Increased serum level of interleukin-33 in Vogt-Koyanagi-Harada correlates with disease activity.

OBJECTIVES: To measure the serum level of IL-33 in patients with Vogt-Koyanagi-Harada disease (VKH) and Behçet's uveitis (BU) in the Chinese Han population and investigate its associations with disease activity and clinical parameters. METHODS: Serum was collected from 41 VKH patients (16 active and 25 inactive patients), 60 BU patients (24 active and 36 inactive patients), and 36 healthy controls. The serum level of IL-33 was measured using the enzyme-linked immunosorbent assay (ELISA) method. Demographic features, clinical manifestations, and intraocular inflammation activity scores (anterior chamber cells score, anterior chamber flare score, and vitreal haze score) were recorded. RESULTS: The serum level of IL-33 significantly increased in all VKH patients, active VKH patients, and inactive VKH patients, as compared to healthy controls (p < 0.001, p < 0.001, and p = 0.002, respectively), and was higher in the active VKH than in the inactive VKH patients (p = 0.049). The serum level of IL-33 positively correlated with the anterior chamber cells score, vitreal haze score, and the annualized number of relapses in VKH patients (Rho = 0.359, p = 0.021; Rho = 0.344, p = 0.028; Rho = 0.537, p < 0.001, respectively). Serum IL-33 level was significantly associated with the annualized number of relapses in patients with BU (Rho = 0.361, p = 0.005). CONCLUSION: Serum IL-33 level is significantly increased in VKH patients in the Chinese Han population. IL-33 level is in positive correlation with the activity and relapses of VKH. Increased IL-33 might contribute to the pathogenesis of VKH and serve as a potential biomarker for VKH disease.

Detection of HIV-1 viral load in tears of HIV/AIDS patients.

OBJECTIVES: The tear, as an important bodily secretion, plays a crucial role in preventing infection and maintaining homeostasis of ocular surfaces. Although accumulating studies have reported on the HIV-1 viral load profile among varying bodily fluids and secretions, little was known concerning HIV-1 dynamics in tears. Therefore, the objectives of this study were to investigate the HIV-1 viral load in tears of HIV/AIDS patients and study factors influencing their tear viral load. METHODS: A cross-sectional study was conducted. 67 patients with a confirmed HIV-1 infection or AIDS were recruited from the Beijing You'an Hospital, China between April 2018 and September 2018. Socio-demographic information and laboratory test results were collected. At the same time, ophthalmic examinations were carried out and tear samples were tested. RESULTS: Of 30 highly active antiretroviral therapy (HAART)-naïve patients, 53.3% had detectable HIV-1 RNA in tears. Of 37 patients on HAART, HIV-1 RNA was undetectable in their tears, regardless of treatment duration and blood viral load. Tear viral load ranged from TND (target not detected) to 13,096 copies/mL. Viral load was lower in tears than in blood plasma (p < 0.001), and was significantly correlated with plasma viral load (Rho = 0.566, p < 0.001) and AIDS stage (Rho = 0.312, p = 0.01), but negatively correlated with CD4 + T cell count, CD4 +/CD8 + T cell count, and duration of HIV infection (Rho = -0.450, Rho = - 0.464, Rho = - 0.565; p < 0.001). CONCLUSIONS: HIV-1 RNA is present in tears of more than half of the HAART-naïve patients, whereas absent in tears of patients on HAART. Tear viral load is positively associated with plasma viral load while it is negatively correlated with CD4 cell count. This study provides novel insights into the area with limited understanding-HIV-1 viral load in tears.

The Functional Roles of IL-33/ST2 Axis in Ocular Diseases.

Interleukin-33 (IL-33), an important member of the IL-1 family, plays a pivotal role in regulating immune responses via combining with its receptor suppression of tumorigenicity 2 (ST2). We have already known IL-33/ST2 axis participates in the pathogenesis of various diseases, including liver diseases, renal diseases, and neurological diseases. Recently, emerging studies are indicating that IL-33/ST2 is also involved in a wide range of ocular diseases, such as allergic eye disease, keratitis and corneal regeneration, dry eye disease, uveitis, vitreoretinal diseases, and neuromyelitis optica spectrum disorder. In this review, we will summarize and discuss the current understanding about the functional roles of IL-33/ST2 in eyes, with an attempt to explore the possible study perspectives and therapeutic alternatives in the future.

Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities.

Tumor-associated macrophages (TAMs) are a heterogeneous population that play diverse functions in tumors. Their identity is determined not only by intrinsic factors, such as origins and transcription factors, but also by external signals from the tumor microenvironment (TME), such as inflammatory signals and metabolic reprogramming. Metabolic reprogramming has rendered TAM to exhibit a spectrum of activities ranging from pro-tumorigenic to anti-tumorigenic, closely associated with tumor progression and clinical prognosis. This review implicates the diversity of TAM phenotypes and functions, how this heterogeneity has been re-evaluated with the advent of single-cell technologies, and the impact of TME metabolic reprogramming on TAMs. We also review current therapies targeting TAM metabolism and offer new insights for TAM-dependent anti-tumor immunotherapy by focusing on the critical role of different metabolic programs in TAMs.

Efficacy and safety of adalimumab for inflammatory flare prevention in paediatric non-infectious anterior uveitis with peripheral retinal vascular leakage: a study protocol for a single-centre, randomised controlled trial.

INTRODUCTION: Paediatric patients with chronic anterior uveitis are more prone to suffer from the chronic course of intraocular inflammation and adverse effects of long-term immunomodulatory therapy, either topical glucocorticosteroids or systemic immunomodulatory agents. The performance of adalimumab has been shown to be fairly favourable in treating refractory non-infectious uveitis, but the detailed indication is still under investigation. This study aims to assess the efficacy and safety of adalimumab for inflammatory flare prevention in non-infectious paediatric anterior uveitis with peripheral retinal vascular leakage, compared with methotrexate. METHODS AND ANALYSIS: Children weighed ≥30 kg and aged between 4 and 16 years old with active non-infectious anterior uveitis with peripheral retinal vascular leakage on ultra-wildfield fluorescein fundus angiography will be included. They will be treated with a predesigned inflammatory control regimen to reach inflammatory quiescence in 1 month. After that they will be treated with either methotrexate 10 mg once a week or adalimumab once every 2 weeks and regularly followed up for 6 months. The primary endpoint is uveitis flare defined as defined as anterior chamber cell count grading increased from 0 to 1 within the observation period. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of Peking Union Medical College Hospital, Beijing, China (Approved protocol V3, dated 27 July 2021. Approval number 25-ZS-3062) and has been registered on ClinicalTrials.gov. Written informed consent will be collected from every patient and their guardians prior to study participation. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: NCT05015335.

Widefield Swept-Source Optical Coherence Tomography Angiography Assessment of Choroidal Changes in Vogt-Koyanagi-Harada Disease.

Purpose: To investigate choroidal changes in patients with Vogt-Koyanagi-Harada disease (VKH) using widefield swept-source optical coherence tomography angiography (SS-OCTA). Methods: In this cross-sectional study, 133 eyes of 69 patients with VKH (52 eyes of 28 active VKH patients and 81 eyes of 41 inactive VKH patients) and 104 eyes of 52 age and sex matched healthy volunteers were imaged using a widefield SS-OCTA instrument. On 12 mm × 12 mm OCTA scans, mean choroidal thickness (MCT), choroidal vascularity index (CVI), choriocapillaris (CC) flow area, and mean retinal thickness (MRT) were separately calculated in the fovea (diameter of 1 mm) and in concentric rings with different radii (1-3, 3-6, 6-9, and 9-12 mm). Results: Eyes with active VKH showed significant increases in MCT, CVI, and MRT, and decreased CC flow area in all central and peripheral regions (0-1, 1-3, 3-6, 6-9, and 9-12 mm) than in the healthy eyes (p ≤ 0.01) and inactive VKH eyes (p < 0.05). Inactive VKH eyes only showed marked decrease in CC flow area in all regions compared with controls (p < 0.05). Flow voids were observed in 51 of 52 (98.1%) active VKH eyes and 50 of 81 (61.7%) inactive VKH eyes on 12 mm × 12 mm OCTA. The MCT of all regions was significantly correlated with age, disease duration, and disease activity, whereas CVI was associated with age and disease activity. The CC flow void was related to visual acuity in all regions (p < 0.05). Conclusion: Widefield SS-OCTA enables a more comprehensive evaluation of chorioretinal changes in patients with VKH disease. Structural and vascular abnormalities are observed in both the central and peripheral choroid and are closely correlated with disease activity.

Comparison of the Safety and Efficacy of Interferon Alpha-2a and Cyclosporine-A When Combined With Glucocorticoid in the Treatment of Refractory Behçet's Uveitis: A Randomized Controlled Prospective Study.

Purpose: To evaluate and compare the efficacy and safety of interferon alpha-2a (IFN-α2a) and cyclosporine-A (CsA) in patients with refractory Behçet's uveitis (BU). Methods: In this 12-month randomized, controlled, prospective trial, 26 participants (44 eyes) completed the study. Patients were randomly allocated to the IFN-α2a or CsA groups. All patients in both groups received a standardized prednisone burst and tapering schedule as per protocol. The primary outcome measures were response rate, complete remission rate, and tolerance rate. The secondary outcome measures included time to achieve complete remission, the logarithm of the minimum angle of resolution (logMAR) of best-corrected visual acuity (BCVA), and Behçet's disease ocular attack score 24 (BOS24). T-tests and non-parametric tests were used to compare quantitative variables, and chi-square tests were performed to compare qualitative variables. Results: The response and complete remission rates were 85.7% (12/14 patients) and 50.0% (7/14 patients) in the IFN-α2a group, compared with 66.7% (8/12 patients) and 25.0% (3/12 patients) in the CsA group, respectively (p > 0.05). Complete remission was achieved at 3.3 and 7.0 months after initiation of IFN-α2a and CsA (p = 0.023). LogMAR BCVA significantly improved 1 month after IFN-α2a initiation (23 eyes) (p = 0.002), and this beneficial effect remained statistically significant during the entire follow-up period (p < 0.05); however, this improvement was not observed in the CsA group (21 eyes). At the endpoint, LogMAR BCVA in the IFN-α2a group was significantly better (0.22 vs. 0.31, p = 0.031) with a higher improvement rate (60.9 vs. 47.6%, p > 0.05). Moreover, compared to the CsA group, more eyes in the IFN-α2a group had a lower BOS24 score (87.0 vs. 57.1%, p = 0.042). None of the patients had any side effects that influenced the medication adherence. Conclusion: Compared to CsA plus corticosteroid, IFN-α2a plus corticosteroid appears to induce a better treatment response, a significantly greater improvement in visual acuity, and more stable remission of intraocular inflammation in a 12-month study period.