The NLRP3 inflammasome has been shown to be involved in the development of uveitis, but the exact mechanism remains elusive. This study was undertaken to explore the role of NLRP3 in the development of uveitis.

BACKGROUND:A 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. METHODS:We 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. RESULTS:Depleted 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. CONCLUSIONS:Our 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.

This study aimed to examine possible causal associations between various components of metabolic syndrome and glaucoma‐related phenotypes.

Vogt-Koyanagi-Harada disease (VKH) is a rare autoimmune disease characterized by diffuse and bilateral uveitis, alopecia, tinnitus, hearing loss, vitiligo and headache. The transcriptional expression pattern of peripheral blood mononuclear cells (PBMC) in VKH remains largely unknown. In this study, mRNA sequencing was conducted in PBMC from VKH patients with active uveitis before treatment (n = 7), the same patients after prednisone combined with cyclosporine treatment (n = 7) and healthy control subjects strictly matched with gender and age (n = 7). We found 118 differentially expressed genes (DEGs) between VKH patients and healthy control subjects, and 21 DEGs between VKH patients before and after treatment. TRIB1 was selected as a potential biomarker to monitor the development of VKH according to the mRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the possible biological functions and signaling pathways of DEGs. Neutrophil degranulation, peptidase regulator activity, secretory granule membrane, cellular response to peptide, growth factor binding and cell projection membrane were enriched as GO annotations of DEGs. Arachidonic acid metabolism and mitogen-activated protein kinase (MAPK) signaling pathway were potential signaling pathways involved in pathogenesis and drug response of VKH. A protein-protein interaction (PPI) network was constructed by STRING, and colony stimulating factor 1 receptor (CSF1R) was identified as the hubgene of all DEGs by Cytoscape. The cell type presumed to contribute to the aberrant expression of DEGs was analyzed with the use of publicly available single-cell sequencing data of PBMC from a healthy donor and single-cell sequencing dataset of monocytes from VKH patients. Our findings may help to decipher the underlying cellular and molecular pathogenesis of VKH and may lead novel therapeutic applications.

Introduction: Immunosuppressive therapy for uveitis may cause liver damage. Methods: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. Results: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80–213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79–6.99; p value = 2.8 × 10−4) and in IPPU (aHR, 3.80; 95% CI, 1.61–9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94–10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). Conclusion: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy.

Purpose: To determine optical coherence tomographic (OCT) features of macular edema (ME) and identify potential prognostic values for ME and visual outcomes in Vogt-Koyanagi-Harada disease (VKH). Methods: In the retrospective case series, a total of 1,377 VKH patients who were seen in a tertiary uveitis center between September 2011 and January 2018 were reviewed on their demographics, visual acuity, ocular and extraocular manifestations, modes of treatment, and OCT examinations. Of these patients, 79 (5.7%) having ME were included for analysis of OCT features. Four patients were missed without ME resolution, and the remaining 75 patients who either had ME resolved or were followed up for 2 years were included for analysis of disease outcomes. Results: Of the 115 affected eyes in these 79 patients, 100 (87.0%) had cystoid ME (CME), accounting for the most common OCT feature of VKH-related ME. Disruption of the inner-segment/outer-segment junction (IS/OS) band seen in 33 (28.7%) affected eyes of 24 (30.4%) patients was found as a risk factor for the development of persistent ME [10 of 62 (16.1%) vs. 13 of 13 (100%); P < 0.001] and a poor visual outcome (1.16 ± 0.42 vs. 1.17 ± 0.46 in logMAR unit; P = 0.89). CME patients with a concurrent choroidal neovascular membrane often had a disrupted IS/OS band, thus becoming refractory cases. A 6-month well-controlled intraocular inflammation following standard treatment regimens was found to associate with complete resolution of the refractory edema [4 of 5 (80%) vs. 2 of 13 (15%); P = 0.02]. Conclusions: Intraretinal cystoid changes are most commonly seen in the edematous macula of VKH patients. Disruption of the IS/OS band is a useful risk sign for poor ME and visual outcomes in VKH-related ME, and a long-term well-controlled intraocular inflammation may be critical for the resolution of refractory cases.

ObjectiveTo explore susceptibility loci associated with uveitis in Behçet's disease (BD).MethodsWe conducted a 2‐stage study, consisting of a genome‐wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD‐related uveitis and 4,388 controls, and the replication stage included 953 cases with BD‐related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1.ResultsThree independent HLA alleles (HLA–B51 [3.75 × 10−190], HLA–A26 [1.50 × 10−18], and HLA–C0704 [3.44 × 10−16]) were identified as having a genome‐wide association with BD‐related uveitis. In the non‐HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta‐analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome‐wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1‐FIBP‐FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1.ConclusionThis GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.

ABSTRACT Purpose Although it has long been recognized that air pollution can affect the immune system and human ocular symptoms, it is uncertain whether air pollutants may also contribute to the development of uveitis. This study aimed to quantify the association of particulate matters less than 2.5 μm (PM2.5) with uveitis onset. Methods We combined monthly averages of PM2.5 concentrations, with data from the largest database of uveitis cases to assess the association between PM2.5 and uveitis onset. We further estimated the uveitis burden that was attributed to PM2.5 exposure and used choropleth maps to precisely characterize geographical variations. Results We found that a 10 μg/m3 increase in PM2.5 concentration was associated with a one-case per 10 individuals increase in uveitis onset across the dataset. Our results further suggest that PM2.5 concentrations above the level of the minimum exposure are responsible for 13% of novel uveitis cases in our cohort. Conclusion: These findings provide evidence supporting the association between fine particulate air pollution and uveitis onset.

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst. The results showed that both partial-least squares discrimination analysis and hierarchical clustering analysis showed specific aqueous metabolite profiles when comparing VKH, BD, and controls. There were 28 differential metabolites in VKH compared to controls and 29 differential metabolites in BD compared to controls. Amino acids and fatty acids were the two most abundant categories of differential metabolites. Furthermore, pathway enrichment analysis identified several perturbed pathways, including pantothenate and CoA biosynthesis when comparing VKH with the control group, and D-arginine and D-ornithine metabolism and phenylalanine metabolism when comparing BD with the control group. Aminoacyl-tRNA biosynthesis was altered in both VKH and BD when compared to controls. Our findings suggest that amino acids metabolism as well as two fatty acids, palmitic acid and oleic acid, may be involved in the pathogenesis of BD and VKH.

Whether ambient temperature influences immune responses leading to uveitis is unknown. We thus tested whether ambient temperature affects the symptoms of experimental autoimmune uveitis (EAU) in mice and investigated possible mechanisms. C57BL/6 mice were kept at a normal (22°C) or high temperature (30°C) housing conditions for 2 weeks and were then immunized with human interphotoreceptor retinoid-binding protein (IRBP651–670) peptide to induce EAU. Histological changes were monitored to evaluate the severity of uveitis. Frequency of Th1 cells and Th17 cells was measured by flow cytometry (FCM). The expression of IFN-γ and IL-17A mRNA was measured by real-time qPCR. The generation of neutrophil extracellular traps (NETs) was quantified by enzyme-linked immunosorbent assay (ELISA). Differential metabolites in the plasma of the mice kept in the aforementioned two ambient temperatures were measured via ultra-high-performance liquid chromatography triple quadrupole mass spectrometry quadrupole time of flight mass spectrometry (UHPLC-QQQ/MS). The differential metabolites identified were used to evaluate their effects on differentiation of Th1 and Th17 cells and generation of NETs in vitro. The results showed that EAU mice kept at high temperature experienced a more severe histopathological manifestation of uveitis than mice kept at a normal temperature. A significantly increased frequency of Th1 and Th17 cells in association with an upregulated expression of IFN-γ and IL-17A mRNA was observed in the splenic lymphocytes and retinas of EAU mice in high temperature. The expression of NETs as evidenced by myeloperoxidase (MPO) and neutrophil elastase (NE), was significantly elevated in serum and supernatants of neutrophils from EAU mice kept at high temperature compared to the normal temperature group. The metabolites in the plasma from EAU mice, fumaric acid and succinic acid, were markedly increased in the high temperature group and could induce the generation of NETs via the NADPH oxidase-dependent pathway, but did not influence the frequency of Th1 and Th17 cells. Our findings suggest that an increased ambient temperature is a risk factor for the development of uveitis. This is associated with the induction of Th1 and Th17 cells as well as the generation of NETs which could be mediated by the NADPH oxidase-dependent pathway.

The NLRP3 inflammasome has been shown to be involved in the development of uveitis, but the exact mechanism remains elusive. Here, we explored the role of NLRP3 in the development of uveitis. Surprisingly, contrary to previous studies, our results show that NLRP3 plays an anti-inflammatory role in two models of experimental autoimmune disease, such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE), and reduces macrophage infiltration during EAU. Additionally, macrophages show an increased pyroptosis in Nlrp3-/- mice. Further experiments indicate that this pyroptosis of macrophages was mediated by the upregulated transcription of Aim2 as a result of Nlrp3 deficiency. In mechanistic studies, Nlrp3 deficiency was implicated in downregulation of p-SIK1 and subsequently the upregulation of SREBF1, which binds to Aim2 and then promotes the latter’s transcription. Finally, RNA silencing of Aim2 or Srebf1 and induced overexpression of Nlrp3 resulted in an attenuated inflammation of EAU. In summary, our data show that NLRP3 inhibits Aim2 inflammasome mediated EAU by regulating the expression of SREBF1, highlighting the therapeutic potential of targeting Nlrp3.

Aim: This study aimed to analyze corneal transplantation trends and voluntary donor characteristics at the Chongqing Eye Bank in China. Methods: We retrospectively reviewed and analyzed data from January 1, 1999, to December 31, 2018, covering 5,397 preregistered voluntary donors, 1,955 actual donors, 3,910 donated tissues, and 2,374 corneal transplantations. Results: The 5,397 preregistered donors included 13 ethnic groups, with an overall mean age of 39.6 years (SD 21.5) and 3,010 were women (55.8%). The most prevalent education level was college and above (2,546, 47.2%), and the most common ethnic group was Han (5,335, 98.85%). Of the 1,955 actual donors, the male-to-female ratio was 3.3, and the mean age was 57.1 (SD 23.0 years). Based on population size in 2018, Jiangbei county was the most active in donation willingness, with ~60 × 10−6 per capita, and the Yuzhong county was the most active in cornea donations, with ~451 × 0−6 per capita. Of the 3,910 donated corneas, 2,540 (65.0%) were clinically used. Of those not used, 978 (71.4%) were rejected for poor corneal quality. The 2,374 (93.5%) corneal transplantation procedures were done at the Department of Ophthalmology of the First Affiliated Hospital of Chongqing Medical University and the rest (n = 166, 6.5%) were performed in other centers. Of those 2,374 corneal transplantations, there were 1,671 penetrating keratoplasty (70.39%), 700 anterior lamellar keratoplasty (29.49%), and three corneal endothelial transplantations in our center (0.13%). The number of annual corneal transplantations increased by nearly 10 times, from 35 cases in 1999 to 327 cases in 2018. Among them, cases of penetrating keratoplasty and anterior lamellar keratoplasty increased from 27, and eight cases in 1999 to 230 and 94 cases in 2018, respectively. Infectious keratitis (37.0%) was the leading indication for keratoplasty, followed by corneal scar (19.8%). Over the study period, corneal scars dropped from the first (41.1% in 1999–2003) to the second indication (20.5% in 2014–2018), while infectious keratitis advanced to take the lead, ranging from 12.2% in 1999–2003 to 26.3% in 2014–2018. Conclusion: Our study reports corneal donation and transplantation trends in Chongqing over 20 years, showing that infectious keratitis is a leading indication for keratoplasty and that penetrating keratoplasty and anterior lamellar keratoplasty show upward trends. The analysis further suggests that a potential preregistered cornea donor is a female Han, with a higher education level.

Purpose: Pediatric idiopathic uveitis typically shows anterior segment involvement. Whether retinal vasculitis is an important manifestation of this disease remains unknown and was therefore the subject of this study. Methods: This study was performed involving patients with pediatric idiopathic uveitis. Fundus fluorescein angiography was used to assess the presence of retinal vasculitis. Results: A total of 1,867 patients with pediatric uveitis were seen between December 2008 and January 2018, of whom 1,364 had undergone fundus fluorescein angiography examination. Idiopathic uveitis was the most common entity, accounting for 81.2%. Among these patients with idiopathic uveitis, 79.6% had retinal vasculitis in at least one eye. After 1-year treatment with oral prednisone mostly combined with cyclosporine, 76.3% patients in the retinal vasculitis group achieved control of their ocular inflammation, which was significantly lower as compared with 85.1% in those without ( P = 0.008). Retinal vasculitis was an independent predictor for a lower probability of inflammation control after 1-year treatment. Visual function (best-corrected visual acuity > 20/25 in the better seeing eye) was worse in the retinal vasculitis group than in the control group after 5 years. Conclusion: Almost 80% of patients with pediatric idiopathic uveitis show manifestations of retinal vasculitis, which is associated with a lower probability of inflammation control resulting in a worse visual prognosis.

Background: Behcet's disease (BD) is an autoimmune disorder with tlhe serious possibility of blindness, calling for further research on its pathogenesis. Our aim was to study the metabolite composition of sweat in BD and to identify possible biomarkers. Methods: Metabolomics analysis was performed on sweat samples from 20 BD patients and 18 normal controls by liquid chromatography tandem mass spectrometry. Results: A significantly different metabolic profile of sweat was observed when BD patients were compared with healthy controls. The result of the orthogonal partial least squared-discrimination analysis (OPLS-DA) showed that these two comparison groups could be separated with a relatively satisfactory fitting degree (R2Y = 0.995 and Q2 = 0.817 in positive ion mode; R2Y = 0.991 and Q2 = 0.721 in negative ion mode). Based on OPLS-DA, a panel of metabolites was selected as candidate biomarkers, including l-citrulline, l-pyroglutamic acid, urocanic acid, 2-oxoadipic acid, cholesterol 3-sulfate, and pentadecanoic acid. Conclusion: This is the first report on the metabolite profile of sweat in BD. Our results demonstrated a significantly different metabolite composition of sweat in BD compared to that of healthy controls.

Aims: The genetic association between Behçet's disease susceptibility and IL-10 has been confirmed in multiple cohorts, but the underlying mechanism of this association remains unclear. Materials & methods: We combined public resources and laboratory experiments (electrophoretic mobility shift assays, chromatin immunoprecipitation, luciferase reporter gene and CRISPR/Cas9 genome editing) to analyze transcription factor binding and enhancer activity controlling IL-10 expression. Results & conclusion: The T allele of noncoding rs3024490 within super-enhancer elements is able to specifically bind TBX1 and, in turn, promotes the enhancer activity and increased expression of IL-10. However, a relative deficiency in TBX1 in Behçet's disease patients leads to the low expression of IL-10 and increased risk of developing Behçet's disease.

PURPOSE:Systemic diseases are frequently associated with uveitis but are often not recognised by clinicians. An estimate of the prevalence in a large-scale uveitis population is essential for understanding the epidemiological profile and may be helpful for clinical practice.DESIGN:A nationwide survey.METHODS:Data were obtained from a national database which included the registration of uveitis cases from 23 provinces, 5 autonomous regions and 4 municipalities across mainland China. The primary outcome was identification of a systemic disease associated with uveitis.RESULTS:From April 2008 through August 2018, 15 373 uveitis patients were included in the study. Males accounted for 52.9%, and the mean (SD) age of uveitis onset was 35.4 (15.9) years. After standardisation for age, the prevalence of systemic disease among patients with uveitis was 30.8% (95% CI, 30.1% to 31.6%). Vogt-Koyanagi-Harada disease (VKH; age-standardised prevalence, 12.7%; 95% CI, 12.1% to 13.2%), Behçet's disease (BD; 8.7%; 95% CI, 8.3% to 9.2%), ankylosing spondylitis (AS; 5.0%; 95% CI, 4.6% to 5.3%) and juvenile idiopathic arthritis (JIA; 1.2%; 95% CI, 1.0% to 1.3%) were the most common entities among 36 different forms of systemic diseases identified. The prevalence was significantly higher in males (37.0%; 95% CI, 36.0% to 38.1%) than in females (23.6%; 95% CI, 22.6% to 24.6%), and also higher in bilateral uveitis patients (41.2%; 95% CI, 40.2% to 42.2%) compared with unilateral cases (14.3%; 95% CI, 13.4% to 15.2%), and was highest in panuveitis (59.5%; 95% CI, 58.2% to 60.8%).CONCLUSION:Approximately one third of uveitis patients in this nationwide survey have an associated systemic disease, whereby VKH, BD, AS and JIA are the most frequent entities seen in China.

The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.

Behcet’s disease (BD) is associated with considerable gut microbiome changes. However, it still remains unknown how the composition of the gut microbiome exactly affects the development of this disease. In this study, transplantation of stool samples from patients with active ocular BD to mice via oral gavage was performed. This resulted in decreases of three short chain fatty acids (SCFAs) including butyric acid, propionic acid and valeric acid in the feces of the BD-recipient group. Intestinal barrier integrity of mice receiving BD feces was damaged as shown by a decreased expression of tight junction proteins and was associated with the release of Lipopolysaccharides (LPS) in the circulation. The mice also showed a higher frequency of splenic neutrophils as well as an enrichment of genes associated with innate immune responses in the neutrophils and CD4 + T cells as identified by single cell RNA sequencing. Analysis of neutrophils and T cells functions in these mice showed an enhanced mesenteric lymph node and splenic Th1 and Th17 cell differentiation in association with activation of neutrophils. Transplantation of BD feces to mice and subsequent induction of experimental uveitis (EAU) or encephalomyelitis (EAE) led to an exacerbation of disease in both models, suggesting a microbial adjuvant effect. These findings suggest that the gut microbiome may regulate an autoimmune response via adjuvant effects including increased gut permeability and enhancement of innate immunity.

Background/aims Fuchs' uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS. Methods The clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020. A total of 593 patients with FUS and 625 patients with non-FUS from northern China were enrolled for the development of diagnostic criteria for FUS. Three hundred and seventy-seven patients with FUS and 503 patients with non-FUS from southern China were used to validate the criteria. Clinical symptoms and ocular signs were collected from all patients with FUS and patients with non-FUS. Multivariate two-step cluster analysis, logistic regression and decision tree algorithms in combination with the clinical judgement of uveitis experts were used to revise diagnostic criteria for FUS. Results Three essential findings including diffuse iris depigmentation, absence of posterior synechiae, mild inflammation in the anterior chamber at presentation and five associated findings including mostly unilateral involvement, cataract, vitreous opacities, absence of acute symptoms and characteristic iris nodules were used in the development of FUS diagnostic criteria. All essential findings were required for the diagnosis of FUS, and the diagnosis was further strengthened by the presence of associated findings. Conclusion Revised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).

Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission. To investigate the role of IDO in immune regulation, an effective inhibitor 1-methyl-L-tryptophan (1-MT) was used to suppress its activity in DCs. The results showed that inhibition of IDO with 1-MT significantly decreased the expression of DC marker CD86. IDO inhibition did not affect the cytokine production of IL-6, IL-1β, TNF-α, IL-10, and TGF-β in DCs. Downregulation of IDO in DCs also led to the reduction of regulatory T (Treg) cells and an increased CD4+ T cell proliferation. Treatment with 1-MT did not affect the phosphorylation of the MAPK pathway in DCs. In general, our study suggests that IDO may play an important role in the pathogenesis of VKH disease by regulating DC and CD4+ T cell function. Tryptophan deficiency and kynurenine accumulation may account for the complicated effects of IDO. Further research is needed to study the precise tryptophan metabolites that may limit immune responses in VKH disease.