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Biomedical subjects

D U Bartsch

Publications and source records attributed to D U Bartsch.

At least 19 recordsLinked to original sources

Age-associated cardiac dysfunction in Drosophila melanogaster.

The fruit fly, Drosophila melanogaster, has served as a valuable model/organism for the study of aging and was the first organism possessing a circulatory system to have its genome completely sequenced. However, little is known about the function of the heartlike organ of flies during the aging process. We have developed methods for studying cardiac function in vivo in adult flies. Using 2 different cardiovascular stress methods (elevated ambient temperature and external electrical pacing), we found that maximal heart rate is significantly and reproducibly reduced with aging in Drosophila, analogous to observations in elderly humans. We also describe for the first time several other aspects of the cardiac physiology of young adult and aging Drosophila, including an age-associated increase in rhythm disturbances. These observations suggest that the study of declining cardiac function in aging flies may serve as a genetically tractable model for genome-wide mutational screening for genes that participate in or protect against cardiac aging and disease.

Aging↗

Retinal nerve fiber layer evaluation in human immunodeficiency virus-positive patients.

PURPOSE: To determine the effect of human immunodeficiency virus (HIV) infection on topographic measures of the optic disk and the retinal nerve fiber layer. METHODS: A cross-sectional study at the Acquired Immunodeficiency Syndrome (AIDS) Ocular Research Unit at the University of California, San Diego. Retinal nerve fiber layer thickness at the optic nerve head was evaluated using the Heidelberg Retinal Tomograph, a confocal scanning laser tomograph in 38 HIV-positive and 24 age-matched HIV-negative subjects. RESULTS: HIV-positive patients without CMV retinitis showed significant differences from HIV-negative normal controls in a number of measures of the retinal nerve fiber layer. This indicated a loss of retinal ganglion cells in HIV-positive patients without retinitis. HIV-positive patients with CMV retinitis were worse in most measurements than both HIV-negative controls and HIV-positive patients without CMV. CONCLUSIONS: Significant thinning of the retinal nerve fiber layer occurs in HIV-positive patients without infectious retinopathy, and there are further changes in the optic disk associated with CMV retinitis. Confocal scanning laser tomography may be of use in the diagnosis of early HIV-associated visual function loss.

AIDS-Related Opportunistic Infections↗

Correlation between static automated and scanning laser entoptic perimetry in normal subjects and glaucoma patients.

OBJECTIVE: To compare the effectiveness of scanning laser entoptic perimetry with static automated perimetry as a noninvasive instrument for screening for glaucomatous damage in visually asymptomatic subjects within the central 60 degrees (diameter) of vision. DESIGN: A masked cross-sectional study comparing entoptic perimetry to achromatic threshold perimetry. PARTICIPANTS: Twenty-three subjects and controls from the Sharp Rees-Stealy Hospital and the Shiley Eye Center at the University of California, San Diego. TESTING: Virtual reality-based entoptic perimetry was compared with achromatic threshold perimetry. MAIN OUTCOME MEASURES: For each testing session, we compared the presence of a disturbance in the entoptic perimetry stimulus with the presence of defects in visual function as measured by Humphrey automated visual field perimetry. RESULTS: Scanning laser entoptic perimetry reasonably estimates the overall visual field loss for moderate-to-severe scotomas as measured by the pattern deviation in standard visual field perimetry. Scanning laser entoptic perimetry has a sensitivity from 27% to 90% and a specificity from 50% to 100% for screening moderate-to-severe visual field defects caused by glaucoma within the central 60 degrees diameter of vision. CONCLUSIONS: Scanning laser entoptic perimetry may be an effective and inexpensive screening test in hospitals and community clinics for diagnosing visual field loss caused by glaucoma.

Cross-Sectional Studies↗

Choroidal melanoma microcirculation with confocal indocyanine green angiography before and 1 year after radiation brachytherapy.

PURPOSE: The authors previously demonstrated that confocal indocyanine green (ICG) angiography is capable of imaging the microcirculation of choroidal melanomas. The purpose of this study is to report their observations regarding the response of the microcirculation using confocal ICG at 1 year after radiation brachytherapy. METHODS: Thirteen patients with unilateral choroidal melanoma were examined once before and several times up to 1 year after radiation brachytherapy (Iodine-125 or Ruthenium-106 plaque). At each visit, a complete ophthalmologic examination including standardized echography and fluorescein and ICG angiography was obtained, the latter using a confocal scanning laser ophthalmoscope. RESULTS: In 10 patients (77%), the tumor microcirculation changed considerably within 1 year after treatment. Distortion, thickening, thinning, and complete obliteration of vessels could be observed. In the other 3 patients (23%), no changes in the microcirculation were noticed within the observation period. CONCLUSIONS: Follow-up with confocal ICG of choroidal melanomas after treatment with local radiation brachytherapy allows for visualization of the microcirculation reaction following radiation brachytherapy. This provides the clinician with additional information for the posttreatment monitoring of these patients. Confocal ICG might also be a useful tool to monitor the effects of future antiangiogenesis-based tumor therapies in choroidal melanomas.

Adult↗

Evaluation of the human choroidal melanoma rabbit model for studying microcirculation patterns with confocal ICG and histology.

The aim of this study was to develop consistently focal elevated choroidal masses of human choroidal melanoma in immunosuppressed rabbits and to correlate the visualization of prognostically significant microcirculation patterns from confocal indocyanine green angiography with histologic microcirculation patterns. A human choroidal melanoma cell line (OCM1) was implanted in the choroid of 40 rabbit eyes using three different techniques: transscleral choroidal injection of a cell suspension, injection of a cell suspension in a surgically induced cyclodialysis cleft, and implantation of solid tumor fragments in a surgically induced cyclodialysis cleft. The rabbits were immunosuppressed with daily injections of Cyclosporin A to prevent host versus graft reaction. The eyes were studied weekly with indirect ophthalmoscopy and fundus photography to monitor tumor growth and indocyanine green angiography using a confocal scanning laser ophthalmoscope to identify microcirculation patterns in vivo and correlate these findings with the histologic demonstration of tumor microcirculation patterns. A tumor mass was identified by indirect ophthalmoscopy in 16 of the 40 implanted rabbit eyes (40%). Each of these tumors was confirmed histologically to represent a focal elevated choroidal mass. All 16 elevated choroidal masses grow in eyes in which solid tumor fragments were implanted. In total, a melanoma was identified histologically in 28 of the implanted 40 eyes (70%). In addition to the 16 eyes where the melanoma appeared as a focal elevated choroidal mass, 4 eyes contained a focal elevated mass in the sclera and 8 eyes contained a flat choroidal tumor. Histologically, microcirculation patterns were identified only in the 16 eyes with focal elevated choroidal masses. Confocal indocyanine green angiography imaged microcirculation patterns in 13 of these 16 eyes (81%). The surgical implantation of small solid fragments of human choroidal melanoma in immunosuppressed rabbit eyes provides the best method to consistently obtain focal elevated choroidal masses. These focal elevated choroidal masses resemble booth the localization and the growth pattern of choroidal melanomas in humans. In addition, they also contain microcirculation patterns similar to those seen in humans that are detectable with confocal indocyanine green angiography. The use of indocyanine green angiography with this animal model may be especially useful in designing and evaluating anti-microcirculation treatments directed at uveal melanoma.

Angiography↗

Evaluation of microvascularization pattern visibility in human choroidal melanomas: comparison of confocal fluorescein with indocyanine green angiography.

BACKGROUND: The presence of specific microvascularization patterns (networks, parallel with and without crosslinking, silent) in histological sections of human choroidal melanomas has prognostic significance for survival. We showed previously in selected patients that the identification of these microvascularization patterns is possible in vivo by using confocal scanning laser indocyanine green angiography and that this technique is superior to fluorescein angiography using a conventional acquisition technique with a fundus camera. We now routinely use simultaneous confocal fluorescein/indocyanine green angiography to study microvascularization patterns in choroidal melanomas. The purpose of this study was to compare the visibility of tumor vessels and microvascularization patterns in fluorescein and indocyanine green angiography in simultaneous confocal series taken with the same instrument in a large prospective series of patients. PATIENTS AND METHODS: The simultaneously procured confocal fluorescein and indocyanine green angiograms of 50 patients with untreated choroidal melanomas (maximal apical height according to standardized A-scan between 2 and 8 mm) were studied for the visibility of tumor vessels and microvascularization patterns. At least one simultaneous confocal optical series (32 images in sequential depth order) during the early arterial venous phase was obtained per patient. RESULTS: Confocal forescein angiography disclosed signs of tumor vascularization in 12 (24%) of the 50 patients examined. However, in only 3 patients (6%) could microvascularization patterns be identified using confocal fluorescein angiography, and only in the very early arterial phase, which is often difficult to capture. In contrast, simultaneously obtained confocal indocyanine green angiograms disclosed tumor vessels in 47 (94%) of the examined 50 patients and microvascularization patterns could be identified in all of these cases. In 3 patients (6%) no tumor vessels could be detected within the tumor borders. CONCLUSION: This study demonstrates that confocal indocyanine green angiography images microvascularization patterns in choroidal melanomas better than fluorescein angiography, even when the images are acquired with the same technique. This can be explained with the different absorption, fluorescence and exudation characteristics of these dyes. In vivo imaging of these microvascularization patterns using confocal indocyanine green angiography offers the possibility of assessing the prognosis of choroidal melanomas without the removal of tissue.

Adult↗

Oral fluorescein angiography with the confocal scanning laser ophthalmoscope.

OBJECTIVE: To evaluate the efficacy of oral fluorescein angiography with a confocal scanning laser ophthalmoscope (SLO) system. DESIGN: Comparative case series. PARTICIPANTS: The authors used a confocal SLO (Heidelberg Retina Angiograph [HRA]) to perform oral fluorescein angiography in 47 patients, 13 of whom were without any retinal disease and 34 with a variety of retinal diseases including macular holes and pucker, inflammatory diseases, retinal vascular diseases, and age-related macular degeneration. The images were also compared to images taken with a fundus camera after intravenous fluorescein injections in patients on whom both studies were done. INTERVENTION: Color fundus photographs were taken of each eye (30 degrees fundus camera) before drinking 4 ml of 25% sodium fluorescein mixed with 60 ml of orange juice. After oral fluorescein ingestion, images of each eye were taken with a fundus camera (TriX film) and the HRA (using 512- x 512-pixel resolution). The images were repeated at 0-, 2.5-, 5-, 7.5-, 10-, 12.5-, 15-, 20-, 25-, and 30-minute intervals. Twenty of the 47 patients underwent intravenous fluorescein angiography performed with the fundus camera. MAIN OUTCOME MEASURE: Images were analyzed by a masked reader, and foveal avascular zone visualization, branch retinal vessel identification, and image quality were scored. Statistical analysis was performed with a t test for paired data with a two-tailed test of significance (alpha = 0.05). RESULTS: Foveal avascular zone was 100% as seen in 16 eyes (47%) in the HRA machine versus 1 eye (2%) in the conventional fundus camera (P < 0.0001). The third-order branch retinal vessels were identified in 59% of eyes in the HRA versus 26% in the fundus camera group (P < 0.0001), and the image quality was considered comparable to an intravenous angiogram in 47% with the HRA versus 9% with the conventional fundus camera (P < 0.0001). CONCLUSIONS: Oral fluorescein angiography using the HRA produces sufficiently detailed images to diagnose, treat, and follow many types of retinal pathology.

Administration, Oral↗

Automated scanning laser ophthalmoscope image montages of retinal diseases.

PURPOSE: To generate wide-field automated seamless retinal montage images. DESIGN: Prospective, observational, case series study. PARTICIPANTS: Eighteen eyes of 14 patients were studied. INTERVENTION: A digital scanning laser ophthalmoscope (SLO), the Heidelberg Retina Angiograph (HRA), was used to obtain overlapping images of the fundus during fluorescein angiograms, indocyanine green angiograms, or monochromatic retinal imaging using infrared or green light. Software was used to generate seamless montages. MAIN OUTCOME MEASURES: Ability to electronically synthesize retinal montages. Four laser wavelengths were used. The wide-field degrees, vertical and horizontal number of pixels, and diameter of the individual images were measured. RESULTS: High-resolution (pixel size, 10 microm), wide-field, typically 100 degrees to 140 degrees, digital montages of the postequatorial retina can be generated from HRA images. CONCLUSIONS: The software automatically and rapidly aligned the retinal blood vessels and synthesized a montage of the entire fundus that could then be overlaid on images taken at different times to illustrate change. These montages will allow improved ability to understand and follow retinal diseases.

Adolescent↗

Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy.

OBJECTIVE: To image the microvasculature of choroidal melanoma with a new confocal scanning laser ophthalmoscope. METHODS: Eighteen consecutive patients, each with a unilateral choroidal melanoma, were examined prospectively. Indocyanine green angiography was performed with a new confocal scanning laser ophthalmoscope that enabled serial optical sectioning through the tumor. Two additional patients were studied with indocyanine green angiography and confocal scanning laser ophthalmoscopy just before enucleation for posterior choroidal melanomas. The histologic identification of microvasculature patterns was compared with the angiograms for these patients. RESULTS: In the series of 18 patients, 16 (89%) indocyanine green angiograms with optical sectioning revealed tubular structures within the melanoma that were identified as tumor vessels based on their angiographic appearance. The microvasculature patterns identified by indocyanine green angiography correlated well with the histologic appearance of these microvasculature patterns in both patients for whom histologic verification was available. CONCLUSIONS: This preliminary study suggests that indocyanine green angiography with confocal scanning laser ophthalmoscopy images the microvasculature of choroidal melanomas and may be capable of detecting microvasculature patterns that have been shown to be prognostically significant from histopathological studies.

Adult↗

Simultaneous indocyanine green and fluorescein angiography using a confocal scanning laser ophthalmoscope.

BACKGROUND: Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections. METHODS: We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients. RESULTS: There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed. CONCLUSIONS: Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.

Choroid↗

Retinal blood flow measurements in branch retinal vein occlusion using scanning laser Doppler flowmetry.

PURPOSE: To determine capillary blood flow measurements in eyes with branch retinal vein occlusion using a scanning laser Doppler flowmeter. METHODS: Retinal capillary blood flow in branch retinal vein occlusion areas and corresponding ipsilateral nonbranch retinal vein occlusion areas, 11 equivalent areas of the contralateral fellow eye of 12 consecutive untreated branch retinal vein occlusion patients, and 16 eyes of 11 age-matched normal control subjects were measured with scanning laser Doppler flowmetry. A template consisting of eight squares, each with a field of 100 x 100 microm (10 x 10 pixel) with space interval of 500 microm equidistant horizontally and vertically was used to obtain blood flow measurements in all subjects. Mean blood volume, flow, and velocity were obtained by averaging the mean values measured in each field. We avoided measurement over large retinal vessels to prevent the aliasing artifact of blood cells from moving faster than the sampling frequency. RESULTS: Branch retinal vein occlusion areas have significantly decreased microvascular blood volume (P = .0009), flow (P = .02), and velocity (P = .016) compared with ipsilateral nonbranch retinal vein occlusion areas in the same eye. Branch retinal vein occlusion areas also have decreased blood volume (P = .001), flow (P = .0042), and velocity (P = .0044) compared with areas of contralateral fellow eyes of branch retinal vein occlusion subjects. Branch retinal vein occlusion areas have significantly decreased blood volume (P = .0012), flow (P = .008), and velocity (P = .02) compared with age-matched normal areas. CONCLUSION: Average retinal blood volume, flow, and velocity in areas of branch retinal vein occlusion are significantly lower than in healthy retinas. The ability to noninvasively measure hemodynamic changes in the retinal capillary bed may be relevant to development of new therapies for retinovascular disease.

Aged↗

Modeling human eye aberrations and their compensation for high-resolution retinal imaging.

We introduced a mathematical eye model using Gullstrand's six-surface eye model modified by clinically measured aspherical data to study human eye aberrations and their compensation for high-resolution retinal imaging. Ray tracing was used to characterize aberrations and point spread functions (PSFs) of the eye model. By using the Zernike polynomial decomposition of the calculated pupil function, we quantified the wavefront aberrations. Based on calculated PSFs, we designed optical inverse filters to reduce the aberrations for a large pupil size and improve the resolution. Spherical aberration and oblique astigmatism were found to be in good agreement with published experimental measurements. Spherical aberration and defocus were the most significant aberrations for on-axis imaging, whereas oblique astigmatism and coma combined with spherical aberration and defocus were most significant for off-axis imaging. The best retinal image resolution occurred at 2- to 3-mm pupil diameter. After aberration correction for an 8-mm diameter pupil, the resolutions for on-axis or 9 degrees off-axis imaging points were very close to diffraction-limited resolutions. Over a limited field of view (FOV), retinal image resolution of the eye model can be greatly improved by aberration correction using aspheric and astigmatic lenses. For imaging large FOVs, space-variant compensation techniques will be required for aberration correction.

Astigmatism↗

Indocyanine green angiography of the peripapillary region in glaucomatous eyes by confocal scanning laser ophthalmoscopy.

PURPOSE: To investigate the peripapillary region in glaucomatous eyes by indocyanine green angiography. METHODS: Indocyanine green angiography of the optic disk and peripapillary region was evaluated by modified confocal scanning laser ophthalmoscopy in 22 eyes of 22 patients with glaucoma and in 10 normal eyes of 10 control patients with unilateral choroidal melanoma. The occurrence and extent of indocyanine green angiographic anomalies were correlated with optic disk morphology and the severity of glaucoma. RESULTS: In the 32 eyes of 32 patients, two types of peripapillary defects were identified in the late-phase angiograms. The first was hypofluorescent areas in the peripapillary region and was more common in eyes with glaucoma (P < .02); their occurrence and extent correlated with age (P < .01). In nine of the 17 eyes, alpha (peripheral) zone peripapillary atrophy corresponded with the areas of peripapillary indocyanine green hypofluorescene. The second defect, hypofluorescent halos adjacent to and extending around the full circumference of the optic disk margins, did not correlate with any of the study factors. CONCLUSIONS: Indocyanine green angiography showed areas of hypofluorescene in the peripapillary region in late-phase angiograms in 68% of glaucomatous eyes compared with 20% of control eyes. These hypofluorescent areas might be either of result of blockage of background fluorescence by pigment or caused by an absence of vascular tissue (choriocapillaris).

Adult↗

Confocal scanning infrared laser ophthalmoscopy for indocyanine green angiography.

PURPOSE: We used indocyanine green to study wavelength-optimized confocal scanning infrared laser angiography in patients with retinal and choroidal disease. METHODS: A confocal scanning laser ophthalmoscope with an excitation wavelength of 795 nm was operated both in tight and wide confocal imaging modes. We examined 77 subjects with and without retinal and choroidal disease (including diabetic retinopathy, age-related macular degeneration, and subretinal neovascularization). RESULTS: The scanning laser ophthalmoscope allowed acquisition of images, in the wide confocal imaging mode, of the retinal circulation and late leakage sites without late injections of dye to outline the retinal vasculature. In the tight confocal imaging mode, optical subtraction of the light contribution of the retinal circulation allowed examination of the choroidal circulation, and vice versa. The wide confocal mode appears equivalent to other scanning laser ophthalmoscopes in recording images from retinal and choroidal layers. CONCLUSIONS: There are three differences between the confocal scanning laser ophthalmoscope and conventional instruments. First, the late images allow excellent visualization of the retinal circulation without a landmark injection. Second, confocal imaging allows optical subtraction of retinal circulation when focusing on the choroid and vice versa. Third, the instrument acquires and processes all data digitally, is personal computer-based, is compact, operates with a mouse-driven graphical user interface, and allows easy data exchange with conventional software. With further modifications in software and hardware, this device offers the possibility of producing a three-dimensional map of the retinal and choroidal vasculature.

Adult↗

Axial intensity distribution analysis of the human retina with a confocal scanning laser tomograph.

We have analysed the change of reflected light intensity along the optical axis or axial intensity distribution in images acquired with a confocal scanning laser tomographic system in human fundus examination. We hypothesized that confocal light detection units used in scanning laser tomographs register light originating from multiple layers within the human macula and that intraretinal structures might also be observable. To test this hypothesis we examined the axial intensity distribution in human maculas of normal volunteers, patients with cystic and other macular abnormalities and in an artificial retina in a plastic eye model. A total of over 140 patients and volunteers were examined. We analysed this distribution in 20 normal healthy volunteer eyes found the origin of the artifacts that cause retinal vessels to appear elevated. We examined four patients with cystic maculas and were able to detect the presence of two structures in axial direction contributing to the axial intensity distribution. A plastic eye model with a cellophane sheet covering a fluid pocket was developed to mimic the appearance of a large macular cyst. The axial intensity distribution analysis showed the presence of two distinct gaussian profiles. The results of this study show that confocal scanning laser tomographic imaging of the human fundus allows extraction of information regarding the axial position of intraretinal layers and that correction for the deeper retinal reflections may allow more precision in imaging of the retinal surface.

Adult↗

Effect of repetitive imaging on topographic measurements of the optic nerve head.

OBJECTIVE: A confocal scanning diode laser ophthalmoscope was used to determine the number of examinations needed to obtain highly reproducible topographic measurements of the optic nerve head and peripapillary retina. DESIGN: Topographic images of the optic nerve head and peripapillary retina were obtained in one randomly selected eye on five separate visits. On each occasion the selected eye had five examinations. For each examination, one image was acquired (a total of 25 images per eye). Reproducibility was calculated as the average SD of all image elements (65,536 pixels). SETTING: Glaucoma referral center. SUBJECTS: Five normal subjects and five patients with glaucoma. INTERVENTION: Topographic imaging of the optic nerve head and peripapillary retina. MAIN OUTCOME MEASURE: Number of examinations needed to obtain highly reproducible topographic measurements. RESULTS: In healthy subjects, reproducibility with one examination per visit was 35.5 microns; this improved to 25.7 microns with three examinations and 22.5 microns with five examinations. In older patients with glaucoma, the reproducibility improved from 40.2 microns with one examination per visit to 28.5 and 24.1 microns with three and five examinations, respectively. CONCLUSION: We recommend a series of three examinations to provide high reproducibility with optimal efficiency in terms of time and materials used.

Adult↗