Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis

Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.

Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis.

Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. METHODS: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. RESULTS: BDNF levels were significantly higher in patients before treatment when compared with controls (p=0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. CONCLUSION: BDNF may be released in the context of the active TR inflammatory response.

Post-prophylaxis Toxoplasma chorioretinitis following donor-recipient mismatched liver transplantation.

Toxoplasmosis may be transferred by organ transplantation. The most common clinical presentation is with multisystem disease, although isolated ocular toxoplasmosis has been described. Many centers have suggested that universal use of co-trimoxazole prophylaxis obviates the need for specific Toxoplasma testing. We report a case of donor-acquired ocular toxoplasmosis after liver transplantation despite co-trimoxazole prophylaxis. The diagnosis was confirmed by Toxoplasma polymerase chain reaction assay in conjunction with seroconversion. The fact that the infection was donor acquired was confirmed by serological mismatch and the absence of sporozoite-specific antigen antibody in the recipient.

Elevated Serum Immune Mediators and Subclinical Inflammation in HLA-A29-associated Birdshot Chorioretinopathy.

PURPOSE: To determine the circulating levels of seven immune mediators in serum samples from patients with birdshot chorioretinopathy (BSCR). METHODS: A single-center prospective case-control study was performed. Serum concentrations of IFN-γ, IL-12p70, IL-1ß, IL-17A, IL-23, TNF-α, and TGF-ß1 of 22 BSCR patients recruited at Hosp6ital Clinic of Barcelona and 16 healthy subjects were determined. RESULTS: Circulating levels of IL-17A were elevated in patients with BSCR in remission (p = 0.008 for BSCR patients with immunomodulatory treatment [IMT] and p = 0.032 for patients without IMT) compared with healthy subjects. Furthermore, patients who were not receiving IMT had significantly higher levels of circulating IL-23 (p = 0.013 vs controls and p = 0.001 vs IMT) and TGF-ß1 (p = 0.009 vs controls and p = 0.001 vs IMT) than patients under IMT or healthy subjects. CONCLUSIONS: Our results support the involvement of a IL-17-response in BSCR and suggest that BSCR patients without IMT due to apparent remission may maintain a subclinical inflammatory background.

Detection of Toxoplasma gondii DNA in peripheral blood and aqueous humor of patients with Toxoplasmic active focal necrotizing retinochoroiditis using real-time PCR.

PURPOSE: To evaluate the ability of real-time quantitative PCR (qPCR) for detectingToxoplasma gondii DNA in the peripheral blood and aqueous humor of patients with toxoplasmic active focal necrotizing retinochoroiditis. METHODS: Fifty-five patients with infectious uveitis seen from 2009 to 2013 at the Department of Ophthalmology and Visual Sciences of the Federal University of São Paulo were enrolled in this study. Forty-three patients had toxoplasmic active focal necrotizing retinochoroiditis, and the remaining 12 had non-toxoplasmic infectious uveitis and served as controls. qPCR analysis forT. gondii DNA was performed on the patients' peripheral blood and aqueous humor samples. RESULTS: The qPCR was positive for T. gondii DNA in 37.21% (16/43) of the aqueous humor samples and 2.33% (1/43) of the peripheral blood samples; further, 16.27% (7/43) of the patients had positive results in both their blood and aqueous humor samples. CONCLUSION: qPCR was able to detect T. gondii DNA in patients with toxoplasmic active focal necrotizing retinochoroiditis in the blood as well as the aqueous humor and can help with the diagnosis of the disease.

Detection of Toxoplasma gondii DNA in peripheral blood and aqueous humor of patients with Toxoplasmic active focal necrotizing retinochoroiditis using real-time PCR / Detecção de DNA do Toxoplasma gondii no sangue periférico e humor aquoso por PCR em tempo real

ABSTRACT Purpose: To evaluate the ability of real-time quantitative PCR (qPCR) for detectingToxoplasma gondii DNA in the peripheral blood and aqueous humor of patients with toxoplasmic active focal necrotizing retinochoroiditis. Methods: Fifty-five patients with infectious uveitis seen from 2009 to 2013 at the Department of Ophthalmology and Visual Sciences of the Federal University of São Paulo were enrolled in this study. Forty-three patients had toxoplasmic active focal necrotizing retinochoroiditis, and the remaining 12 had non-toxoplasmic infectious uveitis and served as controls. qPCR analysis forT. gondii DNA was performed on the patients' peripheral blood and aqueous humor samples. Results: The qPCR was positive for T. gondii DNA in 37.21% (16/43) of the aqueous humor samples and 2.33% (1/43) of the peripheral blood samples; further, 16.27% (7/43) of the patients had positive results in both their blood and aqueous humor samples. Conclusion: qPCR was able to detect T. gondii DNA in patients with toxoplasmic active focal necrotizing retinochoroiditis in the blood as well as the aqueous humor and can help with the diagnosis of the disease.

RESUMO Objetivo: Analisar o uso do PCR em tempo real (qPCR) na detecção do DNA do T. gondii no sangue periférico e no humor aquoso de pacientes com lesões de retinocoroidite focal, ativa por toxoplasmose. Métodos: Cinquenta e cinco pacientes com uveite infecciosa foram incluídos neste estudo. Os pacientes foram atendidos entre 2009 a 2013, no Departamento de Oftalmologia e Ciências Visuais da Universidade Federal de São Paulo. Quarenta e três pacientes tiveram o diagnóstico de lesões de retinocoroidite focal, ativa por toxoplasmose e, os outros 12 tiveram o diagnóstico de uveíte infecciosa não toxoplásmica e, por isso foram usados como grupo controle. A técnica de qPCR foi utilizada na detecção de DNA do T. gondii em amostras de sangue periférico e humor aquoso. Resultados: O qPCR foi positivo para o DNA do T. gondii em 37,21% (16/43) das amostras de humor aquoso, 2,33% (1/43) nas amostras de sangue periférico e, 16,27% (7/43) em ambas amostras simultaneamente. Conclusão: O qPCR foi capaz de detectar o DNA do T. gondii em pacientes com lesões de retinocoroidite focal, ativa por Toxoplasmose, no sangue bem como, no humor aquoso, podendo ajudar no diagnostico.

Interleukin 21, interleukin 23, and transforming growth factor ß1 in HLA-A29-associated birdshot retinochoroidopathy.

PURPOSE: To determine the peripheral levels of 20 immune mediators in serum samples from patients with birdshot retinochoroidopathy (BSRC). DESIGN: Single-center prospective case-control study. METHODS: The serum of 17 BSRC patients during different phases of disease activity and therapy were analyzed with a quantitative multiplex sandwich enzyme-linked immunosorbent assay-based microarray to determine the levels of 20 immune mediators (T cell and proinflammatory). The serum of 12 healthy volunteers was used as controls. RESULTS: Serum levels of interleukin (IL)-21 (P = .0005), IL-23 (P = .0005), and transforming growth factor (TGF)-ß1 (P = .0011) were elevated in BSRC patients with active disease naïve to systemic therapy compared with that of controls. There was no significant difference in the serum levels of immune mediators between controls and BSRC patients who had a current or past history of IMT or who were in remission. The levels of IL-21, IL-23, and TGF-ß1 were positively correlated (IL-23/IL-21, r = 0.91; TGF-ß1/IL-21, r = 0.97; TGF-ß1/IL-23, r = 0.87; for all, P < .0001). CONCLUSIONS: BSRC patients with active disease naïve to systemic therapy have elevated serum levels of 3 key immune mediators known to promote T helper 17 (Th17) cells in autoimmune disease. Our results suggest that IL-21, IL-23, and TGF-ß1 may play an important role in the development of site-specific Th17 cell-mediated inflammation in BSRC, which underscore the importance of systemic therapy and offer new insights into the potential of targeted treatments.

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.

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.

Susceptibility to toxoplasmic retinochoroiditis is associated with HLA alleles reported to be implicated with rapid progression to AIDS.

BACKGROUND/AIMS: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC). METHODS: 98 AIDS patients (25 with TRC, 43 with anti-T. gondii antibodies but without TCR, and 30 without anti-T. gondii antibodies and without TCR) were studied. RESULTS: The HLA-B35 was significantly increased in TRC group (p=0.0038). CONCLUSION: The presence of HLA-B35 may simultaneously predispose to progression to AIDS and TRC.

Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy.

PURPOSE: To determine the levels of 23 immune mediators in paired aqueous humor (AqH) and serum samples from patients with birdshot chorioretinopathy (BSCR). DESIGN: Single-centre case-control study. METHODS: A multiplex immunoassay was used to determine the levels of 23 immune mediators (T-cell, proinflammatory, and vascular-active mediators) in paired AqH and serum of 16 BSCR patients. The AqH of 11 age-related cataract controls served as controls. RESULTS: AqH levels of the T-cell mediators interleukin (IL)-2 (P=.044) and IL-17 (P=.039) and proinflammatory mediators IL-1ß (P=.032), IL-6 (P=.034), and tumor necrosis factor α (P=.041) were elevated compared with that of age-related cataract controls. The elevated intraocular levels of IL-1ß, IL-17, and tumor necrosis factor α in BSCR samples were higher than their concurrent serum levels. A significant positive correlation of intraocular mediators was noted between IL-17 and both IL-2 (r=0.744; P<.0001) and IL-23 (r=0.921; P<.0001) and between IL-2 and IL-23 (r=0.776; P<.0001). AqH levels of vascular-active mediators were not distinct between the groups. CONCLUSIONS: BSCR patients have elevated intraocular levels of proinflammatory and T cell-associated cytokines. Our results suggest the novel pathogenic concept that BSCR is an autoimmune inflammatory disease restricted to the eye and associated with elevated IL-17.

[Toxoplasmic central chorioretinitis]. / Corioretinita centrala toxoplasmozica--1 prezentare de caz.

Toxoplasma gondii is the most frequent cause of chorioretinitis in immunocompetent patients. This paper highlights the case of a 15 years old girl, an immunocompetent patient, with an active chorioretinal focus in the LE and a chorioretinal scar in the RE. Serologically, the IgG antiToxoplasma titre is increased, but the IgM antibodies are negative. It is the bilateral character of the lesions and the serology found that make this case special.

[Toxoplasmic retinochoroiditis: relapse vs choroidal neovascular membrane]. / Retinocoroiditis toxoplásmica: ¿recidiva o membrana neovascular coroidea?

CLINICAL CASE: We report four patients with both decreased visual acuity and retinochoroidal lesions compatible with ocular toxoplasmosis in which a diagnosis of active toxoplasmic retinochoroiditis or choroidal neovascular membrane was made based on a specifically designed diagnostic screening. DISCUSSION: In the context of a compatible clinical picture, with retinochoroidal scars and low grade or absence of inflammation, choroidal neovascular membranes may mimic active toxoplasmic retinochoroiditis and vice-versa. A thorough ophthalmic, serological, and immunological examination (in ocular fluids) may help in the differential diagnosis allowing for proper therapeutic decision-making.

Retinal toxic reactions following photopheresis.

BACKGROUND: Extracorporeal photochemotherapy (ECP), also known as photopheresis, is a generally well-tolerated therapeutic, immunomodulatory approach successfully used in cutaneous T-cell lymphoma and other diseases produced by T-lymphocytes such as graft vs host disease. OBSERVATIONS: On 2 separate occasions, a 54-year-old white man with Sézary syndrome developed cutaneous phototoxic reactions and chorioretinitis after being treated with ECP. A pharmacokinetic study showed therapeutic blood levels of 8-methoxypsoralen as long as 18 weeks after therapy had been terminated. However, the analysis of mutations in genes involved in the drug's disposition could not explain these abnormal levels. CONCLUSIONS: To our knowledge, there has been no previous description of ECP-related retinal toxic effects. This adverse effect was probably linked to impaired drug elimination. Further studies would be needed to determine the underlying mechanism.

Increased serum levels of CXCL8 chemokine in acute toxoplasmic retinochoroiditis.

PURPOSE: Chemokines have been implicated in the control of leucocyte infiltration in uveitis and in modulating angiogenesis in several ocular conditions. Toxoplasmic retinochoroiditis is a common cause of posterior uveitis. This study aimed to evaluate the serum concentrations of CC and CXC chemokines in patients with acute toxoplasmic retinochoroiditis. METHODS: The levels of five chemokines (CCL2, CCL11, CXCL9, CXCL8 and CXCL10) were evaluated in the serum of patients with active toxoplasmic retinochoroiditis (n = 55) and control subjects (n = 40). In a subset of patients (n = 18), a second measure of serum levels of chemokines was performed after the completion of oral treatment with pyrimethamine (25 mg/day), sulphadiazine (1 g, four times per day), folinic acid (7.5 mg/day) and prednisone (initial dose: 1 mg/kg/day) for approximately 30 days. RESULTS: Patients with toxoplasmic retinochoroiditis, notably those presenting with vasculitis, had increased serum levels of CXCL8 (mean +/- standard error of the mean [SEM] 35.1 +/- 6.5 pg/ml) compared with control subjects (mean +/- SEM 16.0 +/- 2.3 pg/ml; p = 0.01). There were no differences between patients and controls in serum levels of the other chemokines measured. The size of ocular lesions correlated significantly with serum levels of CXCL8 and CXCL9. After treatment, there was a significant reduction in serum levels of CXCL8. Severity of vitreous opacities did not correlate with serum levels of these chemokines. CONCLUSIONS: These data suggest a role for CXCL8 in the inflammatory process of acute toxoplasmic retinochoroiditis. Furthermore, CXCL8 may be a useful marker for patient follow-up.

Cytomegalovirus antibodies in tear fluid of patients with retinitis.

The diagnosis of cytomegalovirus retinitis (CMV-R) is difficult and usually based on clinical criteria or invasive diagnostic procedures. The purpose of this study was to investigate a possible association between CMV-R and specific anti-CMV antibodies in tears. Paired tear and serum samples were obtained from 96 individuals, which included 20 children with congenital CMV infection and chorioretinitis, 56 adults with retinitis with clinical signs suggestive of viral infection, and 20 healthy control subjects, and were tested for CMV antibodies using ELISA. The prevalence of anti-CMV antibodies in tears was found to be 80% (16/20) in children, 35% (20/56) in adults, and 5% (1/20) in control subjects. Furthermore, high antibody levels were detected in 35% (7/20) of children and 10.7% (6/56) of adults with retinitis, and were not found in control subjects. There was a strong association between high tear levels of anti-CMV antibodies and active ocular infection. No correlations were found between tear and serum antibodies. ELISA sensitivity was 80% and specificity 95%. Further studies are needed to compare the tear and intraocular levels of CMV-specific antibodies in patients with retinitis to find out if CMV antibody testing in tear fluid could substitute for more invasive diagnostic procedures.

Effect of catecholamine on central serous chorioretinopathy.

The role of catecholamine (CA) in the pathogenesis and development of macular edema of central serous chorioretinopathy (CSC) was studied, and its relations with visual acuity were investigated. Plasma concentrations of epinephrine (E) and norepinephrine (NE) were determined in 30 consecutive eyes with CSC. Central macular thickness analysis was done by RTA and all the data were compared with normal eyes and analyzed with SAS software package. Plasma concentrations of E and NE were increased to (569 +/- 123) ng/L and (721 +/- 104) ng/L respectively in active CSC patients, significantly higher than those in normal subjects (P < 0.01), and decreased to normal in convalescent stage. RTA analysis revealed that the retinal thickness of CSC patients was increased at active and recovery stage as compared with normal subjects; and the plasma concentration of E was significantly correlated with central macular thickness (t = 2.173, P < 0.05). Also, central macular thickness measured by RTA was significantly correlated with the visual acuity (r = -0.8046, P < 0.001) in CSC eyes. RTA analysis might be useful to quantitatively detect and evaluate prognosis in CSC patients. The plasma concentration of E, which was highly correlated with macular edema, might play an important role in the early damage and the pathogenesis of CSC.