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Fundus photography for measurement of macular pigment density distribution in children.

PURPOSE: To evaluate a photographic procedure for reflectometry of the topographic distribution of macular pigment density in normal pediatric subjects. METHODS: Digitized blue (480 nm) and green (540 nm) photographic images were aligned and subtracted to generate optical density difference maps. An 8 degrees x 8 degrees area concentric with the fovea was analyzed. Gaussian curves were fitted through the foveola along the vertical and horizontal meridians. The peak density and full widths at half maximum (FWHMs) were calculated. The subjects (n = 23; median age 10.5 years) had normal eyes and good acuity. RESULTS: The peak macular pigment (MP) density was 0.13 +/- 0.04 density units (DU) which is at the lower end of the range previously obtained by other reflectometry procedures. Density distributions were circularly symmetrical. The FWHM ranged was 2.4 degrees +/- 0.5 degrees. Neither MP nor FWHM varied significantly with age. CONCLUSIONS: The photographic method is feasible and provides quantitative assessment of topographic properties of macular pigment in young subjects. Future application to clinical studies of pediatric patients is envisioned.

Adolescent↗

Effective treatment of diffuse diabetic macular edema by temporal grid pattern photocoagulation.

BACKGROUND AND OBJECTIVE: To determine the effectiveness of laser grid pattern photocoagulation to the macula but not the papillomacular bundle for the treatment of diffuse diabetic macular edema. PATIENTS AND METHODS: Thirty-five eyes of 23 patients with diffuse diabetic macular edema underwent laser grid photocoagulation excluding the papillomacular bundle area. Best-corrected visual acuity by Snellen chart, foveal thickness using a retinal mapping program by optical coherence tomography (OCT), and mean deviation sensitivity by Humphrey automated central perimetry were investigated before and 1, 3, and 6 months after the treatment. RESULTS: Six months after treatment, the visual acuity was improved by 2 or more lines in 16 eyes (43%) and the foveal thickness decreased in 32 eyes (91%). The mean deviation worsened in 34 eyes (97%). There was a significant correlation between the improvement of visual acuity and the initial mean deviation, suggesting that a better visual acuity would be expected with a preoperative mean deviation of approximately -20 dB. CONCLUSION: Grid pattern photocoagulation without treatment to the papillomacular bundle area was effective in treating diffuse diabetic macular edema, especially in eyes with an initial mean deviation showing moderate dysfunction.

Aged↗

Orienting head movements resulting from electrical microstimulation of the brainstem tegmentum in the barn owl.

The size and direction of orienting movements are represented systematically as a motor map in the optic tectum of the barn owl (du Lac and Knudsen, 1990). The optic tectum projects to several distinct regions in the medial brainstem tegmentum, which in turn project to the spinal cord (Masino and Knudsen, 1992). This study explores the hypothesis that a fundamental transformation in the neural representation of orienting movements takes place in the brainstem tegmentum. Head movements evoked by electrical microstimulation in the brainstem tegmentum of the alert barn owl were cataloged and the sites of stimulation were reconstructed histologically. Movements elicited from the brainstem tegmentum were categorized into one of six different classes: saccadic head rotations, head translations, facial movements, vocalizations, limb movements, and twitches. Saccadic head rotations could be further subdivided into two general categories: fixed-direction saccades and goal-directed saccades. Fixed-direction saccades, those whose direction was independent of initial head position, were elicited from the midbrain tegmentum. Goal-directed saccades, those whose direction changed with initial head position, were elicited from the central rhombencephalic reticular formation and from the efferent pathway of the cerebellum. Particular attention was paid to sites from which fixed-direction saccadic movements were elicited, as these movements appeared to represent components of orienting movements. Microstimulation in the medial midbrain tegmentum elicited fixed-direction saccades in one of six directions: rightward, leftward, upward, downward, clockwise roll, and counterclockwise roll. Stimulation in and around the interstitial nucleus of Cajal (InC; a complete list of anatomical abbreviations is given in the Appendix) produced ipsiversive horizontal saccades. Stimulation in the ventral InC and near the dorsal and medial edges of the red nucleus produced upward saccades. Stimulation in the reticular formation near the lateral edge of the red nucleus produced downward saccades. Stimulation in the ventromedial central gray produced ipsiversive roll saccades. The metrics and kinetics of fixed-direction saccades, but not their directions, could be influenced by stimulation parameters. As such, direction was an invariant property of the circuits being activated, whereas movement latency, duration, velocity, and size each demonstrated dependencies on stimulus amplitude, frequency, and duration. The data demonstrate directly that at the level of the midbrain tegmentum there exists a three-dimensional Cartesian representation of head-orienting movements such that horizontal, vertical, and roll components of movement are encoded by anatomically distinct neural circuits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Spatial/temporal correlation of BOLD and optical intrinsic signals in humans.

Comparing the BOLD signal with electrophysiological maps and other perfusion-dependent signals, such as the optical intrinsic signal (OIS), within subjects should provide insight into the etiology of the BOLD signal. Tongue activations were compared in five human subjects using BOLD fMRI, 610-nm OIS, and the electrocortical stimulation map (ESM). Robust fMRI activations centered on the lateral inferior aspect of the central sulcus and extended into pre- and post-central gyri, adjacent to ESM tongue loci. OIS and fMRI maps colocalized, although optical responses were spatially larger (P <.001 across multiple thresholds) and contained more gyral components. The timecourses of the fMRI and OIS signals were similar, appearing within 2.5 s and peaking 6-8 s after task onset. Although many processes contribute to increased 610-nm reflectance, optical spectroscopy and fluorescent dye imaging suggest that a significant part of this signal is due to a concomitant decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations. The spatial/temporal correlation of BOLD and the positive 610-nm response within subjects suggests that the two signals may share similar etiologies. The OIS/fMRI inconsistencies may be due to cell swelling and light-scattering contributions to OIS and fMRI sensitivity. This study also demonstrates that fMRI maps do not precisely colocalize with ESM, rather they emphasize changes in adjacent venous/sulcal structures.

Brain↗

Studies of retinal representations within the cat's optic tract.

The manner in which each retina can be mapped onto a single cross section of the optic tract of the cat has been defined by neuroanatomical methods. It has been found that the contralateral nasal hemi-retina and both temporal hemi-retinae are represented in each tract by multiple, rough maps which partially overlap one another. All maps show the same general orientation, with area centralis represented dorsomedially, lower retina represented dorsolaterally, and upper retina represented ventromedially. The peripheral part of the horizontal meridian is represented ventrolaterally. Labeling all of the fibers from one eye by axonal degeneration or autoradiographic methods shows that the crossed map is displaced dorsally and medially relative to the uncrossed map, leaving a dorsomedial crescent of pure crossed fibers. Localized retinal lesions or injections of 3H-amino acid show the general orientation of the maps. Lesions within the dorsomedial pure crossed crescent show that fibers in this crescent arise from retinal areas close to the optic disc, near the site of the early fetal fissure. Localized injections of horseradish peroxidase into the optic tract show the relationships of the several maps in terms of the retinal distribution of retrogradely labeled retinal ganglion cells. They show that axons of large and small cells map ventrolaterally in the tract while intermediate sizes map dorsomedially. They confirm that the crossed map is displaced relative to the uncrossed maps. It is suggested that the optic tract develops by fibers taking a position in the tract in accordance with their time of arrival at the chiasm. The several maps are displaced because they develop sequentially and the optic tract can be read as a developmental record, the most dorsomedial axons being the oldest.

Animals↗

Hunting increases adaptive auditory map plasticity in adult barn owls.

The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.

Acoustic Stimulation↗

Multiple-site optical recording for characterization of functional synaptic organization of the optic tectum of rainbow trout.

To map the functional synaptic organization over a wide area in the optic tectum, we directly monitored two-dimensional propagation of postsynaptic depolarization evoked by firing of retinotectal afferents in optic tectum slices prepared from rainbow trout (Oncorhynchus mykiss), using a voltage-sensitive dye and a photodiode array system. The postsynaptic responses to afferent stimulation first propagated in the stratum opticum and stratum fibrosum et griseum superficiale in an anterograde fashion in the afferents and then expanded vertically into the deep layers. This vertical propagation appeared to occur along a bundle-like structure that corresponded well with a cluster of neurons whose somata are located in the stratum periventriculare. Pharmacological studies showed that these postsynaptic responses were mediated by ionotropic glutamate receptors. On the other hand, the optical signals appeared to consist of at least two components (a transient signal and a slow signal). The second transient signal summated with the first slow signal by paired stimulation, suggesting that the transient and slow signals originated from different cell types. Taken together, these results showed that the functional synaptic organization of the teleost optic tectum comprises of two depolarization-signal propagating paths along a horizontal layer structure and a vertical bundle-like structure and that these synaptic responses occur via glutamatergic transmission.

Action Potentials↗

Topographic analysis to discriminate glaucomatous from normal optic nerve heads with a confocal scanning laser: new optic disk analysis without any observer input.

PURPOSE: We evaluated the potential ability of a confocal scanning laser ophthalmoscope to differentiate patients with normal visual fields from those with abnormal visual fields with an optic nerve head topographic map. PATIENTS AND METHODS: Twenty normal eyes with normal visual fields, intraocular pressures of less than 22 mm Hg, and no family history of glaucoma and 20 glaucomatous eyes with abnormal visual fields and open angles were selected. Glaucomatous eyes with advanced visual field damage were not included. One eye was chosen randomly from each patient. All eyes were examined with the Heidelberg Retina Tomograph (HRT [Heidelberg Engineering GMBH, Heidelberg, Germany]) and Humphrey Perimeter, program 30-2 (Humphrey Instruments, Inc., San Leandro, CA, USA). Topographic maps were analyzed with different methods based on contour lines, with use of a program able to differentiate glaucomatous from normal optic disks. Sensitivity, specificity, and diagnostic precision were calculated. RESULTS: The analysis had a sensitivity, specificity, and diagnostic precision of 80%, 100%, and 90%, respectively. CONCLUSION: With the topographic map data and this technique, the HRT's capacity to differentiate normal optic disks from glaucomatous disks was improved. In addition, with this method, we avoided any subjective observer input in drawing the optic nerve head outline.

Aged↗

The primary visual system of adult lizards demonstrates that neurogenesis is not obligatorily linked to central nerve regeneration but may be a prerequisite for the restoration of maps in the brain.

Following optic nerve crush in the adult lizard Ctenophorus ornatus, most retinal ganglion cells regrow their axons into visual brain centres: however, the regenerated projections lack retinotopic order and the animals are blind via the experimental eye. Here we have used 3H-thymidine autoradiography to demonstrate that cell division is no longer taking place in the retina of normal adult lizards. We conclude that the optic nerve can regenerate in lizard even though cells are no longer being added to the retina. However, continued retinal neurogenesis may be linked to the ability to restore topographic maps.

Age Factors↗

New near-infrared optical probes of cardiac electrical activity.

Styryl voltage-sensitive dyes (e.g., di-4-ANEPPS) have been widely and successfully used as probes for mapping membrane potential changes in cardiac cells and tissues. However, their utility has been somewhat limited because their excitation wavelengths have been restricted to the 450- to 550-nm range. Longer excitation/emission wavelength probes can minimize interference from endogenous chromophores and, because of decreased light scattering and lower absorption by endogenous chromophores, improve recording from deeper tissue layers. In this article, we report efforts to develop new potentiometric styryl dyes that have excitation wavelengths ranging above 700 nm and emission spectra extending to 900 nm. Three dyes for cardiac optical mapping were investigated in depth from several hundred dyes containing 47 variants of the styryl chromophores. Absorbance and emission spectra in ethanol and multilamellar vesicles, as well as voltage-dependent spectral changes in a model lipid bilayer, have been recorded for these dyes. Optical action potentials were recorded in typical cardiac tissues (rat, guinea pig, pig) and compared with those of di-4-ANEPPS. The voltage sensitivities of the fluorescence of these new potentiometric indicators are as good as those of the widely used ANEP series of probes. In addition, because of molecular engineering of the chromophore, the new dyes provide a wide range of dye loading and washout time constants. These dyes will enable a series of new experiments requiring the optical probing of thick and/or blood-perfused cardiac tissues.

Action Potentials↗

Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy.

Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common form of autosomally inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an insidious onset of bilateral visual loss and they characteristically have temporal optic nerve pallor, centrocaecal visual field scotoma, and a colour vision deficit, which is frequently blue-yellow. Evidence from histological and electrophysiological studies suggests that the pathology is confined to the retinal ganglion cell. A gene for dominant optic atrophy (OPA1) has been mapped to chromosome 3q28-qter, and studies are under way to refine the genetic interval in which the gene lies, to map the region physically, and hence to clone the gene. A second locus for dominant optic atrophy has recently been shown to map to chromosome 18q12.2-12.3 near the Kidd blood group locus. The cloning of genes for dominant optic atrophy will provide important insights into the pathophysiology of the retinal ganglion cell in health and disease. These insights may prove to be of great value in the understanding of other primary ganglion cell diseases, such as the mitochondrially inherited Leber's hereditary optic neuropathy and other diseases associated with ganglion cell loss, such as glaucoma.

Chromosome Mapping↗

Doppler angle and flow velocity mapping by combined Doppler shift and Doppler bandwidth measurements in optical Doppler tomography.

Accurate estimation of flow velocity requires measurement of Doppler angle, which is not available in general clinical applications. We describe a novel method of direct Doppler angle and flow velocity mapping that uses a conventional single-beam optical Doppler tomography system. The Doppler angle is estimated by combination of Doppler shift and Doppler bandwidth measurements, and flow velocity is calculated from the Doppler shift and the estimated Doppler angle. In vivo study of lip microvascularization demonstrates that this method is capable of providing both flow speed and flow direction information.

Blood Flow Velocity↗

Spatial relationship of motion automated perimetry and optic disc topography in patients with glaucomatous optic neuropathy.

PURPOSE: To compare the spatial relationship of focal motion automated perimetry (MAP) visual field defect with focal defect in optic disc topography. METHODS: Patients (n = 12) with focal MAP visual field loss and focal change in optic disc topography were studied. The MAP visual field was divided into 12 field zones representing retinal nerve fiber layer arcuate bundles. Zones of MAP loss were related to rim area ratio (RAR), which was obtained by dividing the rim area, measured by the Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany), into 36 10 degrees sectors and then dividing the area of each sector by the total rim area for each subject. Rim area ratio was compared to a normative database (n = 76) to quantify change in optic disc topography. In these same patients, the spatial relationship between standard automated perimetry (SAP) and short-wavelength perimetry (SWAP) and optic disc topography was also assessed. RESULTS: Motion automated perimetry superior visual field zones 14 through 19 were most often associated with a reduction in RAR for inferior sectors 24 through 29, and inferior visual field zones 4 through 7 were most often associated with a reduction in RAR for superior temporal sectors 11 through 16. Similar spatial relationships were found between SWAP and SAP and the RAR. CONCLUSION: Focal MAP visual field loss and focal changes in optic disc topography are spatially related. This relationship is similar to that found between SWAP and SAP with optic disc topography. Focal thinning or notching detected by RAR analysis might be independent of the specific functional test employed.

Glaucoma, Open-Angle↗

Optical imaging of intrinsic signals in ferret auditory cortex: responses to narrowband sound stimuli.

This paper describes optical imaging of the auditory cortex in the anesthetized ferret, particularly addressing optimization of narrowband stimuli. The types of sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude modulated (SFM and SAM) tones. By employing short illumination wavelengths (546 nm), we have successfully characterized the tonotopic arrangement, in agreement with the well-established electrophysiological tonotopic maps of the ferret auditory primary field (AI). The magnitude of the optical signal increased with sound level, was maximal for a modulation frequency (MF) of 2-4 Hz, and was larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an optimal narrowband stimulus was defined. Thus optical imaging can be used successfully to obtain frequency maps in auditory cortex by an appropriate choice of stimulus parameters. In addition, background noise consisting of 0.1-Hz oscillations could be reduced by introduction of blood pressure enhancing drugs. The optical maps were largely independent of 1) the type of narrowband stimulus, 2) the sound level, and 3) the MF. This stability of the optical maps was not predicted from the electrophysiological literature.

Acoustic Stimulation↗

The development of retinotectal maps: a review of models based on molecular gradients.

Information about the world is often represented in the brain in the form of topographic maps. A paradigm example is the topographic representation of the visual world in the optic tectum/superior colliculus. This map initially forms during neural development using activity-independent molecular cues, most notably some type of chemospecific matching between molecular gradients in the retina and corresponding gradients in the tectum/superior colliculus. Exactly how this process might work has been studied both experimentally and theoretically for several decades. This review discusses the experimental data briefly, and then in more detail the theoretical models proposed. The principal conclusions are that (1) theoretical models have helped clarify several important ideas in the field, (2) earlier models were often more sophisticated than more recent models, and (3) substantial revisions to current modelling approaches are probably required to account for more than isolated subsets of the experimental data.

Animals↗

Analysis of biosensors by chemically specific optical techniques. Chemiluminescence-imaging and infrared spectroscopic mapping ellipsometry.

The standard methods currently used to read out microarrays are fluorescent and chemiluminescent imaging techniques. These methods require labeling of a component with a marker and, usually, only the concentration of the marker molecule is detected. A label-free imaging method that also enables quantitative spectroscopic analysis of the composition and component interaction would be of great advantage. In this article it is shown for the first time that IR mapping ellipsometry enables label-free imaging of a biochip before and after incubation with peptide solution. The measurements prove that IR ellipsometry is a sensitive tool for laterally resolved identification of the different materials and determination of the composition of a biochip. The lateral resolution required was achieved by using radiation from an infrared synchrotron beamline.

Equipment Design↗

Quantitative phase microscopy: a new tool for investigating the structure and function of unstained live cells.

1. The optical transparency of unstained live cell specimens limits the extent to which information can be recovered from bright-field microscopic images because these specimens generally lack visible amplitude-modulating components. However, visualization of the phase modulation that occurs when light traverses these specimens can provide additional information. 2. Optical phase microscopy and derivatives of this technique, such as differential interference contrast (DIC) and Hoffman modulation contrast (HMC), have been used widely in the study of cellular materials. With these techniques, enhanced contrast is achieved, which is useful in viewing specimens, but does not allow quantitative information to be extracted from the phase content available in the images. 3. An innovative computational approach to phase microscopy, which provides mathematically derived information about specimen phase-modulating characteristics, has been described recently. Known as quantitative phase microscopy (QPM), this method derives quantitative phase measurements from images captured using a bright-field microscope without phase- or interference-contrast optics. 4. The phase map generated from the bright-field images by the QPM method can be used to emulate other contrast image modes (including DIC and HMC) for qualitative viewing. Quantitative phase microscopy achieves improved discrimination of cellular detail, which permits more rigorous image analysis procedures to be undertaken compared with conventional optical methods. 5. The phase map contains information about cell thickness and refractive index and can allow quantification of cellular morphology under experimental conditions. As an example, the proliferative properties of smooth muscle cells have been evaluated using QPM to track growth and confluency of cell cultures. Quantitative phase microscopy has also been used to investigate erythrocyte cell volume and morphology in different osmotic environments. 6. Quantitative phase microscopy is a valuable, new, non-destructive, non-interventional experimental tool for structural and functional cellular investigations.

Animals↗

Applying a mapped pseudospectral time-domain method in simulating diffractive optical elements.

A new technique for the analysis of two-dimensional diffractive optical elements, by use of the pseudospectral time-domain (PSTD) method, is presented. In particular, the method uses a nonuniform (NU) grid and a mapping technique to obtain very accurate spatial derivatives in an efficient manner. To this end, we present the formulation of the PSTD method by using a NU grid and compare its application to the analysis with that of the finite-difference time-domain (FDTD) method. Using only a fraction of the memory and a fraction of the computation time used by FDTD, the mapped PSTD was able to obtain very close results to FDTD.

Journal Article↗