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.

[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%).

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.

[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.

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.

Molecular analysis of resolving immune responses in uveitis.

To identify the cellular immune processes underlying intra-ocular inflammation, aqueous humour was obtained at cataract surgery from 22 patients with clinically inactive uveitis and 24 patients with age-related cataract. mRNA expression for the cytokines IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta); T cell subsets CD3, CD4, CD8; monocytes and macrophages (CD14); and B cells (CD19) was measured using reverse transcriptase-polymerase chain reaction (RT-PCR) and radiometric analysis. The majority of uveitis patients demonstrated a T cell-mediated inflammatory response, predominately involving a Th1-like cytokine profile with expression of IL-2 and IFN-gamma in 16/22 and 18/22 samples, respectively. These cytokines were present in only a small number of patients with age-related cataract. This Th1-like polarization was supported by an increased expression of CD8 in a number of patients. IL-1beta was expressed in only six uveitic eyes. Only four patients expressed either IL-4 or IL-10 and no patient expressed both. TGF-beta mRNA could be detected in 18/22 uveitis patients and 15/24 controls. IL-12, the paradigmatic Th1-inducing cytokine, was absent in all samples but CD14 was expressed in the majority of patients and controls. CD19 could not be detected in any sample. The cellular infiltrate in the uveitic eyes showed clear evidence of low IL-1 and absent IL-12 expression despite a Th1-like profile and high expression of macrophages. This strongly suggests that the systemic immunosuppressive therapy used prior to surgery in some patients and/or the chronicity of the uveitis had actively suppressed/switched off macrophage function, leading to resolution of T cell activity.

Antibodies to the 45 kDa DEK nuclear antigen in pauciarticular onset juvenile rheumatoid arthritis and iridocyclitis: selective association with MHC gene.

OBJECTIVE: To study the frequency of autoantibodies to the 45 kDa DEK nuclear antigen, a putative oncoprotein, in a sample of patients with juvenile rheumatoid arthritis (JRA), and to make correlations with disease subtype and complications such as iridocyclitis. Class I and Class II HLA associations with reactivity to the antigen were also sought. METHODS: Sera from 146 HLA typed patients with JRA representing all subtypes were analyzed for reactivity with the 45 kDa DEK protein by immunoblotting. The antigen was purified to near homogeneity from nuclei of HeLa cells. RESULTS: Antibodies to DEK were found in 57% of all patients with JRA compared to 3% of controls (p < 0.0001). Antibodies were detected more frequently in pauciarticular onset (78%) than in polyarticular onset patients (29%; p < 0.01) and controls (3%; p < 0.0001). 97% of patients with JRA (regardless of onset subtype) and iridocyclitis had anti-DEK antibodies compared to 47% of patients without eye disease (p < 0.0001). Anti-DEK antibodies were found more frequently in females compared to males in the pauciarticular onset disease group (84 vs 42%; p < 0.01). The occurrence of anti-DEK antibodies was closely associated with positive antinuclear antibody serology, and a strong association with the Class I gene HLA-A2 was also observed. CONCLUSION: Antibodies to the 45 kDa DEK protein are characteristic of the pauciarticular onset subtype of JRA, particularly in patients with a history of iridocyclitis. The occurrence of anti-DEK antibodies is significantly but paradoxically associated with the presence of the HLA-A2 allele in such patients.

[Pathogenesis of complicated cataract in herpetic kerato-uveitis]. / Zur Genese der Cataracta complicata bei herpetischer Keratouveitis.

BACKGROUND: Keratitis, retinitis and secondary cataract are well known complications of ocular herpes simplex infection. We report on a case of herpetic keratouveitis and cataract. Acute and inflammatory pathogenesis of cataract formation resemble a phacoanaphylactic reaction. CASE REPORT: A 15-year-old girl with recurrent herpes keratitis was referred for acute spontaneous cataract formation accompanied by iridocyclitis and hypotony. Visual acuity was decreased from 0.4 to light projection. During cataract extraction the anterior chamber was tabbed for immunological analysis. The thickened anterior lens capsule was examined by light microscopy. We found a significant local synthesis of herpes antibodies in the aqueous. Histologically the lens capsule depicted a defect and a granulomatous inflammatory infiltrate towards the basal membrane material. The specimen was not suitable to judge on eventual additional phacoanaphylaxis. After cataract extraction and systemic acyclovir and corticosteroids the keratouveitis subsided. Visual acuity improved to 0.4, but was limited by the disciform corneal scar. CONCLUSION: The granulomatous response towards lens capsule shown here, resembles the granulomatous reaction towards Descemet's membrane in advanced herpetic corneal ulcer. We speculate on the pathogenesis of the lens capsule defect as a, so far unknown, herpes-associated autoimmun response against the basal membrane material of the lens. The acuteness of cataract formation may be a consequence of contact of aqueous with lens fibres. Additional phacoanaphylaxis combined with secondary glaucoma is possible.

Toxoplasmose adquirida ganglionar associada á uveíte anterior granulomatosa sem retinocoroidite / Ganglionar acquired toxoplasmosis associated with granulomatous anterior uveites without retinochoroiditis

Os autores relatam um caso de toxoplasmose ganglionar associada com uveíte anterior granulomatosa sem lesäo retiniana e tentam, neste estudo, explicar a fisiopatologia deste achado. É a primeira publicaçäo sobrea presença cancomitante de toxoplasmose ganglionar com iridocicle granulomatosa sem retinocoroidite em paciente imunocompatente.

Oftalmia simpática pós-vitrectomia / Sympathetic ophthalmia following vitrectomy: report of once case

Estudo de um caso de oftalmia simpática pós-vitrectomia via pars plana, cujo quadro clínico no olho simpatizante caracterizou-se por iridociclite näo granulamatosa, turvaçäo vítrea, hiperemia do disco óptico e descolamento seroso de retina. O período de latência entre a vitrectomia e o início dos sintomas foi de 70 dias. Apresentamos, no presente caso, aspectos terapêuticos abordando a necessidade do uso de drogas imunossupressoras. Trata-se do primeiro caso, de nosso conhecimento, de oftalmia simpática pós-vitrectomia via pars plana relatado na literatura nacional

Association to HLA-DRB1*08, HLA-DPB1*0301 and homozygosity for an HLA-linked proteasome gene in juvenile ankylosing spondylitis.

To assess the role of HLA genes other than those encoding B27 in predisposing to JAS and AAS, we analyzed the distribution of B*4001, as well as the DRB1, DPB1, and LMP2 alleles, using PCR-based techniques in 63 JAS and 44 AAS patients (all B27 positive). The NBMDR (N = 4724) provided a source of controls matched with the patients for B27 (or other markers when necessary). We found an increase of the B*4001, DRB1*08, and DPB1*0301 alleles, as well as the LMP2 b/b genotype (the latter was most pronounced among patients with acute iridocyclitis), in JAS compared to B27-positive controls. The increase of DRB1*08 and DPB1*0301 was due to an increase of DRB1*08 and DPB1*0301 in combination, whereas the association with B*4001 could be due to linkage disequilibrium with LMP2b. None of these associations were detected in AAS. We conclude that in JAS, in addition to the association to B27, there are also weaker but distinct associations to the DRB1*08, DPB1*0301 alleles and homozygosity for LMP2b.

Ciclite heterocrômica de Fuchs: associaçäo entre corpúsculos de Russel e imunoglobulinas / Fuchs heterochronic cyclitis: association between Russel corpuscles and immunoglobulins

Descrevemos o caso de uma paciente com ciclíte heterocrômica de Kushs, que apresenta corpúsculos de Russel sobre a superfície anterior da íris, e na qual detectamos níveis elevados de imunoglobulinas plasmáticas e no humor aquoso.

Immune deposits in iris biopsy specimens from patients with Fuchs' heterochromic iridocyclitis.

To investigate whether Fuchs' heterochromic iridocyclitis may be an immune complex vasculitis, we used an immunofluorescence technique to detect immunoglobulins and complement in iris biopsy specimens from nine patients with Fuchs' heterochromic iridocyclitis, 12 patients with other types of uveitis, and nine patients with glaucoma but without uveitis. No specific immune deposits were observed in the irises of the patients with Fuchs' heterochromic iridocyclitis. Immunoglobulin G, IgA, IgM, and complement were detected in patients with Fuchs' heterochromic iridocyclitis and patients with uveitis, and these results differed significantly (P less than .05) from the group without uveitis. The immune deposits were found only in the iris vessel walls. No light-microscopic evidence of an inflammatory vascular process could be detected. Further studies are necessary to investigate whether the immune reactants originate from the circulation or result from local formation.

[Ocular findings in infection-linked immune phenomena and secondary diseases (the so-called Reiter's syndrome)]. / Okuläre Befunde bei infektionsassoziierten Immunphänomenen und Nachkrankheiten (sog. "Reiter-Syndrome").

Between 1981 and 1987 the authors saw 12 patients with Reiter's syndrome. Lesions included 6 cases of bilateral conjunctivitis in patients with chlamydial infection, 3 of unilateral serofibrinous iridocyclitis in patients with Yersinia enterocolitica, 1 case of bilateral iridocyclitis in a patient with positive chlamydial complement-binding reaction, 1 case of bilateral follicular conjunctivitis following acute gonococcal urethritis, and one case of unilateral serofibrinous iridocyclitis, in a patient with Ureaplasma urealyticum. Immunohistologic work-up of the conjunctival biopsy from the patient with Urea-plasma urealyticum urethritis revealed IgM deposits in the vascular endothelium of conjunctival vessels, C-3 deposits in the conjunctival stroma, and intercellular IgG in the conjunctival epithelium. Since Reiter's syndrome is interpreted as a sequela of secondary immune diseases following a primary infection that may persist in HLA-B27-positive patients, the patients were treated with both topical and systemic anti-infectious and anti-inflammatory agents.

Immunohistochemical analysis of iris biopsy specimens from patients with Fuchs' heterochromic cyclitis.

Using immunohistochemical techniques, we analyzed iris biopsy specimens from eight patients with Fuchs' heterochromic cyclitis, seven patients with various other types of uveitis, and eight glaucoma patients without uveitis. No specific abnormalities related to Fuchs' heterochromic cyclitis could be detected. Four of the patients with Fuchs' heterochromic cyclitis and four of the patients with uveitis showed evidence of an inflammatory cell infiltrate, which was a mixture of interleukin-2 receptor-negative T helper and suppressor cells, B lymphocytes, and plasma cells. Only an occasional T lymphocyte could be seen in two of the patients without uveitis. The class II antigen HLA-DR was expressed on iris stromal cells in every patient in the Fuchs' heterochromic cyclitis group and uveitis group and in six of the patients in the nonuveitis group. In six of the Fuchs' heterochromic cyclitis patients, including two without immunohistochemical evidence of inflammatory cell infiltrate, histologic abnormalities were present on hematoxylin and eosin sections.

Aqueous humour analysis in Fuchs' heterochromic cyclitis.

Aqueous humor from 23 patients with Fuchs' heterochromic cyclitis (FHC) was analysed by a number of immunological methods. Intraocular IgG synthesis was found in 65% of patients and oligoclonal IgG bands, mainly of the IgG1 subclass, identified in 57%. There was a relative increase in IgG1 (P less than 0.01) as compared to patients with senile cataract. Local production of the cytokine Interleukin-6 was demonstrated in 63% of patients (P less than 0.01). Analysis of aqueous by HPLC and SDS-PAGE failed to reveal any abnormalities specific for FHC. These findings add further evidence to the theory of immune dysregulation in this condition.