Ординатура / Офтальмология / Английские материалы / Shields Textbook of Glaucoma, 6th edition_Allingham, Damji, Freedman_2010

When the optic disc and peripapillary region was evaluated by modified ICG confocal scanning laser ophthalmoscopy angiography, the hypofluorescent areas in the peripapillary region were more common in eyes with glaucoma; however, hypofluorescent halos that were extending around the optic disc margins did not correlate with any of the study factors. Hypofluorescence was demonstrated in 68% of glaucomatous eyes, compared with 20% of control eyes (558). These observations are similar to those of earlier fluorescein angiographic studies that were previously discussed.

Color Doppler Imaging

The normal vascular anatomy of the eye and orbit, and various conditions with vascular abnormalities, has been studied with the color Doppler imaging, which allows simultaneous imaging with real-time ultrasound and superimposed color-coded vascular flow, allowing visualization of vessels previously beyond the resolution of conventional imaging, such as those in the orbit (559). Combining B-scan ultrasonography and Doppler waveform analysis, color Doppler imaging has been reported to allow noninvasive examination of blood velocity and vascular resistance in the ophthalmic, short posterior ciliary, and central retinal arteries in patients with COAG or normal-tension glaucoma (167).

One investigative team, using color Doppler imaging to evaluate the blood flow in the ophthalmic, posterior ciliary, and central retinal arteries, found significantly reduced mean systolic peak flow velocity in the ophthalmic artery in patients with glaucoma, compared with controls. In patients with glaucoma who had uncontrolled IOP, there was a reduction of end-diastolic flow velocities and an increase of resistivity index in ciliary arteries and the central retinal artery (560). The color Doppler imaging showed a significant decrease in the mean end-diastolic velocity and an increase in the mean resistive index in all blood vessels in patients with glaucoma (561). There were no differences between the patients with COAG and those with normal-tension glaucoma (169).

Another study, testing the reproducibility of the central retinal artery velocity measurements by using color Doppler imaging, showed that large differences existed in measured central retinal artery velocity, depending on the location of the measurement, and that color-flow thresholding was valuable in locating the optimal location for pulsed Doppler spectral recording (562).

The high reproducibility of the color Doppler imaging technique for the peak-systolic and end-diastolic velocities and for the resistance index, taken in the central retinal artery, the ophthalmic artery, and the short posterior ciliary arteries, is suggestive to support the validity of using color Doppler imaging in a clinical setting to measure the hemodynamic parameters of small retrobulbar blood vessels (563).

Laser Doppler Flowmetry

Laser Doppler flowmetry was introduced in 1972 to provide a noninvasive method to measure the perfusion of ocular tissues at individual discrete locations (564). It has been used in experimental and clinical studies (565). This technology can measure blood cell velocity in a volume of tissue and derive an estimate of volumetric blood flow. Laser Doppler flowmetry has also been used to measure microcirculatory blood flow in neural tissue, muscles, skin, bone, and intestine (566, 567).

The principle is to measure the Doppler shift, which is the change of frequency that light undergoes when reflected by moving objects, such as red blood cells. Because the velocity of the red blood cells is extremely low, compared with the speed of light, it is not possible to directly measure the resulting alteration in the frequency or color of the light. However, laser Doppler flowmetry provides an indirect method, in which the low-power coherent laser light that is scattered or reflected by moving red blood cells undergoes a Doppler frequency shift, while light reflected from surrounding tissue remains in its original frequency. The two coherent components of light, with only slightly different frequencies, interfere and result in a phenomenon called beat. This reflected light, together with laser light scattered from static tissue, is detected and processed to provide a blood-flow measurement. As a result, the Doppler shift of the light frequency is translated to an intensity oscillation, which can be measured. The laser Doppler flowmeter uses monochromatic light emitted from a low-power laser. Measurement of the erythrocyte movement is recorded continuously in the outer layer of the tissue under study, with no influence on physiologic blood flow. The output value is defined as the number of red blood cells times their velocity and is reported as microcirculatory perfusion units.

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To obtain the measurement, a low-intensity laser beam is directed to a certain location of the retina and is scanned across a tissue surface in a raster fashion using a moving mirror. The intensity of the light reflected and scattered at that location is measured typically over several seconds. The amplitude of measured intensity is proportional to the number of moving particles, and the frequency of the intensity is proportional to the velocity of the particles. The results are interpreted as a frequency distribution of the number of moving red blood cells and their velocity, providing a simple and quantitative description of the blood flow at the selected retinal location.

Scanning Laser Doppler Flowmetry

Blood flow can be measured by combining laser Doppler flowmetry with confocal scanning laser (568, 569, 570 and 571). The method is noninvasive and results are rapidly obtained, but it requires clear optical media and good fixation and is highly sensitive to illumination changes and eye movement; in addition, it measures blood flow in a relatively small velocity range (572).

The Heidelberg retinal flowmeter, the model currently available, performs laser Doppler measurements in a twodimensional array of points, resulting in two-dimensional perfusion maps. During an examination with the Heidelberg retinal flowmeter, a laser beam enters the eye and focuses on the retinal surface by the optical properties of the eye. The direction of the laser beam entering the eye is periodically changed in two directions by two oscillating mirrors, so that a two-dimensional region of the retina is scanned line by line. The scan field is 10 degrees wide and 2.5 degrees high, corresponding to a size of 2.88 mm × 0.72 mm. During the scan alo ng one line, the reflected light intensity at 256 pixels is measured and digitized

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sequentially. Each of the 64 total lines is scanned 128 times, with the total acquisition time of about 2.5 seconds. After the scanning is complete, for each of the 256 × 64 locations, there are 128 measurement s of the reflected light intensity versus time. When the analysis is performed at each measured location, the result is a matrix of 256 × 64, or 16,384 pixel s (perfusion map), which provides perfusion measurements. For visualization, low perfusion values are displayed in dark colors and high perfusion in light colors, resulting in a color-coded two-dimensional perfusion map, with the parameters of (a) volume, (b) flow, and (c) velocity. The highest flow values occur in the larger vessels. Because of the dual blood-flow supply in the optic nerve and the limited penetration of the laser, the instrument primarily measures the microcirculation in the nerve fiber layer of the anterior optic nerve, which is largely supplied by the central retinal artery rather than the ciliary circulation (573). Blood flow in the laminar and retrolaminar regions makes only a small contribution to the measurements.

The Heidelberg retinal flowmeter has allowed demonstration in healthy volunteers that ocular blood flow increases while inhaling carbogen and decreases while inhaling oxygen or after increasing IOP to 50 mm Hg with a suction cup (574). Although IOP values were significantly reduced by the use of betaxolol and timolol, blood-flow values were significantly decreased only in the timolol group. Laser Speckle Flowmetry

Laser speckle is seen when coherent laser light is scattered from a diffuse object. If instead of being stationary the illuminated object consists of individual moving red blood cells, the speckle pattern fluctuates randomly. The intensity of these fluctuations provides information about the velocity of the object producing the scatter. The structure of the pattern that changes according to blood-flow velocity is called “blurring,” and a square blur rate is an ind ex of blood velocity, calculated by a computer.

One prospective study compared blood-flow measurements in the optic nerve head by laser speckle flowmetry with confocal scanning laser Doppler flowmetry. There was only a weak correlation between the blood-flow indexes, as measured by laser speckle flowmetry and scanning laser Doppler flowmetry because of basic differences in the principles of measurement (575).

Another study has shown significant differences in optic nerve head blood flow in healthy volunteers between the right and left eyes and between the superior and inferior temporal neuroretinal rims using laser speckle flowmetry. These normal data may be useful in understanding the physiology of ocular hemodynamics (576).

Magnetic Resonance Imaging

Qualitative analysis of the perfusion of the human optic nerve with magnetic resonance imaging (MRI) may be used to study optic nerve blood-flow abnormalities (577). MRI can also be used to quantify changes in the optic nerve microcirculation. T2-weighted MRI in rats provided quantification of optic nerve blood flow and has shown that dopaminergic substances increase optic nerve blood flow (578). The Possible Future of Imaging

Exciting areas of innovation are the structural imaging of RGC bodies and the imaging of individual ganglion cell stress and death (579, 580, 581, 582, 583, 584 and 585). These areas are still in experimental development, but may be clinically relevant in the future.

KEY POINTS

The optic nerve head comprises axons from the RGCs, as well as blood vessels and astroglial and collagen support. The normal optic nerve head has considerable variation in size and surface contour.

The pathogenesis of glaucomatous optic atrophy appears to involve obstruction of axoplasmic flow, although whether this is a direct mechanical effect of elevated IOP or secondary to vascular changes is unclear.

Glaucomatous optic atrophy is characterized clinically by a progressive, asymmetric loss of neural rim tissue, which is manifested by an enlargement in the area of cupping and pallor. This most often extends in a focal direction, producing early thinning of the inferior and superior portions of the neural rim. Enlargement of the cup often precedes that of the area of pallor, creating a pallorcup discrepancy. Other important signs of glaucomatous optic atrophy are disc hemorrhages and peripapillary nerve fiber bundle defects.

The differential diagnosis of glaucomatous optic atrophy includes normal variations, developmental anomalies, and nonglaucomatous causes of acquired cupping.

Techniques for evaluating the optic nerve head include a careful office examination and photographic documentation, although newer techniques, such as computed image analysis and blood-flow measures, may provide more precise methods of observation in the clinical management of glaucoma.

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