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

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suggested that the TOP algorithm may not be able to spatially localize defects and accurately estimate sensitivity of visual field defects (187).

Patient Fixation

Patient fixation is monitored in various ways depending on the sophistication of the instrument. Some use a telescope, similar to the Goldmann manual perimeter, whereas others allow the operator to observe the patient's eye on a television screen. Automatic fixation monitoring is also incorporated into most units either by periodically retesting the patient's response in the previously determined blind spot (the Heijl-Krakau method) or by monitoring a light reflex from the patient's cornea. With the latter method, the computer can be programmed to stop the test whenever fixation is lost. Fixation is important, because eye movement has been shown to increase local short-term fluctuation and false-negative rates (188). However, maintaining fixation is difficult for many patients, and a new strategy of kinetic fixation, in which the fixation target is moved between stimuli, has been shown to improve threshold sensitivity (189). On the other hand, another study has found that kinetic fixation was associated with inaccurate fixation and underestimation of the absolute scotoma at the physiologic blind spot (148). New perimeters also use gaze tracking devices, which allow monitoring of the patient's gaze during the test. Interpreting the Results and Analyzing Progression

Determining Test Reliability

Several strategies are used to document variability and reliability of test results. With most fullthresholding programs, a percentage of random locations are retested to determine the reproducibility at those points. As noted earlier, these variations are referred to as short-term fluctuation and are expressed as the square root of the variance. The patient's general reliability is assessed with a series of falsepositives (patient responds when no target is presented) and false-negatives (patient does not respond to a stimulus of maximal intensity where a stimulus was previously reported to be seen), as well as the frequency of fixation losses and the number of stimuli required to complete the test. This current strategy of reliability indices has several problems. With the exception of the number of stimuli, all reliability parameters add to the testing time, which may actually reduce the patient's reliability. Furthermore, because each represents a limited sampling, the usefulness is questionable. Several evaluations of the Humphrey field analyzer, which uses the Heijl-Krakau blind-spot-checking method, revealed a high percentage of tests that were considered unreliable because the patient exceeded the established criteria for fixation losses (190, 191 and 192). Suggestions for modifying reliability indices to reduce testing time have included estimating short-term fluctuation from grids of single threshold determinations; using intermittent monitoring for patients who perform well during the first 1.5 minutes of testing; and substituting all indices with a new reliability parameter, which analyzes the inconsistency of responses to the standard thresholding algorithm (193, 194 and 195).

As discussed earlier, there is a certain degree of short-term fluctuation in the retinal threshold sensitivity profile (or hill of vision) among healthy individuals, especially in the midperiphery and superior quadrant (196, 197 and 198). In addition, each person with normal vision shows some variation from test to test, which is referred to as long-term fluctuation (198). However, both of these normal variations are more likely in glaucomatous visual fields and must be taken into account when attempting to interpret the significance of visual field data. Average total long-term fluctuation in patients with clinically stable glaucoma is similar to that in healthy persons (199). However, long-term fluctuation can be considerable in field areas with moderate loss of sensitivity (200). In addition, short-term fluctuation is increased around both physiologic and glaucomatous scotomas (19, 201, 202). Shortand longterm fluctuations are increased among older patients (203), and short-term fluctuation is often greatest in the patient's first automated field test, indicating the influence of experience (204). In one study, a change in mean sensitivity of approximately 5 to 7 dB between two successive fields was needed to have 95% confidence that the trend would be confirmed by the third field (205).

Printouts and Automated Analyses

In addition to providing indications of patient reliability, as noted above, the computer printout records the threshold for each retinal point tested along with various analyses of these measurements. The clinician can read computerized visual field printouts by looking primarily for NFL defects, such as

paracentral and arcuate scotomas and nasal steps, in the grayscale, numerical values, or symbols representing a decibel range (Fig. 5.15). The Humphrey field analyzer also provides printouts in total deviation (Fig. 5.15A), which is the difference between the measured threshold for each retinal point tested and the age-corrected normal, and in pattern deviation (Fig. 5.15B), which is created from the total deviation by adjusting it an amount equal to an average of the 17 worst test points. This helps eliminate “background noise,” such as the generaliz ed depression of a cataract. Both total and pattern deviations are displayed in numeric and probability plots. Graphic methods have been devised to show the development of visual field defects by analyzing recorded visual fields and displaying changing areas as stripes (206), or triangles, or colored display of pointwise analysis, as in newer Progressor software (discussed later).

Global Indices

Static threshold data can be analyzed mathematically, allowing detection of more subtle visual field abnormalities. The statistical techniques used in this approach are referred to as visual field global indices (Fig. 5.15C). An average of all points

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in the total deviation is referred to as mean deviation. These indices primarily reflect diffuse changes. One way to detect localized defects is to calculate the number of threshold values that deviate significantly from the age-corrected normal, which is called pattern standard deviation. Corrected pattern standard deviation takes into account the short-term fluctuations.

Figure 5.15 Computer printout of visual field of a right eye, measured by automated static technique, showing superior arcuate scotoma and nasal step. A: Total deviation. B: Pattern deviation. C: Global indices. D: Glaucoma hemifield test.

Short-Term Fluctuations

The visibility of the stimulus in standard static perimetry is typically adjusted by changing its intensity. Although in the laboratory threshold sensitivity is considered to be the stimulus intensity at which the patient responds 50% of the time, it is impractical to measure threshold so precisely in the clinical

situation. Standard static threshold perimetry estimates the threshold sensitivity with approximately 2 dB of precision by presenting the stimuli in increments to a certain location in the retina and recording the value of the weakest stimulus seen. In some protocols, this process is repeated in random locations. The difference between the patient's responses at the same location during the same session may be used to calculate the standard deviation of the threshold values, called the shortterm fluctuation or intratest variability.

Long-Term Fluctuation

The difference in threshold values in the same location between separate sessions is called the long-term fluctuation. This typically represents physiologic rather than glaucomatous changes in visual function over time. Although long-term fluctuation is not quantified in routine clinical perimetry, it should be considered in interpretation of a series of visual fields.

Discrete scotomas may be preceded by variable threshold responses to repeated testing in the same area (17, 207, 208). This fluctuation has also been referred to as scatter (209), or

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localized minor disturbances. Studies show that patients with glaucoma have substantially greater shortterm fluctuation, and to a lesser degree, long-term fluctuation (145, 210, 211). Although scatter is not a definitive sign of glaucomatous visual field damage, it should be looked on with suspicion as an early warning sign of impending absolute field loss.

Cluster Analysis

The global indices for localized loss are insensitive to the location of the defects. For example, three abnormal locations could either be randomly distributed or clustered. Attempts to improve the interpretation of data have led to the strategy of cluster analysis, or spatial correction. With this strategy, contiguous clusters of test locations, which have an increased probability of appearing together in typical glaucomatous field loss, are considered together in evaluating the visual field. They can be used in calculating local indices, which should be more sensitive than global indices are, and may help to dampen long-term fluctuation. In several studies, by using different cluster patterns, they have provided an enhanced probability of distinguishing normal from glaucomatous fields, as well as a stable glaucoma field from one that is deteriorating (212, 213, 214 and 215).

Glaucoma Hemifield Test

Another strategy to analyze the result of the visual field test is to compare sums of threshold values in corresponding areas of the superior and inferior hemispheres (216, 217 and 218). In the Humphrey field analyzer Statpac (discussed later), this is called the glaucoma hemifield test (GHT) (Fig. 5.15D). The GHT performs analysis in five corresponding pairs of sectors that are based on the normal anatomy of the retinal NFL. It then looks at the distribution of changes in pattern deviation and analyzes the difference between upper and lower hemifields. It uses a large normal database to calculate the significance of differences between the two hemispheres and has been shown to significantly improve the ability to separate between normal and glaucoma fields (216, 219). It has good sensitivity and specificity, although reproducibility is such that the use of two tests is recommended to improve specificity (220, 221). This method allows a simple but clinically useful analysis of visual field changes in patients with glaucoma. The GHT provides five plain language messages about the results of the visual field test: within normal limits, outside normal limits, borderline, general reduction of sensitivity, and abnormally high sensitivity (216). One study evaluated the repeatability of the GHT and found that, although it was generally good on consecutive testing, there was enough disagreement to justify the use of a second test for improved specificity in a clinical trial setting (221). The GHT “outside normal limits,” used together with the pattern deviation p robability plot, has been shown to provide high sensitivity and specificity for detecting early glaucomatous visual field changes (222).

AGIS and CIGTS Scores

The Advanced Glaucoma Intervention Study (AGIS) investigators have developed a method of interpreting visual field results on the basis of the number and depth of clusters of adjacent depressed test sites in the upper and lower hemifields and in the nasal area of the total deviation plot, using the 24-

2 threshold program of the Humphrey visual field analyzer (223). The Collaborative Initial Glaucoma Treatment Study (CIGTS) investigators used a similar scoring system with a modification to evaluate progression in patients with newly diagnosed glaucoma (224). Both AGIS and CIGTS scores range from 0 (no defect) to 20 (end-stage). Progression is defined as worsening of the score by 4 points in the AGIS system and by 3 points in the CIGTS system.

Trend Analysis

Statistical models are available with some automated perimeters to help the clinician determine the significance of visual field indices and variability. Those that have received several investigations are the Delta program with the Octopus perimeter (225) and the Statpac with the Humphrey field analyzer (226). With both systems, databases are used to calculate the probability of a measured value appearing in a given age-defined population. In the case of the Humphrey field analyzer, the Statpac uses a large normal database, and Statpac II uses a database of stable glaucoma patients. The Statpac printout includes the reliability and global indices, the GHT, and probability maps, which display the field results in terms of the frequency with which the measured findings are seen in the defined population (227, 228). The Statpac II also includes linear regression analysis and glaucoma change probability.

The glaucoma progression analysis (GPA) (Fig. 5.16) replaces the glaucoma change probability that is used for fullthreshold testing. The GPA defines progression as more than three test points in the same location on three consecutive tests.

A third statistical algorithm with the Humphrey field analyzer is the Progressor program for analysis of serial fields, which is downloaded to a personal computer (229). The Progressor uses the data from all visual fields in the series of examinations to perform pointwise linear regression analysis and to generate a color-coded graphic display for simultaneous interpretation of the spatial and temporal changes (230). Although most statistical models provide better agreement than experienced clinical observers do regarding significant change over time, there is currently no generally accepted technique (231). One study, which compared the results of a threshold program on the Octopus perimeter to those from manual perimetry, demonstrated that indices used currently may not be clinically reliable in the assessment of changes in the visual field (232). A study evaluating the three commercially available computed statistical algorithms with serial Humphrey fields showed a high degree of variability among the three, with none correlating well with the clinical impression (229). A study comparing the Statpac II and Progressor showed that these two algorithms detected progression in the same patients, but Progressor detected progression earlier than Statpac II did (233). Until improved statistical algorithms are available, therefore, these data must be used with caution, and physicians should still rely primarily on their own clinical judgment.

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Figure 5.16 Example of the GPA, which plots the mean deviation of sequential visual fields over time. Reversibility of Glaucomatous Field Defects

Although visual field loss from glaucoma has traditionally been thought to be irreversible, central visual acuity and the field of vision may improve if the IOP is reduced in the early stages of the disease (234, 235, 236 and 237). Visual field global indices with automated perimetry improved proportional to the

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amount of IOP reduction in two studies (238, 239). Other investigators, however, could not demonstrate reversibility after pressure reduction was achieved by argon-laser trabeculoplasty (240, 241). These conflicting findings may indicate that a critical level of pressure reduction or intervention at a critical time in the disease process is needed to reverse field loss. Also, the ability to document improvement in visual fields after surgical reduction of IOP may be enhanced by focusing on subgroups of test points with lower baseline sensitivity (242).

Recording and Scoring Manual Visual Field Data

The complex nature of visual field data makes it difficult to reduce the information to simple descriptions or numbers. Therefore, storage of the data in its raw form—that is, as transferred direct ly from the testing screen—is usually the most practic al means of record keeping. However, methods for conversion of visual fields from kinetic and static perimeter charts to computer use, for area calculations, graphic display, and storage in the patient's database, have been described (243, 244). Visual Impairment and Disability Assessment

When it is necessary to estimate the percentage of functional visual field loss, a system is available (the Esterman grids) in which the field is divided into 100 blocks of varying size

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according to functional value, with each representing 1% (245, 246 and 247). The system has been adopted by the American Medical Association as a standard for rating visual field disability (248). Grids are available for scoring the tangent screen, perimeter, or the binocular field (245, 246 and 247). In patients with severe visual loss from glaucoma, the binocular Esterman score of data generated by an automated perimeter correlated well with combined monocular visual field results (249).

Other Types of Perimetry

Glaucoma affects various components of the visual field, and subtle loss of central and peripheral vision can be demonstrated in some patients with glaucoma before visual field changes are detectable with standard techniques. Achromatic stimuli, used in standard automated perimetry, nonselectively stimulate ganglion cells involved in the magnocellular and parvocellular pathways, and therefore are not always sensitive enough to detect early glaucomatous damage. New strategies that are specifically designed to test subgroups of ganglion cells (250, 251) are discussed next.

Short-Wavelength Automated Perimetry

Compared with white-on-white targets, color stimuli may influence the visual field results in one of two ways. Color targets typically have less luminance and a lower stimulus value than white targets do. More significantly, if the luminance is kept constant and the color saturation is varied, the stimulus value might be more sensitive to specific color vision defects, as in some patients with glaucoma (252). Early studies suggested that such a technique could reveal field defects that are larger than those obtained with conventional white-on-white perimetry (253, 254), whereas other studies found color targets to be no more sensitive than white ones in detecting glaucomatous defects (255, 256 and 257). These conflicting results may be related to the colors selected for the test. Continued study has led to the following observations with new test objects.

Testing one subgroup of small ganglion cells, called bistratified blue-yellow ganglion cells, that are sensitive to blue stimuli may detect loss of visual function at much earlier stage of glaucoma than with standard automated perimetry (258). Shortwavelength automated perimetry (SWAP) takes advantage of this glaucoma-induced color vision deficit by presenting standard Goldmann size V, short-wavelength blue targets on a bright yellow background (259, 260). Studies indicate that SWAP deficits represent early glaucomatous damage and that the test may indicate significant change in visual function before it is apparent on standard white-on-white visual fields (261, 262, 263, 264 and 265). Longitudinal studies have demonstrated the ability of blue-on-yellow perimetry to predict the development of glaucoma in patients with ocular hypertension, and in which patients early glaucomatous visual field loss is most likely to progress (266, 267 and 268). Other studies have demonstrated a significant relationship between structural optic nerve damage and SWAP visual field defects (263, 269). However, the test is influenced by age and cataracts, and stringent statistical analysis in interpreting the results is necessary

(270, 271, 272 and 273), but SWAP testing is unaffected by blue-blocking acrylic intraocular lens implants, compared with clear acrylic implants (274). One study investigated whether SWAP, using a screening program, can detect early glaucomatous damage before standard screening perimetric tests can, and found that the SWAP screening program is more advantageous than conventional tests in detecting early glaucomatous visual field defects (275). However, some patients with ocular hypertension and early glaucomatous structural abnormalities may have normal blue-yellow perimetry (276). The SWAP is available on the newer Humphrey field analyzer II. A new generation of SWAP techniques uses more efficient strategies, such as SITA. By using this approach, testing time has been reduced from 12 minutes to less than 4 minutes (277). SITA SWAP testing detects higher sensitivities than fullthreshold SWAP does, and is equal to full-threshold SWAP in its ability to detect visual field abnormalities (278, 279). The topography of the SWAP field is steeper than achromatic automated visual fields (280). SWAP testing is also subject to greater long-term fluctuation and more learning effect artifact, compared with achromatic automated visual fields. Thus, defects found by using this method should be interpreted cautiously, and confirmation with a repeated SWAP test is advisable (281, 282).

Frequency Doubling Technology

Frequency doubling technology (FDT) perimetry is based on the frequency doubling illusion (283). Each test stimulus is a series of white and black bands flickering at 25 Hz (284). FDT perimetry is thought to be mediated by a subset of the largediameter ganglion cells, called the My ganglion cells, that

project to the magnocellular visual pathway (285). These cells are sensitive to motion and contrast and are thought to be more vulnerable to glaucomatous damage (85, 286), although this view has been questioned by some authors (287, 288, 289 and 290). The FDT is a portable (Fig. 5.17) and relatively inexpensive tool with a short testing time (250, 291), qualities that make it a useful screening device (250, 291, 292, 293 and 294). When administered in a suprathreshold screening mode, FDT perimetry can be performed on a healthy eye in less than 90 seconds (284), and provide a higher detection rate for early glaucoma than with SAP (295). (A comparison of FDT and SAP readouts is shown in Fig. 5.18.) FDT showed greater than 96% sensitivity and specificity for detection of moderate and advanced glaucoma, and greater than 85% for early glaucoma, when compared with SAP in a prospective study (296). Because of its relatively quick acquisition times and high sensitivity, FDT is also advocated for use in children. Children older than 14 years have the same normal threshold limits as adults do; for children younger than 14 years, the mean deviations for normal decreased with decreasing age, with a linear best fit of mean deviation of - 11 ± 1 dB for age down to 6 years (297). However, FDT perimetry was reported to be less sensitive to visual field

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damage associated with neurologic disorders, compared with SAP (298). Sensitivity to FDT was found to be reduced in the second tested eye if an opaque occluder was used, because of delayed postocclusion light adaptation; a translucent occluder eliminated this reduction in sensitivity in the second eye (299). The original FDT perimeter tested a maximum of 19 points over the central 20 (C-20) or 30 (N-30) degrees of the visual field with both screening and threshold strategies (300) (Fig. 5.18). A secondgeneration FDT (Humphrey Matrix, 2003) uses smaller stimuli to examine a larger number of test points, which may allow better early detection of glaucoma (300, 301 and 302) and has the following testing strategies available: macula, 10-2; N30-F, 24-2, and 30-2. The GHT algorithm is available for the 24-2 and 30-2 testing strategies. FDT tests are also subject to learning and long-term fluctuation artifacts; thus, abnormal test results should be interpreted cautiously, and confirmation with a repeated test is advisable (303, 304 and 305).

Figure 5.17 Frequency doubling technology perimeter.

Figure 5.18 Pattern deviation plots for SAP-SITA, FDT N-30, and FDT 24-2. Each plot shows the locations tested and the results expressed as a grayscale pattern (denser patterns indicate deeper defects). Probabilities are shown in the corresponding keys. (Reprinted from Racette L, Medeiros FA, Zangwill LM, et al., Diagnostic accuracy of the Matrix 24-2 and original N-30 frequency-doubling technology tests compared with standard automated perimetry. Invest Ophthalmol Vis Sci. 2008;49:954-960, with permission.)

Contrast and Motion Sensitivity

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As noted above, the eye with glaucomatous damage appears to have reduced ability to perceive motion and contrast, both centrally and peripherally (300, 307, 308). This may be related to preferential damage to larger retinal ganglion cells, and motion and contrast perception tests may prove useful in the detection of early glaucoma (306, 307 and 308). The detection of vernier offsets is also affected in glaucoma, but it is not sensitive enough to distinguish patients with glaucoma from controls (309). Various perimetric tests measure contrast and motion sensitivity in glaucoma, including gratings tests for contrast sensitivity, vernier acuity, flickering stimuli, high-pass resolution perimetry, and random motion automated perimetry (309, 310, 311, 312, 313, 314 and 315). (The application of these visual function tests in glaucoma is discussed in Chapter 6.)

High-Pass Resolution Perimetry

High-pass resolution perimetry, or ring perimetry, is presumed to selectively test the parvocellular system (314). The stimuli used in this test are rings of different size projected at different locations on the computer screen. The rings have dark borders and bright centers, creating average luminance of the stimulus equal to the luminance of the background. By also using high-pass spatial filtering, the targets can be detected and resolved at the same ring size, in an effect known as vanishing optotype, allowing rapid definition of the resolution threshold. The results of the test are presumed to correspond to the density of ganglion cells; this test is therefore essentially a peripheral visual acuity test (250). Healthy persons showed increased resolution threshold toward the periphery, a slight but significant decline in sensitivity with age, and high repeatability (316), as well as reliability indices comparable to SAP (317). Patients with glaucoma showed a significant reduction in overall resolution threshold (318), and the results were comparable to standard perimetry in sensitivity and specificity (319, 320). Study findings suggest that high-pass resolution perimetry could identify

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glaucomatous visual field damage in early and moderate stages of the disease (321, 322). Random Dot Motion Automated Perimetry

Yet another technique, random dot motion automated perimetry, takes advantage of reduced motion sense in patients with glaucoma by presenting a shift in position of dots in a defined circular area against a background of fixed dots (306, 323). The patient should tell the direction (up, down, left, right) in which the dots are moving. A preliminary study showed that patients with COAG manifest abnormal motion perception with the test, compared with healthy persons (315). Patients with glaucoma have demonstrated prolonged reaction time to the stimulus and less precise location of the stimuli (324). The test takes approximately 15 minutes to perform (250). Localized visual field loss detected by motion automated perimetry appeared to correspond to focal changes in optic disc topography, similar to those found by SWAP and SAP (325).

Combining results of functional tests with structural tests may identify different elements of glaucomatous damage and improve sensitivity and specificity of the tests (326).

Manual Perimetry

Although automated perimeters are being used with increasing frequency in clinical practice, the older, manual perimeters may still provide valuable information, especially when a skilled observer performs the test.

Tangent Screens

The tangent screen is a flat square of black felt or flannel with a central white fixation target on which 30 degrees of the vi sual field can be studied, The test is performed in mesopic lighting of approximately 7 foot-candles with the patient seated 1 or 2 m from the screen. Both kinetic and supra-threshold static techniques can be used with the tangent screen. With the kinetic approach, the examiner moves a test object from the periphery toward fixation until the patient indicates recognition of the target. The procedure is repeated at various intervals around fixation until the isopter has been mapped. The stimulus value of the test objects can be changed by varying the size and color. The corresponding isopter is designated by the ratio of target diameter to the distance between patient and target, with both expressed in millimeters, for example, “ 2/1000 white” for a 2-mm white test object at 1 m (when the