Decreased retinal-choroidal blood flow in retinitis pigmentosa as measured by MRI.

PURPOSE: To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP). METHODS: MRI studies were performed in 6 RP patients (29-67 years) and 5 healthy volunteers (29-64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial spin-labeling technique at 0.5 × 0.8 × 6.0 mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed. RESULTS: Basal BF in the posterior retinal-choroid was 142 ± 16 ml/100ml/min (or 1.14 ± 0.13 µl/mm(2)/min) in the control group and was 70 ±19 ml/100ml/min (or 0.56 ± 0.15 µl/mm(2)/min) in the RP group. Retinal-choroidal BF was significantly reduced by 52 ± 8 % in RP patients compared to controls (P<0.05). ERG a- and b-wave amplitudes of RP patients were reduced, and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P<0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2). CONCLUSIONS: This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal-choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG.

Nonuniform Exposure to the Cornea from Millimeter Waves.

ABSTRACT: This study examines the nonuniform exposure to the cornea from incident millimeter waves at 94-100 GHz. Two previous studies measured temperature increases in the rhesus cornea exposed to brief (1-6 s) pulses of high-fluence millimeter waves (94 GHz), one of which also estimated thresholds for corneal damage (reported as ED50, the dose resulting in a visible lesion 50% of the time). Both studies noted large variations in the temperature increase across the surface of the cornea due to wave interference effects. This study examines this variability using high-resolution simulations of mm-wave absorption and temperature increase in the human cornea from exposures to plane wave energy at 100 GHz. Calculations are based on an earlier study. The simulations show that the peak temperature increases in the cornea from short exposures (up to 10 s) to high-intensity mm-wave pulses are 1.7-2.8 times the median increase depending on the polarization of the incident energy. A simple one-dimensional "baseline" model provides a good estimate of the median temperature increase in the cornea. Two different estimates are presented for the thresholds for producing thermal lesions, expressed in terms of the minimum fluence of incident 100 GHz pulses. The first estimate is based on thresholds for thermal damage from pulsed infrared energy, and the second is based on a thermal damage model. The mm-wave pulses presently considered far exceed current IEEE or ICNIRP exposure limits but may be produced by some nonlethal weapons systems. Interference effects due to wave reflections from structures in and near the eye result in highly localized variations in energy absorbed in the cornea and surrounding facial tissues and are important to consider in a hazard analysis for exposures to intense pulsed millimeter waves.

Absence of corneal endothelium injury in non-human primates treated with and without ophthalmologic drugs and exposed to 2.8 GHz pulsed microwaves.

Microwave-induced corneal endothelial damage was reported to have a low threshold (2.6 W/kg), and vasoactive ophthalmologic medications lowered the threshold by a factor of 10-0.26 W/kg. In an attempt to confirm these observations, four adult male Rhesus monkeys (Macaca mulatta) under propofol anesthesia were exposed to pulsed microwaves in the far field of a 2.8 GHz signal (1.43 +/- 0.06 micros pulse width, 34 Hz pulse repetition frequency, 13.0 mW/cm(2) spatial and temporal average, and 464 W/cm(2) spatial and temporal peak (291 W/cm(2) square wave equivalent) power densities). Corneal-specific absorption rate was 5.07 W/kg (0.39 W/kg/mW/cm(2)). The exposure resulted in a 1.0-1.2 degrees C increase in eyelid temperature. In Experiment I, exposures were 4 h/day, 3 days/week for 3 weeks (nine exposures and 36 h total). In Experiment II, these subjects were pretreated with 0.5% Timolol maleate and 0.005% Xalatan(R) followed by 3 or 7 4-h pulsed microwave exposures. Under ketamine-xylazine anesthesia, a non-contact specular microscope was used to obtain corneal endothelium images, corneal endothelial cell density, and pachymetry at the center and four peripheral areas of the cornea. Ophthalmologic measurements were done before and 7, 30, 90, and 180 days after exposures. Pulsed microwave exposure did not cause alterations in corneal endothelial cell density and corneal thickness with or without ophthalmologic drugs. Therefore, previously reported changes in the cornea exposed to pulsed microwaves were not confirmed at exposure levels that are more than an order of magnitude higher.

MRI Study of the Posterior Visual Pathways in Primary Open Angle Glaucoma.

PURPOSE OF THE STUDY: The purpose of the study was to evaluate neurodegeneration along brain visual pathways in primary open angle glaucoma (POAG) using improved analysis methods of volumetric and diffusion tensor magnetic resonance imaging (MRI) data. METHODS: Eleven POAG patients (60.0±9.2 y) with primarily mild to moderate POAG and 11 age-matched controls (55.9±7.5 y) were studied using structural and diffusion tensor MRI. Surface-based segmentation was applied to structural MRI to obtain visual cortical area and volume. Fiber tracking was applied to diffusion tensor data to obtain diffusion parameters along the optic tract and optic radiation. MRI parameters in glaucoma patients were compared with the corresponding left and right visual fields and retinal nerve fiber layer thicknesses, instead of with the left and right eye. RESULTS: Area and volume of the primary visual cortex were significantly reduced in POAG patients compared with controls (P<0.05) but did not correlate with visual field loss. Fractional anisotropy was reduced at multiple locations along the optic tracts and optic radiations in POAG patients compared with controls. Axial and radial diffusivity along the fiber tracts showed trends but were not significantly different between POAG patients and controls when averaged over the whole structures. Only fractional anisotropy (P<0.05) of the optic radiations was significantly correlated with visual field loss. No MRI parameters were correlated with retinal nerve fiber layer thickness. CONCLUSIONS: Improved analysis techniques of MRI data improves delineation of degeneration in the brain visual pathways and further supports the notion that neurodegeneration is involved with glaucoma pathogenesis.

Retinotopic fMRI Reveals Visual Dysfunction and Functional Reorganization in the Visual Cortex of Mild to Moderate Glaucoma Patients.

PURPOSE: To investigate retinotopic functional representation in the visual cortex of mild to moderate primary open-angle glaucoma (POAG) participants and age-matched normal volunteers using high-resolution retinotopic blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). METHODS: fMRI was performed on 9 POAG participants (61±11 y old) and 9 age-matched controls (58±5 y old) were studied. A wide-view visual presentation (±55 degrees) was used to evaluate central and peripheral vision. Cortical magnification factors and BOLD% changes as a function of eccentricity. Correlation analysis between BOLD% changes and visual field scores, and between BOLD% changes and retinal nerve fiber layer thicknesses was performed. Comparison of BOLD% changes for individual visual field quadrants between POAG subgroups and normal group was performed. RESULTS: BOLD% changes of POAG participants in peripheral visual regions were reduced compared to normals but similar in central visual regions, consistent with the notion of peripheral vision being affected first and more compared to central vision. fMRI retinotopic mapping revealed enlarged representation of the parafovea in the visual cortex of POAG participants compared to normals. Cortical magnification of the central, but not peripheral, visual representation in the visual cortex was larger in POAG participants, suggesting functional remapping. BOLD% changes of individual visual field quadrants were significantly correlated with visual field scores and with retinal nerve fiber layer thickness in the corresponding quadrants. CONCLUSIONS: These results support the hypothesis that there are functional alteration and remapping in the topographic representation of the visual cortex in POAG participants, and these changes are correlated with disease severity.

Millimeter wave absorption in the nonhuman primate eye at 35 GHz and 94 GHz.

The purpose of this study was to evaluate anterior segment bioeffects of pulsed 35 GHz and 94 GHz microwave exposure in the nonhuman primate eye. Five juvenile rhesus monkeys (Macaca mulatta) underwent baseline anterior segment ocular assessment consisting of slit lamp examination, corneal topography, specular microscopy, and pachymetry. These studies were repeated after exposure of one eye to pulsed 35 GHz or 94 GHz microwaves at varied fluences, with the other eye serving as a control. The mean fluence required to produce a threshold corneal lesion (faint epithelial edema and fluorescein staining) was 7.5 J cm(-2) at 35 GHz and 5 J cm(-2) at 94 GHz. Transient changes in corneal topography and pachymetry were noted at these fluences. Endothelial cell counts remained unchanged. Threshold corneal injury from 35 GHz and 94 GHz microwave exposure is produced at fluences below those previously reported for CO2 laser radiation. These data may help elucidate the mechanism of thermal injury to the cornea, and resolve discrepancies between IEEE C95.1 (1999), NCRP (1986), and ICNIRP (1998) safety standards for exposure to non-ionizing radiation at millimeter wavelengths.

Thermal modeling of millimeter wave damage to the primate cornea at 35 GHz and 94 GHz.

Recent data on damage to the primate cornea from exposure to millimeter wave radiation are interpreted in terms of a simple thermal model. The measured temperature increases during the exposures (duration 1-5 s, 35 or 94 GHz, 2-7 W cm(-2)) agree with the model within the variability of the data. The thresholds for damage to the cornea (staining of the corneal epithelium by fluorescein and corneal edema) correspond to temperature increases of about 20 degrees C at both irradiation frequencies. Within the limits of the one-dimensional model, thresholds for thermal damage to the cornea can be predicted for a range of exposure conditions.

Choroidal blood flow decreases with age: an MRI study.

PURPOSE: To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans. METHODS: The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target. Using this fixation protocol, ChBF was measured with MRI using a 3 Tesla clinical scanner in 17 normal subjects (24-68 years old). Arterial and intraocular pressures (IOP) were measured to calculate perfusion pressure in the same subjects. RESULTS: The mean temporal fluctuations (standard deviation) of the horizontal and vertical displacements were 29 ± 9 µm and 38 ± 11 µm within individual fixation periods, and 50 ± 34 µm and 48 ± 19 µm across different fixation periods. The absolute displacements were 67 ± 31 µm and 81 ± 26 µm. ChBF was negatively correlated with age (R = -0.7, p = 0.003), declining 2.7 ml/100 ml/min per year. There were no significant correlations between ChBF versus perfusion pressure, arterial pressure, or IOP. There were also no significant correlations between age versus perfusion pressure, arterial pressure, or IOP. Multiple regression analysis indicated that age was the only measured independent variable that was significantly correlated with ChBF (p = 0.03). CONCLUSIONS: The visual fixation protocol with cued eye blinks was effective in achieving sufficient stability for MRI measurements. ChBF had a significant negative correlation with age.