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[Topographic distribution of visual evoked potentials in optic neuropathy].

INTRODUCTION: Digital treatment of electrical signals coming from the central nervous system on stimulation of the optic nerve path offers an objective method for evaluation of visual evoked potentials (VEP) shown graphically on a cerebral map. OBJECTIVE: To evaluate the topographical distribution of VEP in cases of optic neuropathy adding this parameter to the usual parameters of latency and amplitude. MATERIAL AND METHODS: We studied 35 patients with suspected optic neuropathy and normal findings on basic ophthalmological examination, in whom VEP and VEP mapping (VEPM) was done. RESULTS: In 26% of the cases there was no response for evaluation with the usual VEP recording techniques, whilst in those with VEPM this percentage was reduced to 11.5%. In the other cases there was a potential with characteristic distribution in the occipital areas and a maximally positive dipole posteriorly. CONCLUSION: VEPM is an objective method for evaluation of the visual pathway offering better discrimination than the usual VEP in more severe cases of neuropathy.

Adolescent↗

Clinical assessment of the macula by retinal topography and thickness mapping.

PURPOSE: To report a quantitative and objective method for assessing pathologic alterations in retinal structures to improve the evaluation of macular diseases. METHODS: We used a system based on the scanning retinal thickness analyzer to generate serial optical section images of the retina and provide mapping of the retinal topography and thickness in a normal subject and in patients with representative maculopathies including traumatic macular hole, central serous chorioretinopathy, branch retinal vein occlusion, diabetic macular edema, and retinal pigment epithelial detachment. RESULTS: The effectiveness of the system in imaging both the vitreoretinal and chorioretinal interfaces was confirmed in the normal subject and in patients with various maculopathies. Mapping of retinal topography and thickness in a normal eye correlated well with normal anatomy, delineating the foveal depression clearly. The retinal thickness map in a patient with diabetic macular edema showed thickening of the retina and absence of a foveal depression. The patients with central serous chorioretinopathy and branch retinal vein occlusion had an elevated vitreoretinal surface. Conversely, the patient with retinal pigment epithelial detachments had a relatively flat vitreoretinal interface but an irregularly elevated chorioretinal surface. CONCLUSION: Quantitative mapping of retinal topography and thickness is a promising tool that may improve evaluation of macular diseases.

Adult↗

Structural changes in tubulin sheets upon removal of microtubule-associated proteins.

Zinc-induced tubulin sheets without microtubule-associated proteins (MAPs) were assembled from tubulin purified by phosphocellulose chromatography. Large, open sheets were obtained in five-minute incubations at pH 5.7. Electron micrographs of negatively stained sheets showed a protofilament arrangement similar to that observed for zinc-induced sheets with MAPs but with altered lattice parameters. The spacings measured from optical diffraction patterns demonstrated that the protofilaments were 2.2 A closer together in the sheets without MAPs. Each MAP-free sheet was also divided roughly in half by a discontinuity which was parallel to the protofilaments and the relationship between the two domains was deduced from computed transforms. Two-dimensional image processing was carried out by conventional Fourier techniques and by correlation analysis. The correlation analysis improved the reconstructions in this application, with the resolution limited by the inherent properties of the negative stain method to about 14 A. A prominent feature of the computed reconstructions was an alternation of light and dark protofilaments due to differential staining, as revealed by a study of folded sheets. Neighboring protofilaments are related by a 2-fold screw axis, as they are in zinc-induced sheets with MAPs, but the symmetry is masked by the differential staining. The major effect of MAP removal on the structure of the sheets is that the bilobed structure of alternate tubulin subunits is no longer observed. This observation and the closer spacing of protofilaments is consistent with the postulate that some of the MAP molecules lie in the groove between protofilaments and bind to several tubulin dimers.

Animals↗

Regeneration of the retinotectal projection following compression onto a half tectum in goldfish.

This study tested whether regeneration of the optic nerve following half-tectal compression in goldfish leads to the immediate reestablishment of the compressed projection or to an initial half map followed by the gradual compression. Half of the tectum was removed and the optic nerve crushed in large 12-18 cm goldfish which were kept at 20 degrees C and later mapped either in air or in water. At 35 to 41 days, the maps showed the presence of the nasal field projection and only the first 27 degrees of the temporal field. Most of the temporal field was represented after 200 days or more. After 253 to 343 days when the compression was largely complete, the optic nerve was recrushed. The projections mapped 35 to 41 days later were always compressed with up to 99% of the temporal field represented, as were projections regenerated at 28 degrees C and mapped at 23-25 days. Regeneration after compression restores the compressed projection, consistent with the concept of altered tectal markers.

Animals↗

Variability of depth measurements of the optic nerve head and peripapillary retina with computerized image analysis.

Computerized topographic mapping of 10 repeated fundus images of one eye each in 10 healthy subjects and in 10 subjects with elevated intraocular pressures (IOPs) was performed with the Humphrey Retinal Analyzer. The variability of depth measurements at 400 to 650 individual locations in the optic nerve head and peripapillary retina was evaluated. The average size of the 95% confidence intervals for individual depth measurements for healthy subjects and those with elevated IOPs were 166 and 232 microns in the optic nerve head and 205 and 261 microns in the peripapillary retina, respectively. Variability was significantly less for healthy subjects than for those with elevated IOPs. Variability was significantly greater for depth measurements in the peripapillary retina than for measurements in the optic head. Knowledge about variability of individual depth measurements is useful for proper interpretation of computerized topographic mapping to detect retinal nerve fiber damage.

Adult↗

Detailed prostatic interstitial thermal mapping during transurethral grooved rollerball electrovaporization and loop electrosurgery for benign prostatic hyperplasia.

OBJECTIVES: To determine the detailed pattern of prostatic interstitial temperature change during rollerball electrovaporization and loop electrosurgery in patients with benign prostatic hyperplasia (BPH). METHODS: Four patients with symptomatic BPH necessitating prostate surgery were subjected to rollerball electrovaporization on one side of their prostate glands, as well as contralateral loop electrosurgery. Continuous temperature readings were recorded from 20 to 24 interstitially implanted fiber-optic thermosensors using a novel stereotactic thermal mapping technique. Ultrasound and video endoscopic visualization were used to evaluate and quantify the spatial relationship between the thermosensors and the rollerball or loop. RESULTS: The patterns of temperature change during rollerbal electrovaporization and loop electrosurgery were substantially similar. Temperatures decreased steeply and significantly with increasing distance from both the rollerball (P < 0.001) and loop (P < 0.001). Marked mean temperature increases occurred at 1 to 2 mm from both the rollerball (30.8 degrees C, 95% confidence interval [CI] 27.8 to 33.8 degrees C) and loop (34.8 degrees C, 95% CI 24.0 to 45.6 degrees C), and temperatures at this distance were significantly higher than those at greater distances (P < 0.05). At 3 to 5 mm, the mean temperature increases declined by 58% for the rollerball and 68% for the loop. Further declines of 68% and 63%, respectively, were observed at 6 to 10 mm, and at distances exceeding 10 mm the temperature changes were minimal (0.5 degree C [95% CI 0.3 to 0.8 degree C] for the rollerball and 0.5 degree C [95% CI 0.1 to 0.8 degree C] for the loop). There was no change in temperature at any of the thermosensors near the neurovascular bundles and rectum. CONCLUSIONS: The patterns of temperature change with rollerball electrovaporization and loop electrosurgery are closely similar. Interstitial temperature changes during use of the rollerball and loop are transient and highly localized, posing minimal risk of unintended thermal damage to adjacent tissues, including the neurovascular bundles and rectum.

Aged↗

Fiber order in the opossum's optic tract.

The distribution of axons by size in the optic tract of the South American opossum, Didelphis marsupialis was studied. Thin and semi-thin sections were examined, and measurements of axonal diameter were made on electron micrographs taken from various locations across the optic tract of normal opossums. In order to determine the contributions of the different axon diameter classes to the crossed and uncrossed retinofugal pathways, measurements were also made from the tracts of opossums in which one eye had been enucleated 5 weeks previously. Within the opossum's optic tract, the axons are partially segregated by their size: the deepest parts of the tract contain only fine and medium-sized axons, whereas coarse axons are also present superficially. In the middle of the tract, all three size classes are present. At increasingly superficial positions, there is a steady reduction in the proportion of medium-diameter axons, and an increase in the number of the finest axons. Medium and coarse axons contribute to both the crossed and uncrossed pathways, and the uncrossed component is displaced superficially relative to the crossed component. The fine axons in the deeper parts of the tract arise from both retinae, while those in the superficial parts of the tract, near the pial surface, are virtually all crossed. The opossum's optic tract thus displays the segregation of axons by size found in placental mammals, and follows a pattern reminiscent of that found in carnivores. Such a common organizational plan, particularly the similarities between the didelphids and carnivores, is suggestive of an early acquisition of parallel visual pathways in mammalian phylogeny. Since the fiber order in the optic tract of eutherians is a chronological map of axonal arrival during development, these results suggest that a conserved developmental mechanism has led to a common organizational plan.

Animals↗

The ldis1 lens mutation in RIIIS/J mice maps to chromosome 8 near cadherin 1.

PURPOSE: We have discovered a spontaneous and severe mutation that leads to partial or complete disruption of the lens and cataract in the RIIIS/J inbred strain of mice. The purpose of this study was to determine the mode of inheritance, specificity, and range of phenotypes using histological, ophthalmic, quantitative electron microscopic, and microarray-based methods. We also have fine-mapped the mutation, ldis1 (lens disrupter 1), and have evaluated positional candidate genes. METHODS: Eyes from mutant RIIIS/J animals and from an F2 intercross between RIIIS/J and DBA/2J were examined and scored to map the ldis1 mutation. Axons in the optic nerve were counted. Messenger RNA from mutant eyes was hybridized to Affymetrix short oligomer microarrays and compared to five control strains. Expression differences were used to evaluate molecular sequellae of the mutation. RESULTS: Mice that are homozygous for ldis1 have small eyes. Lenses are without exception opaque, deformed, dislocated, fragmented, and small. In contrast, retinal architecture and ganglion cell numbers are within normal range. We have not detected any other ldis1-associated ocular or systemic abnormalities. ldis1 is recessive and maps to chromosome 8 at about 106.5 Mb between D8Mit242 and D8Mit199 with a peak LOD score near cadherin 1. The homologous human chromosomal interval is 16q22.1. The expression of several downstream crystallin transcripts are severely affected in the mutant, as are the expression levels of multiple members of the transforming growth factor superfamily and the glutathione S-transferases. CONCLUSIONS: We have discovered and mapped a recessive mutation to mouse chromosome 8 between 105 and 109 Mb. Homozygous mutant mice have a selective and severe effect on lens integrity. On the basis of the phenotype and the locus position, several candidate genes have been identified.

Animals↗

Evaluation of image artifact produced by optical coherence tomography of retinal pathology.

PURPOSE: To determine the frequency and type of optical coherence tomography (OCT) fast macular thickness map (FMTM) scan artifacts, and whether these artifacts depend on patient diagnosis, demographics, and ocular therapy. DESIGN: Retrospective observational case series. METHODS: Records from patients who underwent an ophthalmologic evaluation by a member of the Duke University Eye Center vitreoretinal faculty and had an OCT scan produced by the FMTM protocol between July 7, 2003 and July 31, 2003 were reviewed. The relationships between OCT scan artifacts and ocular diagnosis, ocular treatment, and patient demographics were determined. Logistic regression was used to relate OCT scan artifacts simultaneously with ocular diagnosis and treatment. RESULTS: Scans from 171 eyes were analyzed. Retinal scan artifacts, though not observed in normal eyes, were identified frequently in eyes with macular pathology (P = .049). Artifacts were observed in 43.2% of all scans, and of these, an erroneous retinal thickness measurement was obtained in 62.2%. Six types of OCT surface map artifacts were observed. Of these, inner and outer retinal misidentification, degraded image artifact, and "off center" artifact were significantly associated with central thickness calculation errors (P < .001). Neovascular age-related macular degeneration (AMD), full-thickness macular hole, and photodynamic therapy were all associated with increased artifact (P = .002, .022, and <.001, respectively). CONCLUSION: Optical coherence tomography scan artifacts are seen surprisingly frequently, adversely affect retinal thickness measurements in a high proportion of cases, and are diagnosis-dependent. Recognition of these artifacts will improve retinal thickness measurement accuracy, and will prevent faulty treatment decisions that are based on inaccurate retinal thickness measurements.

Aged↗

Measuring local optical properties: near-field polarimetry of photonic block copolymer morphology.

Ultrahigh molecular weight polystyrene-b-polyisoprene block copolymers (BCs), noted for their photonic behavior, were imaged using transmission near-field scanning optical microscopy (NSOM) and NSOM polarimetry. Our improved scheme for polarization modulation (PM) polarimetry, which accounts for optical anisotropies of the NSOM aperture probe, enables mapping of the local diattenuation and birefringence (with separately aligned diattenuating and fast axes) in these specimens with subdiffraction limited resolution. PM-NSOM micrographs illuminate the mesoscopic optical nature of these BC specimens by resolving individual microphase domains and defect structures.

Butadienes↗

Findings on retinal topography and thickness mapping in age-related macular degeneration.

PURPOSE: To report alterations in the retinal topography and thickness in typical cases of age-related macular degeneration (ARMD). METHODS: An optical imaging system was applied to patients with ARMD with alterations in the retinal structures. The system generates a series of 20 optical section images that encompass a 2 mm x 2 mm retinal area. The optical sections are digitized and analyzed to provide topographic maps of the vitreo-retinal and chorio-retinal surfaces and the retinal thickness. RESULTS: Retinal topography and thickness mapping in a normal eye corresponded to normal anatomy. Topographic mapping in a patient with confluent drusen indicated elevation of the vitreo-retinal surface. Retinal topography in a patient with retinal pigment epithelium detachment displayed localized elevation of the chorio-retinal surface. The thickness map in a patient with geographic atrophy of the retinal pigment epithelium revealed retinal thinning. In the patients with choroidal neovascularization, the vitreoretinal and chorio-retinal surfaces were elevated. The chorio-retinal surface map in a patient with evolving disciform scar displayed topographic variations corresponding to the fibrovascular tissue underlying the serous detachment. CONCLUSION: Retinal topography and thickness mapping is useful for visualization and evaluation of pathologic alterations in retinal structures due to ARMD.

Adult↗

Optical imaging of SI topography in anesthetized and awake squirrel monkeys.

Orderly topographic maps in the primary somatosensory cortex (SI) serve as an anchor for our understanding of somatosensory cortical organization. However, this view is mostly based on data collected in the anesthetized animal. Less is known about these topographies in the awake primate. Even less is known about the relative activations of different subdivisions of SI (areas 3a, 3b, 1, and 2). Toward the goal of understanding the functional activation of SI, we conducted intrinsic signal optical imaging of areas 3b and 1 in awake squirrel monkeys. Monkeys were imaged repeatedly for a period of >2 years in awake and anesthetized states in response to vibrotactile and electrocutaneous stimuli presented to individual fingerpads. During this period, we found stable somatotopic maps in both the anesthetized and awake states, consistent with electrophysiologically recorded maps in areas 3b and 1 in the anesthetized state. In the awake animal, signal sizes were larger, but variability was greater, leading to decreased signal-to-noise ratios. Topographic activations were larger (in both area and amplitude) in the awake animal, suggesting either a less precise topography and/or more complex integration. This brings into question the role of a precise topographic map during behavior. In addition, whereas in the anesthetized animal strongest imaging signals were obtained from area 3b, in the awake animal, area 1 activation dominated over that in area 3b. Differences in relative dominance of area 3b versus area 1 suggest that inter-areal interactions in the alert animal differ substantially from that in the anesthetized animal.

Anesthesia↗

Specification of positional information in retinal ganglion cells of Xenopus: assays for analysis of the unspecified state.

The central connections of retinal ganglion cells are retinotopically organized, producing a "map" of the retina on the surface of the optic tectum. Exactly how and when individual ganglion cells develop the position-dependent properties (termed locus specificities) subserving formation of the map is unknown, but the positional information that each ganglion cell will use in this process is specified in the early Xenopus embryo during a critical period at stages 28-32. We report two methods for isolating eye primordia from the axial cues of the animals during this critical period and for then allowing the eyes to form retinotectal connections in a carrier embryo. The results show that, as early as optic vesicle stages 22-23, the eyes already contain orthogonal reference axes, that positional information can be specified with respect to these axes in vitro, and that the specification process itself may only entail a transition from a reversible to an irreversible state.

Animals↗

Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q.

Wolfram syndrome, which is sometimes referred to as "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an autosomal recessive neurodegenerative disorder for which only insulin-dependent diabetes mellitus and optic atrophy are necessary to make the diagnosis. Researchers have mapped Wolfram syndrome to chromosome 4p16.1, and, recently, a gene encoding a putative transmembrane protein has been cloned and mutations have been identified in patients. To pursue the possibility of locus heterogeneity, 16 patients from four different families were recruited. These patients, who have the Wolfram syndrome phenotype, also have additional features that have not previously been reported. There is an absence of diabetes insipidus in all affected family members. In addition, several patients have profound upper gastrointestinal ulceration and bleeding. With the use of three microsatellite markers (D4S432, D4S3023, and D4S2366) reported to be linked to the chromosome 4p16.1 locus, we significantly excluded linkage in three of the four families. The two affected individuals in one family showed homozygosity for all three markers from the region of linkage on chromosome 4p16.1. For the other three families, genetic heterogeneity for Wolfram syndrome was verified by demonstration of linkage to chromosome 4q22-24. In conclusion, we report the unique clinical findings and linkage-analysis results of 16 patients with Wolfram syndrome and provide further evidence for the genetic heterogeneity of this disorder. We also provide data on a new locus that plays a role in the etiology of insulin-dependent diabetes mellitus.

Adolescent↗

Evaluation of the structure-function relationship in glaucoma.

PURPOSE: While glaucoma is evaluated on the basis of structural and functional test results, the spatial relationship between structure and function is not well defined. This study produces a topographical map to demonstrate how sectors of the optic nerve head (ONH) are related to locations in the visual field, using empiric cross-sectional patient data. METHODS: One hundred nine subjects with healthy eyes and 166 subjects with diagnosed or suspected glaucoma (one test per patient) were evaluated using a retina tomograph and white-on-white standard automated perimetry (SAP). The tomograph ONH images were divided into 36 sectors; and the sector rim areas normalized to account for changes in the total rim area. These were then correlated with SAP thresholds. For each visual field location, a map was produced indicating the strength of correlation between the normalized sector rim areas and thresholds. RESULTS: The highest correlation between a sector's normalized rim area and a SAP location's sensitivity was 0.520. Twenty-seven of the 52 non-blind spot SAP locations exhibited a correlation greater than 0.2 with at least one ONH sector. Locations in the superior hemifield were usually best correlated with the polar inferior temporal sectors of the ONH; locations in the inferior hemifield were usually best correlated with the polar superior temporal sectors of the ONH. CONCLUSIONS: A map relating regions of the ONH to SAP test locations has been produced. This map may be useful in elucidating the structure-function relationship, particularly for cases of localized glaucomatous loss.

Aged↗

The rabbit optic nerve: fibre diameter spectrum, fibre count, and comparison with a retinal ganglion cell count.

This electron microscopic study indicates that the rabbit optic nerve contains 394,000 +/- 20,000 (p less than 0.05) nerve fibers, of which at least 98% are myelinated. The fibre diameter spectrum of the nerve is unimodal and ranges from 0.25-7 mum with its peak at 0.75 mum. The projection of the visual streak fibres is not apparent in local diameter spectra near the optic nerve head. Integration of a ganglion cell density map of the retina from another rabbit indicates a total ganglion cell count lying between 455,000 and 547,000. The optic nerve fibre and ganglion cell counts are both substantially greater than the maximum fibre count previously reported.

Animals↗

The transplantation of eyes to genetically eyeless salamanders: visual projections and somatosensory interactions.

Eyes were transplanted from normal axolotls to eyeless mutants, and several anatomical and physiological observations were made on the central visual centers in these animals. Some central projections were bilateral to the optic centers of the thalamus and midbrain, some traveled ipsilaterally to the same centers, and the rest grew down the spinal cord. This is similar to what has been found in eyes transplanted to normal hosts. The type of projection made in eyeless hosts correlated with the site of nerve entry into the CNS as in control hosts. Thus, the transplanted projection did not appear to be influenced by the host's optic nerves and tracts or lack of them. In spite of the transplanted optic fibers' taking abnormal paths, they made normally organized topographic maps on the host tecta. The visual and somatosensory topographic projections to the tectum were found to be in near perfect register normally, but in eyeless mutants to which rotated eyes had been transplanted, they were not. Acetylcholinesterase activity, found in the primary optic neuropil in normal animals, was greatly diminished in eyeless mutants, yet normal mutants with grafted eyes. Finally, transplantation of an eye to an eyeless mutant corrected the abnormally dark pigmentation caused by eyelessness but only in those cases of bilateral central innervation.

Acetylcholinesterase↗

Polarization modulation-infrared reflection absorption spectroscopic mapping.

Polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS) has been coupled with a stepwise mapping of the sample in order to characterize the molecular orientation across the surface. An optical setup has been developed to facilitate the PM-IRRAS mapping. With PM-IRRAS mapping used in conjunction with a common FT-IR spectrometer, the achievable lateral resolution of approximately 45 mum is energy-limited rather than diffraction-limited. PM-IRRAS mapping was used to study the molecular orientation of octadecanephosphonic acid (OPA) molecules attached on a microstructured aluminum oxide/gold surface. The spectroscopic map reveals that OPA is preferably spotty attached on the aluminum oxide surface. The attached molecules form a highly ordered film. A lower degree of ordering was found for phosphonic acid adsorbed on gold mainly in a tridentate bonding mode. Results demonstrate that PM-IRRAS mapping has a considerable potential for revealing inhomogenities within ultrathin films attached on a surface.

Absorption↗