Bilateral acute acquired toxoplasmic retinochoroiditis after steroid therapy for hantavirus pulmonary syndrome: case report.

Description of a case of acute acquired ocular toxoplasmosis following hantavirus pulmonary syndrome. A 41-year-old man presenting hantavirus pulmonary syndrome, confirmed in the laboratory by detection of IgM antibodies to the virus, was submitted to high doses of intravenous corticosteroids for two months. After clinical improvement of hantavirus pulmonary syndrome the patient presented visual loss in both eyes that was secondary to a toxoplasmosis retinitis. The retinitis resolved with anti-toxoplasma therapy. Acquired toxoplasmic retinochoroiditis can occur following steroid therapy for hantavirus pulmonary syndrome.

Poststreptococcal syndrome uveitis: a descriptive case series and literature review.

PURPOSE: To describe the clinical features in a series of patients with poststreptococcal uveitis and to review literature on the pathophysiology and management. DESIGN: Retrospective and descriptive case series. PARTICIPANTS: Ten consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996 and 2003. METHODS: Review of patient case notes. MAIN OUTCOME MEASURES: Age, laterality, clinical features, and anti-streptococcal lysin O titers. RESULTS: Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All our cases had bilateral nongranulomatous inflammation and raised anti-streptococcal lysin O titers. Collating data from previous reports and this series showed that 96% of the patients were below 40 years of age, and 87.5% had evidence of previous streptococcal infection. One third of the patients had posterior segment involvement. In our patients, this was in the form of vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis. CONCLUSIONS: Poststreptococcal syndrome uveitis should be considered in the etiology of acute bilateral nongranulomatous uveitis in children and young patients.

Parainfluenza 1 (6/94) virus-induced white matter degeneration: enhancement by adoptive transfer of virus-sensitized immunocytes.

Intracerebral (i.c.) inoculation of parainfluenza 1 (6/94) virus into weanling Lewis rats produced meningitis, choroiditis, ependymitis, and a rare noninflammatory white matter degeneration (WMD). Adoptive transfer of immune spleen cells (ISC), 3 to 5 days after virus infection, significantly increased the incidence of WMD. Conversely ISC given 2 days prior to virus infection not only protected rats from developing WMD, but also from developing meningitis, choroiditis, or ependymitis. Thus the temporal relationship of 6/94 virus inoculation to the virus-specific immune response appears critical in determining whether WMD will develop in association with 6/94 virus infection. Although sensitized immunocytes may prevent pathologic changes if given prior to virus inoculation, such immunocytes enhance the production of WMD if given after such inoculation. These studies underline the dual role of the immune response in 6/94 virus infection, and indicate that 6/94 virus-induced WMD is, in part, immunemediated.

Immunopathology of acute experimental histoplasmic choroiditis in the primate.

The immunopathologic features of experimental acute histoplasmic choroiditis were studied in the nonhuman primate. Using an indirect immunoperoxidase technique, a panel of hybridoma-derived anti-human monoclonal antibodies, recognizing distinct lymphoid cell and macrophage surface antigens, have been adapted for use in the primate system. Twenty-two individual foci of histoplasmic choroiditis from five eyes were studied at time periods from 20 to 60 days post intracarotid injection of yeast phase Histoplasma capsulatum. A mononuclear and granulocytic cell infiltration was seen in all lesions. The predominant cell type was the CAPPEL+ T lymphocyte (suppressor/cytotoxic subset). Other cell types found in smaller numbers were OKT4+ T cells (helper/inducer subset), OK7+ (peripheral B lymphocytes), IgD+ (mantle B cells) and OKM1+ cells (macrophages and polymorphonuclear leukocytes). Herein, we present immunopathologic data on the acute phase of experimental ocular histoplasmosis.

Induction of experimental autoimmune anterior uveitis by a self-antigen: melanin complex without adjuvant.

PURPOSE: Experimental autoimmune anterior uveitis (EAAU) is an organ-specific autoimmune disease induced by immunization with bovine melanin-associated antigen (MAA) and two adjuvants (complete Freund's adjuvant and purified pertussis toxin). This study was undertaken to explore whether an adjuvant is required in the induction of EAAU. METHODS: Insoluble MAA was extracted from the bovine iris and ciliary body. Soluble bovine MAA was derived by treatment of insoluble MAA with the proteolytic enzyme, V8 protease. Lewis rats were immunized with the insoluble or soluble antigen, with or without adjuvant (complete Freund's adjuvant and purified pertussis toxin). Adoptive transfer of CD4+ and CD8+ T cells was performed to investigate the pathogenesis of EAAU. RESULTS: Experimental autoimmune anterior uveitis can be induced in Lewis rats by immunization with 100 g insoluble bovine MAA alone without the use of adjuvants. The disease can be adoptively transferred to naive syngenic rats by primed CD4+ T cells. In contrast, soluble bovine MAA was not uveitogenic unless adjuvants were employed. CONCLUSIONS: The data suggest that EAAU can be induced in the Lewis rat without addition of an adjuvant. Future studies concerning the pathogenesis of EAAU can now be performed without the possible confounding effect of an adjuvant.

Cyclosporine therapy suppresses ocular and lacrimal gland disease in MRL/Mp-lpr/lpr mice.

PURPOSE: MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune disease characterized by lymphoproliferation, vasculitis, glomerulonephritis, autoantibody production, and ocular and lacrimal gland inflammation. Lacrimal gland lesions in MRL/lpr mice are a model for the human disorder Sjögren's syndrome. The target organ lesions in MRL/lpr mice, including those in the eye and lacrimal gland, are composed largely of CD4+ T cells, with lesser numbers of CD8+ T cells and B cells. Cyclosporine therapy was evaluated for its effect on the autoimmune disease, particularly in the eye and lacrimal gland. METHODS: MRL/lpr mice were administered cyclosporine intraperitoneally at a dosage of 2 mg daily from age 1 to 5 months. Animals were killed at 5 months and evaluated for the presence of autoimmune disease. Control groups consisted of animals given daily injections with either saline or the cyclosporine diluent. RESULTS: Cyclosporine therapy was effective in reducing the ocular and lacrimal gland disease. Intraocular inflammation was present in 73% of control animals but in only 15% of cyclosporine-treated animals (P < 0.003). Multifocal lacrimal gland inflammatory infiltrates were present in 100% of controls but in only 23% of cyclosporine-treated animals (P < 0.0001). Mean percent area involved by lacrimal gland inflammation was reduced from 19.7% to 4.7% by cyclosporine therapy (P = 0.0003). Systemic autoimmune disease manifestations, including lymphoproliferation, vasculitis, glomerulonephritis, and serologic abnormalities, also were improved. CONCLUSIONS: Chronic cyclosporine therapy, started at an early age, is effective in controlling the autoimmune disease in MRL/lpr mice, including the ocular and lacrimal gland lesions.

Epstein-Barr virus antibodies in multifocal choroiditis and panuveitis.

Although it has been reported that patients with multifocal choroiditis and panuveitis have serologic evidence of a chronic or persistent Epstein-Barr virus infection, our patients did not seem to have other stigmata of Epstein-Barr virus infection. To reappraise the serologic evidence of chronic Epstein-Barr virus infection, the Epstein-Barr antibody levels in 11 patients with multifocal choroiditis and panuveitis and 11 sex- and age-matched control patients were measured. Neither the antiviral capsid antigen IgG (P = .15) nor the antinuclear antigen (P = .2) antibody titers of the patients with multifocal choroiditis and panuveitis were significantly different than those of the control patients. Neither the patients with multifocal choroiditis and panuveitis nor the control patients had increased antiviral capsid antigen IgM titers. One patient with multifocal choroiditis and panuveitis and three control patients had positive anti-early antigen antibody titers (P = .59). The results of this study do not support the hypothesis that patients with multifocal choroiditis and panuveitis have serologic evidence of chronic or persistent Epstein-Barr virus infection as a characteristic finding.

Epstein-Barr viral antibodies in multifocal choroiditis and panuveitis.

A syndrome of multifocal choroiditis, pigment epithelial disturbance, and inflammatory vitreous cells was found to be associated with Epstein-Barr virus specific antibodies. The ten patients in this series had positive viral capsid antigen IgM or Epstein-Barr early antigen antibody titers. Patients with this syndrome were generally healthy and had no history of a clinical episode of infectious mononucleosis. No patient from the control group with other ocular diseases had positive viral capsid antigen IgM or early antibody titers. All patients in the study group and most of the control patients had viral capsid antigen IgG and Epstein-Barr nuclear antigen antibodies, indicating a previous exposure to the virus as expected in an adult population.

Lack of the HLA-DR2 specificity in multifocal choroiditis and panuveitis.

The prevalence of the HLA-B7 and HLA-DR2 specificities in 17 unrelated patients with multifocal choroiditis and panuveitis, 11 with and six without subretinal neovascularisation, was evaluated and compared with those of two different groups. The first group was 17 patients with subretinal neovascularisation associated with presumed ocular histoplasmosis syndrome, and the second was a group of 105 eye patients with no retinal disease. HLA-DR2 was not found in any patient with multifocal choroiditis and panuveitis, but it was found in 13 patients with presumed ocular histoplasmosis syndrome (p = 6.72 x 10(-5), comparison of the groups with subretinal neovascularisation). The lack of HLA-DR2 was also significant in comparison with the control group of eye patients (p = 0.041). This study suggests that patients with multifocal choroiditis and panuveitis and presumed ocular histoplasmosis syndrome have differing genetic predispositions, though the fundus pictures in these entities have many similarities.

The role of T-lymphocytes in the reactivation of presumed ocular histoplasmosis scars.

The surprising finding of viable lymphocytes in clinically inactive scars gives more credence to the immunological theory regarding reactivation of histoplasmosis scars. We feel that the T-lymphocyte theory can explain the mechanism by which an inactive scar becomes active upon reintroduction of the antigen. The clinical course of the disease as well as the response to corticosteroid therapy and photocoagulation are also consistent with this hypothesis.

Koch's stulates and experimental ocular histoplasmosis.

The present study shows clearly that focal choroiditis is produced in rabbits by infecting the animals with a mycelial form of H. capsulatum. Identification of this organism as the pathogenic agent was made by histopathological and mycological observations. This fungus was recovered from infected ocular lesions in those eyes enucleated within four weeks following the appearance of uveitus-a time period consistent with the clinical and pathological appearance of multiple granulomas in the choroid. The absence of organisms in the contralateral eyes of these same animals at eight weeks suggests perhaps that recovery was associated with the emergence of immunity by two months following the appearance of uveitus. This is supported in part by our previous study, which supplied evidence that animals were protected from further uveitis on subsequent reinfections (after they had recovered from their initial infection) by a mycelial or yeast form of the fungus. Similar protection was also seen in animals that had prior exposures to heat-killed organisms. Moreover, onset of the ocular changes occurred usually two weeks after infection. This evidence strongly suggests that the experimental choroiditis may be immunologically induced. H. capsulatum recovered from infected eyes (Groups I and II) produced identical ocular lesions clinically and histopathologically when injected into normal animals (Groups IA and IIA). Fulfillment of Koch's postulates in experimental ocular histoplasmosis was achieved within only one month following the appearance of uveitis. This may be of fundamental importance in that efforts to demonstrate a causal relationship between the ocular picture and benign systemic histoplasmosis have been unsuccessful in man. Because of the striking similarity between the experimental choroiditis in rabbits and the changes observed in presumed ocular histoplasmosis in man, studies in primates are necessary. Since the ocular anatomy is similar in monkeys and in man, there remains the necessity to reproduce the hemorrhagic disciform lesion of the macula, which represents the gravest aspect of presumed ocular histoplasmosis.

Prognostic criteria in macular histoplasmic choroiditis.

1. Fifty percent of 22 patients "desensitized" to histoplasmin developed subsequent activity, as compared to 44% of 23 patients without "desensitization." 2. Prednisone-induced remission of subclinical activity in patients monitoring their own central fields appears to be the most rewarding therapy for these desperate patients.

[Electron microscopic study on the focal immune response in the choroid (author's transl)].

Pigmented rabbits were sensitized by subcutaneous injection of BCG together with Freund's complete adjuvant and heat killed tubercle bacilli together with adjuvant. After the titer of serum antibody to BGG was elevated or tuberculin skin test became positive, choroiditis was induced in these eyes by an injection of BGG or PPD directly through the posterior sclera in the vicinity of the optic nerve. The eyes were enucleated at various intervals and the choroid was studied by light and electron microscopy. In the choroid challenged with BGG, infiltrates such as polymorphonuclear leukocytes and lymphocytes were seen, in early stages, invading in the posterior segment and peripheral area near the ciliary body. These cells decreased in number within a few days, and after one week a few plasma cells were detected in the posterior uvea. In the choroid challenged with PPD, infiltration of monocytes and lymphocytes was seen in early stages, reaching its peak in 48 hours. After 4 and 5 days lymphocytes decreased in number, but monocytes showed mitotic and phagocytotic activity, and accumulated near the sclera. After one week typical epithelioid cells were detected along the suprachoroidal space. These events were restricted within the choroid. The results obtained suggest, that in the focal immune reaction of the choroid, the cellular sequence of events and the range of tissue involved are different depending upon the kinds of antigen used. It may indicate humoral immunity on one side and cell-mediate immunity on the other.

Immunological studies on serpiginous choroiditis.

Immunological studies on 15 patients with serpiginous choroiditis gave no definite indications of the aetiology of the choroidal vascular lesion which appears to be the initial failure in this disorder. On the basis of the patients' history, recurrencies, and clinical and fluorescein angiographic features, it was suspected that the disorder was of inflammatory origin, probably vasculitis due to an abnormal immune response. To some extent this was supported by the laboratory findings. Of the histocompatibility antigens, HLA-B7 was found more frequently than expected in a Finnish population (54.5% versus 24.3%; P less than 0.05). Increased levels of antibacterial antibodies, ASO or ASTA, were found in eight patients and antiviral (herpes simplex) antibodies in two. One patient had earlier been treated due to positive syphilis serology, and one had an increased serum level of IgM as well as positive latex reaction in a dilution of 1:16. The serum concentration of complement component C3 was slightly decreased in three of the six patients studied and at the lower limit of the normal range in one. No manifestations suggesting systemic disease were found.

Immune responsiveness to retinal S-antigen and opsin in serpiginous choroiditis and other retinal diseases.

The immune responsiveness to bovine retinal S-antigen and opsin has been investigated in some retinal disorders by means of in vitro lymphocyte proliferation, leukocyte migration inhibition and enzyme linked immune sorbent assays (ELISA). Sensitisation to S-antigen was observed in serpiginous choroiditis, but not in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or retinitis pigmentosa. No significant immune responsiveness was detected to opsin in any of the three diseases. Elevated antibody titers to S-antigen were observed in some individual patients and healthy subjects. However, none of the patient groups exhibited an elevated antibody titer as compared to the control group. Although serpiginous choroiditis and APMPPE share some prominent clinical characteristics, the sensitisation in the former disease may perhaps be attributed to more severe and prolonged damage of the photoreceptor cells and blood-retina barrier. A combination of previous and present results suggests that in immunological investigations of retinitis pigmentosa patients it is more effective to use human than bovine S-antigen as test antigen because a species specific epitope seems to be involved.