Optimizing Behçet Uveitis Management: A Review of Personalized Immunosuppressive Strategies.

Behçet uveitis poses significant management challenges, owing to its intricate pathogenesis and the severe prognosis it harbors, frequently culminating in irreversible visual impairment and an elevated risk of blindness. This review synthesizes contemporary insights into personalized immunosuppressive strategies for Behçet uveitis, emphasizing the necessity for a customized approach in recognition of the disease's heterogeneity and the variable responsiveness to treatment. This discourse elaborates on the application, efficacy, and safety profiles of traditional immunosuppressants, highlighting a paradigm shift toward integrative combination therapies aimed at diminishing reliance on glucocorticoids and mitigating their associated adverse effects. This thorough evaluation seeks to enlighten clinical practices and spearhead future investigations aimed at refining the management of Behçet uveitis, championing a personalized, multidisciplinary strategy to amplify therapeutic efficacy and enhance patient quality of life.

Use of corticosteroids in non-infectious uveitis - expert consensus in Taiwan.

PURPOSE: To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies. METHODS: Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established. RESULTS: A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS. CONCLUSION: While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.

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.

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.

Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing.

BACKGROUND: Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. METHODS: To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. RESULTS: Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. CONCLUSIONS: DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.

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.

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.

Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

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.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Steroidal nanoformulations for the treatment of uveitis: potential, promises and future perspectives.

BACKGROUND: Intraocular inflammation, commonly referred to as uveitis, is a prevalent ocular disease. The categorization of uveitis may be based on the prevailing anatomical site, which includes anterior, intermediate, and posterior uveitis. There exists a significant body of evidence indicating that T cells play a pivotal role in the pathogenesis of autoimmune uveitis. In addition to the presence of T cells, an elevation in levels of inflammatory cytokines and a reduction in regulatory cytokines were also noted. The primary pharmacological interventions for uveitis comprise of corticosteroids, methotrexate, anti-vascular endothelial growth factor (VEGF) agents, anti-tumor necrosis factor-alpha (TNF-α) antibodies, and sirolimus. These medications offer prompt alleviation for inflammation. Nevertheless, prolonged administration of corticosteroids invariably leads to unfavorable adverse reactions. The traditional topical corticosteroids exhibit certain limitations, including inadequate transcorneal permeation and low corneal retention, leading to reduced ocular bioavailability. Consequently, there is a growing inclination towards the creation of innovative steroid drug delivery systems with the aim of reducing the potential for adverse effects, while simultaneously enhancing the drug's corneal permeation and retention. CONCLUSION: This review is an attempt to compile all the research work done so far in this field and provides a brief overview of the global efforts to develop innovative nanocarrier-based systems for corticosteroids.

Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness-a protocol for a randomised controlled trial (ASTUTE trial).

INTRODUCTION: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care. METHODS AND ANALYSIS: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted. ETHICS AND DISSEMINATION: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available. TRIAL REGISTRATION: ISRCTN31474800. Registered 14 April 2020.

Factors Associated With Intraocular Inflammation in Neovascular Age-Related Macular Degeneration Patients Treated With Brolucizumab.

Purpose: To identify factors associated with intraocular inflammation (IOI) in patients with neovascular age-related macular degeneration (nAMD) treated with brolucizumab. Methods: In this prospective observational study, we collected aqueous humor samples from 96 eyes of 96 patients receiving treatment with brolucizumab; IOI subsequently developed in 19 eyes of 19 patients. To identify cytokines upregulated in eyes with subsequent development of IOI, we compared the aqueous humor cytokine levels between the IOI and non-IOI groups. We also collected plasma from 20 patients who developed IOI and 20 age- and sex-matched controls to identify differences in plasma biomarkers and the subfraction of CD4+ cells. Using stepwise variable selection and multivariate binary regression analysis, we developed an algorithm that accurately assessed the likelihood of IOI occurrence. Results: The IOI group showed elevated aqueous humor levels of P-selectin (584 vs. 324 pg/mL, P = 0.013), TNF-α (0.89 vs. 0.60 pg/mL, P = 0.018), and IL-1α (2.0 vs. 1.4 pg/mL, P = 0.035) compared with the non-IOI group. Serum MMP-9 concentrations were higher in the IOI group than the non-IOI group (18,310 vs. 13,450 pg/mL, P = 0.029). Furthermore, the percentage of Th2 cells was significantly decreased in the IOI compared with the non-IOI group (3.1% vs. 4.2%, P = 0.013). The receiver operating characteristic curves for the optimal models showed an area under the curve ranging from 0.71 to 0.89, indicating good performance. Conclusions: The combination of elevated concentrations of multiple aqueous humor cytokines and of serum MMP-9 and a lower number of plasma Th2 cells is associated with brolucizumab-related IOI in patients with nAMD.

[Diagnostic modalities of a Behçet uveitis]. / Comment j'explore une uvéite de Behçet.

Behçet disease is a chronic multisystemic inflammatory condition. The ocular disease mainly manifests as a bilateral, non-granulomatous, posterior uveitis or panuveitis, associated with occlusive retinal vasculitis. Uveitis is frequent in Behçet disease, it may be severe, and visually threatening. Early diagnosis and aggressive treatment are mandatory to preserve visual function. Therefore, the goal of this review is to describe the new diagnosis tools and therapeutic guidelines allowing for a significant improvement of the visual prognosis.

La maladie de Behçet est une pathologie inflammatoire chronique multisystémique. L'atteinte oculaire se caractérise le plus souvent par une panuvéite ou uvéite postérieure bilatérale récidivante, non granulomateuse, associée à une vascularite rétinienne occlusive. L'uvéite associée à la maladie de Behçet est fréquente, sévère et potentiellement cécitante en l'absence d'un diagnostic précoce et d'un traitement adapté. L'objectif de cette revue est de décrire les outils diagnostiques et thérapeutiques ayant permis une amélioration significative du pronostic visuel.

Leflunomide for the Treatment of Immune-Mediated Uveitis in a Dog.

A 5 yr old castrated male bichon frise presented with chronic bilateral uveitis that had previously been controlled with systemic steroid administration for 6 mo, resulting in weight gain, polyuria, and polydipsia. To control the uveitis without systemic side effects, oral cyclosporine was started after discontinuing oral steroid, but discontinued one month later because of severe vomiting. Leflunomide (2 mg/kg q 12 hr) was initiated, and the uveitis symptoms resolved after 2 mo. The dose was tapered according to the remission of clinical signs, with no relapse during the following 13 mo. Leflunomide therapy was then discontinued due to vomiting caused by severe gastroenteritis and pancreatitis, and topical prednisolone monotherapy was continued . At 8 mo after discontinuation of leflunomide, bilateral uveitis recurred, and leflunomide therapy was resumed. However, the patient lost vision due to the progression of clinical signs at 33 mo after commencing leflunomide, and evisceration of the glaucomatous right eye was performed at 43 mo. Histopathologic examination revealed lymphocyte and plasma cell infiltration and melanin-laden macrophages in the uveal tissue, and the patient was diagnosed with immune-mediated uveitis. This case indicated that oral leflunomide may be a viable treatment option for canine idiopathic immune-mediated uveitis.

New onset or recurrence of uveitis following COVID-19 infection.

BACKGROUND: While the 2019 novel coronavirus disease (COVID-19) pandemic has resulted in millions of cases worldwide, there is increasing recognition of a wide range of ocular manifestations associated with the virus, including uveitis. Uveitis is an inflammatory condition of the uveal tract of the eye that can lead to permanent vision loss if not treated promptly. Here we report a retrospective observational study of patients who presented with new onset or recurrent uveitis following COVID-19 infection. METHODS: This is a retrospective observational study conducted at the Beijing Tongren Hospital. We identified patients who presented with symptoms of non-infectious active uveitis with positive real-time reverse transcription polymerase chain reaction (RT-PCR) of COVID-19 within 4 weeks. All patients received ophthalmic examinations, including anterior and posterior segment imaging, to assess the extent of ocular involvement. RESULTS: The 18 patients with a total of 33 eyes included in this study presented with symptoms of active uveitis within 4 weeks of their positive COVID-19 RT-PCR test. Among them, 9 patients presented with the development of uveitis following COVID-19 infection, and 9 patients had relapsed uveitis after COVID-19 infection. Treatment with corticosteroids resulted in improvement of symptoms and resolution of inflammation in all cases. In this study, all patients did not experience any adverse drug reactions during treatment. CONCLUSION: Our observational study highlights the potential for new onset or recurrence of uveitis following COVID-19 infection. TRIAL REGISTRATION: https://www.chictr.org.cn/ ; identifier: ChiCTR2100044365, date: 03/17/2023.

Epstein-Barr Virus Uveitis Confirmed via Aqueous Humor Polymerase Chain Reaction and Metagenomics-A Case Report.

This is a case report of Epstein-Barr virus (EBV) uveitis confirmed via aqueous humor polymerase chain reaction (PCR) and metagenomics. This 72-year-old male with a history of diabetes and herpes zoster complained of redness and blurred vision in his right eye for eight months. Mild conjunctival injection, anterior chamber cells, mutton-fat keratic precipitates, and vitreous haze were noted. Fluorescein angiography revealed dye leakage from retinal vessels without retinal ischemic changes. Only the serum anti-cytomegalovirus (CMV) IgG was positive while the aqueous humor PCR for VZV (Varicella-zoster virus), HSV (Herpes simplex viruses), CMV, and EBV was initially negative. Inflammation recurred and vitreous haze worsened after discontinuing nine-month topical ganciclovir and oral prednisolone. the aqueous humor PCR was repeated due to persistent low-grade inflammation. The EBV PCR turned out to be positive. Shotgun metagenomics revealed 1459 classified sequences (1.62%) and confirmed the EBV infection. Topical ganciclovir and methylprednisolone treatment was resumed. Conjunctival injection improved while pigmented keratic precipitates lessened. Elderly patients with diabetes or under immunosuppression may be susceptible to chronic uveitis associated with subsequent EBV infection. Repeated aqueous humor PCR and shotgun metagenomics are important tools in the diagnosis of this case of chronic indolent panuveitis.

Efficacy of golimumab in patients with refractory non-infectious panuveitis.

This study investigated the efficacy of golimumab in the management of refractory non-infectious panuveitis. Nineteen patients (38 eyes; mean age, 31 years) were retrospectively reviewed between June 2016 and June 2022. All patients had bilateral eye involvement and Behçet's disease was the most common diagnosis (57.9%). Compared to the period before golimumab treatment, the rate of uveitis relapses after golimumab treatment significantly decreased from 1.73 to 0.62 events per person-years (incidence ratio 0.33, 95% confidence interval 0.19-0.57, P < 0.001). After golimumab therapy, 12 patients (63.2%) were able to reduce the number or dosage of immunosuppressive drugs, and the median dosage of systemic corticosteroids was reduced from 15.0 to 7.5 mg/d (P = 0.013) compared to baseline. The median logMAR visual acuity improved from 0.9 at baseline to 0.6 at the last visit (P = 0.006). Golimumab demonstrated efficacy against refractory non-infectious panuveitis in terms of a corticosteroid-sparing effect and reduced the rate of uveitis relapses to approximately one-third.