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

Figure 4.20 Advanced glaucomatous optic atrophy with total (bean-pot) cupping, shown best in crosssectional view.

Figure 4.21 Vascular changes in glaucomatous optic atrophy. SH, splinter hemorrhage; BCV, baring of circumlinear vessel.

Figure 4.22 Splinter (“ Drance” ) hemorrhage in glaucomatous optic nerve. Inset shows the corresponding automated achromatic visual field with nasal step and superior arcuate defect affecting the papillomacular bundle.

Tortuosity of Retinal Vessels

Tortuosity of retinal vessels on the disc may be seen with advanced glaucomatous optic atrophy, and in some cases with only moderate damage. It is believed to represent loops of collateral vessels in response to chronic central retinal vessel occlusion (356). Venovenous anastomoses associated with chronic branch retinal vessel occlusion, and the typical picture of acute central retinal vessel occlusion with massive flame hemorrhages, also occur with increased frequency in eyes with chronic glaucoma (356). Asymptomatic venous stasis changes on the disc, which are seen as enlargement of collateral vessels, have been estimated to occur in

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3% of patients with early to moderate glaucoma, and may be associated with progression of glaucomatous optic atrophy (357).

Cilioretinal Arteries

One study of 20 patients with bilateral symmetric COAG and unilateral cilioretinal arteries revealed a larger cup-to-disc ratio and more visual field damage in the eye with the cilioretinal artery (358). However, a similar study did not support this observation (359), whereas another suggested that glaucomatous eyes with one or more temporal cilioretinal arteries were more likely to retain central visual field than similar eyes with no cilioretinal artery (360).

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Location of Retinal Vessels The location of retinal vessels in relation to the cup may also have some diagnostic value. The significance of overpass cupping, in which vessels bridge a cup that is becoming deeper (316, 317), is mentioned previously. Another vessel sign with some diagnostic value has been called baring of the circumlinear vessel (361, 362). In many normal optic nerve heads, one or two vessels may curve to outline a portion of the physiologic cup. With glaucomatous enlargement of the cup, these circumlinear vessels may be “bared” from the margin of the cup (Fig. 4.21). This sign may occasionally be seen with nonglaucomatous disorders of the optic nerve and in some individuals with physiologic cups (362, 363), although its presence in a glaucoma suspect group was associated with the development of visual field loss (364).

It was once taught that nasal displacement of the retinal vessels on the optic nerve head was a sign of glaucomatous cupping. However, because these vessels enter and leave the eye along the nasal margin of the cup, their location on the disc is a function of cup size, whether physiologic or glaucomatous, and does not provide a useful diagnostic parameter (298). On the other hand, the vertical eccentricity of the central retinal vessel trunk (where the vessels enter and leave through the disc) may be related to the course of glaucomatous optic atrophy (365). In one study, neural rim loss was more likely to occur in the vertical quadrant that was further from the trunk (366).

Figure 4.23 Nerve fiber layer defect in glaucoma. A: Inferior nerve fiber layer wedge defect. B: Corresponding superior visual field defect. (From Kwon YH, Caprioli J. Primary open-angle glaucoma [Chapter 52]. In: Tasman W, Jaeger EA, eds. Duane's Clinical Ophthalmology. Vol 3. Philadelphia: Lippincott Williams & Wilkins.)

Retinal vessels beyond the disc margins may also undergo changes in glaucoma. One study showed proximal constriction (narrowing of retinal arteries near the disc) in 42% of patients with high-tension and normal-tension glaucoma, which correlated with the sectors of greatest cupping (367). General arterial narrowing (throughout the retinal course) was seen in 52% to 78%, corresponding to the overall severity of optic nerve damage. However, similar findings were also seen in patients with nonarteritic anterior ischemic optic neuropathy.

Peripapillary Changes Associated with Glaucomatous Optic Atrophy Nerve Fiber Bundle Defects

The loss of axonal bundles, which leads to the neural rim changes of glaucomatous optic atrophy, also produces visible defects in the RNFL. These appear as dark stripes or wedge-shaped defects of varying width in the peripapillary area, paralleling the normal retinal striations, or as diffuse loss of the striations (368, 369, 370 and 371) (Fig. 4.23). They often follow disc hemorrhages and correlate highly with visual field changes, neural rim area, and fluorescein-filling defects (343, 368, 369, 370, 371, 372, 373 and 374). RNFL defects are also seen in many neurologic disorders, as well as in patients with ocular hypertension and healthy individuals. However, attention to the appearance of the defects in glaucoma has improved the sensitivity and specificity of this finding, and several studies have shown RNFL defects to be the most useful parameter in the early detection of glaucomatous damage (375, 376, 377

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and 378). The diffuse loss is more common in patients with glaucoma than in patients with ocular hypertension (379), but it is also more common among persons with ocular hypertension than among those with normal IOPs (380). Localized defects

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are more directly associated with localized visual field loss than is the case with diffuse nerve loss (381). Either localized or diffuse loss may be the initial sign of glaucomatous damage (382).

Peripapillary Pigmentary Disturbance

Peripapillary pigmentary disturbance is frequently associated with glaucomatous optic atrophy, but is also seen with other conditions, such as myopia and aging changes. As previously noted, several variations of peripapillary pigmentary change may be seen in healthy eyes. The scleral lip, or peripapillary halo, is a narrow, homogenous light band at the edge of the disc. The incidence of prominent halos is higher in glaucoma, although the average degree of halos is statistically the same as in nonglaucomatous eyes (383). Peripapillary atrophy (both zone beta and zone alpha, as previously described) occurs more frequently and is larger in eyes with glaucomatous damage than in normal eyes, and it has been observed to progressively enlarge in eyes with glaucoma (384, 385, 386 and 387). It increases with decreasing neural rim area and correlates with the quadrants of the greatest rim loss (388). There is evidence that the absence of peripapillary atrophy may be associated with a decreased risk of glaucomatous damage among patients with ocular hypertension (389, 390).

Reversal of Glaucomatous Cupping

It is generally taught that glaucomatous damage of the optic nerve head and visual field is an irreversible process. Although this may be true in many cases, especially when associated with actual loss of axons, there are situations in which glaucomatous damage may be at least partially reversible. Because of increased elasticity of their sclera, this is most commonly observed in children with early stages of glaucoma, particularly during the first year of life, when the IOP is successfully lowered surgically (391, 392). However, improvement in the cup, neural rim, and even the nerve fiber layer height have been described in adults after a marked reduction in IOP by surgical or medical means (393, 394, 395, 396, 397, 398 and 399). It is important to point out that “reversal of cupping” represents a mechanical eff ect of IOP reduction and not an increase in neuroretinal tissue.

Figure 4.24 Colobomas of the optic nerve heads can simulate glaucomatous cupping. This patient would appear to have nearly total cupping and pallor, and yet the IOP was low normal and the visual fields were full with normal central vision.

DIFFERENTIAL DIAGNOSIS OF GLAUCOMATOUS OPTIC ATROPHY Normal Variations

Normal variations in the physiologic cup, the neural rim, and the peripapillary retina, as discussed earlier in this chapter, may be confused with the changes of glaucoma. In addition, developmental anomalies and nonglaucomatous optic atrophies may be sources of diagnostic confusion.

Developmental Anomalies

Colobomas of the optic nerve head can simulate glaucomatous cupping. The defect may involve the entire disc, which is enlarged and excavated (400, 401) (Fig. 4.24). In some cases, the diagnostic

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problem is compounded by associated field defects, which may resemble those of glaucoma, but are typically not progressive. A variation of optic nerve head colobomas, called the morning glory syndrome, is characterized by a large funnelshaped staphylomatous coloboma of the nerve head and peripapillary region with white central tissue, elevated peripapillary pigment disturbance, and multiple radially oriented retinal vessels (402, 403 and 404). Morning glory syndrome is typically seen only in one eye and is usually not inherited; however, bilateral cases, which may be hereditary, have been reported (405, 406).

Another optic nerve head anomaly that may represent an atypical coloboma is the congenital pit (403, 404). This is a localized, pale depression, usually near the temporal or inferotemporal margin of the disc, although it may be found in any area of the nerve head, and there may be two, or even three, pits in some eyes. These anomalies may have associated visual disturbance resulting from macular or extramacular serous detachment (407), in which the optic disc pit may act as a conduit for fluid flow from the schisis cavity into the subarachnoid space (408). The serous detachment may resolve spontaneously (409). Cases have also been reported in which congenital pits were noted to enlarge when observed for many years (410).

Tilted disc syndrome is a congenital anomaly in which the optic disc is tilted on its horizontal axis, with inferior chorioretinal hypoplasia (411). Although tilted disc syndrome is less

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likely than the colobomas to be confused with glaucoma, it can interfere with the recognition of glaucomatous damage, which is compounded by superotemporal visual field loss. Nonglaucomatous Optic Nerve Atrophy

Ophthalmologists cannot always distinguish between glaucomatous and nonglaucomatous optic atrophy on the basis of the optic disc appearance alone (412). Parameters that are most useful in making this differentiation include pallor of the neural rim in nonglaucomatous eyes and obliteration of the rim in glaucoma (413). Nonglaucomatous conditions that may cause acquired cupping include anterior ischemic optic neuropathy (as previously discussed), especially when the ischemia is due to arteritis (256, 257 and 258). A similar entity has been described in which infarction of the optic nerve head caused shallow cupping infratemporally, associated with arcuate field defects (414). This differed from glaucoma in that it was not progressive. Acquired cupping may also occur with compressive lesions of the optic nerve, such as an intracranial aneurysm, which was reported to cause cupping indistinguishable from that of early glaucoma (415). Nonglaucomatous optic neuropathies are also associated with loss of the RNFL, but with minimal cupping (416).

EVALUATION TECHNIQUES

Progressive cupping of the optic nerve head in a patient with glaucoma is the most reliable indicator that the IOP is not being adequately controlled. It is essential, therefore, to evaluate and record the appearance of the nerve head in a way that will accurately reveal subtle glaucomatous changes over the course of follow-up evaluations. In current practice, this involves careful evaluation in the office combined with photographic documentation. In addition, newer automated techniques may provide more precise methods of observation.

Office Evaluation and Recording of the Optic Nerve

In the clinical evaluation of the optic nerve head, the direct ophthalmoscope is occasionally useful, especially when evaluating the nerve fiber layer with a red-free filter. However, this technique does not permit detection of many of the glaucomatous changes in the nerve head and peripapillary area, and the most useful office approach is to carefully study these structures with stereoscopic methods. The most useful stereoscopic technique involves use of a slitlamp and an auxiliary fundus lens, such as the Goldmann contact lens, the handheld 78-D lens or 90-D lens (Fig. 4.25), or the Hruby lens slitlamp attachment. Each of these systems provides the advantages of magnification and stereopsis. However, because the lateral and axial magnifications are unequal, there is a certain amount of image distortion, with the Goldmann and handheld lenses producing a decrease in apparent depth and the Hruby lens producing a slight increase (417).

Several methods have been described for estimating the size of the disc and neural rim. These include use of (a) a direct ophthalmoscope, using either the graticule incorporated in the instrument or the smallest round white light spot of the Welch Allyn direct ophthalmoscope, which projects a 1.5-mm diameter spot on the retina in most eyes (418, 419); (b) an indirect ophthalmoscope with a spacing device on the condensing lens that allows measurement of the disc image with calipers (420, 421); and

(c) a Haag-Streit slitlamp with a 90-D lens or contact lens (422, 423 and 424), in which the height of the slit beam is adjusted to coincide with the disc edges and is then read off the scale. When compared with more quantitative measurements, such as planimetry, these techniques provide reasonably accurate estimates, especially when appropriate correction factors are considered.

Figure 4.25 A 90-D lens used with slitlamp for stereoscopic indirect ophthalmoscopic evaluation of optic nerve head.

Subjective estimates of cup dimensions vary greatly, even among expert observers (425, 426, 427 and 428). These can be improved by paying attention to the many complex optic nerve head and peripapillary retinal parameters associated with glaucomatous damage and to the need for standardized methods for interobserver evaluation of the optic disc (427, 429, 430). Detailed drawings should include the area of cupping and pallor in all quadrants, the position and kinking of major vessels, splinter hemorrhages, and peripapillary changes. However, no degree of attention to detail is sufficient to detect subtle changes in all cases, and the office evaluation should be considered only as an adjunct to the indispensable use of photographic records or other imaging records.

Photographic Techniques Two-Dimensional Photographs

Two-dimensional photographs, whether color or black-andwhite, have the advantages of simplicity and lower cost, compared with stereophotographs and computed images. In addition, the relative dimensions of the pallor and cup can be measured directly on the photograph (431, 432). Although one study found monocular and stereoscopic photographs to afford similar levels of accuracy (433), the former technique is frequently limited by the inability to precisely determine the cup margins. The projection of fine parallel lines onto the disc has been suggested as a way to improve recognition of the cup contours on two-dimensional photographs

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and stereophotographs (434, 435). Techniques have also been developed to electronically scan black- and-white disc photos to obtain an objective measure of the amount of optic disc pallor (436, 437). The main value of two-dimensional photos in the future may be to document the RNFL. Special techniques to enhance the subtle details of this parameter include monochromatic (red-free) filters and highresolution film, crosspolarization photography, a wide-angle fundus camera, a spectral reflectance, and a charge-coupled device with digital filtering (438, 439, 440, 441, 442, 443, 444, 445 and 446). The use of nerve fiber layer photography compared favorably with other glaucoma-screening methods in a general medical clinic setting (442).

Stereoscopic Photographs

A more reliable method for recording disc cupping and the other aspects of glaucomatous optic atrophy is the use of color stereophotographs. Stereophotographs can be obtained by taking two photos in sequence, either by manually repositioning the camera or by using a sliding carriage adapter (Allen separator), or by taking simultaneous photos with two cameras that utilize the indirect ophthalmoscopic principle (Donaldson stereoscopic fundus camera) or a twin-prism separator (447, 448, 449 and 450). These three techniques were compared for reproducibility, and the Donaldson camera was found to be superior (451). However, use of a simultaneous stereo camera, which provides the stereo pair on two halves of the same frame (Nidek 3Dx), had significantly better overall mean stereoscopic quality than the Donaldson camera (452). Transparencies from the Nidek camera can also be used to create lenticular images, which are single prints on a unique, photosensitized plastic base that produces a threedimensional image without use of a stereoviewer (453). Although simultaneous stereophotography may be optimal for assessing the optic nerve head, no manufacturers currently make these cameras. Ultrasonography

Ultrasound can be used to detect glaucomatous cupping of 0.7 cup-to-disc ratio or greater (454). Computed Analysis of the Optic Nerve Head and RNFL

Historical Perspective

Even the most sophisticated fundus photographs are limited in their clinical value by the qualitative, subjective interpretation of the images (426). Efforts to refine the assessment of these subtle findings have included quantitative analyses of optic nerve head topography and pallor, and RNFL height or thickness. These techniques were initially performed manually (455), which was time consuming and impractical for routine clinical practice. With the advent of computers and newer imaging technologies, however, applying these concepts to the clinical management of glaucoma is now a possibility.

The concept of computed image analysis of the optic nerve head was pioneered by Dr. Bernard Schwartz, who developed prototypes for analysis of contour and pallor of the disc (456).

Early instruments used the basic principle of stereopsis, in which disparity between corresponding points of stereo pair images was used to generate contour lines and three-dimensional contour maps (stereophotogrammetry). Commercial instruments in this category were the Rodenstock optic nerve head analyzer (457, 458 and 459), the Topcon Imagenet (460), and the Humphrey retinal analyzer (461). The Topcon Imagenet and Humphrey retinal analyzer measured disparity between existing structures in the stereo images, whereas the optic nerve head analyzer used projected light stripes on the disc to measure image disparity. Stereochronoscopy used the stereoscopic principle to detect subtle changes in photographs of a disc taken at different times (462, 463 and 464). If any progression of the cupping has occurred, the disparity in the cup margins of the superimposed photographs would produce a stereoscopic effect. A modification of this concept, referred to as stereo chronometry, used a stereoplotter to measure the changes created by the two photographs (465). Other modifications for detecting differences in serial fundus photographs involve analysis of flicker while alternately viewing one photograph and then the other, and electronic subtraction, in which areas of disparity between the two images are enhanced (464, 466, 467).

Colorimetric measurements have also been studied to detect reduced or changing color intensity of the optic nerve head (468, 469, 470 and 471). A photographic technique has also been developed to permit quantitative evaluation of the relative brightness of the illuminated optic nerve head (472).

In another technology, rasterstereography, a series of horizontal dark-light line pairs are projected on the disc and peripapillary retina at a fixed angle and the computer scans a video image of the lines in a raster fashion. Raster refers to a scanning pattern that moves from side to side and from top to bottom (the same scanning pattern used in confocal laser scanning). Because the lines are deflected proportional to the height or depth of the disc and retinal surfaces, a computer algorithm can translate the deflections into depth numbers and create a topographic map.

An image analyzer that used the rasterstereography concept was the Glaucoma-Scope, which is no longer available (473, 474). It projected a near infrared light in parallel stripes on the nerve head. The computer analyzed the data points to generate depth measures, which were displayed in microns relative to reference planes. In the initial set of measurements, the actual depth measures were provided, while follow-up studies showed only change of more than 50 µm from baseline.

Despite reasonable reproducibility and accuracy, these instruments never achieved widespread clinical use primarily because of technical complexity, the size and cost of the instrument, and the need for relatively wide pupillary dilatation and clear media. Nevertheless, the experience gained through the study of these instruments provided the basis for much of our understanding of computed image analysis of the optic nerve head and of the potential for clinical application of newer instruments and techniques in the management of glaucoma.

Over the past decade, several commercially available instruments have been described. These instruments use newer techniques, such as confocal laser scanning ophthalmoscopy and

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polarimetry, optical coherence tomography (OCT), and the retinal thickness analyzer. Imaging and computed data processing allow for precise three-dimensional in vivo measurements. However, computed results should always be evaluated in a clinical context (475).

Measure of Clinical Utility

For a structural test to be diagnostically useful, it should be able to (a) differentiate between healthy and glaucomatous eyes, (b) detect glaucomatous changes earlier than functional changes (i.e., preperimetric glaucoma—when psychophysical testing does not show an abnormality), and (c) detect progression of disease.

Optic Nerve Topography

Principles of Confocal Scanning Laser Tomography

Confocal scanning laser ophthalmoscopy is a technique for obtaining high-resolution images by using a focused laser beam to scan over the area of the fundus to be imaged. Only a small spot on the fundus is illuminated at any instant, and the light reflected determines the brightness of the corresponding pixel on a computer monitor. To improve contrast, a pinhole, or confocal aperture, is placed in front of the photodetector to eliminate scattered light (Fig. 4.26). The aperture is conjugate to the laser focus, and the resulting image is said to be confocal. The instantaneous volume of tissue from which reflected light is accepted by the confocal aperture is called a voxel, and the smaller the aperture, the smaller the voxel and the higher the resolution of the image. By scanning the fundus with the laser in a raster pattern, a two-dimensional image can be built up as an array of pixels. If a series of confocal scanning laser ophthalmoscopy images are obtained at successive planes of depth in the tissue, these can be used to construct a three-dimensional image, or confocal scanning laser tomography.

The prototype in this category of instruments was the laser tomographic scanner (476, 477). Although the laser tomographic scanner is no longer commercially available, new-generation units were developed from the original laser tomographic scanner and are similar in basic design.

The HRT-II and HRT-III (Fig. 4.27) are completely automatic instruments designed to be used in routine clinical practice for study of optic nerve head morphology. They are based on the original HRT, which has had the most extensively re ported evaluation and was found to have reproducibility of stereometric parameters comparable with the original HRT (478). The HRT-II uses a 675-nm diode laser as a light source to measure the reflectivity of millions of points in multiple consecutive focal planes in 0.024 second per plane. The first section image is located above the reflection of the first retinal vessel,

and the last is beyond the bottom of the optic nerve head cup, with 16 confocal images acquired per 1 mm of the scan depth, achieving high spatial resolution. The computer then converts the acquired data to a single topographic image with 384 ×384 data point s (pixels) within a 15-degree area. The calculated image is then used to produce quantitative measurements of morphometric parameters of the disc that can be used to classify the nerve as normal or glaucomatous, or to compare topography images to quantify progression of glaucoma.

Figure 4.26 Principles of confocal scanning laser ophthalmoscopy.