Development of chitosan/sodium carboxymethyl cellulose-based polyelectrolyte complex of dexamethasone for treatment of anterior uveitis.

Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose (CMC). The formulations were optimized using Box-Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle size (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, zeta potential, and pH of the optimized formulation were found 451 ± 82.0995 nm, 0.3807 ± 0.1862, +20.33 ± 1.04 mV and 6.8367 ± 0.0737 respectively. The %EE and drug loading of formulation were 61.66 ± 4.2914% and 21.442 ± 1.814% respectively.In vitrodrug release studies of optimized formulation showed the prolonged release up to 12 h whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 h and 98.1462 ± 3.0921% at 6 h, respectively. Fourier transform infrared studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas differential scanning calorimetry and x-ray diffraction studies showed the amorphized nature of the drug in the formulation. Transmission electron microscopy study showed self-assembled, nearly spherical, core-shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. Hen's Eggs test-Chorioallantoic Membrane test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release.

Adalimumab to treat noninfectious pediatric chronic anterior uveitis: a case series.

PURPOSE: Evaluate the response to adalimumab (ADA) in pediatric chronic anterior uveitis (pCAU). METHODS: Retrospective chart review of pCAU patients treated with ADA. Outcomes evaluated included the proportion of patients achieving zero ocular inflammation and discontinuation of topical corticosteroids, visual outcomes, and incidence of uveitis recurrences after ≥ 12 months of prescribing ADA. Incidence and risk factors for developing anti-adalimumab antibodies (AAAs) were also evaluated. RESULTS: Of 27 children aged 11 years, 16 (59%) were Caucasian and 6 (22%) African Americans. Thirteen (48%) patients had idiopathic pCAU, 12 (44%) had juvenile idiopathic arthritis (JIA) related pCAU, and 2 (7%) had tubulointerstitial nephritis and uveitis syndrome. At baseline, African American children had worse visual acuity (p = 0.026). At 1 year, 21 (78%) children achieved zero ocular inflammation (remission). Risk factors associated with non-remission were being African American (20% vs. 94%, p = 0.003) and experiencing ≥ 1 episode of uveitis recurrence (100% vs. 0%, p < 0.001). Six episodes of uveitis recurrence were documented in five children, four of whom were African American. Topical corticosteroids were discontinued in 83% of children, and visual acuity remained stable for 1 year. Twelve children were tested for AAAs due to arthritis or uveitis flare-ups, with five (42%) being positive. No significant factors were associated with the development of AAAs. CONCLUSIONS: We found that ADA is effective in controlling inflammation, reducing the need for topical corticosteroids, and maintaining visual acuity in pCAU. There appears to be racial differences in African American children who had worse baseline disease and poorer outcomes. Studies are necessary to understand better and address these disparities.

Treatment outcomes in cytomegalovirus anterior uveitis.

This retrospective cohort study investigated patients with cytomegalovirus anterior uveitis (CMV AU) and compared treatment outcomes between regional and systemic antiviral therapies. Treatment modalities included topical (2% ganciclovir [GCV] eye drops or 0.2% GCV eye gel) and systemic (intravenous GCV or oral valganciclovir) groups. The comparison parameters included response rates, time to response, recurrence rates, time to recurrence, and complications. Forty-four patients (54.5% male) with a mean age of 56 ± 9.87 years were enrolled, with 31 eyes in the topical group and 13 eyes in the systemic group. The median response time was significantly slower in the topical group (63 days [IQR 28-112]) compared to the systemic group (28 days [IQR 24-59]) (p = 0.04). Treatment response rates were 87.1% (27/31) in the topical group and 100% (13/13) in the systemic group (p = 0.30), while recurrence rates were 37% (10/27) and 69.2% (9/13) (p = 0.056), with a median time to recurrence of 483 days [IQR 145-1388] and 392 days [IQR 203.5-1907.5] (p = 0.20), respectively. In conclusion, both topical and systemic GCV treatments demonstrated favorable outcomes for CMV AU. Systemic GCV showed rapid control of intraocular inflammation.

Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis and axial spondyloarthritis.

HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint and eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger of axSpA. We recently identified a bacterial peptide (YeiH) that can be presented by HLA-B*27 to expanded public T cell receptors in the joint in axSpA and the eye in B27AAU. While YeiH is present in enteric microbiota and pathogens, additional evidence that pathogenic T cells in HLA-B*27-associated autoimmunity may have had a prior antigenic encounter within the gastrointestinal tract remains lacking. Here, we analyzed ocular, synovial, and blood T cells in B27AAU and axSpA, showing that YeiH-specific CD8+ T cells express a mucosal gene set and surface proteins consistent with intestinal differentiation, including CD161, integrin α4ß7, and CCR6. In addition, we found an expansion of YeiH-specific CD8+ T cells in axSpA and B27AAU blood compared with that from individuals acting as healthy controls, whereas influenza-specific CD8+ T cells were equivalent across groups. Finally, we demonstrated the dispensability of TRBV9 for antigen recognition. Collectively, our data suggest that, in HLA-B27-associated autoimmunity, early antigen exposure and differentiation of pathogenic CD8+ T cells may occur in enteric organs.

Choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis.

PURPOSE: To quantitatively analyze choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis. STUDY DESIGN: A retrospective study. METHODS: Medical records of 51 eyes with unilateral HLA-B27-associated anterior uveitis, their fellow eyes and 47 sex and age-matched healthy eyes were retrospectively reviewed. Their choroidal and retinal vasculature were analyzed using swept-source (SS) optical coherence tomography (OCT) and OCT angiography (OCTA) scans. RESULTS: Deep capillary plexus (DCP) vessel density (VD) (p < 0.001), choroidal vascularity index (CVI) (p = 0.012), and choriocapillary flow deficit (CCFD) (p < 0.001) of uveitic and fellow eye group were significantly higher than those of control group. On the contrary, superficial capillary plexus (SCP) VD (p < 0.001) of uveitic and fellow eye group were significantly lower than of control group. The vascular parameters of uveitis and fellow eye group showed no significant difference between uveitic and resolution period. CONCLUSION: Certain choroidal and retinal vascular parameters were significantly changed in both HLA-B27-associated anterior uveitis without posterior segment involvement and the quiet fellow eyes, suggesting their possible effects as a systemic inflammatory disorder.

Exploring the role of gut microbes in spondyloarthritis: Implications for pathogenesis and therapeutic strategies.

The gut microbiota plays a pivotal role in regulating host immunity, and dysregulation of this interaction is implicated in autoimmune and inflammatory diseases, including spondyloarthritis (SpA). This review explores microbial dysbiosis and altered metabolic function observed in various forms of SpA, such as ankylosing spondylitis (AS), psoriatic arthritis (PsA), acute anterior uveitis (AAU), and SpA-associated gut inflammation. Studies on animal models and clinical samples highlight the association between gut microbial dysbiosis, metabolic perturbations and immune dysregulation in SpA pathogenesis. These studies have received impetus through next-generation sequencing methods, which have enabled the characterization of gut microbial composition and function, and host gene expression. Microbial/metabolomic studies have revealed potential biomarkers and therapeutic targets, such as short-chain fatty acids, and tryptophan metabolites, offering insights into disease mechanisms and treatment approaches. Further studies on microbial function and its modulation of the immune response have uncovered molecular mechanisms underlying various SpA. Understanding the complex interplay between microbial community structure and function holds promise for improved diagnosis and management of SpA and other autoimmune disorders.

Ocular inflammation in tsutsugamushi disease - a case report.

A 64-year-old male, working at a mountain site in Taitung County, suffered from primary open angle glaucoma (POAG) post trabeculectomy with well-controlled intraocular pressure (IOP) in both eyes (OU). He presented with headache accompanied by red eyes (OU) for 10 days. Physical examination revealed fever up to 38.2°C, neck stiffness, one eschar at the left forearm and another at the left ankle. Abnormal laboratory data indicated bacterial infection with central nervous system involvement. Ophthalmic examination showed elevated IOP, moderate conjunctival congestion, subconjunctival hemorrhage, anterior uveitis, cotton-wool spots on the retina and multiple white dots on the temporal retina (OU). Under the impression of uveitis in tsutsugamushi disease with atypical meningitis, oral doxycycline, anti-glaucoma and anti-inflammation eye drugs were prescribed. IOP returned to 12 mmHg and anterior uveitis subsided. The lesions of cotton-wool spots on the retina disappeared within 2 weeks, but multiple white dots remained persistently on the temporal retina.

Optical coherence tomography for the screening of anterior chamber inflammation in paediatric patients diagnosed with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT. RESULTS: A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71. CONCLUSIONS: AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.

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.

Genetic variations of IL10 and IL6R genes in acute anterior uveitis in Han Chinese.

BACKGROUND: Several autoimmune disorders have been linked to polymorphisms in IL10 and IL6R genes. This research aimed to study whether single nucleotide polymorphisms (SNPs) in the genes of IL10 and IL6R were associated with acute anterior uveitis (AAU) in Han Chinese. METHODS: Genotyping was carried out by the iPLEX Gold Genotyping Assay. Our study comprised 420 patients with AAU and 918 healthy subjects from Han Chinese. Using the chi-square (χ2) test, alleles and genotypes were analyzed between AAU subjects and healthy controls. RESULTS: All ten SNPs were successfully genotyped and four SNPs (IL10/rs1800871, IL10/rs3021094, IL10/rs2222202, IL6R/rs4845618) exhibited weak associations with AAU, as indicated by their Puncorr values. However, upon applying the Bonferroni correction, there was no significant association between AAU and the control subjects. Additionally, the haplotype analysis of the ten SNPs revealed no association with AAU. CONCLUSION: Our findings suggested that polymorphisms of the tested ten SNPs on the IL10 and IL6R genes did not show any association with the risk of developing AAU among the Han Chinese population.