The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study.

BACKGROUND: The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls. METHODS: The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied. RESULTS: Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test). CONCLUSION: In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA. METHODS: We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo. CONCLUSION: Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.

Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))1. How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8+ T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public ß-chain variable region-complementary-determining region 3ß (BV9-CDR3ß) motif2-4 from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent α-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3ß TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease.

Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis.

Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. Uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27-positive (n = 4) and -negative (n = 2) anterior uveitis and an infectious endophthalmitis control (n = 1) by combining single-cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27-positive uveitis exclusively featured a plasmacytoid and classical dendritic cell (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27-positive uveitis with relevance to DCs.

Uveitis is a form of inflammation in the eye. It can occur in response to infection, or when the immune system mistakenly attacks the eye, in what is known as autoimmune uveitis. In approximately 80 percent of cases, the front part of the eye is affected. During an inflammatory episode, the liquid inside the front part of the eye fills with immune cells, but the nature of these cells remains unknown. This is because uveitis is rare, and doctors cannot routinely take samples from inside the eyes of affected individuals to diagnose the disease. This lack of samples makes research into this disease challenging. There are two main groups of immune cells that could be responsible for uveitis: myeloid cells and lymphoid cells. Myeloid cells form the first line of immune defense against infection by non-specifically attacking and removing pathogens . Lymphoid cells form the second line of immune defense, attacking specific pathogens. Lymphoid cells also have long-term memory, meaning they can 'remember' previous infections and fight them more effectively. Lymphoid cells receive instructions from a type of myeloid cell called a dendritic cell about what to attack. Dendritic cells relay their instructions to lymphoid cells using molecules called human leukocyte antigens (HLA). Autoimmune uveitis affecting the front part of the eye is common in individuals with an HLA type called HLA-B27, suggesting that communication between dendritic and lymphoid cells plays an important role in this type of inflammation. To make the most of limited patient samples, Kasper et al. used single cell techniques to examine the immune cells from the fluid inside the eye. Six samples came from people with autoimmune uveitis, and one from a person with an eye infection. The infection sample contained mainly myeloid cells that might attack bacteria responsible for the infection. In contrast, the autoimmune uveitis samples contained mainly lymphoid cells. Of these samples, four were from individuals with the gene that codes for the HLA-B27 molecule. These samples had a unique pattern of immune cells, with more dendritic cells than the samples from individuals that did not have this gene. This study included only a small number of individuals, but it shows that analysing single immune cells from the eye is possible in uveitis. This snapshot could help researchers understand the local immune response in the eye, and find an optimal treatment.

Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells.

The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.

Classification Criteria for Spondyloarthritis/HLA-B27-Associated Anterior Uveitis.

PURPOSE: The purpose of this study was to determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with spondyloarthritis/HLA-B27-associated anterior uveitis and 8 other anterior uveitides. METHODS: Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated in the validation set. RESULTS: A total of 1,083 cases of anterior uveitides, including 184 cases of spondyloarthritis/HLA-B27-associated anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% CI: 92.4-98.6). Key criteria for spondyloarthritis/HLA-B27-associated anterior uveitis included 1) acute or recurrent acute unilateral or unilateral alternating anterior uveitis with either spondyloarthritis or a positive test result for HLA-B27; or 2) chronic anterior uveitis with a history of the classic course and either spondyloarthritis or HLA-B27; or 3) anterior uveitis with both spondyloarthritis and HLA-B27. The misclassification rates for spondyloarthritis/HLA-B27-associated anterior uveitis were 0% in the training set and 3.6% in the validation set. CONCLUSIONS: The criteria for spondyloarthritis/HLA-B27-associated anterior uveitis had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Clinical Features and Diagnosis of Anterior Segment Inflammation Related to Cytomegalovirus in Immunocompetent African, Asian, and Caucasian Patients.

Objective: To report the clinical features and treatment outcomes in immunocompetent patients with anterior segment inflammation (ASI) related to human cytomegalovirus (HCMV) depending on their ethnic origin.Material and Methods: Multicenter retrospective study of 38 patients with at least one test, either HCMV-positive PCR or GWc.Results: Features of Posner-Schlossman syndrome were observed in 50% of the eyes, Fuchs heterochromic iridocyclitis in 13% of the eyes, chronic nonspecific anterior uveitis in 21% of the eyes, and corneal endotheliitis in 18% of the eyes. PCR and GWc were positive for HCMV in 50% and 96.2% of the eyes, respectively. Glaucoma was diagnosed in 50% of eyes. Treatment was oral valganciclovir in about half of the patients. Other treatments were intravenous ganciclovir and/or ganciclovir topical ointment and/or intravitreal ganciclovir.Conclusions: No obvious association of specific clinical features with individual ethnicity could be identified. We found a high rate of glaucoma in all ethnic groups. There was a delay in diagnosis and specific treatment of HCMV in most patients.

Phenotype of Innate Immune Cells in Uveitis Associated with Axial Spondyloarthritis- and Juvenile Idiopathic Arthritis-associated Uveitis.

Purpose: To analyze circulating immune cells in patients with anterior uveitis (AU) associated to axial spondyloarthritis (SpA), or juvenile idiopathic arthritis (JIA).Methods: Venous blood samples were collected from healthy controls (n = 16), and either SpA (n = 19) or JIA (n = 23) patients with associated anterior uveitis (AU) during active flare, or after ≥3 months of inactivity. Frequencies of CD56+, MHC-I+, and S100A9+ monocytes, CCR7+ dendritic cells, CD56+dim natural killer (NK) cells and CD3+CD56bright T-cells were analyzed via flow cytometry. Serum S100A8/A9 levels were determined via ELISA.Results: SpA patients showed a reduced frequency of CD56+dim NK cells during uveitis activity, a constitutively activated monocyte phenotype, and elevated S100A8/A9 serum levels. In contrast, JIAU patients showed elevated frequencies of CD56+ monocytes and CCR7+ DC.Conclusion: Phenotype of peripheral immune cells differ between patients, probably contributing to different courses of acute onset AU in SpA and insidious onset AU in JIAU patients.Abbreviations: AU: anterior uveitis, AR: arthritis, JIA: juvenile idiopathic arthritis, SpA: axial spondyloarthritis.

Allergic inflammation of the anterior surface of the eye.

Background: Ocular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis and includes tear film dysfunction. With the current advent of both repurposed drugs for ocular allergies, as well as novel drugs, lubricants and methods of administration, there is a need to update new treatments to optimize the care of ocular allergy patients. Methods: An overview of mediators, clinical characteristics and management is provided in a summary format. Results: Lubricants (best when refrigerated provide immediate relief that is short lived (several minutes) due to its dilutional effect on mediators and pollen in the tear film. Immediate and longer-term benefit occurs from different topical and oral medications - primarily histamine receptor agonists. Conclusion: The newest prescription topical ophthalmic histamine H1 receptor antagonist (an inverse agonist) to be approved by the U.S. Food and Drug Administration in the past 10 years (U.S. NDA approved May 30, 2017) is cetirizine ophthalmic solution for the treatment of ocular itching with allergic conjunctivitis in adults and in children more than 2 years old.

Study of ocular manifestations in tuberculosis and its association with HIV AIDS in a tertiary care hospital.

OBJECTIVE: To assess and understand the prevalence and clinical presentation of ocular morbidity in patients suffering from tuberculosis and compare it with ocular involvement in patients coinfected with tuberculosis and HIV AIDS. MATERIALS AND METHODS: This was a non-comparative, observational, cross sectional study done on 580 patients, who were diagnosed cases of tuberculosis, pulmonary or extrapulmonary, on or off treatment, visiting the Ophthalmology OPD, Tuberculosis OPD and ART Centre of the institute in the period from March 2015 to March 2018, screened for ocular morbidity. RESULTS: Out of 580, 408 patients had only tuberculosis and 172 had tuberculosis with HIV AIDS. 108 patients were found to have ocular involvement (18.6%) out of which 63 were males and 45 were females. The prevalence of ocular morbidity in patients with only tuberculosis was found to be 16.4% and in those having both tuberculosis and HIV AIDS was found to be 23.8%. CONCLUSION: Our study concludes that posterior uveitis, pan uveitis, periphlebitis and vitritis are the most common ocular manifestations in tuberculosis. In patients with both tuberculosis and HIV most common ocular findings included vitritis and herpes zoster ophthalmicus. Our study also concludes that lower CD4 counts (less than 200) in HIV AIDS patient is significantly associated with ocular involvement.

Analysis of the role of palmitoleic acid in acute anterior uveitis.

PURPOSE: To study the role of palmitoleic acid (PA) in the pathogenesis of acute anterior uveitis (AAU). METHODS: PA levels in feces from AAU patients were measured by gas chromatography coupled with a mass spectrometer (GC-MS) and compared with samples obtained from healthy individuals. Enzyme linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to assess the effect of PA on dendritic cells (DCs) and CD4+T cells obtained from mice, AAU patients and healthy individuals. C57BL/6 mice were fed with PA or vehicle and experimental autoimmune uveitis (EAU) was induced with a human retinal IRBP651-670 peptide. Disease severity of EAU was evaluated by clinical manifestation and histology. Differentiation of splenic Type 1 helper T cells (Th1) and Th17 cells was evaluated by FCM. Tandem mass tag (TMT)-based proteomics analysis was used to identify differentially expressed proteins following incubation of DCs with PA. RESULTS: The fecal concentration of PA was increased in AAU patients as compared with healthy individuals. In vitro, PA promoted apoptosis of DCs and inhibited the secretion of TNF-α from mouse bone-marrow-derived dendritic cells (BMDCs) as well as in DCs from AAU patients and healthy individuals. It only decreased DCs surface marker expression and IL-12p70 secretion in BMDCs and healthy individuals DCs but not in AAU patient DCs. PA-treated BMDCs inhibited Th cell differentiation from mouse naïve CD4+T cells and IL-17 and IFN-γ secretion in co-culture supernatants. PA also inhibited the differentiation of Th cells and secretion of IFN-γ and IL-17 in CD4+T cells from mice, AAU patients and healthy individuals. In vivo, PA-treated EAU mice showed milder clinical and histopathological intraocular manifestations as compared with the control group. PA feeding inhibited differentiation of splenic Th17 cells, whereas Th1 cells were not affected. Up to 30 upregulated and 77 downregulated proteins were identified when comparing PA-treated DCs with controls. CONCLUSION: An increased expression of fecal PA was observed in AAU patients. PA was shown to have immunoregulatory effects on DCs and CD4+T cells and attenuated disease severity in EAU mice.

A case of severe flare reaction observed in HLA B27 associated acute anterior uveitis.

BACKGROUND: Anterior chamber flare reaction refers to the light reflection from the protein in aqueous humor. We report a case of very severe flare reaction observed in human leukocyte antigen (HLA)- B27 associated acute anterior uveitis (AAU). CASE PRESENTATION: An age 43 male patient visited the uveitis clinic complaining of decreased visual acuity in the right eye which developed 1 week before. The detailed ophthalmic examination revealed very severe flare reaction in the anterior chamber with diffuse conjunctival hyperemia in the right eye. Pupil margin and iris details were barely observable. Oral prednisolone 20 mg daily with topical 1% prednisolone acetate (Pred Forte, Allergan, CA) every 2 h and 1% topical cyclopentolate (Cyclogyl, Alcon, TX) three times daily were immediately prescribed. The next day, the flare reaction of the right eye decreased significantly and inflammatory cells in the anterior chamber were visible. Detailed fundus examination revealed no inflammatory signs on the retina and ciliary body. Later, the blood test revealed positive HLA B27 and autoantibodies against lupus anticoagulant with mild elevation of C reactive protein. There were no signs for ankylosing spondylitis. Continued treatment and tapering of topical 1% prednisolone acetate for 4 weeks led to the complete resolution of the anterior uveitis. CONCLUSIONS: We experienced HLA-B27 AAU with the feature of a very severe flare reaction. Conventional uveitis treatment was successful to acquire the complete resolution of the inflammation.

Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany.

BACKGROUND: To analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome. METHODS: Prospective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis add-on module from the years 2002 to 2016. Cross-sectional data from the years 2002 to 2016 were analyzed. Patients with JIA-associated uveitis and with ANA-positive idiopathic anterior uveitis were included and the disease manifestation investigated in terms of uveitis characteristics and disease course. RESULTS: Of the total cohort of 34,458 patients enrolled in the NPRD, including 3551 patients with uveitis, those with detailed uveitis documentation were taken into account: 62 ANA-positive patients with idiopathic anterior uveitis (group 1), 688 patients with initial uveitis diagnosis after JIA onset (group 2), and 61 JIA patients with initial uveitis diagnosis before arthritis onset (group 3). Anterior uveitis was documented in 100%, 94%, and 80% of patients and with insidious onset of uveitis flare in 50%, 70.9%, and 56.1% each in groups 1, 2, and 3, respectively. Use of topical or systemic corticosteroids and conventional synthetic or biological DMARDs did not significantly differ between the patient groups, either at the initial or the 2-year follow-up (2-FU) visits (mean 2 years, each p > 0.05). At 2-FU, uveitis inactivity was achieved in 64.7%, 55.8%, and 61.5% of patients in groups 1, 2, and 3 (p > 0.05). Uveitis-related complications were more frequent at the initial visit and at 2-FU in groups 1 and 3, as compared to group 2. CONCLUSIONS: ANA-positive idiopathic uveitis and JIA-associated uveitis do not significantly differ concerning clinical course of uveitis, treatment, and response to corticosteroids and DMARDs.

Recent Developments in HLA B27 Anterior Uveitis.

There has been steady progress in understanding the pathogenesis, clinical features, and effective treatment of acute anterior uveitis (AU) over the past 5 years. Large gene wide association studies have confirmed that AU is a polygenic disease, with overlaps with the seronegative arthropathies and inflammatory bowel diseases, associations that have been repeatedly confirmed in clinical studies. The role of the microbiome in AU has received increased research attention, with recent evidence indicating that human leukocyte antigen B27 (HLA B27) may influence the composition of the gut microbiome in experimental animals. Extensive clinical investigations have confirmed the typical features of acute AU (AAU) and its response to topical, regional and systemic immunosuppressive treatment. Increased understanding of the role of cytokines has resulted in studies confirming the value of anti-cytokine therapy [anti-tumor necrosis factor (anti-TNF) and interleukin 6 (IL-6) therapy] in severe and recurrent cases of AAU, particularly in subjects with an associated spondyloarthopathy (SpA) and in juvenile idiopathic arthritis (JIA)-associated AAU.

Aqueous cytokine levels in four common uveitis entities.

To investigate aqueous cytokine profiles in acute anterior uveitis (AAU), Fuchs' syndrome, Vogt-Koyanagi-Harada (VKH) disease and Behcet's disease (BD), we assayed the concentrations of 17 cytokines by multiplex immunoassay in aqueous humor (AqH) collected during cataract surgery from 24 AAU, 29 Fuchs' syndrome, 29 VKH disease, 30 BD and 30 senile cataract control patients. Aqueous cytokine levels were compared between the five groups and analysed by logistic regression. Cytokine levels were then compared between uveitis patients who underwent cataract surgery within 3 months and those who underwent this surgery more than 3 months after complete control of intraocular inflammation. The results showed that aqueous levels of interferon (IFN)-γ, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1ß and tumour necrosis factor (TNF)-α levels in AqH from patients with Fuchs' syndrome were significantly higher than those in the other four groups. Using multivariate analysis, MIP-1ß was found to be significantly associated with Fuchs' syndrome. There was no difference in aqueous cytokine levels between cases having cataract surgery within 3 months compared to those after 3 months of complete control of their intraocular inflammation. The current study shows that Chinese patients with Fuchs' syndrome appear to have a specific cytokine profile. MIP-1ß is an important chemokine in the intraocular environment of Fuchs' syndrome. Aqueous cytokine profiles support the performance of cataract surgery in uveitis within 3 months after intraocular inflammation control.

Anterior uveitis in patients with spondyloarthropathies in a single US academic center: a retrospective study.

Uveitis may represent an opportunity to diagnose spondyloarthropathies (SpA) earlier and influence treatment decisions. We describe the percentage of acute anterior uveitis (AAU) in a diverse group of SpA patients seen at one academic setting and compare demographic and clinical characteristics according to the presence of uveitis. We conducted a retrospective study of patients with SpA and AAU (January 2016-June 2017). Patients were identified using ICD-10 and administrative claim codes, diagnoses were confirmed through chart review. Extracted data included demographics, laboratory, clinical data, treatment and Routine Assessment of Patient Index Data 3 (RAPID3) scores based on Multidimensional Health Assessment Questionnaire (MDHAQ). Baseline description and comparison between the two groups were performed. We included 190 patients, mostly men (59.5%), with a mean age of 45.9 years: 48% with ankylosing spondylitis (AS), 26% with psoriatic arthritis (PsA), 22% with undifferentiated SpA, and 4% with SpA associated with inflammatory bowel disease (IBD). Uveitis was identified in 17% of patients, ranging from 25% in AS to 4% in PsA. Time from symptom onset to SpA diagnosis was longer in patients with uveitis (10.9 versus 5.9 years, p < 0.001). A higher percentage of patients with uveitis were HLA-B27 positive (85% versus 67%, p = 0.02). The prevalence of uveitis in our population was 17%, slightly lower than previously reported in the literature. There was a diagnostic delay of about 7 years, significantly longer in patients with uveitis. New screening strategies in collaboration with ophthalmology may lead to earlier diagnosis and better outcomes.

Inhibitory role of transforming growth factor ß2 in experimental autoimmune anterior uveitis.

PURPOSE: Experimental autoimmune anterior uveitis (EAAU) is a clinically relevant animal model for human idiopathic anterior uveitis (IAU). The role of the immunomodulator transforming growth factor ß2 (TGF-ß2) in EAAU pathology is unknown. In this study, we investigated the regulatory role of TGF-ß2 in EAAU. METHODS: EAAU was induced in male Lewis rats by footpad injection of melanin-associated antigen (MAA). TGF-ß2 was administered intravenously (iv) in MAA-sensitized rats during the induction of EAAU, or after the clinical onset of uveitis. MAA-sensitized rats injected similarly with an equal volume of PBS served as control. Animals were examined daily between days 7 and 30 post-injection for the clinical signs of uveitis using slit lamp biomicroscopy. Animals were sacrificed at various time points and eyes were harvested for histological analysis to assess the course and severity of inflammation. For histopathological analysis, paraffin sections of harvested eyes were stained with hematoxylin and eosin. Popliteal lymph nodes (LNs) were used for CD4+CD25+FoxP3+ T regulatory (Tregs) population analysis and for CD4+ T cell proliferation assay. RESULTS: Administration of recombinant TGF-ß2 during the early stages of EAAU prevented the induction of uveitis. Compared to PBS, the presence of TGF-ß2 in the cell culture significantly (p < 0.05) inhibited the proliferation of CD4+ T cells in response to MAA. In MAA-sensitized Lewis rats, iv treatment with recombinant TGF-ß2 resulted in significantly (p < 0.05) increased percentage of Tregs compared to animals treated similarly with PBS. Thus, TGF-ß2 inhibited the induction of EAAU by inhibiting CD4+ T cell proliferation and increasing the number of Tregs. Injection of TGF-ß2 in rats with active EAAU resulted in diminished disease activity. Unfortunately, this treatment did not lead to the early resolution of EAAU. CONCLUSIONS: TGF-ß2 plays a critical role in regulation of intraocular inflammation in EAAU. Findings reported in this study improve our understanding of immunopathology of IAU and suggest that recombinant TGF-ß2 may be a promising therapeutic agent for human IAU.

Efficacy of anti-tumour necrosis factor-α monoclonal antibodies in patients with non-infectious anterior uveitis.

OBJECTIVES: To assess the efficacy of monoclonal anti-tumour necrosis factor (TNF)-α agents in patients with anterior uveitis (AU) in terms of decrease of recurrences, variation of visual acuity and steroid sparing effect and to identify any demographic, clinical or therapeutic variables associated with a sustained response to monoclonal TNF-α inhibitors. METHODS: Data from patients suffering from AU treated with adalimumab, infliximab, golimumab or certolizumab pegol were retrospectively collected and statistically analysed. RESULTS: Sixty-nine patients (22 males, 47 females), corresponding to 101 eyes, were enrolled. The mean follow-up period was 29.25±23.51 months. The rate of ocular flares decreased from 42.03 events/100 patients/year recorded during the 12 months preceding the start of TNF-α inhibitors to 2.9 flares/100 patients/year after the start of treatment (p<0.0001). The overall decrease in ocular flares was 93.1%. No statistically significant changes were identified in the best corrected visual acuity during the follow-up period (p>0.99). The number of patients treated with corticosteroids at baseline was significantly higher compared with that referred to the 12-month evaluation (p<0.001) and to the last follow-up visit (p=0.006). Concomitant treatment with conventional disease-modifying anti-rheumatic drugs (cDMARDs) represented the sole clinical, demographic or therapeutic variable associated with long-term treatment duration (p=0.045, R2=0.87). CONCLUSIONS: Monoclonal TNF-α inhibitors induce a remarkable decrease in the recurrence of AU during a long-term follow-up period and lead to a significant steroid sparing effect along with stabilisation of visual acuity. Concomitant treatment with cDMARDs represented the sole variable associated with treatment duration in the long-term.

Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis.

Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease.