Evaluation of Dextromethorphan as a Microglia Inhibitor in the treatment of DME

目的： 小胶质细胞是视网膜中主要的天然免疫细胞，它的激活产生了炎症介质，这是糖尿病视网膜病变的基础，包括血管通透性增加。本研究评价右美沙芬治疗糖尿病黄斑水肿的安全性和有效性，右美沙芬是一种能够抑制小胶质细胞激活的药物。 方法： 一项单中心、前瞻性、开放标签的I/II期临床试验招募了5名患有DME的黄斑患者，他们在为期6个月的时间里每天两次口服右美沙芬60毫克。主要观察指标包括视网膜中央亚区厚度(CST)、最佳矫正视力(BCVA)、黄斑敏感度和荧光素血管造影(FA)迟发性渗漏。 结果： 研究用的药物耐受性良好。6个月时，平均CST下降-6.3%6.8%，BCVA增加+0.6±5.11(平均扫描电子显微镜)字母。5只研究眼中有4只眼的FA晚期渗漏评分为改善。这些发现与血红蛋白A1c(HbA1c)、肌酐或血压的变化无关。 结论： 在这项概念验证研究中，右美沙芬作为DME的主要治疗方法与减少血管渗漏有关，这表明可能的治疗效果。进一步研究小胶质细胞激活的调节是有必要的。 翻译相关性： 这些发现强调了小胶质细胞的调节是治疗糖尿病黄斑水肿的一种潜在有用的治疗策略。

Purpose: The activation of microglia, the primary innate immune cell resident in the retina, produces inflammatory mediators, which underlie changes in diabetic retinopathy including increased vascular permeability. This study evaluates the safety and efficacy of dextromethorphan, a drug capable of inhibiting microglial activation, in the treatment of diabetic macular edema (DME). Methods: A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with macular involving DME who received oral dextromethorphan 60 mg twice daily for 6 months as monotherapy. Main outcome variables included central retinal subfield thickness (CST), best-corrected visual acuity (BCVA), macula sensitivity, and late leakage on fluorescein angiogram (FA). Results: The study drug was well tolerated. At the primary end point of 6 months, mean CST decreased by -6.3% 6.8% and BCVA increased by +0.6 5.11 (mean SEM) letters. Late leakage on FA was scored as improved in four of five study eyes. These findings were not correlated with changes in hemoglobin A1c (HbA1c), creatinine, or blood pressure. Conclusions: In this proof-of-concept study, dextromethorphan administration as the primary treatment for DME was associated with decreased vascular leakage, suggesting possible therapeutic effects. Additional studies investigating the modulation of microglial activation is warranted. Translational Relevance: These findings highlight microglial modulation as a potentially useful therapeutic strategy in the treatment of diabetic macular edema.