Behcet's Uveitis Research Articles

Gut microbial signatures and their functions in Behcet's uveitis and Vogt-Koyanagi-Harada disease

BackgroundA number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and Vogt-Koyanagi-Harada disease (VKH). Integrated-analysis and subsequent validation of these results could be a potentially powerful way to understand the microbial signatures and their functions in these two uveitis entities. MethodsWe integrated the sequencing data of our previous metagenomic studies on two major uveitis entities, BU and VKH as well as four other publicly available immune-mediated diseases datasets, including Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Crohn's disease (CD) and Ulcerative Colitis (UC). Alpha-diversity and beta-diversity analysis were used to compare the gut microbiome signatures between both uveitis entities and other immune-mediated diseases and healthy controls. Amino acid homology between microbial proteins and a uveitogenic peptide of the interphotoreceptor retinoid-binding protein (IRBP)161-180 was investigated using a similarity search in the NCBI protein BLAST program (BLASTP). Enzyme-linked Immunosorbent Assay (ELISA) was performed to evaluate the cross-reactive responses of experimental autoimmune uveitis (EAU)-derived lymphocytes and BU patients-derived peripheral blood mononuclear cells (PBMCs) against homologous peptides. The area under the curve (AUC) analysis was used to test the sensitivity and specificity of gut microbial biomarkers. ResultsDepleted Dorea, Blautia, Coprococcus, Erysipelotrichaceae and Lachnospiraceae as well as enriched Bilophila and Stenotrophomonas were identified in BU patients. An enriched Alistipes along with a lower level of Dorea were observed in VKH patients. A peptide antigen (SteTDR) encoded by BU specifically enriched Stenotrophomonas was identified to share homology with IRBP161-180. In vitro experiments showed that lymphocytes from EAU or PBMCs from BU patients reacted to this peptide antigen as shown by the production of IFN-γ and IL-17. Addition of the SteTDR peptide to the classical IRBP immunization protocol exacerbated EAU severity. Gut microbial marker profiles consisted of 24 species and 32 species respectively differentiated BU and VKH from each other as well as from the other four immune-mediated diseases and healthy controls. Protein annotation identified 148 and 119 specific microbial proteins associated with BU and VKH, respectively. For metabolic function analysis, 108 and 178 metabolic pathways were shown to be associated with BU and VKH, respectively. ConclusionsOur study revealed specific gut microbial signatures and their potentially functional roles in BU and VKH pathogenesis that differ significantly from other immune-mediated diseases as well as healthy controls.

Analysis of Vascular Changes of Fundus in Behcet's Uveitis by Widefield Swept-source Optical Coherence Tomography Angiography and Fundus Fluorescein Angiography.

To investigate vascular changes of fundus in quiescent Behçet's uveitis(BU) based on widefield swept-source optical coherence tomography angiography(SS-OCTA) and fluorescein angiography (FA). This case-control study included 33 quiescent BU patients(57eyes)and 35 healthy people(60 eyes) as the control. All participants underwent the widefield SS-OCTA, and BU patients additionally underwent the FA. The quantitative analysis of the widefield SS-OCTA assessed the vessel density(VD) of 9 anatomic locations in the fundus. Vascular leakage and retinal nonperfusion on FA were assessed in BU patients. Compared with the control group using Mann-Whitney U test, BU patients had enlargement of foveal avascular zone (FAZ) (P=0.005, P=0.04, respectively) and decreased VD within a 300μm width around the FAZ(FAZ300μm) (P=0.001, P<0.0001, respectively) both in the superficial and deep retina. Larger FAZ size and lower FAZ300μm were correlated with higher logarithm of the minimum angle of resolution best-corrected visual acuity in BU (P≤0.003, P<0.0001, respectively). VD of choriocapillaris(CC), as the most widely involved of all layers of the retina and choroid, was lower in 6 locations(P≤ 0.03∼0.0001) in the peripheral fundus of BU compared to the controls. Vascular leakage and retinal nonperfusion in the peripheral fundus was observed in 54.4% and 66.7% of the patients on FA. Fovea and peripheral fundus were prone to the damage of ischemia as evidenced by significantly decreased VD of capillaries. Combination of SS-OCTA with FA could accurately evaluate the changes in the retinal and choroidal vasculature in BU.

Effects of Plasma-Derived Exosomal miRNA-19b-3p on Treg/T Helper 17 Cell Imbalance in Behçet's Uveitis.

To explore the potential role of plasma-derived exosomal microRNAs (miRNAs) in the development of regulatory T cell (Treg)/T helper 17 (Th17) cell imbalances in Behçet's uveitis (BU). The exosome treatment was conducted to evaluate the effects of plasma exosomes from patients with active BU and healthy controls on the Treg/Th17 cell balance. miRNA sequencing analysis of plasma exosomes was conducted to identify differentially expressed miRNAs between patients with active BU and healthy controls. miRTarBase analysis and dual-luciferase reporter assays were conducted to identify the target genes of miR-19b-3p. CD4+T cells were transfected with miR-19b-3p mimic or inhibitor to evaluate its regulation of the Treg/Th17 cell balance. The Treg/Th17 cell balance in CD4+T cells was evaluated by flow cytometry and enzyme-linked immunosorbent assay. Exosomes from patients with active BU promoted Th17 cell differentiation and inhibited Treg cell differentiation. MiRNA sequencing analysis revealed 177 upregulated and 274 downregulated miRNAs in plasma exosomes of patients with active BU. Among them, miR-19b-3p was significantly elevated, and its target genes were identified as being involved in T-cell differentiation. miR-19b-3p overexpression downregulated CD46 expression and the Treg/Th17 cell ratio in CD4+T cells from healthy controls, whereas miR-19b-3p inhibition reversed these regulatory effects and restored the Treg/Th17 cell balance of CD4+T cells from patients with active BU. Plasma-derived exosomes from patients with active BU showed a markedly differential miRNA expression in comparison to healthy controls. Highly expressed miRNA-19b-3p could induce a Treg/Th17 cell imbalance, probably by downregulating CD46 expression.

Interferon-α2a induces CD4+ T cell apoptosis and suppresses Th1/Th17 responses via upregulating IRF1-mediated PDL1 expression in dendritic cells from Behcet’s uveitis

Recombinant interferon-α2a (IFNα2a) has been widely used in the treatment of Behcet's uveitis (BU). However, the mechanism underlying its effects remains poorly understood. In this study, we investigated its effect on dendritic cells (DCs) and CD4+ T cells, which are essential for the development of BU. Our results showed that the expression of PDL1 and IRF1 was significantly decreased in DCs from active BU patients, and IFNα2a could significantly upregulate PDL1 expression in an IRF1-dependent manner. IFNα2a-treated DCs induced CD4+ T cells apoptosis and inhibited the Th1/Th17 immune response in association with reduced secretion of IFN-γ and IL-17. We also found that IFNα2a promoted Th1 cell differentiation and IL-10 secretion by CD4+ T cells. Finally, a comparison of patients before and after IFNα2a therapy revealed that the frequencies of Th1/Th17 cells significantly decreased in association with remission of uveitis after IFNα2a therapy. Collectively, these results show that IFNα2a could exert its effects by modulating the function of DCs and CD4+ T cells in BU.

Efficacy and Safety of Adalimumab in Patients with Behçet Uveitis: A Systematic Review and Meta-Analysis

ABSTRACT Purpose To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU). Methods A systematic review and meta-analysis of observational studies was performed. Pooled results are presented as mean difference or standardized mean difference (std diff) and 95% confidence intervals (CI). Visual acuity (VA), intraocular inflammation grade, central macular thickness, corticosteroid (CS) sparing effect and adverse events were evaluated. Results Ten studies were included finally for quantitative and qualitative synthesis. ADA therapy resulted in 0.124 (95%CI: 0.084, 0.165) logMAR improvement in VA. In addition, ADA therapy resulted in decreased grade of intraocular inflammation [std diff, −1.187 (95%CI: -1.508, -0.866)] and macular thickness [std diff, −0.564 (95%CI: -0.843, -0.286)] and caused a decrease in CS dosage [std diff, −1.809 (95%CI: -2.420, -1.198)]. The pooled rate of overall adverse events for ADA in 301 patients was 8.5% (95%CI: 0.039, 0.177). Conclusion ADA is an efficient therapy that improves VA and controls intraocular inflammation, macular edema and retinal vasculitis. As the disease exposure time increased, improvement in VA was less. The safety and CS-sparing effect of ADA were demonstrated with few adverse effects. The results provided evidence that ADA can be used safely and efficiently as the first-line drug in patients with BU.

Correlation between Widefield Fundus Fluorescein Angiography Leakage Score and Anterior Chamber Flare in Behçet Uveitis

ABSTRACT Aims To investigate the correlation between widefield fundus fluorescein angiography (WF-FA) and anterior chamber laser flare photometry (LFP-flare) in Behçet uveitis (BU). Methods Patients with BU who underwent Heidelberg WF-FA between March 2016 and March 2018 were included. Demographics, ocular findings, LFP-flare, central macular thickness were retrospectively analyzed. Results Eighty-six patients (162 eyes) were included. There was a high correlation between WF-FA leakage score and LFP-flare (rho: 0.691, p < .001). For a flare value of 5.75 ph/ms or higher, the sensitivity for predicting angiographic leakage was 70% and the specificity was 94% (AUC: 0.897, p < .001). Flare values that were equal or above 7.6 ph/ms were found to be 100% specific for leakage in the WF-FA. Conclusion A strong correlation was found between WF-FA leakage and LFP-flare in patients with BU. High LFP-flare levels indicate subclinical posterior segment inflammation in clinically inactive BU.

Transcriptomic profiling of iris tissue highlights LCK signaling and T cell-mediated immunity in Behcet's uveitis

Uveitis is the most common form of ocular lesions in Behcet's disease, severely affecting visual function. Molecular pathological changes of ocular lesions in patients with Behcet's uveitis (BU) are largely unknown. In this study, we performed the first comprehensive transcriptomic profiling of iris specimens from BU patients and healthy donors to provide an insight into intraocular immunopathogenesis. The mRNA sequencing identified 1633 differentially expressed genes (DEGs) between the BU group and healthy controls. GO functional enrichment analysis on DEGs showed that T cell activation was the most significantly enriched biological process. KEGG analysis of DEGs also revealed several prominently enriched T cell-related pathways, including the T cell receptor signaling pathway, Th17 cell differentiation, and Th1 and Th2 cell differentiation. The lymphocyte-specific protein tyrosine kinase (LCK) was identified as the key hub gene in the protein interaction network of DEGs. Western blot analysis further showed increased expression of active LCK in the BU group, suggesting activation of LCK signaling. Using publicly accessible single-cell RNA-sequencing data of the healthy iris, LCK was found to be expressed in clusters of activated T cells but not in other iris cell clusters, suggesting an overt association between LCK upregulation and T cell-mediated immune dysregulation. Additionally, 16 drugs were predicted to be potential inhibitors of LCK. Overall, these findings not only highlighted the central role of T cell-mediated immunity and previously unreported LCK signaling in intraocular immunopathogenesis but also revealed the potential value of LCK as a new therapeutic target for BU patients.

Infliximab therapy in Behçet's uveitis

To evaluate the efficacy of infliximab (IFX) therapy in patients with Behçet's uveitis (BU) refractory to conventional immunomodulatory treatment (IMT). This study, trial registration number TCTR20200806007, included cases of BU with a minimum of 18 months follow-up on IFX treatment. Demographic characteristics, ophthalmological examination findings, control of ocular inflammation with IFX, response to treatment and the rate of clinical remission were analyzed in this study. Sixty-two eyes of 35 patients on IFX therapy were included in the study. The mean follow-up was 49.5±25.9months. The mean frequency of recurrences during the IMT was 1.47±0.78 (attacks/year), decreasing to 0.31±0.40 (attacks/year) with IFX (P<0.001). Visual acuity improved significantly in the 1st month of IFX treatment (P=0.026). Partial response to treatment was achieved in 91.4% of cases. IFX is a safe and effective treatment in cases of BU refractory to conventional IMT.

Impacts of smoking &amp; ocular activity on Behcet disease &amp; normal control by optical coherence tomography angiography (OCTA) in Upper Egypt

Retinal vasculitis and vein occlusions are common causes of serious visual loss in Behcet’s disease. The aim of the current work was the comparison of the OCTA results of BU cases, BD without uveitis cases &amp;normal control was further subdivided to smokers &amp;non-smokers to permit us to recognize retinal micro-circulation variations at the macular level in BU cases even in the nonattendance of preceding angiographic diagnosing of vasculitis &amp; impact of smoking on BD clinical results of Behcet uveitis(BU), Behcet disease with no uveitis cases &amp;normal control by the following parameters; Vessel density of macular area (VD) &amp; foveal Avascular zone (FAZ) using OCTA. The conclusion of this study shows reduction of vessel density of macular area in Behcet uveitis (BU) rather than Behcet disease without uveitis &amp;normal control &amp; Enlarged FAZ in BU rather than BD without uveitis &amp; normal control. The study results revealed areas of hypoperfusion of macular area even in BD without clinical signifacnce. Hazards of smoking on uveitis cases . There is a need to larger samples &amp; lack of stable treatment protocols.

How challenging can it be to treat Behçet uveitis?

A 20-year-old male Behçet uveitis (BU) patient presented with visual acuities (VAs) of hand movement in OD and counting fingers at 1 m in OS following treatment with corticosteroid monotherapy elsewhere. He had active intraocular inflammation OU along with macular hole and retinal detachment in OS. Infliximab (IFX) was started and vitreoretinal surgery was performed. He had infusion reaction with IFX, hepatotoxicity and depression with interferon, and resistance to adalimumab and tocilizumab therapies. Cytomegalovirus retinitis developed in OD following intravitreal dexamethasone implant and endophthalmitis developed in OS. At the 33rd month of follow-up, the patient was in clinical remission; however, there was persistent angiographic inflammation under certolizumab pegol, cyclosporine, mycophenolate mofetil, and low-dose prednisolone treatment. The left eye was phthisical and VA was 0.4 in OD. Immunomodulatory treatment is given based on the severity of inflammation in BU and needs to be closely monitored for efficacy and adverse effects.

Determination of serum vascular endothelial growth factor (VEGF) and VEGF receptor levels with VEGF gene polymorphisms in patients with Behçet’s uveitis

Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Vascular Abnormalities in Peripapillary and Macular Regions of Behcet's Uveitis Patients Evaluated by Optical Coherence Tomography Angiography.

Purpose: To investigate the involvement of peripapillary zone vascular abnormalities in Behcet's uveitis (BU) and associated visual dysfunction. We evaluated the retinal and choroidal microvascular features in both macular and peripapillary areas of BU patients to identify vascular abnormalities contributing to reduced best-corrected visual acuity (BCVA) using optical coherence tomography angiography (OCTA).Methods: A prospective, observational study was conducted in 24 eyes of 13 patients with BU and 24 eyes of 15 healthy participants as controls. They received a standard eye examination and were recorded by OCTA measurements of macular and peripapillary areas. The vascular densities of superficial capillary plexus (SCP) and deep capillary plexus (DCP), choroidal flow area, radial peripapillary capillary network (RPCN) density, foveal avascular zone (FAZ) area and perimeter, full retinal thickness (FRT), and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured.Correlations among microvascular, structural, and functional changes were assessed.Results: Our findings uncovered that the vascular density was significantly reduced in the peripapillary zone of BU eyes compared to healthy eyes, especially in the inferior subfield of the RPCN. The vascular densities of SCP and DCP quadrants within the macular zone had no significant difference between BU and control groups except for DCP density of the nasal parafoveal quadrant. Both FAZ area and perimeter were greater but without statistical significance in the BU group. Compared to healthy eyes, the choriocapillaris flow area was smaller while the FRT and pRNFLT were greater in the BU group. Notably, there was a significant correlation between the reduction in RPCN vascular density and decreased BCVA in BU patients.Conclusion: Based on OCTA, vascular changes associated with BU are more prominent in the peripapillary zone than those in the macular zone. The vascular density of the RPCN could serve as a sensitive indicator to monitoring BU pathogenic progression and treatment response using a non-invasively method of OCTA.

Increased serum level of interleukin-33 in Vogt-Koyanagi-Harada correlates with disease activity

ObjectivesTo measure the serum level of IL-33 in patients with Vogt-Koyanagi-Harada disease (VKH) and Behçet's uveitis (BU) in the Chinese Han population and investigate its associations with disease activity and clinical parameters. MethodsSerum was collected from 41 VKH patients (16 active and 25 inactive patients), 60 BU patients (24 active and 36 inactive patients), and 36 healthy controls. The serum level of IL-33 was measured using the enzyme-linked immunosorbent assay (ELISA) method. Demographic features, clinical manifestations, and intraocular inflammation activity scores (anterior chamber cells score, anterior chamber flare score, and vitreal haze score) were recorded. ResultsThe serum level of IL-33 significantly increased in all VKH patients, active VKH patients, and inactive VKH patients, as compared to healthy controls (p < 0.001, p < 0.001, and p = 0.002, respectively), and was higher in the active VKH than in the inactive VKH patients (p = 0.049). The serum level of IL-33 positively correlated with the anterior chamber cells score, vitreal haze score, and the annualized number of relapses in VKH patients (Rho = 0.359, p = 0.021; Rho = 0.344, p = 0.028; Rho = 0.537, p < 0.001, respectively). Serum IL-33 level was significantly associated with the annualized number of relapses in patients with BU (Rho = 0.361, p = 0.005). ConclusionSerum IL-33 level is significantly increased in VKH patients in the Chinese Han population. IL-33 level is in positive correlation with the activity and relapses of VKH. Increased IL-33 might contribute to the pathogenesis of VKH and serve as a potential biomarker for VKH disease.

Optical coherence tomography angiography findings in patients with ocular and non-ocular Behcet disease.

To evaluate the optical coherence tomography angiography findings in patients with Behçet disease with and without ocular involvement. A total of 40 patients with Behçet disease and 30 healthy controls were enrolled in the study. Retinal vessel density in the superficial capillary plexus and deep capillary plexus, foveal avascular zone area and perimeter, acirculatory index, foveal density, and nonflow area in the superficial retina were automatically measured using the optical coherence tomography angiography software AngioVue and compared between the groups. The mean parafoveal and perifoveal vessel densities in the superficial capillary plexus and deep capillary plexus and foveal density were significantly lower in the eyes with Behçet uveitis compared to the eyes without Behçet uveitis and eyes of the healthy controls. In the eyes with Behçet uveitis, logMAR visual acuity showed a moderate correlation with parafoveal and perifoveal vessel densities and foveal density (r=-0.43, p=0.006; r=-0.62, p<0.001; r=-0.42, p=0.008; respectively). Behçet disease with posterior uveitis was associated with significant perifoveal and parafoveal vascular decrements in the superficial and deep retina.

Progress in interferon: A treatment of Behcet syndrome

Behcet syndrome (BS) is a chronic systemic inflammatory disorder involving vessels of all sizes, characterized by relapsing episodes of oral and/or genital ulcers, as well as skin lesions. Ocular, vascular, gastrointestinal, neurological system involvement can cause significant morbidity and mortality. Glucocorticoids and immunosuppressants are the cornerstones for the management of BS. Biologic agents has been recommended for severe and/or refractory BS. Interferon-α (IFN-α) had multiple biological effects, such as antiviral and antiproliferative, that could regulate both innate and adaptive immunity in BS. Growing evidence showed the efficacy of IFN-α in severe and/or refractory BS. Many studies have demonstrated that IFN-α has comparable effectiveness and tolerance profiles as anti-tumor necrosis factor (TNF) agents for Behcet's uveitis with a much lower cost and steroid-and immunosuppressant-sparing effects. IFN-α has been recommended as second-line therapy for ocular involvement of BS in EULAR (The European League Against Rheumatism) 2018. IFN-α also improves mucocutaneous lesions in BS with the dosage from 3 to 9-12 million IU three times per week. A few cases indicated the therapeutic potential of IFN-α in intestinal BS. As a new trial of IFN-α in vascular BS (VBS), a recent study revealed the lower relapse rate and higher recanalization rate with IFN-α in lower extremity deep vein thrombosis (DVT). Another two case reports presented the efficacy of IFN-α in pulmonary artery involvement in BS. Also, case reports have shown successful treatment in refractory neurological involvement. There are two subtypes of IFN-α commonly used in autoimmune diseases, named IFN-α2a and IFN-α2b. IFN-α2a seemed more effective than IFN-α2b, especially in ocular and mucocutaneous involvement of BS. Side effects of IFN-α are dose-dependent and not severe. The most frequent side effects are flu-like syndrome, mild leukopenia and alopecia. Considering the potential risk of tuberculosis (TB) and hepatitis B virus (HBV) reactivation of TNF-α inhibitors, IFN-α is safe due to its anti-HBV effect and protective effect on TB. In conclusion, IFN-α is a promising choice for severe and/or refractory BS patients, especially for those who are intolerant or contraindicant to other biological agents, such as TNF inhibitors. Further prospective controlled studies are warranted to confirm the efficacy and safety of IFN-α in BS.

Behçet's Uveitis: Current Diagnostic and Therapeutic Approach

Behçet’s disease is a chronic, multisystem inflammatory disorder characterized by relapsing inflammation. Although its etiopathogenesis has not yet been clarified, both the adaptive and innate immune systems, genetic predisposition, and environmental factors have all been implicated. It is more frequent and more severe in males in the third and fourth decades of life. The eye is the most frequently involved organ in the course of the disease. Ocular involvement (Behçet’s uveitis) is characterized by bilateral recurrent non-granulomatous panuveitis and occlusive retinal vasculitis. Recurrent inflammatory episodes in the posterior segment may lead to permanent vision loss due to irreversible retinal damage and complications such as macular scarring, macular atrophy, and optic atrophy. Early and aggressive immunomodulatory treatment and the use of biologic agents when needed are crucial for preventing recurrences and improving visual prognosis.

Clinical features of patients with Behcet's uveitis

Objective: To characterize the clinical features of patients with Behcet's uveitis. Methods: Retrospective case series study. Medical records of patients who were diagnosed as Behcet's uveitis in Peking Union Medical College Hospital between January 1998 and November 2015 were retrospectively reviewed. Information about the clinical manifestation, complication, best corrected visual acuity (logarithm of the minimum angle of resolution) and medication was collected. The correlation of visual acuity and the disease course, as well as inflammation relapse times before and after biological agents applied was analyzed. Chi square test and Wilcoxon signed-rank test were applied for statistical analysis. Results: A total of 132 patients (233 eyes) with Behcet's uveitis were included, among which 104 (78.8%) were male and 28 (21.2%) were female, with statistically significant difference (χ(2)=43.76, P<0.01). The average age at the onset of uveitis was (28.9±8.7) years, with most patients at 21-40 years (102 cases, 77.3%). Oral aphthae (132 cases, 100.0%) were the most frequent extraocular manifestations, followed by dermatologic lesions (103 cases, 78.0%), genital ulcers (90 cases, 68.2%), arthritis (44 cases, 33.3%) and positive pathergy test (39 cases, 29.5%). Ocular involvement was bilateral in 76.5% (101 cases) of the patients, and panuveitis was the most common type (110 cases, 83.3%). Complications were seen in 80.7% (188/233) of the eyes, with cataract (58.8%, 137/233) and macular edema (59.1%, 114/193) being the most common anterior and posterior segment complications, respectively. At the eighth year of uveitis, best corrected visual acuity decreased to less than 0.3 in 20.9% (9/43) of the eyes, and more than 1.0 in 39.5% (17/43) of the eyes. A combination of glucocorticoids and immune modulators remained the first line therapy (97.0%, 128/132) for Behcet's uveitis. For 16 refractory cases, an addition of biological agents significantly reduced the inflammation relapse [0.5 (0.0, 1.5) times per year vs. 4.0 (1.0, 5.5) times per year, Z=-2.81, P=0.005]. Conclusions: Behcet's uveitis mainly affects working-age males and manifests as bilateral panuveitis. Complications are commonly seen in uveitic eyes. Patients' visual acuity is significantly impaired. A combination of glucocorticoids and immune modulators is effective for most patients, but for refractory cases, an addition of biological agents provides better effects. (Chin J Ophthalmol, 2020, 56: 217-223).

Golimumab for the Treatment of Refractory Behcet's Uveitis

Golimumab for the Treatment of Refractory Behcet's Uveitis

Changes of peripheral blood leukocyte in Behçet uveitis patients with different stages

Objective To analyze the changes of peripheral blood leukocyte in patients with Behcet uveitis (BU) at different stages. Methods Case control study was performed.Twenty active stage BU patients and 21 quiet stage BU patients were enrolled from July to November 2015 in Peking Union Medical College Hospital.Ten active stage BU patients treated with glucocorticoid and/or immunosuppressive agents were served as improvement stage BU patients.Meanwhile, 82 healthy controls were collected from the physical examination center.Peripheral blood was obtained and then analyzed by using Hematoflow method.The percentages of leukocytes in peripheral blood of different stage BU patients were compared.This study was approved by the Ethics Committee of Peking Union Medical College Hospital (ZS-1341) and all participants signed informed consent. Results The percentage of mature neutrophils, eosinophils, basophils, B lymphocytes, non-cytotoxic T and NK lymphocytes, granular T and NK lymphocytes, T blasts, B blasts and immature granulocytes were all significantly different among active stage BU group, quiet stage BU group and healthy control group (F=42.324, 10.220, 8.660, 11.254, 29.795, 31.305, 23.742, 27.738 and 34.638, all at P<0.001). The percentage of mature neutrophils in active stage BU group and quiet stage BU group were (73.10±10.21)% and (62.40±12.09)%, which were significantly higher than (54.95±6.07)% in healthy control group.The percentage of mature neutrophils in active stage BU group was significantly higher than that in quiet stage BU group (P<0.05). The percentages of non-cytotoxic T, NK lymphocytes, granular T and NK lymphocytes in active stage BU group and quiet stage BU group were significantly lower than that in healthy control group, the percentage of non-cytotoxic T, NK lymphocytes and granular T, NK lymphocytes in active stage BU group were significantly lower than those in quiet stage BU group (all at P<0.05). The percentage of immature granulocytes after treatment was significantly higher than that before treatment in improvement stage BU group (t=-2.469, P=0.036). Conclusions Increase of peripheral blood mature neutrophil was observed in BU patients, which may help to monitor the inflammatory activity of BU. Key words: Behcet syndrome; Uveitis; Peripheral blood leucocyte; Neutrophil

The Results of Interferon-Alpha Treatment in Behçet Uveitis

ABSTRACTPurpose: To assess the efficacy and tolerability of interferon alpha (IFN-α) treatment in patients with refractory Behçet uveitis (BU).Methods: The patients with BU who were treated with subcutaneous IFN-α were divided into groups according to treatment response. Demographic features, best corrected visual acuity (BCVA), central macular thickness (CMT) value, and fluorescein angiography (FA) scores were compared between the groups.Results: Twenty-one (84%) of the 25 patients responded to IFN-α treatment. Active inflammation resolved at the first month’s visit in all patients. The improvement in mean BCVA and CMT achieved at the first month’s visit in all groups; however, the improvement in mean CMT in the non-responder group could not be maintained at the last visit. Main FA score significantly decreased in both the complete and partial remission group; however, it decreased minimally in the non-responder group.Conclusion: IFN-α seems an effective and safe treatment option in the management of refractory BU.