sign in sign up
<<
Home , Acute retinal necrosis, Gross examination, Retinitis

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 : 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 ), Beth Israel Medical Center; 3Ophthalmology, "Medicine (Infectious Disease), and ', Lenox Hill Hospital; ', 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 was cultured from a vitreous biopsy. revealed disseminated cytomegalovirus in both patients. Widespread retinal was evident, with typical nuclear and cytoplasmic inclusions of cytomegalovirus. Electron microscopy showed herpes , 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 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 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 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, , 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 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 . The surface of the was cipitates on the corneal endothelium. Ophthal- unremarkable. The 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 . 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 , 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. ; 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 exam- a herpesfamily virus. The central capsomer displays the ination revealed histologically or by virus isolation typical hexagonal configuration. (x200000). Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

374 Alan H. Friedman, et al.

Fig.

Eit

B''-~~~;f

Fig. 4 L FiP. 3 Fig.

4I,

I'6 *

*.1A.' http://bjo.bmj.com/

fts

:::. w~~~~~~ ~~~ ....~~~~~~~~~~~~~~~~~~~~~~~. 4'' ..%..

J.O...... ft-...0a8

+ ta24 U_ on September 28, 2021 by guest. Protected copyright.

Fig S Fig. 6 -#. j _Fig. 7 .* * .M,, * . Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

Cytomegalovirus retinitis: a manifestation of AIDS 375

..Y4,.....

,ig.10 http://bjo.bmj.com/ on September 28, 2021 by guest. Protected copyright.

Fig. IftB

Fig. 12A Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

376 Alan H. Friedman, et al. inclusions 5-10 ,um in diameter and numerous He was readmitted one month later with fever of eosinophilic intracytoplasmic inclusions 0-5-1 0 Zm 40°C and evidence of dehydration. He appeared in diameter (Fig. 6). Areas of the retinal pigment chronically ill. Scattered patches of 'soft exudates' epithelium were necrotic as well (Fig. 6). The were noted in the fundus of the right eye by the adjacent to the optic nerve was infiltrated with admitting internist. Three days later a complete oph- mononuclear cells. The optic nerve head was thalmological examination was performed. Visual markedly swollen and infiltrated with inflammatory acuity was 20/20 in each eye with a myopic correction cells, and the central retinal artery and vein were both in place. Full ocular motility was noted and the occluded. The inflammatory reaction extended into pupillary responses were normal. There was no the posterior vitreous. Viral particles (virions) were preauricular adenopathy. Applanation tensions and demonstrated in the retina by electron microscopy slit-lamp examination of both eyes were entirely (Fig. 7). Structurally the virions contained a normal. There was no evidence of either anterior or hexagonal central capsid surrounded by an envelope. posterior vitritis. The fundus of the right eye had a The cores of many of the virions contained material, large white retinal infiltrate inferonasally along the while some of the cores were empty. Cytomegalo- distribution of retinal vessels, and intraretinal virus was isolated from post-mortem bloody vitreous haemorrhages. A slight disturbance of retinal fluid of the left eye. pigment epithelial was present. The posterior pole showed a few small scattered white retinal lesions 1/4 CASE 2 to 3/4 disc diameter in size and only an occasional A 38-year-old black homosexual male was admitted small intraretinal haemorrhage (Figs. 8A,B,C). The to Lenox Hill Hospital on 17 March 1981 for fever, 20 left eye revealed a few small (less than '/2 disc lb (9 kg) weight loss, cough, odynophagia, diarrhoea, diameter) intraretinal infiltrates and occasional and perianal ulcer. The white cell count was 2 7 x 109/l haemorrhages in the posterior pole in relation to with a moderate lymphopenia (15% lymphocytes); retinal vessels. Fluorescein angiography showed splenomegaly was noted. The patient was anergic to 3 scattered microaneurysms in both eyes with extensive skin test antigens and purified protein derivative leakage over the large inferonasal area of retinal (PPD). There were no ocular symptoms and involvement OD. (Fig. 9). Several of the retinal funduscopic examination on admission was reported arterioles were narrowed in both eyes. The areas of as negative. Examination revealed candida retinitis appeared to involve mainly the deeper layers. oesophagjtis, pancytopenia with a hypoplastic bone Throughout this time the patient remained marrow, and CMV colitis by colonoscopic biopsy. severely lymphopenic, the white blood count was CMV complement fixation titres were 1:128. After 2 8x 109/l with only 3% lymphocytes. Quantification http://bjo.bmj.com/ being treated with intramuscular penicillin for a positive VDRL and fluorescent treponema antibody absorption test (FTA-abs) the patient left the hospital against medical advice.

8

Fig. A, B, C. Clinicalphotographsoffundus, righteye, on September 28, 2021 by guest. Protected copyright. patient 2, reveal large white intraretinal lesions inferotemporal to the macula. Scattered small haemorrhages are present. Fig. 10 Low-power photomicrograph ofretina, case 2, shows extensive area ofretinal and retinal pigment epithelial necrosis. (Haematoxylin and eosin, x200). Fig. I1 A, B. Higher power views ofretina shown in Fig. 10. Cells display prominent eosinophilic intracytoplasmic and basophilic intranuclear inclusion bodies. (Haematoxylin and eosin, x 1000). Fig. 12 A, B. Immunoperoxidase localisation of cytomegalovirus proteins in a section ofeye (A). Intracellular brown reaction product is seen in numerous cells in the retinal and pigment layers, many ofwhich lack obvious inclusion bodies. Weak endogenous activity within choroidal vessels is also seen in B, an adjacentsection stained Fig. 9 Fluorescein angiogram ofright eye, patient 2, in late with preimmune IgG. Black pigmented epithelial cells and phase. There is marked retinal vascular leakage with chromatophores are also noted in both sections. (Methylene evidence ofinvolvement ofthe retina at all levels. No blue counterstain, x50). choroidal pattern is visible in the involved area. Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

Cytomegalovirus retinitis: a manifestation of AIDS 377 of T cell numbers and function revealed only 5% T Ocularpathology. A posterior segment of the right cells in the peripheral blood (normal 60-80%) and an eye only was removed for histopathological study. abnormal response to mitogen stimulation with Examination revealed extensive areas of full- concanavalin-A and staphylococcal proteins (Dr thickness necrosis of the retina and retinal pigment Gillian Sheppard, New York Hospital, New York, epithelium (Fig. 10). Massively enlarged cells with NY). Oral and esophageal candidiasis persisted intranuclear and intracytoplasmic inclusions were requiring treatment with amphotericin B. Interstitial noted (Figs. 11A, B). pneumonia was diagnosed. Bronchoscopy revealed Indirect immunoperoxidase localisation of cyto- numerous CMV inclusions, and routine cultures grew megalovirus proteins was done on paraffin sections of Haemophilus, parainfluenzae and pneumococcus. the eye with antibody to cytomegalovirus (North- Broad spectrum antibiotics (cefamandole and eastern Biomedical Laboratories, Inc.) absorbed Bactrim (sulphamethoxazole and trimethoprim)) with uninfected cells of the cell line in which the virus were initiated; the patient remained febrile. Two was grown. (Detailed methods for the purification weeks after admission the fundus OD showed and characterisation of this antibody and the staining enlargement of the inferonasal area of retinal procedure will be reported elsewhere.) Numerous infiltration with a more prominent haemorrhagic cells in all layers of the retina and occasional component. The left eye showed minimal enlarge- pigmented epithelial cells contained reaction ment of the lesions previously described. Within 2 product, often in the absence of abnormality (Fig. weeks a massively haemorrhagic area of retinitis was 12A). An adjacent control section stained with noted OD and the left eye appeared similar to the preimmune IgG shows only endogenous peroxidase right, with large areas of retinal infiltration and only a activity within choroidal vessels and black pigment in few haemorrhages. No vitreous haze was noted. The epithelial cells and chromatophores (Fig. 12B). fovea of both eyes were spared, but it was impossible to test visual acuity. Discussion The patient underwent exploratory laporotomy and splenectomy on 30 June 1981 because of suspicion of Cytomegalovirus (CMV) is a species-specific DNA an occult lymphoma. Histopathological examination virus characterised by a bizarre 'cytomegalic' effect of lymph nodes and spleen revealed CMV inclusions. on host cells.'2 Human cytomegalovirus is a herpes Sputum culture at this time, as well as culture of the virus (as are herpes simplex, varicella-zoster, and biopsied lymph nodes and spleen, grew Myco- Epstein-Barr ) morphologically characterised bacterium avium intracellulare. All stains for acid-fast by a capsid composed of 162 elongated hexagonal bacteria (AFB) of the sputum and excised tissues prisms (capsomers) enveloped by a bilaminar http://bjo.bmj.com/ were negative. The patient remained unreactive to membrane probably derived from the host cell purified protein derivative (PPD) of intermediate and nucleus.'2 13 Once infected, the host cell synthesises high strengths, as well as to candida, trichophyton, viral particles and produces the pathognomonic and . The CMV complement fixation titre was 'owl's eye' intranuclear and multiple intracytoplasmic 1:64, and CMV (ELISA) IgG titres had fallen from inclusions and a swollen cytoplasm.'2 Although the 1:128 to 1:32 (Dr Donald Armstrong, Memorial- herpesviruses cannot be distinguished from each Sloan Kettering Cancer Center, New York, NY). other ultrastructurally, the cytopathic effect and on September 28, 2021 by guest. Protected copyright. CMV ELISA IgM titres (indicative ofacute infection) inclusions produced by CMV are so distinctive that it were undetectable. Multiple urine and sputum can be used to distinguish CMV from other members cultures for CMV were negative. The right fundus of the herpesvirus family. 12 showed large confluent patches of haemorrhagic Serological studies indicate that previous infection retinitis in many areas still in a perivascular has occurred in about 80-90% ofmiddle-aged adults. 14 distribution and sparing fixation. The lesions OS also Acute infection may be accompanied by an elevation increased in size and became more haemorrhagic. of serum IgM antibodies for CMV.'5 Complement The appearance of both eyes was now the classic fixing antibodies, when present, demonstrate the tomato sauce ('catsup') and crumbled cheese existence of prior infection with the virus, though appearance of CMV retinitis. Four days later the they may fall to undetectable levels with time.'6 This patient expired. observation may indicate that the incidence of prior General pathology. A general post-mortem infection with CMV is even higher than previous examination performed days later revealed studies suggest.'6 Most authorities believe that once disseminated cytomegalic inclusion disease of the infected, the host carries the CMV genome and lungs, colon, spleen, lymph nodes, liver, and possibly viral particles for a lifetime, though the exact adrenals. Viral cultures were negative. There were no storage sites remain unknown.'4 The clinician may lesions in the brain. diagnose active CMV infection by an increase in Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

378 Alan H. Friedman, et al. complement fixation antibodies, culture of blood or a healthy adults have been reported. Foerster27 lesion, or biopsy confirmation of the classic histo- described a patient with unilateral uveitis in whom pathological picture.6 Excretion of the virus in the histopathological studies of the eye revealed granu- urine, saliva, semen, and from the uterine cervix is lomatous choroiditis and retinal necrosis with typical widespread" and does not necessarily indicate active CMV inclusions. Chawla et al.28 described a disease, but viraemia probably does and correlates previously healthy woman with an Epstein-Barr best with clinical findings in immunosuppressed virus-negative mononucleosis-like syndrome who patients.'4.18 19 Virus has been isolated from tears of had pinpoint chorioretinal lesions. The diagnosis of patients with and without retinitis and does not CID retinitis was made on the basis of an increase in appear to correlate with ocular involvement.20 In complement fixing antibodies. No culture on patho- patients with retinitis cultures of subretinal fluid and logical studies was obtained. There was no retinal vitreous may be positive.35 1621 In patients with haemorrhage or coalescence or expansion of the panuveitis aqueous taps have yielded live virus.'516 lesions as is usually seen in CID retinitis.22 2 26 Serological studies, however, may have certain pit- Ocular involvement in CID is predominantly seen falls, as in one of our patients and in previously in the retina, and the retinitis which may occur is reported cases,3 where complement fixing antibodies characterised by white intraretinal lesions, often may not rise. Alternatively immunohaemagglutina- confluent, retinal haemorrhages, microaneurysms, 29 tion of immunofluorescent titres may confirm retinal oedema, attenuated vessels, perivascular infection.'4 It has also been noted that a fall in sheathing, and exudative detachment.2' An optic complement fixing titres in the presence of active nerve head mass,30 optic , vitritis, and infection signifies a poor prognosis.'4 anterior uveitis are often present.3'132 Other con- Active cytomegalic inclusion disease (CID) may be ditions may mimic the ocular picture of CID and broadly divided into congenital and acquired include herpes simplex retinitis,3334 toxo- infection. Congenital infection classically occurs in plasmosis,35Candida sp. (and other fungi), Beh,et's premature infants and is associated with syndrome, the syndrome of unilateral or bilateral microcephaly, hepatosplenomegaly, thrombocyto- (ARN or BARN syndrome)36 37 penia, purpura, and periventricular calcifications. and subacute sclerosing panencephalitis (SSPE).38 and its sequelae, deafness and intel- The association between male homosexuality and lectual dysfunction, may be observed if the infant acquired sexually transmitted disease is well known. survives. 4 The congenital retinitis is often associated Localised herpes simplex , giardiasis, with optic atrophy. The disease is probably acquired amoebiasis, viral hepatitis, syphilis, and gonorrhoea transplacentally and at times may be devoid of clinical are endemic among homosexual males and have http://bjo.bmj.com/ manifestations. Indeed one-third of infants dying of usually been attributed to venereal transmission and unrelated causes show classical CMV inclusions in the frequent contacts with different partners. A high salivary glands. 3 incidence of cytomegalovirus shedding in urine and Acquired CID infection in adults may affect the semen has been reported in asymptomatic homo- central nervous system, retina, reticuloendothelial sexual men, the significance of which is unclear."' system, kidneys, adrenals, and lungs. 3 The acquired Recently reports have appeared linking homosexual disease in adults usually occurs in one of 3 clinically males with the development of a severe acquired on September 28, 2021 by guest. Protected copyright. different manners: (1) in immunosuppressed patients, immunodeficiency manifested by weight loss, fever, (2) following multiple blood transfusions (post- and severe, unrelenting, often fatal infection with perfusion syndrome), and (3) in an infectious- opportunistic micro-organisms including cyto- mononucleosis-like or infectious hepatitis syndrome. megalovirus, herpes simplex virus, Pneumocystis In immunosuppressed patients CID is manifest carinii, cryptococcosis, and Candida albicans. 8" clinically by viraemia with positive blood cultures, Homosexual males may also develop as part of their arthralgias, fever, leucopenia, pneumonitis, retinitis, spectrum of acquired disease, the 'gay bowel' and hepatitis. In healthy individuals it may present as syndrome9 and Kaposi's sarcoma.'0 A characteristic an Epstein-Barr virus-negative mononucleosis of the acquired immunodeficiency syndrome is a syndrome with atypical lymphocytosis. Until recently reversal of the normal T-helper cell to T-suppressor ocular CID has been reported almost exclusively in cell ratio, with a profound decrease in the absolute patients with well-defined immunodeficiency, such as numbers of T-helper cells." Acute viral infections, those with neoplastic disorders of the haemopoietic especially of the herpesvirus family, including cyto- and reticuloendothelial systems or treatment with megalovirus39 and Epstein-Barr virus,404' have been immunosuppressive therapy, the most common being shown to cause immunosuppression and reversals of renal transplant recipients. 13 14 16 19 22-26 Until the helper/suppressor cell ratio. Although many recently only 2 cases of CID retinitis in normal, theories have been proposed to explain the outbreak Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

Cytomegalovirus retinitis: a manifestation of AIDS 379 of acquired immunodeficiency-including exposure to 10 CDC-Kaposi's sarcoma and pneumocystis pneumonia among homosexual men-New York City and California. Morbid drugs," autoimmunisation due to parenteral Mortal Weekly Rep. 3 July 1981: 30(25): 305-7. exposure to sperm inoculated through colonic 11 Mildvan D, Mathur U, Enlow RW, etal. Opportunistic infections abrasions,43 and/or infection with either known or as and immune deficiency in homosexual men. Ann Intern Med in yet unknown transmissible agents-all are at present press. speculative and need thorough investigation. 12 Schwartz JN, Daniels CA. Shivers JC, Klintworth GK. Experimental cytomegalovirus infection. Am J Pathol 1974; 77: The present cases are noteworthy in that both men 477-92. were exclusively homosexual, presented with a 13 Boniuk I. The and the eye. Int Ophthalmol picture of wasting, diarrhoea, and leucopenia, Clin 1972; 12: 169-90. developed oesophageal candidiasis, showed pro- 14 Weinstein L, Fields B, eds. Seminars in infectious . New York: Thieme-Stratton, 1980; 3: 243-64. gressive CMV retinitis, and died with disseminated 15 Berger BB, Weinberg RS, Tessler HA, et al. Bilateral cyto- CMV. Of potential clinical significance in case 1 was megalovirus panuveitis after high dose corticosteroid therapy. the ability to make the diagnosis of ocular cyto- Am J Ophthalmol 1979; 88:1020-5. megalic inclusion disease ante mortem by means of 16 Nicholson DH. Cytomegalovirus infection of the retina. Int Ophthalmol Clin 1975; 15: 151-62. virus isolation from a vitreous tap. Although antiviral 17 Drew WL, Mintz L, Miner RC, et al. Prevalence of cyto- therapy in this patient was unsuccessful, it is hoped megalovirus infection in homosexual men. J Infect Dis 1981; 143: that earlier suspicion and confirmation of the 188-92. diagnosis in this fashion might improve outcome in 18 Fiala M, Chatterjee SN, Carson S. etal. Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes. Am J future patients. At present, however, the best Ophthalmol 1977; 84: 567-73. treatment has not been identified except for the dis- 19 Fiala M, Payne JE, Berne TV. Epidemiology of cytomegalovirus continuation of immunosuppressive agents. Limited infection after transplantation and immunosuppression. J Infect experiences with transfer factor' and antiviral drugs Dis 1975; 132: 421-33. 20 Cox F, Meyer D, Hughes WT. Cytomegalovirus in tears from such as adenine arabinoside,25 floxacidine (FIAC), patients with normal eyes and with acute cytomegalovirus and and acyclovir have yielded only rare successes.' 31 33 chorioretinitis. Am J Ophthalmol 1975; 80: 817-24. The possible therapeutic role of interferon and 21 Broughton WL, Cupples HP, Parver LM. Bilateral retinal immunomodulators will need to be clarified by detachment following cytomegalovirus retinitis. Arch Ophthalmol 1978; %: 618-9. controlled clinical trials. 22 Murray HW, Knox DL, Green WR, et al. Cytomegalovirus retinitis in adults, a manifestation of disseminated viral infection. We are grateful to Mr Robert Campanile and Mr Bruce Bailey for the Am J Med 1977; 63: 574-84. photography and to Ms Leona Brin for typing the manuscript. 23 Astle JN, Ellis PP. Ocular complications in renal transplant This work was supported in part by an unrestricted grant from Fight patients. Ann Ophthalmol 1974; 6: 1269-74.

for Sight, Inc., New York, NY, and National Eye Institute Core 24 Malek GH, Kisken WA. Problems in diagnosis and treatment in http://bjo.bmj.com/ Grant No. EY 01867. renal transplantation. Am J Surg 197t); 119: 334-6. 25 Pollard RB, Egbert PR, Gallagher JG, et al. Cytomegalovirus References retinitis in immunosuppressed hosts. 1. Natural history and effects of treatment with adenine arabinoside. Ann Intern Med 1980; 93: I Cangir A, Sullivan MP. The occurrence of cytomegalovirus 655-64. infections in childhood leukemia. Report of three cases. JAMA 26 Egbert PR, Pollard RB, Gallagher JG, et al. Cytomegalovirus 1966; 195: 616-22. retinitis in immunosuppressed hosts. II. Ocular manifestations. 2 Duvall CP, Casazza AR, Grimley PM, et al. Recovery of cyto- Ann Intern Med 1980; 93: 664-7t).

megalovirus from adults with neoplastic disease. Ann Intern Med 27 Foerster HW. Pathology of granulomatous uveitis. Surv on September 28, 2021 by guest. Protected copyright. 1966; 64: 531-41. Ophthalmol 1959; 4: 283-326. 3 Aaberg TM, Cessarz TJ, Rytell MW. Correlation of virology and 28 Chawla HB, Ford MD, Munro JF, et al. Ocular involvement clinical course of cytomegalovirus retinitis. Am J Ophthalmol in cytomegalovirus infection in a previously healthy adult. Br Med 1972; 74: 407-15. J 1976;.ii: 281-2. 4 Smith ME. Retinal involvement in adult cytomegalic inclusion 29 Augsburger JJ, Henry RY. Retinal aneurysms in adult cyto- disease. Arch Ophthalmol 1964; 72: 44-9. megalovirus retinitis. Am J Ophthalmol 1978; 86: 794-7. 5 Burns RP. Cytomegalic inclusion disease uveitis. Report of a case 3t) Marmor MF, Egbert PR, Egbert BM, et al. Optic nerve head with isolation from aqueous humor of the virus in tissue culture. involvement with cytomegalovirus in an adult with lymphoma. Arch Ophthalmol 1959; 61: 376-87. Arch Ophthalmol 1978; %: 1252-4. 6 Smith TF. Cytomegalovirus infections: current diagnostic 31 Chumbley LC, Robertson DM, Smith TF, et al. Adult cyto- methods. Mayo Clin Proc 1981; 56: 767. megalovirus inclusion retino-uveitis. Am J Ophthalmol 1975; 80: 7 Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii 807-16. pneumonia and mucosal candidiasis in previously healthy homo- 32 deVenecia G, Rhein GM, Pratt MW, et al. Cytomegalic inclusion sexual men: evidence of a new acquired cellular immuno- retinitis in an adult. A clinical, histopathologic, and ultra- deficiency. N EnglJ Med 198 1; 305:1425-3 1. structural study. Arch Ophthalmol 1971; 86: 44-57. 8 Siegal FP, Lopez C. Hammer GS, et al. Severe acquired immuno- 33 Cogan DG. Immunosuppression and . Am J deficiency in male homosexuals, manifested by chronic perianal Ophthalmol 1977; 83: 777-88. ulcerative herpes simplex lesions. N Engl J Med 1981; 305: 34 Minckler DS, Mcleon EB, Shaw CM, et al. Herpes virus hominis 1439-44. encephalitis and retinitis. Arch Ophthalmol 1976; 94: 9 Phillips SC, Mildvan D, William DC, et al. Sexual transmission of 89-95. enteric protozoa and helminths in a venereal-disease-clinic popu- 35 Friedmann CT, Knox DL. Variations in recent active toxo- lation. N Engl J Med 1981; 305: 603-6. plasmosis. Arch Ophthalmol 1969; 81: 481-93. Br J Ophthalmol: first published as 10.1136/bjo.67.6.372 on 1 June 1983. Downloaded from

380 Alan H. Friedman, et al.

36 Young SJA, Bird AC. Bilateral acute retinal necrosis. Br J 41 De Waele M, Thielemans C, Van Camp BKG. Characterization Ophthalmol 1978; 62: 581-90. of immunoregulatory T cells in EBV-induced infectious mono- 37 Price Jr FW, Schlaegel Jr TJ. Bilateral acute retinal necrosis. Am nucleosis by monoclonal antibodies. N Engl J Med 1981; 304: J Ophthalmol 1980; 89: 419-24. 460-2. 38 et Nelson DA, Weiner A, Yanoff M, al. Retinal lesions in 42 Durack DT. Opportunistic infections and Kaposi's sarcoma in subacute sclerosing panencephalitis. Arch Ophthalmol 1970; 84: homosexual men. N Engl J Med 1981; 305: 1465-7. 613-21. 39 Rinaldo CR Jr, Camey WP, Richter BS, et al. Mechanisms of 43 Hurtenbach U, Shearer GM. Germ cell-induced immune immunosuppression in cytomegalovirus mononucleosis. J Infect suppression in mice: Effect of inoculation of syngeneic Dis 1980; 141: 488-95. spermatozoa on cell-mediated immune responses. J Exp Med in 40 Reinherz EL, O'Brien C, Rosenthal P, et al. The cellular basis for press. viral-induced immunodeficiency: analysis by monoclonal anti- 44 Keith CG, Lanauze J. Cytomegalovirus retinitis. Med J Aust bodies. J Immunol 1980; 125: 1269-74. 1980; i: 24-6. http://bjo.bmj.com/ on September 28, 2021 by guest. Protected copyright.