked on a 35 mm wafer on which 77 different reticules have been processed. Every reticule includes one Hall cross, one Van der Pauw test structure and different TLM patterns. Hall measurements have been made on all 77 different reticules, using an Accent HL5500 Hall System® from BioRad fitted with an home-made support to collect data from room temperature down to about 150 K. At room temperature, we find that the sheet carrier concentration is only 1/4 of the total implanted dose while the average mobility is 80.6 cm2/Vs. The standard deviation is, typically, 1.5 cm2/Vs.

Ahmed glaucoma valve in uveitic patients with fluocinolone acetonide implant-induced glaucoma: 3-year follow-up.

PubMed

Kubaisi, Buraa; Maleki, Arash; Ahmed, Aseef; Lamba, Neel; Sahawneh, Haitham; Stephenson, Andrew; Montieth, Alyssa; Topgi, Shobha; Foster, C Stephen

2018-01-01

To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) in eyes with noninfectious uveitis that had fluocinolone acetonide intravitreal implant (Retisert™)-induced glaucoma. This retrospective study reviewed the safety and efficacy of AGV implantation in patients with persistently elevated intraocular pressure (IOP) after implantation of a fluocinolone acetonide intravitreal implant at the Massachusetts Eye Research and Surgery Institution between August 2006 and November 2015. Nine patients with 10 uveitic eyes were included in this study, none of which had preexisting glaucoma in the study eye. Mean patient age was 42 years; 6 patients were female and 3 were male. Baseline mean IOP was 30.6 mmHg prior to AGV placement while mean IOP-lowering medications were 2.9. In the treatment groups, there was a statistically significant reduction in post-AGV IOP. IOP was lowest at 1-week after AGV implantation (9.0 mmHg). Nine out of 10 eyes achieved an IOP below target value of 22 mmHg and/or a 20% reduction in IOP from baseline 1 month and 1 year following AGV placement. All other postoperative time points showed all 10 eyes reaching this goal. A statistically significant decrease in IOP-lowering medication was seen at the 1-week, 1-month, and 3-year time points compared to baseline, while a statistically significant increase was seen at the 3-month, 6-month, and 2-year post-AGV time points. No significant change in retinal nerve thickness or visual field analysis was found. AGV is an effective and safe method of treatment in fluocinolone acetonide intravitreal implant-induced glaucoma. High survival rate is expected for at least 3 years.

Ahmed glaucoma valve in uveitic patients with fluocinolone acetonide implant-induced glaucoma: 3-year follow-up

PubMed Central

Kubaisi, Buraa; Maleki, Arash; Ahmed, Aseef; Lamba, Neel; Sahawneh, Haitham; Stephenson, Andrew; Montieth, Alyssa; Topgi, Shobha; Foster, C Stephen

2018-01-01

Purpose To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) in eyes with noninfectious uveitis that had fluocinolone acetonide intravitreal implant (Retisert™)-induced glaucoma. Methods This retrospective study reviewed the safety and efficacy of AGV implantation in patients with persistently elevated intraocular pressure (IOP) after implantation of a fluocinolone acetonide intravitreal implant at the Massachusetts Eye Research and Surgery Institution between August 2006 and November 2015. Results Nine patients with 10 uveitic eyes were included in this study, none of which had preexisting glaucoma in the study eye. Mean patient age was 42 years; 6 patients were female and 3 were male. Baseline mean IOP was 30.6 mmHg prior to AGV placement while mean IOP-lowering medications were 2.9. In the treatment groups, there was a statistically significant reduction in post-AGV IOP. IOP was lowest at 1-week after AGV implantation (9.0 mmHg). Nine out of 10 eyes achieved an IOP below target value of 22 mmHg and/or a 20% reduction in IOP from baseline 1 month and 1 year following AGV placement. All other postoperative time points showed all 10 eyes reaching this goal. A statistically significant decrease in IOP-lowering medication was seen at the 1-week, 1-month, and 3-year time points compared to baseline, while a statistically significant increase was seen at the 3-month, 6-month, and 2-year post-AGV time points. No significant change in retinal nerve thickness or visual field analysis was found. Conclusion AGV is an effective and safe method of treatment in fluocinolone acetonide intravitreal implant-induced glaucoma. High survival rate is expected for at least 3 years. PMID:29750012

Ocular Pharmacokinetics of Fluocinolone Acetonide Following Iluvien Implantation in the Vitreous Humor of Rabbits

PubMed Central

Kane, Frances E.

2015-01-01

Abstract Purpose: The purpose of this study was to evaluate the systemic and ocular pharmacokinetics (PK) of fluocinolone acetonide (FAc) following administration of Iluvien® intravitreal implants. Methods: The FAc intravitreal implant was administered to rabbits in 3 doses (0.2, 0.5, and 1.0 μg/day). The concentration of FAc was measured by a validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method in plasma and ocular tissues at various time points through month 24. Results: Following administration of the 0.2 μg/day implant, FAc levels peaked in most tissues at day 2 or 8, reached approximate steady state levels by month 3 and very gradually decreased over the duration of the study. The FAc level in the aqueous humor was not measurable at most time points in the rabbit. FAc was still present in most ocular tissues at 2 years. The 0.5 and 1.0 μg/day dose groups followed the same pattern through month 9. The elimination half lives in the tissues for which it was measurable were greater than 83 days. Exposure to FAc was highest in the choroid/retinal pigment epithelium for all doses, followed by lens and retina. Conclusions: The results of this study demonstrate sustained delivery of FAc from the Iluvien intravitreal implant in the ocular tissue of rabbits. Retina and lens FAc levels with the Iluvien implant were approximately 1/10 those reported with the Retisert® implant. FAc levels in the aqueous were not measureable with Iluvien where they were measured for 12 months with Retisert. PMID:25562126

Combination of platelet-rich plasma within periodontal ligament stem cell sheets enhances cell differentiation and matrix production.

PubMed

Xu, Qiu; Li, Bei; Yuan, Lin; Dong, Zhiwei; Zhang, Hao; Wang, Han; Sun, Jin; Ge, Song; Jin, Yan

2017-03-01

The longstanding goal of periodontal therapy is to regenerate periodontal tissues. Although platelet-rich plasma (PRP) has been gaining increasing popularity for use in the orofacial region, whether PRP is useful for periodontal regeneration is still unknown. The purpose of this study was to determine whether a mixture of periodontal ligament stem cell (PDLSC) sheets and PRP promoted bone regeneration, one of the most important measurement indices of periodontal tissue regenerative capability in vitro and in vivo. In this study, we evaluated the effects of different doses of PRP on the differentiation of human PDLSCs. Then cell sheet formation, extracellular matrix deposition and osteogenic gene expression in response to different doses of PRP treatment during sheet grafting was investigated. Furthermore, we implanted PDLSC sheets treated with 1% PRP subcutaneously into immunocompromised mice to evaluate their bone-regenerative capability. The results revealed that 1% PRP significantly enhanced the osteogenic differentiation of PDLSCs. Based on the production of extracellular matrix proteins, the results of scanning electron microscopy and the expression of the osteogenic genes ALP, Runx2, Col-1 and OCN, the provision of 1% PRP for PDLSC sheets was the most effective PRP administration mode for cell sheet formation. The results of in vivo transplantation showed that 1% PRP-mediated PDLSC sheets exhibited better periodontal tissue regenerative capability than those obtained without PRP intervention. These data suggest that a suitable concentration of PRP stimulation may enhance extracellular matrix production and positively affect cell behaviour in PDLSC sheets. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of the 3D bone-to-implant contact and bone stiffness on the initial stability of a dental implant: micro-CT and resonance frequency analyses.

PubMed

Hsu, J T; Huang, H L; Tsai, M T; Wu, A Y J; Tu, M G; Fuh, L J

2013-02-01

This study investigated the effects of bone stiffness (elastic modulus) and three-dimensional (3D) bone-to-implant contact ratio (BIC%) on the primary stabilities of dental implants using micro-computed tomography (micro-CT) and resonance frequency analyses. Artificial sawbone models with five values of elastic modulus (137, 123, 47.5, 22, and 12.4 MPa) comprising two types of trabecular structure (solid-rigid and cellular-rigid) were investigated for initial implant stability quotient (ISQ), measured using the wireless Osstell resonance frequency analyzer. Bone specimens were attached to 2 mm fibre-filled epoxy sheets mimicking the cortical shell. ISQ was measured after placing a dental implant into the bone specimen. Each bone specimen with an implant was subjected to micro-CT scanning to calculate the 3D BIC% values. The similarity of the cellular type of artificial bone to the trabecular structure might make it more appropriate for obtaining accurate values of primary implant stability than solid-bone blocks. For the cellular-rigid bone models, the ISQ increased with the elastic modulus of cancellous bone. The regression correlation coefficient was 0.96 for correlations of the ISQ with the elasticity of cancellous bone and with the 3D BIC%. The initial implant stability was moderately positively correlated with the elasticity of cancellous bone and with the 3D BIC%. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Improvement of Anal Function by Adipose-Derived Stem Cell Sheets.

PubMed

Inoue, Yusuke; Fujita, Fumihiko; Yamaguchi, Izumi; Kinoe, Hiroko; Kawahara, Daisuke; Sakai, Yusuke; Kuroki, Tamotsu; Eguchi, Susumu

2018-01-01

One of the most troublesome complications of anal preserving surgery is anal sphincter dysfunction. The aim of this study was to evaluate functional recovery after implantation of adipose-derived stem cell (ADSC) sheets, novel biotechnology, for an anal sphincter resection animal model. Eighteen female Sprague-Dawley rats underwent removal of the nearest half of the internal and external anal sphincter muscle. Nine rats received transplantation with ADSC sheets to the resected area while the remaining rats received no transplantation. The rats were evaluated for the anal function by measuring their resting pressure before surgery and on postoperative days 1, 7, 14, 28, and 56. In addition, the rats were examined for the presence of smooth muscle and also to determine its origin. The improvement of the anal pressure was significantly greater in the ADSC sheet transplantation group compared with the control group. Histologically, at the vicinity of the remaining smooth muscle, reproduction of smooth muscle was detected. Using in fluorescence in situ hybridization, the cells were shown to be from the recipient. Regenerative therapy using ADSC sheet has the potential to recover anal sphincter dysfunction due to anorectal surgery. © 2017 S. Karger AG, Basel.

Early Retinal and Choroidal Coat Thickness Changes After Intravitreal Dexamethasone Implant Injection for Diabetic Macular Edema.

PubMed

Horozoğlu, Fatih; Sever, Özkan

2018-06-05

Intravitreal steroid injection is one of the treatment choices in diabetic macular edema (DME). Dexamethasone (Dx) implant is the most novel form of intravitreal steroid therapy. Macular thickness improvement is well known effect of Dx implant however; subfoveal choroidal coat thickness (SFCT) changes need to be investigated. To evaluate the early central macular thickness (CMT) and SFCT alterations after single dose dexamethasone implant injection in DME. Retrospective cross-sectional study. We identified 29 patients with DME (29 eyes) who underwent optical coherence tomography (OCT) and fundus fluoroscein angiography (FFA). All patients received a single dose intravitreal Dx implant and were followed for CMT and SFCT alterations for the post-injection first hour, first day, first week, first month and third month. The preoperative mean CMT and SFCT measurements were 592.3±122.3 (412-879) μm and 264.8±53.7 (165-397) μm, respectively. CMT measurements significantly decreased from the first hour (p<0.050) and kept decreasing till 3 month (p<0.001); while SFCT decrement was just significant at the first day (p<0.05). When we compared the decrease in SFCT and CMT, 1 hour was similar, however not significant, 1.5% SFCT and 5% CMT decrease was, respectively (p>0.050). CMT decrease rate was significantly higher than SFCT at 1 day, 1 week, 1 month and 3 month (p<0.001). Intravitreal Dx implant has got a meaningful effect on CMT in patients with DME while SFCT decreases significantly at first hour and first day.

Photovoltaic Pixels for Neural Stimulation: Circuit Models and Performance.

PubMed

Boinagrov, David; Lei, Xin; Goetz, Georges; Kamins, Theodore I; Mathieson, Keith; Galambos, Ludwig; Harris, James S; Palanker, Daniel

2016-02-01

Photovoltaic conversion of pulsed light into pulsed electric current enables optically-activated neural stimulation with miniature wireless implants. In photovoltaic retinal prostheses, patterns of near-infrared light projected from video goggles onto subretinal arrays of photovoltaic pixels are converted into patterns of current to stimulate the inner retinal neurons. We describe a model of these devices and evaluate the performance of photovoltaic circuits, including the electrode-electrolyte interface. Characteristics of the electrodes measured in saline with various voltages, pulse durations, and polarities were modeled as voltage-dependent capacitances and Faradaic resistances. The resulting mathematical model of the circuit yielded dynamics of the electric current generated by the photovoltaic pixels illuminated by pulsed light. Voltages measured in saline with a pipette electrode above the pixel closely matched results of the model. Using the circuit model, our pixel design was optimized for maximum charge injection under various lighting conditions and for different stimulation thresholds. To speed discharge of the electrodes between the pulses of light, a shunt resistor was introduced and optimized for high frequency stimulation.

A rare case of scleral buckle infection with Curvularia species.

PubMed

Singh, Shalini; Shrivastav, Ankita; Agarwal, Manisha; Gandhi, Arpan; Mayor, Rahul; Paul, Lagan

2018-02-09

Scleral buckling is an established modality of treating retinal detachment. Being an external implant the buckle may be prone to infections. We report such a case with a delayed presentation and a rare etiology. A 45 year old male presented with redness, foreign body sensation and discharge for one month in his right eye. The patient had undergone a retinal detachment surgery elsewhere 14 years back without any visual gain. Right eye demonstrated no perception of light and the best corrected visual acuity in the left eye was 6/6, N6. On downgaze an exposed and anteriorly displaced scleral buckle was identified with black deposits and mucopurulent material overlying the buckle. Scleral buckle removal was done. On microbiological examination Curvularia species was identified. Successful treatment with antifungals was done. Scleral buckle infection with dematiaceous fungi is a rare occurrence. To the best of our knowledge this is the first case report describing a buckle infection caused by the curvularia species.

Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations.

PubMed

Barriga-Rivera, Alejandro; Morley, John W; Lovell, Nigel H; Suaning, Gregg J

2016-08-01

Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.

Extensive regeneration of the stomach using bioabsorbable polymer sheets.

PubMed

Miyazawa, Mitsuo; Aikawa, Masayasu; Watanabe, Yukihiro; Takase, Ken-ichiro; Okamoto, Kojun; Shrestha, Santosh; Okada, Katsuya; Koyama, Isamu; Ikada, Yoshito

2015-11-01

The growing prevalence of endoscopic surgery in recent years has led to the minimization of postoperative scarring. However, this procedure does not allow for the regeneration of the resected digestive tract, which compromises the postoperative maintenance of digestive function. In this preliminary study, we developed an artificial gastric wall (AGW) using bioabsorbable polymer (BAP), and evaluated the ability of this BAP patch to repair and regenerate a widely defective gastric wall in an animal model. Pigs were laparotomized under general anesthesia. An 8 × 8-cm, round portion of the anterior gastric wall was excised and replaced by an AGW. The AGW was composed of a copolymer comprising 50% lactic acid and 50% caprolactone. The animals were relaparotomized 4, 8, or 12 weeks after implantation, after which they underwent resection of the entire stomach for gross and histologic evaluation of the graft sites. All recipient pigs survived until killing. By 4-8 weeks, the graft site revealed progressively fewer mucosal defect after each day. Moreover, the grafted area was indistinguishable from the native stomach 12 weeks after AGW implantation. The structures of the regenerated mucous membrane and muscle layers were identical to those of the native stomach. Furthermore, proton pumps were found in the regenerated tissue. The BAP sheets helped to restore extensive gastric defects without causing any deformation. The use of BAP sheets may become a new therapeutic method that prevents alterations of gastric volume after extensive gastrectomy for stomach cancer and other diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Clock recovery PLL with gated PFD for NRZ ON-OFF Modulated Signals in a retinal implant system.

PubMed

Brendler, Christian; Aryan, Naser Pour; Rieger, Viola; Rothermel, Albrecht

2013-01-01

A Clock Recovery Phase Locked Loop with Gated Phase Frequency Detector (GPLL) for NRZ ON-OFF Modulated Signals with low data transmission rates for an inductively powered subretinal implant system is presented. Low data transmission rate leads to a long absence of inductive powering in the system when zeros are transmitted. Consequently there is no possibility to extract any clock in these pauses, thus the digital circuitry can not work any more. Compared to a commonly used PLL for clock extraction, no certain amount of data transitions is needed. This is achieved by having two operating modes. In one mode the GPLL tracks the HF input signal. In the other, the GPLL is an adjustable oscillator oscillating at the last used frequency. The proposed GPLL is fabricated and measured using a 350 nm High Voltage CMOS technology.

Achieving Small Structures in Thin NiTi Sheets for Medical Applications with Water Jet and Micro Machining: A Comparison

NASA Astrophysics Data System (ADS)

Frotscher, M.; Kahleyss, F.; Simon, T.; Biermann, D.; Eggeler, G.

2011-07-01

NiTi shape memory alloys (SMA) are used for a variety of applications including medical implants and tools as well as actuators, making use of their unique properties. However, due to the hardness and strength, in combination with the high elasticity of the material, the machining of components can be challenging. The most common machining techniques used today are laser cutting and electrical discharge machining (EDM). In this study, we report on the machining of small structures into binary NiTi sheets, applying alternative processing methods being well-established for other metallic materials. Our results indicate that water jet machining and micro milling can be used to machine delicate structures, even in very thin NiTi sheets. Further work is required to optimize the cut quality and the machining speed in order to increase the cost-effectiveness and to make both methods more competitive.

Congenital cheek teratoma with temporo-mandibular joint ankylosis managed with ultra-thin silicone sheet interpositional arthroplasty

PubMed Central

Bhatnagar, Ankur; Verma, Vinay Kumar; Purohit, Vishal

2013-01-01

Primary cheek teratomas are rare with < 5 reported cases. None had associated temporo mandibular joint ankylosis (TMJA). The fundamental aim in the treatment of TMJA is the successful surgical resection of ankylotic bone, prevention of recurrence, and aesthetic improvement by ensuring functional occlusion. Early treatment is necessary to promote proper growth and function of mandible and to facilitate the positive psychological development of child. Inter-positional arthroplasty with ultra-thin silicone sheet was performed. Advantages include short operative time, less foreign material in the joint space leading to negligible foreign body reactions and least chances of implant extrusion. Instead of excising a large bony segment, a thin silicone sheet was interposed and then sutured ensuring preservation of mandibular height. Aggressive post-operative physiotherapy with custom made dynamic jaw exerciser was used to prevent recurrence. PMID:24163567

Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

PubMed Central

Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.; Smit, Andries J.; Los, Leonoor I.

2017-01-01

Purpose Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. Results Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3–7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 μmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). Conclusions Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients. PMID:28264049

Implantation of Spheramine in advanced Parkinson's disease (PD).

PubMed

Bakay, Roy A E; Raiser, Cathy D; Stover, Natividad P; Subramanian, Thyagarajan; Cornfeldt, Michael L; Schweikert, Alfred W; Allen, Richard C; Watts, Ray

2004-01-01

Evaluation of the safety and efficacy of unilateral stereotactic implantation of cultured human retinal pigment epithelial (hRPE) cells attached to microcarriers (Spheramine) in patients with advanced PD in an open label pilot study. Six patients with advanced PD (3 males; 3 females; mean age 52.2 years; mean duration of PD 10.2 years; mean Hoehn and Yahr stage "off" 3.75) were assessed at baseline and post-operatively using the modified CAPIT. Each patient underwent MRI-guided stereotactic transplantation of 325,000 hRPE cells attached to microcarriers in 5 tracts, 5 mm apart in the post-commissural putamen contralateral to the most affected side. Immunosuppression was not used. The UPDRS Motor (UPDR-M) score in the practically defined "off" state was the primary outcome measure. At 6 months post-op, the mean UPDRS-M (off) score improved to 35 (34%) from a pre-op baseline mean of 52 (p <.001). Secondary outcome measures improved including the total UPDRS (33%), Timed Motor Tests (on, 14%; off, 23%), PDQ39 QOL (30%), and Schwab and England score (on, 11%; off, 30%). Bilateral improvements have been observed in motor symptoms, with the greatest effect seen contralateral to the implants. Three of six patients currently have lower Dyskinesia Rating Scale scores than at baseline, while the scores of the other three are unchanged from baseline values. No "off-state" dyskinesias have been observed. Thus Spheramine implantation therapy appears to be safe and well tolerated for 6 months post-implantation.

Defining the Hook Region Anatomy of the Guinea Pig Cochlea for Modeling of Inner Ear Surgery.

PubMed

Lo, Jonathon; Sale, Phillip; Wijewickrema, Sudanthi; Campbell, Luke; Eastwood, Hayden; O'leary, Stephen John

2017-07-01

The aim of this study was to describe the hook region anatomy of the guinea pig cochlea to identify the optimal surgical approach for cochlear implantation and to determine what anatomical structures are at risk. Animal studies investigating hearing loss after cochlear implantation surgery are currently constrained by the lack of a reproducible implantation model. Guinea pig cochleae were imaged using thin-sheet laser imaging microscopy. Images were stitched, reconstructed, and segmented for analysis. Insertion vectors were determined by tracing their paths to the outer wall and converting to Cartesian coordinates. Spherical surface and multiplane views were generated to analyze outer wall and radial forces of the insertion vector. Thin-sheet laser imaging microscopy enabled quantitative, whole specimen analysis of the soft and bony tissue relationships of the complex cochlear hook region in any desired plane without loss of image quality. Round window or cochleostomy approaches in the anteroinferior plane avoided direct damage to cochlear structures. Cochleostomy approach had large interindividual variability of angular depth and outer wall forces but predictable radial force. The guinea pig hook region and lower basal turn have similar structural relationships to humans. Careful cochleostomy placement is essentially for minimizing cochlear trauma and for ensuring a straight insertion vector that successfully advances around the outer wall. Experiments with guinea pigs that control for the surgical approach are likely to provide useful insights into the aetiology and the development of therapies directed at postimplantation hearing loss.

Hard, soft tissue and in vitro cell response to porous nickel-titanium: a biocompatibility evaluation.

PubMed

Rhalmi, S; Odin, M; Assad, M; Tabrizian, M; Rivard, C H; Yahia, L H

1999-01-01

Porous nickel-titanium (NiTi) alloys have demonstrated bone attachment as well as tissue ingrowth in the past. However, very few studies have compared porous NiTi soft and hard tissue reactions, and in vitro cell response. We therefore have evaluated the general muscle and bone reaction to porous nickel-titanium. The latter material was implanted in rabbit tibias and back muscle, and assessed after three, six and twelve weeks of implantation. Porous NiTi specimens did not cause any adverse effect regardless of both implantation site and post-surgery recovery time. Muscle tissue exhibited thin tightly adherent fibrous capsules with fibers penetrating into implant pores. We observed that attachment strength of the soft tissue to the porous implant seemed to increase with post-implantation time. Bone tissue demonstrated good healing of the osteotomy. There was bone remodeling characterized by osteoclastic and osteoblastic activity in the cortex. This general good in vivo biocompatibility with muscle and bone tissue corresponded very well with the in vitro cell culture results we obtained. Fibroblasts seeded on porous nickel-titanium sheets managed to grow into the pores and all around specimen edges showing an another interesting cytocompatibility behavior. These results indicate good biocompatibility acceptance of porous nickel-titanium and are very promising towards eventual NiTi medical device approbation.

Aluminum surface modification by a non-mass-analyzed nitrogen ion beam

NASA Astrophysics Data System (ADS)

Ohira, Shigeo; Iwaki, Masaya

Non-mass-analyzed nitrogen ion implantation into polycrystal and single crystal aluminum sheets has been carried out at an accelerating voltage of 90 kV and a dose of 1 × 10 18 N ions/cm 2 using a Zymet implanter model Z-100. The pressure during implantation rose to 10 -3 Pa due to the influence of N gas feeding into the ion source. The characteristics of the surface layers were investigated by means of Auger electron spectroscopy (AES), X-ray diffraction (XRD), transmission electron diffraction (TED), and microscopy (TEM). The AES depth profiling shows a rectangular-like distribution of N atoms and little migration of O atoms near the surface. The high dose N-implantation forms c-axis oriented aluminum nitride (AIN) crystallines, and especially irradiation of Al single crystals with N ions leads to the formation of a hcp AlN single crystal. It is concluded that the high dose N-implantation in Al can result in the formation of AlN at room temperature without any thermal annealing. Furthermore, non-mass-analyzed N-implantation at a pressure of 10 -3 Pa of the nitrogen atmosphere causes the formation of pure AlN single crystals in the Al surface layer and consequently it can be practically used for AlN production.

Periodic Nanoneedle and Buffer Zones Constructed on a Titanium Surface Promote Osteogenic Differentiation and Bone Calcification In Vivo.

PubMed

Yu, Peng; Zhu, Xiaojing; Wang, Xiaolan; Wang, Shuangying; Li, Weiping; Tan, Guoxin; Zhang, Yu; Ning, Chengyun

2016-02-04

Rapid and effective bone mineralization at the bone/implant interface is required for successful orthopedic and dental implants. In this study, two periodic microscale functionalized zones on titanium (MZT) are created, namely, nanoneedle zones and buffer zones. The aim of this design is to provide spatially regulated topographical cues on titanium to enhance the efficacy of bone regeneration. This goal is achieved using a versatile and effective technique in which nanoneedle structures are hydrothermally constructed on the surface of titanium sheets, after which selective laser irradiation is used to construct buffer zones. The zonal structures of the MZT overcome the suppressive effect of the nanoneedle film on osteoblasts. Additionally, the MZT exhibits zone-selective apatite deposition and protein adsorption. The accelerated in vitro osteoblast differentiation and nodule deposition on the MZT are confirmed. Elemental analysis of the bone nodules formed by the osteoblasts growing on the titanium and MZT demonstrates they have different compositions. Histological and scanning electron microscope analysis of the bone formation on in vivo implants shows that this process is also enhanced by the MZT implant. The concept of constructing functionalized zones on titanium implant could facilitate future research on improving the design of orthopedic and dental implant surfaces. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment Update

PubMed Central

Lee, Christine; Tu, Hong Anh; Wells, David; Holubowich, Corinne

2017-01-01

Background Retinitis pigmentosa is a group of inherited disorders characterized by the degeneration of the photoreceptors in the retina, resulting in progressive vision loss. The Argus II system is designed to restore partial functional vision in patients with profound vision loss from advanced retinitis pigmentosa. At present, it is the only treatment option approved by Health Canada for this patient population. In June 2016, Health Quality Ontario published a health technology assessment of the Argus II retinal prosthesis system for patients with advanced retinitis pigmentosa. Based on that assessment, the Ontario Health Technology Advisory Committee recommended against publicly funding the Argus II system for this population. It also recommended that Health Quality Ontario re-evaluate the evidence in 1 year. The objective of this report was to examine new evidence published since the 2016 health technology assessment. Methods We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences related to the Argus II system. We performed a systematic literature search for studies published since the 2016 Argus II health technology assessment. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care, and we calculated incremental cost-effectiveness ratios over a 20-year time horizon. We also conducted a five-year budget impact analysis. Finally, we interviewed people with retinitis pigmentosa about their lived experience with vision loss, and with the Argus II system. Results Four publications from one multicentre international study were included in the clinical review. Patients showed significant improvements in visual function and functional outcomes with the Argus II system, and these outcomes were sustained up to a 5-year follow-up (moderate quality of evidence). The safety profile was generally acceptable. In the base case economic analysis, the Argus II system was cost-effective compared with standard care if the willingness to pay was more than $97,429 per quality-adjusted life-year. We estimated that funding the Argus II system would cost the province $0.71 to $0.78 million per year over 5 years, assuming 4 implants per year. People with lived experience spoke about the challenges of retinitis pigmentosa, including the gradual but persistent progression of the disease; its impact on their quality of life and their families; and the accessibility challenges they faced. Those who used the Argus II system spoke about its positive impact on their quality of life. Conclusions Based on evidence of moderate quality, the Argus II retinal prosthesis system improved visual function, real-life functional outcomes, and quality of life in patients with advanced retinitis pigmentosa. The Argus II system is expensive, but the cost to publicly fund it would be low, because of the small number of eligible patients. The Argus II system can only enable perception of light/dark and shapes/objects, but these advancements represent important gains for people with retinitis pigmentosa in terms of mobility and quality of life. PMID:29201260

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Baonian; Gossmann, Hans-Joachim; Toh, Terry

Angle control has been widely accepted as the key requirement for ion implantation in semiconductor device processing. From an ion implanter point of view, the incident ion direction should be measured and corrected by suitable techniques, such as XP-VPS for the VIISta implanter platform, to ensure precision ion placement in device structures. So called V-curves have been adopted to generate the wafer-based calibration using channeling effects as the Si lattice steer ions into a channeling direction. Thermal Wave (TW) or sheet resistance (Rs) can be used to determine the minimum of the angle response curve. Normally it is expected thatmore » the TW and Rs have their respective minima at identical angles. However, the TW and Rs response to the angle variations does depend on factors such as implant species, dose, and wafer temperature. Implant damage accumulation effects have to be considered for data interpretation especially for some 'abnormal' V-curve data. In this paper we will discuss some observed 'abnormal' angle responses, such as a) TW/Rs reverse trend for Arsenic beam, 2) 'W' shape of Rs Boron, and 3) apparent TW/Rs minimum difference for high tilt characterization, along with experimental data and TCAD simulations.« less

Follow-up of the original cohort with the Ahmed glaucoma valve implant.

PubMed

Topouzis, F; Coleman, A L; Choplin, N; Bethlem, M M; Hill, R; Yu, F; Panek, W C; Wilson, M R

1999-08-01

To study the long-term results of the Ahmed glaucoma valve implant in patients with complicated glaucoma in whom short-term results have been reported. In this multicenter study, we analyzed the long-term outcome of a cohort of 60 eyes from 60 patients in whom the Ahmed glaucoma valve was implanted. Failure was characterized by at least one of the following: intraocular pressure greater than 21 mm Hg at both of the last two visits less than 6 mm Hg at both of the last two visits, loss of light perception, additional glaucoma surgery, devastating complications, and removal or replacement of the Ahmed glaucoma valve implant. Devastating complications included chronic hypotony, retinal detachment, malignant glaucoma, endophthalmitis, and phthisis bulbi; we also report results that add corneal complications (corneal decompensation or edema, corneal graft failure) as defining a devastating complication. The mean follow-up time for the 60 eyes was 30.5 months (range, 2.1 to 63.5). When corneal complications were included in the definition of failure, 26 eyes (43%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 76%, 68%, 54%, and 45%, respectively. When corneal complications were excluded from the definition of failure, 13 eyes (21.5%) were considered failures. Cumulative probabilities of success at 1, 2, 3, and 4 years were 87%, 82%, 76%, and 76%, respectively. Most of the failures after 12 months of postoperative follow-up were because of corneal complications. The long-term performance of the Ahmed glaucoma valve implant is comparable to other drainage devices. More than 12 months after the implantation of the Ahmed glaucoma valve implant, the most frequent adverse outcome was corneal decompensation or corneal graft failure. These corneal problems may be secondary to the type of eyes that have drainage devices or to the drainage device itself. Further investigation is needed to identify the reasons that corneal problems follow drainage device implantation.

Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

PubMed

Thomas, Biju B; Zhu, Danhong; Zhang, Li; Thomas, Padmaja B; Hu, Yuntao; Nazari, Hossein; Stefanini, Francisco; Falabella, Paulo; Clegg, Dennis O; Hinton, David R; Humayun, Mark S

2016-05-01

To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

Fractal Interfaces for Stimulating and Recording Neural Implants

NASA Astrophysics Data System (ADS)

Watterson, William James

From investigating movement in an insect to deciphering cognition in a human brain to treating Parkinson's disease, hearing loss, or even blindness, electronic implants are an essential tool for understanding the brain and treating neural diseases. Currently, the stimulating and recording resolution of these implants remains low. For instance, they can record all the neuron activity associated with movement in an insect, but are quite far from recording, at an individual neuron resolution, the large volumes of brain tissue associated with cognition. Likewise, there is remarkable success in the cochlear implant restoring hearing due to the relatively simple anatomy of the auditory nerves, but are failing to restore vision to the blind due to poor signal fidelity and transmission in stimulating the more complex anatomy of the visual nerves. The critically important research needed to improve the resolution of these implants is to optimize the neuron-electrode interface. This thesis explores geometrical and material modifications to both stimulating and recording electrodes which can improve the neuron-electrode interface. First, we introduce a fractal electrode geometry which radically improves the restored visual acuity achieved by retinal implants and leads to safe, long-term operation of the implant. Next, we demonstrate excellent neuron survival and neurite outgrowth on carbon nanotube electrodes, thus providing a safe biomaterial which forms a strong connection between the electrode and neurons. Additional preliminary evidence suggests carbon nanotubes patterned into a fractal geometry will provide further benefits in improving the electrode-neuron interface. Finally, we propose a novel implant based off field effect transistor technology which utilizes an interconnecting fractal network of semiconducting carbon nanotubes to record from thousands of neurons simutaneously at an individual neuron resolution. Taken together, these improvements have the potential to radically improve our understanding of the brain and our ability to restore function to patients of neural diseases.

Platinum nanowire microelectrode arrays for neurostimulation applications: Fabrication, characterization, and in-vitro retinal cell stimulation

NASA Astrophysics Data System (ADS)

Whalen, John J., III

Implantable electrical neurostimulating devices are being developed for a number of applications, including artificial vision through retinal stimulation. The epiretinal prosthesis will use a two-dimensional array microelectrodes to address individual cells of the retina. MEMS fabrication processes can produce arrays of microelectrodes with these dimensions, but there are two critical issues that they cannot satisfy. One, the stimulating electrodes are the only part of the implanted electrical device that penetrate through the water impermeable package, and must do so without sacrificing hermeticity. Two, As electrode size decreases, the current density (A cm-2 ) increases, due to increased electrochemical impedance. This reduces the amount of charge that can be safely injected into the tissue. To date, MEMS processing method, cannot produce electrode arrays with good, prolonged hermetic properties. Similarly, MEMS approaches do not account for the increased impedance caused by decreased surface area. For these reasons there is a strong motivation for the development of a water-impermeable, substrate-penetrating electrode array with low electrochemical impedance. This thesis presents a stimulating electrode array fabricated from platinum nanowires using a modified electrochemical template synthesis approach. Nanowires are electrochemically deposited from ammonium hexachloroplatinate solution into lithographically patterned nanoporous anodic alumina templates to produce microarrays of platinum nanowires. The platinum nanowires penetrating through the ceramic aluminum oxide template serve as parallel electrical conduits through the water impermeable, electrically insulating substrate. Electrode impedance can be adjusted by either controlling the nanowire hydrous platinum oxide content or by partially etching the alumina template to expose additional surface area. A stepwise approach to this project was taken. First, the electrochemistry of ammonium hexachloroplatinate solution was characterized, and physical properties of electrodeposited thin films were correlated to deposition conditions used. Second, platinum nanowires were fabricated and their properties characterized, using similar deposition conditions. Third, the feasibility of fabricating platinum nanowire stimulating electrode arrays with a variety of surface structures was demonstrated. Fourth, the enhanced charge transfer characteristics of these structures were demonstrated using electrochemical techniques. Finally, retinal cell stimulation was demonstrated using electrodes from platinum nanowire arrays.

Prevention of recurrent radioulnar heterotopic ossification by combined indomethacin and a dermal/silicone sheet implant: case report.

PubMed

Lytle, Ian F; Chung, Kevin C

2009-01-01

A 27-year-old, right-handed man developed severe radioulnar synostosis at the distal radius 7 months after open reduction and internal fixation of his distal radius fracture. Heterotopic ossification formed at the radius fracture site, requiring excision of the heterotopic bone and plate removal. A bilayer, dermal substitute and silicone sheet was placed between the radius and ulna in the interosseous space to prevent recurrence of the heterotopic ossification. After surgery, the patient was treated with indomethacin 25 mg orally 3 times daily for 6 weeks. At 1 year after surgery, he has retained full pronation and near normal supination. Radiographs demonstrate no new heterotopic bone formation.

Observation of enhanced infrared absorption in silicon supersaturated with gold by pulsed laser melting of nanometer-thick gold films

NASA Astrophysics Data System (ADS)

Chow, Philippe K.; Yang, Wenjie; Hudspeth, Quentin; Lim, Shao Qi; Williams, Jim S.; Warrender, Jeffrey M.

2018-04-01

We demonstrate that pulsed laser melting (PLM) of thin 1, 5, and 10 nm-thick vapor-deposited gold layers on silicon enhances its room-temperature sub-band gap infrared absorption, as in the case of ion-implanted and PLM-treated silicon. The former approach offers reduced fabrication complexity and avoids implantation-induced lattice damage compared to ion implantation and pulsed laser melting, while exhibiting comparable optical absorptance. We additionally observed strong broadband absorptance enhancement in PLM samples made using 5- and 10-nm-thick gold layers. Raman spectroscopy and Rutherford backscattering analysis indicate that such an enhancement could be explained by absorption by a metastable, disordered and gold-rich surface layer. The sheet resistance and the diode electrical characteristics further elucidate the role of gold-supersaturation in silicon, revealing the promise for future silicon-based infrared device applications.

"In situ" observation of the role of chloride ion binding to monkey green sensitive visual pigment by ATR-FTIR spectroscopy.

PubMed

Katayama, Kota; Furutani, Yuji; Iwaki, Masayo; Fukuda, Tetsuya; Imai, Hiroo; Kandori, Hideki

2018-01-31

Long-wavelength-sensitive (LWS) pigment possesses a chloride binding site in its protein moiety. The binding of chloride alters the absorption spectra of LWS; this is known as the chloride effect. Although the two amino acid substitutions of His197 and Lys200 influence the chloride effect, the molecular mechanism of chloride binding, which underlies the spectral tuning, has yet to be clarified. In this study, we applied ATR-FTIR spectroscopy to monkey green (MG) pigment to gain structural information of the chloride binding site. The results suggest that chloride binding stabilizes the β-sheet structure on the extracellular side loop with perturbation of the retinal polyene chain, promotes a hydrogen bonding exchange with the hydroxyl group of Tyr, and alters the protonation state of carboxylate. Combining with the results of the binding analyses of various anions (Br - , I - and NO 3 - ), our findings suggest that the anion binding pocket is organized for only Cl - (or Br - ) to stabilize conformation around the retinal chromophore, which is functionally relevant with absorbing long wavelength light.

Photovoltaic retinal prosthesis for restoring sight to the blind: implant design and fabrication

NASA Astrophysics Data System (ADS)

Wang, Lele; Mathieson, Keith; Kamins, Theodore I.; Loudin, James; Galambos, Ludwig; Harris, James S.; Palanker, Daniel

2012-03-01

We have designed and fabricated a silicon photodiode array for use as a subretinal prosthesis aimed at restoring sight to patients who lost photoreceptors due to retinal degeneration. The device operates in photovoltaic mode. Each pixel in the two-dimensional array independently converts pulsed infrared light into biphasic electric current to stimulate remaining retinal neurons without a wired power connection. To enhance the maximum voltage and charge injection levels, each pixel contains three photodiodes connected in series. An active and return electrode in each pixel ensure localized current flow and are sputter coated with iridium oxide to provide high charge injection. The fabrication process consists of eight mask layers and includes deep reactive ion etching, oxidation, and a polysilicon trench refill for in-pixel photodiode separation and isolation of adjacent pixels. Simulation of design parameters included TSUPREM4 computation of doping profiles for n+ and p+ doped regions and MATLAB computation of the anti-reflection coating layers thicknesses. The main process steps are illustrated in detail, and problems encountered are discussed. The IV characterization of the device shows that the dark reverse current is on the order of 10-100 pA-negligible compared to the stimulation current; the reverse breakdown voltage is higher than 20 V. The measured photo-responsivity per photodiode is about 0.33A/W at 880 nm.

Recent advances in the therapy and prevention of CMV infections.

PubMed

Nichols, W G; Boeckh, M

2000-02-01

The introduction of highly active antiretroviral therapy (HAART) for HIV has had a major impact on the treatment of CMV disease in HIV-infected individuals. There is mounting evidence that in patients with CMV retinitis who have a sustained response to HAART, CMV maintenance treatment can be discontinued without relapse of retinitis. In HAART-naïve individuals with newly diagnosed CMV retinitis, the optimal timing for the initiation of HAART relative to the start of anti-CMV treatment is currently unknown. New local therapies for CMV retinitis (e.g. ganciclovir implant, the new antisense compound fomivirsen) provide treatment options in situations where high local drug delivery is warranted. A treatment algorithm for CMV disease in the HAART era is proposed. In the transplant setting, ganciclovir and foscarnet remain the major compounds used for treatment of CMV disease. In marrow and stem cell transplant recipients, CMV pneumonia still carries a high mortality. Ganciclovir in combination with CMV-specific immunoglobulin or regular intravenous IG remains the treatment of choice for CMV pneumonia; extended antiviral maintenance for several months is recommended in patients with continued immunosuppression. Preemptive treatment based on virologic markers (e.g. pp65 antigenemia, CMV DNA) has been very successful in reducing the incidence of early CMV disease in the transplant setting. The duration of preemptive treatment should be guided by the underlying immunosuppression and virologic markers. Late CMV disease is a challenge in marrow and stem cell transplant recipients, and occurs increasingly in highly immunosuppressed solid organ transplant recipients as well. Recent advances in prophylaxis strategies include oral ganciclovir for liver transplant recipients and valacyclovir for kidney transplant recipients.

Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.

PubMed

Boyer, David S; Yoon, Young Hee; Belfort, Rubens; Bandello, Francesco; Maturi, Raj K; Augustin, Albert J; Li, Xiao-Yan; Cui, Harry; Hashad, Yehia; Whitcup, Scott M

2014-10-01

To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME). Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis. Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography. Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months. The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP). Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (-111.6 μm) and DEX implant 0.35 mg (-107.9 μm) than sham (-41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy. The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Copper diffusion in Ti Si N layers formed by inductively coupled plasma implantation

NASA Astrophysics Data System (ADS)

Ee, Y. C.; Chen, Z.; Law, S. B.; Xu, S.; Yakovlev, N. L.; Lai, M. Y.

2006-11-01

Ternary Ti-Si-N refractory barrier films of 15 nm thick was prepared by low frequency, high density, inductively coupled plasma implantation of N into TixSiy substrate. This leads to the formation of Ti-N and Si-N compounds in the ternary film. Diffusion of copper in the barrier layer after annealing treatment at various temperatures was investigated using time-of-flight secondary ion mass spectrometer (ToF-SIMS) depth profiling, X-ray diffractometer (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) and sheet resistance measurement. The current study found that barrier failure did not occur until 650 °C annealing for 30 min. The failure occurs by the diffusion of copper into the Ti-Si-N film to form Cu-Ti and Cu-N compounds. FESEM surface morphology and EDX show that copper compounds were formed on the ridge areas of the Ti-Si-N film. The sheet resistance verifies the diffusion of Cu into the Ti-Si-N film; there is a sudden drop in the resistance with Cu compound formation. This finding provides a simple and effective method of monitoring Cu diffusion in TiN-based diffusion barriers.

Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure.

PubMed

Akahane, M; Shimizu, T; Kira, T; Onishi, T; Uchihara, Y; Imamura, T; Tanaka, Y

2016-11-01

To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed in vitro, and the appearance of the cell sheets was observed after mechanical retrieval using a scraper. β-tricalcium phosphate (β-TCP) was then wrapped with the cell sheets from the four different groups and subcutaneously implanted into rats. After mechanical retrieval, the osteogenic cell sheets from the MEM, MEM with AscP, and MEM with Dex groups appeared to be fragmented or incomplete structures. The cell sheets cultured with Dex/AscP remained intact after mechanical retrieval, without any identifiable tears. Culture with Dex/AscP increased the mRNA and protein expression of extracellular matrix proteins and cell number compared with those of the other three groups. More bridging bone formation was observed after transplantation of the β-TCP scaffold wrapped with cell sheets cultured with Dex/AscP, than in the other groups. These results suggest that culture with Dex/AscP improves the mechanical integrity of the osteogenic cell sheets, allowing retrieval of the confluent cells in a single cell sheet structure. This method may be beneficial when applied in cases of difficult tissue reconstruction, such as nonunion, bone defects, and osteonecrosis.Cite this article: M. Akahane, T. Shimizu, T. Kira, T. Onishi, Y. Uchihara, T. Imamura, Y. Tanaka. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure. Bone Joint Res 2016;5:569-576. DOI: 10.1302/2046-3758.511.BJR-2016-0013.R1. © 2016 Akahane et al.

Two-year survival of Ahmed valve implantation in the first 2 years of life with and without intraoperative mitomycin-C.

PubMed

Al-Mobarak, Faisal; Khan, Arif O

2009-10-01

To evaluate the effect of intraoperative mitomycin-C (MMC) on polypropylene Ahmed glaucoma valve (AGV) survival 2 years after implantation during the first 2 years of life. Retrospective institutional comparative series (1995-2005). Thirty-one eyes of 27 patients (23 unilateral, 4 bilateral; 16 boys, 11 girls) undergoing AGV implantation at a mean age of 11.1 months (standard deviation [SD], 5.46), all of which had 2 years of regular postoperative follow-up. MMC was applied intraoperatively in those cases in the area of AGV implantation in 16 (52%) and was not applied in 15 (48%). In some eyes, MMC was applied intraoperatively in cases done by the surgeons who routinely used MMC for all AGV implantation in young children. Failure was defined as intraocular pressure (IOP) > 22 mmHg with or without glaucoma medications, the need for an additional procedure for IOP control, or the occurrence of significant complications (e.g., endophthalmitis, retinal detachment, persistent hypotony [IOP < 5 mmHg]). Survival was the absence of failure. Failure or significant complications as defined. Mean survival for the non-MMC eyes (22.15 months; standard error [SE], 1.93) was significantly longer than survival for the MMC eyes (16.25 months; SE, 2.17) by the log-rank test (P = 0.025). The difference in cumulative survival at 2 years was also significantly different by log-rank test (P = 0.001): 80.0% (SE 10.3) and 31.3% (SE 11.6), respectively. Rather than improved survival, intraoperative use of MMC was associated with shorter survival 2 years after AGV implantation during the first 2 years of life. We speculate that MMC-induced tissue death can stimulate a reactive fibrosis around the AGV in very young eyes.

Protective coatings for intraocular wirelessly controlled microrobots for implantation: Corrosion, cell culture, and in vivo animal tests.

PubMed

Pokki, Juho; Ergeneman, Olgaç; Chatzipirpiridis, George; Lühmann, Tessa; Sort, Jordi; Pellicer, Eva; Pot, Simon A; Spiess, Bernhard M; Pané, Salvador; Nelson, Bradley J

2017-05-01

Diseases in the ocular posterior segment are a leading cause of blindness. The surgical skills required to treat them are at the limits of human manipulation ability, and involve the risk of permanent retinal damage. Instrument tethering and design limit accessibility within the eye. Wireless microrobots suturelessly injected into the posterior segment, steered using magnetic manipulation are proposed for procedures involving implantation. Biocompatibility is a prerequisite for these procedures. This article investigates the use of polypyrrole- and gold-coated cobalt-nickel microrobots. While gold has been used in ocular implants, no ocular implantation involving polypyrrole is reported, despite its well-established biocompatibility properties. Coated and uncoated microrobots were investigated for their corrosion properties, and solutions that had contained coated and uncoated microrobots for one week were tested for cytotoxicity by monitoring NIH3T3 cell viability. None of the microrobots showed significant corrosion currents and corrosion potentials were as expected in relation to the intrinsic nobility of the materials. NIH3T3 cell viability was not affected by the release medium, in which coated/uncoated microrobots were stored. In vivo tests inside rabbit eyes were performed using coated microrobots. There were no significant inflammatory responses during the first week after injection. An inflammatory response detected after 2 weeks was likely due to a lack of longer-duration biocompatibility. The results provide valuable information for those who work on implant technology and biocompatibility. Coated microrobots have the potential to facilitate a new generation of surgical treatments, diagnostics and drug-delivery techniques, when implantation in the ocular posterior segment will be possible. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 836-845, 2017. © 2016 Wiley Periodicals, Inc.

Posterior chamber lens implantation with scleral fixation in children with traumatic cataract.

PubMed

Caca, Ihsan; Sahin, Alparslan; Ari, Seyhmus; Alakus, Fuat

2011-01-01

To evaluate the outcomes of posterior chamber lens implantation with scleral fixation (SF-PCIOL) in children with traumatic cataract. Twenty-four eyes of 24 cases were included. All patients had corneal or corneoscleral lacerations that were primarily repaired. Traumatic cataract subsequently developed and SF-PCIOL was performed due to insufficient posterior capsule support. The average age of the patients was 5.8 years (range: 4 to 10 years). All cases had SF-PCIOL implanted via internal route using triangular double scleral flaps made of 9-0 polypropylene after a complete anterior vitrectomy. Average follow-up was 14.6 ± 4.3 months (range: 11 to 18 months). Visual acuity was increased at the last visit in 23 (96%) patients. Common postoperative complications were fibrinous reaction in 6 (25%) patients, transient intraocular pressure increase in 4 (17%) patients, membrane formation requiring removal in 1 (4%) patient, transient intraocular hemorrhage as vitreous hemorrhage in 1 (4%) patient, and retinal detachment in 1 (4%) patient after the postoperative second month. SF-PCIOL is an effective and reliable method in patients with pediatric traumatic cataract who had insufficient posterior capsule support. Copyright 2011, SLACK Incorporated.

High order aberration and straylight evaluation after cataract surgery with implantation of an aspheric, aberration correcting monofocal intraocular lens

PubMed Central

Kretz, Florian T A; Tandogan, Tamer; Khoramnia, Ramin; Auffarth, Gerd U

2015-01-01

AIM To evaluate the quality of vision in respect to high order aberrations and straylight perception after implantation of an aspheric, aberration correcting, monofocal intraocular lens (IOL). METHODS Twenty-one patients (34 eyes) aged 50 to 83y underwent cataract surgery with implantation of an aspheric, aberration correcting IOL (Tecnis ZCB00, Abbott Medical Optics). Three months after surgery they were examined for uncorrected (UDVA) and corrected distance visual acuity (CDVA), contrast sensitivity (CS) under photopic and mesopic conditions with and without glare source, ocular high order aberrations (HOA, Zywave II) and retinal straylight (C-Quant). RESULTS Postoperatively, patients achieved a postoperative CDVA of 0.0 logMAR or better in 97.1% of eyes. Mean values of high order abberations were +0.02±0.27 (primary coma components) and -0.04±0.16 (spherical aberration term). Straylight values of the C-Quant were 1.35±0.44 log which is within normal range of age matched phakic patients. The CS measurements under mesopic and photopic conditions in combination with and without glare did not show any statistical significance in the patient group observed (P≥0.28). CONCLUSION The implantation of an aspherical aberration correcting monofocal IOL after cataract surgery resulted in very low residual higher order aberration (HOA) and normal straylight. PMID:26309872

[Nano-hydroxyapatite/collagen composite for bone repair].

PubMed

Feng, Qing-ling; Cui, Fu-zhai; Zhang, Wei

2002-04-01

To develop nano-hydroxyapatite/collagen (NHAC) composite and test its ability in bone repairing. NHAC composite was developed by biomimetic method. The composite showed some features of natural bone in both composition and microstructure. The minerals could contribute to 50% by weight of the composites in sheet form. The inorganic phase in the composite was carbonate-substituted hydroxyapatite (HA) with low crystallinity and nanometer size. HA precipitates were uniformly distributed on the type I collagen matrix without preferential orientation. The composite exhibited an isotropic mechanical behavior. However, the resistance of the composite to localized pressure could reach the lower limit of that of femur compacta. The tissue response to the NHAC composite implanted in marrow cavity was investigated. Knoop micro-hardness test was performed to compare the mechanical behavior of the composite and bone. At the interface of the implant and marrow tissue, solution-mediated dissolution and macrophage-mediated resorption led to the degradation of the composite, followed by interfacial bone formation by osteoblasts. The process of implant degradation and bone substitution was reminiscent of bone remodeling. The composite can be incorporated into bone metabolism instead of being a permanent implant.

Synthesis of calcium hydrogen phosphate and hydroxyapatite coating on SS316 substrate through pulsed electrodeposition.

PubMed

Chakraborty, Rajib; Sengupta, Srijan; Saha, Partha; Das, Karabi; Das, Siddhartha

2016-12-01

The orthopaedic implants for human body are generally made of different biomaterials like stainless steels or Ti based alloys. However, it has been found that from surface properties point of view, none of these materials is attractive for fast tissue or cell growth on the surface of implant. This is one of the most important criteria to assure quick bonding between implant and body tissues vis-à-vis minimum recovery time for the patient. Keeping in view of the above facts, this work involves the pulsed electro-deposition coating of biocompatible hydroxyapatite and its group compounds from a diluted bath of calcium and phosphate salt at various current densities over the biomaterial sheet of SS316. SEM study confirms different morphologies of the coatings at different current densities. Characterization techniques like X-ray diffraction, SEM with EDX and FTIR have been used to confirm the phase and percentage quantity of hydroxyapatite compound in the depositions. This coating can serve as a medium for faster tissue growth over the metallic implants. Copyright © 2016 Elsevier B.V. All rights reserved.

Dental Cell Sheet Biomimetic Tooth Bud Model

PubMed Central

Monteiro, Nelson; Smith, Elizabeth E.; Angstadt, Shantel; Zhang, Weibo; Khademhosseini, Ali

2016-01-01

Tissue engineering and regenerative medicine technologies offer promising therapies for both medicine and dentistry. Our long-term goal is to create functional biomimetic tooth buds for eventual tooth replacement in humans. Here, our objective was to create a biomimetic 3D tooth bud model consisting of dental epithelial (DE) – dental mesenchymal (DM) cell sheets (CSs) combined with biomimetic enamel organ and pulp organ layers created using GelMA hydrogels. Pig DE or DM cells seeded on temperature-responsive plates at various cell densities (0.02, 0.114 and 0.228 cells 106/cm2) and cultured for 7, 14 and 21 days were used to generate DE and DM cell sheets, respectively. Dental CSs were combined with GelMA encapsulated DE and DM cell layers to form bioengineered 3D tooth buds. Biomimetic 3D tooth bud constructs were cultured in vitro, or implanted in vivo for 3 weeks. Analyses were performed using micro-CT, H&E staining, polarized light (Pol) microscopy, immunofluorescent (IF) and immunohistochemical (IHC) analyses. H&E, IHC and IF analyses showed that in vitro cultured multilayered DE-DM CSs expressed appropriate tooth marker expression patterns including SHH, BMP2, RUNX2, tenascin and syndecan, which normally direct DE-DM interactions, DM cell condensation, and dental cell differentiation. In vivo implanted 3D tooth bud constructs exhibited mineralized tissue formation of specified size and shape, and SHH, BMP2 and RUNX2and dental cell differentiation marker expression. We propose our biomimetic 3D tooth buds as models to study optimized DE-DM cell interactions leading to functional biomimetic replacement tooth formation. PMID:27565550

Long-term outcome after implantation of a suprachoroidal cyclosporine drug delivery device in horses with recurrent uveitis.

PubMed

Gilger, Brian C; Wilkie, David A; Clode, Allison B; McMullen, Richard J; Utter, Mary E; Komaromy, Andras M; Brooks, Dennis E; Salmon, Jacklin H

2010-09-01

To determine the long-term efficacy, complications, and duration of effect of a cyclosporine (CsA) suprachoroidal implant (CSI) in horses with equine recurrent uveitis (ERU). Horses with ERU were treated with a 6-mm diameter, 25 mg, reservoir matrix CsA implant in the deep sclera adjacent to the suprachoroidal space. Horses with follow-up >1 year were examined for frequency of uveitis episodes, complications, and vision at last recheck. Data from 151 eyes of 133 horses from the USA and Europe that had CsA devices implanted for ERU were reviewed. Follow-up time ranged from 13 to 85 months after surgery, with a mean and median follow-up time of 28.9 and 26.3 months, respectively. Overall, at last follow-up 78.8% of eyes were considered visual and the overall mean frequency of uveitis episodes after CSI was 0.09 ± SD 0.08 episodes per month. The most common complications leading to vision loss at last follow-up were persistent uveitis episodes (54%), glaucoma (22%), mature cataracts (16%), and retinal detachment (6%). Persistent uveitis episodes tended to be the highest cause of vision loss in horses with <24 months and >48 months of follow-up. This study demonstrated the long-term maintenance of vision of horses with ERU implanted with a CSI. The increased vision loss related to uveitis episode of inflammation in eyes after the likely depletion of CsA from the CSI suggests that a repeat CSI may be required at or before 48 months after surgery.

Engineering tubular bone using mesenchymal stem cell sheets and coral particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Wenxin; Ma, Dongyang; Yan, Xingrong

Highlights: • We developed a novel engineering strategy to solve the limitations of bone grafts. • We fabricated tubular constructs using cell sheets and coral particles. • The composite constructs showed high radiological density and compressive strength. • These characteristics were similar to those of native bone. -- Abstract: The development of bone tissue engineering has provided new solutions for bone defects. However, the cell-scaffold-based approaches currently in use have several limitations, including low cell seeding rates and poor bone formation capacity. In the present study, we developed a novel strategy to engineer bone grafts using mesenchymal stem cell sheetsmore » and coral particles. Rabbit bone marrow mesenchymal stem cells were continuously cultured to form a cell sheet with osteogenic potential and coral particles were integrated into the sheet. The composite sheet was then wrapped around a cylindrical mandrel to fabricate a tubular construct. The resultant tubular construct was cultured in a spinner-flask bioreactor and subsequently implanted into a subcutaneous pocket in a nude mouse for assessment of its histological characteristics, radiological density and mechanical property. A similar construct assembled from a cell sheet alone acted as a control. In vitro observations demonstrated that the composite construct maintained its tubular shape, and exhibited higher radiological density, compressive strength and greater extracellular matrix deposition than did the control construct. In vivo experiments further revealed that new bone formed ectopically on the composite constructs, so that the 8-week explants of the composite sheets displayed radiological density similar to that of native bone. These results indicate that the strategy of using a combination of a cell sheet and coral particles has great potential for bone tissue engineering and repairing bone defects.« less

Establishment of Epithelial Attachment on Titanium Surface Coated with Platelet Activating Peptide

PubMed Central

Sugawara, Shiho; Maeno, Masahiko; Lee, Cliff; Nagai, Shigemi; Kim, David M.; Da Silva, John; Kondo, Hisatomo

2016-01-01

The aim of this study was to produce epithelial attachment on a typical implant abutment surface of smooth titanium. A challenging complication that hinders the success of dental implants is peri-implantitis. A common cause of peri-implantitis may results from the lack of epithelial sealing at the peri-implant collar. Histologically, epithelial sealing is recognized as the attachment of the basement membrane (BM). BM-attachment is promoted by activated platelet aggregates at surgical wound sites. On the other hand, platelets did not aggregate on smooth titanium, the surface typical of the implant abutment. We then hypothesized that epithelial BM-attachment was produced when titanium surface was modified to allow platelet aggregation. Titanium surfaces were coated with a protease activated receptor 4-activating peptide (PAR4-AP). PAR4-AP coating yielded rapid aggregation of platelets on the titanium surface. Platelet aggregates released robust amount of epithelial chemoattractants (IGF-I, TGF-β) and growth factors (EGF, VEGF) on the titanium surface. Human gingival epithelial cells, when they were co-cultured on the platelet aggregates, successfully attached to the PAR4-AP coated titanium surface with spread laminin5 positive BM and consecutive staining of the epithelial tight junction component ZO1, indicating the formation of complete epithelial sheet. These in-vitro results indicate the establishment of epithelial BM-attachment to the titanium surface. PMID:27741287

Evaluation of Autologous Fascia Implantation With Controlled Release of Fibroblast Growth Factor for Recurrent Laryngeal Nerve Paralysis Due to Long-term Denervation.

PubMed

Nagai, Hiromi; Nishiyama, Koichiro; Seino, Yutomo; Tabata, Yasuhiko; Okamoto, Makito

2016-06-01

Paralyzed tissue due to long-term denervation is resistant to many treatments because it induces irreversible histological changes and disorders of deglutition or phonation. We sought to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on long-term unilateral vocal fold paralysis (UVFP). Unilateral recurrent laryngeal nerve (RLN) section was performed on 20 rats. Five rats were implanted with autologous fascia only (fascia group), and 10 rats were implanted with autologous fascia and a gelatin hydrogel sheet with 1 μg (1 μg bFGF + fascia group) or 0.1 μg (0.1 μg bFGF + fascia group) of bFGF 4 months after RLN section. We evaluated the normalized glottal gap and laryngeal volume and histological changes 3 months after implantation. The normalized glottal gap was significantly reduced in the 3 fascia implantation groups. Normalized laryngeal volume, fat volume, and lateral thyroarytenoid muscle volume were significantly increased in the 2 fascia implantation with bFGF groups. The ATFV with controlled release of bFGF repaired the glottal gap and laryngeal volume after RLN section and may reduce the occurrence of aspiration and hoarseness. We speculate that this treatment improves laryngeal function in long-term RLN denervation. © The Author(s) 2016.

Ultra-Shallow Junctions Fabrication by Plasma Immersion Implantation on PULSION registered Followed by Laser Thermal Processing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torregrosa, Frank; Etienne, Hasnaa; Sempere, Guillaume

In order to achieve the requirements for P+/N junctions for <45 nm ITRS nodes, ultra low energy and high dose implantations are needed. Classical beamline implantation is now limited in low energies, compared to Plasma Immersion Ion Implantation (PIII) which efficiency is no more to prove for the realization of Ultra-Shallow Junctions (USJ) in semiconductor applications : this technique allows to get ultimate shallow profiles (as implanted) due to no lower limitation of energy and high dose rate. Electrical activation is also a big issue since it has to afford high electrical activation rate with very low diffusion. Laser annealingmore » is one of the candidates for the 45 nm node. This paper presents electrical and physico-chemical characterizations of junctions realized with BF3 PIII followed by laser thermal processing with aim to obtain ultra-shallow junctions. Different implantation conditions (acceleration voltage/dose) and laser conditions (laser types, fluence/number of shots) are used for this study. Pre-amorphization is also used to confine the junction depth, and is shown to have a positive effect on junction depth but leads in higher junction leakage due to the remaining of EOR defects. The characterization is done using Optical characterization tool (SEMILAB) for sheet resistance and junction leakage measurements. SIMS is used for Boron profile and junction depth.« less

Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model.

PubMed

Krishnan, Rahul; Arora, Rajan P; Alexander, Michael; White, Sean M; Lamb, Morgan W; Foster, Clarence E; Choi, Bernard; Lakey, Jonathan R T

2014-01-01

Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Juvenile X-linked retinoschisis responsive to intravitreal corticosteroids.

PubMed

Ansari, Waseem H; Browne, Andrew W; Singh, Rishi P

2017-04-01

To report the case of an adult male with X-linked retinoschisis (XLRS) who presented with cystoid macular edema (CME) that responded consistently to treatment with intravitreal steroids. A 39 year old male with unilateral presentation of CME after repair of a retinal detachment secondary to XLRS responded initially to an injection of intravitreal triamcinolone acetonide (IVTA). Central subfield thickness on OCT was reduced. Three months later, the CME recurred and he was unresponsive to topical treatment so repeat IVTA was given, and the CME once again was reduced dramatically. After the next recurrence, intravitreal dexamethasone implant treatment was initiated and successful at treating recurrences in 3 month intervals for 5 additional injections. Finally, an intravitreal fluocinolone acetonide implant was surgically placed with control of CME. Corticosteroids have never been reported to be effective in CME related to XLRS. Here, we document a case of a man who successfully had decrease of intraretinal fluid and schisis with treatment of intravitreal corticosteroids as demonstrated by spectral domain optical coherence tomography.

Multiple Independent Oscillatory Networks in the Degenerating Retina

PubMed Central

Euler, Thomas; Schubert, Timm

2015-01-01

During neuronal degenerative diseases, microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. This can be particularly well observed in the retina, where photoreceptor degeneration triggers rewiring of connections in the retina’s first synaptic layer (e.g., Strettoi et al., 2003; Haq et al., 2014), while the synaptic organization of inner retinal circuits appears to be little affected (O’Brien et al., 2014; Figures 1A,B). Remodeling of (outer) retinal circuits and diminishing light-driven activity due to the loss of functional photoreceptors lead to spontaneous activity that can be observed at different retinal levels (Figure 1C), including the retinal ganglion cells, which display rhythmic spiking activity in the degenerative retina (Margolis et al., 2008; Stasheff, 2008; Menzler and Zeck, 2011; Stasheff et al., 2011). Two networks have been suggested to drive the oscillatory activity in the degenerating retina: a network of remnant cone photoreceptors, rod bipolar cells (RBCs) and horizontal cells in the outer retina (Haq et al., 2014), and the AII amacrine cell-cone bipolar cell network in the inner retina (Borowska et al., 2011). Notably, spontaneous rhythmic activity in the inner retinal network can be triggered in the absence of synaptic remodeling in the outer retina, for example, in the healthy retina after photo-bleaching (Menzler et al., 2014). In addition, the two networks show remarkable differences in their dominant oscillation frequency range as well as in the types and numbers of involved cells (Menzler and Zeck, 2011; Haq et al., 2014). Taken together this suggests that the two networks are self-sustained and can be active independently from each other. However, it is not known if and how they modulate each other. In this mini review, we will discuss: (i) commonalities and differences between these two oscillatory networks as well as possible interaction pathways; (ii) how multiple self-sustained networks may hamper visual restoration strategies employing, for example, microelectronic implants, optogenetics or stem cells, and briefly; and (iii) how the finding of diverse (independent) networks in the degenerative retina may relate to other parts of the neurodegenerative central nervous system. PMID:26617491

Rabbits with naturally occurring cataracts referred for phacoemulsification and intraocular lens implantation: a preliminary study of 12 cases.

PubMed

Sanchez, Rick F; Everson, Richard; Hedley, Joanna; Dawson, Charlotte; Lam, Richard; Priestnall, Simon L; Garcia de Carellan, Alejandra; de Miguel, Cristina; Seymour, Christopher

2017-12-04

To describe the presentation of 15 rabbits with naturally occurring cataracts referred for phacoemulsification surgery, the procedure in 13 cases and the follow-up in 12. Fifteen rabbits (30 eyes), nine of which stopped following visual cues in association with cataract progression. Rabbits underwent preoperative ophthalmic and ocular ultrasound examination. Thirteen rabbits (22 eyes) had mature cataracts. Ten were bilateral and three unilateral. Two rabbits had an anterior chamber abscess. The cataract in one of these was incipient. One rabbit had bilateral immature cataracts. One rabbit had a subluxated lens, and one had a retinal detachment. Thirteen rabbits (22 eyes) underwent phacoemulsification. Eighteen, 13.5-mm capsular tension rings (CTRs) and seventeen, 13-mm IOLs (Acrivet ® , Berlin, Germany) were fitted including one 41D 60V-model, and three 49D and thirteen 58D 20S-models. Intraoperative complications included one unilateral posterior-capsular tear, one lens subluxation, and one expulsive choroidal hemorrhage. One rabbit died during anesthetic recovery. Nine cases were PCR-tested for Encephalitozoon cuniculi, and only three were positive. The median follow-up time was 12 months (4-24 months). Rabbits that were not following visual cues preoperatively did so postoperatively, and surgery resulted in a clear visual axis for the follow-up period in every case except in two, due to reasons other than the surgery. Phacoemulsification with CTR and IOL implantation offers good long-term results and can improve the quality of life of pet rabbits. Retinal detachment, lens luxation, expulsive choroidal hemorrhage, and anesthetic death are potential complications. © 2017 American College of Veterinary Ophthalmologists.

Expanding MIRAgel scleral buckle simulating an orbital tumor in four cases.

PubMed

Shields, Carol L; Demirci, Hakan; Marr, Brian P; Mashayekhi, Arman; Materin, Miguel A; Shields, Jerry A

2005-01-01

To describe four patients with an enlarging orbital mass from a swollen MIRAgel scleral buckle that simulated an orbital neoplasm. In a retrospective, single-center case series at the Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, 4 eyes of 4 patients were referred for evaluation and treatment of a suspected orbital tumor. The initial presenting features were orbital mass (case 1), strabismus (case 2), and conjunctival mass with orbital extension (cases 3 and 4). Each patient vaguely recalled previous uncomplicated retinal detachment surgery 12 to 20 years earlier. Confirmation of the buckling implant material was made with the retina surgeon in 3 cases. A nontender, forniceal conjunctival mass, deep to the Tenon fascia and appearing as a translucent firm elevation was seen in all 4 cases. Axial CT (case 1) revealed a circumscribed anterior temporal orbital mass, believed to be a large inclusion cyst, 4 times thicker than the nasal scleral buckle. Ocular ultrasonography depicted an echolucent mass in the episcleral region (cases 3 and 4) that was 2 times thicker than the nasal scleral buckle (case 3). Excision was attempted in case 1, but only piecemeal removal was achieved, leading to extensive postoperative inflammation and decreased vision. The other 3 cases were followed conservatively without excision because they were each recognized to be a swollen MIRAgel implant and not an orbital tumor. MIRAgel scleral buckle material can greatly enlarge over a period of 10 years and simulate an orbital tumor or orbital cyst. Patients often do not recall details of the retinal surgery. Caution is advised regarding excision of this material because it is friable and can lead to extensive postoperative inflammation.

Intraocular camera for retinal prostheses: Refractive and diffractive lens systems

NASA Astrophysics Data System (ADS)

Hauer, Michelle Christine

The focus of this thesis is on the design and analysis of refractive, diffractive, and hybrid refractive/diffractive lens systems for a miniaturized camera that can be surgically implanted in the crystalline lens sac and is designed to work in conjunction with current and future generation retinal prostheses. The development of such an intraocular camera (IOC) would eliminate the need for an external head-mounted or eyeglass-mounted camera. Placing the camera inside the eye would allow subjects to use their natural eye movements for foveation (attention) instead of more cumbersome head tracking, would notably aid in personal navigation and mobility, and would also be significantly more psychologically appealing from the standpoint of personal appearances. The capability for accommodation with no moving parts or feedback control is incorporated by employing camera designs that exhibit nearly infinite depth of field. Such an ultracompact optical imaging system requires a unique combination of refractive and diffractive optical elements and relaxed system constraints derived from human psychophysics. This configuration necessitates an extremely compact, short focal-length lens system with an f-number close to unity. Initially, these constraints appear highly aggressive from an optical design perspective. However, after careful analysis of the unique imaging requirements of a camera intended to work in conjunction with the relatively low pixellation levels of a retinal microstimulator array, it becomes clear that such a design is not only feasible, but could possibly be implemented with a single lens system.

Preparation and characterization of carbon nanofibrous/hydroxyapatite sheets for bone tissue engineering.

PubMed

Abd El-Aziz, A M; El Backly, Rania M; Taha, Nahla A; El-Maghraby, Azza; Kandil, Sherif H

2017-07-01

Critical size bone defects are orthopedic defects that will not heal without intervention or that will not completely heal over the natural life time of the animal. Although bone generally has the ability to regenerate completely however, critical defects require some sort of scaffold to do so. In the current study we proposed a method to obtain a carbon nanofibrous/Hydroxyapatite (HA) bioactive scaffold. The carbon nanofibrous (CNF) nonwoven fabrics were obtained by the use of the electrospinning process of the polymeric solution of poly acrylonitrile "PAN" and subsequent stabilization and carbonization processes. The CNFs sheets were functionalized by both hydroxyapatite (HA) and bovine serum albumin (BSA). The HA was added to the electrospun solution, but in case of (BSA), it was adsorbed after the carbonization process. The changes in the properties taking place in the precursor sheets were investigated using the characterization methods (SEM, FT-IR, TGA and EDX). The prepared materials were tested for biocompatibility via subcutaneous implantation in New Zealand white rabbits. We successfully prepared biocompatible functionalized sheets, which have been modified with HA or HA and BSA. The sheets that were functionalized by both HA and BSA are more biocompatible with fewer inflammatory cells of (neutrophils and lymphocytes) than ones with only HA over the period of 3weeks. Copyright © 2017 Elsevier B.V. All rights reserved.

Fabrication, vascularization and osteogenic properties of a novel synthetic biomimetic induced membrane for the treatment of large bone defects

PubMed Central

Browne, Christopher; Bishop, Julius; Yang, Yunzhi

2014-01-01

The induced membrane has been widely used in the treatment of large bone defects but continues to be limited by a relatively lengthy healing process and a requisite two stage surgical procedure. Here we report the development and characterization of a synthetic biomimetic induced membrane (BIM) consisting of an inner highly pre-vascularized cell sheet and an outer osteogenic layer using cell sheet engineering. The pre-vascularized inner layer was formed by seeding human umbilical vein endothelial cells (HUVECs) on a cell sheet comprised of a layer of undifferentiated human bone marrow-derived mesenchymal stem cells (hMSCs). The outer osteogenic layer was formed by inducing osteogenic differentiation of hMSCs. In vitro results indicated the undifferentiated hMSCs cell sheet facilitated the alignment of HUVECs and significantly promoted the formation of vascular-like networks. Furthermore, seeded HUVECs rearranged the extracellular matrix produced by hMSCs sheet. After subcutaneously implantation, the composite constructs showed rapid vascularization and anastomosis with the host vascular system, forming functional blood vessels in vivo. Osteogenic potential of the BIM was evidenced by immunohistochemistry staining of osteocalcin, tartrate-resistant acid phosphatase (TRAP) staining, and alizarin red staining. In summary, the synthetic BIM showed rapid vascularization, significant anastomoses, and osteogenic potential in vivo. This synthetic BIM has the potential for treatment of large bone defects in the absence of infection. PMID:24747351

Guided bone regeneration using individualized ceramic sheets.

PubMed

Malmström, J; Anderud, J; Abrahamsson, P; Wälivaara, D-Å; Isaksson, S G; Adolfsson, E

2016-10-01

Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice.

PubMed

Hu, Jingchao; Cao, Yu; Xie, Yilin; Wang, Hua; Fan, Zhipeng; Wang, Jinsong; Zhang, Chunmei; Wang, Jinsong; Wu, Chu-Tse; Wang, Songlin

2016-09-09

Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model. In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation. Our study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm(3)) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm(3)) (P < 0.05). The percentage of bone in the periodontium in the hDPSC injection group was 12.8 ± 4.4 %, while it was 17.4 ± 5.3 % in the hDPSC sheet group (P < 0.05). Both hDPSC injection and cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.

Sudden visual loss after cardiac resynchronization therapy device implantation.

PubMed

De Vitis, Luigi A; Marchese, Alessandro; Giuffrè, Chiara; Carnevali, Adriano; Querques, Lea; Tomasso, Livia; Baldin, Giovanni; Maestranzi, Gisella; Lattanzio, Rosangela; Querques, Giuseppe; Bandello, Francesco

2017-03-10

To report a case of sudden decrease in visual acuity possibly due to a cardiogenic embolism in a patient who underwent cardiac resynchronization therapy (CRT) device implantation. A 62-year-old man with severe left ventricular systolic dysfunction and a left bundle branch block was referred to our department because of a sudden decrease in visual acuity. Nine days earlier, he had undergone cardiac transapical implantation of a CRT device, which was followed, 2 days later, by an inflammatory reaction. The patient underwent several general and ophthalmologic examinations, including multimodal imaging. At presentation, right eye (RE) best-corrected visual acuity (BCVA) was counting fingers and RE pupil was hyporeactive. Fundus examination revealed white-centered hemorrhagic dots suggestive of Roth spots. Fluorescein angiography showed delay in vascular perfusion during early stage, late hyperfluorescence of the macula and optic disk, and peripheral perivascular leakage. The first visual field test showed complete loss of vision RE and a normal left eye. Due to suspected giant cell arteritis, temporal artery biopsy was performed. Thirty minutes after the procedure, an ischemic stroke with right hemisyndrome and aphasia occurred. The RE BCVA worsened to hands motion. Four months later, RE BCVA did not improve, despite improvement in fluorescein angiography inflammatory sign. We report a possible cardiogenic embolism secondary to undiagnosed infective endocarditis causing monocular visual loss after CRT device implantation. It remains unclear how the embolus caused severe functional damage without altering the retinal anatomical structure.

Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens Implantation and Wavefront-guided Laser in Situ Keratomileusis

PubMed Central

Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kawamorita, Takushi

2015-01-01

This study aimed to investigate the effect of myopic defocus on visual acuity after phakic intraocular lens (IOL) implantation and wavefront-guided laser in situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg-LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic and non-cycloplegic correction. We also calculated the modulation transfer function by optical simulation and estimated visual acuity from Campbell & Green’s retinal threshold curve. Visual acuity in the phakic IOL group was significantly better than that in the wfg-LASIK group at myopic defocus levels of 0, –1, and –2 D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus of –3 D (p = 0.30). Similar results were also obtained in a cycloplegic condition. Decimal visual acuity values at a myopic defocus of 0, −1, −2, and -3 D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group, respectively. From clinical and optical viewpoints, phakic IOL implantation was superior to wfg-LASIK in terms of the postoperative visual performance, even in the presence of low to moderate myopic regression. PMID:25994984

Study of the neovascularisation of prefabrication of flaps using a silicone sheet and an isolated arterial pedicle: experimental study in rabbits.

PubMed

Nguyen, The Hoang; Kloeppel, Marcus; Staudenmaier, Rainer; Werner, Jürgen; Biemer, Edgar

2005-01-01

Use of an isolated artery as an implanted pedicle in prefabricated flaps has rarely been reported either clinically or experimentally. In Chinchilla Bastard rabbits (n = 36), we dissected an isolated arterial pedicle from the femoral and saphenous artery, anastomosed it end-to-end to the femoral vein at the inguinal ligament and created an isolated arterial loop pedicle. This was implanted and fixed with polyglactin 9/0 under a random-pattern vascularised abdominal fasciocutaneous flap. The neovascularisation in the prefabricated flaps was evaluated macroscopically, by blood analysis, selective microangiography, and histology. The results showed a progressive degree of neovascularisation that corresponded to the increasing length of time that the pedicle was implanted in the flaps. Twenty days after prefabrication, the abdominal fasciocutaneous flap was readily perfused by the blood supply from the arterial pedicle. The capacity of the vessels in this group as seen on angiograms had increased to 258 vessels (108%) compared with the control group (239 vessels, 100%).

Angle Performance on Optima XE

DOE Office of Scientific and Technical Information (OSTI.GOV)

David, Jonathan; Satoh, Shu

2011-01-07

Angle control on high energy implanters is important due to shrinking device dimensions, and sensitivity to channeling at high beam energies. On Optima XE, beam-to-wafer angles are controlled in both the horizontal and vertical directions. In the horizontal direction, the beam angle is measured through a series of narrow slits, and any angle adjustment is made by steering the beam with the corrector magnet. In the vertical direction, the beam angle is measured through a high aspect ratio mask, and any angle adjustment is made by slightly tilting the wafer platen during implant.Using a sensitive channeling condition, we were ablemore » to quantify the angle repeatability of Optima XE. By quantifying the sheet resistance sensitivity to both horizontal and vertical angle variation, the total angle variation was calculated as 0.04 deg. (1{sigma}). Implants were run over a five week period, with all of the wafers selected from a single boule, in order to control for any crystal cut variation.« less

[Surgical Regeneration Therapy Using Myoblast Sheets for Severe Heart Failure].

PubMed

Sawa, Yoshiki

2017-01-01

Heart failure is a life-threatening disorder worldwide, and the current end-stage therapies for severe heart failure are replacement therapies such as ventricular-assist devices and heart transplantation. Although these therapies have been reported to be useful, there are many issues in terms of the durability, complications, limited donors, adverse effect of continuous administration of immunosuppressive agents, and high costs involved. Recently, regenerative therapy based on genetic, cellular, or tissue engineering techniques has gained attention as a new therapy to overcome the challenges encountered in transplantation medicine. We focused on skeletal myoblasts as the source of progenitor cells for autologous cell transplantation and the cell-sheet technique for site-specific implantation. In vitro studies have reported that myoblast sheets secrete cytoprotective and angiogenic cytokines such as hepatocyte growth factor (HGF). Additionally, in vivo studies using large and small animal models of heart failure, we have shown that myoblast sheets could improve diastolic and systolic performance and enhance angiogenesis and antifibrosis as well as the expression of several cytokines including HGF and vascular endothelial growth factor(VEGF) in the tissues at the transplanted site. Based on the results of these studies, we performed clinical trials using autologous myoblast sheets in ischemic cardiomyopathy (ICM) and dilated cardiomyopathy patients. Some patients showed left ventricular reverse remodeling and improved symptoms and exercise tolerance. Recently, multiple medical institutions including our institution successfully conducted an exploratory, uncontrolled, open-label phase II study in subjects with ICM to validate the efficacy and safety of autologous myoblast sheets. Moreover, as a novel cell source for regenerative medicine, our recent studies demonstrated that induced pluripotent stem cell-derived cardiomyocyte sheets showed electrical and microstructural homogeneity with heart tissue in vitro and in vivo, thus establishing proof of concept in small and large animal models of heart failure.

Au3+ ion implantation on FTO coated glasses: Effect on structural, electrical, optical and phonon properties

NASA Astrophysics Data System (ADS)

Sahu, Bindu; Dey, Ranajit; Bajpai, P. K.

2017-06-01

Effects of 11.00 MeV Au3+ ions implanted in FTO coated (thickness ≈300 nm) silicate glasses on structural, electrical optical and phonon behavior have been explored. It has been observed that metal clustering near the surface and sub-surface region below glass-FTO interface changes electrical and optical properties significantly. Ion implantation does not affect the crystalline structure of the coated films; however, the unit cell volume decreases with increase in fluence and the tetragonal distortion (c/a ratio) also decreases systematically in the implanted samples. The sheet resistivity of the films increases from 11 × 10-5 ohm-cm (in pristine) to 7.5 × 10-4 ohm-cm for highest ion beam fluence ≈1015 ions/cm2. The optical absorption decreases with increasing fluence whereas, the optical transmittance as well as reflectance increases with increasing fluence. The Raman spectra are observed at ∼530 cm-1 and ∼1103 cm-1 in pristine sample. The broad band at 530 cm-1 shifts towards higher wave number in the irradiated samples. This may be correlated with increased disorder and strain relaxation in the samples as a result of ion beam irradiation.

Characteristics of exudative age-related macular degeneration determined in vivo with confocal and indirect infrared imaging.

PubMed

Hartnett, M E; Elsner, A E

1996-01-01

To evaluate the current and future interventions in age-related macular degeneration (AMD), it is essential to delineate the early clinical features associated with later visual loss. The authors describe the retinal pigment epithelium (RPE)/Bruch membrane region in ten patients with advance exudative AMD using current angiographic techniques and a noninvasive method: infrared (IR) imaging with the scanning laser ophthalmoscope. Ten patients with exudative AMD, evidence by choroidal neovascularization (CNV), fibrovascular scar formation, pigment epithelial detachment, or serous subretinal fluid,were examined using IR imaging, fluorescein angiography, indocyanine green angiography, and stereoscopic viewing of fundus slides. The authors determined the number and size of drusen and subretinal deposits and the topographic character of the RPE/Bruch membrane area and of CNV. In all patients, IR imaging yielded the greatest number of drusen and subretinal deposits. Sheets of subretinal material, but few lesions consistent with soft drusen, were seen. Infrared imaging provided topographic information of evolving CNV. Choroidal neovascularization appeared as a complex with a dark central core, an enveloping reflective structure which created a halo-like appearance in the plane of focus, and outer retinal/subretinal striae. Infrared imaging provides a noninvasive, in vivo method to image early changes in the RPE/Bruch membrane. It offers advantages over current imaging techniques by minimizing light scatter through cloudy media and enhancing the ability to image through small pupils, retinal hyperpigmentation, blood, heavy exudation, or subretinal fluid. It provides additional information regarding early CNV, and the character of drusen and subretinal deposits.

Ahmed Glaucoma Valve Implantation for Uveitic Glaucoma Secondary to Behçet Disease.

PubMed

Satana, Banu; Yalvac, Ilgaz S; Sungur, Gulten; Eksioglu, Umit; Basarir, Berna; Altan, Cigdem; Duman, Sunay

2015-01-01

To evaluate outcomes of patients with uveitic glaucoma secondary to Behçet disease (BD) who underwent Ahmed glaucoma valve (AGV) implantation. A retrospective chart review of 14 eyes of 10 patients with uveitic glaucoma associated with BD who underwent AGV implantation at a tertiary referral center. Treatment success was defined as intraocular pressure (IOP) between 6 and 21 mm Hg with or without antiglaucoma medication, without further additional glaucoma surgery or loss of light perception. The main outcome measures were IOP, best-corrected visual acuity measured with Snellen charts, and number of glaucoma medications. Mean duration of postoperative follow-up was 18.2±6.6 months (range, 6 to 31 mo). Of the 14 eyes, 10 (71.4%) were pseudophakic and 5 (35.7%) had primary AGV implantation without a history of previous glaucoma surgery. At the most recent follow-up visit, 13 of the 14 eyes had an IOP between 6 and 21 mm Hg. Mean IOP was significantly reduced during follow-up, as compared with preoperative values (P≤0.005). The cumulative probability of surgical success rate was 90.9% at 18 months based on Kaplan-Meier survival analysis. The mean number of antiglaucoma medications required to achieve the desired IOP decreased from 3.4±0.5 preoperatively to 1.0±1.1 postoperatively (P≤0.05). Visual acuity loss of >2 lines occurred in 4 eyes (28.5%) due to optic atrophy associated with retinal vasculitis. Temporary hypotony developed during follow-up in 4 eyes (28.5%) at first postoperative week. For the management of uveitic glaucoma associated with BD, AGV implantation is a successful method for glaucoma control but requires additional surgical interventions for high early hypotony rates.

Visual outcomes after lensectomy and iris claw artisan intraocular lens implantation in patients with Marfan syndrome.

PubMed

Rabie, Hossein Mohammad; Malekifar, Parviz; Javadi, Mohammad Ali; Roshandel, Danial; Esfandiari, Hamed

2017-08-01

To review our experience with crystalline lens extraction and iris claw Artisan IOL implantation in patients with lens subluxation secondary to Marfan syndrome. A retrospective analysis of 12 eyes of 9 patients with lens subluxation due to Marfan syndrome who underwent crystalline lens removal and Artisan IOL (Ophtec, Groningen, Netherlands) implantation. A questionnaire of pre- and post-operative data, including demographics, pre- and postoperative comorbidities and complications was completed. Patients were evaluated for visual outcome and occurrence of complications. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and spherical equivalents (SE) were compared before and after lens extraction and IOL insertion. The mean age of the participants was 30.03 ± 15.02 years, and mean post-operative follow-up time was 44.5 ± 16.4 months. Mean BCVA also showed a significant improvement from 0.5 ± 0.3 at the baseline to 0.2 ± 0.2 post-operatively (P = 0.006). SE changed significantly from -11.38 ± 1.99 preoperatively to -0.45 ± 1.65 post-operatively (P = 0.003). All eyes had the IOL implanted at desired position. Post-operative complications were retinal detachment in one case and IOL dislocation in another patient. No other complication such as ocular hypertension, angle abnormalities, clinical cystoids macular edema, and corneal decompensation was observed during the follow-up period. Artisan IOL implantation after lens extraction appears to be an attractive alternative for optical correction in cases of Marfan syndrome with ectopia lentis. It confers a significant improvement in visual acuity with reasonable risk profile.

Culture-expanded mesenchymal stem cell sheets enhance extraction-site alveolar bone growth: An animal study.

PubMed

Mu, S; Tee, B C; Emam, H; Zhou, Y; Sun, Z

2018-04-06

Impaired bone formation of the buccal alveolar plate after tooth extraction during adolescence increases the difficulty of future implant restoration. This study was undertaken to assess the feasibility and efficacy of transplanting autogenous scaffold-free culture-expanded mesenchymal stem cell (MSC) sheets to the buccal alveolar bone surface to stimulate local bone growth. Mandibular bone marrow was aspirated from 3-month-old pigs (n = 5), from which MSCs were isolated and culture expanded. Triple-layer MSC sheets were then fabricated using temperature-responsive tissue culture plates. One month after bone marrow aspirations, the same pigs underwent bilateral extraction of mandibular primary molars, immediately followed by transplantation of 3 autogenous triple-layer MSC sheets on to the subperiosteal buccal alveolar surface of 1 randomly chosen side. The contralateral side (control) underwent the same periosteal reflection surgery without receiving MSC sheet transplantation. Six weeks later, the animals were killed and specimens from both sides were immediately harvested for radiographic and histological analysis. Buccal alveolar bone thickness, tissue mineral density (TMD), mineral apposition and bone volume fraction (BV/TV) were quantified and compared between the MSC sheet and control sides using paired t-tests. Triple-layer MSC sheets were reliably fabricated and the majority of cells remained vital before transplantation. The thickness of buccal bone tended to increase with MSC sheet transplantation (P = .18), with 4 of 5 animals showing an average of 1.82 ± 0.73 mm thicker bone on the MSC sheet side than the control side. After being normalized by the TMD of intracortical bone, the TMD of surface cortical bone was 0.5-fold higher on the MSC sheet side than the control side (P < .05). Likewise, the BV/TV measurements of the buccal surface region were also 0.4-fold higher on the MSC sheet side than the control side (P < .05) after being normalized by measurements from the intracortical region. Mineral apposition measurements were not different between the 2 sides. Mandibular marrow-derived MSCs can be fabricated into cell sheets and autogenous transplantation of MSC sheets onto the subperiosteal buccal alveolar bone surface at the tooth-extraction site may increase local bone density. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

EDITORIAL: Special issue containing contributions from the 39th Neural Interfaces Conference Special issue containing contributions from the 39th Neural Interfaces Conference

NASA Astrophysics Data System (ADS)

Weiland, James D.

2011-07-01

Implantable neural interfaces provide substantial benefits to individuals with neurological disorders. That was the unequivocal message delivered by speaker after speaker from the podium of the 39th Neural Interfaces Conference (NIC2010) held in Long Beach, California, in June 2010. Giving benefit to patients is the most important measure for any biomedical technology, and myriad presentations at NIC2010 made clear that implantable neurostimulation technology has achieved this goal. Cochlear implants allow deaf people to communicate through speech. Deep brain stimulators give back mobility and dexterity necessary for so many daily tasks that are often taken for granted. Chronic pain can be alleviated through spinal cord stimulation. Motor prosthesis systems have been demonstrated in humans, through both reanimation of paralyzed limbs and neural control of robotic arms. Earlier this year, a retinal prosthesis was approved for sale in Europe, providing some hope for the blind. In sum, current clinical implants have been tremendously beneficial for today's patients and experimental systems that will be translated to the clinic promise to expand the number of people helped through bioelectronic therapies. Yet there are significant opportunities for improvement. For sensory prostheses, patients report an artificial sensation, clearly different from the natural sensation they remember. Neuromodulation systems, such as deep brain stimulation and pain stimulators, often have side effects that are tolerated as long as the side effects are less impactful than the disease. The papers published in the special issue from NIC2010 reflect the maturing and expanding field of neural interfaces. Our field has moved past proof-of-principle demonstrations and is now focusing on proving the longevity required for clinical implementation of new devices, extending existing approaches to new diseases and improving current devices for better outcomes. Closed-loop neuromodulation is a strategy that can potentially optimize dosing, reduce side effects and extend implant battery life. The article by Liang et al investigates methods for closed loop control of epilepsy, using neural recording to detect imminent seizures and stimulation to halt the aberrant neural activity leading to seizure. Liu et al report on a model of basal ganglia function that could lead to optimized, closed-loop stimulation to reduce symptoms of Parkinson's disease while avoiding side effects. Our laboratory, as described in Ray et al, is investigating the interface between stimulating microelectrodes and the retina, to inform the design of a high-resolution retinal prosthesis. Three contributions address the issue of long-term stability of cortical recording, which remains a major hurdle to implementation of neural recording systems. The Utah group reports on the in vitro testing of a completely implantable, wireless neural recording system, demonstrating almost one year of reliable performance under simulated implant conditions. Shenoy's laboratory at Stanford demonstrates that useful signals can be recorded from research animals for over 2.5 years. Lempka et al describe a modeling approach to analyzing intracortical microelectrode recordings. These findings represent real and significant progress towards overcoming the final barriers to implementation of a reliable cortical interface. Planning is well underway for the 40th Neural Interfaces Conference, which will be held in Salt Lake City, Utah, in June 2012. The conference promises to continue the NIC tradition of showcasing the latest results from clinical trials of neural interface therapies while providing ample time for dynamic exchange amongst the interdisciplinary audience of engineers, scientists and clinicians.

Low-Temperature Carrier Transport in Ionic-Liquid-Gated Hydrogen-Terminated Silicon

NASA Astrophysics Data System (ADS)

Sasama, Yosuke; Yamaguchi, Takahide; Tanaka, Masashi; Takeya, Hiroyuki; Takano, Yoshihiko

2017-11-01

We fabricated ionic-liquid-gated field-effect transistors on the hydrogen-terminated (111)-oriented surface of undoped silicon. Ion implantation underneath electrodes leads to good ohmic contacts, which persist at low temperatures down to 1.4 K. The sheet resistance of the channel decreases by more than five orders of magnitude as the gate voltage is changed from 0 to -1.6 V at 220 K. This is caused by the accumulation of hole carriers. The sheet resistance shows thermally activated behavior at temperatures below 10 K, which is attributed to hopping transport of the carriers. The activation energy decreases towards zero with increasing carrier density, suggesting the approach to an insulator-metal transition. We also report the variation of device characteristics induced by repeated sweeps of the gate voltage.

Solute diffusion through fibrotic tissue formed around protective cage system for implantable devices.

PubMed

Prihandana, Gunawan Setia; Ito, Hikaru; Tanimura, Kohei; Yagi, Hiroshi; Hori, Yuki; Soykan, Orhan; Sudo, Ryo; Miki, Norihisa

2015-08-01

This article presents the concept of an implantable cage system that can house and protect implanted biomedical sensing and therapeutic devices in the body. Cylinder-shaped cages made of porous polyvinyl alcohol (PVA) sheets with an 80-µm pore size and/or stainless steel meshes with 0.54-mm openings were implanted subcutaneously in the dorsal region of rats for 5 weeks. Analysis of the explanted cages showed the formation of fibrosis tissue around the cages. PVA cages had fibrotic tissue growing mostly along the outer surface of cages, while stainless steel cages had fibrotic tissue growing into the inside surface of the cage structure, due to the larger porosity of the stainless steel meshes. As the detection of target molecules with short time lags for biosensors and mass transport with low diffusion resistance into and out of certain therapeutic devices are critical for the success of such devices, we examined whether the fibrous tissue formed around the cages were permeable to molecules of our interest. For that purpose, bath diffusion and microfluidic chamber diffusion experiments using solutions containing the target molecules were performed. Diffusion of sodium, potassium and urea through the fibrosis tissue was confirmed, thus suggesting the potential of these cylindrical cages surrounded by fibrosis tissue to successfully encase implantable sensors and therapeutic apparatus. © 2014 Wiley Periodicals, Inc.

Comparative evaluation of absorbable hemostats: advantages of fibrin-based sheets.

PubMed

Krishnan, Lissy K; Mohanty, Mira; Umashankar, P R; Lal, Arthur Vijayan

2004-11-01

Bioactive hemostats and wound dressings consist of either inherently active materials or act as delivery vehicles which contain such materials. Fibrin is a natural hemostat and scaffold, guiding the direction of wound contraction and closure. In order to improve the ease of application of liquid fibrin glue, we have made a freeze-dried form of polymerized fibrin that supports hemostasis and wound healing. The bleeding from the middle ear artery of rabbits was found to be arrested instantaneously on application of fibrin sheets, even when the animal was heparinized systemically. As the fibrin sheet was found to be fragile, gelatin was incorporated to the sheet and thus the mechanical stability was improved without compromising the hemostatic effect. The efficacy of the fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was compared with commercially available hemostats, Abgel (cross-linked gelatin) and Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was studied by analyzing the liver tissue 15 days after application. While the hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel and Abgel were not capable of arresting the bleeding quickly. Gross analysis of tissue on the 15th day of application, visibly, Abgel was not only degraded but resulted in severe adhesions of internal organs and histologically capsule formation around the implant was evident. Though Surgicel was also seen as cream soft material on the site of application that joined two pieces of liver, there was no adhesion of other internal organs and histologically, immune reaction and foreign-body-type giant cells were present in large amounts. Fibrin was not found grossly on application site whereas fibrin-gelatin was seen as a small white spot. Granulation tissue formation and cell migration into the fibrin-based sheets were evident, and therefore, fibrin-based sheets are not only efficient hemostats but showed optimum degradation and wound healing.

Outer retinal corrugations in age-related macular degeneration.

PubMed

Ooto, Sotaro; Vongkulsiri, Sritatath; Sato, Taku; Suzuki, Mihoko; Curcio, Christine A; Spaide, Richard F

2014-07-01

Optical coherence tomography (OCT) abnormalities of age-related macular degeneration (AMD) have not been fully characterized because of the complex morphology and a lack of correlative histologic studies. Expansion of our ability to interpret increasing attributes brings us closer to the goal of in vivo histologic analysis of the eye by OCT. To describe a new outer retinal finding of AMD using spectral-domain (SD) OCT and suggest histopathologic correlates. Twenty-five eyes of 16 patients with AMD with severe atrophy due to either choroidal neovascularization (CNV) or geographic atrophy (GA) and 53 donor eyes of 53 patients with late AMD were included. Imaging studies were conducted at a referral retinal practice and histopathology was done at a university research laboratory. Findings in the outer retina were evaluated in SD-OCT images in eyes with atrophy of the retinal pigment epithelium (RPE) and compared with histopathologic findings in eyes with GA or CNV that also showed loss of the RPE. Spectral-domain OCT and histologic characteristics of the outer retina. The mean (SD) age of the 16 patients was 82.7 (7.9) years. Twenty eyes had CNV and 5 eyes had GA. The mean best-corrected visual acuity was 0.800 logMAR (interquartile range, 0.350-1.000 logMAR), a Snellen equivalent of 20/126. A curvilinear hyperreflective density was identified above the Bruch membrane line within the atrophic area in the SD-OCT images. At the internal border, the material was contiguous with the outer portion of the RPE band. Below the material was a relatively hyporeflective space. The material was thrown into folds in cases with atrophy following CNV or was seen as a sheet with numerous bumps in eyes with GA. Review of histopathologic findings of eyes with advanced GA and CNV revealed a rippled layer of basal laminar deposits in an area of RPE atrophy that was located in the same level as the curvilinear line seen in the OCT images. We have described a new entity, termed outer retinal corrugations, which may correspond to histological findings of basal laminar deposits, extracellular deposits that persist in eyes with late AMD. Observation of this undulating band does not necessarily mean there is exudation or leakage; as a consequence, these patients do not need treatment based on this solitary finding.

Computational study of culture conditions and nutrient supply in a hollow membrane sheet bioreactor for large-scale bone tissue engineering.

PubMed

Khademi, Ramin; Mohebbi-Kalhori, Davod; Hadjizadeh, Afra

2014-03-01

Successful bone tissue culture in a large implant is still a challenge. We have previously developed a porous hollow membrane sheet (HMSh) for tissue engineering applications (Afra Hadjizadeh and Davod Mohebbi-Kalhori, J Biomed. Mater. Res. Part A [2]). This study aims to investigate culture conditions and nutrient supply in a bioreactor made of HMSh. For this purpose, hydrodynamic and mass transport behavior in the newly proposed hollow membrane sheet bioreactor including a lumen region and porous membrane (scaffold) for supporting and feeding cells with a grooved section for accommodating gel-cell matrix was numerically studied. A finite element method was used for solving the governing equations in both homogenous and porous media. Furthermore, the cell resistance and waste production have been included in a 3D mathematical model. The influences of different bioreactor design parameters and the scaffold properties which determine the HMSh bioreactor performance and various operating conditions were discussed in detail. The obtained results illustrated that the novel scaffold can be employed in the large-scale applications in bone tissue engineering.

Image Processing Strategies Based on a Visual Saliency Model for Object Recognition Under Simulated Prosthetic Vision.

PubMed

Wang, Jing; Li, Heng; Fu, Weizhen; Chen, Yao; Li, Liming; Lyu, Qing; Han, Tingting; Chai, Xinyu

2016-01-01

Retinal prostheses have the potential to restore partial vision. Object recognition in scenes of daily life is one of the essential tasks for implant wearers. Still limited by the low-resolution visual percepts provided by retinal prostheses, it is important to investigate and apply image processing methods to convey more useful visual information to the wearers. We proposed two image processing strategies based on Itti's visual saliency map, region of interest (ROI) extraction, and image segmentation. Itti's saliency model generated a saliency map from the original image, in which salient regions were grouped into ROI by the fuzzy c-means clustering. Then Grabcut generated a proto-object from the ROI labeled image which was recombined with background and enhanced in two ways--8-4 separated pixelization (8-4 SP) and background edge extraction (BEE). Results showed that both 8-4 SP and BEE had significantly higher recognition accuracy in comparison with direct pixelization (DP). Each saliency-based image processing strategy was subject to the performance of image segmentation. Under good and perfect segmentation conditions, BEE and 8-4 SP obtained noticeably higher recognition accuracy than DP, and under bad segmentation condition, only BEE boosted the performance. The application of saliency-based image processing strategies was verified to be beneficial to object recognition in daily scenes under simulated prosthetic vision. They are hoped to help the development of the image processing module for future retinal prostheses, and thus provide more benefit for the patients. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Development of a Magnetic Attachment Method for Bionic Eye Applications.

PubMed

Fox, Kate; Meffin, Hamish; Burns, Owen; Abbott, Carla J; Allen, Penelope J; Opie, Nicholas L; McGowan, Ceara; Yeoh, Jonathan; Ahnood, Arman; Luu, Chi D; Cicione, Rosemary; Saunders, Alexia L; McPhedran, Michelle; Cardamone, Lisa; Villalobos, Joel; Garrett, David J; Nayagam, David A X; Apollo, Nicholas V; Ganesan, Kumaravelu; Shivdasani, Mohit N; Stacey, Alastair; Escudie, Mathilde; Lichter, Samantha; Shepherd, Robert K; Prawer, Steven

2016-03-01

Successful visual prostheses require stable, long-term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Elevated intracranial pressure causes optic nerve and retinal ganglion cell degeneration in mice.

PubMed

Nusbaum, Derek M; Wu, Samuel M; Frankfort, Benjamin J

2015-07-01

The purpose of this study was to develop a novel experimental system for the modulation and measurement of intracranial pressure (ICP), and to use this system to assess the impact of elevated ICP on the optic nerve and retinal ganglion cells (RGCs) in CD1 mice. This system involved surgical implantation of an infusion cannula and a radiowave based pressure monitoring probe through the skull and into the subarachnoid space. The infusion cannula was used to increase ICP, which was measured by the probe and transmitted to a nearby receiver. The system provided robust and consistent ICP waveforms, was well tolerated, and was stable over time. ICP was elevated to approximately 30 mmHg for one week, after which we assessed changes in optic nerve structure with transmission electron microscopy in cross section and RGC numbers with antibody staining in retinal flat mounts. ICP elevation resulted in optic nerve axonal loss and disorganization, as well as RGC soma loss. We conclude that the controlled manipulation of ICP in active, awake mice is possible, despite their small size. Furthermore, ICP elevation results in visual system phenotypes of optic nerve and RGC degeneration, suggesting that this model can be used to study the impact of ICP on the visual system. Potentially, this model can also be used to study the relationship between ICP and IOP, as well diseases impacted by ICP variation such as glaucoma, idiopathic intracranial hypertension, and the spaceflight-related visual impairment intracranial pressure syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Computed tomographic assessment of the causal factors of unsuccessful medialization thyroplasty.

PubMed

Iwahashi, Toshihiko; Ogawa, Makoto; Hosokawa, Kiyohito; Mochizuki, Ryuichi; Inohara, Hidenori

2015-03-01

The present results demonstrate that a small implant size, undercorrection of the vocal fold, antero-posterior implant malposition, and the use of expanded polytetrafluoroethylene (ePTFE) are the primary factors that cause a poor outcome of medialization thyroplasty (MT). To assess the postoperative laryngeal condition using computed tomography (CT) in patients with unilateral vocal fold paralysis who underwent MT alone, and to identify the primary causal factors in terms of the surgical procedures that affect the outcomes of MT. Twenty-two patients who underwent MT alone were divided into two groups based on either the maximal phonation time or the perceived vocal breathiness. Two laryngologists assessed the postoperative laryngeal CT images during sustained vowel phonation and judged whether there were abnormalities of the arytenoid cartilage position, window position, implant size, and implant position, as well as the degree of correction of the vocal fold. As implant material, a silicone block, ePTFE, and hydroxyapatite had been inserted in 2, 9, and 11 patients, respectively. Comparisons of the prevalence of abnormalities in the abovementioned factors between the different outcomes and between the types of material used for the implant were performed. Twelve patients with a poor outcome and 10 with a good outcome showed 36 and 18 abnormal findings identified by either of the two laryngologists, respectively. In the poor outcome group, a smaller implant size and undercorrection of the vocal fold showed both high kappa values and a significantly higher prevalence than those in the good outcome group (p < 0.001 and p < 0.05), respectively. The comparison between material types demonstrated that the sheet-like material (ePTFE) group exhibited a significantly higher prevalence of undercorrection than the block-like material group (p < 0.05).

Learning to see again: biological constraints on cortical plasticity and the implications for sight restoration technologies

NASA Astrophysics Data System (ADS)

Beyeler, Michael; Rokem, Ariel; Boynton, Geoffrey M.; Fine, Ione

2017-10-01

The ‘bionic eye’—so long a dream of the future—is finally becoming a reality with retinal prostheses available to patients in both the US and Europe. However, clinical experience with these implants has made it apparent that the visual information provided by these devices differs substantially from normal sight. Consequently, the ability of patients to learn to make use of this abnormal retinal input plays a critical role in whether or not some functional vision is successfully regained. The goal of the present review is to summarize the vast basic science literature on developmental and adult cortical plasticity with an emphasis on how this literature might relate to the field of prosthetic vision. We begin with describing the distortion and information loss likely to be experienced by visual prosthesis users. We then define cortical plasticity and perceptual learning, and describe what is known, and what is unknown, about visual plasticity across the hierarchy of brain regions involved in visual processing, and across different stages of life. We close by discussing what is known about brain plasticity in sight restoration patients and discuss biological mechanisms that might eventually be harnessed to improve visual learning in these patients.

Learning to see again: Biological constraints on cortical plasticity and the implications for sight restoration technologies

PubMed Central

Beyeler, Michael; Rokem, Ariel; Boynton, Geoffrey M.; Fine, Ione

2018-01-01

The “bionic eye” – so long a dream of the future – is finally becoming a reality with retinal prostheses available to patients in both the US and Europe. However, clinical experience with these implants has made it apparent that the vision provided by these devices differs substantially from normal sight. Consequently, the ability to learn to make use of this abnormal retinal input plays a critical role in whether or not some functional vision is successfully regained. The goal of the present review is to summarize the vast basic science literature on developmental and adult cortical plasticity with an emphasis on how this literature might relate to the field of prosthetic vision. We begin with describing the distortion and information loss likely to be experienced by visual prosthesis users. We then define cortical plasticity and perceptual learning, and describe what is known, and what is unknown, about visual plasticity across the hierarchy of brain regions involved in visual processing, and across different stages of life. We close by discussing what is known about brain plasticity in sight restoration patients and discuss biological mechanisms that might eventually be harnessed to improve visual learning in these patients. PMID:28612755

Experimental study on axial pedicled composite flap prefabrication with high density porous polyethylene implants: medporocutaneous flap.

PubMed

Kocman, A Emre; Kose, Aydan A; Karabagli, Yakup; Baycu, Cengiz; Cetin, Cengiz

2008-01-01

Composite flaps including soft tissues with bone or cartilage are widely used in reconstruction of three-dimensional defects, but have some disadvantages. Flap prefabrication with alloplastic implants is an alternative procedure. Axial pattern vascularised high density porous polyethylene (HDPP) implants are capable of sustaining skin grafts. The purpose of this study was to examine the vascularisation pattern of the skin island in a composite flap prefabrication model prepared with vascularised HDPP implants. Forty male Wistar rats divided into four groups were used. A 9.5 x 6 x 2 mm HDPP block was centered on the dissected saphenous pedicle and anchored under the abdominal skin in the experimental group I (n=10). In experimental group II (n=10) saphenous artery and vein were put between the skin and the implant. Thus, the structures were laid as skin, HDPP block, pedicle in experimental group I and skin, pedicle, HDPP block in experimental group II. HDPP block-implanted and pedicle-implanted only groups served as control groups I and II, respectively. Eight weeks after prefabrication, skin islands 1.5 x 5 cm in size incorporated with implants were elevated based on saphenous vessels in the experimental groups and skin islands only based on the pedicle in control group II. Skin islands of the same dimensions were raised as grafts in control group I. Nylon sheets were put under the flaps and grafts to prevent vascularisation from the recipient bed. Flap viability was assessed by measuring the surface area on the 7th day. Total necrosis developed in composite grafts of control group I. Flap survival was higher in experimental group II and control group II (45% and 46.8%) than in group I (29.28%). Histologic studies demonstrated fibrovascular ingrowth into the HDPP implants, except in control group I, with significant inflammatory response and necrosis. Vascularisation of skin and implants from the pedicle was seen also microangiographically. In conclusion, a composite flap prefabrication model including vascularised HDPP implant, skin and vascular carrier was developed. This new flap was termed a 'medporocutaneous flap'.

Collective epithelial cell sheet adhesion and migration on polyelectrolyte multilayers with uniform and gradients of compliance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, Jessica S.; Schlenoff, Joseph B.; Keller, Thomas C.S., E-mail: tkeller@bio.fsu.edu

Polyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked, UV-crosslinked to a uniform stiffness, or UV-crosslinked with an edge mask or through a neutral density optical gradient filter to form continuous compliance gradients were used to investigate how differences in PEMU stiffness affect the adhesion andmore » migration of epithelial cell sheets from scales of the fish Poecilia sphenops (Black Molly) and Carassius auratus (Comet Goldfish). During the progressive collective cell migration, the edge cells (also known as ‘leader’ cells) in the sheets on softer uncrosslinked PEMUs and less crosslinked regions of the gradient formed more actin filaments and vinculin-containing adherens junctions and focal adhesions than formed in the sheet cells on stiffer PEMUs or glass. During sheet migration, the ratio of edge cell to internal cell (also known as ‘follower’ cells) motilities were greater on the softer PEMUs than on the stiffer PEMUs or glass, causing tension to develop across the sheet and periods of retraction, during which the edge cells lost adhesion to the substrate and regions of the sheet retracted toward the more adherent internal cell region. These retraction events were inhibited by the myosin II inhibitor Blebbistatin, which reduced the motility velocity ratios to those for sheets on the stiffer PEMUs. Blebbistatin also caused disassembly of actin filaments, reorganization of focal adhesions, increased cell spreading at the leading edge, as well as loss of edge cell-cell connections in epithelial cell sheets on all surfaces. Interestingly, cells throughout the interior region of the sheets on uncrosslinked PEMUs retained their actin and vinculin organization at adherens junctions after treatment with Blebbistatin. Like Blebbistatin, a Rho-kinase (ROCK) inhibitor, Y27632, promoted loss of cell-cell connections between edge cells, whereas a Rac1 inhibitor, NSC23766, primarily altered the lamellipodial protrusion in edge cells. Compliance gradient PAH-PEMUs promoted durotaxis of the cell sheets but not of individual keratocytes, demonstrating durotaxis, like plithotaxis, is an emergent property of cell sheet organization. - Highlights: • Fish scale cell sheets migrate on PAH-PAABp polyelectrolyte multilayers. • Sheets migrating on softer PEMUs periodically retract. • Sheets durotax on modulus gradients. • Myosin II inhibitors inhibit sheet integrity and migration.« less

Spectroscopic studies of the silicone oil impact on the ophthalmic hydrogel based materials conducted in time dependent mode

NASA Astrophysics Data System (ADS)

Chamerski, Kordian; Stopa, Marcin; Jelen, Piotr; Lesniak, Magdalena; Sitarz, Maciej; Filipecki, Jacek

2018-03-01

Silicone oil is the one of the artificial materials used in vitreoretinal surgery for retinal detachment treatment. Since the silicone oil is sometimes applied along with intraocular lens (IOL) implantation the direct influence of silicone oil on the artificial implant should be taken into account. Presented study was performed in order to determine the time-dependent impact of silicone oil on hydrogel based ophthalmic materials. Two kinds of IOLs based on hydroxyethyl 2-methacrylate (HEMA) hydrogel material were immersed in silicone oil based on linear poly(dimethylsiloxane) (PDMS). Incubation in oil medium was performed in 37 °C for 1, 3 and 6 months. After appropriate period of the incubation samples were examined by means of FTIR-ATR method as the technique of surface study as well as Positron Annihilation Lifetime Spectroscopy (PALS) as the method of internal structure investigation. Results obtained during the study revealed that silicone oil is not capable to penetrate the internal structure of investigated materials and its impact has come down to interaction with the samples surfaces only.

Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study

PubMed Central

2014-01-01

Background Adverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes. Methods Consecutive patients presenting with ALTR from two major hip implant classes (N = 54 patients with Dual-Modular Neck implant; N = 14 patients with Metal-on-Metal implant) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy and cellular composition was assessed using immunohistochemistry. Results Length of implantation was shorter in the DMN group versus MoM THA group (21.3 [8.4] months versus 43.6 [13.8] months respectively; p < 0.005) suggesting differences in implant performance. Morphologic examination revealed a common spectrum of neo-synovial proliferation and necrosis in both groups. Macrophages were more commonly present in diffuse sheets (Grade 3) in the MoM relative to DMN group (p = 0.016). Perivascular lymphocytes with germinal centers (Grade 4) were more common in the DMN group, which trended towards significance (p = 0.066). Qualitative differences in corrosion product morphology were seen between the two groups. Immunohistochemistry showed features of a CD4 and GATA-3 rich lymphocyte reaction in both implants, with increased ratios of perivascular T-cell relative to B-cell markers in the DMN relative to the MoM group (p = 0.032). Conclusion Our results demonstrate that both implant classes display common features of neo-synovial proliferation and necrosis with a CD4 and GATA-3 rich inflammatory infiltrate. Qualitative differences in corrosion product appearance, macrophage morphology, and lymphocyte distributions were seen between the two implant types. Our data suggests that ALTR represents a histological spectrum with implant-based features. PMID:25242891

Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study.

PubMed

Perino, Giorgio; Ricciardi, Benjamin F; Jerabek, Seth A; Martignoni, Guido; Wilner, Gabrielle; Maass, Dan; Goldring, Steven R; Purdue, P Edward

2014-01-01

Adverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes. Consecutive patients presenting with ALTR from two major hip implant classes (N = 54 patients with Dual-Modular Neck implant; N = 14 patients with Metal-on-Metal implant) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy and cellular composition was assessed using immunohistochemistry. Length of implantation was shorter in the DMN group versus MoM THA group (21.3 [8.4] months versus 43.6 [13.8] months respectively; p < 0.005) suggesting differences in implant performance. Morphologic examination revealed a common spectrum of neo-synovial proliferation and necrosis in both groups. Macrophages were more commonly present in diffuse sheets (Grade 3) in the MoM relative to DMN group (p = 0.016). Perivascular lymphocytes with germinal centers (Grade 4) were more common in the DMN group, which trended towards significance (p = 0.066). Qualitative differences in corrosion product morphology were seen between the two groups. Immunohistochemistry showed features of a CD4 and GATA-3 rich lymphocyte reaction in both implants, with increased ratios of perivascular T-cell relative to B-cell markers in the DMN relative to the MoM group (p = 0.032). Our results demonstrate that both implant classes display common features of neo-synovial proliferation and necrosis with a CD4 and GATA-3 rich inflammatory infiltrate. Qualitative differences in corrosion product appearance, macrophage morphology, and lymphocyte distributions were seen between the two implant types. Our data suggests that ALTR represents a histological spectrum with implant-based features.

Cochlear Implantation in Patients With Usher Syndrome Type IIa Increases Performance and Quality of Life.

PubMed

Hartel, Bas P; van Nierop, Josephine W I; Huinck, Wendy J; Rotteveel, Liselotte J C; Mylanus, Emmanuel A M; Snik, Ad F; Kunst, Henricus P M; Pennings, Ronald J E

2017-07-01

Usher syndrome type IIa (USH2a) is characterized by congenital moderate to severe hearing impairment and retinitis pigmentosa. Hearing rehabilitation starts in early childhood with the application of hearing aids. In some patients with USH2a, severe progression of hearing impairment leads to insufficient speech intelligibility with hearing aids and issues with adequate communication and safety. Cochlear implantation (CI) is the next step in rehabilitation of such patients. This study evaluates the performance and benefit of CI in patients with USH2a. Retrospective case-control study to evaluate the performance and benefit of CI in 16 postlingually deaf adults (eight patients with USH2a and eight matched controls). Performance and benefit were evaluated by a speech intelligibility test and three quality-of-life questionnaires. Patients with USH2a with a mean age of 59 years at implantation exhibited good performance after CI. The phoneme scores improved significantly from 41 to 87% in patients with USH2a (p = 0.02) and from 30 to 86% in the control group (p = 0.001). The results of the questionnaire survey demonstrated a clear benefit from CI. There were no differences in performance or benefit between patients with USH2a and control patients before and after CI. CI increases speech intelligibility and improves quality of life in patients with USH2a.

Objective measurement of the optical image quality in the human eye

NASA Astrophysics Data System (ADS)

Navarro, Rafael M.

2001-05-01

This communication reviews some recent studies on the optical performance of the human eye. Although the retinal image cannot be recorded directly, different objective methods have been developed, which permit to determine optical quality parameters, such as the Point Spread Function (PSF), the Modulation Transfer Function (MTF), the geometrical ray aberrations or the wavefront distortions, in the living human eye. These methods have been applied in both basic and applied research. This includes the measurement of the optical performance of the eye across visual field, the optical quality of eyes with intraocular lens implants, the aberrations induced by LASIK refractive surgery, or the manufacture of customized phase plates to compensate the wavefront aberration in the eye.

Management of enophthalmos and superior sulcus deformity induced by the silent sinus syndrome.

PubMed

Ando, Andre; Cruz, Antonio Augusto Velasco

2005-01-01

Silent sinus syndrome is a dysfunction of the maxillary sinus that induces a progressive and asymptomatic enophthalmos with prominent deep superior sulcus deformity. Two cases of silent sinus syndrome are reported, and the simultaneous management of both enophthalmos and superior sulcus deformity caused by this syndrome is discussed. The patients underwent surgical endoscopic maxillary meatotomy and transconjunctival subperiosteal implantation of porous polyethylene sheets. The treatment successfully corrected both the enophthalmos and the upper eyelid sulcus deformity. However, small degrees of vertical eye dystopia were observed. Silent sinus syndrome is a rare cause of enophthalmos and superior sulcus deformity. Orbital floor implants can be used to increase the volume of the orbital contents, but vertical eye dystopia is likely to be induced if this method of treatment is the only option chosen.

Patch esophagoplasty using an in-body-tissue-engineered collagenous connective tissue membrane.

PubMed

Okuyama, Hiroomi; Umeda, Satoshi; Takama, Yuichi; Terasawa, Takeshi; Nakayama, Yasuhide

2018-02-01

Although many approaches to esophageal replacement have been investigated, these efforts have thus far only met limited success. In-body-tissue-engineered connective tissue tubes have been reported to be effective as vascular replacement grafts. The aim of this study was to investigate the usefulness of an In-body-tissue-engineered collagenous connective tissue membrane, "Biosheet", as a novel esophageal scaffold in a beagle model. We prepared Biosheets by embedding specially designed molds into subcutaneous pouches in beagles. After 1-2months, the molds, which were filled with ingrown connective tissues, were harvested. Rectangular-shaped Biosheets (10×20mm) were then implanted to replace defects of the same size that had been created in the cervical esophagus of the beagle. An endoscopic evaluation was performed at 4 and 12weeks after implantation. The esophagus was harvested and subjected to a histological evaluation at 4 (n=2) and 12weeks (n=2) after implantation. The animal study protocols were approved by the National Cerebral and Cardiovascular Centre Research Institute Committee (No. 16048). The Biosheets showed sufficient strength and flexibility to replace the esophagus defect. All animals survived with full oral feeding during the study period. No anastomotic leakage was observed. An endoscopic study at 4 and 12weeks after implantation revealed that the anastomotic sites and the internal surface of the Biosheets were smooth, without stenosis. A histological analysis at 4weeks after implantation demonstrated that stratified squamous epithelium was regenerated on the internal surface of the Biosheets. A histological analysis at 12weeks after implantation showed the regeneration of muscle tissue in the implanted Biosheets. The long-term results of patch esophagoplasty using Biosheets showed regeneration of stratified squamous epithelium and muscular tissues in the implanted sheets. These results suggest that Biosheets may be useful as a novel esophageal scaffold. Copyright © 2017 Elsevier Inc. All rights reserved.

An array of highly flexible electrodes with a tailored configuration locked by gelatin during implantation-initial evaluation in cortex cerebri of awake rats.

PubMed

Agorelius, Johan; Tsanakalis, Fotios; Friberg, Annika; Thorbergsson, Palmi T; Pettersson, Lina M E; Schouenborg, Jens

2015-01-01

A major challenge in the field of neural interfaces is to overcome the problem of poor stability of neuronal recordings, which impedes long-term studies of individual neurons in the brain. Conceivably, unstable recordings reflect relative movements between electrode and tissue. To address this challenge, we have developed a new ultra-flexible electrode array and evaluated its performance in awake non-restrained animals. An array of eight separated gold leads (4 × 10 μm), individually flexible in 3D, were cut from a gold sheet using laser milling and insulated with Parylene C. To provide structural support during implantation into rat cortex, the electrode array was embedded in a hard gelatin based material, which dissolves after implantation. Recordings were made during 3 weeks. At termination, the animals were perfused with fixative and frozen to prevent dislocation of the implanted electrodes. A thick slice of brain tissue, with the electrode array still in situ, was made transparent using methyl salicylate to evaluate the conformation of the implanted electrode array. Median noise levels and signal/noise remained relatively stable during the 3 week observation period; 4.3-5.9 μV and 2.8-4.2, respectively. The spike amplitudes were often quite stable within recording sessions and for 15% of recordings where single-units were identified, the highest-SNR unit had an amplitude higher than 150 μV. In addition, high correlations (>0.96) between unit waveforms recorded at different time points were obtained for 58% of the electrode sites. The structure of the electrode array was well preserved 3 weeks after implantation. A new implantable multichannel neural interface, comprising electrodes individually flexible in 3D that retain its architecture and functionality after implantation has been developed. Since the new neural interface design is adaptable, it offers a versatile tool to explore the function of various brain structures.

Histologic Evaluation of a Polylactic Acid Confluent Sheet in the Treatment of Osseous Defects,

DTIC Science & Technology

1992-01-01

Cobb, DDS, PhD * John C. Reed, DDS + Caesar E. Solano, DMD + W. Robert Hiatt, DDS + • Departments of Periodontics and Oral Biology, University of...may be employed as a matrix for osseous grafting, for the occlusion of large bony defects, for soft tissue contour defects, and also as a bone plating...trabecular bone. Further, the periosteum regenerated as a confluent layer of fibrous connective tissue covering the superior aspect of the implant material

A technique of experimental and numerical analysis of influence of defects in the intraocular lens on the retinal image quality

NASA Astrophysics Data System (ADS)

Geniusz, Malwina; ZajÄ c, Marek

2016-09-01

Intraocular lens (IOL) is an artificial lens implanted into the eye in order to restore correct vision after the removal of natural lens cloudy due to cataract. The IOL prolonged stay in the eyeball causes the creation of different changes on the surface and inside the implant mainly in form of small-size local defects such as vacuoles and calcium deposites. Their presence worsens the imaging properties of the eye mainly due to occurence of scattered light thus deteriorating the vision quality of patients after cataract surgery. It is very difficult to study influence the effects of these changes on image quality in real patients. To avoid these difficulties two other possibilities were chosen: the analysis of the image obtained in an optomechanical eye model with artificially aged IOL as well as numerical calculation of the image characteristics while the eye lens is burdened with adequately modeled defects. In experiments the optomechanical model of an eye consisting of a glass "cornea", chamber filled with liquid where the IOL under investigation was inserted and a high resulution CCC detector serving as a "retina" was used. The Modulation Transfer Function (MTF) of such "eye" was evaluated on the basis of image of an edge. Experiments show that there is significant connection between ageing defects and decrease in MTF parameters. Numerical part was performed with a computer programme for optical imaging analysis (OpticStudio Professional, Zemax Professional from Radiant Zemax, LLC). On the basis of Atchison eye model with lens burdened with defects Modulation Transfer Functio was calculated. Particular parameters of defects used in a numerical model were based on own measurements. Numerical simulation also show significant connection between ageing defects and decrease of MTF parameters. With this technique the influence of types, density and distribution of local defect in the IOL on the retinal image quality can be evaluated quickly without the need of performing very difficult and even dangereous experiments on real human patients.

Fourier Transform Infrared and Resonance Raman Spectroscopic Studies of Bacteriorhodopsin.

NASA Astrophysics Data System (ADS)

Earnest, Thomas Nixon

Fourier transform infrared and resonance Raman spectroscopy were used to investigate the structure and function of the light-activated, transmembrane proton pump, bacteriorhodopsin, from the purple membrane of Halobacterium halobium. Bacteriorhodopsin (bR) is a 27,000 dalton integral membrane protein consisting of 248 amino acids with a retinylidene chromophore. Absorption of a photon leads to the translocation of one or two protons from the inside of the cell to the outside. Resonance Raman spectroscopy allows for the study of the configuration of retinal in bR and its photointermediates by the selective enhancement of vibrational modes of the chromophore. This technique was used to determine that the chromophore is attached to lysine-216 in both the bR _{570} and the M _{412} intermediates. In bR with tyrosine-64 selectively nitrated or aminated, the chromophore appears to have the same configuration in that bR _{570} (all- trans) and M _{412} (13- cis) states as it does in unmodified bR. Polarized Fourier transform infrared spectroscopy (FTIR) permits the study of the direction of transition dipole moments arising from molecular vibrations of the protein and the retinal chromophore. The orientation of alpha helical and beta sheet components was determined for bR with the average helical tilt found to lie mostly parallel to the membrane normal. The beta sheet structures also exhibit an IR linear dichroism for the amide I and amide II bands which suggest that the peptide backbone is mostly perpendicular to the membrane plane although it is difficult to determine whether the bands originate from sheet or turn components. The orientation of secondary structure components of the C-1 (residues 72-248) and C-2 (residues 1-71) fragments were also investigated to determine the structure of these putative membrane protein folding intermediates. Polarized, low temperature FTIR -difference spectroscopy was then used to investigate the structure of bR as it undergoes phototransitions from the light-adapted state, bR_{570} , to the K_{630} and M_{412} intermediates. The linear dichroism of C=C and C-C stretching modes, and the hydrogen out-of-plane (HOOP) modes of the chromophore show that the long axis of the polyene is 20-25^ circ out of the membrane plane and that the polyene plane is oriented mostly perpendicular to the membrane plane. Transition dipole moments from protein components are also investigated to determine the orientation of protein groups which undergo changes during the photocycle.

IFESS 2005 Special Session 5 Artifical Vision. Final progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiland, James D.

A special session on visual prostheses was held during the Annual Meeting of the International Functional Electrical Stimulation Society (IFESS), in Montreal, Canada, July 5-9, 2005. IFESS is a meeting that typically attracts researchers in implantable nerve stimulators, functional electrical stimulation, and rehabilitation. All of these areas have significant overlap with the retinal prosthesis, but these areas have decades of research behind them. The special session provided a forum for researchers with vast experience in nerve stimulation to interact with leading research in retinal and cortical visual prostheses. The grant paid for the travel and conference costs of the presentersmore » in the session. The session was chaired by James Weiland (the PI on this grant). The session co-chair was Phil Troyk, Ph.D., from the Illinois Institute of Technology. The Department of Energy was acknowledged at the start of the session as the sponsor. The following talks were delivered: Clinical Trial of a Prototype Retinal Prosthesis James Weiland, Ph.D. Doheny Eye Institute, Los Angeles, California The U.S. Department of Energy's Artificial Sight Program Elias Greenbaum, Ph.D. Oak Ridge National Laboratory, Oak Ridge, Tennessee A 16-Channel stimulator ASIC for use in an intracortical visual prosthesis Phillip R. Troyk, Ph.D. Illinois Institute of Technology, Chicago, Illinois Two approaches to the Optic Nerve Visual Prosthesis Jean Delbeke, M.D. University Cath de Louvain, Louvain, Belgium Design and Implementation of High Power Efficiency Modules for a Cortical Visual Stimulator Mohammad Sawan, Ph.D. Ecole Polytechnique de Montreal, Montreal, Canada Remaining funds from the grant were used to support Dr. Weiland's travel to the Association for Research in Vision and Ophthalmology in May 2006, with DOE approval, where several projects, supported by the DOE artificial retina program, were presented.« less

A Bruch's membrane substitute fabricated from silk fibroin supports the function of retinal pigment epithelial cells in vitro.

PubMed

Shadforth, Audra M A; Suzuki, Shuko; Theodoropoulos, Christina; Richardson, Neil A; Chirila, Traian V; Harkin, Damien G

2017-06-01

Silk fibroin provides a promising biomaterial for ocular tissue reconstruction, including the damaged outer blood-retinal barrier of patients afflicted with age-related macular degeneration (AMD). The aim of the present study was to evaluate the function of retinal pigment epithelial (RPE) cells in vitro, when grown on fibroin membranes manufactured to a thickness similar to that of Bruch's membrane (3 µm). Confluent cultures of RPE cells (ARPE-19) were established on fibroin membranes and maintained under conditions designed to promote maturation over 4 months. Control cultures were grown on polyester cell culture well inserts (Transwell ® ). Cultures established on either material developed a cobblestone morphology, with partial pigmentation, within 12 weeks. Immunocytochemistry at 16 weeks revealed a similar distribution pattern between cultures for F-actin, ZO-1, ezrin, cytokeratin pair 8/18, RPE-65 and Na + /K + -ATPase. Electron microscopy revealed that cultures grown on fibroin displayed a rounder apical surface with a more dense distribution of microvilli. Both cultures avidly ingested fluorescent microspheres coated with vitronectin and bovine serum albumin (BSA), but not controls coated with BSA alone. VEGF and PEDF were detected in the conditioned media collected from above and below the two membrane types. Levels of PEDF were significantly higher than for VEGF on both membranes and a trend was observed towards larger amounts of PEDF in apical compartments. These findings demonstrated that RPE cell functions on fibroin membranes are equivalent to those observed for standard test materials (polyester membranes). As such, these studies support advancement to studies of RPE cell implantation on fibroin membranes in a preclinical model. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

[Clinical experiences after implantation of various lens types in silicon oil tamponade].

PubMed

Effert, R; Lommatzsch, A; Wessing, A

1996-06-01

A tamponade of the vitreous space with silicone oil will obligatory lead to cataract after 6 to 12 months. Today it is easily possible, to implant an artificial lense in silicone oil filled eyes. However the combination of an artificial lense and silicone oil will lead to a strong inflammation in the anterior segment of the eye. 22 pseudophacic patients with silicone oil tamponade were examined 2 to 6 months after the operation. In 12 patients simple artificial lenses were implanted, in 10 patients heparin modified lenses were implanted. In 10 cases the lens was implanted followed by the insufflation of silicone oil in the vitreous cavity, in 2 cases a lens was implanted in a silicone oil filled eye and the silicon oil was not removed. In 8 cases the implantation of the artificial lens has been performed some months to years before the insufflation of the silicone oil. The indication for the silicon oil tamponade was a PVR retinal detachment in all cases. The following parameters were examined: Reaction of the pupil to light, pupil round or oval in miosis, examination of the fundus peripherie possible after mydriasis, fixation of the iris with parts of the capsula or with the anterior surface of the lens? In addition in 12 cases the postoperative refraction was compared with the results of the biometry, which was performed before the operation. In the cases with a simple lens in about 50% an incomplete miosis or an oval pupil because of fixation of the iris with parts of the capsula or with the anterior surface of the lense could be observed. In the cases with heparin modified lenses these complications could be observed in 20%. In all cases a strong opacification of the capsula was seen. In 8 of 12 cases with combined procedure a small hyperopia was measured, in 4 cases a large deviation was measured. The implantation of an artificial lens in silicone oil filled eyes is an alternative to the aphacic status with an Ando Iridectomy. Obviously heparin modified lenses have advantages in these cases. Because of the strong cataract formation we suggest to remove the anterior and the posterior capsula in the first operative session and to implant the haptics of the lens into the sulcus. Because of the high rate of complications generally first a stable retina condition should be reached before the implanation of an artificial lens is performed.

Mechanical and biological evaluations of beta-tricalcium phosphate/silicone rubber composite as a novel soft-tissue implant.

PubMed

Zhang, Yi-ming; Wang, Shao-liang; Lei, Ze-yuan; Fan, Dong-li

2009-09-01

Although silicone rubber (SR) implants are most commonly used and effective for soft-tissue augmentation, they still have been implicated in many adverse reactions. To overcome this problem, a novel composite beta-tricalcium phosphate/silicone rubber (beta-TCP/SR) was prepared by adding beta-TCP into a SR matrix. This study was to evaluate its application potential by investigating the mechanical properties and biocompatibility of beta-TCP/SR. Mechanical properties, including Shore A hardness and tensile strength, were evaluated with 3-mm-thick samples and a universal testing machine. Cytocompatibility tests were conducted in vitro using 0.2-mm-thick beta-TCP/SR samples by seeding fibroblasts onto different samples. Soft-tissue response to beta-TCP/SR and pull-out measurements were investigated 4 weeks and 24 weeks after implantation. The main mechanical properties were all significantly changed after mixing beta-TCP into the SR matrix, except for tearing strength. The cytocompatibility test showed enhanced adhesion and proliferation of fibroblasts onto beta-TCP/SR. Fibrous tissue ingrowth after resorption of beta-TCP was observed by in vivo histologic analysis. The peri-implant capsules in the beta-TCP/SR group were thinner than in the SR group 24 weeks after implantation. In a 24-week test, the maximum force required to pull out the beta-TCP/SR sheet was about six times greater than that needed for SR. Although some mechanical properties were significantly changed, the results of the cytocompatibility test and in vivo animal study still suggest that beta-TCP/SR may be more suitable as a soft-tissue implant than SR and has the potential to be used in plastic surgery.

Comparison of Visian toric collamer lens and toric acrylic intraocular lens implantation for the treatment of myopia with astigmatism

PubMed Central

Ammar, Hatem; Anbar, Mohamed; Abdellah, Marwa M

2017-01-01

Purpose To compare the efficacy and outcome of phakic toric implantable collamer lens (TICL) and refractive clear lens extraction with AcrySof Toric intraocular lens (TIOL) implantation for the treatment of myopic astigmatism. Patients and methods This study assessed eyes with myopic astigmatism >−1 D and ≤−4 D with a spherical equivalent >10 D or <10 D if the patients were unsuitable for corneal refractive surgery. These eyes were divided into group A, in which Visian Toric ICL™ Phakic TICL was implanted, and group B, which involved clear lens extraction with implantation of an AcrySof IQ toric SN60T3-9™ IOL. The outcome and complications were evaluated. Results This study enrolled 63 eyes of 38 patients with a follow-up period of at least 6 months. The mean postoperative spherical equivalent was −0.19±0.31 D in group A and −0.21±0.28 D in group B (P=0.69). The mean postoperative cylinder value was −0.46±0.53 D in group A and −0.32±0.41 D in group B (P=0.35). Postoperative cylinder was <1 D in 76.47% and 79.31% of eyes in groups A and B, respectively. The mean endothelial cell count was reduced by 4.32% in group A and by 5.32% in group B (P=0.003). The mean postoperative intraocular pressure increased insignificantly in group A (P=0.22) and reduced significantly in group B (P=0.004). The complication rate was 11.76% in group A and 6.90% in group B. Conclusion Both procedures showed predictable results and good visual results. However, the loss of accommodation and risk of retinal complications in the TIOL group suggest that the use of TICL for myopic astigmatism is a better choice in younger patients. PMID:28096654

Correlating optical bench performance with clinical defocus curves in varifocal and trifocal intraocular lenses.

PubMed

Plaza-Puche, Ana B; Alió, Jorge L; MacRae, Scott; Zheleznyak, Len; Sala, Esperanza; Yoon, Geunyoung

2015-05-01

To investigate the correlations existing between a trifocal intraocular lens (IOL) and a varifocal IOL using the "ex vivo" optical bench through-focus image quality analysis and the clinical visual performance in real patients by study of the defocus curves. This prospective, consecutive, nonrandomized, comparative study included a total of 64 eyes of 42 patients. Three groups of eyes were differentiated according to the IOL implanted: 22 eyes implanted with the varifocal Lentis Mplus LS-313 IOL (Oculentis GmbH, Berlin, Germany); 22 eyes implanted with the trifocal FineVision IOL (Physiol, Liege, Belgium), and 20 eyes implanted with the monofocal Acrysof SA60AT IOL (Alcon Laboratories, Inc., Fort Worth, TX). Visual outcomes and defocus curve were evaluated postoperatively. Optical bench through-focus performance was quantified by computing an image quality metric and the cross-correlation coefficient between an unaberrated reference image and captured retinal images from a model eye with a 3.0-mm artificial pupil. Statistically significant differences among defocus curves of different IOLs were detected for the levels of defocus from -4.00 to -1.00 diopters (D) (P < .01). Significant correlations were found between the optical bench image quality metric results and logMAR visual acuity scale in all groups (Lentis Mplus group: r = -0.97, P < .01; FineVision group: r = -0.82, P < .01; Acrys of group: r = -0.99, P < .01). Linear predicting models were obtained. Significant correlations were found between logMAR visual acuity and image quality metric for the multifocal and monofocal IOLs analyzed. This finding enables surgeons to predict visual outcomes from the optical bench analysis. Copyright 2015, SLACK Incorporated.

Study on electrical properties of metal/GaSb junctions using metal-GaSb alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishi, Koichi, E-mail: nishi@mosfet.t.u-tokyo.ac.jp; Yokoyama, Masafumi; Kim, Sanghyeon

2014-01-21

We study the metal-GaSb alloy formation, the structural properties and the electrical characteristics of the metal-alloy/GaSb diodes by employing metal materials such as Ni, Pd, Co, Ti, Al, and Ta, in order to clarify metals suitable for GaSb p-channel metal-oxide-semiconductor field-effect transistors (pMOSFETs) as metal-GaSb alloy source/drain (S/D). It is found that Ni, Pd, Co, and Ti can form alloy with GaSb by rapid thermal annealing at 250, 250, 350, and 450 °C, respectively. The Ni-GaSb and Pd-GaSb alloy formation temperature of 250 °C is lower than the conventional dopant activation annealing for ion implantation, which enable us to lower the processmore » temperature. The alloy layers show lower sheet resistance (R{sub Sheet}) than that of p{sup +}-GaSb layer formed by ion implantation and activation annealing. We also study the electrical characteristics of the metal-alloy/GaSb junctions. The alloy/n-GaSb contact has large Schottky barrier height (ϕ{sub B}) for electrons, ∼0.6 eV, and low ϕ{sub B} for holes, ∼0.2 eV, which enable us to realize high on/off ratio in pMOSFETs. We have found that the Ni-GaSb/GaSb Schottky junction shows the best electrical characteristics with ideal factor (n) of 1.1 and on-current/off-current ratio (I{sub on}/I{sub off}) of ∼10{sup 4} among the metal-GaSb alloy/GaSb junctions evaluated in the present study. These electrical properties are also superior to those of a p{sup +}-n diode fabricated by Be ion implantation with activation annealing at 350 °C. As a result, the Ni-GaSb alloy can be regarded as one of the best materials to realize metal S/D in GaSb pMOSFETs.« less

Scale-up of water-based spider silk film casting using a film applicator.

PubMed

Agostini, Elisa; Winter, Gerhard; Engert, Julia

2017-10-30

Spider silk proteins for applications in drug delivery have attracted an increased interest during the past years. Some possible future medical applications for this biocompatible and biodegradable material are scaffolds for tissue engineering, implantable drug delivery systems and coatings for implants. Recently, we reported on the preparation of water-based spider silk films for drug delivery applications. In the current study, we describe the development of a manufacturing technique for casting larger spider silk films from aqueous solution employing a film applicator. Films were characterized in terms of morphology, water solubility, protein secondary structure, thermal stability, and mechanical properties. Different post-treatments were evaluated (phosphate ions, ethanol, steam sterilization and water vapor) to increase the content of β-sheets thereby achieving water insolubility of the films. Finally, the mechanical properties of the spider silk films were improved by incorporating 2-pyrrolidone as plasticizer. Copyright © 2017 Elsevier B.V. All rights reserved.

[Medpor plus titanic mesh implant in the repair of orbital blowout fractures].

PubMed

Han, Xiao-hui; Zhang, Jia-yu; Cai, Jian-qiu; Shi, Ming-guang

2011-05-10

To study the efficacy of porous polyethylene (Medpor) plus titanic mesh sheets in the repair of orbital blowout fractures. A total of 20 patients underwent open surgical reduction with the combined usage of Medpor and titanic mesh. And they were followed up for average period of 14.5 months (range: 9 - 18). There is no infection or extrusion of medpor and titanic mesh in follow-up periods. There was no instance of decreased visual acuity at post-operation. And all cases of enophthalmos were corrected. The post-operative protrusion degree of both eyes was almost identical at less than 2 mm. The movement of eye balls was satisfactory in all directions. Diplopia disappeared in 18 cases with a cure rate of 90%, 1 case improved and 1 case persisted. Medpor plus titanic mesh implant is a safe and effective treatment in the repair of orbital blow out fractures.

Optimum DMOS cell doping profiles for high-voltage discrete and integrated device technologies

NASA Astrophysics Data System (ADS)

Shenai, Krishna

1992-05-01

It is shown that the implantation and activation sequences of B and As result in significant variations in the contact resistance and p-base sheet resistance beneath the n+-source diffusion of a DMOSFET cell. For identical process parameters, the contact resistance of As-doped n+ silicon was significantly improved when high-dose B was implanted due to higher As surface concentration. The SUPREM III process modeling results were found to be in qualitative agreement with the measured spreading resistance profiles and the discrepancies could be attributed to larger high-temperature diffusion constants used in SUPREM III and the coupled As-B diffusion/activation effects that are not accounted for in process modeling. The experimental results are discussed within the framework of fabricating high-performance DMOSFET cells and CMOS high-voltage devices on the same chip for discrete and smart-power applications.

Solvent-free biodegradable scleral plugs providing sustained release of vancomycin, amikacin, and dexamethasone--an in vivo study.

PubMed

Peng, Yi-Jie; Kau, Yi-Chuan; Wen, Chin-Wei; Liu, Kuo-Sheng; Liu, Shih-Jung

2010-08-01

Delivering effective drugs at sufficiently high concentrations to the area of infection is a standard treatment for infectious disease, such as endophthalmitis. This is currently done by empirical trans pars plana intravitreal injection of both antibiotics directed against gram-positive and gram-negative microorganisms and steroids. However, injections by needles repeatedly may increase the risks of intraocular infection and hemorrhage, as well as retinal detachment. This article explores the alternative of using biodegradable polymers as scleral plugs for a long-term drug release in vivo. To manufacture plugs, poly(lactide-glycolide) copolymers were first mixed with vancomycin, amikacin, and dexamethasone. The mixture was compressed and sintered at 55 degrees C to form scleral plugs 1.4 mm in diameter. Biodegradable scleral plugs released high concentrations of antibiotics (well above the minimum inhibitory concentrations, MIC) and steroids in vivo for the period of time needed to treat intraocular infection. In addition, no major complications such as infectious or sterile endophthalmitis, retinal detachment, ocular phthisis, or uvea protrusion at sclerotomy site were observed throughout the experiment. The sclerotomy wound healed after total degradation of the scleral implants without leakage or local necrosis. Antibiotic/steroid-impregnated biodegradable scleral plugs may have a potential role in the treatment of various intraocular infections. (c) 2010 Wiley Periodicals, Inc.

Prewarping techniques in imaging: applications in nanotechnology and biotechnology

NASA Astrophysics Data System (ADS)

Poonawala, Amyn; Milanfar, Peyman

2005-03-01

In all imaging systems, the underlying process introduces undesirable distortions that cause the output signal to be a warped version of the input. When the input to such systems can be controlled, pre-warping techniques can be employed which consist of systematically modifying the input such that it cancels out (or compensates for) the process losses. In this paper, we focus on the mask (reticle) design problem for 'optical micro-lithography', a process similar to photographic printing used for transferring binary circuit patterns onto silicon wafers. We use a pixel-based mask representation and model the above process as a cascade of convolution (aerial image formation) and thresholding (high-contrast recording) operations. The pre-distorted mask is obtained by minimizing the norm of the difference between the 'desired' output image and the 'reproduced' output image. We employ the regularization framework to ensure that the resulting masks are close-to-binary as well as simple and easy to fabricate. Finally, we provide insight into two additional applications of pre-warping techniques. First is 'e-beam lithography', used for fabricating nano-scale structures, and second is 'electronic visual prosthesis' which aims at providing limited vision to the blind by using a prosthetic retinally implanted chip capable of electrically stimulating the retinal neuron cells.

Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.

PubMed

Riahi, Zied; Bonnet, Crystel; Zainine, Rim; Lahbib, Saida; Bouyacoub, Yosra; Bechraoui, Rym; Marrakchi, Jihène; Hardelin, Jean-Pierre; Louha, Malek; Largueche, Leila; Ben Yahia, Salim; Kheirallah, Moncef; Elmatri, Leila; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

2015-01-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3) are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys), in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24), and a nonsense mutation, c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss.

The effect of physiologic aqueous solutions on the perovskite material lead-lanthanum-zirconium titanate (PLZT): potential retinotoxicity.

PubMed

Foster, William J; Meen, James K; Fox, Donald A

2013-03-01

Perovskite compounds, including lead-lanthanum-zirconium titanate (PLZT), have wide technological application because of their unique physical properties. The use of PLZT in neuro-prosthetic systems, such as retinal implants, has been discussed in a number of publications. Since inorganic lead is a retinotoxic compound that produces retinal degeneration, the long-term stability of PLZT in aqueous biological solutions must be determined. We evaluated the stability and effects of prolonged immersion of a PLZT-coated crystal in a buffered balanced salt solution. Scanning Electron Microscopy and Electron Dispersive Spectroscopy (EDS) using a JEOL JSM 5410 microscope equipped with EDS were utilized to evaluate the samples before and after prolonged immersion. We found that lead and other constituents of PLZT leached into the surrounding aqueous medium. By comparing the unit cell of PLZT with that of CaTiO(3), which has been found to react with aqueous fluids, Lead is in the same site in PLZT as Ca is in CaTiO(3). It is thus reasonable that PLZT will react with aqueous solutions. The results suggest that PLZT must either be coated with a protective layer or is not appropriate for long-term in vivo or in vitro biological applications.

Erosion and intrusion of silicone rubber scleral buckle. Presentation and management.

PubMed

Nguyen, Q D; Lashkari, K; Hirose, T; Pruett, R C; McMeel, J W; Schepens, C L

2001-01-01

To describe the clinical presentation and management of erosion and intrusion of silicone rubber implants that are used in scleral buckling procedures for the treatment of retinal detachment. The authors identified four patients from their practices during the last 20 years (1978-1998) who had erosion or intrusion of silicone rubber scleral buckles that were used to manage retinal detachment. Approximately 4400 scleral buckling procedures were performed during this period. A retrospective review of the medical records of all patients was performed. Factors that influenced management decisions concerning the intruding buckle are emphasized. All four patients had myopia. The interval between placement of the scleral buckle and development of intrusion ranged from 1 to 20 years. The buckles were intrascleral in three cases and episcleral in one. Recurrent detachment and vitreous hemorrhage were indications for surgical intervention in three cases. After the surgical removal of buckling elements, visual acuity stabilized in all patients and the retina remained attached in all cases. Erosion and intrusion of scleral buckle are rare complications of scleral buckling procedures. The intruding buckle may be left intact unless there is significant threat to the integrity of ocular structures, recurrent detachment, or hemorrhage. Manipulation of the encircling band or buckle does not necessarily alter the visual acuity or the status of the retina.

The effect of physiologic aqueous solutions on the perovskite material lead-lanthanum-zirconium titanate (PLZT)

PubMed Central

Foster, William J.; Meen, James K.; Fox, Donald A.

2016-01-01

Context Perovskite compounds, including Lead-Lanthanum-Zirconium Titanate (PLZT), have wide technological application because of their unique physical properties. The use of PLZT in neuro-prosthetic systems, such as retinal implants, have been discussed in a number of publications. Since inorganic lead is a retinotoxic compound that produces retinal degeneration, the long-term stability of PLZT in aqueous biological solutions must be determined. Objective We evaluated the stability and effects of prolonged immersion of a PLZT-coated crystal in a buffered balanced salt solution. Materials and Methods Scanning Electron Microscopy and Electron Dispersive Spectroscopy (EDS) using a JEOL JSM 5410 microscope equipped with EDS were utilized to evaluate the samples before and after prolonged immersion. Results We found that lead and other constituents of PLZT leached into the surrounding aqueous medium. Discussion By comparing the unit cell of PLZT with that of CaTiO3, which has been found to react with aqueous fluids, Lead is in the same site in PLZT as Ca is in CaTiO3. It is thus reasonable that PLZT will react with aqueous solutions. Conclusion The results suggest that PLZT must either be coated with a protective layer or is not appropriate for long-term in vivo or in vitro biological applications. PMID:22697294

Intraocular retinal prosthesis.

PubMed Central

Humayun, M S

2001-01-01

PURPOSE: An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can generate millions of pixels/light points to create useful vision. METHODS: For electrophysiologic experiments, 2 different setups were used. In the first setup, charge-balanced pulses were delivered to the retinal surface via electrodes inserted through an open sky approach in normal or blind retinal degenerate (rd) mice. In the second setup, the rabbit retina was removed under red light conditions from an enucleated eye and then maintained in a chamber while being superfused with oxygenated, heated Ames media. In both setups, stimulating electrodes and recording electrodes were positioned on the retinal surface to evaluate the effect of varying stimulation parameters on the orthodromic retinal responses (i.e., recording electrode placed between stimulating electrodes and optic nerve head). For psychophysical experiments, visual images were divided into pixels of light that could be projected in a pattern on the retina in up to 8 sighted volunteers. Subjects were asked to perform various tasks ranging from reading and face recognition to various activities of daily living. RESULTS: Electrophysiologic experiments: In a normal mouse, a single cycle of a 1-kHz sine wave was significantly more efficient than a 1-kHz square wave (P < .05), but no such difference was noted in either of the 8- or 16-week-old rd mouse groups (8-week-old, P = .426; 16-week-old, P = .078). Charge threshold was significantly higher in 16-week-old rd mouse versus both 8-week-old rd and normal mouse for every stimulus duration (P < .05). In all groups, short duration pulses (40, 80, and 120 microseconds) were more efficient in terms of total charge (the product of pulse amplitude and pulse duration) than longer (500 and 1,000 microseconds) pulses (P < .05). In all groups, applying a pulse train did not lead to more efficient charge usage (P < .05). Psychophysical experiments: In high-contrast tests, facial recognition rates of over 75% were achieved for all subjects with dot sizes of up to 31.5 minutes of arc when using a 25 x 25 grid with 4.5 arc minute gaps, a 30% dropout rate, and 6 gray levels. Even with a 4 x 4 array of pixels, some subjects were able to accurately describe 2 of the objects. Subjects who were able to read the 4-pixel letter height sentences (on the 6 x 10 and 16 x 16 array) seemed to have a good scanning technique. Scanning at the proper velocity tends to bring out more contrast in the lettering. The reading speed for the 72-point font is a bit slower than for the next smaller font. This may be due to the limited number of letters (3) visible in the window with this large font. CONCLUSIONS: Specific parameters needed to stimulate the retina were identified. Delineating the optimum parameters will decrease the current requirements. Psychophysical tests show that with limited pixels and image processing, useful vision is possible. Both these findings should greatly simplify the engineering of an electronic retinal prosthesis. PMID:11797315

Micromachined electrode array

DOEpatents

Okandan, Murat; Wessendorf, Kurt O.

2007-12-11

An electrode array is disclosed which has applications for neural stimulation and sensing. The electrode array, in certain embodiments, can include a plurality of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. In other embodiments of the electrode array, the electrodes can be fixed to the substrate. The electrode array can be formed from a combination of bulk and surface micromachining, and can include electrode tips having an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis.

A polymer optoelectronic interface restores light sensitivity in blind rat retinas

PubMed Central

Ghezzi, Diego; Antognazza, Maria Rosa; Maccarone, Rita; Bellani, Sebastiano; Lanzarini, Erica; Martino, Nicola; Mete, Maurizio; Pertile, Grazia; Bisti, Silvia; Lanzani, Guglielmo; Benfenati, Fabio

2013-01-01

Interfacing organic electronics with biological substrates offers new possibilities for biotechnology due to the beneficial properties exhibited by organic conducting polymers. These polymers have been used for cellular interfaces in several fashions, including cellular scaffolds, neural probes, biosensors and actuators for drug release. Recently, an organic photovoltaic blend has been exploited for neuronal stimulation via a photo-excitation process. Here, we document the use of a single-component organic film of poly(3-hexylthiophene) (P3HT) to trigger neuronal firing upon illumination. Moreover, we demonstrate that this bio-organic interface restored light sensitivity in explants of rat retinas with light-induced photoreceptor degeneration. These findings suggest that all-organic devices may play an important future role in sub-retinal prosthetic implants. PMID:27158258

Angle performance on optima MDxt

DOE Office of Scientific and Technical Information (OSTI.GOV)

David, Jonathan; Kamenitsa, Dennis

2012-11-06

Angle control on medium current implanters is important due to the high angle-sensitivity of typical medium current implants, such as halo implants. On the Optima MDxt, beam-to-wafer angles are controlled in both the horizontal and vertical directions. In the horizontal direction, the beam angle is measured through six narrow slits, and any angle adjustment is made by electrostatically steering the beam, while cross-wafer beam parallelism is adjusted by changing the focus of the electrostatic parallelizing lens (P-lens). In the vertical direction, the beam angle is measured through a high aspect ratio mask, and any angle adjustment is made by slightlymore » tilting the wafer platen prior to implant. A variety of tests were run to measure the accuracy and repeatability of Optima MDxt's angle control. SIMS profiles of a high energy, channeling sensitive condition show both the cross-wafer angle uniformity, along with the small-angle resolution of the system. Angle repeatability was quantified by running a channeling sensitive implant as a regular monitor over a seven month period and measuring the sheet resistance-to-angle sensitivity. Even though crystal cut error was not controlled for in this case, when attributing all Rs variation to angle changes, the overall angle repeatability was measured as 0.16 Degree-Sign (1{sigma}). A separate angle repeatability test involved running a series of V-curves tests over a four month period using low crystal cut wafers selected from the same boule. The results of this test showed the angle repeatability to be <0.1 Degree-Sign (1{sigma}).« less

Current situation regarding central venous port implantation procedures and complications: a questionnaire-based survey of 11,693 implantations in Japan.

PubMed

Shiono, Masatoshi; Takahashi, Shin; Takahashi, Masanobu; Yamaguchi, Takuhiro; Ishioka, Chikashi

2016-12-01

We conducted a nationwide questionnaire-based survey to understand the current situation regarding central venous port implantation in order to identify the ideal procedure. Questionnaire sheets concerning the number of implantation procedures and the incidence of complications for all procedures completed in 2012 were sent to 397 nationwide designated cancer care hospitals in Japan in June 2013. Venipuncture sites were categorized as chest, neck, upper arm, forearm, and others. Methods were categorized as landmark, cut-down, ultrasound-mark, real-time ultrasound guided, venography, and other groups. We received 374 responses (11,693 procedures) from 153 centers (38.5 %). The overall complication rates were 7.4 % for the chest (598/8,097 cases); 6.8 % for the neck (157/2325); 5.2 % for the upper arm (54/1,033); 7.3 % for the forearm (9/124); and 6.1 % for the other groups (7/114). Compared to the chest group, only the upper arm group showed a significantly lower incidence of complications (P = 0.010), and multivariate logistic regression (odds ratio 0.69; 95 % confidence interval 0.51-0.91; P = 0.008) also showed similar findings. Real-time ultrasound-guided puncture was most commonly used in the upper arm group (83.8 %), followed by the neck (69.8 %), forearm (53.2 %), chest (41.8 %), and other groups (34.2 %). Upper arm venipuncture with ultrasound guidance seems the most promising technique to prevent complications of central venous port implantation.

Comparison of implant cast accuracy of multiple implant impression technique with different splinting materials: An in vitro study

PubMed Central

Selvaraj, Sunantha; Dorairaj, Jayachandran; Mohan, Jayashree; Simon, Paul

2016-01-01

Introduction: An accurate and passive fit of implant framework prosthesis, as well as the successful surgical operation is suggested as one of the critical requirements for long-term implant success. Objective: The purpose of this in vitro study was to evaluate the accuracy of the master cast using open tray impression technique with conventional and novel splinting materials. Methodology: A mandibular reference model with four ADIN implants was done. Ten custom trays were fabricated using the light curable resin sheets. Medium body polyether impression material was used. These trays were randomly divided between the two groups, with five trays in each group. Impression techniques were divided into two groups namely: Group A: Direct impression technique with open tray impression copings splinted with autopolymerizing acrylic resin (GC pattern resin). Group B: Direct impression technique with open tray impression copings splinted with Pro-temp TM 4 (bis-GMA) syringable temporization material. Thus, final impressions were made. Total of 10 master casts were fabricated. Evaluation of casts using Dynascope-Vision Engineering, TESA microhite two- dimension and coordinate measuring machine were used. Results: Statistical comparisons were made using ANOVA test and post-hoc test. Same amount of deviation values obtained with resin splinted and bis-GMA splinted impression copings. Conclusion: The master cast obtained by both the splinting material exhibits no difference from the reference model. So bis-GMA can be used, which is easy to handle, less time consuming, less technique sensitive, rigid, and readily available material in clinics. PMID:27141167

Mapping the mechanical heterogeneity of the brain, and why this matters (Conference Presentation)

NASA Astrophysics Data System (ADS)

Guck, Jochen R.

2017-02-01

It is increasingly recognized that cells measure and respond to the mechanics of their environment. We are especially interested in this mechanosensing during CNS development and pathologies. Using quantitative scanning force microscopy we have shown that various neural tissues are very compliant (shear modulus < 1 kPa) and mechanically heterogeneous. We have recreated compliant polyacrylamide gel substrate with shear moduli between 0.1 and 30 kPa to match and exceed those of CNS tissue. Various primary neurons and glial cells have been cultured on these gels and their reaction studied. Both primary microglia and astrocytes responded to increasing substrate stiffness by changes in morphology and upregulation of inflammatory genes. Upon implantation of composite hydrogel stripes into rat brains, foreign body reactions were significantly enhanced around the stiff parts of the implant. It appears that the mechanical mismatch between a neural implant and native tissue might be at the root of foreign body reactions. Also oligodendrocytes are mechanosensitive as their survival, proliferation, migration, and differentiation capacity in vitro depend on substrate stiffness. This finding might be linked to the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis. And finally, we have also shown retinal ganglion axon pathfinding in the early embryonic Xenopus brain development to be instructed by stiffness gradients. These results form the basis for further investigations into the mechanobiology of cell function in the CNS. Ultimately, this research could help treating previously incurable neuropathologies such as spinal cord injuries and neurodegenerative disorders.

Ultrathin Graphene-Protein Supercapacitors for Miniaturized Bioelectronics.

PubMed

Mosa, Islam M; Pattammattel, Ajith; Kadimisetty, Karteek; Pande, Paritosh; El-Kady, Maher F; Bishop, Gregory W; Novak, Marc; Kaner, Richard B; Basu, Ashis K; Kumar, Challa V; Rusling, James F

2017-09-06

Nearly all implantable bioelectronics are powered by bulky batteries which limit device miniaturization and lifespan. Moreover, batteries contain toxic materials and electrolytes that can be dangerous if leakage occurs. Herein, an approach to fabricate implantable protein-based bioelectrochemical capacitors (bECs) employing new nanocomposite heterostructures in which 2D reduced graphene oxide sheets are interlayered with chemically modified mammalian proteins, while utilizing biological fluids as electrolytes is described. This protein-modified reduced graphene oxide nanocomposite material shows no toxicity to mouse embryo fibroblasts and COS-7 cell cultures at a high concentration of 1600 μg mL -1 which is 160 times higher than those used in bECs, unlike the unmodified graphene oxide which caused toxic cell damage even at low doses of 10 μg mL -1 . The bEC devices are 1 μm thick, fully flexible, and have high energy density comparable to that of lithium thin film batteries. COS-7 cell culture is not affected by long-term exposure to encapsulated bECs over 4 d of continuous charge/discharge cycles. These bECs are unique, protein-based devices, use serum as electrolyte, and have the potential to power a new generation of long-life, miniaturized implantable devices.

Evaluation of a new composite prosthesis for the repair of abdominal wall defects.

PubMed

Losi, Paola; Munaò, Antonella; Spiller, Dario; Briganti, Enrica; Martinelli, Ilaria; Scoccianti, Marco; Soldani, Giorgio

2007-10-01

The degree of integration of biomaterials used in the repair of abdominal wall defects seems to depend upon the structure of the prosthesis. The present investigation evaluates the behaviour in terms of adhesion formation and integration of a new composite prosthesis that could be employed in this clinical application. Full-thickness abdominal wall defects (7 x 5 cm) were created in 16 anaesthetized New Zealand white rabbits and the prosthesis were placed in direct contact with the visceral peritoneum during the experiment. The defects were repaired with a composite prosthesis or pure polypropylene mesh to establish two study groups (n = 8 each). The composite device was constituted by a polypropylene mesh physically attached to a poly(ether)urethane-polydimethylsiloxane laminar sheet. Animals were sacrificed 7, 14, 21 and 30 days after implant and prosthesis/surrounding tissue specimens subjected to light and electron microscopy. Firm adhesions were detected in the polypropylene implants, while they were not present in the composite implants. The excellent behaviour of the composite prosthesis shown in this study warrants further investigation on its use for the repair of abdominal wall defects when a prosthetic device needs to be placed in contact with the intestinal loops.

Oriental nose elongation using an L-shaped polyethylene sheet implant for combined septal spreading and extension.

PubMed

Zhou, Jia; Huang, Xiaolu; Zheng, Danning; Li, Haizhou; Herrler, Tanja; Li, Qingfeng

2014-04-01

The currently recommended strategies for short nose elongation were designed primarily for the Caucasian nasal framework. For Oriental patients, more elongation often is required because a hypoplastic septal cartilage requires more elongation, resulting in a higher risk of complications. This report proposes a modified technique for Oriental nose elongation, which adjusts the pressure points after nasal elongation using an L-shaped implant. Between January 2007 and December 2009, 58 patients underwent Oriental nose elongation using an L-shaped, porous, high-density polyethylene sheet implant. Augmentation rhinoplasty and conchal cartilage shield grafts were performed depending on the nasal shape. Pre- and postoperative nasal length, height, and projection as well as columella-labial angle, columella-lobular angle, and nasal tip angle were measured and compared. A patient satisfaction survey was performed postoperatively. All occurring complications were recorded. The postoperative nasal length was significantly elongated from 47.0±10.4 mm to 49.3±10.1 mm (p=0.003), and the nasal height increased significantly from 48.5±9.1 mm to 50.4±8.5 mm (p=0.011). The initially obtuse columella-labial angle improved significantly from 100.8°±12.1° to 92.5°±15.5° (p=0.014). No significant changes were found regarding nasal projection, nasal tip angle, or columella-lobular angle. The majority of the patients (91.3%) were highly satisfied or satisfied with the aesthetic results. A major complication in terms of implant exposure was observed in one case. The minor complications included stiffness of the nasal tip (3 patients) and tip redness (1 patient). In Oriental nose elongation, the use of an L-shaped graft is a feasible and safe treatment option that allows for an excellent aesthetic outcome and reduces the incidence of complications. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Newly Developed Biocompatible Material: Dispersible Titanium-Doped Hydroxyapatite Nanoparticles Suitable for Antibacterial Coating on Intravascular Catheters.

PubMed

Furuzono, Tsutomu; Okazaki, Masatoshi; Azuma, Yoshinao; Iwasaki, Mitsunobu; Kogai, Yasumichi; Sawa, Yoshiki

2017-01-01

Thirteen patients with chlorhexidine-silver sulfadiazine-impregnated catheters have experienced serious anaphylactic shock in Japan. These adverse reactions highlight the lack of commercially available catheters impregnated with strong antibacterial chemical agents. A system should be developed that can control both biocompatibility and antibacterial activity. Hydroxyapatite (HAp) is biocompatible with bone and skin tissues. To provide antibacterial activity by using an external physical stimulus, titanium (Ti) ions were doped into the HAp structure. Highly dispersible, Ti-doped HAp (Ti-HAp) nanoparticles suitable as a coating material were developed. In 3 kinds of Ti-HAp [Ti/(Ca + Ti) = 0.05, 0.1, 0.2], the Ti content in the HAp was approximately 70% of that used in the Ti-HAp preparation, as determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). ICP-AES and X-ray diffraction showed Ti ions were well substituted into the HAp lattice. The nanoparticles were almost uniformly coated on a polyethylene (PE) sheet in a near-monolayer with a surface coverage ratio >95%. The antibacterial activity of the Ti-HAp nanoparticles containing 7.3% Ti ions and coating the sheet was evaluated by calculating the survival ratio of Pseudomonas aeruginosa on the coated sheet after ultraviolet (UV) irradiation. The Ti-HAp-coated sheet showed a 50% decrease in the number of P. aeruginosa compared with that on an uncoated control PE sheet after UV irradiation for 30 s. Key Messages: A system of biocompatibility and antibacterial activity with an on/off switch controlled by external UV stimulation was developed. The system is expected to be applicable in long-term implanted intravascular catheters. © 2017 S. Karger AG, Basel.

Metabolic Prosthesis for Oxygenation of Ischemic Tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenbaum, Elias

2009-01-01

This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer,more » suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.« less

Feasibility of microelectrode array (MEA) based on silicone-polyimide hybrid for retina prosthesis.

PubMed

Kim, Eui Tae; Kim, Cinoo; Lee, Seung Woo; Seo, Jong-Mo; Chung, Hum; Kim, Sung June

2009-09-01

To adopt micropatterning technology in manufacturing silicone elastomer-based microelectrode arrays for retinal stimulation, a silicone-polyimide hybrid microelectrode array was proposed and tested in vivo. Gold microelectrodes were created by semiconductor manufacturing technology based on polyimide and were hybridized with silicone elastomer by spin coating. The stability of the hybrid between the two materials was flex and blister tested. The feasibility of the hybrid electrode was evaluated in the rabbit eye by reviewing optical coherence tomography (OCT) findings after suprachoroidal implantation. The flex test showed no dehiscence between the two materials for 24 hours of alternative flexion and extension from -45.0 degrees to +45.0 degrees . During the blister test, delamination was observed at 8.33 +/- 1.36 psi of pressure stress; however, this property was improved to 11.50 +/- 1.04 psi by oxygen plasma treatment before hybridization. OCT examination revealed that the implanted electrodes were safely located in the suprachoroidal space during the 4-week follow-up period. The silicone-polyimide hybrid microelectrode array showed moderate physical properties, which are suitable for in vivo application. Appropriate pretreatment before hybridization improved electrode stability. In vivo testing indicated that this electrode is suitable as a stimulation electrode in artificial retina.

Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer.

PubMed

Tomita, Hiroshi; Sugano, Eriko; Yawo, Hiromu; Ishizuka, Toru; Isago, Hitomi; Narikawa, Satoko; Kügler, Sebastian; Tamai, Makoto

2007-08-01

To investigate whether the channelopsin-2 (Chop2) gene would restore visual responses in 10-month-old dystrophic Royal College of Surgeons (aged RCS; rdy/rdy) rats, the authors transferred the Chop2 gene into the retinal cells of aged RCS rats using the adenoassociated virus (AAV) vector. The N-terminal fragment (residues 1-315) of Chop2 was fused to a fluorescent protein, Venus, in frame at the end of the Chop2 coding fragment. The viral vector construct (AAV-Chop2V) for the expression of the Chop2V in the retina was made by subcloning into an adenoassociated virus vector, including the CAG promoter. To evaluate the expression profile of Chop2V in the retina, the rats were killed and the eyes were removed and fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline. Retinal wholemount specimens and cryosections were made. Under anesthetized conditions, electrodes for the recording of visually evoked potentials (VEPs) were implanted onto the visual cortex in aged-RCS (rdy/rdy) rats. AAV-Chop2V vectors were then injected into the vitreous cavity of the left eyes. As a control, AAV-Venus vectors were applied to the right eyes. VEPs were evoked by the flash of a blue, white, or red light-emitting diode (LED) and were recorded from the visual cortex of the rats at various time points after the AAV vector injection. Chop2V fluorescence was predominantly observed in retinal ganglion cells (RGCs). Some fluorescence was observed in the inner nuclear layer and the inner plexiform layer neurites. A tendency of recovery was observed in the VEPs of aged RCS (rdy/rdy) rats after the AAV-Chop2V injection but not after the AAV-Venus injection. The visual response of AAV-Chop2V-injected aged RCS (rdy/rdy) rats was less sensitive to the blue LED flash than that of nondystrophic RCS (+/+) rats. The AAV-Chop2V-injected aged RCS (rdy/rdy) rats were insensitive to the red LED flash, which evoked a robust VEP in the RCS (+/+) rats. The visual response of aged RCS (rdy/rdy) rats was partially restored by transduction of the Chop2 gene through AAV into the inner retinal neurons, mainly RGCs. These results suggest that the transduction of Chop2 would provide a new strategy to treat some retinitis pigmentosa (RP) symptoms independent of their etiology.

Effects of B{sub 18}H{sub x}{sup +} and B{sub 18}H{sub x} dimer ion implantations on crystallinity and retained B dose in silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawasaki, Yoji; Shibahara, Kentaro; Research Institute for Nanodevice and Bio Systems, Hiroshima University, 1-4-2 Kagamiyama, Higashihiroshima, Hiroshima 739-8527

2012-01-15

The effects of B{sub 18}H{sub x}{sup +} and B{sub 18}H{sub x} dimer ion (B{sub 36}H{sub y}{sup +}) implantations on Si crystallinity and the retained B dose in Si were investigated using B{sub 18}H{sub x} bombardment and compared with the effects of B{sup +} implantation. Crystallinity was estimated for the implantation dose using molecular dynamic simulations (MDSs) and was quantified using the optical thickness obtained from spectroscopic ellipsometry. The authors focused on the crystallinity at a low B dose and compared the amorphized zones predicted by MDS for B{sub 18}H{sub x}{sup +} implantation with those measured using transmission electron microscopy; themore » predicted and measured results were in reasonable agreement. The authors then used their understanding of B{sub 18}H{sub x} bombardment to discuss the process for the generation of larger amorphized zones and thicker amorphized layers, as observed in B{sub 36}H{sub y}{sup +} implantation. The retained B dose and the sputtering were examined with secondary ion mass spectroscopy, focusing on a comparison of the retained B and the sputtering of Si and SiO{sub 2} surfaces. The retained B dose was lower for B{sub 18}H{sub x}{sup +} and B{sub 36}H{sub y}{sup +} implantations, with and without surface SiO{sub 2}, than for B{sup +} implantation, although no sputtering was observed. The reduction of the retained B dose was more severe in the samples with SiO{sub 2}. The origin of the differences between Si and SiO{sub 2} surfaces was considered to be Si melting; this was predicted by the MDSs, and observed indirectly as flat B profiles in the Si region. To examine the effects of both crystallinity and retained B dose on the electrical characteristics, the sheet resistance (R{sub S}) was measured. The R{sub S} for B{sub 18}H{sub x}{sup +} implantation was lower than that for B{sup +} implantation at both B doses studied. Additionally, the B{sub 36}H{sub y}{sup +} implantation under conditions that produced a thicker amorphized layer led to lower R{sub S} than B{sub 18}H{sub x}{sup +} implantation. These results indicate that both the amorphized layer and the amorphized zone contribute to the activation of more B atoms.« less

EDITORIAL: The Eye and The Chip 2008 The Eye and The Chip 2008

NASA Astrophysics Data System (ADS)

Rizzo, Joseph F.; O'Malley, Edward R.; Hessburg, Philip C.

2009-06-01

Over the course of the past decade, The Eye and The Chip world congress on visual neuro-prosthetic devices has become a premier meeting for those who believe that 'artificial' vision will one day be used to improve the quality of life of visually impaired patients. Although substantial progress has been made, there are numerous unresolved issues, like the preferred methods for wireless communication, placement of devices, and materials and design among others. The Eye and The Chip meeting of 2008, held in Detroit on 12-14 June 2008, provided important new information about these and other important topics, and thus served to advance this field of scientific research. From a research seedling a decade ago to the crowd of superb presentations in Detroit last June, a very real sense of justifiable optimism has developed. The prospects of artificial vision are no longer remote. Many of the researchers expressed confidence that implantable devices will provide the hoped-for level of vision to justify their widespread use in the future. The often dramatic successes of cochlear implants continues to provide credence that artificial stimulation of nerve tissue is a plausible strategy to restore vision. The Eye and The Chip 2008 attracted researchers from four continents (North America, Europe, Asia and Australia). The meeting also benefited from the attendance and presentations by representatives of the FDA, who have been present for all The Eye and The Chip meetings. The 2008 meeting was also enhanced by the inclusion of a new and related scientific field that shares the goal of restoring vision to the blind—the field of molecular restoration of retinal function by insertion of channelrhodopsin. Just as the field of ophthalmology went from Ridley's primitive intraocular lens replacement to implants useful in virtually every cataract patient in one surgeon's clinical lifetime, the field of retinal prostheses seems to be following a very similar trajectory. Likewise, the field of visual prosthetics continues to amass evidence that suggests that its long-term future is promising. We are grateful to the scientists who made the congress a success, to the Journal of Neural Engineering for organizing this special issue, to the financial supporters who made the congress possible and to the Detroit Institute of Ophthalmology staff who worked tirelessly and without complaint to bring home a superb congress. We invite you to attend the next The Eye and The Chip meeting, which will be held in 2011.

Bimorph Silk Microsheets with Programmable Actuating Behavior: Experimental Analysis and Computer Simulations.

PubMed

Ye, Chunhong; Nikolov, Svetoslav V; Geryak, Ren D; Calabrese, Rossella; Ankner, John F; Alexeev, Alexander; Kaplan, David L; Tsukruk, Vladimir V

2016-07-13

Microscaled self-rolling construct sheets from silk protein material have been fabricated, containing a silk bimorph composed of silk ionomers as an active layer and cross-linked silk β-sheet as the passive layer. The programmable morphology was experimentally explored along with a computational simulation to understand the mechanism of shape reconfiguration. The neutron reflectivity shows that the active silk ionomers layer undergoes remarkable swelling (eight times increase in thickness) after deprotonation while the passive silk β-sheet retains constant volume under the same conditions and supports the bimorph construct. This selective swelling within the silk-on-silk bimorph microsheets generates strong interfacial stress between layers and out-of-plane forces, which trigger autonomous self-rolling into various 3D constructs such as cylindrical and helical tubules. The experimental observations and computational modeling confirmed the role of interfacial stresses and allow programming the morphology of the 3D constructs with particular design. We demonstrated that the biaxial stress distribution over the 2D planar films depends upon the lateral dimensions, thickness and the aspect ratio of the microsheets. The results allow the fine-tuning of autonomous shape transformations for the further design of complex micro-origami constructs and the silk based rolling/unrolling structures provide a promising platform for polymer-based biomimetic devices for implant applications.

Tumor Growth Suppression Induced by Biomimetic Silk Fibroin Hydrogels

NASA Astrophysics Data System (ADS)

Yan, Le-Ping; Silva-Correia, Joana; Ribeiro, Viviana P.; Miranda-Gonçalves, Vera; Correia, Cristina; da Silva Morais, Alain; Sousa, Rui A.; Reis, Rui M.; Oliveira, Ana L.; Oliveira, Joaquim M.; Reis, Rui L.

2016-08-01

Protein-based hydrogels with distinct conformations which enable encapsulation or differentiation of cells are of great interest in 3D cancer research models. Conformational changes may cause macroscopic shifts in the hydrogels, allowing for its use as biosensors and drug carriers. In depth knowledge on how 3D conformational changes in proteins may affect cell fate and tumor formation is required. Thus, this study reports an enzymatically crosslinked silk fibroin (SF) hydrogel system that can undergo intrinsic conformation changes from random coil to β-sheet conformation. In random coil status, the SF hydrogels are transparent, elastic, and present ionic strength and pH stimuli-responses. The random coil hydrogels become β-sheet conformation after 10 days in vitro incubation and 14 days in vivo subcutaneous implantation in rat. When encapsulated with ATDC-5 cells, the random coil SF hydrogel promotes cell survival up to 7 days, whereas the subsequent β-sheet transition induces cell apoptosis in vitro. HeLa cells are further incorporated in SF hydrogels and the constructs are investigated in vitro and in an in vivo chick chorioallantoic membrane model for tumor formation. In vivo, Angiogenesis and tumor formation are suppressed in SF hydrogels. Therefore, these hydrogels provide new insights for cancer research and uses of biomaterials.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN CYTOMEGALOVIRUS RETINITIS: A Longitudinal Study.

PubMed

Invernizzi, Alessandro; Agarwal, Aniruddha; Ravera, Vittoria; Oldani, Marta; Staurenghi, Giovanni; Viola, Francesco

2018-01-01

To evaluate the vitreal, retinal, and choroidal features using spectral domain optical coherence tomography (SD-OCT) in eyes affected by cytomegalovirus (CMV) retinitis. Patients diagnosed with either active or inactive CMV retinitis were included in the study. Complete ophthalmic examination, serial color fundus photography, and SD-OCT (with and without enhanced depth imaging function) were performed for all the subjects at baseline and follow-up visits. The SD-OCT images were analyzed by two independent graders to evaluate the structural changes in areas of CMV retinitis. Prevalence data for vitreal, retinal, and choroidal SD-OCT features were collected. Twelve eyes from 9 patients (6 males, mean age: 52.7 ± 10.3 years) were enrolled. Nine eyes were diagnosed with active CMV retinitis at baseline. Active disease SD-OCT characteristic findings included nebulous vitritis (100%), posterior hyaloid thickening (83.3%), epiretinal membrane (100%), and retinal swelling (100%). Two distinct patterns of chorioretinal involvement were observed in active retinitis: 1) full-thickness retinitis (Full thickness retinitis) (n = 7 eyes) with choriocapillaris alterations and retinal pigment epithelial thickening and 2) cavernous retinitis (n = 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing. Patients with cavernous retinitis develop retinal detachment during follow-up. Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. There are two distinct patterns of chorioretinal involvement in CMV retinitis. SD-OCT is a useful tool in the diagnosis, management, and prediction of the outcome of CMV retinitis.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN MACULA-INVOLVING CYTOMEGALOVIRUS RETINITIS.

PubMed

Gupta, Mrinali P; Patel, Sarju; Orlin, Anton; Marlow, Elizabeth; Chee, Ru-Ik; Nadelmann, Jennifer; Chan, R V Paul; DʼAmico, Donald J; Kiss, Szilard

2018-05-01

To evaluate the microstructural features of cytomegalovirus (CMV) retinitis by spectral domain optical coherence tomography (OCT). Subjects were patients with macula-involving CMV retinitis with OCT imaging. The leading edge of retinitis in the macula was identified based on fundus imaging, and OCT findings were longitudinally evaluated in three areas: within the area of active retinitis, at the leading edge of retinitis, and just beyond the leading edge of retinitis. Optical coherence tomography imaging of macular CMV retinitis identified vitreous cells in 10 eyes (100%), posterior vitreous detachment in four eyes (40%), broad-based vitreomacular traction in one eye (10%), epiretinal membrane in eight eyes (80%), and lamellar hole-associated epiretinal proliferation associated with an atrophic hole in one eye (10%). Retinal architectural disruption, disruption of inner retinal layers, disruption of the external limiting membrane, and ellipsoid zone abnormalities were noted within the area of retinitis in all eyes and decreased in frequency and severity at and beyond the leading edge of retinitis, although all 10 eyes (100%) exhibited one of these abnormalities, especially outer retinal microabnormalities, beyond the leading edge of retinitis. Microstructural abnormalities were frequently noted on OCT of CMV retinitis, including within the retina beyond the leading edge of retinitis identified by corresponding fundus imaging. Outer retinal abnormalities were noted more frequently than inner retinal abnormalities beyond the leading edge of retinitis. These findings provide insight into the effects of CMV retinitis on retinal microstructure and potentially on vision and highlight the potential utility of OCT for monitoring microprogression of macula-involving CMV retinitis.

A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ® Wafer) for Japanese Patients with Malignant Gliomas

PubMed Central

AOKI, Tomokazu; NISHIKAWA, Ryo; SUGIYAMA, Kazuhiko; NONOGUCHI, Naosuke; KAWABATA, Noriyuki; MISHIMA, Kazuhiko; ADACHI, Jun-ichi; KURISU, Kaoru; YAMASAKI, Fumiyuki; TOMINAGA, Teiji; KUMABE, Toshihiro; UEKI, Keisuke; HIGUCHI, Fumi; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; TAKESHIMA, Hideo; YAMASHITA, Shinji; ARITA, Kazunori; HIRANO, Hirofumi; YAMADA, Shinobu; MATSUTANI, Masao

2014-01-01

Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe. PMID:24739422

The effect of micro-ECoG substrate footprint on the meningeal tissue response

NASA Astrophysics Data System (ADS)

Schendel, Amelia A.; Nonte, Michael W.; Vokoun, Corinne; Richner, Thomas J.; Brodnick, Sarah K.; Atry, Farid; Frye, Seth; Bostrom, Paige; Pashaie, Ramin; Thongpang, Sanitta; Eliceiri, Kevin W.; Williams, Justin C.

2014-08-01

Objective. There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. Approach. The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. Main results. It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. Significance. These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

A hydroxyapatite coating covalently linked onto a silicone implant material.

PubMed

Furuzono, T; Sonoda, K; Tanaka, J

2001-07-01

A novel composite consisting of hydroxyapatite (HAp) microparticles covalently coupled onto a silicone sheet was developed. Initially, an acrylic acid (AAc) -grafted silicone sheet with a 16.7 microg/cm(2) surface graft density was prepared by corona-discharge treatment. The surface of sintered, spherical, carbonated HAp particles with an average diameter of 2.0 microm was subsequently modified with amino groups. The amino group surface density of the HAp particles was calculated to be approximately one amino molecule per 1.0 nm(2) of particle surface area. These samples were characterized with Fourier transform infrared spectrometry and X-ray photoelectron spectroscopy. After the formation of ammonium ionic bonds between both samples under aqueous conditions, they were reacted at 180 degrees C for 6 h in vacuo to form covalent bonds through a solid-phase condensation. The HAp particles were coupled to the AAc-grafted silicone surface by a covalent linkage. Further improvements in the adhesive and bioactive properties of the HAp-coated silicone material are expected.

Chitosan reinforced apatite-wollastonite coating by electrophoretic deposition on titanium implants.

PubMed

Sharma, Smriti; Soni, Vivek P; Bellare, Jayesh R

2009-07-01

A novel bioactive porous apatite-wollastonite/chitosan composite coating was prepared by electrophoretic deposition. The influence of synthesis parameters like pH of suspension and current density was studied and optimized. X-ray diffraction confirmed crystalline phase of apatite-wollastonite in powder as well as composite coating with coat crystallinity of 65%. Scanning electron microscope showed that the porosity had interconnections with good homogeneity between the phases. The addition of chitosan increased the adhesive strength of the composite coating. Young's modulus of the coating was found to be 9.23 GPa. One of our key findings was sheet-like apatite growth unlike ball-like growth found in bioceramics. Role of chitosan was studied in apatite growth mechanism in simulated body fluid. In presence of chitosan, dense negatively charged surface with homogenous nucleation was the primary factor for sheet-like evolution of apatite layer. The results suggest that incorporation of chitosan with apatite-wollastonite in composite coating could provide excellent in vitro bioactivity with enhanced mechanical properties.

Electrical isolation, thermal stability and rf loss in a multilayer GaAs planar doped barrier diode structure bombarded by H+ and Fe+ ions

NASA Astrophysics Data System (ADS)

Vo, V. T.; Koon, K. L.; Hu, Z. R.; Dharmasiri, C. N.; Subramaniam, S. C.; Rezazadeh, A. A.

2004-04-01

Electrical isolation in multilayer GaAs planar doped barrier (PDB) diode structures produced by H+ and Fe+ ion implantation were investigated. For an H+ bombardment with a dose of 1×1015cm-2, a sheet resistivity as high as 3×108 Ω/sq and thermal stability up to 400 °C has been achieved. For samples bombarded by Fe+ ions, a similar high sheet resistivity has also been achieved although a longer annealing time (15 min) and a higher annealing temperature (550 °C) were needed. The rf dissipation losses of coplanar waveguide (CPW) "thru" lines fabricated on bombarded multilayer PDBD structure samples were also examined. The measured rf losses were 1.65 dB/cm at 10 GHz and 3 dB/cm at 40 GHz, similar to the values that a CPW line exhibits on a semi-isolating GaAs substrate.

Hybrid microfabrication of nanofiber-based sheets and rods for tissue engineering applications.

PubMed

Park, Suk-Hee; Kim, Min Sung; Lee, Dasom; Choi, Yong Whan; Kim, Deok-Ho; Suh, Kahp-Yang

2013-12-01

Electrospun nanofibers have been developed into a variety of forms for tissue engineering scaffolds to regulate the cellular functions guided by nanotopographical cues. Here, we have successfully fabricated nanofiber-based scaffold complexes of rod and sheet type by combining the three microfabrication techniques of electrospinning, spin coating, and polymer melt deposition. It was demonstrated that this hybrid fabrication could produce uniaxially aligned nanofiber scaffolds supported by a thin film, allowing for a mechanically enforced substrate for cell culture as well as facile scaffold manipulation. The results of cell analysis indicated that nanofibers on spin-coated films could provide contact guidance effects on cells and retain them even after manipulation. As an application of the cell-laden nanofiber film, we built a rod-type structure by rolling up the film around a mechanically supporting core microfiber, which was incorporated by polymer melt deposition. A biocompatible and biodegradable polymer, polycaprolactone, was used throughout the processes and thus could be used as a directly implantable substitute in tissue regeneration.

Eye health care in the Czech Republic.

PubMed

Kocur, Ivo; Kuchynka, Pavel

2002-01-01

An analysis of eye health care in the Czech Republic as of 1998 was performed. A questionnaire was used to obtain information from all 59 in-patient eye departments. The number of ophthalmologists per 1 million inhabitants was 95. The number of cataract operations per 1 million inhabitants was 4,209: phaco-emulsification (36,926 surgeries, 85.2%), extracapsular extraction (6,094 surgeries, 14.1%) and intracapsular extraction (90 surgeries, 0.2%). Intra-ocular lenses were implanted in 99% of cases; 404 corneal transplantations and 1,220 operations for retinal detachment were performed. The number of pars plana vitrectomies for diabetic eye complications was 661. Selected regional clinical centres should be equipped and preferred by health insurance companies to provide comprehensive eye health care services and training. Copyright 2002 S. Karger AG, Basel

Biodegradable polymer film as a source for formation of human fetal retinal pigment epithelium spheroids.

PubMed

Rezai, K A; Farrokh-Siar, L; Botz, M L; Godowski, K C; Swanbom, D D; Patel, S C; Ernest, J T

1999-05-01

To evaluate the attachment of human fetal rctinal pigment epithelial (HFRPE) cells to a biodegradable polymer film with subsequent formation of spheroids in vitro. Ten biodegradable polymer films with different compositions were examined for their physical properties and ease of manipulation under a dissecting microscope. The film with the most suitable handling characteristics was chosen, and a purely isolated sheet of HFRPE cells was attached to it. The purity of the cells was assessed by their pigmentation and expression of cytokeratin. Proliferation was assessed by incorporation of 5-bromo-2'-deoxyuridine (BrdtJ). Cellular structure was analyzed under light and electron microscopes, and the functional capability of the cells was evaluated by rod outer segment (ROS) phagocytosis. The polymer film with composition 50:50 poly (DL-lactide) (PLA)/poly (DL-lactide-co-glycolide) (PLG) with an inherent viscosity of 1.03 dl/g was found to be the most suitable for handling under the microscope. Sheets of HFRPE cells attached to the polymer films within 48 hours and began to form spheroids. All the isolated cells were pigmented and expressed cytokeratin. They possessed a cuboidal morphology, numerous apical microvilli, and no sign of dedifferentiation. HFRPE cells produced extracellular matrix (collagen filaments) on their basal side, filling the cavities of the polymer film. The cells subsequently proliferated, incorporated BrdU, migrated onto the culture plate to form monolayers, and phagocytized ROS. Biodegradable polymer films can be used as a scaffold for the adhesion of the HFRPE sheet and formation of spheroids. Spheroids represent a source of high density and well-differentiated HFRPE cells that are easy to transfer. Furthermore, the stricture of the membrane makes it suitable for additional applications.

First Implantation of Silicon Nanopore Membrane Hemofilters

PubMed Central

Kensinger, Clark; Karp, Seth; Kant, Rishi; Chui, Benjamin W.; Goldman, Kenneth; Yeager, Torin; Gould, Edward R.; Buck, Amanda; Laneve, David C.; Groszek, Joseph J.; Roy, Shuvo; Fissell, William H.

2016-01-01

An implantablehemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3–8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5–8 nm 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics predictions of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20–50 ml of transudative (albumin sieving coefficient 0.5 – 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3–4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (∼ 0.2 – 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood–material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation. PMID:26978710

Electrical Characterization of 3D Au Microelectrodes for Use in Retinal Prostheses.

PubMed

Lee, Sangmin; Ahn, Jae Hyun; Seo, Jong-Mo; Chung, Hum; Cho, Dong-Il Dan

2015-06-17

In order to provide high-quality visual information to patients who have implanted retinal prosthetic devices, the number of microelectrodes should be large. As the number of microelectrodes is increased, the dimensions of each microelectrode must be decreased, which in turn results in an increased microelectrode interface impedance and decreased injection current dynamic range. In order to improve the trade-off envelope between the number of microelectrodes and the current injection characteristics, a 3D microelectrode structure can be used as an alternative. In this paper, the electrical characteristics of 2D and 3D Au microelectrodes were investigated. In order to examine the effects of the structural difference, 2D and 3D Au microelectrodes with different base areas but similar effective surface areas were fabricated and evaluated. Interface impedances were measured and similar dynamic ranges were obtained for both 2D and 3D Au microelectrodes. These results indicate that more electrodes can be implemented in the same area if 3D designs are used. Furthermore, the 3D Au microelectrodes showed substantially enhanced electrical durability characteristics against over-injected stimulation currents, withstanding electrical currents that are much larger than the limit measured for 2D microelectrodes of similar area. This enhanced electrical durability property of 3D Au microelectrodes is a new finding in microelectrode research, and makes 3D microelectrodes very desirable devices.

Versatile Stimulation Back-End With Programmable Exponential Current Pulse Shapes for a Retinal Visual Prosthesis.

PubMed

Maghami, Mohammad Hossein; Sodagar, Amir M; Sawan, Mohamad

2016-11-01

This paper reports on the design, implementation, and test of a stimulation back-end, for an implantable retinal prosthesis. In addition to traditional rectangular pulse shapes, the circuit features biphasic stimulation pulses with both rising and falling exponential shapes, whose time constants are digitally programmable. A class-B second generation current conveyor is used as a wide-swing, high-output-resistance stimulation current driver, delivering stimulation current pulses of up to ±96 μA to the target tissue. Duration of the generated current pulses is programmable within the range of 100 μs to 3 ms. Current-mode digital-to-analog converters (DACs) are used to program the amplitudes of the stimulation pulses. Fabricated using the IBM 130 nm process, the circuit consumes 1.5×1.5 mm 2 of silicon area. According to the measurements, the DACs exhibit DNL and INL of 0.23 LSB and 0.364 LSB, respectively. Experimental results indicate that the stimuli generator meets expected requirements when connected to electrode-tissue impedance of as high as 25 k Ω. Maximum power consumption of the proposed design is 3.4 mW when delivering biphasic rectangular pulses to the target load. A charge pump block is in charge of the upconversion of the standard 1.2-V supply voltage to ±3.3V.

New light for old eyes: comparing melanopsin-mediated non-visual benefits of blue-light and UV-blocking intraocular lenses.

PubMed

Schmoll, Conrad; Khan, Ashraf; Aspinall, Peter; Goudie, Colin; Koay, Peter; Tendo, Christelle; Cameron, James; Roe, Jenny; Deary, Ian; Dhillon, Bal

2014-01-01

Melanopsin-expressing photosensitive retinal ganglion cells form a blue-light-sensitive non-visual system mediating diverse physiological effects including circadian entrainment and cognitive alertness. Reduced blue wavelength retinal illumination through cataract formation is thought to blunt these responses while cataract surgery and intraocular lens (IOL) implantation have been shown to have beneficial effects on sleep and cognition. We aimed to use the reaction time (RT) task and the Epworth Sleepiness Score (ESS) as a validated objective platform to compare non-visual benefits of UV- and blue-blocking IOLs. Patients were prospectively randomised to receive either a UV- or blue-blocking IOL, performing an RT test and ESS questionnaire before and after surgery. Optical blurring at the second test controlled for visual improvement. Non-operative age-matched controls were recruited for comparison. 80 participants completed the study. Those undergoing first-eye phacoemulsification demonstrated significant improvements in RT over control (p=0.001) and second-eye surgery patients (p=0.03). Moreover, reduced daytime sleepiness was measured by ESS for the first-eye surgery group (p=0.008) but not for the second-eye group (p=0.09). Choice of UV- or blue-blocking IOL made no significant difference to magnitude of cognitive improvement (p=0.272). Phacoemulsification, particularly first-eye surgery, has a strong positive effect on cognition and daytime alertness, regardless of IOL type.

Randomized controlled trial of anterior-chamber intraocular lenses in Nepal: long-term follow-up.

PubMed Central

Evans, J. R.; Henning, A.; Pradhan, D.; Foster, A.; Lagnado, R.; Poulson, A.; Johnson, G. J.; Wormald, R. P.

2000-01-01

Most of the estimated 20 million people who are blind with cataracts live in rural areas of developing countries, where expert surgical resources are scarce. We have studied the use of multiflex open-loop anterior-chamber intraocular lenses (ACIOL) in high-volume low-cost surgery. Between 1992 and 1995, a total of 2000 people attending Lahan Eye Hospital, Nepal, with bilateral cataracts reducing vision to < or = 6/36 were randomly allocated to receive intracapsular extraction (ICCE) with aphakic spectacles, or ICCE with an ACIOL. We re-examined the cohort (1305/2000, 65%) between November 1996 and April 1997 and report the findings in this article. There were 13 new cases of poor visual outcome (best corrected vision < 6/60) arising after one year: 9 in the ACIOL group and 4 in the control group; odds ratio 2.1 (95% confidence interval, 0.59-9.55). The causes of poor outcome were as follows: ACIOL group--retinal detachment (4 cases), cystoid macular oedema (2), epiretinal membrane (1), age-related macular degeneration (1), and late endophthalmitis (1); control group--retinal detachment (2 cases), late endophthalmitis (1), and primary open-angle glaucoma with age-related macular degeneration (1). In rural areas of developing countries, well-manufactured multiflex open-loop ACIOLs can be implanted safely by experienced ophthalmologists after routine ICCE, avoiding the disadvantages of aphakic spectacle correction. PMID:10812737

The Advanced Human Eye Model (AHEM): a personal binocular eye modeling system inclusive of refraction, diffraction, and scatter.

PubMed

Donnelly, William

2008-11-01

To present a commercially available software tool for creating eye models to assist the development of ophthalmic optics and instrumentation, simulate ailments or surgery-induced changes, explore vision research questions, and provide assistance to clinicians in planning treatment or analyzing clinical outcomes. A commercially available eye modeling system was developed, the Advanced Human Eye Model (AHEM). Two mainstream optical software engines, ZEMAX (ZEMAX Development Corp) and ASAP (Breault Research Organization), were used to construct a similar software eye model and compared. The method of using the AHEM is described and various eye modeling scenarios are created. These scenarios consist of retinal imaging of targets and sources; optimization capability; spectacles, contact lens, and intraocular lens insertion and correction; Zernike surface deformation on the cornea; cataract simulation and scattering; a gradient index lens; a binocular mode; a retinal implant; system import/export; and ray path exploration. Similarity of the two different optical software engines showed validity to the mechanism of the AHEM. Metrics and graphical data are generated from the various modeling scenarios particular to their input specifications. The AHEM is a user-friendly commercially available software tool from Breault Research Organization, which can assist the design of ophthalmic optics and instrumentation, simulate ailments or refractive surgery-induced changes, answer vision research questions, or assist clinicians in planning treatment or analyzing clinical outcomes.

Mechanism by which Untwisting of Retinal Leads to Productive Bacteriorhodopsin Photocycle States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolter, Tino; Elstner, Marcus; Fischer, Stefan

2014-01-01

Relaxation of the twisted-retinal photoproduct state triggers proton-coupled reaction cycle in retinal proteins. A key open question is whether the retinal relaxation path is governed by the intrinsic torsional properties of the retinal or rather by the interactions of the retinal with protein and water groups, given the crowded protein environments in which the retinal resides. We address this question by performing systematic quantum mechanical/molecular mechanical molecular dynamics computations of retinal dynamics in bacteriorhodopsin at different temperatures, reaction path computations, and assessment of the vibrational fingerprints of the retinal molecule. Our results demonstrate a complex dependence of the retinal dynamicsmore » and preferred geometry on temperature. As the temperature increases, the retinal dihedral angle samples values largely determined by its internal conformational energy. The protein environment shapes the energetics of retinal relaxation and provides hydrogen-bonding partners that stabilize the retinal geometry.« less

Federal regulation of vision enhancement devices for normal and abnormal vision

NASA Astrophysics Data System (ADS)

Drum, Bruce

2006-09-01

The Food and Drug Administration (FDA) evaluates the safety and effectiveness of medical devices and biological products as well as food and drugs. The FDA defines a device as a product that is intended, by physical means, to diagnose, treat, or prevent disease, or to affect the structure or function of the body. All vision enhancement devices fulfill this definition because they are intended to affect a function (vision) of the body. In practice, however, FDA historically has drawn a distinction between devices that are intended to enhance low vision as opposed to normal vision. Most low vision aids are therapeutic devices intended to compensate for visual impairment, and are actively regulated according to their level of risk to the patient. The risk level is usually low (e.g. Class I, exempt from 510(k) submission requirements for magnifiers that do not touch the eye), but can be as high as Class III (requiring a clinical trial and Premarket Approval (PMA) application) for certain implanted and prosthetic devices (e.g. intraocular telescopes and prosthetic retinal implants). In contrast, the FDA usually does not actively enforce its regulations for devices that are intended to enhance normal vision, are low risk, and do not have a medical intended use. However, if an implanted or prosthetic device were developed for enhancing normal vision, the FDA would likely decide to regulate it actively, because its intended use would entail a substantial medical risk to the user. Companies developing such devices should contact the FDA at an early stage to clarify their regulatory status.

Layering PLGA-based electrospun membranes and cell sheets for engineering cartilage-bone transition.

PubMed

Mouthuy, P-A; El-Sherbini, Y; Cui, Z; Ye, H

2016-04-01

It is now widely acknowledged that implants that have been designed with an effort towards reconstructing the transition between tissues might improve their functionality and integration in vivo. This paper contributes to the development of improved treatment for articular cartilage repair by exploring the potential of the combination of electrospinning technology and cell sheet engineering to create cartilage tissue. Poly(lactic-co-glycolic acid) (PLGA) was used to create the electrospun membranes. The focus being on the cartilage-bone transition, collagen type I and hydroxyapatite (HA) were also added to the scaffolds to increase the histological biocompatibility. Human mesenchymal stem cells (hMSCs) were cultured in thermoresponsive dishes to allow non-enzymatic removal of an intact cell layer after reaching confluence. The tissue constructs were created by layering electrospun membranes with sheets of hMSCs and were cultured under chondrogenic conditions for up to 21 days. High viability was found to be maintained in the multilayered construct. Under chondrogenic conditions, reverse-transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry have shown high expression levels of collagen type X, a form of collagen typically found in the calcified zone of articular cartilage, suggesting an induction of chondrocyte hypertrophy in the PLGA-based scaffolds. To conclude, this paper suggests that layering electrospun scaffolds and cell sheets is an efficient approach for the engineering of tissue transitions, and in particular the cartilage-bone transition. The use of PLGA-based scaffold might be particularly useful for the bone-cartilage reconstruction, since the differentiated tissue constructs seem to show characteristics of calcified cartilage. Copyright © 2013 John Wiley & Sons, Ltd.

Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity.

PubMed

Coca, Mircea; Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

2017-08-23

We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise.

Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense Physical Activity

PubMed Central

Tecle, Nahom; Amde, Wendewessen; Mehta, Ankur

2017-01-01

We report a case of combined central retinal vein occlusion and branch retinal artery occlusion. A previously healthy 47-year-old male presented with decreased vision in the right eye after completing a half marathon. A fundus exam and retinal imaging revealed a combined central retinal vein and branch retinal artery occlusion. In the present report, we review the literature and discuss the possible mechanisms behind combined retinal vessel occlusions. To our knowledge, this is the first reported case of combined central retinal vein occlusion and branch retinal artery occlusion following intense exercise. PMID:29067224

Antithrombotic Protein Filter Composed of Hybrid Tissue-Fabric Material has a Long Lifetime.

PubMed

Inoue, Yusuke; Yokota, Tomoyuki; Sekitani, Tsuyoshi; Kaneko, Akiko; Woo, Taeseong; Kobayashi, Shingo; Shibuya, Tomokazu; Tanaka, Masaru; Kosukegawa, Hiroyuki; Saito, Itsuro; Isoyama, Takashi; Abe, Yusuke; Yambe, Tomoyuki; Someya, Takao; Sekino, Masaki

2017-05-01

There are recent reports of hybrid tissue-fabric materials with good performance-high biocompatibility and high mechanical strength. In this study, we demonstrate the capability of a hybrid material as a long-term filter for blood proteins. Polyester fabrics were implanted into rats to fabricate hybrid tissue-fabric material sheets. The hybrid materials comprised biological tissue grown on the fabric. The materials were extracted from the rat's body, approximately 100 days post-implantation. The tissues were decellularized to prevent immunological rejection. An antithrombogenicity test was performed by dropping blood onto the hybrid material surface. The hybrid material showed lesser blood coagulation than polysulfone and cellulose. Blood plasma was filtered using the hybrid material to evaluate the protein removal percentage and the lifetime of the hybrid material in vitro. The hybrid material showed a comparable performance to conventional filters for protein removal. Moreover, the hybrid material could work as a protein filter for 1 month, which is six times the lifetime of polysulfone.

Silkworm Gut Fiber of Bombyx mori as an Implantable and Biocompatible Light-Diffusing Fiber

PubMed Central

Cenis, Jose Luis; Aznar-Cervantes, Salvador D.; Lozano-Pérez, Antonio Abel; Rojo, Marta; Muñoz, Juan; Meseguer-Olmo, Luis; Arenas, Aurelio

2016-01-01

This work describes a new approach to the delivery of light in deeper tissues, through a silk filament that is implantable, biocompatible, and biodegradable. In the present work, silkworm gut fibers (SGFs) of Bombyx mori L., are made by stretching the silk glands. Morphological, structural, and optical properties of the fibers have been characterized and the stimulatory effect of red laser light diffused from the fiber was assayed in fibroblast cultures. SGFs are formed by silk fibroin (SF) mainly in a β-sheet conformation, a stable and non-soluble state in water or biological fluids. The fibers showed a high degree of transparency to visible and infrared radiation. Using a red laser (λ = 650 nm) as source, the light was efficiently diffused along the fiber wall, promoting a significant increment in the cell metabolism 5 h after the irradiation. SGFs have shown their excellent properties as light-diffusing optical fibers with a stimulatory effect on cells. PMID:27438824

Trends and techniques for space base electronics. [mathematical models, ion implantation, and semiconductors

NASA Technical Reports Server (NTRS)

Gassaway, J. D.; Mahmood, Q.; Trotter, J. D.

1978-01-01

A system was developed for depositing aluminum and aluminum alloys by the D.C. sputtering technique. This system which was designed for a high level of cleanliness and ion monitoring the deposition parameters during film preparation is ready for studying the deposition and annealing parameters upon double level metal preparation. The finite element method was studied for use in the computer modeling of two dimensional MOS transistor structures. An algorithm was developed for implementing a computer study which is based upon the finite difference method. The program was modified and used to calculate redistribution data for boron and phosphorous which had been predeposited by ion implantation with range and straggle conditions typical of those used at MSFC. Data were generated for 111 oriented SOS films with redistribution in N2, dry O2 and steam ambients. Data are given showing both two dimensional effects and the evolution of the junction depth, sheet resistance and integrated dose with redistribution time.

Retinal oximetry in patients with ischaemic retinal diseases.

PubMed

Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

2017-03-01

The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO 2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO 2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO 2 was reduced, but raSatO 2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO 2 and might also be related to increased raSatO 2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO 2 but unrelated to raSatO 2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Retinitis Pigmentosa

MedlinePlus

... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to ...

Coated with nanomaterials intraocular lenses, ophthalmic and human body implantable devices with high catalytic antioxidant activities: a new nanotechnology strategy of peroxidase cellular enzyme mimics increasing the biocompatibility and therapeutic deployment of the medical prosthetic device.

PubMed

Babizhayev, Mark A

2013-04-01

While cataract surgery is generally recognized as being one of the safest operations, there is still a significant complication rate. From 30 to 50% of all patients in the United States having cataract extraction develop opacification of the posterior lens capsule within two years and require laser treatment with its own significant risk of complications. Of the patients having cataract surgery, 0.8% develop retinal detachments, from 0.6% to 1.3% were rehospitalized for corneal edema or required corneal transplantation and about 0.1% presented with endophthalmitis . Thus, aside from secondary cataract, about 2% of 1.3 million people, or 26,000 individuals in the United States annually develop serious complications as a result of cataract surgery. The aim of this investigation was to increase the safety and effectiveness of an individual intraocular lens (IOL) preventing an impairment in peroxide metabolism of the mature human cataractous lenses compared to normal lenses employing the specific nanotechnology coating which substitutes the inhibitory effect of the implantable device towards the active species of oxygen and the ability of IOL to regulate the H2O2 and lipid hydroperoxides levels in the surrounding medium. The implantation of IOLs with metabolic activity improves the capability of the surrounding ocular tissues to withstand oxidative stress induced in ocular humors by the photochemical and other metabolic reactions. The coated implantable medical device with thin film of platinum applied with magnetron sputtering, reacts as a body enzyme with deleterious peroxide compounds and free radical oxygen species in body fluids and tissue when said device is implanted into human body. The IOL having haptics coated with thin film of platinum, catalyzes the reduction of peroxide compounds to decrease their levels within the aqueous humor. Further, the coatings also scavenge toxic free radicals of oxygen, thus preventing cellular dysfunction resulting from oxidative attack. Coated IOLs according to the patented nanotechnology can address the vast majority of cataract surgery-induced complications, such as secondary cataract, intraocular inflammation (endophthalmitis) and foreign body reactions, cystoid macular oedema, corneal edema. The nanotechnology offers physicians and surgeons to develop and commercialize costeffective therapeutic medical implantable devices, products and support systems with metabolic activities for the treatment of ophthalmic diseases and of a wide range of pathological states and disorders which are treated by insertion of the implantable and prosthetic (polymeric) devices.

Comparison of ranibizumab versus dexamethasone for macular oedema following retinal vein occlusion: 1-year results of the COMRADE extension study.

PubMed

Feltgen, Nicolas; Hattenbach, Lars-Olof; Bertelmann, Thomas; Callizo, Josep; Rehak, Matus; Wolf, Armin; Berk, Hüsnü; Eter, Nicole; Lang, Gabriele E; Pielen, Amelie; Schmitz-Valckenberg, Steffen; Quiering, Claudia; Rose, Uwe; Hoerauf, Hans

2018-05-31

The COMRADE studies are the first randomized controlled head-to-head trials comparing the efficacy and safety of intravitreal ranibizumab versus dexamethasone (DEX) in patients with macular oedema secondary to retinal vein occlusion (RVO). The COMRADE extension trial was designed to provide additional 6-month data of patients who completed the core studies. In this open-label, phase IV study patients who completed the COMRADE core studies were prospectively enrolled. Overall, 92 branch RVO (BRVO) patients (ranibizumab 52, DEX 40) and 83 central RVO (CRVO) patients (ranibizumab 61, DEX 22) were treated, and 94.6% of BRVO patients and 97.6% of CRVO patients completed the extension study. Patients were assigned to the same treatment group as in the core studies. Patients were monitored monthly and received either 0.5 mg ranibizumab or a 0.7 mg DEX implant as needed. Over the course of the extension, treatment-emergent adverse events (TEAEs) of the study eye occurred in 55.8% of BRVO patients on ranibizumab and in 62.5% of those on DEX. Among CRVO patients, 65.5% in the ranibizumab group and 59.1% in the DEX group developed TEAEs. Overall, elevated intraocular pressure (IOP) was more frequent with DEX than ranibizumab treatment. Mean average change in best-corrected visual acuity (BCVA) in BRVO patients was significantly better for ranibizumab than DEX (p = 0.0249). The CRVO results were consistent with BRVO's, although not significant (p = 0.1119). When used according to the European labels, ranibizumab revealed a better ocular safety profile and produced greater average BCVA gains than DEX. By the end of the additional 6-month study period, this difference in BCVA was more pronounced in BRVO as in CRVO patients. The main limitation of the COMRADE studies was that DEX patients received only a single intravitreal treatment during the first 6 months, which is presumably not adequate. However, frequent DEX implants could lead to more steroid-related side effects, especially to an increased intraocular pressure. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Retinal expression of Fgf2 in RCS rats with subretinal microphotodiode array.

PubMed

Ciavatta, Vincent T; Kim, Moon; Wong, Paul; Nickerson, John M; Shuler, R Keith; McLean, George Y; Pardue, Machelle T

2009-10-01

To test the hypothesis that subretinal electrical stimulation from a microphotodiode array (MPA) exerts a neuroprotective effect in Royal College of Surgeons (RCS) rats through the induction of growth factors. At postnatal day 21, RCS rats were divided into four groups in which one eye per rat received treatment: (A) active MPA, (M) minimally active MPA, (S) sham surgery, or (C) no surgery and the opposite eye was unoperated. Dark- and light-adapted ERGs were recorded 1 week after surgery. A second set of A-, M-, and C-treated RCS rats had weekly ERG recordings for 4 weeks. Real-time RT-PCR was used to measure relative expression of mRNAs (Bdnf, Fgf2, Fgf1, Cntf, Gdnf, and Igf1) in retina samples collected 2 days after the final ERG. One week after surgery, there was a slight difference in dark-adapted ERG b-wave at the brightest flash intensity. Mean retinal Fgf2 expression in the treated eye relative to the opposite eye was greater for the A group (4.67 +/- 0.72) than for the M group (2.80 +/- 0.45; P = 0.0501), S group (2.03 +/- 0.45; P < 0.01), and C group (1.30 +/- 0.22; P < 0.001). No significant change was detected for Bdnf, Cntf, Fgf1, Gdnf, and Igf1. Four weeks after surgery, the A group had significantly larger dark- and light-adapted ERG b-waves than for the M and C groups (P < 0.01). Simultaneously, mean relative Fgf2 expression was again greater for the A group (3.28 +/- 0.61) than for the M (1.28 +/- 0.32; P < 0.05) and C (1.05 +/- 0.04; P < 0.05) groups. The results show subretinal implantation of an MPA induces selective expression of Fgf2 above that expected from a retina-piercing injury. Preservation of ERG b-wave amplitude 4 weeks after implantation is accompanied by elevated Fgf2 expression. These results suggest that Fgf2 may play a role in the neuroprotection provided by subretinal electrical stimulation.

Safety and efficacy of a low-cost glaucoma drainage device for refractory childhood glaucoma.

PubMed

Kaushik, Sushmita; Kataria, Pankaj; Raj, Srishti; Pandav, Surinder Singh; Ram, Jagat

2017-12-01

To evaluate the safety and efficacy of a low-cost glaucoma drainage device (GDD), Aurolab aqueous drainage implant (AADI), similar in design to the Baerveldt glaucoma implant (BGI), in refractory childhood glaucoma. This prospective interventional study was conducted in a tertiary care postgraduate teaching institute. Children aged <16 years with uncontrolled intraocular pressure (IOP) refractory to medical treatment and considered at high risk of failure following trabeculectomy were recruited. Eligible children were implanted with the AADI. Those completing minimum 6-month follow-up were included. Main outcome measures were IOP reduction from preoperative values and postoperative complications. 34 eyes of 31 patients were analysed. Average follow-up was 18.3±6.9 months. Mean IOP reduced from 27.4±7.5 mm Hg on maximum medication to 14.6±10.74 mm Hg, 13.8±7.5 mm Hg, 12.8±5.6 mm Hg and 14.7±5.8 mm Hg at 1 week, 6 months, 1 year (32 eyes of 29 children) and 2 years (25 eyes of 22 children) postoperatively, respectively (p<0.001). The cumulative probability of success was 91.18% at 6 months and 81.7% at 18-24 months. Mean number of topical medications decreased from 3.1±0.6 to 1.8±1.3 at 6 months and 1.6±1.1 at 24 months (p<0.001). Preoperatively, 25 patients required systemic acetazolamide, decreasing to three patients at 2 years. There was no tube erosion or infection. One eye developed retinal detachment. The AADI appears to be a viable low-cost GDD with effectiveness and safety profile comparable with published reports of the BGI and Ahmed glaucoma valve implant in children. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Outcomes of Ahmed glaucoma valve implantation in advanced primary congenital glaucoma with previous surgical failure.

PubMed

Huang, Jingjing; Lin, Jialiu; Wu, Ziqiang; Xu, Hongzhi; Zuo, Chengguo; Ge, Jian

2015-01-01

The purpose of this study was to evaluate the intermediate surgical results of Ahmed glaucoma valve (AGV) implantation in patients less than 7 years of age, with advanced primary congenital glaucoma who have failed previous surgeries. Consecutive patients with advanced primary congenital glaucoma that failed previous operations and had undergone subsequent AGV implantation were evaluated retrospectively. Surgical success was defined as 1) intraocular pressure (IOP) ≥6 and ≤21 mmHg; 2) IOP reduction of at least 30% relative to preoperative values; and 3) without the need for additional surgical intervention for IOP control, loss of light perception, or serious complications. Fourteen eyes of eleven patients were studied. Preoperatively, the average axial length was 27.71±1.52 (25.56-30.80) mm, corneal diameter was 14.71±1.07 (13.0-16.0) mm, cup-to-disc ratio was 0.95±0.04 (0.9-1.0), and IOP was 39.5±5.7 (30-55) mmHg. The mean follow-up time was 18.29±10.96 (5-44, median 18) months. There were significant reductions in IOPs and the number of glaucoma medications (P<0.001) postoperatively. The IOPs after operation were 11.3±3.4, 13.6±5.1, 16.3±2.7, and 16.1±2.6 mmHg at 1 month, 6 months, 12 months, and 18 months, respectively. Kaplan-Meier estimates of the cumulative probability of valve success were 85.7%, 71.4%, and 71.4% at 6, 12, and 18 months, respectively. Severe surgical complications, including erosion of tube, endophthalmitis, retinal detachment, choroidal detachment, and delayed suprachoroidal hemorrhage, occurred in 28.6% cases. AGV implantation remains a viable option for patients with advanced primary congenital glaucoma unresponsive to previous surgical intervention, despite a relatively high incidence of severe surgical complications.

Long-term outcomes of uveitic glaucoma treated with Ahmed valve implant in a series of Chinese patients.

PubMed

Bao, Ning; Jiang, Zheng-Xuan; Coh, Paul; Tao, Li-Ming

2018-01-01

To report long-term outcomes of secondary glaucoma due to uveitis treated with Ahmed glaucoma valve (AGV) implantation in a series of Chinese patients. The retrospective study included 67 eyes from 56 patients with uveitic glaucoma who underwent AGV implantation. Success of the treatment was defined as patients achieving intraocular pressure (IOP) levels between 6 and 21 mm Hg with or without additional anti-glaucoma medications and/or a minimum of 20% reduction from baseline IOP. The main outcome measurements included IOP, the number of glaucoma medications at 1, 3, 6, 12, 24, 36, 48 and 60mo after surgery, surgical complications, final best-corrected vision acuity (BCVA), visual field (VF) and retinal nerve fiber layer (RNFL). The mean follow-up was 53.3±8.5 (range 48 to 60)mo. The cumulative probability of success rate was 98.5%, 95.5%, 89.6%, 83.6%, 76.1%, 70.1%, 65.7% and 61.2% at 1, 3, 6, 12, 24, 36, 48 and 60mo, respectively. IOP was reduced from a baseline of 30.8±6.8 to 9.9±4.1, 10.1±4.2, 10.9±3.7, 12.9±4.6, 13.8±3.9, 13.2±4.6, 12.3±3.5 and 13.1±3.7 mm Hg at 1, 3, 6, 12, 24, 36, 48 and 60mo, respectively ( P <0.01). The number of postoperative glaucoma medications was significantly decreased compared with baseline at all time points during the study period ( P <0.05). There was no significant difference between preoperative and postoperative BCVA. Remarkable surgical complications were not found after surgery. The VF and RNFL of the patients were stable after the surgery. AGV implantation is safe and effect in terms of reducing IOP, decreasing the number of glaucoma medications, and preserving vision for patients with uveitic glaucoma.

Outcomes of Ahmed glaucoma valve implantation in advanced primary congenital glaucoma with previous surgical failure

PubMed Central

Huang, Jingjing; Lin, Jialiu; Wu, Ziqiang; Xu, Hongzhi; Zuo, Chengguo; Ge, Jian

2015-01-01

Purpose The purpose of this study was to evaluate the intermediate surgical results of Ahmed glaucoma valve (AGV) implantation in patients less than 7 years of age, with advanced primary congenital glaucoma who have failed previous surgeries. Patients and methods Consecutive patients with advanced primary congenital glaucoma that failed previous operations and had undergone subsequent AGV implantation were evaluated retrospectively. Surgical success was defined as 1) intraocular pressure (IOP) ≥6 and ≤21 mmHg; 2) IOP reduction of at least 30% relative to preoperative values; and 3) without the need for additional surgical intervention for IOP control, loss of light perception, or serious complications. Results Fourteen eyes of eleven patients were studied. Preoperatively, the average axial length was 27.71±1.52 (25.56–30.80) mm, corneal diameter was 14.71±1.07 (13.0–16.0) mm, cup-to-disc ratio was 0.95±0.04 (0.9–1.0), and IOP was 39.5±5.7 (30–55) mmHg. The mean follow-up time was 18.29±10.96 (5–44, median 18) months. There were significant reductions in IOPs and the number of glaucoma medications (P<0.001) postoperatively. The IOPs after operation were 11.3±3.4, 13.6±5.1, 16.3±2.7, and 16.1±2.6 mmHg at 1 month, 6 months, 12 months, and 18 months, respectively. Kaplan–Meier estimates of the cumulative probability of valve success were 85.7%, 71.4%, and 71.4% at 6, 12, and 18 months, respectively. Severe surgical complications, including erosion of tube, endophthalmitis, retinal detachment, choroidal detachment, and delayed suprachoroidal hemorrhage, occurred in 28.6% cases. Conclusion AGV implantation remains a viable option for patients with advanced primary congenital glaucoma unresponsive to previous surgical intervention, despite a relatively high incidence of severe surgical complications. PMID:26082610

SU-E-T-570: Management of Radiation Oncology Patients with Cochlear Implant and Other Bionic Devices in the Brain and Head and Neck Regions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, F.Q; Chen, Z; Nath, R

Purpose: To investigate the current status of clinical usage of cochlear implant (CI) and other bionic devices (BD) in the brain and head and neck regions (BH and N) and their management in patients during radiotherapy to ensure patient health and safety as well as optimum radiation delivery. Methods: Literature review was performed with both CIs and radiotherapy and their variants as keywords in PubMed, INSPEC and other sources. The focus was on CIs during radiotherapy, but it also included other BDs in BHȦN, such as auditory brainstem implant, bionic retinal implant, and hearing aids, among others. Results: Interactions betweenmore » CIs and radiation may cause CIs malfunction. The presence of CIs may also cause suboptimum dose distribution if a treatment plan was not well designed. A few studies were performed for the hearing functions of CIs under irradiations of 4 MV and 6 MV x-rays. However, x-rays with higher energies (10 to 18 MV) broadly used in radiotherapy have not been explored. These higher energetic beams are more damaging to electronics due to strong penetrating power and also due to neutrons generated in the treatment process. Modern CIs are designed with more and more complicated integrated circuits, which may be more susceptible to radiation damage and malfunction. Therefore, careful management is important for safety and treatment outcomes. Conclusion: Although AAPM TG-34, TG-63, and TG-203 (update of TG-34, not published yet) reports may be referenced for management of CIs and other BDs in the brain and H and N regions, a site- and device-specified guideline should be developed for CIs and other BDs. Additional evaluation of CI functions under clinically relevant set-ups should also be performed to provide clinicians with better knowledge in clinical decision making.« less

Real-life clinical data for dexamethasone and ranibizumab in the treatment of branch or central retinal vein occlusion over a period of six months.

PubMed

Winterhalter, Sibylle; Eckert, Annabelle; Vom Brocke, Gerrit-Alexander; Schneider, Alice; Pohlmann, Dominika; Pilger, Daniel; Joussen, Antonia M; Rehak, Matus; Grittner, Ulrike

2018-02-01

To evaluate the therapeutic outcome for dexamethasone implant (DEX) or intravitreal ranibizumab (IVR) injections over 6 months in patients with macular edema due to branch or central retinal vein occlusion (BRVO, CRVO), in a real-life setting. A total of 107 patients with BRVO or CRVO were included into this retrospective single-center observational study. Patients were treated with monotherapy consisting of DEX or three monthly IVR injections following a pro re nata regimen (PRN). Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP) were compared between the two therapy groups after 1, 3 and 6 months. BRVO patients treated with DEX achieved a statistically significant gain in BCVA measured in logMAR after 1 month (mean gain, 95% CI: 0.21, 0.08-0.34, p = 0.001), 3 months (0.16, 0.03-0.28, p = 0.012) and 6 months (0.19, 0.07-0.32, p = 0.002), whereas patients treated with IVR showed a statistically significant BCVA gain in month 3 (mean improvement, 95% CI: 0.13, 0.01-0.26, p = 0.039) and month 6 (0.16, 0.03-0.29, p = 0.018). BCVA in CRVO patients with DEX worsened slightly at month 6 (mean worsening, 95% CI: -0.08, -0.24 to 0.08, p = 0.305), while IVR treated-patients achieved a statistically significant BCVA gain at 3 months (mean improvement, 95% CI: 0.14, 0.02-0.25, p = 0.021). Both therapies were accompanied by statistically significant CRT reductions of 150 to 200 μm (median). Adverse events reported were predictable and limited. In a clinical setting, comparable improvement in BCVA and CRT were observed after DEX and IVR injections for treatment of BRVO. CRVO patients showed greater benefit with IVR.

Retinal Oximetry Discovers Novel Biomarkers in Retinal and Brain Diseases.

PubMed

Stefánsson, Einar; Olafsdottir, Olof Birna; Einarsdottir, Anna Bryndis; Eliasdottir, Thorunn Scheving; Eysteinsson, Thor; Vehmeijer, Wouter; Vandewalle, Evelien; Bek, Toke; Hardarson, Sveinn Hakon

2017-05-01

Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimer's disease. Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy. In diabetic retinopathy, venous oxygen saturation increases and arteriovenous difference decreases. Both correlate with diabetic retinopathy severity as conventionally classified on fundus photographs. In CRVO, vein occlusion causes hypoxia, which is measured directly by retinal oximetry to confirm the diagnosis and measure severity. In both diseases, the change in oxygen levels is a consequence of disturbed blood flow with resulting tissue hypoxia and vascular endothelial growth factor (VEGF) production. In atrophic diseases, such as retinitis pigmentosa and glaucoma, retinal oxygen consumption is reduced and this is detected by retinal oximetry. Retinal oximetry correlates with visual field damage and retinal atrophy. It is an objective metabolic measure of the degree of retinal atrophy. Finally, the retina is part of the central nervous system tissue and reflects central nervous system diseases. In Alzheimer's disease, a change in retinal oxygen metabolism has been discovered. Retinal oximetry is a novel, noninvasive technology that opens the field of metabolic imaging of the retina. Biomarkers in metabolic, ischemic, and atrophic diseases of the retina and central nervous system have been discovered.

Superficial retinal precipitates in patients with syphilitic retinitis.

PubMed

Fu, Evelyn X; Geraets, Ryan L; Dodds, Emilio M; Echandi, Laura V; Colombero, Daniel; McDonald, H Richard; Jumper, J Michael; Cunningham, Emmett T

2010-01-01

The purpose of this study was to describe the occurrence of superficial retinal precipitates in patients with syphilitic retinitis. This was a retrospective, observational case series of nine eyes of eight patients with syphilitic retinitis associated with superficial retinal precipitates. The clinical, photographic, angiographic, and laboratory records were reviewed. Characteristics and treatment response of these superficial retinal precipitates were observed. All patients were Caucasian men, including 5 men who have sex with men (62.5%) and 6 (75.0%) who were positive for human immunodeficiency virus. None of the patients were previously diagnosed with syphilis. All patients developed panuveitis and a distinctly diaphanous or ground-glass retinitis associated with creamy yellow superficial retinal precipitates. In 3 patients (37.5%), the retinitis had a distinctive wedge-shaped appearance. Five patients (62.5%) had associated retinal vasculitis, 3 (37.5%) had serous retinal detachment, 2 (22.2%) had intraretinal hemorrhage, and 2 (22.2%) had papillitis. Within 2 weeks of initiating intravenous penicillin treatment, 7 patients (87.5%) experienced visual recovery to >or= 20/40. All affected eyes showed rapid resolution of clinical signs with minimal alternations of the retinal pigment epithelium in areas of prior retinitis after completion of antibiotic therapy. Characteristic superficial retinal precipitates may occur over areas of syphilitic retinitis. Improved recognition of this highly suggestive clinical sign may aid in early diagnosis and treatment.

Formation and Decay of the Arrestin·Rhodopsin Complex in Native Disc Membranes*

PubMed Central

Beyrière, Florent; Sommer, Martha E.; Szczepek, Michal; Bartl, Franz J.; Hofmann, Klaus Peter; Heck, Martin; Ritter, Eglof

2015-01-01

In the G protein-coupled receptor rhodopsin, light-induced cis/trans isomerization of the retinal ligand triggers a series of distinct receptor states culminating in the active Metarhodopsin II (Meta II) state, which binds and activates the G protein transducin (Gt). Long before Meta II decays into the aporeceptor opsin and free all-trans-retinal, its signaling is quenched by receptor phosphorylation and binding of the protein arrestin-1, which blocks further access of Gt to Meta II. Although recent crystal structures of arrestin indicate how it might look in a precomplex with the phosphorylated receptor, the transition into the high affinity complex is not understood. Here we applied Fourier transform infrared spectroscopy to monitor the interaction of arrestin-1 and phosphorylated rhodopsin in native disc membranes. By isolating the unique infrared signature of arrestin binding, we directly observed the structural alterations in both reaction partners. In the high affinity complex, rhodopsin adopts a structure similar to Gt-bound Meta II. In arrestin, a modest loss of β-sheet structure indicates an increase in flexibility but is inconsistent with a large scale structural change. During Meta II decay, the arrestin-rhodopsin stoichiometry shifts from 1:1 to 1:2. Arrestin stabilizes half of the receptor population in a specific Meta II protein conformation, whereas the other half decays to inactive opsin. Altogether these results illustrate the distinct binding modes used by arrestin to interact with different functional forms of the receptor. PMID:25847250

The eyes of Tullimonstrum reveal a vertebrate affinity.

PubMed

Clements, Thomas; Dolocan, Andrei; Martin, Peter; Purnell, Mark A; Vinther, Jakob; Gabbott, Sarah E

2016-04-28

Tullimonstrum gregarium is an iconic soft-bodied fossil from the Carboniferous Mazon Creek Lagerstätte (Illinois, USA). Despite a large number of specimens and distinct anatomy, various analyses over the past five decades have failed to determine the phylogenetic affinities of the 'Tully monster', and although it has been allied to such disparate phyla as the Mollusca, Annelida or Chordata, it remains enigmatic. The nature and phylogenetic affinities of Tullimonstrum have defied confident systematic placement because none of its preserved anatomy provides unequivocal evidence of homology, without which comparative analysis fails. Here we show that the eyes of Tullimonstrum possess ultrastructural details indicating homology with vertebrate eyes. Anatomical analysis using scanning electron microscopy reveals that the eyes of Tullimonstrum preserve a retina defined by a thick sheet comprising distinct layers of spheroidal and cylindrical melanosomes. Time-of-flight secondary ion mass spectrometry and multivariate statistics provide further evidence that these microbodies are melanosomes. A range of animals have melanin in their eyes, but the possession of melanosomes of two distinct morphologies arranged in layers, forming retinal pigment epithelium, is a synapomorphy of vertebrates. Our analysis indicates that in addition to evidence of colour patterning, ecology and thermoregulation, fossil melanosomes can also carry a phylogenetic signal. Identification in Tullimonstrum of spheroidal and cylindrical melanosomes forming the remains of retinal pigment epithelium indicates that it is a vertebrate; considering its body parts in this new light suggests it was an anatomically unusual member of total group Vertebrata.

Cellular regeneration strategies for macular degeneration: past, present and future.

PubMed

Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H

2018-05-01

Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

Ahmed glaucoma valve in eyes with preexisting episcleral encircling element.

PubMed

Choudhari, Nikhil Shreeram; George, Ronnie; Shantha, Balekudaru; Neog, Aditya; Tripathi, Shweta; Srinivasan, Bhaskar; Vijaya, Lingam

2014-05-01

To describe the use of Ahmed glaucoma valve (AGV) in the management of intractable glaucoma in eyes with a preexisting episcleral encircling element. This is a retrospective, consecutive, noncomparative study. The study included 12 eyes of 12 patients with a preexisting episcleral encircling element that underwent implantation of silicone AGV to treat intractable glaucoma during January 2009 to September 2010. The mean patient age was 25.6 (standard deviation 17.1) years. Five (41.6%) patients were monocular. The indications for AGV were varied. The mean duration between placement of episcleral encircling element and implantation of AGV was 30.5 (33.8) months. The mean follow-up was 37.4 (22.9) weeks. Preoperatively, the mean intraocular pressure (IOP) was 31.4 (7.9) mmHg and the mean antiglaucoma medications were 2.8. At the final postoperative follow-up, the mean IOP was 12.5 (3.5) mmHg and the mean number of antiglaucoma medications was 0.8 (P < 0.001). The complications observed over the follow-up period did include corneal graft failure in three eyes, tube erosion in two eyes and rhegmatogenous retinal detachment in one eye. AGV is an effective option in the management of intractable glaucoma in eyes with a preexisting episcleral encircling element keeping in mind the possibility of significant postoperative complications.