Association of a NOD2 gene polymorphism and T-helper 17 cells with presumed ocular toxoplasmosis.

Retinochoroiditis manifests in patients infected with Toxoplasma gondii. Here, we assessed 30 sibships and 89 parent/case trios of presumed ocular toxoplasmosis (POT) to evaluate associations with polymorphisms in the NOD2 gene. Three haplotype-tagging single-nucleotide polymorphisms (tag-SNPs) within the NOD2 gene were genotyped. The family-based association test showed that the tag-SNP rs3135499 is associated with retinochoroiditis (P = .039). We then characterized the cellular immune response of 59 cases of POT and 4 cases of active ocular toxoplasmosis (AOT). We found no differences in levels of interferon γ (IFN-γ) and interleukin 2 produced by T-helper 1 cells when comparing patients with AOT or POT to asymptomatic individuals. Unexpectedly, we found an increased interleukin 17A (IL-17A) production in patients with POT or OAT. In patients with POT or AOT, the main cellular source of IL-17A was CD4(+)CD45RO(+)T-bet(-)IFN-γ(-) T-helper 17 cells. Altogether, our results suggest that NOD2 influences the production of IL-17A by CD4(+) T lymphocytes and might contribute to the development of ocular toxoplasmosis.

Vogt-Koyanagi-Harada-like Disease following Yellow Fever Vaccination.

Purpose: To report the manifestation of Vogt-Koyanagi-Harada-like disease (VKH) following yellow fever vaccination.Methods: Case report.Results: A 34-year-old immunocompetent male had tinnitus, headache, and decreased vision after a booster dose of yellow fever vaccine. Visual acuity was 20/100 in the right eye and 20/80 in the left, with serous retinal detachment (SRD) and choroidal thickening identified on clinical examination and multimodal imaging. Lumbar puncture revealed pleocytosis and an increased protein content, but extensive investigations ruled out infectious/neurological diseases. Pulse intravenous methylprednisolone was given, followed by a tapering regimen of high-dose oral prednisone. Azathioprine was started early, 3 weeks after initiation of oral steroids. Intraocular inflammation and SRD rapidly resolved, with visual acuity reaching 20/20 in both eyes, after 3 weeks. No recurrence of intraocular inflammation or sign of depigmentation was so far noticed, at 2 years of follow-up.Conclusion: Yellow fever vaccine may be a possible trigger for VKH.

Congenital toxoplasmosis in southeastern Brazil: results of early ophthalmologic examination of a large cohort of neonates.

OBJECTIVE: To report results of early ophthalmologic examinations in a large cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening. DESIGN: Cross-sectional analysis of a cohort. PARTICIPANTS: A total of 178 newborns with confirmed CT from 146,307 screened babies (95% of live births) from Minas Gerais state, southeastern Brazil. METHODS: From November 2006 to May 2007, newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried blood samples. On all positive or suspected cases, confirmative serology was performed on babies and their mothers. Congenital toxoplasmosis was confirmed in newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic studies of the central nervous system were also performed. In selected cases, biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B-scan) was performed. MAIN OUTCOME MEASURES: Prevalence of retinochoroidal lesions, either cicatricial or active, and their location and associated findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal detachment, were evaluated. The occurrence of cataract, microphthalmia, microcephaly, intracranial calcification, and hydrocephalus was also recorded. RESULTS: Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in 770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic examination at an average age of 55.6+/-16.6 days. Of these 178 infants, 142 (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye. Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in 142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes (12.4%). CONCLUSIONS: A high prevalence of CT was encountered (1/770) with high rates of early retinochoroidal involvement ( approximately 80%) and many active lesions (in approximately 50%), indicating a possibly more severe ocular involvement by CT in Brazil than in other parts of the world. The hypotheses of higher parasite virulence and increased individual susceptibility are being currently investigated.

Interleukin-10 gene polymorphism (-1082G/A) is associated with toxoplasmic retinochoroiditis.

PURPOSE: Experimental data have demonstrated a relevant role for IL-10, an anti-inflammatory cytokine, in the modulation of acute ocular toxoplasmosis. Therefore, this study was conducted to investigate the possible association between an IL10 gene polymorphism at position -1082 and toxoplasmic retinochoroiditis (TR) in humans. METHODS: One hundred patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, one hundred healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -1082 of IL10 (-1082G/A). PCR products were subjected to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish allele G and A of the IL-10 gene, allowing the detection of the polymorphism and determination of genotypes. RESULTS: There was a significant difference in the genotype distribution between TR patients and control subjects (chi(2) = 6.33, P = 0.04). Carriers of the IL10 -1082 A allele (AA+AG genotypes) were more often patients with TR than control subjects (chi(2) = 5.97, P = 0.01, OR, 2.55; 95% CI, 1.11 < OR < 5.55). In a subgroup analysis, there was no significant difference in genotypes and allele carriage regarding visual acuity, involvement of both eyes and TR recurrence. CONCLUSIONS: This study suggests that the genotypes related with a low production of IL-10 may be associated with the occurrence of TR.

Interleukin-1 gene polymorphisms and toxoplasmic retinochoroiditis.

PURPOSE: It has been proposed that cytokine gene polymorphisms can predispose individuals to disease by enhancing inflammatory processes. Considering the relevance of interleukin-1 (IL-1) in the pathogenesis of toxoplasmic retinochoroiditis (TR), we investigated whether IL1A -889 C/T and IL1B +3954C/T promoter polymorphisms are associated with TR in humans. METHODS: We performed a cross-sectional study that involved 100 Brazilian TR patients and 100 age- and gender-matched control subjects. Genomic DNA was obtained from oral swabs of all participants and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -889 of IL1A and +3954 of IL1B. PCR products were submitted to digestion and analyzed by PAGE to distinguish C and T alleles. RESULTS: There was no significant difference in the genotype or allele distributions of the IL1A -889 C/T and IL1B +3954C/T polymorphisms in patients with TR when compared with controls. However, in a subgroup analysis, the frequency of genotype and allele distributions of IL1A -889 C/T differed significantly between TR patients with and without recurrent episodes. CONCLUSION: This study suggests that the genotypes related with a high production of IL-1a may be associated with the recurrence of TR.

Intravenous Ceftriaxone for Syphilitic Uveitis.

PURPOSE: Report of clinical/multimodal imaging outcomes of patients with syphilitic uveitis alternatively treated with intravenous(IV) ceftriaxone, due to unavailability of penicillin G. METHODS: Chart review of all cases of syphilitic uveitis presenting to Hospital São Geraldo/HC-UFMG and treated with intravenous ceftriaxone, between January and August 2014. Clinical, serological and ophthalmological data were collected. RESULTS: Twelve consecutive patients with syphilitic uveitis receiving IV ceftriaxone were identified. All 24 eyes had active intraocular inflammation on clinical examination. All patients received IV ceftriaxone (2-4 g daily) for 14-21 days, supplemented with oral corticosteroid as needed in 9 patients (75%), after documented clinical response. Improvement in intraocular inflammation was seen in all 24 eyes, with median best-corrected visual acuity (BCVA) increasing from 20/50 to 20/20, after a mean follow-up of 5.3 months. CONCLUSION: IV ceftriaxone may be an effective alternative for treatment of syphilitic uveitis, in the setting of unavailability of penicillin G.

T cell immunoregulation in active ocular toxoplasmosis.

Toxoplasma gondii infection is an important cause of infectious ocular disease. The physiopathology of retinochoroidal lesions associated with this infection is not completely understood. The present study was undertaken to investigate cytokine production by T cells from individuals with active toxoplasmic retinochoroiditis (TR) comparing with controls. Eighteen patients with active TR and 15 healthy controls (6 controls IgG+ to Toxoplasma and 9 negative controls) were included in the study. Peripheral blood mononuclear cells were incubated in the presence or absence of T. gondii antigen (STAg), and stained against CD4, CD8, TNF, IL-10 and IFN-γ. Baseline expression of cytokines was higher in TR/IgG+ patients in comparison with controls. Cytokine expression was not increased by STAg in vitro stimulation in controls. After stimulation, TR/IgG+ patients' lymphocytes increased cytokine as compared to cultures from both controls. While T cells were the main source of IL-10, but also IFN-γ and TNF, other lymphocyte populations were relevant source of inflammatory cytokines. Interestingly, it was observed a negative correlation between ocular lesion size and IL-10 expression by CD4+ lymphocytes. This study showed that T cells are the main lymphocyte populations expressing IL-10 in patients with TR. Moreover, expression of IL-10 plays a protective role in active TR.

Ocular manifestation of cat-scratch disease in HIV-positive patients.

PURPOSE: To characterize ocular manifestations of cat-scratch disease in HIV-positive patients. DESIGN: Retrospective case series study. METHODS: Records and photography of patients with the diagnosis of cat-scratch disease and HIV were reviewed. RESULTS: From 2001 and 2004 three patients with cat-scratch disease and HIV were identified. All patients presented with subretinal mass associated with an abnormal vascular network. Fluorescein angiography revealed this abnormal vascular network more clearly. All patients were treated with antibiotics alone with good response. CONCLUSIONS: Subretinal mass associated with abnormal vascular network is characteristic of cat-scratch disease in HIV-positive patients. Fluorescein angiography is important to characterize this vascular pattern, and patients may benefit from systemic treatment.

Tuberculosis.

Tuberculosis is caused by Mycobacterium tuberculosis, transmitted primarily by inhalation of aerosolized droplets containing the organisms. There is an infection of the respiratory tract and the tubercle bacilli spread via lymphatic system and bloodstream to many different organs. Generally, the pulmonary tuberculosis infections are asymptomatic and a positive skin test result is the only indication of it. Approximately 10% of infected individuals develop active disease. Immunosuppression caused by systemic diseases or medication increases the risk of developing tuberculosis. In addition to the pulmonary tract, tuberculosis may affect many organs and systems, including lymph nodes, larynge, middle ear, genitourinary tract, musculoskeletal system, central nervous system, gastrointestinal tract, pericardium, and skin. Ocular involvement is an uncommon event in tuberculous infection, and there are several presentations involving the iris, ciliary body, choroid, retina and optic nerve. The diagnosis is based in the detection of mycobacteria in fluids and tissues. If there is no available material for analysis, a presumptive diagnosis is made and therapeutic test initiated. The therapy is based in anti-tuberculous drugs and corticosteroids. The standard treatment protocol in Brazil includes isoniazid, rifampim, and pyrazinamid for two months, followed by isoniazid and rifampin for four months for susceptible organisms. Alternative regimens are necessary in the presence of drug resistance.

Posterior scleritis in Cogan's syndrome.

PURPOSE: To describe an unusual case of atypical Cogan's syndrome with features of posterior scleritis. METHODS: Interventional case report. RESULTS: A 53-year-old man presented with bilateral posterior scleritis, along with sensorineural hearing loss and systemic vasculitis. Systemic corticosteroid therapy was started with resolution of ophthalmic findings and improvement of vestibuloauditory symptoms. CONCLUSIONS: In the setting of atypical Cogan's syndrome, ophthalmic manifestations may be the first sign of disease.

Interleukin-6 gene polymorphism (-174 G/C) is associated with toxoplasmic retinochoroiditis.

PURPOSE: Experimental data have demonstrated a relevant role for IL-6 in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate the possible association between the IL-6 gene polymorphism at position -174 and toxoplasmic retinochoroiditis (TR) in humans. METHODS: Ninety-seven patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, 83 healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -174 of IL-6 (-174G/C). PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish allele G and C of the IL-6 gene, allowing the detection of the polymorphism and determination of genotypes. RESULTS: There was a significant difference in the genotype (χ(2) = 12.9, p = 0.001) and allele (χ(2) = 6.62, p = 0.01) distribution between TR patients and control subjects. In a subgroup analysis, there was no significant difference in genotypes and allele frequencies regarding TR recurrence. CONCLUSIONS: This study suggests that the genotypes related with a lower production of IL-6 may be associated with the occurrence of TR.

Increased serum levels of soluble tumor necrosis factor receptor-2 (sTNFR2) in patients with active toxoplasmic retinochoroiditis.

This study aimed to investigate the serum levels of the cytokine TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with toxoplasmosis retinochoroiditis (TR) and controls. 37 patients with TR and 30 subjects with positive serology for toxoplasmosis but without history and signs of uveitis were included in this study. Serum concentrations of TNF-α, sTNFR1, and sTNFR2 were determined by ELISA. Serum concentrations of TNF-α and sTNFR1 were similar in controls (mean ± SD median values; 56.57±141.96 and 504.37±163.87, respectively) and TR patients (mean ± SD values, 121.62±217.56 and 511.15±189.30, respectively). Serum concentrations of sTNFR2 were higher in the uveitis group when compared to the control group (respectively, mean ± SD values, 1734.84±379.32 and 1442.75±309.47; p=0.002). There was no association between the serum levels of the molecules and the time of first symptoms, severity of vitreous haze, size or localization of active lesions, levels of visual acuity, and presence of vasculitis. These results suggest that TR is associated with changes in the circulating levels of inflammatory biomarkers, but they are not correlated with local/ocular signs.

Increased serum levels of soluble tumor necrosis factor receptor-2 (sTNFR2) in patients with active toxoplasmic retinochoroiditis

This study aimed to investigate the serum levels of the cytokine TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with toxoplasmosis retinochoroidits (TR) and controls. 37 patients with TR and 30 subjects with positive serology for toxoplasmosis but without history and signs of uveitis were included in this study. Serum concentrations of TNF-α, sTNFR1, and sTNFR2 were determined by ELISA. Serum concentrations of TNF-α and sTNFR1 were similar in controls (mean ± SD median values; 56.57 ± 141.96 and 504.37 ± 163.87, respectively) and TR patients (mean ± SD values, 121.62 ± 217.56 and 511.15 ± 189.30, respectively). Serum concentrations of sTNFR2 were higher in the uveitis group when compared to the control group (respectively, mean ± SD values, 1734.84 ± 379.32 and 1442.75 ± 309.47; p=0.002). There was no association between the serum levels of the molecules and the time of first symptoms, severity of vitreous haze, size or localization of active lesions, levels of visual acuity, and presence of vasculitis. These results suggest that TR is associated with changes in the circulating levels of inflammatory biomarkers, but they are not correlated with local/ocular signs.

Asymptomatic intracranial gumma in a patient with syphilitic uveitis and human immunodeficiency virus infection.

The case is described of a 51-y-old man with uveitis as the first clinical manifestation of syphilis and in whom laboratory work-up disclosed human immunodeficiency virus infection and asymptomatic brain gummata. The case illustrates the need for a comprehensive work-up in previously asymptomatic patients with uveitis.

Periflebite retiniana aguda congelada: relato de um caso atípico / Acute frosted retinal periphebitis. Report of an atypical case

Os autores relatam um caso de vasculite retiniana aguda bilateral em uma paciente de 31 anos de idade, que apresentou, em um dos olhos acometidos, um aspecto fundoscópico semelhante ao quadro descrito na literatura como "periflebite retiniana aguda congelada" ou "angelite de ramos congelados".

Iridociclite bilateral causada pelo "Mycobacterium leprae" diagnosticada através da punçäo de câmara anterior / Bilateral iridocyclitis caused by Mycobacterium leprae diagnosed through paracentesis

Os AAs realizaram Punçäo de Câmara Anterior em uma paciente portadora de Hanseníase, com quadro de iridociclite bilateral. A Punçäo foi realizada sob anestesia tópica, em regime ambulatorial, e o humor aquoso foi submetido à coloraçäo pelo método de Ziehl-Nielsen, tendo sido isolado o M. Leprae na Câmara Anterior. O trabaho mostra que o M.Leprae é uma das causas de uveítes na Hanseníase, merecendo ser procurado em casos de uveítes em pacientes portadores de Hanseníase