ACUTE POSTERIOR MULTIFOCAL PLACOID P I G M E N T E P I T H E L I O P A T H Y ASSOCIATED W I T H CEREBRAL VASCULITIS AND HOMONYMOUS HEMIANOPIA J E S S E S I G E L M A N , M.D., M Y L E S B E H R E N S , M.D., AND SADEK H I L A L , M.D. New York, New York The ophthalmic manifestations of acute posterior multifocal placoid pigment epitheliopathy have been established by Gass. 1 Both the original case descriptions and subsequent reports have shown an association of this disease with a variety of ophthalmic and systemic manifesta­ tions including a significant association with central nervous system disease. We describe herein a case of acute posterior multifocal placoid pigment epithelio­ pathy associated with cerebral vasculitis and probable occipital infarction. These findings add further evidence to the con­ cept of a common underlying vascular inflammatory basis for the ophthalmic and systemic manifestations in patients with acute posterior multifocal placoid pigment epitheliopathy. To the best of our knowledge, this is the first reported case with such concomitant visual de­ fects. CASE REPORT On Aug. 5, 1977, an 18-year-old man awoke with bilateral blurred vision and retrobulbar pain with severe headache. The night before he had drunk large amounts of bourbon and beer, vomited, and slept. He had a family history of migraine headaches and a five-day long episode of headache and vomit­ ing in April 1977 while taking parenteral antibiotics for chronic bronchitis. On Aug. 9, 1977, he was hospitalized because of blurred vision and a suggestion of a left homonyFrom the E. S. Harkness Eye Institute, ColumbiaPresbyterian Medical Center, New York, New York (Drs. Sigelman and Behrens); and the Department of Radiology and the New York Neurological Institute, Columbia-Presbyterian Medical Center, New York, New York (Dr. Hilal). Dr. Sigelman was supported in part by the Glorney-Raisbeck Foundation of the New York Academy of Medicine. Reprint requests to Jesse Sigelman, M.D., 635 W. 165th St., New York, NY 10032. mous hemianopia. Results of laboratory tests in­ cluding a complete blood cell count and urinalysis were normal. T h e cerebrospinal fluid had a normal glucose level and negative culture but a protein level of 55 mg/100 ml with a red blood cell count of 90/mm 3 . A computed axial tomography scan was initially considered negative, but then suggested a right occipital abnormality and the electroencepha­ logram showed slow alpha rhythm in the right occipital area. On Aug. 11, 1977, corrected visual acuity was R.E.: 6/21 (20/70) and L.E.: 6/6 (20/20). Visual fields then showed a central scotoma in the right eye without obvious homonymous hemiano­ pia. Pigmentary disturbance of the right macula was noted. On Aug. 16, 1977, visual acuity was R.E.: 6/21 (20/70) and L.E.: 6/6 (20/20). Color vision was normal in each eye as measured by the AO H-R-R plates. Visual field (Fig. 1) and Amsler grid testing showed a central scotoma in the right eye that was densest nasally and a temporal central scotoma in the left eye that extended slightly across the midline. Inferior left homonymous hemianopic depression was evident, which was more marked in the right eye. Ophthalmoscopic examination of the right eye showed a central pigmentary lesion with creamcolored placoid lesions (Fig. 2). The posterior pole of the left eye showed no placoid lesions or pigmen­ tary disturbance. Peripheral flat pigmentary lesions without fresh placoid lesions were present in the periphery of each eye. These were more marked in the right eye (Fig. 3). Fluorescein angiography (Fig. 4) showed blocking defects at the areas of the posterior pole pigmentary disturbance and placoid lesions in the right eye with late staining and slight leakage at the placoid lesion sites (Fig. 5). An electroencephalogram showed an abnormality in the right occipital region and right occipital infarction was suggested by dynamic technetium scan. A computed axial tomographic scan also sug­ gested probable right occipital infarction. Transfemoral selective cerebral angiography showed mul­ tiple disseminated areas of focal narrowing compati­ ble with vasculitis (Fig. 6). Lumbar puncture again showed a high protein level (52 mg/100 ml with IgG of 3.3 mg/100 ml with five mononuclear cells and a normal glucose level. Other laboratory results were normal including complete blood cell count, erythrocyte sedimentation rate, latex fixation, antistreptolysin O titer, cold agglutinins, lupus erythematosus preparation, antinuclear antibody, and antiDNA antibody. During the eight days of hospitalization, visual AMERICAN JOURNAL O F OPHTHALMOLOGY 88:919-924, 1979 919 920 AMERICAN JOURNAL OF OPHTHALMOLOGY NOVEMBER, 1979 3W/I000 120 105 240 255 90 75 60 120 105 270 285 300 240 255 LEFT 90 75 60 270 285 300 RIGHT Fig. 1 (Sigelniau, Behrens, and Hilal). The central scotoma was densest nasally in the right eye. The temporal central scotoma of the left eye extended slightly across midline. Inferior homonymous hemianopic depression was mori' marked in the right eye. acuity in the right eye improved to 6/12 (20/40) with progression of pigmentation (Fig. 7). The left eye maintained visual acuity of 6/6 (20/20) despite devel­ opment of small plaeoid lesions inferior and superoteinporal to the macula (Fig. 8). The severity of the Fig. 2 (Sigelman, Behrens, and Hilal). The pigment epithelium of the posterior pole showed uneven thickness and pigmentation with a yellow-white coloration of the borders of the lesion and of the satellite lesion. The overlying retina and vitreous were uninvolved. headache gradually decreased by the time of dis­ charge on Aug. 26, 1978. By Sept. 30, 1978, symptoms were essentially gone and examination then as well as on March 9, 1978, showed visual acuity of K.E.: 6/7.5 (20/25) and L.E.: 6/6 (20/20). Visual fields showed a persistent left homonymous hemianopic scotoma. The right Fig. 3 (Sigelman, Behrens, and Hilal). Flatpigmentary lesion without fresh pigment epithelial swelling as seen in both peripheries. VOL. 88, NO. 5 PIGMENT EPITHELIOPATHY Fig. 4 (Sigelman, Behrens, and Hilal). Arteriovenous phase fluorescein angiogram showing blocking defects by both the original central lesion and the later onset satellite lesion. macula showed a diffuse but mottled pigment epi­ thelial hypertrophy and pigment scatter. The left macula had no visible lesion. The peripheral retinal lesions were unchanged. DISCUSSION The sudden appearance of cream-col­ ored placoid lesions in the posterior pole Fig. 6 (Sigelman, Behrens, and Hilal). Magnifica­ tion, lateral view, of a selective right internal carotid angiogram with substraction. Multiple segments of focal narrowing are evident. The most pronounced change is seen in the middle cerebral branch origi­ nating in the center of the sylvian group (black solid arrow). Another segment of narrowing is seen in the posterior temporal branch supplying the temporal occipital region (double hollow arrows). Close scru­ tiny of the angiogram shows multiple areas of focal narrowing disseminated throughout. The changes are compatible with those seen in vasculitis. 921 Fig. 5 (Sigelman, Behrens, and Hilal). Late angio­ gram shows staining and slight leakage of the cen­ tral and satellite lesions. of one eye in a young adult followed by development of similar lesions in the pos­ terior pole of the opposite eye character­ izes acute posterior multifocal placoid pigment epitheliopathy. 1 - 4 Positive scotomas develop corresponding to the Fig. 7 (Sigelman, Behrens, and Hilal). Eight days after their appearance as shown in Figure 2, both the central and satellite lesions showed evolving pig­ ment disturbance. Visual acuity improved during the pigmentation. 922 AMERICAN JOURNAL OF OPHTHALMOLOGY Fig. 8 (Sigelman,Behrens, and Hilal). Yellow-white placoid lesions of the pigment epithelium devel­ oped in the posterior pole of the left eye one week after the discovery of the peripheral lesions in both eyes and the macular lesions in the right eye. points of the placoid lesions. Visual acu­ ity decreases if a lesion occurs at the fovea. The course of acute posterior multifocal placoid pigment epitheliopathy is rapid, both with acute onset, in hours, and resolution over a period of weeks. Visual impairment and positive seotomas resolve more slowly than does the ophthalmoscopic appearance of the lesions whose pigment scattering may appear sta­ ble months before final resolution of visu­ al acuity. The acute placoid lesions, on contact lens examination, are deeper than the retina with the lesions always involving the pigment epithelium. The overlying vitreous, retina, retinal vessels, and optic nerve characteristically are normal except for occasional cases with evidence of reti­ nal arteritis and secondary vitreous in­ flammation. Although rare, the associated occurrence of papillitis, 3 ' 5 ^ 7 episcleritis 8 and marginal corneal thinning 8 have been interpreted to be additional manifesta­ tions of an underlying vasculitis as the NOVEMBER, 1979 basis of acute posterior multifocal placoid pigment epitheliopathy. The characteristic fluorescein angiographic pattern in acute posterior multifocal placoid pigment epitheliopathy consists of an early blocking defect at the site of the lesions with late staining and occasional late leakage. 1,9 This pattern has been interpreted as the result of swelling of the pigment epithelial cells with occasional breakdown of their tight junctions at the lesion sites. An angiographic finding of Deutman and Lion 1 0 has suggested that localized blockage of choriocapillaris perfusion may be the pri­ mary cause of the problem. In one case, Deutman and Lion 1 0 found absence of choriocapillaris perfusion at the site of a placoid lesion where choroidal circula­ tion could be seen. It had been thought previously that the lack of visibility of choroidal circulation at the site of the lesions was caused by swelling of the overlying pigment epithelial cells. Our case was the second to show an association between acute posterior mul­ tifocal placoid pigment epitheliopathy and cerebral vasculitis. 7 The only ocular finding in our case that deviated from the classic description of acute posterior mul­ tifocal placoid pigment epitheliopathy was the homonymous hemianopia appar­ ently the result of cerebral vasculitis with occipital lobe infarction. The combined visual field defects of these two diseases produced a complex visual field defect. The existence of cerebral vasculitis with occlusion was documented by cerebral arteriography with occipital lobe infarc­ tion suggested by a computed axial tomographic scan. The existence of central nervous system inflammation was fur­ ther suggested by the high cerebrospinal fluid protein level and slight pleiocytosis. Review of 60 published case reports of acute posterior multifocal placoid pig- VOL. 88, N O . 5 PIGMENT EPITHELIOPATHY 923 TABLE ACCOMPANYING DISORDERS IN 60 R E P O R T E D CASES O F A C U T E P O S T E R I O R MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY Disorder Neurologic Headache three to four days before onset of acute posterior multifocal placoid pigment epitheliopathy Headache simultaneous with onset of acute posterior multifocal placoid pigment epitheliopathy Transient expressive aphasia with cerebral vasculitis Abnormal electroencephalogram Cerebrospinal fluid pleiocytosis Cases with cerebrospinal fluid evaluation Cases with cerebrospinal fluid pleiocytosis or elevated protein Systemic Erythema multiforme Thyroiditis Ocular Papillitis No. of Cases 12 Authors Ryan and Maumenee 2 Holt, Regan, and Trempe 7 6 Gass 1 Ryan and Maumenee 2 Holt, Regan, and Trempe 7 Reuscher 14 Bullock, Thomas, and Fletechur 1 5 1 1 Holt, Regan, andTrempe 7 Savino and associates 3 Holt, Regan, amd Trempe 7 Kirkman, Ffytche, and Sanders 5 Fishman, Baskin, and Jednock 1 6 5 3 1 1 Van Buskirk, Lessel, and Friedman 1 1 Jacklin 8 6 Posterior uveitis 4 Retinal vasculitis with serous retinal detachment Serous retinal detachment without arteritis Iridocyclitis 1 Savino and associates 3 Kirkman, Ffytche, and Sanders 5 Jenkins, Savino, and Pilkerton 6 Jacklin 6 Savino and associates 3 Kirkman, Ffytche, and Sanders 5 Jacklin 8 Reuscher 14 2 Bird and Hamilton 1 2 2 Peripheral corneal thinning Episcleritis 1 2 Anneseley, Tomer, and Shields 4 Deutman, Oesterhuis, and Bven-Tan 9 Jacklin 8 Anneseley, Tomer, and Shields 4 Holt, Regan, and Trempe 7 ment epitheliopathy 1 " 1 6 suggests a high rate of concomitant central nervous sys­ tem involvement (Table). The high inci­ dence of both ocular and systemic associ­ ations with acute posterior multifocal placoid pigment epitheliopathy may indi­ cate that it is a specific ocular manifesta­ tion of a systemic vascular inflammatory disease. The association with an influen­ za type of syndrome in some patients before development of acute posterior multifocal placoid pigment epitheli­ opathy has suggested a possible viral cause. The differential diagnosis of acute pos­ terior multifocal placoid pigment epithe­ liopathy should include the maculopathy of Dawson's subacute sclerosing panencephalitis, 17 ' 18 serous or hemorrhagic de­ tachments of the pigment epithelium, 1 9 inactive foci of presumed ocular histoplasmosis, 2 0 retinal pigment epitheliitis, 21 924 AMERICAN JOURNAL OF OPHTHALMOLOGY Best's vitellieruptive degeneration, 22 and acute herpes simplex retinitis. 23 SUMMARY An 18-year-old man developed acute posterior multifocal placoid pigment epitheliopathy and homonymous hemianopia. Cerebral angiography showed cere­ bral vasculitis probably with occipital infarction. To the best of our knowledge, this is the first reported case with such concomitant visual defects. Other pub­ lished reports suggest that such cerebral vasculitis may not be unusual in acute posterior multifocal placoid pigment epitheliopathy. REFERENCES 1. Gass, J. D. M.: Acute posterior multifocal plac­ oid pigment epitheliopathy. Arch. Ophthalmol. 80:177, 1968. 2. Ryan, S. J., and Maumenee, A. E.: Acute pos­ terior multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 74:1066, 1972. 3. Savino, P. J., Weinberg, R. J., Yassin, J. G., and Pilkerton, A. R.: Diverse manifestations of acute posterior multifocal placoid pigment epitheli­ opathy. Am. J. Ophthalmol. 77:659, 1974. 4. Anneseley, W. H., Tomer, T. L., and Shields, J. A.: Multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 76:511, 1973. 5. Kirkman, T., Ffytche, T., and Sanders, M.: Placoid pigment epitheliopathy with retinal vasculi­ tis and papillitis. Br. J. Ophthalmol. 56:875, 1972. 6. Jenkins, R. B., Savino, P. J., and Pilkerton, A. R.: Placoid pigment epitheliopathy with swelling of the optic discs. Arch. Neurol. 29:204, 1973. 7. Jacklin, H. N.: Acute posterior multifocal plac­ oid pigment epitheliopathy and thyroiditis. Arch. Ophthalmol. 95:995, 1977. 8. Holt, W. S., Regan, C. D. J., and Trempe, C.: Acute posterior multifocal placoid pigment epitheli­ opathy. Am. J. Ophthalmol. 81:403, 1976. 9. Deutman, A. F., Oesterhuis, J. A., and Bven- NOVEMBER, 1979 Tan, T. N.: Acute posterior multifocal placoid pig­ ment epitheliopathy. Br. J. Ophthalmol. 56:863, 1972. 10. Deutman, A., and Lion, F.: Choriocapillaris nonperfusion in acute multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 84:652, 1977. 11. Van Buskirk, E. B., Lessel, S., and Friedman, E.: Pigment epitheliopathy and erythema nodosum. Arch. Ophthalmol. 85:369, 1971. 12. Bird, A. C., and Hamilton, A. M.: Placoid pigment epitheliopathy presenting with bilateral serous retinal detachments. Br. J. Ophthalmol. 56:881, 1972. 13. Laatikainen, L., and Erkkila, H.: Clinical and fluorescein angiographic findings of acute multifo­ cal central subretinal inflammation. Acta Ophthal­ mol. 51:645, 1973. 14. Reuscher, A.: Zur pathogenese der segenanten akuten hinteren multifokalex placeiden pigment ep­ itheliopathy. Klin. Monatsbl. Augenheilkd. 165:775, 1974. 15. Bullock, J. D., Thomas, E. R., and Fletechur, R. L.: Cerebrospinal fluid abnormalities in acute posterior multifocal placoid pigment epitheli­ opathy. Presented at the Association for Research in Vision and Opthalmology Central Section meeting, Ann Arbor, Michigan, Oct. 15, 1975. 16. Fishman, G. A., Baskin, M., and Jednock, N.: Spinal fluid pleocystosis in acute posterior placoid pigment epitheliopathy. Ann. Ophthalmol. 9:33, 1977. 17. Nelsen, D. A., Weiner, A., Yanoff, M., and de Peralta, J.: Retinal lesions in SSPE. Arch. Oph­ thalmol. 84:613, 1970. 18. La Piana, F., Tso, M. O., and Jenis, E. H.: The retinal lesions of subacute sclerosing panencephalitis. Ann. Ophthalmol. 6:603, 1974. 19. Maumenee, A. E., and Emery, J. M.: An anatomic classification of diseases of the macula. Am. J. Ophthalmol. 74:594, 1972. 20. Schlaegel, T. F., Jr., Weber, J. C , Helveston, E., and Kenney, D.: Presumed histoplasmic choroiditis. Am. J. Ophthalmol. 63:919, 1967. 21. Krill, A. E., and Deutman, A. F.: Acute retina] pigment epitheliitis. Am. J. Ophthalmol. 74:193, 1972. 22. Falls, H. F.: The polymorphous manifesta­ tions of Best's disease. Trans. Am. Ophthalmol. Soc. 67:265, 1969. 23. Bloom, J. N., Katz, J. I., and Kaufman, H. E.: Herpes simplex retinitis and encephalitis in an adult. Arch. Ophthalmol. 95:1798, 1977.