Purpose: We conducted a systematic review and meta-analysis to determine the effectiveness and safety of anti-tumor necrosis factor-alpha (TNF-a) agents in the treatment of Behcets' disease (BD)-associated uveitis. Method: Three electronic databases, Embase, MEDLINE, and the Cochrane Library, were searched for eligible papers focusing on the anti-TNF-a agents treatment in BD-associated uveitis with at least 6 months follow-up time. A systematic review and meta-analysis was conducted on selected papers with appropriate clinical and methodological homogeneity. The effectiveness outcomes included inflammation remission, visual acuity (VA) improvement, central macular thickness (CMT) decrease, corticosteroid (CS)-sparing effects, and the safety outcomes included minor and severe drug-related adverse events (AEs). Result: From Jan 2010 to Dec 2019, there were 504 records produced in total, in which 18 clinical trials were selected for meta-analysis (15 trials were retrospective studies, and 3 were prospective studies). The number of patients in each study ranged from 11 to 163 and the mean follow-up time from 0.9 to 6.44 years. During the follow-up, the pooled inflammation remission rate was 68% with a 95% confidence interval (CI) of 0.59-0.79, VA improvement rate was 60% (95% CI 0.47-0.77), CMT decrease was 112.70 mm (95% CI 72.8-153.0 mm). The proportions of patients who had CS-suspended and CS-tapered reached 38% (95% CI 0.23-0.65) and 34% (95% CI 0.16-0.70), respectively. The severe AEs were reported but not common, which included severe infusion reactions, pneumonia, bacteremia, tuberculosis, melanoma, and lymphoma. Conclusion: Anti-TNF-a agents treatment has high effectiveness including efficient inflammation remission, satisfactory VA improvement, obvious CMT reduction, and significant CS-sparing effects. Although some drug-related AEs were reported, the incidence of severe AEs was acceptable. Anti-TNF-a agents treatment is a promising option for controlling BD-associated uveitis.
Chinese Clinical Trial Registry (TRC-13003122).
Background Melatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis. Methods EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1–20 (IRBP1–20). Melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were graded to evaluate the disease progression. T lymphocytes accumulation and the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR, respectively. T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells were detected via flow cytometry for both in vivo and in vitro experiments. Reactive-oxygen species (ROS) from CD4 + T cells was tested via flow cytometry. The expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α) proteins were quantified via western blot. Results Melatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells by suppressing their transcription factors and potentiated Treg cells. In vitro studies corroborated that melatonin restrained the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU. Conclusions Melatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.
The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma (PCNSL), is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as the application of ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies (AFs). However, the genetic alterations detected in cerebrospinal fluid (CSF) ctDNA only partially overlapped with those from simultaneously-collected AH/VF samples, with much lower AFs. Serial post-treatment AH or VF samples were available for five patients and their ctDNA AF changes displayed a similar trend as the changes in interleukin 10 (IL-10) levels; an indicator of treatment responses. A cohort of 23 PCNSL patients was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of PCNSL than VRL patients. The objective response rate of ibrutinib treatment was much higher for PCNSL patients (64.7%, 11/17) than VRL (14.3%, 1/7) patients. In summary, we provided valuable clinical evidence that AH is a good source of tumor genomic information and can be substituted for VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring.
Background: No study has evaluated the effectiveness of Adalimumab (ADA) as first-line in treatment-naïve patients with retinal vasculitis due to Behçet’s Uveitis (BU).Objective: To compare the efficacy of ADA plus conventional therapy and conventional therapy alone as initial treatments in naïve BU patients characterized by retinal vasculitis.Methods: Medical records of BU patients characterized by retinal vasculitis treated with conventional therapy (CT, refers to glucocorticoid and immunosuppressive agents) alone or ADA plus conventional therapy with at least 6 months of follow-up between February 2015 and June 2020 were analyzed. Only patients who were first diagnosed with BU without previous systemic treatment were reviewed. The retinal vasculitis score based on fluorescein angiography (FA), best-corrected visual acuity, glucocorticoid-sparing effect, the number of relapses and ocular complications were evaluated.Results: A total of 45 patients (87 eyes) were included. Twenty-four patients (55.33%) in the CT group were treated with conventional therapy and 21 patients (46.67%) in the ADA group were treated with ADA plus conventional therapy. The inflammatory parameters improved in both groups. FA scores showed significantly greater improvement in ADA group than CT group (p < 0.001). The median number of relapses was significantly lower, and the duration of remission was longer in ADA group than CT group (p < 0.001). At the last visit, a significantly better BCVA improvement (p = 0.024), better inflammation control (anterior chamber inflammation p = 0.017 and vitritis p < 0.001) and lower daily glucocorticoid dosage (p = 0.005) were identified in patients received ADA therapy. In CT group, 1 patient suffered hepatitis B and tuberculosis, 1 had growth retardation, 1 patient had with osteoporosis, then followed by other mild AEs (mostly respiratory upper tract infections); while in ADA group, 1 patient experienced a mild pneumonia (n = 1) while milder AEs were represented mostly by respiratory upper tract infections followed by gastrointestinal discomfort.Conclusion: ADA plus conventional therapy achieved superiority over conventional therapy as initial treatment in naïve BU patients with retinal vasculitis.
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