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American Journal of Ophthalmology Case... Jun 2022To report a case of hypertensive granulomatous anterior uveitis in the setting of IgG4-related disease (IgG4-RD).
PURPOSE
To report a case of hypertensive granulomatous anterior uveitis in the setting of IgG4-related disease (IgG4-RD).
OBSERVATIONS
A 69-year-old man presented with no light perception vision in both eyes and bilateral granulomatous anterior uveitis with iris neovascularization and hyphema in the right eye. He also demonstrated concurrent polyuria, polydipsia, and altered mental status, and was diagnosed with new-onset diabetes mellitus. MRI revealed no orbital abnormalities, but showed bilateral occipital strokes attributed to hyperglycemic hyperosmolar syndrome. Chest CT revealed pleural-based nodules and mediastinal and abdominal lymphadenopathy, and a liver biopsy confirmed fibroinflammatory nodules with increased IgG4 positive plasma cell infiltrates, diagnostic of IgG4-RD. Serum IgG4 levels were 1381 mg/dL. The patient was treated with a combination of systemic and topical steroids, and later initiated on rituximab.
CONCLUSION AND IMPORTANCE
IgG4-related ophthalmic disease may present as an isolated hypertensive granulomatous anterior uveitis without associated scleral or orbital involvement.
PubMed: 35274064
DOI: 10.1016/j.ajoc.2022.101465 -
Journal of Neuroinflammation May 2024The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion,...
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 IV 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.
Topics: Humans; HLA-B27 Antigen; Female; Male; Gastrointestinal Microbiome; Middle Aged; Uveitis, Anterior; Adult; Case-Control Studies; Aged
PubMed: 38715051
DOI: 10.1186/s12974-024-03109-4 -
Tropical Medicine and Infectious Disease Jun 2022Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that... (Review)
Review
Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain-Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host's immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus' ability to cross both the blood-brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host's immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.
PubMed: 35736984
DOI: 10.3390/tropicalmed7060106 -
American Journal of Ophthalmology Aug 2021The purpose of this study was to determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this study was to determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with spondyloarthritis/HLA-B27-associated anterior uveitis and 8 other anterior uveitides.
METHODS
Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated in the validation set.
RESULTS
A total of 1,083 cases of anterior uveitides, including 184 cases of spondyloarthritis/HLA-B27-associated anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% CI: 92.4-98.6). Key criteria for spondyloarthritis/HLA-B27-associated anterior uveitis included 1) acute or recurrent acute unilateral or unilateral alternating anterior uveitis with either spondyloarthritis or a positive test result for HLA-B27; or 2) chronic anterior uveitis with a history of the classic course and either spondyloarthritis or HLA-B27; or 3) anterior uveitis with both spondyloarthritis and HLA-B27. The misclassification rates for spondyloarthritis/HLA-B27-associated anterior uveitis were 0% in the training set and 3.6% in the validation set.
CONCLUSIONS
The criteria for spondyloarthritis/HLA-B27-associated anterior uveitis had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.
Topics: Adolescent; Adult; Female; HLA-B27 Antigen; Humans; Machine Learning; Male; Middle Aged; Spondylarthritis; Translational Research, Biomedical; Uveitis, Anterior; Young Adult
PubMed: 33845004
DOI: 10.1016/j.ajo.2021.03.049 -
Atencion Primaria Apr 2020
Topics: Adult; Behcet Syndrome; Colchicine; Glucocorticoids; Humans; Male; Prednisone; Stomatitis, Aphthous
PubMed: 31351751
DOI: 10.1016/j.aprim.2019.05.013 -
Translational Vision Science &... Apr 2022The purpose of this study was to develop an automated artificial intelligence (AI) based method to quantify inflammation in the anterior chamber (AC) using...
PURPOSE
The purpose of this study was to develop an automated artificial intelligence (AI) based method to quantify inflammation in the anterior chamber (AC) using anterior-segment optical coherence tomography (AS-OCT) and to explore the correlation between AI assisted AS-OCT based inflammation analyses and clinical grading of anterior uveitis by Standardization of Uveitis Nomenclature (SUN).
METHODS
A prospective double blinded study of AS-OCT images of 32 eyes of 19 patients acquired by Tomey CASIA-II. OCT images were analyzed with proprietary AI-based software. Anatomic boundaries of the AC were segmented automatically by the AI software and Spearman's rank correlation between parameters related to AC cellular inflammation were calculated.
RESULTS
No significant (p = 0.6602) differences were found between the analyzed AC areas between samples of the different SUN grading, suggesting accurate and unbiased border detection/AC segmentation. Segmented AC areas were processed by the AI software and particles within the borders of AC were automatically counted by the software. Statistical analysis found significant (p < 0.001) correlation between clinical SUN grading and AI software detected particle count (Spearman ρ = 0.7077) and particle density (Spearman ρ = 0.7035). Significant (p < 0.001) correlation (Pearson's r = 0.9948) between manually and AI detected particles was found. No significant (p = 0.8080) difference was found between the sizes of the AI detected particles for all studies.
CONCLUSIONS
AI-based image analysis of AS-OCT slides show significant and independent correlation with clinical SUN assessment.
TRANSLATIONAL RELEVANCE
Automated AI-based AS-OCT image analysis suggests a noninvasive and quantitative assessment of AC inflammation with clear potential application in early detection and management of anterior uveitis.
Topics: Acute Disease; Anterior Chamber; Artificial Intelligence; Cell Count; Double-Blind Method; Humans; Inflammation; Prospective Studies; Tomography, Optical Coherence; Uveitis; Uveitis, Anterior
PubMed: 35394486
DOI: 10.1167/tvst.11.4.7 -
Frontiers in Immunology 2021Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by... (Review)
Review
Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet's disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet's disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by , is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient's genetic make-up is expected.
Topics: Genetic Predisposition to Disease; Humans; Uveitis
PubMed: 33912164
DOI: 10.3389/fimmu.2021.640473 -
Nature Communications Nov 2023Anterior Uveitis (AU) is the inflammation of the anterior part of the eye, the iris and ciliary body and is strongly associated with HLA-B*27. We report AU exome... (Meta-Analysis)
Meta-Analysis
Anterior Uveitis (AU) is the inflammation of the anterior part of the eye, the iris and ciliary body and is strongly associated with HLA-B*27. We report AU exome sequencing results from eight independent cohorts consisting of 3,850 cases and 916,549 controls. We identify common genome-wide significant loci in HLA-B (OR = 3.37, p = 1.03e-196) and ERAP1 (OR = 0.86, p = 1.1e-08), and find IPMK (OR = 9.4, p = 4.42e-09) and IDO2 (OR = 3.61, p = 6.16e-08) as genome-wide significant genes based on the burden of rare coding variants. Dividing the cohort into HLA-B*27 positive and negative individuals, we find ERAP1 haplotype is strongly protective only for B*27-positive AU (OR = 0.73, p = 5.2e-10). Investigation of B*27-negative AU identifies a common signal near HLA-DPB1 (rs3117230, OR = 1.26, p = 2.7e-08), risk genes IPMK and IDO2, and several additional candidate risk genes, including ADGFR5, STXBP2, and ACHE. Taken together, we decipher the genetics underlying B*27-positive and -negative AU and identify rare and common genetic signals for both subtypes of disease.
Topics: Humans; Uveitis, Anterior; Inflammation; Haplotypes; Genes, MHC Class I; HLA-B Antigens; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Aminopeptidases; Minor Histocompatibility Antigens
PubMed: 37949852
DOI: 10.1038/s41467-023-43036-1 -
JAMA Ophthalmology Apr 2021Although experimental studies support the hypothesis that exposure of infectious agents may trigger an aberrant immune response and contribute to noninfectious uveitis,...
IMPORTANCE
Although experimental studies support the hypothesis that exposure of infectious agents may trigger an aberrant immune response and contribute to noninfectious uveitis, the association of a definite pathogen with human noninfectious uveitis conditions appears not to have been well established in a population.
OBJECTIVE
To evaluate associations of tuberculosis infection with risk of several noninfectious uveitis conditions.
DESIGN, SETTING, AND PARTICIPANTS
These mendelian randomization and observational analyses were conducted with the genetic data of a Chinese cohort enrolled between April 2008 and January 2018 and a Japanese cohort enrolled between January 2002 and June 2009. We recruited participants for T-SPOT.TB (Oxford Immunotec) assays between July and November 2019. The Chinese cohort included patients with uveitis associated with Behçet disease or other uveitis conditions and control participants. The Japanese cohort and the group given T-SPOT.TB assays included individuals with Behçet disease and control participants. Data analyses for this study were completed from July 2019 to January 2020.
EXPOSURES
Genetic variants associated with tuberculosis as natural proxies for tuberculosis exposure.
MAIN OUTCOMES AND MEASURES
The primary outcome was the odds ratio (OR) for Behçet disease, estimated by an inverse variance weighted mean of associations with genetically determined tuberculosis susceptibility. The T-SPOT.TB positivity rate was examined in individuals with Behçet disease and compared with that of control participants.
RESULTS
The Chinese cohort included 999 patients with uveitis associated with Behçet disease, 1585 with other uveitis conditions, and 4417 control participants. The Japanese cohort included 611 individuals with Behçet disease and 737 control participants. The group given T-SPOT.TB assays included 116 individuals with Behçet disease and 121 control participants. Of the Chinese individuals with Behçet disease and control participants, 2257 (41.7%) were female and the mean (SD) age was 35.4 (12.5) years. In the Japanese cohort, 564 (41.8%) were female and the mean (SD) age was 39.1 (12.7) years. Genetically determined tuberculosis susceptibility was associated with an increased risk for Behçet disease. The OR for Behçet disease per 2-fold increase in tuberculosis incidence was 1.26 (95% CI, 1.12-1.43; P = 1.47 × 10-4). Replication using the Japanese cohort yielded similar results (OR, 1.16 [95% CI, 1.08-1.26]). In T-SPOT.TB assays, having a positive result, indicating a history of tuberculosis infection, was found to be an independent risk factor for Behçet disease (OR, 2.26 [95% CI, 1.11-4.60]).
CONCLUSIONS AND RELEVANCE
These human genetic and biomarker data demonstrated that tuberculosis exposure was a risk factor for Behçet disease. This study provides novel evidence linking an infectious agent to the risk of a noninfectious uveitis condition.
Topics: Adult; Behcet Syndrome; Female; Humans; Interferon-gamma Release Tests; Male; Tuberculosis; Tuberculosis, Ocular; Uveitis
PubMed: 33599689
DOI: 10.1001/jamaophthalmol.2020.6985 -
Indian Journal of Ophthalmology Feb 2024To study the long-term clinical outcome and treatment strategies of recurrent and chronic non-infectious anterior uveitis.
PURPOSE
To study the long-term clinical outcome and treatment strategies of recurrent and chronic non-infectious anterior uveitis.
METHODS
Multicenter study of anterior uveitis patients from 2001 to 2022. Outcome measures included ocular complications, medical and surgical therapies, and visual acuity measured at the beginning of follow-up and at 1, 2, and 5 years thereafter.
RESULTS
In total, 76 patients were included, with a mean follow-up of 6.8 years. Idiopathic anterior uveitis was the most common etiology (56%). Immunomodulatory agents (IMAs) were used in almost half of the cohort. Early initiation of IMAs was associated with a lower risk of developing glaucoma ( P = 0.019). Mean best corrected visual acuity (BCVA) improved after 5 years in both groups. Early use of immunomodulation was correlated with a better visual outcome at 2 years ( P = 0.024).
CONCLUSION
Chronic and recurrent anterior uveitis were associated with greater risk than expected for ocular complications, surgeries, and vision impairment. Early initiation of immunomodulation should be strongly considered to improve clinical course and outcome.
Topics: Humans; Follow-Up Studies; Retrospective Studies; Uveitis, Anterior; Chronic Disease; Glaucoma; Uveitis; Treatment Outcome
PubMed: 38146973
DOI: 10.4103/IJO.IJO_1042_23