Evaluation of Sensitivity and Specificity of Spatial Resolution and Humphrey Automated Perimetry in Pseudotumor Cerebri Patients and Normal Subjects

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1 nvestigative Ophthalmology & Visual Science, Vol., No., December 99 Copyright Association for Research in Vision and Ophthalmology Evaluation of Sensitivity and Specificity of Spatial Resolution and Humphrey Automated Perimetry in Pseudotumor Cerebri Patients and Normal Subjects Michoel Wall,*t Mandi D. Conwoy,* Philip H. House, and Rosalie Allely* To determine the sensitivity and specificity of high-pass resolution perimetry ("ring test")) 8 patients with pseudotumor cerebri (PTC) and 8 age-matched controls were examined with the Humphrey program - and the ring test. Goldmann perimetry also was done to determine if defects found with the ring test were present with another method. Testing with Humphrey perimetry revealed defects in PTC patients and four control subjects; with the ring test, PTC patients and two control subjects had abnormalities. The disturbed areas in the control subjects with both automated tests were not reproducible. Humphrey perimetry had a sensitivity of 8% and the ring test, 7%. The specificities were Humphrey perimetry, 78% and the ring test, 89%. These differences were not statistically significant. Qualitative assessment of the presence and extent of damage using the pointwise probability plots and graphically displayed raw data showed good correlation of the tests in of the 8 patients. The lack of correlation in four of the patients was caused by the presence of a generalized depression or a peripheral contraction on the Humphrey test; this defect, not present on retesting, may have been related to fatigue or poor motivation. The ring test is a sensitive and specific perimetric technique in patients with PTC. nvest Ophthalmol Vis Sci :6-,99 Differential light sensitivity threshold automated perimetry is more sensitive than Goldmann perimetry. ' Because the test is time consuming and monotonous, some patients become fatigued and change head position. This may lead to visual field defects from various artifacts or unreliable performance. ' t has been reported up to % of glaucoma patients and % of normal subjects tested did not meet the reliability criteria of a conventional automated perimeter. This source of measurement error can cause falsepositive results and led to a loss of specificity. Also, the simple discrimination of a white target on a white background may limit the sensitivity of each method and the correlation with the underlying anatomy. 6 One attempt to overcome these problems was reported with high-pass resolution perimetry (the "ring From the Departments of ""Ophthalmology and fpsychiatry & Neurology, Tulane University School of Medicine, New Orleans, Louisiana, and the ^Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia. Supported in part by an unrestricted grant from Research to Prevent Blindness, nc., New York, NY. Presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, April to May, 989. Submitted for publication: November, 99; accepted July, 99. Reprint requests: Michael Wall, MD, Tulane University School of Medicine, Department of Psychiatry & Neurology, Tulane Avenue, New Orleans, LA 7. test"). 7 " 9 n this test, the stimuli areringsgenerated by processing doughnut-shaped targets with a high-pass filter (Fig. ). This produces a spatial resolution target of low contrast and high spatial frequency with the average target luminance equal to the background. This target has the property of a "vanishing optotype," ie, detection and spatial resolution thresholds are theoretically equivalent. The targets are available in sizes with a step factor of.6. The acuity at each of test locations is scored as the smallest ring size the subject can discern; therefore, the better the acuity, the lower the score (Fig. ). After ring presentation, each legal patient response is acknowledged by a black square image displayed on the screen at the tested location. The test takes approximately. min per eye. To determine its ability to distinguish accurately those with disease from those who are disease-free (sensitivity and specificity), we tested 8 patients with pseudotumor cerebri (PTC) and 8 normal subjects. n addition, we attempted to correlate qualitatively the extent and similarity of visual field defects detected by the ring test with those of other perimetric tests. Patients and Methods Eighteen patients with known PTC and 9 agematched normal subjects consented to participate in 6 Downloaded From: on 9/9/8

2 No. SENSTVTY AND SPECFCTY N PTC / Wall er al Fig.. Examples of high-pass resolution targets. The intratarget contrast is equal to the background. the study. The mean age of the patients was 7.9 ±. yr and of the control subjects,. ±. yr. The controls and patients all underwent a complete neuro-ophthalmologic examination. Normal subjects were recruited from Tulane Medical Center employees and residents. Potential normal subjects all underwent Goldmann perimetry. One had a visual field defect and was excluded. All patients first underwent Goldmann perimetry followed by the automated methods done in a random order. Both eyes were tested. Program - of the Humphrey field analyzer (Allergan-Humphrey, San Leandro, CA) was chosen because it has approximately the same number of test loci () as the ring test (). However, the - test loci are separated equally in a 6 grid, and the ring test uses a nerve fiber bundle-related pattern and eliminates the pericecal points and test loci in the central (Fig. ). We did Goldmann perimetry using a modified ArmalyDrance strategy. The perimetrist did not know the results of automated perimetry. All tests were done on 7 the same day with the examinations separated by at least min to decrease the effect of fatigue. All patients fulfilled the modified Dandy criteria for PTC (Table )." The patients with PTC and five normal subjects were experienced in manual and automated perimetry. No patients or normal subjects were experienced in the ring test. However, ten patients and ten subjects were retested four times as part of another study; their second examination was used for our analysis. We administered the ring test according to the recommendations of the manufacturer's operating manual (Ophthimus system; HighTech Vision). The patients' appropriate near correction was given with care taken to prevent lens rim artifact. Patient fixation was monitored by the visual field technician and with intermittent blind-spot testing (Heijl-Krakau method). We examined the results of Goldmann perimetry in a masked fashion. Localized defects were tabulated by noting step defects of more than in one isopter or more than in two adjacent isopters; any scotomas (other than the physiologic blind spot) not eliminated by refraction were tabulated. We considered constriction present when isopters fell at least from where they were expected (based on the data of Egge). We used the pointwise probabilities of the Humphrey Statpac to determine the presence of localized defects for the - fields. For the ring test, the determination was made using an age-corrected probability plot analysis based on values in normal subjects. RNGPROB (a BASC program written by MW) was used for the analysis (available free on request). Test loci scores were interpreted as abnormal if they fell outside the 9% confidence limits of the control population. The important differences between the design of these two probability plots are the Humphrey Statpac data base has approximately fourfold as many subjects and uses a formula that weights the values for the central points. This central weighting is not necessary for the ring test because variability does not rise with increasing eccentricity." We defined a localized defect for both automated testing methods as the presence of three disturbed Table. Modified Dandy criteria for PTC Fig.. test results of a right eye of a normal subject. The area surrounding the physiologic blind spot and the central five degrees are not tested. Note the gradually increasing ring size with increasing eccentricity. *. Signs and symptoms of increased intracranial pressure. Absence of localizing findings on neurologic examination. Absence of deformity, displacement, or obstruction of the ventricular system and otherwise normal neurodiagnostic studies, except for increased cerebrospinal fluid pressure. Awake and alert patient. No other cause of increased intracranial pressure present Downloaded From: on 9/9/8

3 ::::::::::::::;.!- 8 NVESTGATVE OPHTHALMOLOGY & VSUAL SCENCE / December 99 Vol. points in contiguity (P <.) or one markedly disturbed point (P <.) next to a suspicious point (. < P <.). We determined global loss by using the Statpac P <. confidence limits for the mean defect. A similar global deviation and its 9% confidence limits were was used for the ring test. We calculated the sensitivity and specificity for each test for each subject by determining if a visual field defect was present in either eye and compared this result with the subject's known diagnostic group (PTC or control). The visualfields then were assessed qualitatively using graphic displays of the raw data and pointwise probability plots for the extent and possible similarity of the defects. Results Goldmann perimetry was abnormal in nine of 8 patients. Humphrey perimetry detected visual field loss in of 8 patients; the ring test detected this in patients. However, by the Humphrey - test, four of the patients had a peripheral contraction or a generalized depression that was not present with repeat testing within the next 6 weeks (Fig. ). Humphrey perimetry disclosed a visual field disturbance in four control subjects; two others had a disturbed field with the ring test. None of these defects were reproducible with repeat testing. The defects present according to test, subject, and group are found in Table. The extent and similarity of defects present in the patients is found in Table. n general, the defects were similar in shape and extent within subjects. Eleven patients had good correlation of the defects of the perimetric tests. Three patients had defects found with automated perimetry in clinically suspicious areas (visual field areas where defects are common in PTC) on only one of the two automated tests. The defects occurred in two visual fields in one patient with the ring test and two visualfieldsin two patients with the Humphrey perimeter. Four patients had a generalized depression or a peripheral contraction only on the Humphrey test; these defects were not present on retesting. Specificities and sensitivities are found in Table. The differences between the three groups in specificity and sensitivity were not significant (P >., by Fisher's exact test). Figure shows a patient with PTC and an inferior nasal defect found with all three tests. The extent of..:: r.v.'ivivivr.v.": ::::::::" iiiisii::.. : :viiiii ::::::::::! i::!::::: ::::::::::, :::::::::- :::::;?!::::: TOTfL OEVPTOH " : ' : B ' :. S XfXf :: k «:: PROGflBinYSmS :=P< R CP< R 8P< X P<.R TOTPL DEVRTON Fig.. A peripheral contraction present on testing with Humphrey perimetry (left). The Goldmann visualfieldand theringtest were normal. The disturbance was not present on retest week later (right). Downloaded From: on 9/9/8

4 No. SENSTVTY AND SPECFCTY N PTC / Wall er ol 9 Table. Visual field defects found with various forms of perimetry in patients and controls Goldmann test Humphrey Visualfielddefect Patients Normal 6 9 Generalized constriction Nasal loss* nferior nasal loss Sup. nasal loss Bjerrum scotoma sup. Bjerrum scotoma inf. Cecocentral scotoma nf. altitudinal loss Enlarged blind spot 6 Total defects 6 Global/mean deviation Normals Normal Nasal loss* Generalized constriction nferir nasal loss Bjerrum scotoma inf. Total defects Global/mean deviation o o o o * Nasal loss = superior nasal and inferior nasal loss. Table. Comparison of the presence, extent, and similarity of visual field defects of the ring test and conventional automated perimetry Pt no. Correlation Extent* Similarity G = R H-nc G = H R-c G = H R-nc G = R H-nc Cen Dep G = H H-c G = H R-c G = R H-c Key: = conventional automated perimetry (Humphrey -); G = Goldmann defect; R =ringtest defect; H = Humphrey perimetry defect; c = defect occurred in a clinically suspicious area; nc = defect occurred in a nonclinically suspicious area (the type of defect follows): Cen = central defect; Gen = generalized; Dep = depression. * Extent was graded as the results of the two automated methods being approximately the same, or either the ring test or conventional automated perimetry showing a defect with greater area. Downloaded From: on 9/9/8

5 NVESTGATVE OPHTHALMOLOGY b VSUAL SCENCE / December 99 Vol. Table. Estimated sensitivity and specificity calculations PTC patient with defect PTC patient without defect Control with defect Control without defect Sensitivity Specificity - test 6 the defect was greatest with the ring test (note the nasal depression on the ring test's probability plot). Results from another patient are found in Figure. The ring test showed an inferior nasal depression; an inferior nasal defect and an enlarged blind spot extending into the inferior Bjerrum area were found with Humphrey perimetry. Goldmann perimetry (not shown) demonstrated the inferior Bjerrum and inferior nasal defects. 7% Discussion Elevated mean thresholds or significant interocular differences were found with the ring test in of patients with elevated intraocular pressure. 6 Differential light sensitivity automated perimetry was not abnormal using similar criteria. Others compared the ring test and automated perimetry (Gl program of Octopus perimeter [nterzeag, Schlieren, Switzerland]) in 6 eyes of 6 patients with glaucoma, low-tension glaucoma, and ocular hypertension. 7 They found an excellent correlation between the two tests for mean sensitivity of the entire field (r =.9) and each quadrant (r =.9). We did not find a relationship between the scores of the mean sensitivity difference from normal between the two tests. Humphrey perimetry was more sensitive for this global index (Table ); however, this should be interpreted in light of the probable falsepositive findings and possible fatigue effect. When the ring test and automated perimetry (Octopus program ) were compared in 6 patients with O O -O o OD O ram DEVOTON / MBBUY sms?< s «?.p< a»p< u p < O.R Symbols - score normal for age - abnormal at p =. level - abnormal at p». level Fig.. Comparison of Goldmann perimetry (A), Humphrey - (B), and the ring test (C). Note the inferior nasal defect present with all three tests. The extent of the defect is greatest with the ring test. Downloaded From: on 9/9/8

6 No. SENSTVTY AND SPECFCTY N PTC / Wall er al <> e o * O «o "O "D o TOTflL (EVflTON / % u m a» a ROWUTYSmS "P< S SP< u P<O.R Symbols - score normal for age - abnormal at p -.OS level - abnormal at p -. level B Fig.. Comparison of Humphrey - (A) and theringtest (B). Note the inferior nasal step defect detected by both tests. The defect extends into the inferior Bjerrum area with the - test. chiasmal lesions, a good correlation was found in the loss of quadrant sensitivity when compared with the scores in adjacent normal quadrants. 8 n 6 patients with absolute defects with the ring test, there was some remnant of visual function using differential light sensitivity automated perimetry. This is caused by the strategy of the ring test. f a subject at the beginning of the test twice misses a ring target filling the entire quadrant, no further stimuli are presented in that quadrant. n this study, program took at least twice as long to administer as the ring test. When defects are detected with any new sensory visual test, it should be questioned whether they relate to true pathologicfindingsor are an artifact associated with the technique. n this study, most defects found with the ring test appear to be true defects because most have a similar shape and defect extent among the three tests (Table ). The agreement among the tests was even better if the four patients with PTC and unreproducible field defects on the - test were ignored. These defects probably were related to fatigue or declining motivation from the prolonged testing time required in conventional automated perimetry. Although an acuity stimulus is a more complex target than the stimulus used for differential light sensitivity perimetry, the ring test does not appear to be more sensitive than the light sensitivity method. This finding agrees with that of others who used a different method of acuity perimetry. 9 They found acuity perimetry results similar to those of light sensitivity perimetry in optic neuropathies. A problem with this type of study is the lack of a "gold standard" for perimetry. We used the clinical diagnosis of PTC as such a standard. Because not all patients with PTC have visualfielddefects (even those with marked papilledema ), the sensitivity is less than %. Also, although the ring test is the newest method of those tested, defects found with the other tests must be validated. For example, four normal subjects had visualfielddisturbances with Humphrey perimetry (two normal subjects had defects found with the ring test). None were present on repeat testing. Although our criteria for abnormality were similar for both automated tests, legitimately changing criteria for abnormality could give very different results. Downloaded From: on 9/9/8

7 NVESTGATVE OPHTHALMOLOGY & VSUAL SCENCE / December 99 Vol. Also, it may not be fair to insist on three contiguous disturbed test points for an abnormality when the test locations and measuring techniques of the two tests are so different. There is a problem with false-positive results in automated perimetry from artifacts and fatigue. This may be especially true for differential light threshold perimetry because patients must sit in an uncomfortable position for long periods during which concentration is imperative. Changes in head position, including tilt, can occur. For these and other reasons, some subjects have difficulty doing this test. These problems appear lessened with the ring test because of the better ergonomics and feedback to the subject. For example, after each legal response, a black square target is presented to provide immediate visual confirmation of the test location. nappropriate responses call various messages. A constantly changing fixation mark and a message to "look here" decrease monotony. A message also prompts poor fixaters to "look here" at the fixation target. 79 n conclusion, the sensitivity and specificity of the ring test is similar to differential light sensitivity automated perimetry. Most of the defects found with the ring test had a similar defect present with at least one of the other two tests. Theringtest has the characteristics of an excellent screening test for patients with optic neuropathies; it has high sensitivity and specificity with low variability. Because the ring test also has a short testing time, is ergonomically designed, and has a patient feedback strategy, we recommend it as a test to detect and follow patients with optic neuropathies. Key words: automated perimetry, intracranial hypertension, pseudotumor cerebri, visualfield,visual testing Acknowledgments The authors thank Dr. Paul Siegel for his excellent editorial assistance. References. Beck RW, Bergstrom TJ, and Lichter PR: A clinical comparison of visualfieldtesting with a new automated perimeter, the Humphreyfieldanalyzer, and the Goldmann perimeter. Ophthalmology 9:77, 98.. Katz J and Sommer A: Reliability indexes of automated perimetric tests. Arch Ophthalmol 6:, Anderson DL: Perimetry with and without automation. St. Louis, CV Mosby, 988, pp Bickler-Bluth M, Trick GL, Kolker AE, and Cooper DG: Assessing the utility of reliability indices for automated visual fields: Testing ocular hypertensives. Ophthalmology 96:66, Katz J and Sommer A: Screening for glaucomatous visual loss: The effect of patient reliability. Ophthalmology 97:, Frisen L: Acuity perimetry: Estimation of neural channels. nt Ophthalmol :69, Frisen L: A computer graphics visualfieldscreener using highpass spatial frequency resolution targets and multiple feedback devices. Doc Ophthalmol Proc Ser :, Frisen L: High-pass resolution targets in peripheral vision. Ophthalmology 9:, Frisen L: Computerized perimetry: Possibilities for individual adaptation and feedback. Doc Ophthalmol 69:, Wall M and George D: diopathic intracranial hypertension: A prospective study of patients. Brain :, 99.. Smith JL: Whence pseudotumor cerebri? J Clin Neuro Oph-. thalmol :, 98. '. Egge K: The visual field in normal subjects. Acta Ophthalmol (Copenh) 69(Suppl):, 98.. House P, Schulzer M, Drance S, and Douglas G: Characteristics of the normal central visualfieldmeasured with resolution perimetry. Graefes Arch Clin Exp Ophthalmol 9:8, 99.. Douglas GR, Drance SM, Mikelberg FS, Shulzer M, and Wijsman K: Variability of the Frisen ring perimeter: Perimetry update 988/89. n Proceedings of the VHth nternational Perimetric Society Meeting, Heijl A, editor. 989, pp Wall M, Lefante J, and Conway MD: High-pass resolution perimetry in normals and patients with idiopathic intracranial hypertension. nvest Ophthalmol Vis Sci :9, Wanger P and Persson HE: Pattern reversal electroretinograms and high-pass resolution perimetry in suspected or early glaucoma. Ophthalmology 9:98, Dannheim F, Abramo F, and Verlohr D: Comparison of automated conventional and spatial resolution perimetry in glaucoma: Perimetry update 988/89. n Proceedings of the Vlllth nternational Perimetric Society Meeting, Heijl A, editor. Amstelveen, The Netherlands, Kugler and Ghendi, 989, pp Dannheim F and Roggenbuck C: Comparison of automated conventional and spatial resolution perimetry in chiasmal lesions: Perimetry update 988/89. n Proceedings of the VHth nternational Perimetric Society Meeting, Heijl A, editor: Amstelveen, The Netherlands, Kugler and Ghendi, 989, pp Johnson CA, Keltner JL, and Balestrery FG: Acuity profile perimetry: Description of technique and preliminary clinical trials. Arch Ophthalmol 97:68, 979. Downloaded From: on 9/9/8