Cytokine Changes in the Aqueous Humor in Rubella-Related Fuchs Heterochromic Iridocyclitis.

This retrospective study is aimed at determining the correlation between cytokine levels and virus status in the aqueous humor of 38 patients with Fuchs heterochromic iridocyclitis (FHI) with/without a viral presence between May 2017 and January 2020. The levels of cytokines were analyzed in the groups with and without virus-related FHI. Among the patients, 50% had rubella virus, 5.26% had cytomegalovirus, and 2.63% had herpes simplex virus infections. The expression of interleukin-6 (IL-6) and IL-8 was significantly higher, and that of basic fibroblast growth factor (bFGF) was significantly lower in the virus-positive group than in the virus-negative group (P = 0.015, P = 0.001, and P = 0.001, respectively). Although there was no significant difference in the mean expression of vascular cell adhesion protein 1 (VCAM-1), IL-10, and vascular endothelial growth factor (VEGF), that of VCAM-1 and IL-10 was higher (M = 1338 and M = 1390, respectively; M = 6.225 and 10.600, respectively) and that of VEGF was lower (M = 134.5 and M = 38.70, respectively) in the virus-positive group than in the virus-negative group. Similar findings were observed for the expressions of IL-6, IL-8, and bFGF in the rubella-positive and rubella-negative groups. Viral presence was highly related to FHI, especially that of the rubella virus. High levels of inflammatory cytokines and low levels of neovascularization-related factors are involved in rubella-related FHI. These study findings could be helpful in the diagnosis and treatment of FHI.

Predictive Factors of Intraocular Pressure Level Evolution Over Time and Glaucoma Severity in Fuchs' Heterochromic Iridocyclitis.

Purpose: To investigate the clinical and virologic-associated and predictive factors of intraocular pressure (IOP) evolution over time and its severity in Fuchs' heterochromic iridocyclitis (FHC). Methods: Consecutive patients with both clinical FHC and intraocular synthesis of rubella virus (RV)-specific antibodies were included in this study. Specific ocular production of RV antibodies was confirmed using the quotient of serum/aqueous humor ratio of RV IgGs (Crv) and control antiviral IgGs (Cctl), using quantitative serology methods. Epidemiologic, clinical, biological, and virologic data at referral were collected and correlated with IOP values over time, occurrence, and severity of glaucoma. Results: Sixty-eight eyes of 68 patients were included. Mean age at diagnosis was 40.7 ± 11.1 years. Mean follow-up was 4.3 ± 4.3 years. Mean baseline Crv and Cctl values were 12.34 ± 14.67 and 216.70 ± 98.4, respectively. Mean baseline IOP was 17.2 ± 7.2 mm Hg (range, 9-40) and 15.6 ± 5.6 (range, 3-30) 5 years after referral. The predictive factors for pejorative IOP evolution over time and glaucoma severity were male sex (P = 0.03) and decreased Crv (P = 0.04) and presence of iris nodules (P < 0.001) and decreased Cctl (P = 0.02), respectively. Diagnostic delay was associated with increased likelihood of undergoing glaucoma surgery (P = 0.02). Conclusions: Time to diagnosis, male sex, presence of iris nodules at baseline, and decreased Crv and Cctl ratios were associated with increased likelihood of pejorative IOP evolution over time. Given the aggressiveness of glaucoma in FHC, these results provide interesting insight into what category of patients should need the closest screening.

[Determination of cytomegalovirus IgG synthesis by the albumin correction in the aqueous humor of posner-schlossmann syndrome].

Objective: To evaluate the usefulness of albumin correction in determination of cytomegalovirus IgG in the aqueous humor of Posner-Schlossman syndrome (PSS) patients. Methods: Cases series studies. Forty-two patients (26 men and 16 women) who were diagnosed as PSS were enrolled from Oct. 2009 to Oct. 2015 at the Eye and ENT Hospital. During the same period, 20 patients with primary open-angle glaucoma (POAG) and 30 patients with bacterial endophthalmitis or retinal necrosis were enrolled as negative control group and inflammatory disease control group, respectively. Aqueous humor and serum samples were assayed to detect CMV IgG by enzyme-linked immunosorbent assay (ELISA), and albumin by scattering immunonephelometry. CMV DNA in aqueous humor was assayed by polymerase chain reaction (PCR). The ratio which was calculated as the (aqueous humor CMV IgG/serum CMV IgG)/(aqueous humor concentration of albumin/serum albumin concentration) over 0.6 was considered as intraocular antibody formation. Performance of differentiating control eyes from eyes with CMV-positive PSS was evaluated by the receiver operating characteristic curve. The ANOVA test, Mann-Whitney test and Chi-square test were performed to compare the differences among groups. Results: The detectable rate of CMV IgG antibody in the aqueous humor was 76.2%, 100.0% and 10.0% in PSS, inflammatory disease control and POAG groups, respectively. The levels of CMV IgG antibody in the PSS groups were significantly higher than that of POAG groups (Z=4.23, P<0.001).The positive rate corrected by the albumin was 71.4%, 3.3% and 0.0%.The corrected positive rate in PSS groups was significantly higher than that of the inflammatory disease control and POAG groups (χ(2)=30.38, P<0.01; χ(2)= 24.89, P<0.01), with a sensitivity of 75.0% and a specificity of 98.0%. The area under the curve for calibrated ratio was 0.942 (95%CI: 0.859 to 0.984) which was higher than that of CMV IgG (Z=6.19, P<0.001).The corrected positive rate of CMV IgG antibody (71.4%) was higher than that of CMV DNA (47.6%, χ(2)=4.003, P=0.045). Conclusions: CMV IgG antibody ratio which was corrected by aqueous humor and serum albumin could effectively improve aqueous antibody specificity in PSS patients. Furthermore, CMV IgG antibody ratio combined with PCR could improve the sensitivity of CMV detection. All of which help clarify the CMV infection in PSS in CMV DNA negative eyes. (Chin J Ophthalmol, 2017, 53: 104-108).

[Endotoxin Is a Companent in Pathogenesis of Chronic Viral Diseases].

The level of endotoxin and indicators of activity of antiendotoxin immunity (antibody concentration to glycolipid Re-chemotype and general antigen of enterobacteria) were estimated in serum of 174 patients with persistent viral infections (viruses: herpes simplex, hepatitis C, human immunodeficiency). The presence of markers of systemic inflammatory response syndrome (interleukin IL-1ß) and acquired immunodeficiency (CD4+) in HIV-infected patients were also determined. Persistent viral infections are accompanied by endotoxin aggression intestinal origin (caused by them), which is able to induce the development of systemic inflammatory response syndrome. In HIV-infected patients with this syndrome is cyclical, when the phase of hyperactivity replaced immunodeficiency. Schematically, this process can be represented as the following sequence of events: HIV-mediated damage to the intestinal barrier--the development of endotoxin aggression--induction ofsystemic inflammatory response syndrome--the depletion of the immune system, which is transient and is related to the duration of activity of the virus replication cycle, i.e., with damage to enterocytes. Using antiendotoxin component (means of reducing levels of endotoxin in the blood) in the scheme of treatment of persistent viral infections can serve as an element of a successful prevention of complications.

[Post-operational acute iridocyclitis and immune shifts in intraocular humor of patients with cataracts].

The negative tendency of cataracts growth, which is a consequence of various diseases of the organism including those of eyes, combined in the concept "the complicated cataract" is clearly traced now. In the concept of such a complication of cataracts as the acute autoimmune iridocyclitis, the important role, in our opinion, should be given to regional immunopathological disorders, which testify to the withdrawal of the known phenomenon underlying in the immunological tolerance of post-barrier eye membrane "a syndrome of eye anterior chamber-associated immune deviation (ACAID). Microcoaxial phacoemulsification was carried in three hundred patients with senile and complicated cataracts. The intraocular humor of the operated patients was subjected to immune-enzyme immunomorphological analysis for СD4, СD8, IgG and B-lymphocytic populations. On the base of performed clinical-laboratory research we found that the gravest inflammatory process in eye tissues manifested in the form of autoimmune aseptic iridocyclitis was observed particularly in patients with complicated cataracts, proceeding on the background of glaucoma, diabetes and the previous trauma of an eye. The high indicators of IgG, СD4 were registered on the background of low СD8 indicators in the intraocular humour at these patients. The revealed regional inflammatory reaction in eye tissues testifies, in our opinion, in favour of in situ withdrawal of ACAID; this latter brings to origination of acute aseptic autoimmune iridocyclitis in the early post-operational course of the complicated cataracts.

High concordance of intraocular antibody synthesis against the rubella virus and Fuchs heterochromic uveitis syndrome in Slovenia.

PURPOSE: To prospectively study the relationship between Fuchs heterochromic uveitis syndrome (FHUS) and intraocular production of specific antibodies against the rubella virus (RV) in Slovenia. METHODS: Using the Goldmann-Witmer coefficient technique, intraocular synthesis of specific antibodies against RV, herpes simplex virus, varicella-zoster virus, cytomegalovirus (CMV) and Toxoplasma gondii-specific immunoglobulin G antibodies was performed in 12 consecutive patients with clinically diagnosed FHUS and 12 patients with idiopathic recurrent unilateral anterior uveitis (AU) without clinical features of FHUS. RESULTS: Specific intraocular antibody synthesis against RV with a positive Goldmann-Witmer coefficient was proven in 11 of 12 (92%) FHUS patients, and in none of the non-FHUS AU patients (Fisher's exact test <0.0001). In one patient with FHUS, specific antibodies against RV and varicella-zoster virus were concurrently detected. Specific antibodies against cytomegalovirus were detected in one patient with unilateral recurrent AU. CONCLUSIONS: Intraocular production of specific immunoglobulin G against RV was proven in the majority of tested cohort of FHUS patients from Slovenia as compared to the group of patients with idiopathic AU, which suggests that RV is involved in the pathogenesis of FHUS in this geographic area.

[Ocular involvement in spondyloarthropathies: HLA B27 associated uveitis]. / Augenbeteiligung bei Spondyloarthritiden: HLA-B27-assoziierte Uveitis.

The most frequent extraarticular manifestation in spondyloarthropathies (SpA) is eye involvement, which is found in 30%-50% of patients. HLA B27 positive patients in particular--mostly those in the subgroup with ankylosing spondylitis--are affected. Prevalence of uveitis increases with duration of disease. Typical eye involvement is sudden-onset unilateral anterior uveitis (iridocyclitis). Most cases respond well to topical corticosteroids. Frequently relapsing or chronic cases may require oral corticosteroids in addition to classical immunosuppressive drugs and, to an increasing extent, also TNF-alpha inhibitors. In the case of the latter, monoclonal antibodies are preferred over receptor antagonists. Acute anterior uveitis may occur as a minimal variation or initial symptom of SpA. These patients should also be seen by a rheumatologist since undiagnosed SpA may be present in a significant percentage and should be included in therapeutic considerations.

Intraocular antibody synthesis against rubella virus and other microorganisms in Fuchs' heterochromic cyclitis.

INTRODUCTION: Fuchs' heterochromic cyclitis (FHC) is a common intraocular disease of uncertain etiology that has recently been related to rubella virus (RV) infection. METHODS: We investigated the synthesis of RV-specific IgG using aqueous humor and serum samples from 63 consecutive patients with FHC. In addition, intraocular immunoglobulin G production against herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV) and toxoplasma gondii was determined. In 20 patients, the detection of RV RNA was additionally performed by RT-PCR on the E1 gene. Forty-six patients with HSV- and VZV-associated uveitis, HLA B-27 positive anterior uveitis, and Posner-Schlossman syndrome served as controls. RESULTS: Specific intraocular antibody synthesis against RV was confirmed in all 63 FHC patients, whereas none of the 46 controls was positive for RV IgG. Interestingly, in 11 patients with positive RV IgG synthesis, additional HSV (eight), VZV (one) and CMV (two) specific antibodies could be detected. Only twice was viral RNA detectable by PCR in a patient with FHC. CONCLUSIONS: In this largest reported series of FHC patients, we detected a strong association between FHC and intraocular antibody synthesis against rubella virus. Furthermore, in 11 patients, it was possible to confirm an additional intraocular antibody synthesis, in particular HSV. PCR-positive results in the aqueous humor were exclusively obtained for RV. In contrast to other studies, the RV genome could only be identified in two patients (10%).

Association between Helicobacter pylori infection and Posner-Schlossman syndrome.

OBJECTIVE: To investigate possible association between Helicobacter pylori infection and Posner-Schlossman syndrome. METHODS: In a prospective study, 40 subjects with Posner-Schlossman syndrome were examined. As a control group, 73 subjects without Posner-Schlossman syndrome were selected for comparison with the study group. All participants underwent serologic analysis for the presence of H. pylori infection by an enzyme-linked immunosorbent assay. Positive rate of serum anti-H. pylori IgG was compared between Posner-Schlossman syndrome patients and control participants. RESULTS: The rate of positive titre (>15 U/ml) of H. pylori was 80.0% in the Posner-Schlossman syndrome group and 56.2% in control group, showing significant difference (Fischer's exact, P=0.014). Multivariate analysis adjusted for various systemic factors revealed that positive titre of anti-H. pylori IgG was a significant risk factor for Posner-Schlossman syndrome with an odds ratio, (4.84, 95.0% CI: 1.10-21.24, P=0.037). CONCLUSIONS: H. pylori infection occurred significantly more often in Posner-Schlossman syndrome patients. This study suggests that exposure to H. pylori infection is associated with Posner-Schlossman syndrome in Korea.

Immunohistochemical study of chronic nongranulomatous anterior uveitis in juvenile idiopathic arthritis.

PURPOSE: To provide a detailed immunohistochemical analysis of juvenile idiopathic arthritis (JIA)-associated anterior uveitis. DESIGN: Interventional case report. PARTICIPANT: One patient. INTERVENTION: A 12-year-old patient had recurrent pauciarticular JIA and smoldering anterior uveitis in the right eye. Despite treatment with local and systemic corticosteroids and an anti-tumor necrosis factor agent, the right eye became hypotonous and painful and eventually was enucleated. The clinical history and histopathologic and immunohistochemical analyses of the enucleated globe were reviewed. MAIN OUTCOME MEASURES: Histopathologic and immunohistochemical features of JIA-associated anterior uveitis. RESULTS: The iris and ciliary body showed nongranulomatous chronic inflammation predominantly made up of plasma cells, Russell bodies, and plasmacytoid lymphocytes. The ciliary processes and pars plana ciliaris showed focal aggregates of CD20-positive cells with several CD3- and CD8-positive cells and occasional CD4- and CD68-positive cells. Pancytokeratin stain showed ciliary epithelial proliferation admixed with lymphocytes. The iris revealed kappa-positive cells within the stroma and lambda-positive cells on the surface. The iris infiltrate primarily was made up of immunoglobulin (Ig) G-positive cells with occasional IgA- and IgM-positive cells. The anterior chamber exudate was mainly positive for IgG and IgA. CONCLUSIONS: The immunohistochemical findings suggest that JIA-associated nongranulomatous iridocyclitis is a primarily B-cell-infiltrative process.

The antitoxoplasma gondii antibodies incidence to the different ocular diseases patients cases of human ocular toxoplasmosis infections in Romania.

Toxoplasmosis is an anthropo-zoonosis widely spread around the earth, whose ocular complications are very frequent and are often a first sign of infestation. This is a retrospective statistic research based on the clinical survey and periodic control of a lot of 135 patients with toxoplasmosis, out of which 90 presented ocular toxoplasmosis.

Rubella virus-associated uveitis in a nonvaccinated child.

PURPOSE: To report presumed Fuchs heterochromic uveitis (FHU) associated with Rubella virus (RV)-specific intraocular antibody production in a child who was not vaccinated against rubella. DESIGN: Observational case report. METHODS: We examined a 13-year-old boy with chronic anterior uveitis complicated by mature cataract. Two aqueous humor (AH) samples taken with an interval of four weeks were analyzed for intraocular antibody production against RV by calculation of the Goldmann-Witmer coefficient. RESULTS: The patient showed all the clinical signs for FHU: iris atrophy, stellate keratic precipitates, and cataract. Analysis of the AH demonstrated intraocular antibody production against RV in two sequential samples. CONCLUSIONS: The data show that RV-associated uveitis can already present during childhood. Moreover, this finding suggests that nonvaccinated children may be at risk to develop uveitis after RV infection.

Fuchs heterochromic cyclitis and ocular toxocariasis.

PURPOSE: To report the association of Fuchs heterochromic cyclitis (FHC) and ocular toxocariasis in a young adult. DESIGN: Observational case report. METHODS: A 26-year-old patient was referred for the management of a unilateral intermediate uveitis associated with a lower peripheral subretinal fibrotic lesion near the pars plana. Diagnosis of FHC was clinically confirmed. Laboratory examination was performed to exclude an infectious condition. RESULTS: LISA assay detected significant levels of IgG directed against Toxocara canis. Toxoplasmic serology was negative, excluding this differential diagnosis. Other examinations, including complete blood cell count, urinalysis, serum angiotensin-converting enzyme, lysosyme, chest CT scan, and syphilis serology were noncontributive. CONCLUSIONS: Previous studies have reported on the association of FHC and other parasitic conditions, such as toxoplasmosis but also on herpetic ocular infections. Serologic analysis for toxocariasis may be proposed in patients with FHC and retinal scars in the absence of toxoplasmosis.

Intracellular T lymphocyte cytokine profiles in the aqueous humour of patients with uveitis and correlation with clinical phenotype.

This study aimed to investigate whether T cells in aqueous humour are different in different types of uveitis and correlate with clinical phenotype. Patients with clinically different types of uveitis, but all displaying active anterior uveitis, were phenotyped and samples of aqueous humour (AH) and peripheral blood (PB) collected. Cells from AH and PB were separated by centrifugation and by density gradient centrifugation (to obtain mononuclear cells PBMC), respectively. Cells were activated with PMA and ionomycin in the presence of Brefeldin A, stained for surface markers and intracellular cytokines, and analysed by flow cytometry. The cytokine profile was correlated with the clinical phenotype. Increased percentages of interleukin (IL)-10+-, but not interferon (IFN)-gamma+ T lymphocytes were found in AH compared with PB in patients with acute anterior uveitis (AAU), FHC or chronic panuveitis (PU). There was a trend towards elevated levels of IL-10+ T cells in AH from patients with FHC compared with AH from acute uveitis and panuveitis patients. Increased levels of IL-10+ T cells in AH compared with PB were also found in samples from patients with isolated uveitis, but not those with associated systemic disease. Levels of cytokine-positive T cells were not associated with the use of topical steroids or to the severity of the anterior uveitis. While type I cytokine-producing T lymphocytes are present in AH during AU, the presence of increased proportions of IL-10+ T lymphocytes in AH from patients with uveitis may be indicative of an anti-inflammatory mechanism that may influence the type and course of ocular inflammation in these patients.

[Ocular symptoms of autoagression in patients with idiopathic inflammatory bowel disease]. / Oczne objawy autoagresji u pacjentów z przewleklym nieswoistym zapaleniem jelit.

PURPOSE: of this research was to present a prospective estimation of the ocular symptoms appearance in a group of patients with ulcerous colitis (CU) or Crohn disease (CD). It was also, to demonstrate dependence between the frequency, intensity, and duration of the main disease and the way of its treatment. The research program established a retrospective analysis of symptoms presented typically in non-specific colitis in a group of patients with recurrence acute iridocyclitis (IA) and HLA B27 positive. MATERIALS AND METHODS: The research group contained 63 patients: 51 with CU and 12 with CD. Clinical symptoms and inflammatory indicators such as CRP, OB, pulse, and body temperature were taken into consideration by designation of intensity of main disease. Second group contained 28 patients with IA and duration of CU or CD symptom was analyzed in it. RESULTS: Symptoms of iridocyclitis acute non granulomatous were observed in 7.9% of cases. In 6.3% episcleritis was diagnosed and in one patient with CU scleritis (1.5%). In the second group of patients only in one case (3.5%) typical symptoms for chronic colitis were presented. CONCLUSIONS: In patients with non-specific chronic colitis careful ophthalmological examination should be performed, especially oriented for uveitis diagnosis.

Highly focused clonal composition of CD8(+) CD28(neg) T cells in aqueous humor of fuchs heterochromic cyclitis.

Fuchs heterochromic cyclitis (FHC) is characterized by a predominant CD8(+) T cell subset infiltrating the anterior chamber, but the clonal composition of these T cells is unknown. In the present study, T cell repertoire diversity of the accumulating T cells was analyzed to investigate if a high degree of restriction could indicate antigen-driven immune response. Aqueous humor (AH) and peripheral blood cells were collected in two patients with FHC. T cell repertoire diversity was screened by T cell receptor (TCR) BV family expression. In one patient, several BV gene segments were used by lymphocytes from the AH but with over-representation of BV16 that accounted for around half of the expressed intraocular repertoire. In the other patient, a more restricted TCRBV usage was found in AH, as only BV15 and BV18 were expressed in the ocular sample. In this patient, virtually all AH CD8(-) T-cells were CD28- and CD57-negative by three-color flow cytometry, an immunophenotype suggestive of past antigenic stimulation. High resolution immunoscope analysis of TCRBV CDR3 profiles and sequencing of subcloned TCRBV-BJ PCR products evidenced a highly restricted TCRBV-BJ usage, since virtually all the intraocular cells comprise only five clonotypes in this patient. Unique peaks of CDR3 length were found in BV15 joined to BJ2S1, BJ2S3 and especially BJ2S5, in AH but did not predominate in blood. Conversely, identical clonotypes using rearranged BV18 and BJ2S7 gene segments were detected in both AH and peripheral blood. Maintenance of the TCRBV18-BJ2S7 clonotypes in aqueous humor was demonstrated over 6 months in this patient, with a switch in the predominance of two clonotypes. Our results show the presence of a finite number of CD8(+)CD28(neg) T cell clonotypes, which suggests an antigen-driven process and the involvement of these T cells in the pathogenesis of FHC.

Herpes simplex virus DNA identification from aqueous fluid in Fuchs heterochromic iridocyclitis.

PURPOSE: To report the presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis. METHODS: In an eye with a clinical diagnosis of Fuchs heterochromic iridocyclitis, samples of aqueous humor and anterior capsule of the lens were obtained during cataract surgery. Polymerase chain reaction was performed on the samples to detect the presence of viral DNA including herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Serologic analysis was also performed for antiviral immunoglobulins. RESULTS: Herpes simplex virus DNA was identified in the aqueous humor but not in the anterior capsule. Serum immunoglobulin G was positive for herpes simplex virus, varicella-zoster virus, and cytomegalovirus. CONCLUSIONS: The presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis suggests that herpes simplex virus infection may play a role in the pathogenesis of Fuchs heterochromic iridocyclitis.