Biomedical subjects

Mark S Humayun

Publications and source records attributed to Mark S Humayun.

At least 19 recordsLinked to original sources

PubMed2007

A novel method to oxygenate intraocular irrigation fluids with an in-line oxygenator.

PURPOSE: We describe a novel method to oxygenate intraocular irrigation solutions involving an in-line oxygenator. METHODS: Either lactated Ringer (LR) solution or balanced salt solution (BSS) was oxygenated with the FE390 Stainless In-line Oxygenation Assembly (Beer, Beer, and More Beer, Concord, CA). After running a 100-mL of solution through the in-line oxygenator, oxygen saturation was measured with a dissolved oxygen meter. A control experiment involving the oxygenator without oxygen perfusion was performed. Paired t-tests were used to compare oxygen saturation changes before and after oxygenation. RESULTS: In comparison with the original BSS, there was an increase in oxygen saturation of 162 +/- 47% (n = 40; P < 0.05). Without oxygenation perfusion, there was only a 24 +/- 14% (n = 40) increase in oxygen levels in BSS, which was significantly lower than that in treated BSS (P < 0.05). In comparison with the original LR solution, there was an increase in oxygen saturation of 208 +/- 21% (n = 40; P < 0.05). Without oxygenation perfusion, there was only a 21 +/- 9% (n = 40) gain in oxygen saturation in the control LR solution, which was statistically lower as well (P < 0.05). CONCLUSION: The in-line oxygenator is an efficient tool for oxygenating BSS and LR solution. It represents a potential efficient and convenient method to oxygenate irrigating solutions for vitreoretinal surgeries.

Acetates↗

PubMed2007

Effect of oxygenated intraocular irrigation solutions on the electroretinogram after vitrectomy.

PURPOSE: To investigate the effect of oxygenated intraocular irrigating solutions on electroretinograms (ERGs) for postvitrectomy rabbits. METHODS: Eight groups of five rabbits each underwent pars plana vitrectomy on the right eye; the left eye of each rabbit served as control. The intraocular irrigating solutions were balanced salt solution (BSS), BSS-plus, BSS + oxygen (BSS + O2), BSS-plus + O2, and combinations of each with the addition of endoillumination (L). All animals were evaluated by single-flash scotopic electroretinography on the operated and nonoperated eyes before surgery and at 1 hour, 1 day, 1 week, and 1 month after surgery by an unmasked observer. The main outcome measures were dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios. The results for the different groups were compared by analysis of variance. RESULTS: Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS-plus and BSS-plus + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.01 +/- 0.09, 0.50 +/- 0.11, 0.95 +/- 0.11, 0.97 +/- 0.11, and 0.99 +/- 0.08 and 0.98 +/- 0.08, 0.59 +/- 0.10, 0.92 +/- 0.06, 0.97 +/- 0.08, and 0.97 +/- 0.10, respectively. At both 1 hour and 1 day after surgery, rabbits treated with BSS-plus + O2 had an earlier b-wave return to baseline findings, but the differences were not statistically significant (P > 0.05). Mean dark-adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS and BSS + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.02 +/- 0.10, 0.47 +/- 0.09, 0.77 +/- 0.07, 0.89 +/- 0.07, and 0.89 +/- 0.07 and 1.02 +/- 0.06, 0.62 +/- 0.16, 0.94 +/- 0.09, 0.97 +/- 0.08, and 0.96 +/- 0.06, respectively. One hour and 1 day after surgery, ERG readings for rabbits treated with BSS + O2 exhibited a statistically significantly earlier return of ERG voltage to baseline values compared with both BSS and BSS + L (P = 0.05 and P = 0.02, respectively). One day after surgery, rabbits treated with BSS alone had the lowest ERG ratios. One week and 1 month after surgery, for all solutions tested other than BSS, ERG values were within normal limits. CONCLUSION: The use of oxygenated solutions appears to affect ERG readings after pars plana vitrectomy. Further studies to evaluate the role of oxygenated solutions in different vitreoretinal surgical procedures are warranted.

Acetates↗

PubMed2006

Electrical stimulation in normal and retinal degeneration (rd1) isolated mouse retina.

Stimulus threshold and response latencies were measured for electrically elicited retinal ganglion cell responses in retina isolated from the eyes of normal and retinal degenerate (rd1) mice. Stimulation of the ganglion cell-side in normal retina yielded a significantly lower mean threshold and shorter latency when compared with stimulation of the photoreceptor side in normal retina. The latency of the ganglion cell-side stimulation in normal retina also proved to be significantly shorter than the latency for stimulation of the ganglion cell side in rd1 retina. Thus both the electrode positioning as well as the health of the retinal tissue play a role in the stimulating current required to elicit a retinal response.

Animals↗

PubMed2006

In vitro and in vivo evaluation of ultrananocrystalline diamond for coating of implantable retinal microchips.

In this work, ultrananocrystalline diamond (UNCD) thin films were evaluated for use as hermetic and bioinert coatings for a retinal microchip. These films were deposited on highly conductive Si substrates at different temperatures (from 400 to 800 degrees C), using microwave plasma enhanced chemical vapor deposition with argon-rich Ar/CH4 gas mixtures and different relative amounts of hydrogen (0-20%). Scanning electron microscopy studies showed that all the films are dense and continuous. Results of cyclic voltammetry test revealed that when there was <2% of hydrogen in the plasma, the film obtained renders the surface electrochemically inactive, with very low leakage currents ( approximately 4 x 10(-7) A/cm2 at +/-5 V). In addition, in vivo tests of the UNCD-coated Si samples were performed by implanting them in the eyes of rabbits for 4-6 months within the eye physiological environment. According to all these results, it was concluded that UNCD is a promising candidate for use as the encapsulating coatings for implantable retinal microelectronic devices.

Animals↗

PubMed2006

Electrical stimulation in isolated rabbit retina.

Experiments were conducted to assess the effect of stimulating electrode parameters (size, position, and waveform shape) on electrically elicited ganglion cell action potentials from isolated rabbit retina. Thirty-eight isolated rabbit retinas were stimulated with bipolar stimulating electrodes (either 125 or 25 microm in diameter) positioned on either the ganglion or the photoreceptor side. Recording electrodes were placed between the optic disc and the stimulating electrodes. Cathodic-first, biphasic, current waveforms of varying pulse durations (0.1, 0.5, 1 ms) were used. For the four conditions tested (125-electrode and 25-microm electrode, ganglion cell, and photoreceptor positions) threshold currents ranged from 6.7 to 23.6 microA, depending on location and pulse duration. With 1-ms pulse duration, no statistically significant difference was seen between threshold currents when either size electrode was used to stimulate either the ganglion cell side or the photoreceptor side. For all groups, the threshold currents using the 1-ms pulse were lower than those using 0.1 ms, but the 0.1-ms pulses used less charge. These experiments provide a number of valuable insights into the relative effects of several stimulation parameters critical to the development of an implanted electronic retinal prosthesis.

Action Potentials↗

PubMed2006

Paragraph text reading using a pixelized prosthetic vision simulator: parameter dependence and task learning in free-viewing conditions.

PURPOSE: To investigate the feasibility of adequate reading by recipients of future prosthetic visual implants through simulation in sighted observers. METHODS: Four normally sighted subjects used a video headset to view short-story segments at a sixth grade reading level, presented in 6- to 11-word paragraphs through a pixelizing grid defined by five parameters (dot size, grid size, dot spacing, random dropout percentage, and gray-scale resolution). Grid parameters were varied individually, and four character sizes and two contrast levels were used. RESULTS: Reading speeds of 30 to 60 words per minute without errors were recorded for some parameter combinations. In general, reading accuracy and speed were influenced by all parameters. Reading accuracy exceeded 90% if the following conditions were met: At least 3 dots/charwidth were presented, and dropout did not exceed 50%. Reading speed deteriorated below 20 words per minute if accuracy fell below 90% and at low contrast if the grid spanned less than two characters. CONCLUSIONS: It is uncertain whether and to what extent retinal reorganization may limit the perception of multiple phosphenes by blind prosthesis recipients. If distinct phosphenes can be perceived, these results suggest that a 3 x 3-mm2 prosthesis with 16 x 16 electrodes should allow paragraph reading. The effects of stabilizing the dot grid on the retina must be investigated further.

Adult↗

PubMed2006

Retinal prostheses for the blind.

INTRODUCTION: Using artificial means to treat extreme vision impairment has come closer to reality during the past few decades. The goal of this research has been to create an implantable medical device that provides useful vision for those patients who are left with no alternatives. Analogous to the cochlear implants for some forms of hearing loss, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that excite the remaining viable inner retinal neurons in patients with retinitis pigmentosa or age-related macular degeneration. METHODS: Data for this review were selected through a comprehensive literature search. RESULTS: Advances in microtechnology have facilitated the development of a variety of prostheses that can be implanted in the visual cortex, around the optic nerve, or in the eye. Some of these approaches have shown the promise of providing useful visual input to patients with visual impairments. CONCLUSION: While the development of various retinal prostheses have shown promise in limited clinical trials, there are distinct advantages and disadvantages for each type of prosthesis. This review will focus primarily on the Epiretinal Intraocular Retinal Prosthesis, studied by our group, but will also briefly review other modalities: the subretinal prosthesis, cortical prosthesis, and optic nerve prosthesis.

Electric Stimulation Therapy↗

PubMed2005

Nanobiolistic delivery of indicators to the living mouse retina.

The development of a technique to load functional indicators into living neurons is an ongoing challenge in retinal neurophysiology. In a number of live-cell preparations, fluorescence-based indicators have been of particular importance for investigating ionic concentrations, protein localization, and other physiological parameters. In the present study, we demonstrate a novel technique that uses a modified gene gun to propel silver nanoparticles coated with indicators into live retinal neurons, and we highlight the advantages of using this technique to deliver these functional indicators.

Animals↗

PubMed2005

Implantation of an inactive epiretinal poly(dimethyl siloxane) electrode array in dogs.

The aim of this study is to investigate the long-term, mechanical biocompatibility of a polymer microtechnology that can be used to position electrodes in close proximity to the retina. Poly(dimethylsiloxane) (PDMS) arrays were manufactured by soft-lithography at Lawrence Livermore National Laboratory. The PDMS implant measured 4 mm x 40 mm x 55-60 microm and included 4-8 electrodes. Micromolded ribs were placed at the perimetry for strength and ease of manipulation. The PDMS arrays were implanted epiretinally in four normal dogs, with a single retinal tack used in each case to hold the device on the retina. The mechanical effects of the implant were followed up after surgical implantation by photography, fluorescein angiography, optical coherence tomography (OCT), and electrophysiologic tests. An intraoperative retinal tear occurred in the first implanted dog, causing retinal detachment and necessitating termination. The remaining dogs experienced no gross complications secondary to the array implantation procedure. During the follow-up period of 2 months in one eye and 6 months in three eyes, OCT demonstrated that the arrays were in close contact with the retina. Fluorescein angiography showed good perfusion of the retina under the array. At the end of 6 months, there was no statistical difference from baseline in mean retinal thickness under the array (P=0.43) or peripapillary retinal nerve fibre layer thickness corresponding to the implanted area (P=0.34). The mean distance between the array and the retinal surface varied from 32 to 68 microm throughout the follow-up. Histopathologic evaluation of the retinal implantation site in eyes followed for 6 months showed a general preservation of the normal, layered retinal structure, except for some localized retinal thinning in two eyes, where the array frame had been in direct retinal contact. The PDMS substrate micro array is a new and promising technology that can be scaled to support a high-density retinal stimulating array. Its implantation and handling is surgically manageable, and it forms a mechanically stable, acceptable interface with the inner retinal surface.

Animals↗

PubMed2005

Long-term stimulation by active epiretinal implants in normal and RCD1 dogs.

An epiretinal prosthesis, consisting of an extraocular microelectronic stimulator and an intraocular electrode array, was implanted in one eye of three blind and three sighted dogs. Three dogs (2 blind, 1 normal) were stimulated for 120 days, and two dogs (both normal) for 60 and 103 days respectively for 8-10 h/day at levels of 0.1 mC cm(-2) and 0.05 mC cm(-2), with each stimulus level presented to half of the array. One blind dog was kept as an inactive implant control. During the study period, electroretinograms (ERG) and fundus photographs were recorded. At the end of the study period, the dogs were sacrificed and histological and morphometric evaluation was made of the retina. No inflammatory reaction, neovascularization or hemorrhage was observed during the follow-up examinations. ERGs were unchanged. Stimulus levels used were of sufficient amplitude to elicit cortical evoked potentials. Histological evaluation showed no inflammatory infiltrates or changes in retina morphometry related to electrical stimulation when compared to the unstimulated control eye. Morphometric analysis revealed no consistent differences relating to electrical stimulation. In summary, chronic electrical stimulation of the dog retina at up to 0.1 mC cm(-2) with an epiretinal prosthesis does not appear to adversely affect the retina.

Animals↗

PubMed2005

Outcomes of 140 consecutive cases of 25-gauge transconjunctival surgery for posterior segment disease.

PURPOSE: To evaluate the safety and efficacy of 25-gauge instrumentation for a variety of vitreoretinal conditions on previously nonvitrectomized eyes. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: One-hundred forty eyes of 140 patients were evaluated at the Doheny Retina Institute from July 2002 to July 2003. INTERVENTION: All patients underwent surgical procedures using the Millennium 25-gauge Transconjunctival Standard Vitrectomy system. Twenty eyes (14.3%) underwent procedures without vitrectomy. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), intraocular pressure, surgical time, postoperative inflammation, complications, and number of sutured sites. RESULTS: No intraoperative complications were noted. No cases required conversion to 20-gauge machines. Ten cases (7.1%) involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure, but 5 of these entry sites were enlarged to facilitate larger instrumentation for tissue manipulation. Median VA improved from 20/250 (logarithm of the minimum angle of resolution, 1.08+/-0.47) preoperatively to 20/60 (0.47+/-0.30) (P<0.0001) at final visit. Mean follow-up was 33.8+/-9.7 weeks, and all eyes were observed for a minimum of 12 weeks. Mean total surgical time was 17.4+/-6.9 minutes. Intraocular pressures remained stable throughout the postoperative course. Five eyes (3.8%) presented on day 1 with shallow choroidal detachments, but all resolved by day 7, and none required volume infusion during the postoperative period. All but one of these cases was within the first 50 procedures performed. No detectable inflammation was noted in any eyes by 4 weeks postoperatively. No case of retinal detachment or endophthalmitis was recorded. CONCLUSIONS: Transconjunctival surgery using 25-gauge instrumentation may hasten postoperative recovery by decreasing overall surgical time and postoperative inflammation. Procedures requiring minimal intraocular manipulation did not require sutures and, thus, may be better suited for this surgical modality.

Aged↗

PubMed2005

Rapid recurrence of geographic atrophy after full macular translocation for nonexudative age-related macular degeneration.

OBJECTIVE: To report the recurrence of geographic atrophy (GA) in a patient with nonexudative age-related macular degeneration (AMD) after full macular translocation. DESIGN: Observational case report. METHODS: Review of the clinical, photographic, and angiographic records of a patient with GA who underwent full macular translocation. MAIN OUTCOME MEASURES: Progression of GA. RESULTS: A 73-year-old man with GA secondary to nonexudative AMD underwent a macular translocation with 360 peripheral retinectomy (MT 360) in his left eye. On postoperative month 4, fundus photography showed subtle alterations of the pigment underneath the translocated foveal region. On postoperative month 9, the visual acuity worsened to preoperative levels and there was frank retinal pigment epithelium atrophy involving the new macular region. CONCLUSIONS: The rapid recurrence and development of GA in the translocated fovea after MT 360 raise new questions regarding the pathogenesis of GA. They also raise concerns regarding the use of MT 360 in the management of nonexudative AMD.

Aged↗

PubMed2005

Perceptual thresholds and electrode impedance in three retinal prosthesis subjects.

Three test subjects blind from retinitis pigmentosa were implanted with retinal prostheses as part of a FDA-approved clinical trial. The implant consisted of an extraocular unit that contained electronics for wireless data, power, and generation of stimulus current, and an intraocular unit that consisted of 16 platinum stimulating electrodes arranged in a 4 x 4 pattern within a silicone rubber substrate. The array was held to the retina by a small tack. The stimulator was connected to the array by a multiwire cable and was controlled by a computer based external system that allowed precise control over each electrode. Perception thresholds and electrode impedance were obtained on each electrode from the subjects over several months of testing. The electrode distance from the retina was determined from optical coherence tomography imaging of the array and retina. Across all subjects, average thresholds ranged from 24-702 microA (1-ms pulse). The data show that proximity to the retina played a role in determining the threshold and impedance, but only for electrodes that were greater than 0.5 mm from the retina.

Blindness↗

PubMed2005

Retinal prosthesis.

Retinal prostheses represent the best near-term hope for individuals with incurable, blinding diseases of the outer retina. On the basis of the electrical activation of nerves, prototype retinal prostheses have been tested in blind humans and have demonstrated the capability to elicit the sensation of light and to give test subjects the ability to detect motion. To improve the visual function in implant recipients, a more sophisticated device is required. Simulations suggest that 600-1000 pixels will be required to provide visual function such as face recognition and reading. State-of-the-art implantable stimulator technology cannot produce such a device, which mandates the advancement of the state of the art in areas such as analog microelectronics, wireless power and data transfer, packaging, and stimulating electrodes.

Animals↗

PubMed2005

Laser-induced changes in intraretinal oxygen distribution in pigmented rabbits.

PURPOSE: To make the first measurements of intraretinal oxygen distribution and consumption after laser photocoagulation of the retina and to compare the efficiency of micropulsed (MP) and continuous wave (CW) laser delivery in achieving an oxygen benefit in the treated area. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth before and after laser treatment in anesthetized, mechanically ventilated, Dutch Belted rabbits (n = 11). Laser lesions were created by using a range of power levels from an 810-nm diode laser coupled with an operating microscope delivery system. MP duty cycles of 5%, 10%, and 15% were compared with CW delivery in each eye. RESULTS: Sufficient power levels of both the CW and MP laser reduced outer retinal oxygen consumption and increased oxygen level within the retina. At these power levels, which correlated with funduscopically visible lesions, there was histologically visible damage to the RPE and photoreceptors. Retinal damage was energy dependent but short-duty-cycle MP delivery was more selective in terms of retinal cell damage, with a wider safety range in comparison with CW delivery. CONCLUSIONS: The relationship between laser power level and mode of delivery and the resultant changes in oxygen metabolism and oxygen level in the retina was determined. Only partial destruction of RPE and photoreceptors is necessary, to produce a measurable oxygen benefit in the treated area of retina.

Animals↗

PubMed2004

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis.

PURPOSE: Pigment epithelium-derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models. In this study, we sought to measure the levels of PEDF and vascular endothelial growth factor (VEGF) in the vitreous of patients with and without ocular neovascular disorders. DESIGN: Case-control study of patients undergoing intraocular surgery for a variety of neovascular and nonneovascular conditions. METHODS: Vitreous samples were collected from 65 eyes of 65 patients with no neovascular disorder (n = 24), choroidal neovascularization (n = 9), active proliferative diabetic retinopathy (n = 16), and inactive proliferative diabetic retinopathy (n = 16). The levels of VEGF and PEDF in these vitreous samples were determined by enzyme-linked immunosorbent assay. RESULTS: The VEGF levels were at or below the level of detectability in the reference and choroidal neovascularization groups. The VEGF levels were significantly elevated in both the active and inactive PDR groups, and significantly higher in the active PDR group as compared with the inactive PDR group. The PEDF levels, which were present at relatively high concentrations in all groups, were higher in patients with active PDR compared with the control and choroidal neovascularization groups. CONCLUSIONS: High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or nonneovascular retinal diseases. Although these results do not preclude the possibility that endogenous PEDF helps to modulate ocular neovascularization, they do not support ischemia-induced downregulation of PEDF as a mechanism for such modulation.

Adult↗

PubMed2004

Use of rotational sutures for limited retinal translocation: a new technique for superior limited macular translocation.

PURPOSE: To report a modified surgical technique for retinal translocation in eyes with subfoveal choroidal neovascularization. DESIGN: Experimental animal study. METHODS: Nine pigmented rabbits were used consecutively to apply this technique. Placement of inferotemporal scleral imbrication sutures was followed by vitrectomy with posterior hyaloid separation. Balanced saline solution (BSS) was injected subretinally with a 30G needle or with a 39G hydrodissection cannula and viscous fluid injector to detach one retinal quadrant. Under low intraocular pressure, the imbrication sutures were tied, the sclerotomy sites were closed, and intravitreal air tamponade was injected. Rotation sutures were passed and the eye globe was rotated approximately 90 degrees counterclockwise. The rotation sutures were removed after 24 hours. Retinal photographs were taken and fundus examination was performed on postoperative days 1, 2 and 7. The animals were sacrificed after 7 to 10 days for postmortem macroscopic examination. RESULTS: The entire procedure was performed in nine eyes of nine rabbits. In eight eyes, translocation could be seen on the first postoperative day after removal of the rotation sutures. The average amount of translocation was 667 microm (range: 500-800 microm) in a nasal to inferonasal direction. Vitreous hemorrhage occurred at the end of surgery in one eye due to hypotony. Iatrogenic small retinal breaks occurred in 2 eyes but did not prevent completion of the procedure. There was only a temporary hyperemia of the eyelids and conjunctiva. CONCLUSION: Limited retinal translocation using rotational sutures provided a predictable amount of translocation in the planned direction. This technique is expected to be useful for superior macular translocation in humans.

Animals↗

PubMed2004

Retinal vein cannulation with prolonged infusion of tissue plasminogen activator (t-PA) for the treatment of experimental retinal vein occlusion in dogs.

PURPOSE: To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model. DESIGN: Experimental animal study. METHODS: This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 mug, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology. RESULTS: A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only. CONCLUSIONS: Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.

Animals↗