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Cytomegalovirus Retinitis: a Manifestation of the Acquired Immune Deficiency Syndrome (AIDS)*

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Cytomegalovirus Retinitis: a Manifestation of the Acquired Immune Deficiency Syndrome (AIDS)* Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from British Journal ofOphthalmology, 1983, 67, 372-380 Cytomegalovirus retinitis: a manifestation of the acquired immune deficiency syndrome (AIDS)* ALAN H. FRIEDMAN,' JUAN ORELLANA,'2 WILLIAM R. FREEMAN,3 MAURICE H. LUNTZ,2 MICHAEL B. STARR,3 MICHAEL L. TAPPER,4 ILYA SPIGLAND,s HEIDRUN ROTTERDAM,' RICARDO MESA TEJADA,8 SUSAN BRAUNHUT,8 DONNA MILDVAN,6 AND USHA MATHUR6 From the 2Departments ofOphthalmology and 6Medicine (Infectious Disease), Beth Israel Medical Center; 3Ophthalmology, "Medicine (Infectious Disease), and 'Pathology, Lenox Hill Hospital; 'Ophthalmology, Mount Sinai School ofMedicine; 'Division of Virology, Montefiore Hospital and Medical Center; and the 8Institute for Cancer Research, Columbia University College ofPhysicians and Surgeons, New York, USA SUMMARY Two homosexual males with the 'gay bowel syndrome' experienced an acute unilateral loss of vision. Both patients had white intraretinal lesions, which became confluent. One of the cases had a depressed cell-mediated immunity; both patients ultimately died after a prolonged illness. In one patient cytomegalovirus was cultured from a vitreous biopsy. Autopsy revealed disseminated cytomegalovirus in both patients. Widespread retinal necrosis was evident, with typical nuclear and cytoplasmic inclusions of cytomegalovirus. Electron microscopy showed herpes virus, while immunoperoxidase techniques showed cytomegalovirus. The altered cell-mediated response present in homosexual patients may be responsible for the clinical syndromes of Kaposi's sarcoma and opportunistic infection by Pneumocystis carinii, herpes simplex, or cytomegalovirus. http://bjo.bmj.com/ Retinal involvement in adult cytomegalic inclusion manifestations of the syndrome include the 'gay disease (CID) is usually associated with the con- bowel syndrome9 and Kaposi's sarcoma. 0 comitant presence of a neoplastic disorder of the We herewith describe the ocular findings in 2 haemopoietic and reticuloendothelial systems or previously normal homosexual males who developed treatment with immunosuppressive drugs following a severe immunodeficiency and widespread CID. In allotransplantation.1-3 While the diagnosis of CID one patient cytomegalovirus (CMV) was cultured on September 28, 2021 by guest. Protected copyright. can often be suggested by the ophthalmoscopic from the eye ante mortem as well as post mortem, appearance,4 confirmation is made by demon- while in the second patient cytomegalovirus was strating the inclusion bodies in urine, saliva, and demonstrated in the retina by immunoperoxidase biopsy specimens, rising serum titres, or positive staining post mortem. cultures.6 Recently a syndrome has been described involving homosexual males comprising a severe, Case reports acquired immunodeficiency and characterised by weight loss, fever, and severe, unrelenting, often fatal CASE 1 infection with opportunistic micro-organisms The patient, fully reported medically elsewhere," including cytomegalovirus, herpes simplex virus, was a 33-year-old Caucasian exclusively homosexual Pneumocystis carinii, and Candida albicans.78 Other male who was admitted to Beth Israel Medical Center in September 1980 because of bloody diarrhoea, *Presented at the Eastern Ophthalmic Pathology Society Meeting, fever, 40 lb (18 kg) weight loss, and blurred vision in Hamilton, Bermuda, I October 1981. the left eye in association with significant leucopenia. Correspondence to Alan H. Friedman, MD, Department of Oph- Examination revealed a wasted male with a thalmology, Mount Sinai School of Medicine, One Gustave L. Levy temperature of 40°C, generalised lymphadenopathy, Place, New York, NY 10029. USA. perianal ulcerations, and inflammatory colitis. Oph- 372 Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from Cytomegalovirus retinitis: a manifestation of AIDS 373 thalmological examination showed a visual acuity of disseminated cytomegalic inclusion disease of the 20/20 in the right eye and hand motion in the left eye. lungs, central nervous system, gastrointestinal tract, The intraocular pressure was 14 mmHg bilaterally, by and liver. Herpes simplex virus was also isolated from applanation tonometry. The right eye was entirely these organs. normal. A marked afferent pupillary defect was Ocular pathology. Gross examination: The left eye present in the left eye. Slit-lamp examination revealed was obtained for histopathological study and was a moderate anterior uveitis in the left eye, manifested intact, measuring 25 x2 x 24 mm with 5 mm of by moderate aqueous flare and cells and keratic pre- attached optic nerve. The surface of the globe was cipitates on the corneal endothelium. Ophthal- unremarkable. The cornea was clear and measured moscopic examination disclosed an oedematous 11x 10 mm. Transillumination of the eye revealed retina with numerous opaque, white intraretinal some decrease posteriorly. The eye was opened lesions (Fig. 1). The lesions were elliptically shaped horizontally, showing many white infiltrates in the and were orientated towards the optic disc. They fundus which were confluent posteriorly (Fig. 3). were confluent in the macular area, where they There were many scattered haemorrhages. appeared brown tinged. Scattered haemorrhages Microscopic examination: The limbal tissues, were present in the posterior pole and were noted cornea, and angle were clear. The anterior chamber intermittently to the ora serrata on the temporal side. contained a fibrinous, eosinophilic exudate with The optic disc margin was blurred and the disc itself erythrocytes and assorted leucocytes. Much of the was pale yellow. There was a very mild cellular remainder of the anterior segment was unremarkable reaction in the vitreous posteriorly. A fluorescein except for a mild lymphocytic infiltration in the ciliary angiogram in the right eye was unremarkable and in body. Posteriorly the retina showed extensive areas the left eye revealed marked vascular leakage along of necrosis (Fig. 4). The areas of retinal necrosis were the superior and inferior temporal arcades and a diffuse and full-thickness in many areas. Massively relative hypofluorescence in the macular area. enlarged cells with owl's eye appearance were present Extensive serological testing was nondiagnostic, (Fig. 5). Scrutiny of cells in the areas of retinal and multiple cultures, including an aqueous aspirate necrosis revealed intracytoplasmic as well as for bacteria, fungi, and acid-fast bacilli, were intranuclear inclusions (Fig. 6). The majority of the negative. Sequential courses of treatment with enlarged cells were in the range 20 ,um to 30 ,um in amphotericin B initiated for oesophageal candidiasis, diameter and contained intranuclear basophilic broad-spectrum antibiotics, and prednisone produced no significant improvement in either the colitis or the retinal lesions. During the fourth week in hospital, Fig. I Fundus photograph, left eye, case 1. On admission http://bjo.bmj.com/ when the status of the left eye was noted to to the hospital several white intraretinal lesions which are deteriorate, a vitreous tap for virus isolation was confluentin the macular area. There are haemorrhages in the performed. Cytological examination showed macula. Note overlying vitreous haze. lymphocytes; and 6 weeks later the vitreous material Fig. 2 Fundus photograph, left eye, case 1. About 4 weeks after admission. The vitreous is slightly hazy, the optic nerve as well as urine yielded cytomegalovirus. The serum is quitepale, andretinal vessels show narrowing andsclerosis complement fixing antibody titre to this virus was ofthe arteries and sheathing ofthe veins. The white lesions repeatedly 1:128. During the interval fresh retinal have greatly enlarged and become confluent and diffuse. on September 28, 2021 by guest. Protected copyright. lesions had developed in the previously uninvolved Fig. 3 Gross photograph ofleft eye, case 1. The lesions right eye similar to those seen on admission in the left extendfrom the disc to theperiphery and display eye. The lesions in the left eye by this time involved haemorrhages on a white background. A posterior vitreous large areas of the fundus. The optic disc was markedly aspiration, ante mortem, grew out cytomegalovirus. pale, the retinal arteries were narrowed and sclerotic, Fig. 4 Photomicrograph ofleft eye, case 1. A prominent and the retinal veins were sheathed. Diffuse white area ofretinalandretinalpigmentepithelial necrosis atright. multifocal retinal opacifications with focal haem- (Haematoxylin and eosin, x 120). orrhages were scattered throughout fundus (Fig. 2). Fig. 5 Higherpower view ofretina shown in Fig. 4 reveals The patient became progressively obtunded, and necrotic retina with haemorrhage, a cell with many cytoplasmic inclusions (lower left), and a markedly enlarged despite a 10-day course of treatment with intravenous cell, centre. (Haematoxylin and eosin, x 1000). adenine arabinoside (Ara-A), initiated in an effort to Fig. 6 Photomicrograph ofnecrotic retina shows an treat both the cytomegalovirus retinitis and the peri- enlarged cell with many intracytoplasmic inclusions. rectal ulcerations from which herpes simplex virus (Haematoxylin and eosin, x 1800). (type II) had been isolated, he lapsed into coma and Fig. 7 Electron micrograph ofthe nucleus ofa retinal cell died approximately 3 months after admission. demonstrates many viralparticles consistent in structure with General pathology. A general post-mortem
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