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Biomedical subjects

Michael F Marmor

Publications and source records attributed to Michael F Marmor.

At least 19 recordsLinked to original sources

Precision and safety of the pulsed electron avalanche knife in vitreoretinal surgery.

BACKGROUND: We have developed a new surgical instrument, called the pulsed electron avalanche knife (PEAK; Carl Zeiss Meditec, Jena, Germany), for precise, "cold," and tractionless dissection of tissue in liquid media. OBJECTIVE: To evaluate the 3-dimensional damage zone induced by the PEAK compared with 2 other standard intraocular surgical instruments, diathermy and retinal scissors. METHODS: Damage zone and minimum safe distance were measured in vitro on chick chorioallantoic membrane and in vivo on rabbit retina with the use of propidium iodide staining. RESULTS: The PEAK produced a paracentral zone of cellular structure disruption surrounding a crater and a peripheral zone of structurally intact but abnormally permeable cells. The instrument induced a damage radius that varied from 55 to 300 micro m for the range of voltages and pulses typically used during surgery. For comparison, damage radius for microsurgical scissors was 50 micro m, and for diathermy, 400 to 850 micro m. The PEAK also damaged tissue up to 1.4 mm away by the creation of water flow that formed at the tip of convex probes during collapse of a cavitation bubble. Concave probes, which prevent formation of the water jet, eliminated this effect. CONCLUSIONS: The PEAK operated well within accept-able safety limits and may greatly facilitate both posterior segment surgeries (eg, membrane dissection and sheathotomy) and anterior segment procedures (eg, capsulotomy, nonpenetrating trabeculectomy, and iridectomy).

Allantois↗

The lens-coating agent and the electroretinogram.

PURPOSE: To investigate the effects of 0.5, 1.0 and 2.5% methylcellulose coating agents on the ERG in normals. METHODS: A total of 15 healthy volunteers underwent photopic ERG recordings in three experimental protocols comparing 0.5, 1.0 and 2.5% methylcellulose solutions. The conductivity of the solutions was measured. RESULTS: The difference between 0.5 and 1.0% solutions showed significant changes (p < 0.05) in ERG amplitudes. The 0.5% solution produced approximately 15% higher ERG amplitudes than the 1.0% solution. Comparison between 1.0 and 2.5% solutions did not show significant changes in ERG amplitudes. The conductivity was essentially the same for 0.5 and 1.0% solutions, but conductivity of the 2.5% solution was roughly half of that of the other two solutions. CONCLUSIONS: Although the 0.5% solution did yield significantly higher ERG values than the 1.0% and 2.5% solutions, the exact mechanism by which this occurs is not known. The source of these differences could arise from a combination of factors such as conductivity, viscosity, or other unknown components of the solutions. ERG laboratories should be consistent in the use of coating agents, and be aware that any change in solution might alter normative values by a modest percentage.

Adult↗

Comparison of conventional ERG parameters and high-intensity A-wave analysis in a clinical setting.

Computational analysis of high-intensity a-waves yields direct information about the rod and cone receptor potential. However, it is not clear whether such information adds materially to the diagnostic value of the standard ERG in a routine clinical setting. We recorded both conventional ISCEV standard and computational high intensity ERG parameters from 38 patients referred to a clinical laboratory for ERG testing, and also from eight normal volunteers. The patients were grouped as: (1) macular dysfunction; (2) diffuse cone dysfunction; (3) diffuse rod-cone dysfunction. The results showed moderate variation in both conventional and computational parameters, but in general a similar pattern of normality or abnormality for both among the disease groups. There were only a few outlying subjects for which one or the other approach seemed more sensitive. We conclude that a-wave analysis is an important tool for clinical research and the study of special patients, but adding it to the standard ERG protocol does not, at our present state of knowledge, add markedly to clinical evaluations in a routine clinical setting.

Adult↗

Retinal evaluation of patients on chronic amiodarone therapy.

PURPOSE: To determine whether retinal electrophysiologic changes can be detected and correlated with funduscopic findings in patients with the long-term use of amiodarone. METHODS: Eleven patients ranging in age from 52 to 67 years were recruited from the Stanford University Medical Center Department of Cardiology for ophthalmologic examination. Patients had received amiodarone at various dosages ranging from 100 to 800 mg daily for at least 15 months. Clinical indications for the use of amiodarone included atrial fibrillation, ventricular arrhythmias, and congestive heart failure. All patients underwent retinal electrophysiology studies (full-field and multifocal electroretinograms) in addition to a complete ophthalmologic examination and fluorescein angiography. RESULTS: No patients were found to have significant vision loss. Funduscopic examination and fluorescein angiography showed mild age-related changes in four patients, three of whom had nonspecific foveal pigmentary alterations. Multifocal and full-field electroretinograms were mostly unremarkable, and the mildly subnormal findings in a few patients showed no consistent pattern to suggest a toxic cause. Dosage, duration of amiodarone exposure, patient age, and underlying cardiac disease did not appear to correlate with these findings. CONCLUSIONS: No significant adverse retinal funduscopic changes or electrophysiologic effects could be correlated with amiodarone exposure in this small series of patients. Routine electrophysiologic and funduscopic screening of patients receiving amiodarone does not seem warranted, although future prospective controlled studies may be required to exclude the possibility of progressive abnormalities in patients with preexisting age-related macular degeneration.

Aged↗

Localized neurotransmitter release for use in a prototype retinal interface.

PURPOSE: Current neural prostheses use electricity as the mode of stimulation, yet information transfer in neural circuitry is primarily through chemical transmitters. To address this disparity, this study was conducted to devise a prototype interface for a retinal prosthetic based on localized chemical delivery. The goal was to determine whether fluidic delivery through microfabricated apertures could be used to stimulate at single-cell dimensions. METHODS: A drug delivery system was microfabricated based on a 5- or 10- microm aperture in a 500-nm thick silicon nitride membrane to localize and limit transmitter release. The aperture overlies a microfluidic delivery channel in a silicone elastomer. To demonstrate the effectiveness of this transmitter-based prosthesis, rat pheochromocytoma cells (PC12 cell line) were grown on the surface of the device to test the precision of stimulation, using bradykinin as a stimulant and measuring fluorescence from the calcium indicator, fluo-4. RESULTS: The extent of stimulation could be controlled accurately by varying the concentration of stimulant, from a single cell adjacent to the aperture to a broad area of cells. The stimulation radius was as small as 10 microm, corresponding to stimulation volumes as small as 2 pL. The relationship between the extent of stimulation and concentration was linear. CONCLUSIONS: The demonstration of localized chemical stimulation of excitable cells illustrates the potential of this technology for retinal prostheses. Although this is only a proof of concept of neurotransmitter stimulation for a retinal prosthesis, it is a significant first step toward mimicking neurotransmitter release during synaptic transmission.

Aniline Compounds↗

Microcontact printing on human tissue for retinal cell transplantation.

OBJECTIVES: To demonstrate that microcontact printing, a modern materials fabrication technique, can be used to engineer the surface of human tissue and to show that inhibitory molecules can be used to pattern the growth of retinal pigment epithelial cells or iris pigment epithelial cells on human lens capsule for transplantation. METHODS: Photolithographic techniques were used to fabricate photoresist-coated silicon substrates into molds. Poly(dimethylsiloxane)stamps for microcontact printing were made from these molds. The poly(dimethylsiloxane) stamps were then used to "wet-transfer" growth inhibitory molecules to the surface of prepared human lens capsules that were obtained during cataract surgery. Human retinal pigment epithelial and rabbit iris pigment epithelial cells were grown on a lens capsule substrate in the presence and absence of a patterned array of inhibitory factors. RESULTS: We found that human lens capsule could be microprinted with a precision similar to that obtained on glass or synthetic polymers. Retinal pigment epithelial cells and iris pigment epithelial cells cultured onto an untreated lens capsule showed spreading and formed into fusiform-appearing cells. In contrast, cells cultured on a lens capsule with a hexagonal micropattern of growth inhibitory molecules retained an epithelioid form within the inhibitory hexagons. CONCLUSION: Inhibitory growth molecules can be micropatterned onto human lens capsule, and these micropatterns can control the organization of retinal pigment epithelial cells or iris pigment epithelial cells cultured onto the lens capsule surface. CLINICAL RELEVANCE: Microprinting on autologous human tissue may facilitate efforts to effectively organize cell cultures and transplantations for the replacement of vital ocular tissues such as the retinal pigment epithelium in age-related macular degeneration.

Animals↗

Effects of the pulsed electron avalanche knife on retinal tissue.

OBJECTIVES: To evaluate the precision of retinal tissue dissection by the pulsed electron avalanche knife (PEAK) and to assess possible toxic effects from this device. METHODS: To demonstrate precision of cutting, bovine retina (in vitro) and rabbit retina (in vivo) were incised with the PEAK. Samples were examined by scanning electron microscopy and histologic examination (light microscopy). To evaluate possible toxic effects in rabbit eyes, 30 000 pulses were delivered into the vitreous 1 cm above the retina. Histologic examinations and electroretinography were performed at intervals up to 1 month after exposure. RESULTS: Cuts in postmortem bovine retina showed extremely sharp edges with no signs of thermal damage. Full-thickness cuts in living attached rabbit retina were similarly sharp and were typically less than 100 microm wide. No signs of retinal toxic effects were detected by histologic examination or electroretinography. CONCLUSIONS: The PEAK is capable of precise cutting through retinal tissue, and there are no demonstrable retinal toxic effects from its use. The precision and tractionless nature of PEAK cutting offers advantages over mechanical tools and laser-based instrumentation. We believe this new device will prove useful in a variety of vitreoretinal surgical applications.

Animals↗

Intravascular drug delivery with a pulsed liquid microjet.

Occlusions of the retinal veins and arteries, associated with diseases such as hypertension and arteriosclerosis, are a major cause of severe and irreversible loss of vision. Treatments for retinal vascular diseases have been unsatisfactory owing in part to the difficulty of delivering drugs to the site of disease within the eye. In this article, we demonstrate that a new device, the vapor bubble-driven pulsed liquid microjet, can deliver drugs into the lumen of small vessels such as those found in the retina. A 15- micro m-diameter liquid jet traveling at more than 60 m/s was shown to penetrate and deliver fluid through the wall of a blood vessel that was 60 micro m in diameter. Perforation of the wall of the blood vessel did not extend beyond the jet diameter.

Allantois↗

Recognition of small stimulus screen masks using the multifocal ERG.

To evaluate the ability of the multifocal ERG (mfERG) to detect small defects in the stimulus array was the objective of this paper. Seven normal subjects had mfERGs recorded with a VERIS system. Stimulus arrays composed of 61, 103 or 241 hexagons were covered in part by small masks of different light transmittance properties. Only masks that covered at least one-half of a single 103 hexagon stimulus cell caused a significant reduction in signal. Different-shaped masks of about 5 degrees diameter were detectable using a 61-hexagon array only when they fully covered a stimulus cell. Detection was better, but marginal for some of the masks, with the 103 hexagon array. The 241 hexagon array showed sharp defects for all masks. Masking the stimulus screen is not equivalent to having a pathologic scotoma, but it demonstrates the greatest possible spatial sensitivity of the mfERG system. Thus, the mfERG appears to be able to detect small retinal lesions if they reduce local retinal function by at least 50% and correspond to at least half the area of one stimulus hexagon. Scotomas 5 degrees or smaller would be best detected using a fine (241 hexagon) stimulus array. With coarser stimulus arrays (e.g. 103 or 61 hexagons), the effect of a small scotoma depends on its location relative to the stimulus cells. These issues should be considered when selecting mfERG recording conditions.

Adult↗

Effects of pre-adaptation conditions and ambient room lighting on the multifocal ERG.

The purpose of the study was to evaluate the effects of pre-adaptation and ambient room luminance on the multifocal ERG (mfERG). We recorded mfERGs on 18 normal subjects (average age 32) using a VERIS system, with either 61 or 103 stimulus hexagons. mfERGs were recorded sequentially under different conditions of pre-adaptation and room lighting. Changing pre-adaptation conditions between darkness for 20 min, or light at 1.43 log cd/m2 for 10 min, had essentially no effect on the mfERG, regardless of ambient room lighting. However, mfERG parameters were sensitive to the level of ambient room lighting during the recordings. As room luminance was increased from darkness, there was a gradual attenuation of N1 and P1 amplitudes both centrally and peripherally that approached 25% reduction at 1.6 log cd/m2, and a decrease in P1 time-to-peak. These effects were greatest in the blind spot. The mfERG is largely independent of pre-adaptation conditions, but waveform amplitudes and times-to-peak diminish with increasing ambient room luminance. The exaggerated attenuation of signals in the blind spot with room lighting suggests that mfERGs recorded in the dark are contaminated by light scattered to dark-adapted peripheral retina. The most stable mfERG recording condition appears to be a fully lighted room (1.6 log cd/m2).

Adaptation, Ocular↗

Retinal evaluation after 810 nm Dioderm laser removal of eyelashes.

BACKGROUND: When operating hair removal lasers on the face or in the periorbital region, even with an ocular shield in place, patients often report seeing "flashing lights" each time the laser is fired. This phenomenon suggests stimulation of retinal photoreceptors and raises laser safety issues. OBJECTIVE: To perform retinal electrophysiologic studies to evaluate the safety of hair removal lasers in the periorbital region. METHODS: Five patients with severe trichiasis secondary to trachoma were studied. The 810 nm Dioderm laser (Cynosure, Inc., Chelmsford, MA) was used to treat the eyelash follicles on the lower eyelid of each patient. Cox III metal eye shields (Oculo-Plastik, Inc., Montreal, Canada) were placed behind the eyelids of both eyes during the laser procedure. Prior to irradiation, a comprehensive ophthalmic evaluation including pupillary and slit-lamp examination, funduscopy, and full-field electroretinograms (ERGs) was performed. A comprehensive ophthalmic evaluation including ERG testing was repeated 30 minutes and 3-6 months after completion of treatment. An independent blinded assessor evaluated the ERG studies. Subjective reports of laser light sensation, pain, and discomfort during and after the laser procedure were also assessed. RESULTS: There was no detectable change in slit-lamp, pupillary, or funduscopic evaluations after periorbital laser irradiation. Similarly the pre- and posttreatment ERGs were unchanged. Three patients reported seeing flashing lights during the procedure. CONCLUSION: We found no ERG evidence of retinal damage after laser hair removal in the periorbital region, with Cox III-type ocular shields over the eyes, even when patients subjectively reported "flashing lights" during laser irradiation.

Aged↗

The ophthalmic trials of G. H. A. Hansen.

G. H. A. Hansen (1841-1912) is widely known as the discoverer of the infectious cause of leprosy. It is less well known that his career was threatened by an episode involving experimentation on the eye. As a staff physician at the leprosy hospitals of Bergen, Norway, early in his career, Hansen learned about ocular involvement in leprosy and co-authored Leprous Diseases and the Eye. In 1873 he observed bacilli in leprous nodules, but proof of an infectious origin was difficult to obtain because the agent could not be cultured and no one had demonstrated direct transmission. Hansen tried several unsuccessful experiments, and in 1879 he passed a cataract knife that had incised an active leprous nodule into a woman's conjunctiva. No nodule developed, but the woman complained of pain and said she was never asked for permission. Hansen was brought to trial where eminent physicians testified on his behalf-but Hansen himself readily admitted that no permission had been sought for fear the woman would say no. He was convicted, and relieved of his post as staff physician, but he was allowed to retain an appointment as Chief Medical Officer of Health for Leprosy, in which capacity he worked for the rest of his life.

Disease Transmission, Infectious↗