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Biomedical subjects

Michael F Marmor

Publications and source records attributed to Michael F Marmor.

At least 37 records · Page 2Linked to original sources
PubMed2003

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↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMedDate not supplied

Alcohol- and light-induced electro-oculographic responses: variability and clinical utility.

The alcohol-induced electro-oculographic (EOG) response has been proposed by Arden as an indicator of retinal pigment epithelial (RPE) integrity. We have evaluated the consistency of the alcohol-EOG with respect to clinical applicability and compared this response to the ISCEV-standard EOG. We recorded, in a group of normal subjects (n=29, 14 men with mean age 42+/-11 years and 15 women with mean age 36+/-13 years), the alcohol response to a single oral dose of ethanol at 160 mg/kg (as 40 proof vodka, drunk in 15 s after 12 h of fasting), followed by an ISCEV-standard EOG 90 min after alcohol administration. Blood alcohol levels were monitored at regular intervals with a breath analyzer. We found a wide range of amplitudes in both light and alcohol responses among participants, from minimal to large values. Subjects had a wide range of blood alcohol concentrations from 0.02 to 0.10%; near the time of the response peak, but there was no relationship between alcohol levels and peak/baseline ratios. In addition, there was no relationship between alcohol peak/baseline ratio and the Arden ratio. Neither the alcohol nor the light response parameters showed any relationship with age or gender. Some of the inter-individual variability in the EOG response to alcohol may reflect variable absorption of oral alcohol. The alcohol-induced EOG has too broad a range of responses to be useful clinically for the one-time evaluation of individual patients. We have similar concerns regarding clinical applications of the standard light-induced EOG.

Adult↗
PubMedDate not supplied

Alcohol- and light-induced electro-oculographic responses in age-related macular degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG responses in ARMD & CSC.

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Adult↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Escher and the ophthalmologist.

The Dutch graphic artist, Maurits C. Escher (1898-1972) is famous for intricate and sometimes illusory images which challenge our sensibility. Over many years, from the 1920s to the 1960s, he made designs with interlocking figures that confuse the distinction between object and background. His correspondence and writings suggest that these designs were largely self-created until the 1950s when fame brought him increasingly into contact with scholars from disciplines such as mathematics, crystallography, and psychology. One of these contacts was with an ophthalmologist, Johan W. Wagenaar (1911-), who had been using Escher's designs to illustrate lectures about vision during night driving. A correspondence began that extended for almost a decade and altered Escher's concept of his own work. It is an intriguing footnote to the career of this extraordinary artist.

Art↗
PubMedDate not supplied

Rod and cone visual cycle consequences of a null mutation in the 11-cis-retinol dehydrogenase gene in man.

Vertebrate vision starts with photoisomerization of the 11-cis-retinal chromophore to all-trans-retinal. Biosynthesis of 11-cis-retinal is required to maintain vision. A key enzyme catalyzing the oxidation of 11-cis-retinol is 11-cis-retinol dehydrogenase (11-cis-RDH), which is encoded by the RDH5 gene. 11-cis-RDH is expressed in the RPE and not in the neural retina. The consequences of a lack of 11-cis-RDH were studied in a family with fundus albipunctatus. We identified the causative novel RDH5 mutation, Arg157Trp, that replaces an amino acid residue conserved among short-chain alcohol dehydrogenases. Three-dimensional structure modeling and in vitro experiments suggested that this mutation destabilizes proper folding and inactivates the enzyme. Studies using RPE membranes indicated the existence of an alternative oxidizing system for the production of 11-cis-retinal. In vivo visual consequences of this null mutation showed complex kinetics of dark adaptation. Rod and cone resensitization was extremely delayed following full bleaches; unexpectedly, the rate of cone recovery was slower than rods. Cones showed a biphasic recovery with an initial rapid component and an elevated final threshold. Other unanticipated results included normal rod recovery following 0.5% bleach and abnormal recovery following bleaches in the 2-12% range. These intermediate bleaches showed rapid partial recovery of rods with transitory plateaux. Pathways in addition to 11-cis-RDH likely provide 11-cis-retinal for rods and cones and can maintain normal kinetics of visual recovery but only under certain constraints and less efficiently for cone than rod function.

Adaptation, Ocular↗
PubMedDate not supplied

Effects of sildenafil citrate (Viagra) on choroidal congestion.

This study evaluates the effect of sildenafil on choroidal vascular congestion and its correlation with visual effects. Thirteen healthy subjects were randomized to a sildenafil group (n = 7, 3 M, 4 F), who received 200 mg of sildenafil, and a control (n = 6, 5 F, 1 M) group, who received no drug. Measurements of choroidal thickness with ultrasonography, color vision with Desaturated Panel D-15 Test, and contrast sensitivity with CSV-1000e charts (Vector Vision) were performed at baseline and at 90 and 180 min. Mean choroidal thickness and contrast sensitivity did not change significantly relative to baseline in either group. However, the variance in differences between repeat and baseline measurements of choroidal thickness was significantly higher at 90 min (p = 0.003) in the sildenafil subjects. Color discrimination error scores increased after sildenafil but did not correlate with changes in choroidal thickness. An oral dose of 200 mg of sildenafil caused small inconsistent changes in choroidal thickness, which did not correlate with visual effects.

Adult↗