[CLINICAL MANIFESTATIONS OF AUTOIMMUNE DISEASES].

INTRODUCTION: Ocular inflammation, uveitis, represents over 40 distinct diseases, caused by infectious or non-infectious etiologies. Non-infectious uveitis may be related to systemic autoimmune diseases. Most uveitis patients are of working age, and prolonged disease may affect their independence and ability to work. Uveitis has various clinical manifestations and may result in the development of ocular complications and vision loss. Uveitis accounts for 10-15% of blindness in the developed world. Autoimmune diseases are increasing globally and often involve the eyes. Most cases occur in young active people and therefore any ocular changes have a longer effect. Symptoms may be mild but they might be severe, even blindness. It accounts for 10% to 15% of all causes of blindness among people of working age in the developed world. OBJECTIVES: To describe the ocular manifestation of uveitis related to systemic autoimmune diseases. We will describe ocular signs related to the disease and discuss the treatment approach to prevent the development of ocular complications and vision loss. METHODS: Review of clinical findings and treatment approach to non-infectious uveitis. CONCLUSIONS: Ocular involvement is commonly found in many autoimmune diseases. The severity of ocular disease varies between cases and complications may result in vision loss. Early diagnosis and treatment may prevent the development of ocular complications, maintaining visual acuity and patient independence.

Prevalence, clinical characteristics, and independent predictors of uveitic macular edema in an Asian population: a retrospective cohort study.

BACKGROUND: To determine the prevalence, clinical characteristics, and independent predictors of uveitic macular edema (UME) in patients with intermediate, posterior and panuveitis. METHODS: We retrospectively reviewed the records of patients with intermediate, posterior, and panuveitis who underwent macular assessment using optical coherence tomography between January 2015 and February 2020. The prevalence of UME and clinical characteristics of the patients were described. Predictors of UME were identified using multivariate regression analysis. RESULTS: A total of 349 patients were included. The mean age was 41 years, female: male ratio was 1.3:1. The prevalence of UME was 51.9%. UME was found in 33.9%, 56.9%, and 54.1% of the intermediate, posterior, and panuveitis cases, respectively. Among patients with UME, 47% had infectious uveitis, 32.6% had idiopathic uveitis, and 20.4% had immune-mediated uveitis. Diffuse macular edema was the most frequently observed pattern (36.5%). Multivariate analysis showed that factors independently associated with UME included age at uveitis onset (adjusted odds ratio [aOR] 1.01, 95% confidence interval [CI] 1.00-1.03, P = 0.036), PU and panuveitis compared with intermediate uveitis (aOR 2.09, 95% CI 1.14-3.86, P = 0.018), and infectious uveitis compared with noninfectious uveitis (aOR 2.13, 95% CI 1.34-3.37, P = 0.001). CONCLUSIONS: Increasing age at uveitis onset, posterior/panuveitis, and infectious etiology are predictive factors for UME in patients with intermediate, posterior and panuveitis.

Masquerade syndrome: A review of uveitic imposters.

Masquerade syndromes in uveitis are complex clinical conditions where non-inflammatory diseases mimic uveitic manifestations, often leading to diagnostic and therapeutic challenges. This review delves into the diverse spectrum of masquerade syndromes, categorizing them into neoplastic and non-neoplastic entities. We explore the prevalence of primary intraocular lymphoma, leukaemia, retinoblastoma, and other malignancies, as well as conditions like retinitis pigmentosa and endophthalmitis that can present as uveitis. Through detailed analysis of symptoms, diagnostic methods, and treatment approaches, the review emphasizes the importance of considering masquerade syndromes in differential diagnoses to prevent mismanagement. The synthesis of current knowledge aims to enhance clinicians' ability to discern these complex presentations, advocating for a multidisciplinary approach to diagnosis and care, thereby improving patient outcomes in cases of uveitic masquerade syndromes.

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study.

BACKGROUND: Clinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AIM: To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. METHODS: Two large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. RESULTS: Between 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. CONCLUSIONS: High-risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Serum Biomarkers of Vascular Involvement in Childhood Uveitis.

Purpose: Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis. Methods: We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis-associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group. Results: In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups. Conclusions: Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future. Translational Relevance: Our targeted proteomics analysis in serum of pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.

New-onset or relapse of uveitis after rapid spreading of COVID-19 infection in China and risk factor analysis for relapse.

BACKGROUND: The aim of this study was to report the clinical profile of new-onset and relapse of uveitis following rapid spreading of coronavirus disease 2019 (COVID-19) infection due to change of anti-COVID-19 policies in China and investigate potential risk factors for inflammation relapse. METHODS: In this retrospective case-control study, patients with new-onset or a history of uveitis between December 23, 2022, and February 28, 2023, were included to assess the influence of COVID-19 infection on uveitis. Detailed information on demographic data, clinical characteristics, treatment measures, treatment response, and ocular inflammatory status before and after COVID-19 infection was collected. RESULTS: This study included 349 patients with a history of uveitis. The uveitis relapse rate was higher (28.8%, n = 288) in those with COVID-19 infection than in patients without COVID-19 infection (14.8%, n = 61) (P = 0.024). Among the relapse cases, 50.8% experienced a relapse of anterior uveitis, while 49.2% had a relapse of uveitis involving the posterior segment. Multivariable regression analysis indicated a positive correlation between disease duration and uveitis relapse, while the last relapse exceeding one year before COVID-19 infection and the use of methotrexate during COVID-19 infection were negatively correlated with relapse of uveitis. Thirteen patients who developed new-onset uveitis following COVID-19 infection were included; among them, three (23.1%) had anterior uveitis and 10 (76.9%) had uveitis affecting the posterior segment. Regarding cases involving the posterior segment, four patients (30.8%) were diagnosed with Vogt-Koyanagi-Harada disease. CONCLUSIONS: COVID-19 infection increases the rate of uveitis relapse. Long disease duration is a risk factor, while time since the last relapse more than 1 year and methotrexate use are protective factors against uveitis relapse.

New onset of uveitis during infliximab treatment: A case report.

INTRODUCTION: Anti-tumor necrosis factor α (anti-TNF α) agents are an effective treatment for a variety of inflammatory and autoimmune diseases. In ophthalmology anti-TNF α began to emerge as a possible therapy for non-infectious uveitis, paradoxically their administration may result in the onset or recurrence of inflammatory eye disease such as uveitis. We reported a case of new onset of bilateral anterior and intermediate uveitis in a patient with rheumatoid arthritis (RA) while being treated with infliximab and we performed a review of literature. OBSERVATION: A 25-year-old female with RA under infliximab, presented with bilateral blurred vision. Anterior segment examination demonstrated retrodescmetic fine precipates, 1+ cells in the anterior chamber on both eyes. The fundus examination was difficult because of the vitritis. Fluorescein angiography demonstrated mild optic disc edema, and bilateral diffuse peripheral fern leaf cappilaritis. Optical coherence tomography showed severe cystoid macular edema bilaterally. The diagnosis of bilateral anterior and intermediate uveitis caused by infliximab was retained after exclusion of infectious and autoimmune aetiologies. She was treated with corticosteroid with good visual outcome. CONCLUSION: In our case, new onset of uveitis may be considered as paradoxical effect of anti-TNF α therapy. Rheumatologists and ophthalmologists should be aware of this effect. Careful monitoring of patients under infliximab is necessary for appropriate diagnosis and early treatment.

Risk of uveitis in autoimmune diseases patients treated with hydroxychloroquine: A population-based retrospective cohort study.

OBJECTIVE: Uveitis is a common manifestation of various autoimmune diseases and can lead to severe visual impairment. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used to treat autoimmune diseases. The aim of this study was to investigate the association between HCQ use and the incidence of uveitis in patients with autoimmune diseases, as well as to identify potential risk factors for the development of uveitis in this study. METHODS: We conducted a population-based cohort study using a nationwide database to investigate the incidence of uveitis in patients with autoimmune diseases who received HCQ treatment. We selected non-HCQ comparison cohort at a 1:1 ratio by propensity score matching on age, sex, index date, urbanization, income, comorbidities, and medications. The data were analyzed using Cox proportional hazards models, and propensity score matching (PSM) was used to reduce selection bias. RESULTS: Our study included 15 822 patients with autoimmune diseases. After 1:1 PSM, there were 4555 individuals in both the HCQ group (n = 4555) and the non-HCQ group (n = 4555). The multiple Cox proportional hazard regression analysis was used for the estimation of adjusted hazard ratios on uveitis. After PSM, the adjusted hazard ratio for the HCQ group was 0.74 (95% CI = 0.58-0.95). These findings suggest that HCQ may play a protective role in reducing the risk of uveitis in patients with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus groups. The Kaplan-Meier survival curves also showed a significantly lower incidence of uveitis in the HCQ group (log-rank = 0.0229) after PSM. CONCLUSION: HCQ use is associated with a lower incidence of uveitis in patients with autoimmune diseases. Further studies are needed to confirm this association and to investigate the underlying mechanisms.

Association between advanced glycation end products and uveitis/scleritis activity in patients with active immune-mediated ocular inflammatory diseases.

PURPOSE: To investigate for association between skin autofluorescence (SAF) advanced glycation end products (AGEs) and uveitis/scleritis activity in systemic inflammatory disease-related active non-infectious uveitis/scleritis patients. METHODS: This cross-sectional study was conducted at Siriraj Hospital during October 2019 to March 2020. AGEs were measured by SAF method in systemic immune-related disease patients with active uveitis/scleritis, and those results were compared with those of healthy age-matched controls. RESULTS: Thirty-one active non-infectious uveitis/scleritis patients and 31 age-matched controls were enrolled. The mean age of patients was 40.0 ± 12.8 years, and most were female (55.0%). The most common associated systemic immune-related disease was Vogt-Koyanagi-Harada disease (n = 14). Mean SAF AGE level in the study group compared to the control group was 2.38 ± 0.66 arbitrary units (AU) versus 2.58 ± 0.56 AU, respectively (p = 0.20). Multivariate analysis showed decreased SAF AGE level to be significantly associated with active ocular inflammation, (odds ratio: 0.01, 95% confidence interval: 0.00004-0.81; p = 0.04). CONCLUSIONS: SAF AGE level was not so far found to be a reliable biomarker for indicating uveitis/scleritis activity in systemic immune-related disease patients with active ocular inflammation. CLINICAL TRIAL REGISTRATION: Thai Clinical Trials Registry, https://www.thaiclinicaltrials.org/ . (Reg. No. TCTR20200114004, registered date 01/01/2020, beginning date of the trial 10/01/2019).

Unilateral Acute Retinal Necrosis with Contralateral Non-necrotizing Herpetic Uveitis.

PURPOSE: The objective of this study is to report a case of unilateral acute retinal necrosis (ARN) with contralateral eye presenting as non-necrotizing herpetic uveitis. CASE REPORTS: Case 1: A 48-year-old female presented at our clinic with blurred vision in the right eye for 7 days. She was diagnosed with ARN in the left eye 2 weeks ago. Ophthalmic examination revealed reduced visual acuity in the right eye (20/33) with the presence of optic disc swelling and macular exudation without peripheral necrotic lesions. With systemic antiviral therapy, optic disc swelling of the right eye vanished gradually, and the visual acuity improved to 20/20. Loss of retinal nerve fiber layer (RNFL) and decreased retinal thickness in the corresponding area occurred during follow-up. CONCLUSION: Non-necrotizing herpetic uveitis may occur in the contralateral eye of unilateral ARN under rare conditions. Structure abnormities, including loss of RNFL and focal decreased retinal thickness, are irretrievable.

Long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha treatment for patients with Behcet's uveitis: A systematic review and meta-analysis.

AIM: This study aims to evaluate the long-term efficacy, safety, and cumulative retention rate of antitumor necrosis factor-alpha (anti-TNF-α) therapy for patients with Behcet's uveitis (BU) using meta-analysis. METHODS: We searched the Web of Science and PubMed databases for eligible studies up to December 1, 2022. The quality of each identified study was assessed using the Joanna Briggs Institute's case series literature quality assessment tool. Statistical analysis was conducted using Stata 16.0 software with a random-effects model. RESULTS: Twelve studies comprising 1156 patients with BU were included in our analysis. We found that 85.0% of patients achieved ocular inflammation remission after receiving anti-TNF-α treatment, with a 95% confidence interval (CI) ranging from 78.7% to 90.5%. Additionally, 77.4% (95% CI: 57.5%-92.5%) experienced an improvement in visual acuity (VA). Moreover, the pooled dose reduction of glucocorticoids (GCs) was 11.08 mg (95% CI: -13.34 mg to -8.83 mg). Throughout the follow-up period, the cumulative retention rate of the medication was 67.3% (95% CI: 53.7%-79.6%). Serious adverse events occurred in 5.8% (95% CI: 3.1%-8.9%) of cases, with the three most common types being severe infusion or injection reactions (2.7%; 95% CI: 0.8%-5.4%), tuberculosis (1.3%; 95% CI: 0.0%-3.9%), and bacterial pneumonia (1.3%; 95% CI: 0.1%-3.4%). Subgroup analysis revealed that ocular inflammation remission rates were 89.3% (95% CI: 81.2%-95.5%) for adalimumab treatment and 83.7% (95% CI: 75.3%-90.8%) for infliximab treatment. The drug retention rate after adalimumab therapy was 70.3% (95% CI: 62.0%-78.0%) compared to 66.4% (95% CI: 48.6%-82.2%) for infliximab treatment. Furthermore, the incidence of severe infusion or injection reactions was 2.2% (95% CI: 0.1%-5.8%) following adalimumab treatment and 3.5% (95% CI: 0.7%-7.7%) following infliximab treatment. CONCLUSIONS: Anti-TNF-α therapy represents an effective treatment for BU patients with favorable safety profile and high drug retention rate and a potential advantage of adalimumab over infliximab in terms of ocular inflammation remission, drug retention, and the incidence of severe infusion or injection reactions.

Insights into the diagnosis and management of sarcoid uveitis: A review.

Sarcoidosis is a leading cause of non-infectious uveitis that commonly affects middle-aged individuals and has a female preponderance. The disease demonstrates age, sex and ethnic differences in clinical manifestations. A diagnosis of sarcoidosis is made based on a compatible clinical presentation, supporting investigations and histologic evidence of non-caseating granulomas, although biopsy is not always possible. Multimodal imaging with widefield fundus photography, optical coherence tomography and angiography can help in the diagnosis of sarcoid uveitis and in the monitoring of treatment response. Corticosteroid remains the mainstay of treatment; chronic inflammation requires steroid-sparing immunosuppression. Features on multimodal imaging such as vascular leakage may provide prognostic indicators of outcome. Female gender, prolonged and severe uveitis, and posterior involving uveitis are associated with poorer visual outcomes.

Tubulointerstitial Nephritis and Uveitis Syndrome During the COVID-19 Pandemic: A Case Series.

Objectives: To report the ocular findings, laboratory results, and management of patients with tubulointerstitial nephritis and uveitis syndrome (TINU), whose numbers increased during the 2019 coronavirus disease (COVID-19) pandemic. Materials and Methods: Demographic characteristics, ophthalmic examination findings, laboratory results including polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serum SARS-CoV-2 immunoglobulin G (IgG) antibody, and treatment of patients diagnosed with TINU between March 2020 and March 2022 were evaluated retrospectively. Results: The study included 19 eyes of 10 patients (6 female/4 male). The mean age was 13.5±2.4 years (range: 8-16 years). The mean follow-up duration was 13.5±6.1 months (range: 6-24 months). All patients presented with anterior uveitis. Anterior uveitis was bilateral in 9 patients (90%) and unilateral in 1 patient (10%). Posterior segment findings were normal in 8 patients (80%), and bilateral optic disc edema was observed in only 2 patients (20%). None of the patients had a previous SARS-CoV-2 infection and/or vaccination history. The SARS-CoV-2 PCR test was negative in all patients at presentation. The SARS-CoV-2 IgG antibody test was reactive in 7 patients (70%). Recurrent uveitis developed in 8 patients (80%) during follow-up. Systemic immunomodulatory therapy was required for the control of ocular inflammation in 7 patients (70%) with severe uveitis flare-ups. Conclusion: TINU is a multisystemic autoimmune disease, especially in response to environmental triggering factors such as viral infections. Although TINU is a rare disease, the number of cases increased during the COVID-19 pandemic. SARS-CoV-2 antibodies were detected at a significant rate of 70% in these patients, who did not have a history of SARS-CoV-2 infection and vaccination. Previous asymptomatic SARS-CoV-2 infection in children may be a triggering factor in the development of TINU.

Role of screening for uveitis in subjects with sarcoidosis.

BACKGROUND AND OBJECTIVES: Ocular involvement is common in sarcoidosis. Our study aimed to evaluate the role of screening for uveitis in subjects with sarcoidosis. METHODS: Retrospective case series of 88 subjects with a pre-existing diagnosis of sarcoidosis, with no previous diagnosis of uveitis, reviewed by Ophthalmology at Auckland District Health Board between January 2016 and May 2022. RESULTS: Among those undergoing a screening examination, uveitis was observed in 27.8% (15 out of 54 subjects). In those presenting with acute eye symptoms, uveitis was observed in 94.1% (32 out of 34 subjects). Sarcoid uveitis was diagnosed in a total of 50 out of 88 subjects (56.8%). 45 subjects required ocular treatment. Sarcoid uveitis was observed in 6 out of 27 subjects (22.2%) who were entirely asymptomatic at screening. On multivariate analysis, blurring of vision (OR 26.2 p < 0.001), eye pain (OR 7.3 p = 0.014) and respiratory disease (OR 7.1 p = 0.044) were associated with increased risk of sarcoid uveitis. In the 41 subjects with no uveitis at initial examination, 3 subjects (7.3%) subsequently developed uveitis. CONCLUSION: Our study highlights the importance of ophthalmic screening of all patients with systemic sarcoidosis, even in asymptomatic patients. With a high correlation of ocular symptoms in diagnosis of sarcoid uveitis, ophthalmologists should educate patients to look out for the development of symptoms of ocular inflammation, and clinicians who continue follow up for systemic sarcoidosis should remind patients to watch carefully for these symptoms to facilitate timely diagnosis and intervention.

Causes of infectious pediatric uveitis: A review.

Infectious pediatric uveitis is a rare disease that can cause severe ocular damage if not detected rapidly and treated properly. Additionally, early identification of an infection can protect the child from life-threatening systemic infection. Infectious uveitis can be congenital or acquired and may manifest as a primary ocular infection or as a reactivation. Nevertheless, publications on infectious paediatric uveitis are usually limited to a small number of patients or a case report. So far, most studies on uveitis in children have focused primarily on noninfectious uveitis, and a systematic study on infectious uveitis is lacking. In this review, we summarize the literature on infectious uveitis in pediatric populations and report on the epidemiology, pathophysiology, clinical signs, diagnostic tests, and treatment. We will describe the different possible pathogens causing uveitis in childhood by microbiological group (i.e. parasites, viruses, bacteria, and fungi). We aim to contribute to early diagnosis and management of infectious pediatric uveitis, which in turn might improve not only visual outcome, but also the general health outcome.

Association between Tubulointerstitial Nephritis and Uveitis Syndrome and Small-Vessel CNS Vasculitis: A Case of Polyautoimmunity.

INTRODUCTION: We report a case study of two male pediatric patients presenting with anterior uveitis and elevated renal function parameters. Both were diagnosed with tubulointerstitial nephritis and uveitis syndrome and subsequently developed diffuse cerebral symptoms such as headache, fatigue, and diziness. METHODS: Magnetic resonance images (MRIs) of the brain showed T2-hyperintense lesions with and without gadolinium enhancement leading to brain biopsy and diagnosis of small-vessel central nervous system (CNS) vasculitis in both cases. Both patients were treated according to BrainWorks small-vessel vasculitis protocol and symptoms vanished over the course of treatment. Follow-up MRIs up to 12 months after initiation of therapy showed no signs of recurrence indicating a monophasic disease. CONCLUSION: Small-vessel CNS vasculitis can occur simultaneously to other autoimmune diseases (ADs) in the scope of polyautoimmunity. As clinical findings of CNS vasculitis are often unspecific, neurological symptoms in nonneurological ADs should be adressed thoroughly. Under suspicion of small-vessel CNS vasculitis brain biopsy is still the gold standard and only secure way of definitive diagnosis.