Acute Anterior Uveitis Research Articles

Two Case Reports of Zoledronic Acid-Induced Acute Anterior Uveitis

Two Case Reports of Zoledronic Acid-Induced Acute Anterior Uveitis

Comprehensive single-cell profiling of monocytes in HLA-B27-positive ankylosing spondylitis with acute anterior uveitis.

Acute anterior uveitis (AAU) is a common extra-articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)-B27 genetic marker. To explore the underlying mechanisms of HLA-B27+ AS-associated AAU, we employed single-cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA-B27+ AS-associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune-associated proteins, Th17-related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X-inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA-B27+ AS-associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

8476 Case of Zoledronic Acid Induced Acute Anterior Uveitis In A 63-Year-Old Woman

8476 Case of Zoledronic Acid Induced Acute Anterior Uveitis In A 63-Year-Old Woman

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

ABSTRACT 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.

Frequency of Elevated Intraocular Pressure in Patients with Acute and Chronic Anterior Uveitis

Background: Elevated intraocular pressure (IOP) is a frequent and serious complication in patients with uveitis, potentially leading to secondary glaucoma and permanent vision loss. Understanding the frequency and associated risk factors of elevated IOP in patients with acute and chronic anterior uveitis is essential for effective management and prevention of visual morbidity. Objective: This study aimed to determine the frequency of elevated IOP in patients with acute and chronic anterior uveitis and to identify the associated demographic and clinical factors. Methods: This This descriptive, cross-sectional study was conducted over six months at the Outpatient Department of Al-Shifa Trust Eye Hospital, Rawalpindi, involving 160 patients aged 20 to 60 years diagnosed with anterior uveitis. Patients were excluded if they were on anti-glaucoma medications, had specific ocular conditions, or had a pre-existing diagnosis of glaucoma or elevated IOP. Intraocular pressure was measured using Goldmann Applanation Tonometry, with elevated IOP defined as >21 mmHg. Demographic data and clinical history, including the duration and grade of uveitis, were recorded. Data were analyzed using SPSS version 25, with qualitative variables presented as frequencies and percentages, and statistical significance assessed using chi-square tests (p ≤ 0.05). Results: The mean age of the study participants was 33.19 years (SD ± 7.26). Elevated IOP was observed in 38.75% of the patients. A significantly higher frequency of elevated IOP was found in females (61.7% vs. 25% in males, p = 0.000), patients over 30 years of age (46.4% vs. 30.3%, p = 0.026), and those with hypertension (69.8% vs. 23.4% in non-hypertensive patients, p = 0.000). Grade I uveitis had the highest frequency of elevated IOP (100%), followed by grade III (42.9%), grade IV (4.1%), and grade II (0%) (p = 0.000). No significant association was found between elevated IOP and diabetes mellitus or the duration of uveitis. Conclusion: The study found a substantial frequency of elevated IOP in patients with anterior uveitis, particularly among females, older patients, and those with hypertension. These findings highlight the need for regular IOP monitoring and tailored management strategies in high-risk patients to prevent the development of secondary glaucoma and associated vision loss.

Characterisation of delayed severity flares in patients with HLA-B27-associated anterior uveitis

Background/aimsTo explore and characterise the clinical phenotype of acute anterior uveitis flares with delayed severity in patients with human leucocyte antigen B27 (HLA-B27)-associated anterior uveitis.MethodsRetrospective chart review of patients with...

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 (TCRs) 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 analyze 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 α4β7, and CCR6. In addition, we find an expansion of YeiH-specific CD8 T cells in the blood of axSpA and B27AAU over healthy controls, whereas influenza-specific CD8 T cells were equivalent across groups. Lastly, we demonstrate 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.

Ultrasound imaging for sternoclavicular joint involvement in enthesitis-related arthritis: A closer look at capsular enthesitis

Introduction: Enthesitis-related arthritis is a specific subtype of juvenile idiopathic arthritis characterised by the co-presence of arthritis and enthesitis or the evidence of one of them coupled with at least two among sacroiliac joint tenderness, inflammatory back pain, presence of human leukocyte antigen-B27, acute symptomatic anterior uveitis, onset in a male child aged 6 years or older or history of spondyloarthropathy in a first-degree relative. Small joints like the sternoclavicular joint are rarely affected, and the prevalence of their involvement in enthesitis-related arthritis has been poorly assessed in the pertinent literature. Case report: The authors report an atypical case of left sternoclavicular joint arthritis/enthesitis in a 12-year-old male child with juvenile idiopathic arthritis. The B-mode sonographic findings of articular effusion, synovial hypertrophy and capsular bulging, coupled with the microvascular mapping with colour Doppler of the sternoclavicular joint, have been crucial to optimising the pharmacological approach in clinical practice. In this sense, the sonographic examination presented as a natural extension of the physical examination to accurately define the poor control of disease activity using first-line pharmacological agents. Discussion: The present case report can be considered the first to accurately report the B-mode and the colour Doppler findings of a pathological sternoclavicular joint in a patient enthesitis-related arthritis. Ultrasound imaging demonstrated intra-articular effusion, capsular bulging and synovial hypertrophy clearly defining sternoclavicular joint arthritis. Interestingly, the hypervascularisation involved both the synovial tissue and the capsule–bone interface – that is, the enthesis of the joint capsule – suggesting a potential co-existence of arthritis and enthesitis of the sternoclavicular joint in enthesitis-related arthritis patients. Conclusion: The high-resolution point-of-care ultrasound seems to be a potential ‘game changer’ in paediatrics to promptly optimise the pharmacological management in enthesitis-related arthritis patients. Indeed, unlike other imaging modalities such as magnetic resonance imaging, modern high-frequency ultrasound transducers guarantee a superior spatial resolution of superficial joints and allow an accurate mapping of small-size and low-flow vascular elements of synovial and capsular tissues optimising the grading of disease activity and avoiding the use of contrast agent.

Risk of Recurrence in Acute Anterior Uveitis

PurposeTo examine the frequency of recurrence and identify risk factors for recurrence in patients with acute anterior uveitis (AAU). DesignRetrospective cohort study from a single tertiary ophthalmic clinical centre. ParticipantsAll subjects with AAU identified from a database of Inflammatory Eye Disease presenting to Te Whatu Ora (Auckland, New Zealand) between 2008 and 2021. MethodsData was collected retrospectively from chart review and electronic patient records for all patients during the study period. Rates of recurrence were reported using Kaplan Meier estimator. Multivariate analysis of risk factors for recurrence were calculated using a marginal Cox regression model. Main Outcome MeasuresThe primary outcome measure was disease recurrence. Secondary outcome measure was moderate vision loss (≤20/50). Results2763 eyes of 2092 subjects with AAU were studied, with a median follow up time of 8.9 years, and a total follow up of 19,794.9 eye-years. Recurrence occurred in the ipsilateral eye in 1258 eyes (45.5%) and in the contralateral eye in 522 eyes (27.3%). Rates of ipsilateral recurrence over ten years were 38.1% for idiopathic disease, 43.2% for HLAB27/inflammatory arthritis, and 44.9% for viral uveitis. On multivariate analysis the following were associated with increased risk of ipsilateral recurrence: older age (p<0.001); Māori ethnicity (p=0.006); Asian ethnicity (p<0.001); HLA-B27/inflammatory arthritis (p<0.001); viral uveitis (p=0.018). There was no association with gender, smoking, bilateral disease, or hypertensive uveitis. Rates of contralateral eye involvement were significantly lower than ipsilateral eye recurrence. Contralateral recurrence at ten years was 15.2% in idiopathic uveitis, 37.6% in HLAB27/inflammatory arthritis, and 2.0% in viral uveitis. Risk factors identified for contralateral eye involvement were Māori ethnicity (p=0.003), Pasifika (Pacific Islanders) ethnicity (p=0.021), HLAB27/inflammatory arthritis (p<0.001). Moderate vision loss (≤20/50) was present in 411 eyes (14.9%) at final follow up and was more common if time to first recurrence was shorter (p<0.001). ConclusionsApproximately half of patients with AAU will develop recurrence in the ipsilateral eye and a quarter will have recurrence in the contralateral eye. Patients with viral disease have the highest risk of ipsilateral recurrence and lowest risk of contralateral recurrence. Patients with risk factors for recurrence should be managed and counselled appropriately to minimise the risk of visual loss and complications of uveitis.

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

BackgroundSeveral 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.MethodsGenotyping 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.ResultsAll 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.ConclusionOur 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.

Роль С3-, С4-компонентов системы комплемента в патогенезе герпетического увеита

Herpetic anterior uveitis is mainly considered as acute unilateral anterior uveitis with non-granulomatous, granulomatous, or stellate keratic precipitates, which is associated with iris atrophy, decreased corneal sensation, and an acute rise in the intraocular pressure. The diagnosis of herpetic anterior uveitis usually is based on clinical findings. We presented several clinical cases with atypical manifestations. Our study aims to understand the role of the complement system’s C3 and C4 fractions in the pathogenesis of herpetic anterior uveitis.

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

ABSTRACT 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.

Management of Acute Non-Infectious Anterior Uveitis in Adults – Practice Patterns Among Uveitis Specialists in North America

ABSTRACT Purpose This study aims to understand the practice patterns among ophthalmologists in North America who manage patients with acute, non-infectious anterior uveitis. Methods An eight-question survey was designed to elucidate the practice patterns of ophthalmologists across various geographic locations and practice settings regarding the management of anterior uveitis. This survey was distributed via the American Uveitis Society and Young Uveitis Specialists email listserv to ophthalmologists who self-identify as uveitis specialists and have a patient population that is at least 30% uveitis. Results A total of 102 responses were received and analyzed (37% response rate). Respondents practiced predominantly in North America, and 40% had received subspecialty training in uveitis. All respondents chose topical corticosteroid therapy as first-line treatment for acute, unilateral, or bilateral non-infectious idiopathic anterior uveitis. The most common initial frequency for prednisolone acetate administration was six times/day while the patient was awake (29.7%) and patients are typically seen in follow-up within a week (75% of respondents). If there is a lack of treatment response within 2–3 weeks with the initial topical treatment, 42 respondents (41.2%) chose to switch to difluprednate eye drops and 29 (28.4%) recommended switching to oral prednisone. Conclusion Our results show that topical corticosteroid, most frequently prednisolone acetate 1%, is the treatment of choice for patients with acute noninfectious anterior uveitis. Reported initial medication dosing and follow-up care approaches are highly variable, which suggests heterogeneity in practice patterns. Further research on the optimal initial dosing is needed.

HLA-B27 Associated Acute Fibrinous Anterior Uveitis

This case describes the clinical course of a patient with severe acute anterior uveitis with fibrin formation in the anterior chamber. Rheumatological as well as infectious testing revealed HLA-B27 involvement to be likely. HLA-B27 associated uveitis tends to show a greater inflammatory reaction including fibrin production. A discussion of HLA-B27 and possible pathogenicity is discussed.

The Risk of Depressive Symptoms Increases in Radiographic Axial Spondyloarthritis Patients with Acute Anterior Uveitis

Abstract Background This study aimed to assess the psychological status of radiographic axial spondyloarthritis (r-axSpA) patients with/without acute anterior uveitis (AAU) and to investigate whether the emotional status was different and associated with disease activity and other clinical variables. Patients and Methods This cross-sectional study included a total of 145 r-axSpA in-patients who fulfilled the modified New York criteria for ankylosing spondylitis. AAU was established by ophthalmologists. Clinical variables were collected from patient charts. All patients received a comprehensive rheumatologic assessment for disease activity, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). The Short Form (SF)-36 Health Survey, the revised Self-Rating Anxiety Scale (SAS) and the revised Self-Rating Depression Scale (SDS) were applied to all participants by psychiatrists. Results Fifty-seven patients were diagnosed as having the first onset of AAU. Compared with the group of r-axSpA without AAU, the risk of depressive symptoms was higher in the group of r-axSpA with AAU (p=0.008). However, there was no significant difference in terms of the risk of anxious symptoms between these groups (p=0.868). In addition, r-axSpA patients with AAU had higher scores of ASDAS-C-reactive protein (ASDAS-CRP) but lower scores of ASDAS-erythrocyte sedimentation rate (ASDAS-ESR) (p=0.032 and p=0.019). Furthermore, there was a negative correlation between SDS scores and duration in r-axSpA patients with AAU. Among all patients, the group of r-axSpA with depressive symptoms had increased CRP levels and ASDAS-CRP scores and lower vitality in SF-36. Conclusion The risk of depressive symptoms increases in r-axSpA patients with AAU. Moreover, r-axSpA patients with uveitis had a higher disease activity as measured by ASDAS-CRP. Physicians should pay more attention to depressive symptoms and AAU in addition to the disease of r-axSpA itself.

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

ABSTRACT 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.

Topiramate: Connecting dot of acute angle closure with myopic shift and missing link with acute anterior uveitis

An interesting case of a 38-year-old male who presented with bilateral, sudden onset, painful diminution of vision. He had raised intraocular pressure (IOP), Oculus Uterque (OU) and bilateral acute onset myopia. Ultrasound biomicroscopy (UBM) revealed bilateral (B/L) ciliochoroidal effusion. This made us revisit his history to justify the acute onset myopia associated with raised IOP, which was established to be Topiramate (TPM) induced. Fourteen days after withdrawal of TPM, he also developed unilateral acute non-granulomatous anterior uveitis that was managed conservatively. Finally, his uncorrected visual acuity was 6/6 OU, and IOP was normal without any drugs. This case illustrates the significance of meticulous history and a step-wise approach to clinch the diagnosis. It is also imperative for clinicians to recognize these conditions and educate patients about the serious adverse effects when prescribing TPM.

Zoledronate-induced Anterior Uveitis: A Case Report and Literature Review

ABSTRACT Zoledronate is one of the treatments used for postmenopausal osteoporosis. Acute febrile reactions are common with zoledronate therapy. However, zoledronate-induced uveitis is rarely reported in the global literature. In this work, we report a case of bilateral acute anterior uveitis following zoledronate infusion. A 56-year-old, postmenopausal woman presented with symptoms of fever, bilateral periorbital swelling, watering from eyes, pain, photophobia, and blurring of vision 2 days after zoledronate infusion. On examination, there was conjunctival hyperemia, aqueous cells, fibrinous reaction, pigments in the anterior lens capsule, keratic precipitates, and posterior synechiae, suggestive of acute anterior uveitis. Her symptoms resolved completely over 2 weeks of topical administration of betamethasone and atropine. Uveitis is one of the rare complications of bisphosphonates, with zoledronate having a higher risk. The mechanism is not fully known. Knowledge about this adverse event is essential for prompt diagnosis and timely management.

High-Dose-Rate Yttrium-90 (90Y) Episcleral Plaque Brachytherapy for Iris and Iridociliary Melanoma

PurposeTo describe a pilot study on the use of single-session, high-dose-rate, FDA-cleared, yttrium-90 (90Y) plaque brachytherapy for iris and iridociliary melanoma. DesignA single-center, clinical case series. ParticipantsSix consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy. MethodsEach tumor was staged according to AJCC criteria and received 90Y eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression. ResultsHigh-dose-rate 90Y plaque brachytherapy was used to treat small (AJCC cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Due to short treatment durations, high-dose-rate 90Y did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. high-dose-rate 90Y treatment durations averaged 8.8 minutes (median 7.9, range 5.8-12.9). High-dose-rate 90Y brachytherapy was associated with no periorbital, corneal (Descemet’s folds), and/or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. Follow-up was a mean of 16.0 (range 12 to 24) months. Evidence of local control included a lack of expansion of tumor borders (n=6, 100%), darkening and/or atrophy of the tumor surface (n=5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease. ConclusionHigh-dose-rate 90Y brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas.

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

BackgroundPatients 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.MethodsTo 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.ResultsMendelian 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, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group.ConclusionsAIF1 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.