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Acute Posterior Multifocal Placoid Pigment Epitheliopathy Associated with an Adenovirus Type 5 Infection
ACUTE POSTERIORJUILIIFOCAL PLACOID PIGMENT EPITHELIOPATHY ASSOCIATED WITH AN ADENOVIRUS TYPE 5 INFECTION i
P A U L A Z A R , J R . , M.D.,
R O B E R T S. G O H D , P H . D . , D E N N I S W A L T M A N , AND K U R T A .
GITTER,
M.D.,
M.D.
New Orleans, Louisiana
Acute posterior multifocal placoid pig ment epitheliopathy is a rare disease thought to be an inflammatory reaction in either the retinal pigment epithelium or the choriocapillaris, or both.1 Toxoplasmosis,2 vi ruses,1'3-5 tuberculosis, and erythema nodosum6 have been suggested as possible etiologic agents, but the true cause has not yet been determined. We describe a pa tient who presented with the typical clinical and fluorescein angiographic findings of acute posterior multifocal placoid pigment epitheliopathy with positive viral cultures and rising antibodies to adenovirus t£pe_5. CASE REPORT In March 1974, a 19-year-old black man was seen with complaints of painless loss of vision in both eyes of two weeks' duration. The patient first no ticed a gradual loss in vision of the left eye over a period of several days, followed a week later by considerable loss of vision in his right eye, which then prompted his visit. He could not recall any similar previous occurrences, antecedent infectious episodes, or unexplained fevers, and there was no history of past trauma. He denied taking any medi cation. The family history was also negative. Corrected visual acuity was 20/300 in each eye. Intraocular pressures were normal. A trace of flare and + 1 cells were present in the anterior chamber. The positive findings were limited to both posterior poles where grayish-white lesions of irregular shape (54 to Yi disk diameters) were scattered through out the paramacular area but not involving either fovea. These lesions appeared to be subretinal on contact lens biomicroscopic examination (Fig. 1). Fluorescein angiographic study showed partial early blockage of fluorescein dye with late fluorescein staining of the lesions (Fig. 2). Other than the visual loss, the patient was asymptomatic and in good physical health. Physical examination after hospitalization disclosed enlarged
tonsils. Urinalysis, hemograms, and chest x-ray film results were normal. Bacterial cultures of blood, stool, and urine were negative. Skin tests for histoplasmosis, tuberculosis, coccidioidomycosis, and blastomycosis were negative. The urine was nega tive for cytomegalic inclusions. The VDRL and fluorescent treponemal antibody absorption (FTA) tests were nonreactive. Antibody tests for rubella, herpes zoster, herpes simplex, and toxoplasmosis with acute and convalescent sera showed no sig nificant change in titer. On the fifth hospital day the patient developed a low-grade fever, associated with inflamed tonsils, general malaise, and anorexia. RESULTS
Blood was drawn on the first, eighth, and 60th day of observation for viral and bacterial cultures and antibody titers. Cultures of the throat were obtained on the fourth day and a tonsillar biopsy specimen was obtained on the seventh day (Table). Adenovirus type 5 was isolated from both the throat swab and from the homogenate of the tonsillar
From the Department of Ophthalmology, Louisi ana State University Medical Center (Drs. Azar and Waltman), Laboratory of Virology, Depart ment of Pathology, Charity Hospital at New Or Fig. 1 (Azar and associates). Red-free photo leans (Dr. Gohd), and Touro Eye Research Lab graph of right eye when patient was first seen; oratory (Dr. Gitter), New Orleans, Louisiana. visual acuity, 20/300. Multiple grayish-white nonReprint requests to Paul Azar, Jr., M.D., 516 discrete subretinal placoid lesions scattered through out the posterior pole. St. Landry, Lafayette, LA 70501. 1003
1004
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER, 1975
to 32 after 60 days. The isolation of virus from two sources, accompanied by a serologic rise in antibody titer by two tests, provided firm evidence of adenovirus infection occurring concurrently with the acute phase of the patient's ocular disease. The patient remained in the hospital for two weeks and received no medication during that time. On discharge, visual acuity was R.E.: 20/100, and L.E.: 20/30, and pigmentation had increased in the placoid lesions. Six weeks from the onset of the illness, visual acuity was 20/20 in each eye. Six months later, the ophthalmoscopic examination showed multiple focal chorioretinal scars of the posterior pole at the exact loci of the prior acute placoid irregular lesions (Fig. 3). DISCUSSION
The ocular problems of this healthy young adult began with a marked decrease in visual acuity, first in one eye and then in both eyes. The ophthalmoscopic picture showed multiple circumscribed nonelevated subret-
Fig. 2 (Azar and associates). Top, Early arteriovenous phase angiogram of right eye demonstrating multiple areas of choroidal nonfilling at locus of placoid lesions. Some retinal pigment epithelium is visible and may be secondary to the two to three weeks' presence of this disorder, explaining the absense of total blockage of dye in these zones. Bottom, Late phase (15 minutes) dye staining of placoid lesions.
biopsy tissue. Complement-fixation antibody tests for adenovirus type 5 were negative for blood drawn on the first and eighth days, but rose to 16 in the last specimen taken on the 60th day. Serum obtained on the eighth day had an adenovirus type 5 neutralizing antibody titer of less then 8· the titer rose
Fig. 3 (Azar and associates). Late arteriovenous phase angiogram of right eye six weeks later; visual acuity, 20/20, pigment clumping surrounding the macula with multiple zones of retinal pigment epithelium atrophy. The late phase of the angiogram (30 minutes) showed no evidence of late dye leakage
VOL. 80, NO. 6
PIGMENT EPITHELIOPATHY
1005
TABLE SUMMARY OF VIROLOGIC STUDIES
Serology Titers Date
Specimen
3/8/74 3/11/74 3/14/74 3/15/74 5/7/74
Serum Throat swab Tonsil biopsy specimen Serum Serum
Result
Adenovirus type 5 Adenovirus type 5
Complement Fixation
Neutralization with Adenovirus Type 5
Negative*
Negative*
Negative 16
8 32
* Negative at serum dilutions of 1:8, the lowest dilution tested.
inal lesions, superficially resembling dissemi nated choroiditis. These early grayish-white plaque-like lesions changed in three to four weeks into depigmentations of the retinal pigment epithelium, with irregular clumping of pigment, and gradually progressed to in active pigmented scars. The poor visual acuity dramatically resolved in six weeks after the onset of the disease. During the acute phase partial blockage of early choroidal fluorescence was noted. We presume that the absence of total blockage of underlying fluorescence was because the lesion was not at its most acute form when first studied. The patchy nonfluorescence of the choroid may represent a delay in choriocapillaris perfusion or an isolated retinal pigment epithelial abnormality. The late phase angiography (15 minutes) of these same lesions showed definite fluorescein staining. The cause of this form of pigment epitheliopathy is unknown. Viral disease has been suggested by several observers on clinical grounds alone.1'3-5 Ryan and Maumenee3 reported a viral-like syndrome ac companying acute posterior multi focal placoid pigment epitheliopathy in more than one half of their patients. In our study, viral isola tion and serologic data indicate that an adeno virus type 5 infection occurred concurrently with the clinical syndrome of acute posterior multifocal placoid pigment epitheliopathy.
This observation, considered with the re ports of others, supports the thesis that a respiratory virus may be implicated in this disorder. To riur knnwlprjfjr^ mjrs is the second re ported case occurring in a black person.4 SUMMARY
A 19-year-old black man with acute pos terior multifocal placoid pigment epitheliop athy had concurrent positive viral cultures and rising antibodies to adenovirus type 5. This finding, considered together with earlier reports of viral-like syndromes accompany ing the disease, supports the implication of a respiratory virus as a possible etiologic fac tor. REFERENCES
1. Gass, J. D. M.: Acute posterior multifocal pigment epitheliopathy. Arch. Ophthalmol. 80:177, 1968. 2. Kirkham, T. H., Ffytche, T. J., and Sanders, M. D.: Placoid pigment epitheliopathy with retinal vasculitis and papillitis. Br. J. Ophthalmol. 56:875, 1972. 3. Ryan, S. J., and Maumenee, A. E.: Acute posterior multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 74:1066, 1972. 4. Annesley, W. H., Tomer, T. L., and Shields, J. A.: Multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 76:511, 1973. 5. Fitzpatrick, P. J., and Robertson, D. M.: Acute posterior multifocal placoid pigment epi theliopathy. Arch. Ophthalmol. 89:373, 1973. 6. Van Buskirk, E. M., Lessell, S., and Fried man, E.: Epitheliopathy and ervthema nodosum. Arch. Ophthalmol. 85 :369, 1971.
P A U L A Z A R , J R . , M.D.,
R O B E R T S. G O H D , P H . D . , D E N N I S W A L T M A N , AND K U R T A .
GITTER,
M.D.,
M.D.
New Orleans, Louisiana
Acute posterior multifocal placoid pig ment epitheliopathy is a rare disease thought to be an inflammatory reaction in either the retinal pigment epithelium or the choriocapillaris, or both.1 Toxoplasmosis,2 vi ruses,1'3-5 tuberculosis, and erythema nodosum6 have been suggested as possible etiologic agents, but the true cause has not yet been determined. We describe a pa tient who presented with the typical clinical and fluorescein angiographic findings of acute posterior multifocal placoid pigment epitheliopathy with positive viral cultures and rising antibodies to adenovirus t£pe_5. CASE REPORT In March 1974, a 19-year-old black man was seen with complaints of painless loss of vision in both eyes of two weeks' duration. The patient first no ticed a gradual loss in vision of the left eye over a period of several days, followed a week later by considerable loss of vision in his right eye, which then prompted his visit. He could not recall any similar previous occurrences, antecedent infectious episodes, or unexplained fevers, and there was no history of past trauma. He denied taking any medi cation. The family history was also negative. Corrected visual acuity was 20/300 in each eye. Intraocular pressures were normal. A trace of flare and + 1 cells were present in the anterior chamber. The positive findings were limited to both posterior poles where grayish-white lesions of irregular shape (54 to Yi disk diameters) were scattered through out the paramacular area but not involving either fovea. These lesions appeared to be subretinal on contact lens biomicroscopic examination (Fig. 1). Fluorescein angiographic study showed partial early blockage of fluorescein dye with late fluorescein staining of the lesions (Fig. 2). Other than the visual loss, the patient was asymptomatic and in good physical health. Physical examination after hospitalization disclosed enlarged
tonsils. Urinalysis, hemograms, and chest x-ray film results were normal. Bacterial cultures of blood, stool, and urine were negative. Skin tests for histoplasmosis, tuberculosis, coccidioidomycosis, and blastomycosis were negative. The urine was nega tive for cytomegalic inclusions. The VDRL and fluorescent treponemal antibody absorption (FTA) tests were nonreactive. Antibody tests for rubella, herpes zoster, herpes simplex, and toxoplasmosis with acute and convalescent sera showed no sig nificant change in titer. On the fifth hospital day the patient developed a low-grade fever, associated with inflamed tonsils, general malaise, and anorexia. RESULTS
Blood was drawn on the first, eighth, and 60th day of observation for viral and bacterial cultures and antibody titers. Cultures of the throat were obtained on the fourth day and a tonsillar biopsy specimen was obtained on the seventh day (Table). Adenovirus type 5 was isolated from both the throat swab and from the homogenate of the tonsillar
From the Department of Ophthalmology, Louisi ana State University Medical Center (Drs. Azar and Waltman), Laboratory of Virology, Depart ment of Pathology, Charity Hospital at New Or Fig. 1 (Azar and associates). Red-free photo leans (Dr. Gohd), and Touro Eye Research Lab graph of right eye when patient was first seen; oratory (Dr. Gitter), New Orleans, Louisiana. visual acuity, 20/300. Multiple grayish-white nonReprint requests to Paul Azar, Jr., M.D., 516 discrete subretinal placoid lesions scattered through out the posterior pole. St. Landry, Lafayette, LA 70501. 1003
1004
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER, 1975
to 32 after 60 days. The isolation of virus from two sources, accompanied by a serologic rise in antibody titer by two tests, provided firm evidence of adenovirus infection occurring concurrently with the acute phase of the patient's ocular disease. The patient remained in the hospital for two weeks and received no medication during that time. On discharge, visual acuity was R.E.: 20/100, and L.E.: 20/30, and pigmentation had increased in the placoid lesions. Six weeks from the onset of the illness, visual acuity was 20/20 in each eye. Six months later, the ophthalmoscopic examination showed multiple focal chorioretinal scars of the posterior pole at the exact loci of the prior acute placoid irregular lesions (Fig. 3). DISCUSSION
The ocular problems of this healthy young adult began with a marked decrease in visual acuity, first in one eye and then in both eyes. The ophthalmoscopic picture showed multiple circumscribed nonelevated subret-
Fig. 2 (Azar and associates). Top, Early arteriovenous phase angiogram of right eye demonstrating multiple areas of choroidal nonfilling at locus of placoid lesions. Some retinal pigment epithelium is visible and may be secondary to the two to three weeks' presence of this disorder, explaining the absense of total blockage of dye in these zones. Bottom, Late phase (15 minutes) dye staining of placoid lesions.
biopsy tissue. Complement-fixation antibody tests for adenovirus type 5 were negative for blood drawn on the first and eighth days, but rose to 16 in the last specimen taken on the 60th day. Serum obtained on the eighth day had an adenovirus type 5 neutralizing antibody titer of less then 8· the titer rose
Fig. 3 (Azar and associates). Late arteriovenous phase angiogram of right eye six weeks later; visual acuity, 20/20, pigment clumping surrounding the macula with multiple zones of retinal pigment epithelium atrophy. The late phase of the angiogram (30 minutes) showed no evidence of late dye leakage
VOL. 80, NO. 6
PIGMENT EPITHELIOPATHY
1005
TABLE SUMMARY OF VIROLOGIC STUDIES
Serology Titers Date
Specimen
3/8/74 3/11/74 3/14/74 3/15/74 5/7/74
Serum Throat swab Tonsil biopsy specimen Serum Serum
Result
Adenovirus type 5 Adenovirus type 5
Complement Fixation
Neutralization with Adenovirus Type 5
Negative*
Negative*
Negative 16
8 32
* Negative at serum dilutions of 1:8, the lowest dilution tested.
inal lesions, superficially resembling dissemi nated choroiditis. These early grayish-white plaque-like lesions changed in three to four weeks into depigmentations of the retinal pigment epithelium, with irregular clumping of pigment, and gradually progressed to in active pigmented scars. The poor visual acuity dramatically resolved in six weeks after the onset of the disease. During the acute phase partial blockage of early choroidal fluorescence was noted. We presume that the absence of total blockage of underlying fluorescence was because the lesion was not at its most acute form when first studied. The patchy nonfluorescence of the choroid may represent a delay in choriocapillaris perfusion or an isolated retinal pigment epithelial abnormality. The late phase angiography (15 minutes) of these same lesions showed definite fluorescein staining. The cause of this form of pigment epitheliopathy is unknown. Viral disease has been suggested by several observers on clinical grounds alone.1'3-5 Ryan and Maumenee3 reported a viral-like syndrome ac companying acute posterior multi focal placoid pigment epitheliopathy in more than one half of their patients. In our study, viral isola tion and serologic data indicate that an adeno virus type 5 infection occurred concurrently with the clinical syndrome of acute posterior multifocal placoid pigment epitheliopathy.
This observation, considered with the re ports of others, supports the thesis that a respiratory virus may be implicated in this disorder. To riur knnwlprjfjr^ mjrs is the second re ported case occurring in a black person.4 SUMMARY
A 19-year-old black man with acute pos terior multifocal placoid pigment epitheliop athy had concurrent positive viral cultures and rising antibodies to adenovirus type 5. This finding, considered together with earlier reports of viral-like syndromes accompany ing the disease, supports the implication of a respiratory virus as a possible etiologic fac tor. REFERENCES
1. Gass, J. D. M.: Acute posterior multifocal pigment epitheliopathy. Arch. Ophthalmol. 80:177, 1968. 2. Kirkham, T. H., Ffytche, T. J., and Sanders, M. D.: Placoid pigment epitheliopathy with retinal vasculitis and papillitis. Br. J. Ophthalmol. 56:875, 1972. 3. Ryan, S. J., and Maumenee, A. E.: Acute posterior multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 74:1066, 1972. 4. Annesley, W. H., Tomer, T. L., and Shields, J. A.: Multifocal placoid pigment epitheliopathy. Am. J. Ophthalmol. 76:511, 1973. 5. Fitzpatrick, P. J., and Robertson, D. M.: Acute posterior multifocal placoid pigment epi theliopathy. Arch. Ophthalmol. 89:373, 1973. 6. Van Buskirk, E. M., Lessell, S., and Fried man, E.: Epitheliopathy and ervthema nodosum. Arch. Ophthalmol. 85 :369, 1971.