Asymmetric Papilledema in Idiopathic Intracranial Hypertension: Prospective Interocular Comparison of Sensory Visual Function

Home , Papilledema

Michael Wall1'2 and William N. White II13

PURPOSE. Visual loss is the main morbidity of idiopathic intracranial hypertension (UH). The relationship between papilledema grade and visual loss is unclear. The goal of this study was to determine whether there is a relationship between papilledema grade and visual loss. METHODS. Fundus photographs of 478 patients with IIH were reviewed, and their degree of papilledema was graded using Frisen's scheme. We identified 46 patients (10%) with IIH and highly asymmetric papilledema, as defined by an interocular difference of two or more grades. Nine of these patients with active asymmetry agreed to return for a series of visual tests. They underwent three visual field tests—Humphrey visual field analyzer 24-2, motion perimetry, and ring perimetry. The perimetry outcome measures were mean deviation, foveal threshold, and means for eccentric zones (3°, 9°, 15°, and 21°). The patients participated also in visual acuity, Farnsworth-Munsell 100-hue, Pelli-Robson contrast sensitivity, and foveal flicker fusion testing. Their relative afferent pupillary defect was graded using neutral density filters.

RESULTS. The intereye comparisons showed vision to be worse in the eye with the high-grade papilledema for all outcome measures. The magnitude of the loss with the perimetry tests increased with eccentricity. The measures of central visual function, although in the normal range, were relatively depressed in the eye with high-grade papilledema. CONCLUSIONS. Visual loss in patients with asymmetric papilledema caused by IIH was most pro- nounced in the eye with the higher grade of papilledema. Foveal visual functions, although they remained in the normal range, were also decreased in patients with high-grade papilledema. In patients with high-grade papilledema, visual loss appeared to affect the entire visual field, and the peripheral field showed the most deficit. Our findings showed that high-grade papilledema was associated with visual dysfunction in patients with IIH. (Invest Ophthalmol Vis Set. 1998;39: 134-142)

diopathic intracranial hypertension (IIH) is a disorder of selective loss of either magnocellular or parvocellular func- elevated intracranial pressure of unknown cause. Visual tions. To accomplish this we analyzed sensory visual function Iloss caused by papilledema is the most important compli- data from patients with highly asymmetric papilledema. Our cation of IIH. Patients at risk for permanent visual loss include premise was: If there was no difference in visual function those with severe or high-grade papilledema.1"3 Those with between the two eyes with highly asymmetric papilledema, moderate or less severe papilledema, however, also demon- then there was no relationship between visual loss and papill- strate visual loss using sensitive psychophysical testing tech- edema grade. However, if visual functions were systematically niques.4'5 Rush reported no correlation between papilledema worse in the eye with high-grade papilledema, then the grade and degree of visual loss.6 Others have reported an amount of visual loss was related to the degree of papilledema. association between higher grades of papilledema and more We retrospectively identified patients with highly asymmetric severe visual dysfunction.1"3 papilledema and analyzed their visual functions. We then pro- Our main goal in this study was to investigate the ques- spectively tested nine patients with highly asymmetric papill- tion: Is the amount of visual loss related to the degree of edema with a battery of sensor)' visual function tests. papilledema? Our secondary goal was to look for evidence of SUBJECTS AND METHODS

From the Departments of 'Ophthalmology and 2Neurology, Col- We reviewed the optic disc photography files and charts of 478 lege of Medicine, University of Iowa, Iowa City, Iowa, and 'University patients with the diagnosis of IIH evaluated at the University of Eye Specialists, Warsaw, New York. Iowa Neuro-ophthalmology Clinic from 1972 to 1995. Patients Supported by a VA Merit Review Grant and by an unrestricted were excluded if they failed to meet the five modified Dandy grant to the Department of Ophthalmology from Research to Prevent 4 Blindness, New York, New York. criteria for idiopathic intracranial hypertension : there was Submitted for publication May 23, 1997; revised July 23, 1997; presence of signs and symptoms of increased intracranial pres- accepted September 19, 1997. sure; the patient was alert and oriented; the neurologic exam- Proprietary interest category: N. ination was normal except for papilledema and its associated Reprint requests: Michael Wall, Department of Neurology, College of Medicine, University of Iowa, 200 Hawkins Drive, 2007 RCP, Iowa visual loss and sixth nerve palsies; neurodiagnostic studies City, 1A 52242-1053. were normal except for increased cerebrospinal fluid pressure;

Downloaded from iovs.arvojournals.org on 09/25/2021 IOVS, January 1998, Vol. 39, No. 1 Asymptomatic Papilledema in DH 135

and there was no secondary cause of intracranial hypertension 36 -I found. Initial Visit - High Grade The IIH patients all had fundus photography, and each 34 - Initial Visit - Low Grade patient's papilledema was graded according to Frisen's Final Visit - High Grade scheme.7 Grade 0 defines an optic disc without swelling; Grade 9 32 -I Final Visit - Low Grade 5 represents severe papilledema. Nine patients from these 38 that still had asymmetry of two or more grades present agreed ^ 30 ^ to take part in the study. All participants were reimbursed for their time and travel. The mean patient age was 318 ± 92 2 28 years. I 26 The protocol was approved by the University of Iowa Investigational Review Board and fulfilled the tenets of the 24 - Declaration of Helsinki. Normal subjects for the perimetry tests were randomly chosen from our database of normal control 22 subjects and matched to the patients by age (two control 0 5 10 15 20 25 subjects to each patient). All normal subjects had a normal neuro-ophthalmologic examination and no history of eye dis- Degrees from Fixation ease except refractive error and normal automated perimetry FIGURE 1. Retrospectively collected data on the threshold- results (Program 24-2, Humphrey Field Analyzer; Hvimphrey automated perimetry of 12 patients with highly asymmetric Instruments, San Leandro, CA). papilledema. Note the generalized depression of the visual field The subjects were tested for the following: visual acuity from the fovea to the periphery. Improvement occurred in using the Early Treatment of Diabetic Retinopathy Study chart, both the high-grade and low-grade eyes with treatment. foveal flicker fusion,8 Pelli-Robson contrast sensitivity, relative afferent pupillary defect quantitation using neutral density filters, Farnsworth-Munsell color, and three types of perimetry. targets are circular random dot cinematograms within which We used conventional automated perimetry with the Hum- 50% of the dots move in one of four directions relative to phrey visual field analyzer 24-2, high-pass resolution perimetry fixation (up, down, left, or right) and 50% move in random (Frisen's ring test),9'10 and motion perimetry11. directions.14 The stimulus presentation time was 128 msec. The targets were of 20 different sizes. The angle subtended by Conventional Automated Perimetry the targets ranged from 0.25° to 21°. Using the Humphrey visual field analyzer, and following the The size of the stimulus window varied from trial to trial, manufacturer's recommendations, we performed conventional and a 2 to 1 staircase procedure was used to bracket the automated perimetry. The patients' appropriate near correc- threshold. The test, therefore, continued until the smallest tion was used. Subjects were tested with a program using a circle size seen (size threshold) at each test point was brack- 6°-spaced grid of the central 21°. Rest periods were given eted by the staircase procedure. We tested 44 locations. These when requested. matched the 24-2 Humphrey perimetry test points, except for the absence of the top and bottom rows (y = 21° and —21°) High-Pass Resolution Perimetry and the two points along the nasal horizontal (x = —27°)- The test time for the 44-test loci was approximately 15 minutes. High-pass resolution perimetry was administered according to The perimetry measures were analyzed by calculating the the recommendations of the manufacturer (Ophthimus system; mean score for the ring test and motion perimetry and tabu- HighTech Vision, Goteborg, Sweden) except that, inadver- 2 lating the mean deviation for conventional automated perime- tently, we calibrated the background to 100 cd/m brighter try and by compacting the data for the three tests into concen- than the standard level. Therefore, we will only report differ- tric zones.1015 We excluded the region of the blind spot and ences between the eyes with this test. The patients' appropri- the adjacent-test locations for this analysis so that visual loss ate near correction was used and care was taken to prevent from elevation of peripapillary retina would be minimized. lens rim artifact. Patients' fixation was monitored by the visual The patient's best-corrected visual acuity was recorded field technician and with intermittent blind spot testing (Heijl- using the Early Treatment of Diabetic Retinopathy Study chart Krakau method). and method. The total number of letters read correctly for each eye was summed. Foveal flicker fusion was tested three times, Motion Perimetry and the mean for each eye was recorded. The details of this In a darkened room, motion perimetry was conducted using an method can be found in a publication by Brenton and co- IBM-compatible 486 computer with software we have devel- workers.8 The patient's relative afferent pupillary defect was oped previously.'l>12 The patients' appropriate near correction quantitated using the method reported previously by Thomp- was again used. Care was taken to prevent lens rim artifact by son.16 asking each subject if he or she could see each corner of the The Pelli-Robson contrast chart is a contrast letter chart video display while looking at the fixation target. The details of with three letters for each contrast.17 A score was recorded at this testing method can be found in other publications.1213 the lowest contrast line at which the patient could read at least In summary, the test background is composed of 5000 two letters correctly. The line number for each eye was used as randomly positioned white dots with 2.2% of the pixels illumi- the subjects' outcome measure. nated. The dots are one pixel in size and are illuminated to 580 Color vision testing was performed using one rack of the asb. The white dots are randomly displayed on a 315-asb gray Farnsworth-Munsell 100-hue test monocularly and Type C background using a 640- x 480-pixel video display. The motion lighting (as provided by Munsell) which provided a luminance

Downloaded from iovs.arvojournals.org on 09/25/2021 136 Wall and White IOVS, January 1998, Vol. 39, No. 1

TABLE 1. Results of Conventional Automated Perimetry Analyzed by Eye Involvement, Examination, and Visual Field Eccentricity in Retrospectively Collected Data Visual Field Zone Mean SD Minimum Maximum P value High Grade Eye—Initial Exam Fovea 33.3 1.8 31.0 37.0 Cecocentral 30.9 2.3 26.5 33.5 Pericentral 28.8 2.0 24.9 30.9 Midperipheral 26.4 3.9 18.6 31.6 Peripheral 24.5 4.4 15.1 28.7 Entire field 25.7 3.3 19.2 296 Low Grade Eye—Initial Exam Fovea 35.0 1.0 33.0 36.0 0.07 Cecocentral 32.3 1.6 30.5 35.5 0.07 Pericentral 30.9 1.3 29.3 33.3 0.03 Midperipheral 29.2 1.8 26.0 32.3 0.09 Peripheral 27.7 2.2 22.6 30.7 0.05 Entire field 28.8 1.6 25.9 31.4 0.01 High Grade Eye—Final Exam Fovea 35.2 1.0 34.0 37.0 Cecocentral 32.2 2.2 27.5 36.0 Pericentral 30.6 1.8 26.7 34.1 Midperipheral 28.5 2.8 21.8 33.5 Peripheral 26.6 3.6 18.4 32.0 Entire field 27.8 2.7 21.7 32.5 Low Grade Eye—Final Exam Fovea 35.1 1.6 33.0 37.0 0.01 Cecocentral 33.0 2.0 29.5 36.5 0.09 Pericentral 31.8 1.7 291 34.3 0.01 Midperipheral 29.8 2.1 26.4 33.1 0.02 Peripheral 28.4 2.5 231 31.4 0.003 Entire field 29.6 2.0 26.5 32.7 0.002

P values are from comparisons of high-grade papilledema eyes with low-grade papilledema eyes. (SD = one standard deviation).

of 500 lux evenly distributed across the testing area. The chips the age-matched normal results. A Kruskal-Wallis test (ANOVA were scrambled, and the patient was instructed to arrange the on ranks) was done for data that were not normally distributed colored caps in order according to their hue. Bar codes on the or had unequal variances. Differences among groups of the test undersurface of the ordered chips were scanned into a per- results were interpreted as significant if the probability of their sonal computer for scoring and plotting with custom software. occurrence was less than 0.05. We used only one rack (21 chips, numbers 22-42), because this rack has been shown to have a similar sensitivity and specificity for clinical diagnosis compared with the full test.18 RESULTS Of the nine patients, one patient did not complete the contrast sensitivity tests and the color test and was lost to Retrospective Data follow-up. This patient and one other did not perform the ring Of the 478 charts reviewed, we identified 46 patients (10%) perimetry test. with IIH and highly asymmetric papilledema, as defined by an Because of the small number of patients, a predefined interocular difference of two or more Frisen grades. Two number of questions for statistical analysis were designated as patients had amblyopia, one had traumatic optic atrophy, and study outcomes to compare the eyes of the patients and the one had Fuch's dystrophy. These four patients were eliminated normal subjects. These were: mean and concentric zone pe- from the analysis. Four others did not have elevated cerebro- rimetry scores for the three perimetry tests, Early Treatment of spinal fluid (CSF) pressures recorded and were excluded. The Diabetic Retinopathy Study acuity, flicker fusion scores, rela- remaining 38 patients met the entry criteria for the study. tive afferent pupillary difference with neutral density filters, Twenty-seven (71%) were women; 11 (29%) were men. The and defect Farnsworth color vision total error scores. Other mean age was 35.7 ± 9-8 years. Their mean CSF opening statistical tests were performed for description and hypothesis pressure was 358.9 ± 102.5 mm H2O. At the initial visit the generation. median papilledema grade in the eyes with the highest grade Differences between scores of the nine patients from the was 3 (range, 2-5) and was 1 (range, 0-2) in the low-grade various tests between the high-grade and low-grade papill- eyes. At the finalvisit , the high-grade eye values fell to 2 (range, edema groups were tested for statistical significance. A two- 0-4); the low-grade eyes improved to a median of 0 (range, tailed paired f-test was used for normally distributed quantita- 0-1). tive data. The Wilcoxon test was used for corresponding The visual acuity in the eyes with high-grade papilledema nonparametric data. An ANOVA test was used for differences at the initial visits in Snellen equivalents, had a median of 1.00 between the high-grade and low-grade papilledema results and with a range of 0.5 to 1.33; in the low-grade eyes it was 1.00

Downloaded from iovs.arvojournals.org on 09/25/2021 IOVS, January 1998, Vol. 39, No. 1 Asymptomatic Papilledema in IIH 137

6 FIGURE 2. Box plots showing measures of central visual func- A tion in nine prospectively tested patients comparing eyes with high-grade papilledema with eyes with low-grade papilledema. I Box shows 75th, 50th, and 25th percentiles. Error bars show 60 - 90th and 10th percentiles. In each example, the high-grade eye CO showed less sensitive visual function than the low-grade eye. u (A) Early Treatment of Diabetic Retinopathy Study acuity 8 T scores. (B) Foveal critical flicker fusion. (C) The second box of CO I 55 - the Farnsworth-Munsell 100-hue test. CO 3 50 - with a range of 0.8 to 1.54. At the final visit these values improved to 1.00 (range, 0.8-1.67) and 1.25 (range, 0.67- 1.67), respectively. Flicker fusion values in the eyes with high- 45 grade papilledema at the initial visit was 30.29 ± 2.69 Hz, and 5 in the other eyes it was 31 17 ± 2.36 Hz; these values changed with treatment to 30.08 ± 2.03 and 30.83 ± 2.06, respectively. The mean relative afferent pupillar)' defect was 0.26 (median High Low 0.1, range 0-1.2) at the initial examination and was 0.23 at the Papilledema Grade final examination (median 0.2, range 0-0.9). Twelve patients had conventional automated perimetry B 35 -, (Humphrey visual field analyzer, programs 30-2 or 24-2) at an early and final visit. No subjects had cecocentral or central scotomas. Figure 1 and Table 1 show the results of the initial T and final perimetry results analyzed by eccentricity. Data for 30 - the age-matched normal subjects was not shown, because it was similar to the data of the low-grade eyes at the final visit. Surprisingly, the initial visit results show a generalized depression of the visual field in the eyes with high-grade papilledema, i most marked peripherally but including the foveal threshold. At the final visit, sensitivity improved but the results for the high-grade eyes still showed more visual loss. PH •—I Prospective Data a 20 The mean age of the nine patients was 35.7 ± 98 years. Their O mean CSF opening pressure was 347.2 ± 90.9 nim H2O. The mean relative afferent pupillary defect was 0.3 log units (median 0.3, range 0-0.6); all but one patient (with no relative High Low afferent pupillary defect) had a relative afferent pupillary defect on the side of the eye with high-grade papilledema. The Papilledema Grade visual testing results in this group are similar to the retrospectively collected results (Tables 2-5, Figs. 2, 3). We found visual 35 -, function to be worse in the high-grade papilledema eyes for all

CD visual function tests, although statistical significance was not 8 30 reached for every one. This finding occurred whether the tests CO were biased for the magnocellular or parvocellular system.

O OR • The data shown in Figure 3 support the findings of a generalized depression of the visual field and extend the findings of the retrospective data by showing this depression to be § 20 present to motion testing and peripheral acuity testing (high- pass resolution perimetry). The differences in the foveal O threshold are not as marked with the prospective as with the q 15 retrospective data. The most likely explanation for this is: The retrospectively collected data were obtained during the acute 10 - x phase of the patient's presentation, whereas the prospectively o collected data were obtained during the chronic, treated phase PQ 5 - of the patient's disease in which the magnitude of the papill- d O edema severity and, consequently, the visual loss were less. To evaluate visual loss as a function of visual field eccentricity, we used the slope of a regression of visual field sensi- High Low tivity on eccentricity. We looked for differences among the Papilledema Grade results of eyes with high- and low-grade papilledema and nor-

Downloaded from iovs.arvojournals.org on 09/25/2021 138 Wall and White IOVS, January 1998, Vol. 39, No. 1

40 -, Hieh Grade FIGURE 3- Visual field sensitivity by concentric zone for (A) Low Grade conventional automated perimetry, (B) motion perimetry, and Normal (C) high-pass resolution (ring) perimetry. Note how visual sensitivity was lowest for high-grade eyes, intermediate for low-grade eyes, and highest for age-matched normal eyes and how sensitivity decreased with eccentricity.

mal eyes. For all three types of perimetry, the slopes were significantly different (Table 4). In all cases, the steepest slope was found with the high-grade eyes, and the flattest slope was found with the normal eyes. The low-grade eyes were intermediate, indicating an increasing magnitude of visual loss with eccentricity. Post-hoc comparisons showed significant differences in the slopes of the high-grade eyes compared with the normal eyes in all three perimetry types; with motion perimetry, the comparison between the high- and low-grade eyes was 3 9 15 21 also significant. Concentric Zone (degrees) There was a weak relationship between mean visual field sensitivity (excluding the test locations around the blind spot) B Hieh Grade and papilledema grade for the three perimetry tests. Although Low Grade the r2 values ranged from 0.4 to 0.18, in all cases there was a Normal trend of increasing visual loss with increasing papilledema grade. A typical example of one of our patients is shown in Figure 4. This woman, aged 36 years, had transient visual obscurations of vision in her left, high-grade papilledema eye (Fig. 4; left). Her conventional automated perimetry results are shown in Figure 4; right. Note the generalized depression of the visual field, which is most evident peripherally in the patient's left, high-grade papilledema eye.

DISCUSSION Our main finding is that there was a generalized depression of the visual field in eyes with nigh-grade papilledema. The visual loss increased in magnitude with increasing visual field eccen- 3 9 15 21 tricity- However, this finding is only appreciated when compared with low-grade papilledema eyes. The results of the Concentric Zone (degrees) foveal visual function tests in high-grade papilledema eyes are, for the most part, still in the normal range. C 8. I I Hieh Grade ••I Low Grade Our data showed that the amount of visual loss correlated with the severity of disc edema— eyes with more disc edema have more visual loss. However, there was considerable inter- individual variation. That is, some patients with marked optic disc edema appeared to have mild or no visual loss unless the loss was compared with a fellow eye with less disc edema. This relationship of degree of papilledema with visual loss implied CD that visual loss in I1H was caused by papilledema and not by a a 4j retrolaminar mechanism. Based on these results, we propose the following scenario for visual loss in 1IH (Fig. 5). High CSF pressure at the optic buo nerve head causes high tissue pressure there.19'20 This leads to CS • I—I blockage of slow axoplasmic transport (axoplasmic flow stasis)2 L'22 and resultant optic disc edema. There appears to be related compression of the intraneuronal microvascular supply with resultant nerve fiber ischemia.21 This may result in diffuse damage to optic nerve fibers. An explanation for the character 5 10 15 20 25 30 of the visual loss observed might be as follows. Because there appears to be more redundancy of visual processing elements Concentric Zone (degrees) subserving the central visual field,23 testing may not show as much visual loss as that found in the periphery. The loss we

Downloaded from iovs.arvojournals.org on 09/25/2021 IOVS, January 1998, Vol. 39, No. 1 Asymptomatic Papilledema in IIH 139

TABLE 2. Descriptive Statistics of Central Visual Function Measurements (Prospective Study) ETDRS* PRCS FM CFF

Error Error Acuity High Acuity Low High Low High Low High Low Mean 56.11 60.22 14.63 15.13 13.75 11.25 28.5 30.0 SD 4.11 3.31 0.52 0.35 10.91 7.55 2.81 2.40 95% CI 1.37 1.10 0.18 0.13 3.86 2.67 0.94 0.80 99% CI 3.16 2.54 0.43 0.30 912 6.32 2.16 1.84 P value 0.03 0.04 0.6 0.25

Abbreviations used: *ETDRS, Early Treatment of Diabetic Retinopathy Study; PR CS, Pelli-Robson contrast sensitivity; FM, Farnsworth-Munsell; CFF, critical flicker fusion; SD, one standard deviation; CI, confidence interval.

have observed is so mild in the central visual field that it usually met the modified Dandy criteria for IIH. Six of 26 (23%) had falls within the normal range. It is only by comparison with the unilateral or highly asymmetric papilledema. He found those fellow eye, with less disc edema, that some degree of central with unilateral papilledema were significantly older (37.5 ver- visual function can be confirmed. This analysis is based on sus 25.7 years). Six patients with asymmetric papilledema had summing data from nine patients. In this analysis, localized enlarged blind spots, and two had temporal constriction of the defects such as arcuate scotomas and nasal step defects con- visual field. Our mean age was similar at 35.7 years. Of the 18 tribute to the eccentric zone in which they occur, but their patients with asymmetric papilledema identified from the pe- spatial relationships within that zone are lost. Our patients did rimetric examinations, five have more visual loss in the eye have these localized defects. They presumably occurred when with high-grade papilledema (excluding blind spot enlarge- intraneuronal ischemia affected nerve fibers in groups (bun- ment).26"30'32'33 However, our perimetry was manually per- dles) instead of diffusely. formed; we did not use automation. Highly asymmetric papilledema in IIH is not rare. We Why does asymmetric papilledema occur in patients with observed it in approximately 10% of patients with IIH. Unilat- raised intracranial pressure? The occurrence of papilledema is eral or highly asymmetric papilledema in IIH has been reported by others.24"32 These case reports provide few data regarding thought to be dependent on the relationship of three factors: CSF pressure, intraocular pressure, and systemic blood pres- interocular comparisons of sensory visual function in patients 34 with asymmetric papilledema. sure. Either elevated CSF pressure, low intraocular pressure, Lepore30 reviewed his case records over a 10-year period, or low perfusion pressure can cause axoplasmic flow stasis, and, using subjective criteria for asymmetry, found 26 patients optic disc edema, and resultant intraneuronal ischemia.

TABLE 3. Descriptive Statistics and Pairwise Comparisons of Papilledema Grade and Conventional Automated Perimetry Results (Prospective Study). Edema Grade HVF MD HVFFT

High Low High Low High Low Mean 2.44 0.33 -2.83 -1.28 36.78 37.11 SD 0.73 0.50 1.42 1.39 1.56 2.62 Range 2 to 4 0 to 2 -0.14 to -4.31 0.71 to -3.61 35 to 39 32 to 41 Median 2 0 -2.72 -1.85 36 37 P value 0.03 0.74

'Abbreviations used: HVF, Humphrey field analyzer; MD, mean deviation; FT, foveal threshold; SD, one standard deviation.

TABLE 4. Visual Loss as a Function of Visual Field Eccentricity as Shown by the Slope of a Regression of Visual Field Sensitivity on Eccentricity Comparing the Perimetric Types (Conventional Automated Perimetry (Humphrey), Motion and High-Pass Resolution Perimetry (Ring)) Humphrey Motion Ring

High Low Normal High Low Normal High Low Normal Mean -0.390 -0.332 -0.299 0.035 0.019 0.014 0.056 0.077 0.128 SD 0.114 0.055 0.055 0.012 0.011 0.010 0.070 0.081 0.030 95% CI 0.087 0.042 0.027 0.009 0.008 0.005 0.065 0.075 0.017 99% CI 0.127 0.061 0.038 0.014 0.012 0.007 0.098 0.113 0.024 P value 0.037 <0.001 0.024

'Abbreviations used: SD, one standard deviation; CI, confidence interval.

Downloaded from iovs.arvojournals.org on 09/25/2021 140 Wall and White IOVS, January 1998, Vol. 39, No. 1

TABLE 5. Relationship between Papilledema Grade and Visual Field Sensitivity Comparison R2 Conventional Automated Perimetry High Grade eye to mean sensitivity 0.09 Low Grade eye to mean sensitivity 0.12 Motion Perimetry High Grade eye to mean sensitivity 0.04 Low Grade eye to mean sensitivity 0.08 Ring Perimetry High Grade eye to mean 70 50 30 10 0 30 50 70 90 sensitivity 0.18 Low Grade eye to mean sensitivity 0.07 FIGURE 5. Model of the visual islands (plots of sensitivity versus eccentricity) for visual loss in IIH comparing high-grade papilledema (dashed line), low-grade papilledema (dotted line), and normal visual island (solid line). Note the depression of the visual island, most evident peripherally with increasing First, it was unlikely that there was any difference in optic papilledema grade. disc perfusion pressure in the patients in the present study. Our group of patients was young; therefore, a postulate, that enough premature vascular disease was present to cause suffi- Second, it is possible that intraocular pressures between cient carotid or ophthalmic artery stenosis, that would in turn the eyes could be asymmetric. Kirkham and co-workers28 stud- account for the asymmetry, was not plausible. Also, Kirkham28 ied five patients with chronic unilateral papilledema and found did not find any difference in ophthalmodynamometry values intraocular pressures were normal and symmetric in all. between the eyes of his patients with asymmetric papilledema This leaves higher CSF pressure at the optic disc as the to implicate asymmetric perfusion pressures. This finding im- remaining possibility. The effects of optic nerve sheath fenes- plies that there is no difference in ophthalmic artery pressure tration in monkeys with experimental papilledema and hu- between the two eyes. It does not negate the suggestion that mans prove that relief of the elevated pressure within the optic optic nerve damage can be the result of CSF pressure-related nerve sheath is associated with defervescence of papilledema. optic nerve head edema with resultant intraneuronal ischemia, Therefore, the effect of asymmetric CSF pressure at the optic because factors that are distal to the ophthalmic artery are nerve heads is a viable mechanism. However, in patients with likely important in the latter. asymmetric or unilateral papilledema, optic nerve sheath width

-3 1' -i -3 -t -1 -5 -2 -8 -4 -1 -1 -I -1 -1 -2 -4 -4. -1 -5 -1 -1 e -5 0 1 -8 X t -Z e -1 1 -4 -3 -2 -l -2 •3 -1 -3 -5 -I -l 2 •I e •11 l -2 •1

FIGURE 4. Typical example of conventional automated perimetry testing results from a patient with IIH with highly asymmetric papilledema showing gray scales and difference plots. High-grade papilledema was shown in the left eye, and low-grade papilledema was shown in the right eye (left). Note the generalized depression of the visual field, most evident peripherally in the high-grade papilledema left eye (right).

Downloaded from iovs.arvojournals.org on 09/25/2021 JOVS, January 1998, Vol. 39, No. 1 Asymptomatic Papilledema in HH l4l

is increased and symmetric.29'31'32'35 This appears to suggest range may well have visual loss; however, their values have not that CSF pressures must be equal in the two optic nerve yet reached the abnormal range. Our data therefore suggest sheaths or the sheath width would be wider in the sheath that these patients with high-grade papilledema may be losing under higher pressure. However, Hayreh36 showed that the vision and, therefore, treatment should be considered. High- nerve sheath is composed of fibroustissu e and, after it unfolds, grade papilledema should be regarded as a risk factor for visual it cannot expand any further. Therefore, there may be a high loss. enough pressure within the sheath to distend it but not high enough to cause optic disc edema. The pressure could be Acknowledgments elevated in both nerve sheaths but could be higher on one side. If this is the cause then what is the mechanism of the asym- The authors thank H. Stanley Thompson for measuring the relative metric pressures? afferent pupillary defects with neutral density niters and Kim Kutzko The width of the optic nerve is greatest just behind the for performing the visual testing. globe and narrowest within the optic canal. Thick fibrous bands within the canalicular nerve sheath interrupt the sub- References arachnoid space. Hayreh36 found that the number of these 1. Orcutt JC, Page NG, Sanders MD. Factors affecting visual loss in bands varied from animal to animal and was occasionally benign intracranial hypertension. Ophthalmology. 1984;91:1303- scanty. He observed in monkeys and humans that when dye is 1312. injected into the optic nerve sheath, it usually passed easily 2. Smith TJ, Baker RS. Perimetric findings in pseudotumor cerebri into the cranial cavity. The force needed appeared to depend using automated techniques. Ophthalmology. 1986;93:887-894. on the quality of the fibrous bands within the subarachnoid 3. Wall M. The morphology of visual field damage in idiopathic space. Although the dye usually flowed freely, it concentrated intracranial hypertension: an anatomic region analysis. In: Mills RP, Heijl A, eds. Perimetry Update 1990-1991. Amsterdam: Kugler in the subarachnoid space adjacent to the optic canals. We Publications; 1991:20-27. suggest that there may be differences among subjects in the 4. Wall M, George D. Idiopathic intracranial hypertension. A prospec- trabecular meshwork of the optic nerve sheath subarachnoid tive study of 50 patients. Brain. 1991;ll4:155-180. space contigtious with the optic canal. When there is elevated 5. Verplanck M, Kaufman DI, Parsons T, Yedavally S, Kokinakis D. CSF pressure, the pressure in the nerve sheath rises enough to Electrophysiology versus psychophysics in the detection of visual distend the sheath, but there is not enough pressure at the loss in pseudotumor cerebri. Neurology. 1988;38:1789-1792. optic nerve head to cause high-grade papilledema with result- 6. Rush JA. Pseudotumor cerebri: clinical profile and visual outcome in 63 patients. Mayo Clin Proc. 198O;55:54l-546. ant high tissue pressure and intraneuronal ischemia in the eyes 7. Frisen L. Swelling of the optic nerve head: a staging scheme. with low-grade papilledema. / Neurol Neurosurg Psychiatr. 1982;45:13-18. We1' and others37 have suggested that, as in glaucoma, 8. Brenton RS, Thompson HS, Maxner C. Critical flicker frequency. A there may be selective large fiber loss in patients with papill- new look at an old test. In: Wall M, Sadun AA, eds. New Methods of Sensory Visual Testing. New York: Springer-Verlag; 1989:29- edema. In these reports, sensitive tests of parvocellular func- 52. tion were not used for comparison. Our data show a loss of 9. Frisen L. High-pass resolution targets in peripheral vision. Ophthal- many different visual functions when high-grade papilledema mology. 1987;94:1104-1108. eyes are compared with low-grade eyes. This is true whether 10. Wall M, Lefante J, Conway M. Variability of high-pass resolution the tests are biased toward the magnocellular system (motion perimetry in normals and patients with idiopathic intracranial perimetry and flicker fusion) or the parvocellular system (visual hypertension. Invest Ophthalmol Vis Sci. 1991;32:3091-3095- 11. Wall M, Montgomery EB. Using motion perimetry to detect visual acuity, color vision testing, and high-pass resolution perime- field defects in patients with idiopathic intracranial hypertension: try). In other words, there appears to be just as much loss of a comparison with conventional automated perimetry. Neurology. magnocellular function as parvocellular. Therefore, our data 1995;45:1169-H75. support concurrent damage to both the magnocellular and 12. Wall M, Ketoff KM. Random dot motion perimetry in glaucoma parvocellular systems. patients and normal subjects. Am J Ophthalmol. 1995;120:587- 596. Transient visual obscurations potentially confound visual 13. Wall M, Jennisch CJ, Munden PM. Motion perimetry identifies testing done on patients with IIH. They are unilateral or bilat- nerve fiber bundlelike defects in ocular hypertension. Arch Oph- eral episodes of transient visual loss that occur in three of four thalmol. 1997; 115:26-33. patients with IIH. Most patients experience several transient 14. Nawrot M, Steinman SB. Real-time color-frame animation for visual obscurations per week, and most obscurations last 5 to 30 psychophysics on the Macintosh computer. Behav Res Methods seconds. However, this low rate of obscurations makes their lustrum & Comput. 1992;24:439-452. 15. Wall M. Sensory visual testing in idiopathic intracranial occurrence unlikely during a test sequence. If they are re- hypertension: measures sensitive to change. Neurology. 1990;40: ported by a patient during examination, our procedure is to 1859-1864. give the patient a rest period. Another potential confounding 16. Thompson HS, Corbett JJ. Asymmetry of pupillomotor input. Eye. factor with regard to papilledema grade—with death of axons 1991;5:36-39. there is less axoplasmic flow stasis and optic disc edema 17. Pelli DG, Robson JG, Wilkins AJ. The design of a new letter chart lessens. However, because our composite visual function mea- for measuring contrast sensitivity. Clin Vis Sci. 1988;2:187-199. 18. Nichols BE, Thompson HS, Stone EM. Evaluation of a significantly sures were never worse in low-grade papilledema eyes, this shorter version of the Farnsworth-Munsell 100-Hue test in patients factor is not likely to be of much magnitude. with three different optic neuropathies. / Neuro-ophthalmol. Patients have more visual loss in their eyes with high-grade 1997;17:l-6. papilledema than in those eyes with low-grade papilledema. 19- Hedges TR, Zaren HA. The relationship of optic nerve tissue This visual loss involves foveal function, and its magnitude pressure to intracranial and systemic arterial pressure. Am] Oph- thalmol. 1973;75:90-98. increases with visual fieldasymmetry . It occurs across both the 20. Ernest JT, Potts AM. Pathophysiology of the distal portion of the magnocellular and parvocellular systems. Patients with high- optic nerve. II. Vascular relationships. Am J Ophthalmol. 1968;66: grade papilledema and perimetric results within the normal 380-387.

Downloaded from iovs.arvojournals.org on 09/25/2021 142 Wall and White IOVS, January 1998, Vol. 39, No. 1

21. Hayreh SS. Optic disc edema in raised intracranial pressure. VI. 29. To KW, Warren FA. Unilateral papilledema in pseudotumor cere- Associated visual disturbances and their pathogenesis. Arch Oph- bri. Arch Ophthalmol. 1990; 108:644-645. thalmol. 1977;95:1566-1579. 30. Lepore FE. Unilateral and highly asymmetric papilledema in 22. Tso MO, Hayreh SS. Optic disc edema in raised intracranial pres- pseudotumor cerebri. Neurology. 1992;42:676-678. sure. IV. Axoplasmic transport in experimental papilledema. Arch 31. Muci-Mendoza R, Amiga J, Hoyt WF. Distension bilateral del Ophthahnol. 1977;95:1458-1462. espacio subaracnoideo perioptico en el pseudotumor cerebral con 23. Johnson CA. Selective versus nonselective losses in glaucoma. / papiledema unilateral. Rev Neurol (Barcelona). 1981;39:11-15. Glaucoma. 1994;3:S32-S44. 32. Strominger MB, Weiss GB, Mehler MF. Asymptomatic unilateral 24. Monteiro ML, Hoyt WF, Imes RK, Narahara M. Unilateral papill- papilledema in pseudotumor cerebri. / Clin Neuroophthalmol. edema in pseudotumor cerebri. Arq Neuropsiquiatr. 1985;43: 1992;12:238-24l. 154-159. 33. Maxner CE, Freedman MI, Corbett JJ. Asymmetric papilledema and 25. Muci-Mendoza R. Unilateral and asymmetric optic disk swelling visual loss in pseudotumour cerebri. Can J Neurol Sci. 1987; 14: with intracranial abnormalities. Am J Ophthalmol. 1984;97: 593-596. 253. 34. Hayreh SS. Optic disc edema in raised intracranial pressure. V. 26. Sher NA, Wirtschafter J, Shapiro SK, See C, Shapiro I. Unilateral Pathogenesis. Arch Ophthalmol. 1977;95:1553-1565. papilledema in 'benign' intracranial hypertension (pseudotumor 35. Rosenberg M, Huna R, Warren FA, Kupersmith MJ. Unilateral cerebri)./^m Med Assoc. 1983;250:2346-2347. papilledema due to increased intracranial pressure. [ARVO Ab- 27. Sedwick LA, Burde RM. Unilateral and asymmetric optic disk swell- stract.] Invest Ophthalmol Vis Sci. 1996;37:S690. ing with intracranial abnormalities. Am J Ophthalmol. 1983;96: 36. Hayreh SS. The sheath of the optic nerve. Ophthalmologica. 1984; 484-487. 189:54-63. 28. Kirkham TH, Sanders MD, Sapp GA. Unilateral papilledema in benign 37. Tytla ME, Buncic JR. Optic nerve compression impairs low spatial intracranial hypertension. Can J Ophthalmol. 1973:8:533-538. frequency vision in man. Clin Vis Sci. 1988;2:179-186.

Downloaded from iovs.arvojournals.org on 09/25/2021