Review

Authors: Jing Zhang, Koju Kamoi, Yuan Zong...

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.

Topics: Male; Humans; Cytomegalovirus; Eye Infections, Viral; Ganciclovir; Antiviral Agents; Cytomegalovirus Infections; Uveitis, Anterior; Glaucoma; Retrospective Studies; DNA, Viral

PubMed: 36680225
DOI: 10.3390/v15010185

Review

Authors: Kalpana Babu, Vinaya Kumar Konana, Sudha K Ganesh...

Viral anterior uveitis (VAU) needs to be suspected in anterior uveitis (AU) associated with elevated intraocular pressure, corneal involvement, and iris atrophic changes. Common etiologies of VAU include herpes simplex, varicella-zoster, cytomegalovirus, and rubella virus. Clinical presentations can vary from granulomatous AU with corneal involvement, Posner-Schlossman syndrome, Fuchs uveitis syndrome, and endothelitis. Due to overlapping clinical manifestations between the different viruses, diagnostic tests like polymerase chain reaction and Goldmann-Witmer coefficient analysis on the aqueous humor may help in identifying etiology to plan and monitor treatment.

Topics: Aqueous Humor; Cytomegalovirus; DNA, Viral; Eye Infections, Viral; Herpes Simplex; Humans; Rubella virus; Uveitis; Uveitis, Anterior

PubMed: 32823392
DOI: 10.4103/ijo.IJO_928_20

Review

Authors: Denis Wakefield, Daniel Clarke, Peter McCluskey...

There has been steady progress in understanding the pathogenesis, clinical features, and effective treatment of acute anterior uveitis (AU) over the past 5 years. Large gene wide association studies have confirmed that AU is a polygenic disease, with overlaps with the seronegative arthropathies and inflammatory bowel diseases, associations that have been repeatedly confirmed in clinical studies. The role of the microbiome in AU has received increased research attention, with recent evidence indicating that human leukocyte antigen B27 (HLA B27) may influence the composition of the gut microbiome in experimental animals. Extensive clinical investigations have confirmed the typical features of acute AU (AAU) and its response to topical, regional and systemic immunosuppressive treatment. Increased understanding of the role of cytokines has resulted in studies confirming the value of anti-cytokine therapy [anti-tumor necrosis factor (anti-TNF) and interleukin 6 (IL-6) therapy] in severe and recurrent cases of AAU, particularly in subjects with an associated spondyloarthopathy (SpA) and in juvenile idiopathic arthritis (JIA)-associated AAU.

Topics: Acute Disease; Animals; Bacteria; Cytokines; Gastrointestinal Microbiome; Genetic Predisposition to Disease; HLA-B27 Antigen; Haplotypes; Humans; Immunosuppressive Agents; Intestines; Tumor Necrosis Factor Inhibitors; Uvea; Uveitis, Anterior

PubMed: 33469457
DOI: 10.3389/fimmu.2020.608134

Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics.

Authors: Shuming Chen, Weidi Huang, Qiaoqian Wan...

BACKGROUND

Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment.

METHODS

To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved.

RESULTS

Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141CLEC9A classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group.

CONCLUSIONS

AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.

Topics: Humans; Acute Disease; Bayes Theorem; Gene Expression Profiling; Genome-Wide Association Study; HLA-B27 Antigen; Spondylarthritis; Uveitis, Anterior

PubMed: 38475831
DOI: 10.1186/s12967-024-05077-y

Review

Authors: Zifan Ye, Yumei Yang, Weishaer Ke...

Cytomegalovirus anterior uveitis is the most common ocular inflammatory disease caused by cytomegalovirus infection. It mainly occurs in middle-aged males with competent immunologic function, and the incidence is higher in Asia. The clinical manifestations vary from Posner-Schlossman syndrome and corneal endotheliitis to Fuchs uveitis syndrome, and are often accompanied by intraocular hypertension. Secondary glaucoma is a potentially blinding ocular complication with a pathogenesis that includes complicated immunological factors, intraocular inflammation, different types of angle abnormalities, and the administration of steroids, which may result in physical discomfort and visual impairment. Diagnostic tests, such as the polymerase chain reaction, optical coherence tomography, ocular microscopy, and confocal microscopy, might help in identifying anterior uveitis caused by other viruses. Combinations of antiviral medications and anti-inflammatory agents are effective treatments. If pharmacological therapy cannot reduce intraocular pressure or slow the progression of glaucomatous optic neuropathy, surgical intervention is required as a last resort.

Topics: Male; Middle Aged; Humans; Cytomegalovirus; Glaucoma; Uveitis, Anterior; Eye; Cytomegalovirus Infections

PubMed: 36935679
DOI: 10.3389/fpubh.2023.1117412

Authors: Sophia C Morandi, Elio L Herzog, Marion Munk...

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

Authors: Veronika Kotingová, Marek Fichtl, Michaela Brichová...

AIM

The aim of the article is to summarize observations on cytomegalovirus (CMV) anterior uveitis, and in short case reports present cases of patients treated at our Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague.

MATERIAL AND METHODS

Retrospective analysis of patients at the Centre for diagnosis and treatment of uveitis from 2003 to 2024. Presentation of our experiences with CMV anterior uveitis confirmed by polymerase chain reaction (PCR) in aqueous humor in case reports.

RESULTS

From a cohort of 3844 patients with uveitis, 3 patients were diagnosed with CMV anterior uveitis, confirmed by PCR in the aqueous humor. The clinical presentation was as acute recurrent hypertensive anterior uveitis in all patients, with a switch to chronic form with elevated intraocular pressure (IOP). Despite local anti-inflammatory and antiglaucomatous therapy, there was high recurrence of uveitis with decompensation of IOP when the medication was reduced. Patients underwent antiglaucoma surgery because of persistent high IOP despite maximal local antiglaucomatous therapy. An anterior chamber tap was taken for PCR analysis, with a CMV-positive result. After the initiation of antiviral therapy with local ganciclovir, patients manifested compensated IOP and a pronounced reduction of recurrences of uveitis and progression of glaucoma.

CONCLUSIONS

CMV anterior uveitis is a rare pathology in our geographic region, but it is important to consider this etiology in cases of recurrent anterior hypertensive uveitis with a low response to local anti-inflammatory medication. Timely verification of the etiological agent with prompt diagnosis and treatment is essential in order to achieve a favorable prognosis. Long-term, low maintenance doses of antiviral therapy with local ganciclovir for several months reduce relapses of uveitis and lead to compensation of IOP.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Antiviral Agents; Aqueous Humor; Cytomegalovirus; Cytomegalovirus Infections; Retrospective Studies; Uveitis, Anterior

PubMed: 39648037
DOI: 10.31348/2024/40

Review

Authors: Charlotte van Meerwijk, Jonas Kuiper, Joeri van Straalen...

Juvenile idiopathic arthritis (JIA) is the most common cause of uveitis in children. While symptoms are usually mild, persistent eye inflammation could lead to severe complications and impaired vision. It is essential that JIA patients at risk are diagnosed with uveitis early, receive adequate treatment, and avoid developing complications, such as cataract, glaucoma, and amblyopia. The purpose of this mini-review is to summarize the screening strategies and clinical management for JIA-associated uveitis (JIA-U) as well as the current state of molecular markers linked to this condition. Because glaucoma is one of the most common causes of visual loss in JIA-U, special focus will be put on this serious complication. We conclude by describing the current evidence regarding the long-standing question of whether chronic anterior uveitis without arthritis may be the same disease entity as JIA-U.

Topics: Child; Humans; Arthritis, Juvenile; Uveitis; Glaucoma; Endophthalmitis; Uveitis, Anterior

PubMed: 37966463
DOI: 10.1080/09273948.2023.2278060

Authors: Rikke Tetzschner, Sasikala Thineshkumar, Laleh Molander...

This is a case report of a 3-year-old boy who presented with unilateral anterior uveitis and tonic pupil following varicella-zoster virus (VZV) Infection. The patient had red and irritated eyes and photophobia. Ophthalmological findings included anterior uveitis and tonic pupil accompanied by reduced vision and accommodation. An MRI of the cerebrum was normal. To ease the symptoms the patient was prescribed photophobia glasses with correction of hyperopia. Tonic pupil due to VZV infection is a rare complication, but may have long-term consequences, why patients with eye-involving VZV infection need to be examined by an ophthalmologist.

Topics: Male; Humans; Child; Child, Preschool; Chickenpox; Tonic Pupil; Photophobia; Herpesvirus 3, Human; Uveitis, Anterior; Acute Disease

PubMed: 38018730
DOI: No ID Found

Review

Authors: James T Rosenbaum

Acute anterior uveitis is the most common extra-articular clinical manifestation of spondyloarthropathy. Rheumatologists should be aware of uveitis, know how it presents, understand the differential diagnosis of uveitis and arthritis, and be familiar with the role of systemic medications in the treatment or prevention of uveitis.

Topics: Acute Disease; Animals; Diagnosis, Differential; Glucocorticoids; Humans; Spondylarthritis; Uveitis, Anterior

PubMed: 31779847
DOI: 10.1016/j.semarthrit.2019.09.014