Frequency of HLA-B27 Haplotype Among Patients with Acute Anterior Uveitis and Controls in Ethiopia.

PURPOSE: We compared the distribution of the HLA-B27 allele among Ethiopian patients with acute anterior uveitis (AAU) and controls without that disease. METHODS: The clinical features of patients were collected from their medical records. HLA-B27 genotyping was performed for 64 patients, with AAU using the real-time polymerase chain reaction (RT-PCR), and the results were compared to those from a panel of 192 healthy, unrelated volunteer control participants (refraction patients and volunteers) free of signs of anterior uveitis. Other outcomes were assessed comparing HLA-B27 positive vs. negative patients. RESULTS: The histocompatibility antigen HLA-B27 was identified in 6 out of 64 (9.4%) AAU patients, compared with 1.0% in controls (Odds Ratio = 9.8, 95% CI (1.93, 50.01)). Sub-group analysis of the cases revealed that patients with HLA-B27 positivity had a higher incidence of ocular hypertension (Odds Ratio = 5.93, 95% CI (1.29, 27.2)). CONCLUSION: The antigen HLA-B27 was represented ~10-fold more frequently in the patient group than in the control group. HLA-B27 allele distribution in both cases and controls is lower than in reports from Caucasian and Asian populations, but similar to South Africa.

Differential Composition and Structure of the Microbiota from Active and Inactive Stages of HLA-B27-associated Uveitis by Paired Fecal Metagenomes.

PURPOSE: To compare the diversities and abundances of bacterial taxa in the microbiome of patients with HLA B27-positive acute anterior uveitis (AAU) in the active and inactive phases. METHODS: An observational descriptive prospective and comparative study was conducted in ten HLA-B27-positive AAU patients (44.6 ± 13.4 years). The microbiome of the stool samples obtained in the active and inactive stages was analyzed by sequencing the V3 region of the 16S rRNA gene. RESULTS: The differences in the bacteria profile between active and inactive stages in each individual were confirmed (p < 0.0001). Ten OTUs were found exclusively in the active phase of 90% of the individuals, suggesting a proinflammatory association. Blautia OUT_4 and Faecalibacterium OUT_2 abundances showed a direct relationship between abundance and severity of ocular inflammation. Two OTUs were exclusive of the inactive stage, suggesting an anti-inflammatory role. CONCLUSION: The metagenomic profile of the fecal microbiota differs in the acute phase of the AAU compared to when the inflammation subsides, despite being the same individual and a short time-lapse. AAU is a fertile field for studying the connection between subtle rapid changes in microbiota and their systemic consequences.

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.

Changes in peripapillary retinal nerve fibre layer and ocular parameters in acute anterior uveitis.

CLINICAL RELEVANCE: Acute anterior uveitis (AAU) can lead to the thickening of the peripapillary retinal nerve fibre layer (pRNFL) and induce refractive changes during its active phase. BACKGROUND: AAU is a common form of uveitis characterised by inflammation in the anterior chamber. A notable prevalence of optical coherence tomography - defined pRNFL thickening was observed among patients with AAU. The alterations in pRNFL thickness and their associations with other relevant ocular parameters in patients with AAU were investigated. METHODS: A retrospective, consecutive case series was conducted at a specialised uveitis referral clinic in Taiwan. This study gathered data on various demographic characteristics and various ocular parameters, namely anterior chamber cell grading, refractive error, best-corrected visual acuity, intraocular pressure, and optical coherence tomography measurements. A comparative analysis of baseline and subsequent follow-up data was conducted. Additionally, this study examined the correlations between alterations in pRNFL thickness and various ocular parameters. Twenty-one patients with AAU (21 affected eyes/21 unaffected eyes) were examined. RESULTS: Initial measurements revealed pRNFL thickening in 20 patients. Treatment led to significant improvements in best-corrected visual acuity, intraocular pressure recovery, and pRNFL thickening (p < 0.01). The correlation between changes in pRNFL thickness and best-corrected visual acuity was weak (r = 0.20, p = 0.41). By contrast, a significant negative correlation was identified between changes in pRNFL thickness and refractive error alterations (r = -0.71, p = 0.01). CONCLUSION: This study demonstrated that AAU is associated with pRNFL thickening, which in turn is inversely correlated with changes in refractive error alterations throughout the disease course. Monitoring changes in pRNFL thickness can be effective in assessing ocular inflammation status.

Factors associated with acute anterior uveitis history in patients with axial spondyloarthritis: Results of a longitudinal study.

BACKGROUNDS: Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA). OBJECTIVES: The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36-month follow-up period. METHODS: In total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis. RESULTS: Overall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow-up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU. CONCLUSIONS: AAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.

Associations of IL6R and IL10 Gene Polymorphisms with Susceptibility to Ankylosing Spondylitis with or without Acute Anterior Uveitis.

BACKGROUND: This research aims to explore the associations between ten candidate single nucleotide polymorphisms (SNPs) on Interleukin-6 receptor (IL6R) and Interleukin-10 (IL10) genes and ankylosing spondylitis (AS) patients with or without acute anterior uveitis (AAU). METHODS: This study involved a case-control approach that examined 354 cases with AS and AAU, 377 AS cases without AAU, and 918 healthy controls. Genotyping of ten SNPs of IL10 and IL6R genes was performed using iPLEX Gold genotyping method. The allele and genotype frequencies of cases and healthy individuals were contrasted using the chi-square test. The IL10 mRNA level in various IL10 genotypes was tested using real-time PCR. RESULTS: Two loci associated with AS with AAU were identified: IL10//rs3790622 (OR = 0.664; 95%CI = 0.503-0.878; Pc = 0.038); IL10//rs3021094 (OR = 1.365; 95%CI = 1.110-1.679; Pc = 0.032). The other eight loci located on IL10 and IL6R did not show significant associations with the diseases. Additionally, as shown by functional experiments, there was no correlation between the mRNA expression of IL10 and various genotypes. CONCLUSION: Our study suggests that the IL10 gene contributes to the susceptibility of the Chinese population to AS with AAU.

HLA-B27-positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management, and treatment.

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Bilateral acute anterior uveitis and optic nerve edema as a manifestation of coronavirus disease-2019 (COVID-19): A case report.

Key clinical message: Acute anterior uveitis and optic disk edema could be a manifestation of COVID-19 infection, and healthcare providers should be aware of this possible consequence for in-time diagnosis and treatment. Abstract: Since the beginning of the coronavirus disease-2019 (COVID-19) pandemic, a wide range of clinical manifestations have been associated with this novel infection. The objective of this study was to show that acute anterior uveitis and optic disk edema could be possible manifestations of COVID-19 infection. The patient was a nine-year-old girl presenting with prolonged fever, myalgia, cough, diarrhea, and skin rashes. She also reported blurred vision, Photophobia, and eye redness. PCR test for COVID-19 returned positive. Imaging investigations showed pleural and pericardial effusion, mediastinal lymphadenopathy, and heart valve regurgitation. She was diagnosed with MIS-C and treated with methylprednisolone and IVIG. Bilateral acute anterior uveitis and optic disk edema was detected by slit lamp and fundus examination. She was successfully treated and follow-up ophthalmologic examinations showed improvement.

Changes of peripheral blood Th cytokines in acute anterior uveitis and their relationships with recurrence.

Acute anterior uveitis (AAU) can cause great pain to patients. Th cytokines in peripheral blood are significantly changed in these patients, including serum interleukin-23 (IL-23), interleukin-17 (IL-17), interleukin-4 (IL-4), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1) increase. However, the relationship between Th cytokines and recurrence of AAU is still unclear. Ninety-two cases of AAU were enrolled from January 2020 to April 2022 in our hospital (observation group). Levels of peripheral blood Th cytokines were detected, which were compared between acute and remission stages. After 6 months of follow-up, the relationships between Th cytokines in peripheral blood and recurrence in the observation group were analyzed. The prediction of Th cytokines on recurrence was analyzed. (1) The recurrence rate was 25.00%, and there were no statistical differences in the serum IL-23, IL-17, IL-4, IFN-γ, TNF-α and TGF-ß 1 levels between patients with bilateral disease and unilateral disease (P < 0.05). (2) The serum IL-23, IL-17, IL-4, IFN-γ, TNF-α and TGF-ß 1 levels of recurrence patients were higher than those of non-recurrence (t = 2.971, 5.357, 2.197, 2.766, 4.395, 2.983, P < 0.05). (3) The serum IL-23, IL-17, TNF-α levels were risk factors for recurrence (OR = 1.035, 1.210, 1.155, P < 0.05). (4) There were positive relationships between serum IL-23, IL-17, IL-4, IFN-γ, TNF-α and TGF-ß 1 levels and recurrence (r = 0.317, 0.526, 0.248, 0.304, 0.480, 0.325, P < 0.05). .

Association of TBX21 gene polymorphisms and acute anterior uveitis risk in a Chinese population: A case-control study.

Copy number variations (CNVs) in TBX21 gene have been reported to be significantly and positively correlated with acute anterior uveitis (AAU). Our study was performed to further determine whether single nucleotide polymorphisms (SNPs) in TBX21 gene confer susceptibility to AAU in a Chinese population. In our case-control study, 420 AAU patients and 918 healthy controls were included. SNP genotyping was conducted via the MassARRAY™ iPLEX Gold platform. Association and haplotype analyses were performed via SPSS 23.0 and SHEsis software. No significant association was observed between two candidate SNPs of TBX21 gene (rs4794067, rs11657479) and susceptibility to AAU (Pc > 0.05). In stratification analysis, the result also showed no significant difference between the HLA-B27 positive AAU patients and non-typed healthy controls. Additionally, no association was detected between TBX21 haplotypes and AAU risk. In conclusion, the polymorphisms rs4794067 and rs11657479 in TBX21 gene did not confer disease susceptibility to AAU in a Chinese population.

[HLA-B27 positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management and treatment]. / HLA-B27-positive Uveitis anterior : Klinik, Diagnostik, interdisziplinäres Management und Therapie.

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Assessment of the Anti-inflammatory Effects of NORFLO® ORO in Acute Relapses of HLA-B27-associated Autoimmune Uveitis: A Multicenter, Randomized, Placebo-controlled, Double-blind Clinical Study.

BACKGROUND: An effective therapy to reduce the number and severity of HLA-B27-related acute anterior uveitis (AAU) recurrences represents a clinical need. Curcumin is a promising therapeutic option in various inflammatory eye diseases. To enhance its absorption and eye tissue selectivity, a phospholipidic-curcumin complex (PHBC) has been formulated (Iphytoone®, Eye Pharma S.p.A.). AIMS: This study investigates if PHBC is effective and safe to decrease the number and intensity of HLA-B27-related AAU relapses. METHODS: HLA-B27-related AAU patients were randomly divided to receive PHBC or placebo for 12 months (NCT03584724). RESULTS: Compared with the previous year, the number of relapses decreased in both groups. The proportion of responders was significantly higher in the PBHC group. The severity of attacks was comparable. The study drug was well tolerated. CONCLUSIONS: A beneficial effect of PHBC treatment is suggested because the proportion of responders was significantly higher in this group of patients.

The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies.

The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi. Moreover, the unique disease model afforded by AAU to study the gut microbiota has been neglected. This review critically evaluates the current literature and prevailing hypotheses on the link between the gut microbiota and HLA-B27-associated disease. We propose a new potential role for HLA-B27-driven altered antibody responses to gut microbiota in disease pathogenesis and outline recommendations for future well-controlled human studies, focusing on AAU.

Epidemiology and characteristics of common forms of anterior uveitis at initial presentation in a tertiary facility in Japan.

PURPOSE: To elucidate detailed epidemiological profile of common types of anterior uveitis (AU) in real-world clinical setting of a tertiary facility in Japan, and to evaluate the characteristic clinical findings at initial presentation. STUDY DESIGN: Retrospective cohort study. METHODS: Clinical charts of 275 patients (335 eyes) aged 52.5 ± 19.1 years were reviewed retrospectively. Herpetic AU was diagnosed by multiplex polymerase chain reaction tests using aqueous humor. Time of uveitis onset, gender, laterality, disease course since the initial onset of AU, visual acuity (VA) and intraocular pressure (IOP) at first visit, and definitive diagnosis were collected from clinical charts. RESULTS: Acute AU (AAU) was the most common (21.8%) form of AU; followed by herpetic AU (20.7%) comprising Herpes Simplex Virus (HSV) (8.0%), Varicella Zoster Virus (VZV) (9.1%) and cytomegalo virus (CMV) (3.6%); scleritis (13.5%); diabetic iritis (7.6%), and Posner-Schlossman syndrome (5.5%). Unilateral AU constituted 78.2%, and VA less than 20/30 accounted for 31.2%. Of all the eyes, 16.1% had an IOP higher than 20 mmHg, out of which 37.0% had herpetic AU, followed by scleritis in 25.9%, and Posner-Schlossman syndrome (PSS) in 11.1%. AU patients over 60 years of age were 40.4%, in which 34.2% had herpetic AU, followed by scleritis in 14.4% and AAU in 13.5%. Herpetic AU patients were significantly older and had higher IOP compared with AAU patients. CONCLUSION: The most frequent AU was AAU, followed by herpetic AU. Herpetic AU patients were older and had higher intraocular pressure than AAU patients, although VA was equally impaired in both groups.

Extra-Articular Manifestations in Patients with Ankylosing Spondylitis: Baseline Characteristics from the RBSMR Study.

Objectives: To describe and analyse the prevalence of extra-articular manifestations (EAMs) including acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD) in patients with ankylosing spondylitis (AS) in the Moroccan registry of biological therapies in rheumatic diseases RBSMR (Registre des Biothérapies de la Société Marocaine de Rhumatologie). Methods: A cross-sectional, multicentre and analytical study based on the RBSMR database, which included 170 AS. Incidence rates for the development of AAU, psoriasis and IBD were calculated, and risk factors were analysed. Results: Prevalence of EAMs in AS was 13.5%, 4.7% and 11.2% for AAU, psoriasis and IBD respectively. No significant differences were found while establishing a comparison of the prevalence of these EAMs between AS patients with and without peripheral arthritis. Interestingly, AAU was the most common EAM, and was positively associated in multivariable regression with family history of spondyloarthritis (OR= 7.21, CI 95%: 2.23-23.24). Conclusions: AAU was the leading EAM in patients with AS included in the Moroccan biotherapy registry (RBSMR) and it was associated with family history of spondyloarthritis.

Covid-19 association with anterior uveitis (post-covid acute anterior uveitis).

The Covid-19 outbreak in Wuhan on 31st December 2019 soon became a pandemic. Ocular manifestations in post covid patients have been widely reported. Anterior uveitis is a common form of intraocular inflammation observed on a daily basis by Ophthalmologists. Diagnosis of AAU is relatively simple but identification of its etiology is difficult, specifically with Covid-19. Post Covid-19 AAU is not reported in Pakistan yet. The patient in the given case is investigated thoroughly, no possible cause of AAU is identified. The patient was managed for uveitis.

The Risk of Major Adverse Cardiovascular Events in Ankylosing Spondylitis Patients With a History of Acute Anterior Uveitis: A Nationwide, Population Based Cohort Study.

Background: To investigate the association between a history of acute anterior uveitis (AAU) and the risk of major adverse cardiovascular events (MACE) among patients with ankylosing spondylitis (AS). Methods: We identified 38,691 newly diagnosed AS patients between 2003 and 2013 from the Taiwan National Health Insurance Research Database. The exposure group was defined as people with uveitis diagnosis by ophthalmologist before AS diagnosis date. The incidence of MACE in patients with AS according to the International Classification of Diseases, Ninth Revision. We randomly selected a comparison group without a history of AAU at a 1:4 ratio matched by age, sex, and index year in relation to the risk of developing MACE. We used cox proportional hazard regression model to compare the risk of MACE between groups, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). Further subgroup analysis and sensitivity tests were also performed. Results: There were 3,544 patients in the AAU group and 14,176 patients in the non-AAU group. The aHR of MACE for the AAU group was 0.79 (95% CI = 0.57-1.10) at a 1:4 ratio for age, sex and index year. Sensitivity analyses using various adjustment variables showed consistent results. Cox proportional hazard regression model demonstrated that use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of MACE in this cohort (HR = 3.44; 95% CI = 2.25-5.25). Conclusion: This cohort study showed that subjects with AAU was not associated with the risk of MACE among AS patients, compared to non-AAU controls.

'Can you touch your toes?' spondyloarthropathies and acute anterior uveitis for primary eyecare practitioners.

The rheumatological diseases known as spondyloarthropathies (SpAs) are reviewed with respect to the current classifications of SpAs and from the perspective of ophthalmic practitioners. The focus is on the most common spondyloarthropathy, ankylosing spondylitis (AS), and the key symptoms, such as inflammatory back pain. The association with HLA-B27 and acute anterior uveitis (AAU) and the major clinical considerations for primary eye care practitioners are reviewed. An atypical case study illustrates difficulties in the detection and diagnosis of ankylosing spondylitis.

Association of Killer Cell Immunoglobulin-like Receptor and Human Leukocyte antigen-C Genotype with HLA-B27 Associated Acute Anterior Uveitis and Idiopathic Acute Anterior Uveitis in a Chinese Han Population.

PURPOSE: whether killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigens C (HLA-C) are associated with HLA-B27 associated acute anterior uveitis (B27AAU) and idiopathic AAU (IAAU) remains unclear. METHODS: PCR with sequence-specific primers was used to analyze KIR genes and HLA-C alleles in a Chinese Han population of 196AAU patients and 210 control subjects. RESULTS: The higher frequencies of HLA-C2 and KIR2DL1/HLA-C2 (p = .009 and p = .044, respectively) and the lower frequencies of HLA-C1C1 and HLA-C1 (p = .034 and p = .009, respectively) were observed in B27AAU than control group. The higher frequencies of KIR2DL2 and KIR2DL2/HLA-C1 (p = .009 and p = .044, respectively) and the lower frequencies of KIR2DL3 and KIR2DL3/HLA-C1 (p = .000 and p = .001, respectively) were observed in IAAU than control group. CONCLUSIONS: HLA-C2 and KIR2DL1/HLA-C2, KIR2DL2, and KIR2DL2/HLA-C1 might be susceptible for B27AAU and IAAU, respectively. HLA-C1C1 and HLA-C1, KIR2DL3 and KIR2DL3/HLA-C1 might protect from B27AAU and IAAU, respectively.