- Email: [email protected]
Pattern visual evoked potential in the diagnosis of functional visual loss1
Pattern Visual Evoked Potential in the Diagnosis of Functional Visual Loss Shizhao Xu, MD, David Meyer, MD, Seth Yoser, MD, Dennis Mathews, OD, John L. Elfervig, MD Objective: To study the pattern visual evoked potential (P-VEP) in the diagnosis of functional visual loss. Study Design: Retrospective study of observational case series. Participants: Seventy-two subjects whose best corrected visual acuity (VA) was 20/50 or worse, with or without visual field defect, and whose visual abnormalities could not be explained by the findings of ophthalmologic and neurologic examination were included in this study. Main Outcome Measures: To compare the P-VEP estimated acuity to the initial subjective VA and to the best-performed VA. Results: Seventy-two subjects with functional visual loss had normal P-VEPs. The initial subjective VA was 20/50 in 9 subjects and ⱕ20/200 in 42 subjects. After clinical examination and reassurance, the best-performed VA was ⱖ20/50 in 53 subjects and ⱕ20/200 in 8 subjects. The discrepancy between the P-VEP estimated acuity and the best-performed VA was less than 3 lines of Snellen acuity in 63 of 72 (87.5%) subjects and more than 4 lines in 6 subjects. These six subjects were three women with loss of vision of unknown origin and three men with injury-related visual loss. Conclusions: P-VEP has the advantage of objectively predicting VA and is a useful test in the diagnosis of functional visual loss. Ophthalmology 2001;108:76 – 81 © 2001 by the American Academy of Ophthalmology. The term functional visual loss (FVL) refers to clinical situations in which the degree of a subject’s subjective visual symptoms cannot be explained by the results of objective evaluation. Such cases are commonly encountered in clinical practices and pose challenges to the ophthalmologist. A comprehensive examination should be performed to rule out organic causes of visual loss. The visual evoked potential (VEP) test has been used to evaluate the function of the visual pathway, and the pattern visual evoked potential (P-VEP) has been used as an objective assessment of visual acuity (VA).1– 8 In the literature, numerous articles have been written about FVL9 –15 and VEP in diagnosing FVL.9,12–16 However, the clinical value of P-VEP in the diagnosis of FVL has been controversial.9,12–21 The purpose of this paper is to report our results and experience in performing P-VEP tests on subjects having FVL and to verify the valuation of P-VEP in the diagnosis of FVL.
Subjects and Methods A retrospective study was performed on 138 subjects who were suspected of having FVL and referred to the electrophysiologic Received: October 23, 1999. Accepted: August 16, 2000. Manuscript no. 99418. From the Crippled Children Vitreoretinal Research Foundation and the University of Tennessee, Department of Ophthalmology, Memphis, Tennessee. Presented in part at the American Academy of Ophthalmology Annual Meeting, Orlando, Florida, October 1999. The authors have no proprietary interest in any of the materials used in this study. Reprint requests to Shizhao Xu, MD, Vitreoretinal Foundation, 825 Ridge Lake Blvd., Memphis, TN 38120.
76
© 2001 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
laboratory at the Vitreoretinal Foundation for VEP from 1991 to 1999. The records of these subjects, including medical history, clinical examination, visual fields (VFs), fluorescein angiography, ultrasonography, magnetic resonance imaging, computed tomography, x-ray studies, laboratory tests results, VEP, and consultant letters, were reviewed. Subjects were referred to a neuro-ophthalmology specialty clinic for evaluation when indicated. Subjects were scheduled for follow-up at 1 to 2 weeks in the first month, 3 months for the first year, and 6 months for 3 years. Efforts have been made to have subjects return for follow-up. Forty-one subjects with normal VEP who did not have follow-up visits were excluded. Eight subjects with abnormal VEP with either abnormal electroretinogram or abnormal magnetic resonance imaging were excluded. Seventeen subjects whose VA was equal to or better than 20/40 with VF defects were also excluded from this study. Seventy-two subjects with normal P-VEP response and follow-up from 1 day to 45 months were included in this study. Their corrected VA was equal to or worse than 20/50 with or without VF loss. The VA and VF abnormalities could not be explained by ocular and neurologic examination findings. There were 46 women and 26 men, 55 White, 16 African American, and one uncertain. Ages ranged from 8 to 73 years, with a mean of 32 years. Twenty-one subjects were 18 years old or younger. Twenty-six of 72 subjects, including 6 subjects under age 18, stated that the visual loss was caused by an injury. Twenty-three of the 72 subjects had underlying ophthalmic disorders with functional overlay, such as subconjunctival hemorrhage, corneal abrasion, cataract, macular drusen, eyelid laceration, or refractive error. The Universal Testing and Analysis System, Electrophysiologic 2000 (UTAS-E 2000, LKC Technologies, Inc., Gaithersburg, MD) was used to record the VEP stimulated by reversal checkerboard patterns. The field size of the checkerboard stimulus was 23 ⫻ 28 cm2, the average luminance of the screen was 171.3 cd/m2, and the contrast was 100%. The checks reversed at 1.9 alternations/sec, and analysis time was 256 msec. An artifact rejection module was imbedded in the system. During VEP tests, ISSN 0161-6420/00/$–see front matter PII S0161-6420(00)00478-4
Xu et al. 䡠 P-VEP in FVL
Figure 1. Initial and best-performed subjective visual acuity (VA). CF ⫽ count fingers; HM ⫽ hand movement; LP ⫽ light perception; NLP ⫽ non light perception.
Figure 2. Difference between pattern visual evoked potential estimated acuity and initial subjective visual acuity.
Results
glasses, prism, polarizing lenses, autorefraction, potential acuity meter, and hand shaking. The best-performed VA ranged from 20/20 to hand movement. The VA was ⱖ20/30 in 31 subjects and ⱕ20/200 in 8 subjects (Fig 1). A significant difference was found between the initial VA and the best-performed VA (paired t test P ⬍ 0.01). The discrepancy between best-performed VA and P-VEP estimated acuity was less than 3 lines in 63 (87.5%) of 72 subjects, was 3 to 4 lines in 3 (4.2%), and more than 4 lines in 6 (8.3%) of 72 subjects (Fig 3). Six subjects whose subjective VA showed no obvious improvement were three women with loss of vision of unknown origin and three men with injury-related FVL. None of the six subjects showed any new symptoms at neuroophthalmologist and/or neurologist consultation in a 9-day to 45-month follow-up period. After reassurance, the subjective VA improved in 60 of 72 (83.3%) subjects. The effect of reassurance was different among young subjects, adult noninjury-related subjects, and adult with injury-related FVL subjects. The subjective VA improved with reassurance or spontaneously in 95.2%, 90.3%, and 60.0% in young, adult noninjury-related, and adult injury-related subjects, respectively. The discrepancy between subjective VA and the P-VEP estimated acuity was significantly statistically different among these three groups (chi-square ⫽ 20.475, P ⬍ 0.01) (Fig 4). In this study, 12 subjects were seen with VA ⱖ20/30 in one eye and ⱕ20/100 in the other eye, but symmetrical P-VEPs were obtained from both eyes. In the follow-up visits, VA of the worse eye improved in all 12 subjects, reaching ⱖ20/30 in 7 of the 12 subjects. A symmetrical P-VEP in both eyes of a 15-year-old girl with subjective VA of no light perception in the right eye and 20/20 in the left eye at initial visit is illustrated (Fig 5). At 3 years follow-up, the VA was 20/20 in both eyes.
In a total of 72 subjects, unilateral visual loss was noted in 25 subjects and bilateral visual loss in 47 subjects. The VAs of both eyes were similar in bilateral visual loss subjects. The initial best-corrected subjective VA ranged from 20/50 to no light perception. The VA was 20/50 in 9 subjects and ⱕ20/200 in 42 subjects (Fig 1). The P-VEP estimated VA ranged from 20/30 to 20/100 and was 20/30 in 43 subjects, 20/50 in 25 subjects, and 20/100 in 4 subjects. Comparing the subjective VA and the P-VEP estimated acuity, the difference was less than 3 lines of Snellen visual acuity gradations in 14 (19.5%) of 72 subjects, was between 3 and 4 lines in 33 (45.8%), and more than 4 lines in 25 (34.7%) of 72 subjects (Fig 2). After notification to the subject of the negative clinical examinations and reassurance by the physician, VA was remeasured with the Snellen chart at their follow-up visits. In nine subjects, the best-performed VA was obtained with certain technical procedures and behavior observation, such as red-green
Figure 3. Difference between pattern visual evoked potential estimated acuity and best-performed subjective visual acuity.
any movement of the examined eye led to artifact rejection and the unwanted artifacts were not stored. Monocular VEPs were recorded using gold cup scalp electrodes, which were placed 1.5 to 3 cm (depending on the size of the subject’s skull) above the external occipital protuberance on the midline to serve as an active, on the vertex as a reference, and on the forehead as a ground. Each subject sat in a moderately lighted room, one meter in front of a black-and-white video display monitor. Reversal checkerboard patterns were generated and displayed on the monitor. Subjects were instructed to fixate on a red marker at the center of the screen. Fixation was monitored closely by the examiner throughout the entire testing period. Tests were performed with best-corrected vision (i.e., subjects wore spectacles or contact lenses or trial lenses). Five sizes of checkerboard patterns (8 ⫻ 8, 16 ⫻ 16, 32 ⫻ 32, 64 ⫻ 64, 128 ⫻ 128 equivalent to visual angles of 1° 40’, 50’, 25’, 12’, 6’, respectively) were tested in each eye. If the results of the test series were inconsistent, retest was performed with encouragement or suggestion. If normal latency and amplitude of P100 response (as established in our laboratory criteria) were recorded from the 32, 64, and 128 displayed check sizes, then corresponding VA was estimated to be better than 20/100, 20/50, and 20/30, respectively. The paired t test was used to study the changes of VA. The chi-square test was used to compare the effect of reassurance on VA among groups. The statistics were analyzed using Primer of Biostatistics program 4.0 for Windows. (McGraw-Hill Health Professions Division, New York, NY)
77
Ophthalmology Volume 108, Number 1, January 2001
Figure 4. Difference between pattern visual evoked potential estimated acuity after reassurance and subjective visual acuity in the groups of 18-year-olds or younger, noninjury-related, and injury-related visual loss.
Discussion When a subject complains of vision loss or VF loss that is inconsistent with the physical, objective examination of the eye and visual system, FVL should be suspected. Ocular hysteria and malingering are two major forms of FVL. Hysterical amblyopia subjects manifest visual loss unconsciously. Some have underlying organic problems with functional overlay. Some show psychiatric or psychosocial
Figure 5. The results of pattern visual evoked potentials of right eye (A), and left eye (B), from a 15-year-old girl with visual acuity of no light perception in the right eye and 20/20 in the left eye. R ⫽ right eye; L ⫽ left eye.
78
problems, yet in most no origin could be disclosed.9,10,12–14 Malingering subjects often have consciously chosen to exaggerate their visual symptoms for personal gain. An inciting event can often be identified; work-related injuries and motor vehicle accidents are the most common causes. In this study, 26 of 72 (36.1%) had an injury-related FVL. VEP is one of a variety of old and new techniques used to differentiate functional from organic vision loss.3,12–19 Clinically, the VEP, including transient and sweep steadystate VEP, has been used as an objective means of measuring visual function in infants, preverbal children,3,5–7,18,22,23 and adults who cannot cooperate for regular Snellen chart visual testing.4,6,8,12–19 Kramer et al12 suggested that the VEP provides a method of objectively determining the VA, and they routinely use both flash and pattern VEPs in the evaluation of subjects with unexplained visual loss. Table 1 demonstrates a comparative view of the P-VEP studies on subjects with FVL from different authors.15,16,18,19 Barris et al15 reported that normal P-VEP, flash electroretinogram, and magnetic resonance imaging were obtained in all 45 neuro-ophthalmologic subjects diagnosed with visual impairment in hysteria. Steele and co-authors16 reported a good correlation between subjective (Snellen) acuity and VEP estimated acuity in optically corrected normal subjects, and that subjects with unexplainable claims of decreased VA could be diagnosed as having FVL on the basis of objective VEP acuity. In FVL subjects, VEP estimated acuity was significantly better than measured Snellen acuity. In their report, only 2 of 17 (11.8%) subjects suspected of having FVL had less than a 3-line discrepancy between VEP estimated acuity and measured Snellen acuity compared with 14 of 72 (19.5%) subjects found in our study (Fig 2). Table 1 also illustrates that in most FVL subjects, especially in young children, a strong reassurance led to eventual resolution of their symptoms.11,15,18 In this study, VA improved after reassurance in 95.2% of the young age group, 90.3% in adult noninjury-related group, and 60% in adult injury-related subjects. Controversy does exist, however, regarding the clinical usefulness of the P-VEP in the diagnosis of FVL. Thompson9 stated that electrical tests such as P-VEPs were not very useful for FVL, the presumption being that response of P-VEP could be consciously repressed by convergence maneuvers, by meditation or by fixating away from the center of the monitor. Morgan et al20 and Bumgartner and Epstein21 found that 26% and 33% of normal subjects could alter or extinguish their P-VEP, respectively. They suggested that an extinguished or unrecognizable VEP could not be used with certainty to distinguish between organic and functional loss of vision. It is well documented that a normal VEP provides objective evidence of a subject’s normal afferent visual pathways. Caution must be exercised in interpreting the VEP results in subjects suspected of having FVL. Flash VEP and even P-VEP with absence of N1 responses can be recorded from individuals with “cortical blindness” caused by cerebral disease.19,24 –26 The response of VEP is probably mediated by the remaining minute areas of the striate cortex.19,25 However, despite these potential problems, interpretable P-VEPs were obtained in all subjects with
Xu et al. 䡠 P-VEP in FVL Table 1. Studies of Subjects with Functional Visual Loss Authors
Number of Patients
Age
Pattern Visual Evoked Potential Obtained (%)
Visual Activity Improved After Reassurance (%)
Follow-up Time
Steele et al16 Bobak et al19 Catalano et al11 Mouriaux et al18 Baris et al15
17 30 23 25 45
7–68 14–66 6–17 9–11 7–65
100 87 N/A 88 100
N/A N/A 1day–2 mos 16 mos 4 days–37 mos
Xu et al
72
8–73
100
N/A N/A 74 100 92 (age ⱕ 15) 66.7 (age ⬎15) 95.2 (age ⱕ 18) 90.3 (age ⬎ 18, noninjury) 60 (age ⬎ 18, injury related)
1 day–5 mos
N/A not available.
FVL in this study and the studies by Steele et al16 and Barris et al15 In 87.5% of our subjects, the discrepancy between the P-VEP estimated acuity and the best-performed VA was less than 3 lines (Fig 3). Advanced technology and computerization have made the electrophysiologic equipment more stable, effective, and affordable. The amplifiers, filters, average, storage, artifact rejection, and data analysis programs provide a system that makes VEP studies more accurate and convenient. From our experience, to obtain an accurate response of P-VEP, which is essential to assess the value of this test, technical factors including the examiner’s experience are extremely important in the testing of subjects suspected of hysteria or malingering. Refractive error of the examined eye must be optically corrected. Recording the P-VEP from the best eye first can establish a pleasant impression and test confidence. Direct observation of the examined eye, with the subject aware of such observation, will often result in improved compliance. The examiner should also carefully observe the developing average waveform. A tendency of the P100 component to broaden or decrease in amplitude suggests that accommodation or fixation is unsatisfactory. A short time break and comforting words can improve test results. The P-VEP test could not be completed on only one suspect FVL subject in our laboratory in 9 years. Variations of electrophysiologic testing have been developed that may help to differentiate functional disorders. Sweep P-VEP using high spatial frequency is an advanced and rapid way of measuring visual acuity.6 – 8 Towle et al27 recorded P300 Table 2. Normal Range of Latency and Amplitude of P100 of P-VEP* P100 Latency (msec)
P100 Amplitude (V)
Age Range
Female
Male
Female
Male
⬍35 35–49 50–59 60–70
100.1 ⫾ 4.0 100.0 ⫾ 4.02 101.9 ⫾ 3.89 107.2 ⫾ 2.18
100.7 ⫾ 3.95 102.9 ⫾ 3.96 105.8 ⫾ 3.22 108.6 ⫾ 3.92
12.56 ⫾ 6.68 12.16 ⫾ 5.08 11.38 ⫾ 3.84 11.27 ⫾ 5.68
12.06 ⫾ 6.13 10.55 ⫾ 5.49 10.06 ⫾ 3.01 9.31 ⫾ 2.66
*From Electrophysiologic Laboratory of the Vitreoretinal Foundation, Memphis, Tennessee. P-VEP ⫽ pattern visual evoked potential.
component of the VEP. Rover and Bach28 reported simultaneously recorded pattern electroretinogram and VEPs. In conclusion, P-VEP has the advantage of objectively predicting visual acuity and is a useful test in the diagnosis of functional vision loss. The physician can detect inconsistencies in visual performance that make it possible to offer credible reassurance to the subject. The examiner’s effort is very important in the testing of subjects suspected of hysteria or malingering.
References 1. Sokol S. Visually evoked potentials: theory, techniques and clinical applications [review]. Surv Ophthalmol 1976;21:18 – 44. 2. Feinsod M, Hoyt WF, Wilson WB, Spire JP. Visually evoked response. Use in neurologic evaluation of posttraumatic subjective visual complaints. Arch Ophthalmol 1976;94:237– 40. 3. Sokol S. The visually evoked cortical potential in optic nerve and visual pathway disorders. In: Fishman GA, Sokol S, eds. Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway. San Francisco: American Academy of Ophthalmology, 1990: chap 3, 105–28 (Ophthalmol Monogr Ser; 2). 4. Howe JW, Mitchell KW, Robson C. Electrophysiological assessment of visual acuity. Trans Ophthalmol Soc U K 1981; 101:105– 8. 5. Sokol S. Pattern visual evoked potentials: their use in pediatric ophthalmology. Int Ophthalmol Clin 1980;20:251– 68. 6. Tyler CW, Apkarian P, Levi DM, Nakayama K. Rapid assessment of visual function: an electronic sweep technique for the pattern visual evoked potential. Invest Ophthalmol Vis Sci 1979;18:703–13. 7. Gottlob I, Fendick MG, Guo S, et al. Visual acuity measurements by swept spatial frequency visual-evoked-cortical potentials (VECPs): clinical application in children with various visual disorders. J Pediatr Ophthalmol Strabismus 1990;27: 40 –7. 8. Arai M, Katsumi O, Paranhos FRL, et al. Comparison of Snellen acuity and objective assessment using the spatial frequency sweep PVER. Graefes Arch Clin Exp Ophthalmol 1997;235:442–7. 9. Thompson HS. Functional visual loss. Am J Ophthalmol 1985;100:209 –13. 10. Kathol RG, Cox TA, Corbett JJ, Thompson HS. Functional
79
Ophthalmology Volume 108, Number 1, Month 2001
11. 12. 13. 14. 15. 16. 17.
18. 19.
visual loss. Follow-up of 42 cases. Arch Ophthalmol 1983; 101:729 –35. Catalano RA, Simon JW, Krohel GB, Rosenberg PN. Functional visual loss in children. Ophthalmology 1986;93:385– 90. Kramer KK, La Piana FG, Appleton B. Ocular malingering and hysteria: diagnosis and management. Surv Ophthalmol 1979;24:89 –96. Bienfang DC, Kurtz D. Management of functional vision loss. J Am Optom Assoc 1998;69:12–21. Bose S, Kupersmith MJ. Neuro-ophthalmologic presentations of functional visual disorders [review]. Neurol Clin 1995;13: 321–39. Barris MC, Kaufman DI, Barberio D. Visual impairment in hysteria. Doc Ophthalmol 1992;82:369 – 82. Steele M, Seiple WH, Carr RE, Klug R. The clinical utility of visual-evoked potential acuity testing. Am J Ophthalmol 1989;108:572–7. Holder GE. Electrodiagnostic testing in malingering and hysteria. In: Heckenlivily JR, Arden GB, eds. Principles and Practice of Clinical Electrophysiology of Vision. St. Louis: Mosby Year Book, 1991; chap. 72, 573–7. Mouriaux F, Defoort-Dhellemmes S, Kochman F, et al. Le pithiatisme oculaire chez l’enfant et l’adolescent [Eng abstr]. J Fr Ophtalmol 1997;20:175– 82. Bobak P, Khanna P, Goodwin J, Brigell M. Pattern visual evoked potentials in cases of ambiguous acuity loss. Doc Ophthalmol 1993;85:185–92.
20. Morgan RK, Nugent B, Harrison JM, O’Connor PS. Voluntary alteration of pattern visual evoked responses. Ophthalmology 1985;92:1356 – 63. 21. Bumgartner J, Epstein CM. Voluntary alteration of visual evoked potentials. Ann Neurol 1982;12:475– 8. 22. Marg E, Freeman DN, Peltzman P, Goldstein PJ. Visual acuity development in human infants: evoked potential measurements. Invest Ophthalmol 1976;15:150 –3. 23. Harter MR, Deaton FK, Odom JV. Maturation of evoked potentials and visual preference in 6-45-day-old infants: effects of check size, visual acuity, and refractive error. Electroencephalogr Clin Neurophysiol 1977;42:595– 607. 24. Spehlmann R, Gross RA, Ho SU, et al. Visual evoked potentials and postmortem findings in a case of cortical blindness. Ann Neurol 1977;2:531– 4. 25. Celesia GG, Archer CR, Kuroiwa Y, Goldfader PR. Visual function of the extrageniculo-calcarine system in man: relationship to cortical blindness [case report]. Arch Neurol 1980; 37:704 – 6. 26. Frank Y, Torres F. Visual evoked potentials in the evaluation of “cortical blindness” in children. Ann Neurol 1979; 6:126 –9. 27. Towle VL, Sutcliffe E, Sokol S. Diagnosing functional visual deficits with the P300 component of the visual evoked potential. Arch Ophthalmol 1985;103:47–50. 28. Rover J, Bach M. Pattern electroretinogram plus visual evoked potential: a decisive test in subjects suspected of malingering. Doc Ophthalmol 1987;66:245–51.
Discussion by Larry Frohman, MD The authors correctly state that the primary tool that the ophthalmologist has in his or her clinical armamentarium when assessing subjects for functional visual loss (FVL) is a careful and complete ocular examination to rule out organic causes of seemingly inexplicable visual loss. This article deals with the “what comes next?”; that is, what test might the ophthalmologist use to confirm suspicions of unexplained visual loss? The authors contribute three points with this study. First, the study size is larger than any prior reported series that has used pattern visual evoked potentials (P-VEPs) to study subjects with functional visual loss. Second, it compares the measured Snellen acuity with the visual acuity predicted by analyzing the responses obtained by recording during visual evoked potentials with stimuli of varying check sizes. Third, it reports the “What happens after?” portion; that is, what happens to the subjects’ measured visual function after you reassure them that both the examination and the P-VEP are normal. The study screened 138 subjects with suspected FVL who were referred for visual evoked potential testing. Fortyone subjects who did not have clinical follow-up were excluded. A criterion for entry was initial acuity of no better
From the Departments of Ophthalmology and Neurosciences, UMD-New Jersey Medical School, Newark, New Jersey. Supported in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Address correspondence to Larry Frohman, MD, 90 Bergen Street, Newark, NJ 07103.
80
than 20/50 in the involved eye(s), thus, an additional 17 were excluded. Of note is that eight subjects who had an abnormal electroretinogram (ERG) or visual evoked potential (VEP) were excluded from this study. This left the study cadre of 72 subjects as the subjects of this study. Subjects with suspected FVL with visual acuity of better than 20/50, but with nonorganic visual fields were excluded from this study, thus, the reader must remember that its conclusions cannot be absolutely applied to this group when they are encountered in clinical practice. Because FVL manifesting as field loss with preserved central acuity is not a rare finding, a similar study to this would be beneficial to look at this group’s responses on P-VEP. When one looks at the data, the study reports that 19.5% of their subjects had a Snellen acuity that was within 3 lines of the VEP estimated visual acuity, and in 34.7% of their cases there was a difference of greater than 4 lines. A problem in the data analysis is that although the authors report that 45 of the 72 subjects had bilateral visual loss, the data analysis speaks of subjects, not of eyes. Thus, the reader cannot know how a subject who had a difference of less than 3 lines in one eye and greater than 4 lines in the other eye was tabulated (if such a case existed). For instance, let us say we had a bilateral FVL case who was 20/400 in both eyes at onset, had abnormal P-VEP predicting acuities of at least 20/30, and was reassured, and then retested, and showed acuities of 20/20 and 20/400. Would this subject be counted as no improvement or as the highest level of improvement?
Subjects and Methods A retrospective study was performed on 138 subjects who were suspected of having FVL and referred to the electrophysiologic Received: October 23, 1999. Accepted: August 16, 2000. Manuscript no. 99418. From the Crippled Children Vitreoretinal Research Foundation and the University of Tennessee, Department of Ophthalmology, Memphis, Tennessee. Presented in part at the American Academy of Ophthalmology Annual Meeting, Orlando, Florida, October 1999. The authors have no proprietary interest in any of the materials used in this study. Reprint requests to Shizhao Xu, MD, Vitreoretinal Foundation, 825 Ridge Lake Blvd., Memphis, TN 38120.
76
© 2001 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
laboratory at the Vitreoretinal Foundation for VEP from 1991 to 1999. The records of these subjects, including medical history, clinical examination, visual fields (VFs), fluorescein angiography, ultrasonography, magnetic resonance imaging, computed tomography, x-ray studies, laboratory tests results, VEP, and consultant letters, were reviewed. Subjects were referred to a neuro-ophthalmology specialty clinic for evaluation when indicated. Subjects were scheduled for follow-up at 1 to 2 weeks in the first month, 3 months for the first year, and 6 months for 3 years. Efforts have been made to have subjects return for follow-up. Forty-one subjects with normal VEP who did not have follow-up visits were excluded. Eight subjects with abnormal VEP with either abnormal electroretinogram or abnormal magnetic resonance imaging were excluded. Seventeen subjects whose VA was equal to or better than 20/40 with VF defects were also excluded from this study. Seventy-two subjects with normal P-VEP response and follow-up from 1 day to 45 months were included in this study. Their corrected VA was equal to or worse than 20/50 with or without VF loss. The VA and VF abnormalities could not be explained by ocular and neurologic examination findings. There were 46 women and 26 men, 55 White, 16 African American, and one uncertain. Ages ranged from 8 to 73 years, with a mean of 32 years. Twenty-one subjects were 18 years old or younger. Twenty-six of 72 subjects, including 6 subjects under age 18, stated that the visual loss was caused by an injury. Twenty-three of the 72 subjects had underlying ophthalmic disorders with functional overlay, such as subconjunctival hemorrhage, corneal abrasion, cataract, macular drusen, eyelid laceration, or refractive error. The Universal Testing and Analysis System, Electrophysiologic 2000 (UTAS-E 2000, LKC Technologies, Inc., Gaithersburg, MD) was used to record the VEP stimulated by reversal checkerboard patterns. The field size of the checkerboard stimulus was 23 ⫻ 28 cm2, the average luminance of the screen was 171.3 cd/m2, and the contrast was 100%. The checks reversed at 1.9 alternations/sec, and analysis time was 256 msec. An artifact rejection module was imbedded in the system. During VEP tests, ISSN 0161-6420/00/$–see front matter PII S0161-6420(00)00478-4
Xu et al. 䡠 P-VEP in FVL
Figure 1. Initial and best-performed subjective visual acuity (VA). CF ⫽ count fingers; HM ⫽ hand movement; LP ⫽ light perception; NLP ⫽ non light perception.
Figure 2. Difference between pattern visual evoked potential estimated acuity and initial subjective visual acuity.
Results
glasses, prism, polarizing lenses, autorefraction, potential acuity meter, and hand shaking. The best-performed VA ranged from 20/20 to hand movement. The VA was ⱖ20/30 in 31 subjects and ⱕ20/200 in 8 subjects (Fig 1). A significant difference was found between the initial VA and the best-performed VA (paired t test P ⬍ 0.01). The discrepancy between best-performed VA and P-VEP estimated acuity was less than 3 lines in 63 (87.5%) of 72 subjects, was 3 to 4 lines in 3 (4.2%), and more than 4 lines in 6 (8.3%) of 72 subjects (Fig 3). Six subjects whose subjective VA showed no obvious improvement were three women with loss of vision of unknown origin and three men with injury-related FVL. None of the six subjects showed any new symptoms at neuroophthalmologist and/or neurologist consultation in a 9-day to 45-month follow-up period. After reassurance, the subjective VA improved in 60 of 72 (83.3%) subjects. The effect of reassurance was different among young subjects, adult noninjury-related subjects, and adult with injury-related FVL subjects. The subjective VA improved with reassurance or spontaneously in 95.2%, 90.3%, and 60.0% in young, adult noninjury-related, and adult injury-related subjects, respectively. The discrepancy between subjective VA and the P-VEP estimated acuity was significantly statistically different among these three groups (chi-square ⫽ 20.475, P ⬍ 0.01) (Fig 4). In this study, 12 subjects were seen with VA ⱖ20/30 in one eye and ⱕ20/100 in the other eye, but symmetrical P-VEPs were obtained from both eyes. In the follow-up visits, VA of the worse eye improved in all 12 subjects, reaching ⱖ20/30 in 7 of the 12 subjects. A symmetrical P-VEP in both eyes of a 15-year-old girl with subjective VA of no light perception in the right eye and 20/20 in the left eye at initial visit is illustrated (Fig 5). At 3 years follow-up, the VA was 20/20 in both eyes.
In a total of 72 subjects, unilateral visual loss was noted in 25 subjects and bilateral visual loss in 47 subjects. The VAs of both eyes were similar in bilateral visual loss subjects. The initial best-corrected subjective VA ranged from 20/50 to no light perception. The VA was 20/50 in 9 subjects and ⱕ20/200 in 42 subjects (Fig 1). The P-VEP estimated VA ranged from 20/30 to 20/100 and was 20/30 in 43 subjects, 20/50 in 25 subjects, and 20/100 in 4 subjects. Comparing the subjective VA and the P-VEP estimated acuity, the difference was less than 3 lines of Snellen visual acuity gradations in 14 (19.5%) of 72 subjects, was between 3 and 4 lines in 33 (45.8%), and more than 4 lines in 25 (34.7%) of 72 subjects (Fig 2). After notification to the subject of the negative clinical examinations and reassurance by the physician, VA was remeasured with the Snellen chart at their follow-up visits. In nine subjects, the best-performed VA was obtained with certain technical procedures and behavior observation, such as red-green
Figure 3. Difference between pattern visual evoked potential estimated acuity and best-performed subjective visual acuity.
any movement of the examined eye led to artifact rejection and the unwanted artifacts were not stored. Monocular VEPs were recorded using gold cup scalp electrodes, which were placed 1.5 to 3 cm (depending on the size of the subject’s skull) above the external occipital protuberance on the midline to serve as an active, on the vertex as a reference, and on the forehead as a ground. Each subject sat in a moderately lighted room, one meter in front of a black-and-white video display monitor. Reversal checkerboard patterns were generated and displayed on the monitor. Subjects were instructed to fixate on a red marker at the center of the screen. Fixation was monitored closely by the examiner throughout the entire testing period. Tests were performed with best-corrected vision (i.e., subjects wore spectacles or contact lenses or trial lenses). Five sizes of checkerboard patterns (8 ⫻ 8, 16 ⫻ 16, 32 ⫻ 32, 64 ⫻ 64, 128 ⫻ 128 equivalent to visual angles of 1° 40’, 50’, 25’, 12’, 6’, respectively) were tested in each eye. If the results of the test series were inconsistent, retest was performed with encouragement or suggestion. If normal latency and amplitude of P100 response (as established in our laboratory criteria) were recorded from the 32, 64, and 128 displayed check sizes, then corresponding VA was estimated to be better than 20/100, 20/50, and 20/30, respectively. The paired t test was used to study the changes of VA. The chi-square test was used to compare the effect of reassurance on VA among groups. The statistics were analyzed using Primer of Biostatistics program 4.0 for Windows. (McGraw-Hill Health Professions Division, New York, NY)
77
Ophthalmology Volume 108, Number 1, January 2001
Figure 4. Difference between pattern visual evoked potential estimated acuity after reassurance and subjective visual acuity in the groups of 18-year-olds or younger, noninjury-related, and injury-related visual loss.
Discussion When a subject complains of vision loss or VF loss that is inconsistent with the physical, objective examination of the eye and visual system, FVL should be suspected. Ocular hysteria and malingering are two major forms of FVL. Hysterical amblyopia subjects manifest visual loss unconsciously. Some have underlying organic problems with functional overlay. Some show psychiatric or psychosocial
Figure 5. The results of pattern visual evoked potentials of right eye (A), and left eye (B), from a 15-year-old girl with visual acuity of no light perception in the right eye and 20/20 in the left eye. R ⫽ right eye; L ⫽ left eye.
78
problems, yet in most no origin could be disclosed.9,10,12–14 Malingering subjects often have consciously chosen to exaggerate their visual symptoms for personal gain. An inciting event can often be identified; work-related injuries and motor vehicle accidents are the most common causes. In this study, 26 of 72 (36.1%) had an injury-related FVL. VEP is one of a variety of old and new techniques used to differentiate functional from organic vision loss.3,12–19 Clinically, the VEP, including transient and sweep steadystate VEP, has been used as an objective means of measuring visual function in infants, preverbal children,3,5–7,18,22,23 and adults who cannot cooperate for regular Snellen chart visual testing.4,6,8,12–19 Kramer et al12 suggested that the VEP provides a method of objectively determining the VA, and they routinely use both flash and pattern VEPs in the evaluation of subjects with unexplained visual loss. Table 1 demonstrates a comparative view of the P-VEP studies on subjects with FVL from different authors.15,16,18,19 Barris et al15 reported that normal P-VEP, flash electroretinogram, and magnetic resonance imaging were obtained in all 45 neuro-ophthalmologic subjects diagnosed with visual impairment in hysteria. Steele and co-authors16 reported a good correlation between subjective (Snellen) acuity and VEP estimated acuity in optically corrected normal subjects, and that subjects with unexplainable claims of decreased VA could be diagnosed as having FVL on the basis of objective VEP acuity. In FVL subjects, VEP estimated acuity was significantly better than measured Snellen acuity. In their report, only 2 of 17 (11.8%) subjects suspected of having FVL had less than a 3-line discrepancy between VEP estimated acuity and measured Snellen acuity compared with 14 of 72 (19.5%) subjects found in our study (Fig 2). Table 1 also illustrates that in most FVL subjects, especially in young children, a strong reassurance led to eventual resolution of their symptoms.11,15,18 In this study, VA improved after reassurance in 95.2% of the young age group, 90.3% in adult noninjury-related group, and 60% in adult injury-related subjects. Controversy does exist, however, regarding the clinical usefulness of the P-VEP in the diagnosis of FVL. Thompson9 stated that electrical tests such as P-VEPs were not very useful for FVL, the presumption being that response of P-VEP could be consciously repressed by convergence maneuvers, by meditation or by fixating away from the center of the monitor. Morgan et al20 and Bumgartner and Epstein21 found that 26% and 33% of normal subjects could alter or extinguish their P-VEP, respectively. They suggested that an extinguished or unrecognizable VEP could not be used with certainty to distinguish between organic and functional loss of vision. It is well documented that a normal VEP provides objective evidence of a subject’s normal afferent visual pathways. Caution must be exercised in interpreting the VEP results in subjects suspected of having FVL. Flash VEP and even P-VEP with absence of N1 responses can be recorded from individuals with “cortical blindness” caused by cerebral disease.19,24 –26 The response of VEP is probably mediated by the remaining minute areas of the striate cortex.19,25 However, despite these potential problems, interpretable P-VEPs were obtained in all subjects with
Xu et al. 䡠 P-VEP in FVL Table 1. Studies of Subjects with Functional Visual Loss Authors
Number of Patients
Age
Pattern Visual Evoked Potential Obtained (%)
Visual Activity Improved After Reassurance (%)
Follow-up Time
Steele et al16 Bobak et al19 Catalano et al11 Mouriaux et al18 Baris et al15
17 30 23 25 45
7–68 14–66 6–17 9–11 7–65
100 87 N/A 88 100
N/A N/A 1day–2 mos 16 mos 4 days–37 mos
Xu et al
72
8–73
100
N/A N/A 74 100 92 (age ⱕ 15) 66.7 (age ⬎15) 95.2 (age ⱕ 18) 90.3 (age ⬎ 18, noninjury) 60 (age ⬎ 18, injury related)
1 day–5 mos
N/A not available.
FVL in this study and the studies by Steele et al16 and Barris et al15 In 87.5% of our subjects, the discrepancy between the P-VEP estimated acuity and the best-performed VA was less than 3 lines (Fig 3). Advanced technology and computerization have made the electrophysiologic equipment more stable, effective, and affordable. The amplifiers, filters, average, storage, artifact rejection, and data analysis programs provide a system that makes VEP studies more accurate and convenient. From our experience, to obtain an accurate response of P-VEP, which is essential to assess the value of this test, technical factors including the examiner’s experience are extremely important in the testing of subjects suspected of hysteria or malingering. Refractive error of the examined eye must be optically corrected. Recording the P-VEP from the best eye first can establish a pleasant impression and test confidence. Direct observation of the examined eye, with the subject aware of such observation, will often result in improved compliance. The examiner should also carefully observe the developing average waveform. A tendency of the P100 component to broaden or decrease in amplitude suggests that accommodation or fixation is unsatisfactory. A short time break and comforting words can improve test results. The P-VEP test could not be completed on only one suspect FVL subject in our laboratory in 9 years. Variations of electrophysiologic testing have been developed that may help to differentiate functional disorders. Sweep P-VEP using high spatial frequency is an advanced and rapid way of measuring visual acuity.6 – 8 Towle et al27 recorded P300 Table 2. Normal Range of Latency and Amplitude of P100 of P-VEP* P100 Latency (msec)
P100 Amplitude (V)
Age Range
Female
Male
Female
Male
⬍35 35–49 50–59 60–70
100.1 ⫾ 4.0 100.0 ⫾ 4.02 101.9 ⫾ 3.89 107.2 ⫾ 2.18
100.7 ⫾ 3.95 102.9 ⫾ 3.96 105.8 ⫾ 3.22 108.6 ⫾ 3.92
12.56 ⫾ 6.68 12.16 ⫾ 5.08 11.38 ⫾ 3.84 11.27 ⫾ 5.68
12.06 ⫾ 6.13 10.55 ⫾ 5.49 10.06 ⫾ 3.01 9.31 ⫾ 2.66
*From Electrophysiologic Laboratory of the Vitreoretinal Foundation, Memphis, Tennessee. P-VEP ⫽ pattern visual evoked potential.
component of the VEP. Rover and Bach28 reported simultaneously recorded pattern electroretinogram and VEPs. In conclusion, P-VEP has the advantage of objectively predicting visual acuity and is a useful test in the diagnosis of functional vision loss. The physician can detect inconsistencies in visual performance that make it possible to offer credible reassurance to the subject. The examiner’s effort is very important in the testing of subjects suspected of hysteria or malingering.
References 1. Sokol S. Visually evoked potentials: theory, techniques and clinical applications [review]. Surv Ophthalmol 1976;21:18 – 44. 2. Feinsod M, Hoyt WF, Wilson WB, Spire JP. Visually evoked response. Use in neurologic evaluation of posttraumatic subjective visual complaints. Arch Ophthalmol 1976;94:237– 40. 3. Sokol S. The visually evoked cortical potential in optic nerve and visual pathway disorders. In: Fishman GA, Sokol S, eds. Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway. San Francisco: American Academy of Ophthalmology, 1990: chap 3, 105–28 (Ophthalmol Monogr Ser; 2). 4. Howe JW, Mitchell KW, Robson C. Electrophysiological assessment of visual acuity. Trans Ophthalmol Soc U K 1981; 101:105– 8. 5. Sokol S. Pattern visual evoked potentials: their use in pediatric ophthalmology. Int Ophthalmol Clin 1980;20:251– 68. 6. Tyler CW, Apkarian P, Levi DM, Nakayama K. Rapid assessment of visual function: an electronic sweep technique for the pattern visual evoked potential. Invest Ophthalmol Vis Sci 1979;18:703–13. 7. Gottlob I, Fendick MG, Guo S, et al. Visual acuity measurements by swept spatial frequency visual-evoked-cortical potentials (VECPs): clinical application in children with various visual disorders. J Pediatr Ophthalmol Strabismus 1990;27: 40 –7. 8. Arai M, Katsumi O, Paranhos FRL, et al. Comparison of Snellen acuity and objective assessment using the spatial frequency sweep PVER. Graefes Arch Clin Exp Ophthalmol 1997;235:442–7. 9. Thompson HS. Functional visual loss. Am J Ophthalmol 1985;100:209 –13. 10. Kathol RG, Cox TA, Corbett JJ, Thompson HS. Functional
79
Ophthalmology Volume 108, Number 1, Month 2001
11. 12. 13. 14. 15. 16. 17.
18. 19.
visual loss. Follow-up of 42 cases. Arch Ophthalmol 1983; 101:729 –35. Catalano RA, Simon JW, Krohel GB, Rosenberg PN. Functional visual loss in children. Ophthalmology 1986;93:385– 90. Kramer KK, La Piana FG, Appleton B. Ocular malingering and hysteria: diagnosis and management. Surv Ophthalmol 1979;24:89 –96. Bienfang DC, Kurtz D. Management of functional vision loss. J Am Optom Assoc 1998;69:12–21. Bose S, Kupersmith MJ. Neuro-ophthalmologic presentations of functional visual disorders [review]. Neurol Clin 1995;13: 321–39. Barris MC, Kaufman DI, Barberio D. Visual impairment in hysteria. Doc Ophthalmol 1992;82:369 – 82. Steele M, Seiple WH, Carr RE, Klug R. The clinical utility of visual-evoked potential acuity testing. Am J Ophthalmol 1989;108:572–7. Holder GE. Electrodiagnostic testing in malingering and hysteria. In: Heckenlivily JR, Arden GB, eds. Principles and Practice of Clinical Electrophysiology of Vision. St. Louis: Mosby Year Book, 1991; chap. 72, 573–7. Mouriaux F, Defoort-Dhellemmes S, Kochman F, et al. Le pithiatisme oculaire chez l’enfant et l’adolescent [Eng abstr]. J Fr Ophtalmol 1997;20:175– 82. Bobak P, Khanna P, Goodwin J, Brigell M. Pattern visual evoked potentials in cases of ambiguous acuity loss. Doc Ophthalmol 1993;85:185–92.
20. Morgan RK, Nugent B, Harrison JM, O’Connor PS. Voluntary alteration of pattern visual evoked responses. Ophthalmology 1985;92:1356 – 63. 21. Bumgartner J, Epstein CM. Voluntary alteration of visual evoked potentials. Ann Neurol 1982;12:475– 8. 22. Marg E, Freeman DN, Peltzman P, Goldstein PJ. Visual acuity development in human infants: evoked potential measurements. Invest Ophthalmol 1976;15:150 –3. 23. Harter MR, Deaton FK, Odom JV. Maturation of evoked potentials and visual preference in 6-45-day-old infants: effects of check size, visual acuity, and refractive error. Electroencephalogr Clin Neurophysiol 1977;42:595– 607. 24. Spehlmann R, Gross RA, Ho SU, et al. Visual evoked potentials and postmortem findings in a case of cortical blindness. Ann Neurol 1977;2:531– 4. 25. Celesia GG, Archer CR, Kuroiwa Y, Goldfader PR. Visual function of the extrageniculo-calcarine system in man: relationship to cortical blindness [case report]. Arch Neurol 1980; 37:704 – 6. 26. Frank Y, Torres F. Visual evoked potentials in the evaluation of “cortical blindness” in children. Ann Neurol 1979; 6:126 –9. 27. Towle VL, Sutcliffe E, Sokol S. Diagnosing functional visual deficits with the P300 component of the visual evoked potential. Arch Ophthalmol 1985;103:47–50. 28. Rover J, Bach M. Pattern electroretinogram plus visual evoked potential: a decisive test in subjects suspected of malingering. Doc Ophthalmol 1987;66:245–51.
Discussion by Larry Frohman, MD The authors correctly state that the primary tool that the ophthalmologist has in his or her clinical armamentarium when assessing subjects for functional visual loss (FVL) is a careful and complete ocular examination to rule out organic causes of seemingly inexplicable visual loss. This article deals with the “what comes next?”; that is, what test might the ophthalmologist use to confirm suspicions of unexplained visual loss? The authors contribute three points with this study. First, the study size is larger than any prior reported series that has used pattern visual evoked potentials (P-VEPs) to study subjects with functional visual loss. Second, it compares the measured Snellen acuity with the visual acuity predicted by analyzing the responses obtained by recording during visual evoked potentials with stimuli of varying check sizes. Third, it reports the “What happens after?” portion; that is, what happens to the subjects’ measured visual function after you reassure them that both the examination and the P-VEP are normal. The study screened 138 subjects with suspected FVL who were referred for visual evoked potential testing. Fortyone subjects who did not have clinical follow-up were excluded. A criterion for entry was initial acuity of no better
From the Departments of Ophthalmology and Neurosciences, UMD-New Jersey Medical School, Newark, New Jersey. Supported in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Address correspondence to Larry Frohman, MD, 90 Bergen Street, Newark, NJ 07103.
80
than 20/50 in the involved eye(s), thus, an additional 17 were excluded. Of note is that eight subjects who had an abnormal electroretinogram (ERG) or visual evoked potential (VEP) were excluded from this study. This left the study cadre of 72 subjects as the subjects of this study. Subjects with suspected FVL with visual acuity of better than 20/50, but with nonorganic visual fields were excluded from this study, thus, the reader must remember that its conclusions cannot be absolutely applied to this group when they are encountered in clinical practice. Because FVL manifesting as field loss with preserved central acuity is not a rare finding, a similar study to this would be beneficial to look at this group’s responses on P-VEP. When one looks at the data, the study reports that 19.5% of their subjects had a Snellen acuity that was within 3 lines of the VEP estimated visual acuity, and in 34.7% of their cases there was a difference of greater than 4 lines. A problem in the data analysis is that although the authors report that 45 of the 72 subjects had bilateral visual loss, the data analysis speaks of subjects, not of eyes. Thus, the reader cannot know how a subject who had a difference of less than 3 lines in one eye and greater than 4 lines in the other eye was tabulated (if such a case existed). For instance, let us say we had a bilateral FVL case who was 20/400 in both eyes at onset, had abnormal P-VEP predicting acuities of at least 20/30, and was reassured, and then retested, and showed acuities of 20/20 and 20/400. Would this subject be counted as no improvement or as the highest level of improvement?