Robert Y. Foos

Acquired Immune Deficiency Syndrome: Ocular Manifestations

The acquired immune deficiency syndrome (AIDS) is a recently described disorder of cellular immunity in homosexuals, intravenous drug abusers, and Haitians. Manifestations include Kaposis sarcoma, Pneumocystis carinii pneumonia, and other opportunistic infections. Ophthalmic and autopsy examinations of 30 patients at UCLA revealed frequent ocular abnormalities. Findings included cotton-wool spots (16 patients), cytomegalovirus retinitis (eight patients), conjunctivitis and keratitis (four patients), conjunctival Kaposis sarcoma (three patients), Mycobacterium avium intracellulare choroidal granulomas (one patient), and retinal periphlebitis (one patient). We feel that the presence of cotton-wool spots in patients with this syndrome indicates a poor prognosis. Immunologic and electronmicroscopic studies of cotton-wool spots revealed no infectious agents or immunoglobulin deposition. Cytomegalovirus retinitis always was associated with a fatal outcome. The retinitis was characterized by an acute inflammatory reaction in 50% of patients. Ophthalmologists should be aware of the syndrome and its ocular manifestations.

Acquired Immune Deficiency Syndrome: Pathogenic Mechanisms of Ocular Disease

A gross, light, and electron microscopic study of the eyes from 35 consecutive autopsy cases of the acquired immune deficiency syndrome revealed cotton-wool spots (71% of cases), retinal hemorrhage in areas without cytomegalovirus infection (40%), cytomegalovirus retinitis (34%) with associated retinal detachment, Roths spots (23%), retinal microaneurysms (20%), papilledema (14%), conjunctival Kaposis sarcoma (9%), cryptococcal chorioretinitis (6%), Mycobacterium avium-intracellulare in retina and in choroidal granulomas (6%), ischemic maculopathy (6%), bilateral keratitis (3%), and herpes simplex retinitis (3%). Ocular infection with candida or toxoplasmosis were not found in this autopsy series. Immunocytologic studies demonstrated deposition of immunoglobulins in arteriolar walls, consistent with immune complex mediated disease. Ultrastructural studies showed a vasculopathy in the areas near cotton-wool spots. A mechanism is proposed linking the deposition of immune complexes with subsequent small vessel lesions, ischemia, cotton-wool spots and later spread of cytomegalovirus to retina via damaged vascular endothelium.

Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome

In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.

Vitreoretinal juncture —Simple epiretinal membranes

Simple epiretinal membranes are delicate cellular membranes occurring at the vitreoretinal juncture. They produce no symptoms or macroscopically detectable change, but are a common microscopic finding in enucleated eyes. The ultrastructural features of these membranes were studies in eight eyes surgically enucleated for unrelated ocular conditions or for orbital lesions. Simple epiretinal membranes are composed exclusively of glial cells. Evidence is presented that these cells derive from accessory glia of the superficial retina which react to a variety of stimuli and migrate through breaks in the retinal surface (which may later heal). This pathogenic sequence is discussed in light of present knowledge of retinal accessory glia and their role in retinal disease.

Concurrent Herpes Simplex and Cytomegalovirus, Retinitis and Encephalitis in the Acquired Immune Deficiency Syndrome (AIDS)

We present a case of bilateral herpes simplex and cytomegalovirus retinitis and concurrent encephalitis following acyclovir therapy in a homosexual male with the acquired immune deficiency syndrome (AIDS). At autopsy, herpes simplex virus antigens were readily detected in all retinal layers, retinal pigment epithelium, and choriocapillaris, using an immunoperoxidase technique, whereas herpes simplex antigens in the brain were localized in restricted foci of vascular and subependymal parenchymal cells. Cytomegalovirus antigens were identified in cells in all layers of retina, in retinal pigment epithelium, and in subependymal parenchymal cells in the brain. No cytomegalovirus antigens were detected in any vascular endothelium, in choroid, or anterior to the ora serrata. The widespread expression of herpes simplex virus antigens in this patients retinas is in marked contrast to the restricted foci of herpes simplex antigens limited to the subependymal region of the brain, and is similar to that seen in murine models of herpes simplex retinitis produced by acyclovir-resistant viral mutants.

Myelinated Retinal Nerve Fibers

In a series of 3,968 consecutive autopsies, myelinated nerve fibers of the retina were presented in 39 (0.98%) cases and bilateral in three (7.7%) affected cases; thus, 42 (0.54%) of the 7,936 eyes examined were affected. Myelinated nerve fiber lesions appeared as white or gray-white striated patches corresponding in shape to the distribution of retinal nerve fibers and demonstrated frayed borders. Myelinated retinal nerve fibers were continuous with the optic nerve head in 14 (33%) and discontinuous with the optic nerve head in 28 (66%) affected eyes. By light microscopy and electron microscopy, myelinated retinal fibers were marked by a ganglion cell axon surrounded by concentric lipoprotein lamellae that formed the myelin sheath. Glial cells were often prominent near the myelin sheaths, but other components of the sensory retina were morphologically normal. Clinically, 32 patients with myelinated retinal nerve fibers had comparable overall features, visual field defects less extensive than expected on the basis of ophthalmoscopic appearance, and normal findings on fluorescein angiography. Four patients had a syndrome characterized by ipsilateral extensive myelinated retinal nerve fibers, anisometropic myopia, amblyopia, and strabismus.

Detection of HLA class I and II antigens in rejected human corneal allografts.

We compared the distribution of HLA-ABC (class I) and HLA-DR (class II) antigens on fresh human donor corneal tissue, donor corneas following a 72-hour storage in McCarey-Kaufman (M-K) medium, and corneal buttons from patients with allograft rejection and with chronic herpetic stromal keratitis. Incubation in M-K media had little or no effect on the distribution of HLA antigens as compared with fresh tissue. In contrast to control corneas, both HLA class I and II antigens were detected on corneal endothelial cells, cells in the stroma, and on basal epithelial cells in rejected allografts. Corneal endothelium in herpetic buttons did not express detectable HLA antigens. HLA-DR positive Langerhans cells were demonstrated in the central corneal epithelium of rejected allografts, as well as in herpetic corneas, but not in control corneas except at the limbus. Based upon these observations, a theory of corneal allograft rejection in humans is proposed based upon the induction of class I HLA-ABC and class II HLA-DR antigens on cells in the donor button by a factor(s) associated with cellular inflammation.

Quantitation of tumor seeding from fine needle aspiration of ocular melanomas.

Twenty-two fine needle (30 gauge) aspirations were performed in eyes enucleated for the clinical diagnosis of melanoma. Cytologic preparations were evaluated for adequacy of material, and needle tracts were evaluated for tumor implantation. A scleral marking method was used to identify all needle tracts. The number of tumor cells in tracts of direct transscleral aspirates was compared to those in tracts of indirect aspirates that traversed the anterior chamber or vitreous. Cellular material obtained with 30-gauge needles was sufficient for the diagnosis of malignant melanoma in all but one case. While 14 of 21 (67%) of all fine needle aspiration tracts and eight of 15 (53%) of indirect tracts contained tumor cells, the number of tumor cells was less than that associated with tumor growth in experimental models. Indirect aspirate tracts contained significantly fewer cells than tracts of direct aspirates (P less than .001).

Dual Infection of Retina With Human Immunodeficiency Virus Type 1 and Cytomegalovirus

We examined retinal tissue from eight human immunodeficiency virus type 1 (HIV-1) seropositive patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex for evidence of dual infection with HIV-1 and cytomegalovirus. Culture demonstrated simultaneous infection with HIV-1 and cytomegalovirus in two of 13 retinal specimens. This was confirmed by both immunofluorescence and immunohistochemical staining. Moreover, coinfection of individual cells with cytomegalovirus and HIV-1 was observed by immunohistochemical staining. Infection of retina with cytomegalovirus or HIV-1 alone occurred in one and six of the 13 retinal specimens, respectively. HIV-1 antigens were present on scattered cells in all layers of the retina and on retinal vascular endothelium. HIV-1 was isolated from retinal tissue derived from eyes both with and without gross ocular lesions. Cytomegalovirus antigens were found in all layers of the retina, but not on vascular endothelial cells. The atypically rapid clinical progression of retinitis in one of the patients with dual HIV-1 and cytomegalovirus infection suggests the possibility that interactions between these two viruses may influence retinal disease in patients with AIDS.

Retinal Periphlebitis and Retinitis in Multiple Sclerosis: I. Pathologic Characteristics

Eyes from 47 autopsy cases of multiple sclerosis were studied pathologically. Lymphocytic or granulomatous retinal periphlebitis was found in four cases (seven eyes); focal lymphocytic or granulomatous retinitis was present in three cases (five eyes). These findings were correlated with optic nerve changes (periphlebitis, neuritis, leptomeningitis, and atrophy), retinal venous sclerosis, uveitis, central nervous system involvement, clinical activity of disease at death, and with ultrastructural and immunopathological retinal findings.