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

examination technique used. When the discs were studied by direct ophthalmoscopy, the distribution was found to be nongaussian, with most eyes having a cup-to-disc ratio of 0.0 to 0.3 and only 1% to 2% being 0.7 or greater (287). However, when stereoscopic views were used, a gaussian distribution was found with a mean cup-to-disc ratio of 0.4, and approximately 5% were 0.7 (288). In another study, the two techniques of optic nerve head evaluation were compared, and stereoscopic examination with a Hruby lens gave consistently larger cup-to-disc ratio estimates, with a mean of 0.38, compared with 0.25 by direct ophthalmoscopy (289). The investigators noted that the disparity between estimated cup-to- disc ratios for the same eye at different times seldom exceeds 0.2, so that the documentation of such a difference over time should be viewed with suspicion (289). Also of note, physiologic cups tend to be symmetric between the two eyes of the same individual (287, 288, 289, 290 and 291), with a cup-to-disc ratio difference of greater than 0.2 between fellow eyes occurring in only 1% to 6% of the normal population but in 24% of patients with COAG (287, 292). However, asymmetry alone was not found useful in identifying patients with COAG (292).

The size of the physiologic cup is frequently similar to that of the individual's parents and siblings (287, 293, 294). In other cases, the large cup may be the earliest sign of glaucoma in relatives (295). The size of the physiologic cup is thought to be genetically determined on a polygenic, multifactorial basis (287, 296). The heritability has been estimated at two thirds, with the remaining variance attributed to environmental factors (294). Therefore, examining other family members is helpful in distinguishing between a large physiologic cup and glaucomatous cupping. The physiologic cup-to-disc ratio does not appear to correlate with a family history of COAG (287, 297), although some studies have suggested a weak correlation with higher IOP, abnormal tonographic outflow facilities, or highly positive pressure responses to topical corticosteroid use (269, 288, 297, 298 and 299). Other studies, looking primarily at disc area, showed significantly larger discs in patients with normal-tension glaucoma than in patients with COAG or control participants, and suggested that large discs have increased susceptibility to glaucomatous damage at normal pressures (300, 301). However, another study found no apparent differences between COAG and normal-tension glaucoma in morphometric parameters measured by scanning laser ophthalmoscopy (302).

Most studies have shown no significant correlation between age and the size of the physiologic cup (5, 267, 293, 303), whereas other investigations suggest that both the cup and pallor do enlarge slightly with increasing age (269, 288, 289, 304, 305). Any

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enlargement of the cup with age is gradual and should not be confused with the more rapid progression of glaucomatous cupping.

Racial differences in optic nerve head parameters have been shown, with African-Americans having a larger disc and cupto-disc ratio than whites (303, 306, 307, 308 and 309). This racial difference has also been demonstrated in children (310). Cup area and depth were larger in African-Americans than in whites in one study; however, structural characteristics of the optic nerve head associated with glaucoma were independent of differences in disc area (309).

Most studies have found no correlation between cup size and sex (287, 288, 293, 294), although one investigation revealed larger relative areas of pallor in white male patients than in white female patients (305), and others showed that men had slightly larger discs than women (5, 303). Refractive errors do not appear to correlate with the diameter of the physiologic cup (267, 269, 287, 293, 303), although a study of highly myopic eyes (>8.00 diopters [D]) revealed a significant correlation between refraction and disc size (275).

In the differential diagnosis of glaucomatous optic atrophy, it is important to distinguish between a large physiologic cup and glaucomatous enlargement of the cup (Fig. 4.13). One distinguishing feature is symmetry of cup size between the right and left eyes in the physiologic state, taking into consideration the normal variations. Another helpful feature is the configuration of the cup and neural rim and the appearance of the peripapillary pigmentation and RNFL, which are the same in eyes with large or normal-size physiologic cups (311). The most important feature, however, is documented progressive

cup enlargement, which is highly suggestive of glaucoma.

Figure 4.13 A: Large physiologic optic nerve head cups that are symmetrical and intact. B: Corresponding OCT image shows normal retinal NFL measurements.

Shape

The shape of the physiologic cup is roughly correlated with the shape of the disc, which means that the margins of cup and disc tend to run more or less parallel (312). However, as previously noted, the inferior neural rim is the broadest of the four quadrants, followed by the superior, nasal, and temporal rims (267). Consequently, the cup has a horizontally oval shape in most normal eyes; thus, a vertical cup-to-disc ratio greater than the horizontal cup-to-disc ratio should be considered suspicious (267, 289). Morphology of Glaucomatous Optic Atrophy

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The disc changes associated with glaucoma are typically progressive and asymmetric and present in various characteristic clinical patterns. It may be helpful to think of these in three categories: (a) disc patterns, (b) vascular signs, and (c) peripapillary changes.

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Figure 4.14 Inferior enlargement of cup (arrow) from original cup margin (dotted line) in glaucomatous optic atrophy, creating a polar notch (PN).

Disc Patterns of Glaucomatous Optic Atrophy

As bundles of axons are destroyed in an eye with glaucoma, the neural rim begins to thin in one of several patterns. One study, using confocal scanning laser ophthalmoscopy, found that half of patients with early glaucoma had smaller disc area with focal rim damage or no detectable damage, and the other half had larger discs with diffuse rim damage (313).

Focal Atrophy

Selective loss of neural rim tissue in glaucoma occurs primarily in the inferotemporal region of the optic nerve head and, to a somewhat lesser extent, in the superotemporal sector in the early stages of damage, which leads to enlargement of the cup in a vertical or oblique direction (314, 315, 316, 317, 318, 319,

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320, 321, 322, 323 and 324) (Fig. 4.14). In contrast to the normal optic nerve head, the inferior temporal rim in the glaucomatous eye is usually thinner than the superior temporal area, and the horizontal-to- vertical cup-to-disc ratio is reduced (321, 322). The neural rim area is typically smaller in glaucomatous discs than in nonglaucomatous discs, and this is a better parameter than cup-to-disc ratio in distinguishing eyes with early glaucoma from healthy eyes (321, 325, 326). As previously noted, however, the wide range of neural rim areas in normal eyes even limits the usefulness of this parameter. As the glaucomatous process continues, the temporal neural rim is typically involved after the vertical poles, with the nasal quadrant being the last to be destroyed (322).

The focal atrophy of the neural rim often begins as a small, discrete defect, usually in the inferotemporal quadrant, which has been referred to as polar notching, focal notching, or pitlike changes (316, 317, 318 and 319). As the focal defect enlarges and deepens, it may develop a sharp nasal margin (316). When the local thinning of neural rim tissue reaches the disc margin (i.e., no visible neural rim remains in that area), a sharpened rim is said to be produced. If a retinal vessel crosses the sharpened rim, it will bend sharply at the edge of the disc, creating what has been termed bayoneting at the disc edge.

Concentric atrophy

In contrast to focal atrophy, glaucomatous damage may less commonly lead to enlargement of the cup in concentric circles, which are sometimes horizontal, but are more often directed infratemporally or superotemporally (317). Because the loss of neural rim tissue usually begins temporally and then progresses circumferentially toward these poles, this has been called temporal unfolding (316, 317). In one study, this generalized expansion of the cup, with retention of its “round” appearance, was the mo st common form of early glaucomatous damage (327). Because distinguishing this type of glaucomatous cup from a physiologic cup is difficult, it is important to compare the cup in the fellow eye for symmetry and to study serial photographs for evidence of progressive change.

A thinning of the neural rim may be seen as a crescentic shadow adjacent to the disc margin as the intense beam of a direct ophthalmoscope passes across the neural rim (328). The histologic explanation for this phenomenon is uncertain, but it is thought to be associated with early glaucomatous damage and should not be confused with the previously discussed gray crescent in the optic nerve head (274, 329). Deepening of the Cup

In some cases, the predominant pattern of early glaucomatous optic atrophy is a deepening of the cup, which has been said to occur only when the lamina is not initially exposed (330). This may produce the picture of overpass cupping, in which vessels initially bridge the deepened cup and later collapse into it (316, 317). Exposure of the underlying lamina cribrosa by the deepening cup is often recognized by the gray fenestra of the lamina, which has been referred to as the laminar dot sign (316). In most cases, the fenestrae of the lamina cribrosa have a dotlike appearance on ophthalmoscopy, although some are more striate and the latter configuration may have a higher association with glaucoma (331, 332). Pallor-Cup Discrepancy

In the early stages of glaucomatous optic atrophy, enlargement of the cup may progress ahead of that of the area of pallor. This biphasic pattern differs from other causes of optic atrophy in which the area of pallor is typically larger than the cup (121). A potential pitfall in interpreting optic nerve head cupping is to look only at the area of pallor and miss the larger area of cupping. The latter can usually be recognized by observing kinking of vessels at the cup margin or by examining the disc with stereoscopic techniques. Although the pallor-cup discrepancy is typical and strongly suggests glaucomatous cupping, it may also be seen in some normal optic nerve heads (333).

Pallor-cup discrepancy may occur with diffuse or focal enlargement of the cup. Saucerization refers to a pattern of early glaucomatous change in which diffuse, shallow cupping extends to the disc margins with retention of a central pale cup (Figs. 4.15 and 4.16) and may be an early sign of glaucoma (334, 335).

Focal saucerization refers to a more localized shallow, sloping cup, usually in the inferotemporal quadrant (317). The retention of normal neural rim color in the area of focal saucerization has been called the tinted hollow (316). As the glaucomatous damage progresses, the color is replaced by a grayish hue, termed the shadow sign, or by the laminar dot sign (Figs. 4.17 and 4.18).

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Figure 4.15 Glaucomatous optic atrophy. Pallor-cup discrepancy. A: Saucerization with corresponding cross-sectional view. B: Focal saucerization with tinted hollow (TH) between pallor margin (PM) and cup margin (CM). Note kinking of vessels in both cases.

Figure 4.16 A: Saucerization of optic nerve head, evidenced by gradual sloping of vessels (arrowheads). B: Topographic map using confocal scanning laser ophthalmoscopy (HRT-II) of the same optic nerve shows the loss of neuroretinal tissue. The vessel path gives the appearance of saucerization.

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Figure 4.17 Inferotemporal loss of neural rim in glaucomatous optic atrophy, creating a sharpened rim (SR) at the disc margin, a sharpened polar nasal edge (SPNE) along the cup margin, bayoneting at the disc edge (BDE) where the vessels cross the sharpened rim, and laminar dot sign (LDS) due to exposure of fenestrae in lamina cribrosa.

Figure 4.18 A: Thinning of neural rim and “ bayoneting” of a blood vessel at the site of a hemorrhage 2 years earlier. B: Corresponding visual field. Note the development of a superior paracentral scotoma. (From Jindal A, Fudemberg S. Primary open-angle glaucoma [Chapter 52]. In: Tasman W, Jaeger EA, eds. Duane's Clinical Ophthalmology Vol 3. Philadelphia: Lippincott Williams & Wilkins; 2010.)

Figure 4.19 A:: Advanced glaucomatous optic atrophy with nearly total cupping of the optic nerve head associated with the presence of shunt vessels inferotemporally and nasally. B: Confocal scanning laser ophthalmoscopic topography demonstrates only a small amount of nasal rim remaining.

Advanced Glaucomatous Cupping

If the progressive changes of glaucomatous optic atrophy are not arrested by appropriate measures to reduce the IOP, the typical course is eventual loss of all neural rim tissue. The ultimate result is total cupping, which is seen clinically as a white disc with loss of all neural rim tissue and bending of all vessels at the margin of the disc (Fig. 4.19). This has also been called bean-pot cupping, because the cross section of a histologic specimen reveals extreme posterior displacement of the lamina cribrosa and undermining of the disc margin (Fig. 4.20) (317, 318).

Vascular Signs of Glaucomatous Optic Atrophy Optic Disc Hemorrhages

Splinter hemorrhages, usually near the margin of the optic nerve head (Figs. 4.21 and 4.22), are a common feature of glaucomatous damage (336, 337, 338 and 339). They occur more commonly P.69

in patients with normal-tension glaucoma than in patients with COAG or suspected glaucoma, with cumulative incidences of 35.3%, 10.3%, and 10.4%, respectively (338). They tend to come and go, so that they may be seen on one visit and be gone the next, only to reappear at a later date in the same or a

new location (340). One study has shown that 95.3% of disc hemorrhages were localized on or within 2 clock hours of an RNFL defect (341). Although they typically cross the disc margin, the papillary portion often disappears first during resorption, leaving the appearance of an extrapapillary hemorrhage (340). The most common location is the inferior quadrant, although they may be seen superiorly or at any other point around the disc margin. They are seen most often in the early to middle stages of glaucomatous damage and decline in frequency with advanced damage, rarely appearing in quadrants with absent neural rim (339); however, a thin neuroretinal rim was found to be a risk factor for the development of optic disc hemorrhages (342). Although not pathognomonic of glaucoma, disc hemorrhages are a significant finding, because they may be the first sign of glaucomatous damage, often preceding RNFL defects, notches in the neural rim, and glaucomatous visual field defects (343, 344, 345 and 346). They are especially suggestive of glaucoma when associated with high IOP (347). However, as previously noted, disc hemorrhages commonly occur with minimal pressure elevation or in eyes with normal-tension glaucoma (338, 348). If the glaucoma patient also has diabetes, disc hemorrhages are more common. Disc hemorrhages occur more commonly in diabetic versus nondiabetic patients with glaucoma (349, 350). Although disc hemorrhages are not invariably associated with an increased rate of disc damage, they are often associated with progressive changes of the visual field and should be viewed as a sign that the glaucoma may be out of control (336, 337, 347, 350, 351, 352, 353 and 354). It has also been noted that patients with hightension glaucoma and disc hemorrhages have a significantly higher prevalence of neurosensorial dysacousia than those without hemorrhages do, which was thought to suggest a common vascular denominator in both conditions (355).