Conectar
Chronic central serous chorioretinopathy (CSC) can cause progressive and permanent vision loss. Although photodynamic therapy (PDT) is a primary treatment option globally, it is not approved for CSC worldwide, limiting therapeutic access. The REPLAY trial is a phase III, investigator-initiated trial to evaluate the efficacy and safety of reduced-fluence PDT (rf-PDT) for chronic CSC to seek the first regulatory approval globally.
This study comprises two cohorts. The ‘untreated cohort’ is a multicentre, randomised, placebo-controlled, double-masked trial involving 60 patients with untreated, fovea-involving chronic CSC, randomised 2:1 to receive a single rf-PDT or placebo treatment. The ‘previously treated cohort’ is a single-arm, open-label trial for up to 10 patients with recurrent CSC after PDT. The primary endpoint for both cohorts is the proportion of eyes with a complete resolution of subfoveal fluid at 12 weeks post-treatment, assessed by optical coherence tomography. Secondary endpoints include changes in best-corrected visual acuity, central choroidal thickness, recurrence rates and incidence of adverse events over a 48 week follow-up.
The study protocol was approved by the Kyoto University Hospital Institutional Review Board, IRB of Chiba University Hospital, Tokyo Women’s Medical University Institutional Review Board and Institutional Review Board of Kansai Medical University Hospital. Written informed consent is obtained from all participants. The results will be disseminated through publication in a peer-reviewed journal and presentations at scientific conferences.
jRCT2051230156 (URL: https://jrct.mhlw.go.jp/latest-detail/jRCT2051230156).
by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Genki Inui, Hiroki Kohno, Miyu Nishigami, Miki Takata, Masato Morita, Akira Yamasaki
BackgroundThe interaction between viral components and type 1 or type 2 cytokines during asthma exacerbations in the airway epithelium may contribute to worsening inflammation. However, these interactions in the small airway epithelium—particularly those involving alarmins (TSLP, IL-25, and IL-33) and IL-8—remain unclear. Dupilumab, a biologic agent used in severe asthma, blocks IL-4 receptor alpha (IL-4Rα) and may offer therapeutic benefits in virus-induced asthma exacerbations. In this study, we evaluate the effects of double-stranded RNA (dsRNA), in combination with various cytokines and dupilumab, on the Human Small Airway Epithelial Cells (HSAECs) line.
MethodsPrimary HSAECs were preincubated with dsRNA to induce the gene and protein expression of alarmins and IL-8. To evaluate the effects of cytokines on dsRNA-induced alarmin and IL-8 expression, various type 1 and type 2 cytokines were co-stimulated with dsRNA. Dupilumab was used as a pretreatment prior to co-stimulation with dsRNA and IL-4 or IL-13. Gene expression of TSLP, IL-25, IL-33, and IL-8 was assessed by quantitative PCR, and protein expression was evaluated by Western Blotting.
ResultsdsRNA significantly increased the expression of TSLP and IL-8. IL-4 and IL-13 further enhanced dsRNA-induced TSLP and IL-8 gene and protein expression. In contrast, TNF-α reduced dsRNA-induced TSLP expression but enhanced IL-8 gene and protein expression. Dupilumab attenuated the expression of TSLP and IL-8 induced by co-stimulation with dsRNA and IL-4 or IL-13 in HSAECs.
ConclusionIn the microenvironment of small airway epithelial cells, particularly during viral infections, the presence of IL-4 or IL-13 may enhance the expression of TSLP and IL-8. Dupilumab attenuates this expression, potentially offering additional benefits in the treatment of asthma, especially during virus-induced asthma exacerbations.
FreshRSS 