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Uveitis is a major cause of severe visual impairment throughout the world and can be initiated by various infectious and non-infectious causes. Early recognition of specific infections is important as the treatment with antimicrobial agents might stop the progression or even cure the eye disease. To determine the infectious causes of uveitis in Thailand, intraocular fluid samples of 100 HIV-negative patients and 47 HIV-positive patients with uveitis were examined using real-time PCR analysis for herpes simplex virus, varicella zoster virus, cytomegalovirus and Toxoplasma gondii. Positive PCR results were found in 33/100 (33%) HIV-negative patients and in 33/47 (70%) HIV-positive patients with uveitis. In Thailand, cytomegalovirus was identified as the most frequent cause of infectious uveitis in both HIV-negative and HIV-positive patients (49 and 91%, respectively). PCR analysis of intraocular samples in uveitis was a valuable diagnostic assay. The pattern of uveitis observed in the Far East differs from that found in the West., (Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Background: the immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS occurring in up to 38% of patients with CMV retinitis. Although the pathologic immune responses occur in the eye, immune dysregulation that allows for development of pathologic responses is presumably caused by faulty systemic immune cell reconstitution., Methods: we examined CMV-specific T cell responses, regulatory T (T(reg)) cell function and polyclonal T cell responses, including IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects with CMV retinitis who did not develop IRU., Results: patients with CMV IRU had poor CMV-specific CD4(+) T cell responses, as compared with control subjects, whereas CD8(+) T cell responses were comparable. Patients with CMV IRU were characterized by smaller numbers of circulating Th17 cells. Deficiency in anti-CMV responses was not associated with differences in T(reg) cell function., Conclusions: the T(reg) cell compartment is intact in patients with CMV IRU, and these patients do not develop exaggerated systemic CMV-specific or polyclonal immune responses. Cases are instead characterized by more profound depletion of Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to develop in persons experiencing the greatest degree of immune dysfunction before initiating highly active antiretroviral therapy.

Background: Uveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context., Methods: Using a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract., Results: Five mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-gamma, IL-6, and macrophage inflammatory protein-1beta were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis., Conclusions: We found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatment.

Intraocular infection with herpes simplex virus (HSV) can cause uveitis, a potentially sight-threatening disease. The disease is characterized by an ocular infiltration of inflammatory cells such as macrophages and B and T cells. The characteristics of the local humoral and cellular immune responses elicited on intraocular HSV infection are poorly understood. The local HSV-specific antibody production, which are used routinely for confirmation of a clinical diagnosis of herpetic uveitis, has never been analyzed in detail. This study analyzed the humoral immune response against HSV type 1 (HSV-1) in paired samples of intraocular fluid and serum of patients with intraocular herpesvirus infection. In addition, the B cell epitope distribution on a single HSV-1 type-specific antigen, glycoprotein G, was compared for these paired samples. The results presented here indicate that the inflamed eyes of patients with HSV-induced uveitis display a compartmentalized B cell response directed toward the triggering virus.

Cytomegalovirus (CMV) causes serious infection in individuals with deficient T cell immunity. In acquired immunodeficiency syndrome, the retina is a major site of progressive infection, despite the availability of therapy that targets CMV. The administration of highly active antiretroviral therapy to suppress human immunodeficiency virus frequently results in resolution of CMV retinitis, but this may be complicated by ocular inflammation termed "immune recovery uveitis" (IRU). To provide insight into the pathogenesis of IRU, the phenotype and specificity of intraocular T cells in a single patient were analyzed. The T cell infiltrate consisted of a diverse population of CD8(+) CMV-specific T cells, but only a minority of these T cells recognized the CMV phosphoprotein 65 and immediate early protein 1, which have been considered major targets of the host response. These results imply that reconstitution of CMV-specific T cells plays a role in IRU and suggest that the specificity of T cells engaged in the control of CMV at local sites of reactivation may be broad.

The genetic background of human T-cell lymphotropic virus type I (HTLV-I) uveitis (HU) was investigated by studying the distribution of 5 polymorphisms of the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-alpha gene in patients with HU, together with patients with adult T-cell leukemia (ATL), asymptomatic HTLV-I carriers, and healthy controls. The frequencies of the -1,031C allele (T-->C transition at position -1,031) and -863A allele (C-->A transition at position -863) in the HU patients, but neither in the ATL patients nor in the carriers, were significantly higher than those in the controls. The -1,031C and -863A alleles, in the absence of the HLA B61 or the DRB1*0901 allele which is in linkage disequilibrium with these alleles, were associated with increased susceptibility to HU. These results suggest that the -1,031C and -863A alleles might be genetic risk factors for HU.

Guinea pigs immunized with recombinant varicella-zoster virus (VZV) glycoproteins E (gE) and I (gI) developed antigen-specific antibodies in the sera, vitreous, and conjunctival washes. Sera from immunized animals neutralized both cell-free and cell-associated VZV, and peripheral blood lymphocytes proliferated in vitro in response to recombinant gE and gI and to antigens from VZV-infected cells. Immunized guinea pigs were inoculated intravitreally with VZV, which induces chronic uveitis. VZV DNA was more rapidly cleared and infectious VZV was isolated less frequently from the retinas of animals immunized with gE and gI compared with that in controls receiving adjuvant alone. Nonetheless, cellular infiltrates in the vitreous, retina, and choroid were prevalent 21 days after VZV inoculation in both the adjuvant-alone- and gE-gI-immunized animals. Immunization with VZV gE and gI induced potent humoral and cellular responses that accelerated the clearance of VZV DNA and may neutralize virus within the eye.

There is no small animal model that replicates chickenpox and herpes zoster, which are caused by varicella-zoster virus (VZV). Therefore, to detect VZV in tissues of infected animals, the Escherichia coli beta-galactosidase gene was inserted into the viral genome. Intravitreal inoculation of guinea pigs with virus-infected cells resulted in a chronic uveitis, with mononuclear cells in the vitreous cavity of the eye of nearly all animals. Staining with X-gal demonstrated the presence of VZV in the ciliary body or iris of approximately 40% of the animals and in retinal pigmented epithelial cells in 4 animals. X-gal staining showed VZV in the eye of 1 animal 140 days after inoculation. These experiments indicate that VZV expressing beta-galactosidase is useful for detecting virus in tissues and that VZV can cause a chronic uveitis in which virus can be detected in some animals for up to 4 months.

Human T-lymphotropic virus type I (HTLV-I) is responsible for a certain form of uveitis [HTLV-I-associated uveitis (HAU)]. A previous history of Graves' disease has been reported in 9-17% of the patients with HAU. In this study, the prevalence of patients with either HTLV-I antibody or uveitis was evaluated in 819 consecutive patients with thyroid disorders between 1991 and 1992. Serum HTLV-I antibody was found in 25 of 392 patients with Graves' disease, 19 of 257 with chronic thyroiditis, and 3 of 170 with nodular goiter. Five of 25 HTLV-I-positive patients with Graves' disease developed HAU. All of these 5 patients had been treated with methylmercaptoimidazole (MMI). Within a few months before the onset of uveitis, 3 patients were hyperthyroid, and 2 were hypothyroid. In 2 of 5 patients, an exacerbation of uveitis occurred soon after the readministration of MMI for the relapse of hyperthyroidism. None of the 367 HTLV-I negative patients with Graves' disease nor 22 HTLV-I-positive patients with chronic thyroiditis or nodular goiter developed uveitis. It was therefore suggested that Graves' disease, thyroid dysfunction and/or MMI administration might be related to the development of HAU.