Steroids and Cross-linking for Ulcer Treatment (SCUT II)

项目概要/摘要 研究减轻感染炎症反应的因素可能对以下方面产生最大影响： 细菌性角膜炎的临床结局。设计良好的随机对照试验，比较不同的局部 抗生素无法确定治疗成功率的任何显著差异。活化的免疫细胞 导致角膜组织破坏的分泌细胞因子和胶原酶。同时治疗 炎症可减少角膜散光和混浊，从而改善视力结果。的 类固醇治疗角膜溃疡试验（SCUT）无法确定使用辅助类固醇的益处或危害 然而，在细菌性溃疡的总体治疗中， 表明早期类固醇治疗严重的非诺卡氏菌溃疡是有益的。 在这里，我们提出了类固醇和交联溃疡治疗II（SCUT II），一个国际， 一项旨在评价辅助性角膜交联的获益的随机、双盲、临床试验 (CXL)和早期类固醇治疗细菌性溃疡。患者出现在Aravind眼之一 印度医院或UCSF，涂片阳性典型（即非诺卡氏菌或分枝杆菌）细菌性角膜 溃疡和中度至重度视力丧失，定义为Snellen视力为20/40或更差，将有资格参加 包容。同意参与的患者将被随机分配至三个治疗组之一： 第1组：标准治疗组，局部0.5%阿氟沙星+局部安慰剂+假CXL 第2组：早期类固醇组，外用0.5%氟诺沙星+0.05%二氟泼尼酯+假CXL 第3组：复方新诺明组，外用0.5%氟诺沙星+0.05%二氟泼尼酯+复方新诺明 这种方法是创新的，原因有很多，包括它对新治疗方法的测试，如局部给药， 0.05%二氟泼尼酯和角膜交联。它也符合NEI的优先事项，包括研究 感染过程，以及研究新的高分辨率成像技术，如共聚焦 显微镜，前节光学相干和Pentacam Scheimflug成像，以指导治疗 角膜溃疡，并在未来试验中作为潜在的替代试验终点。普罗克特有一个良好的记录， 通过NEI资助的大型试验研究角膜溃疡的最佳治疗方法。角膜混浊仍然是一个 全球失明的主要原因，我们预计这项研究将指导临床医生 角膜感染的最佳管理，以减少与这种情况相关的发病率。

PROJECT SUMMARY/ABSTRACT Investigating factors that mitigate the inflammatory response to infection may have the greatest impact on clinical outcomes in bacterial keratitis. Well-designed randomized controlled trials comparing different topical antibiotics have been unable to identify any significant difference of treatment success. Activated immune cells secret cytokines and collagenases which lead to destruction of corneal tissue. Simultaneous treatment of inflammation may reduce corneal astigmatism and opacity, thus improving visual acuity outcomes. The Steroids for Corneal Ulcer Trial (SCUT) was unable to identify a benefit or harm to the use of adjuvant steroids in the treatment of bacterial ulcers overall, however, hypothesis-generating subgroup analysis consistently suggested a benefit in severe, non-Nocardia ulcers treated with early steroids. Here, we propose the Steroids and Cross-linking for Ulcer Treatment II (SCUT II), an international, randomized, double-masked, clinical trial designed to evaluate the benefit of adjuvant corneal cross-linking (CXL) and early steroids in the treatment of bacterial ulcers. Patients presenting to one of the Aravind Eye Hospitals in India or to UCSF with smear-positive typical (i.e. non-Nocardia or Mycobacteria) bacterial corneal ulcers and moderate to severe vision loss, defined as Snellen visual acuity of 20/40 or worse, will be eligible for inclusion. Those who agree to participate will be randomized to one of three treatment groups: Group 1: Standard Therapy Group, topical 0.5% moxifloxacin plus topical placebo plus sham CXL Group 2: Early Steroid Group, topical 0.5% moxifloxacin plus topical 0.05% difluprednate plus sham CXL Group 3: CXL Group, topical 0.5% moxifloxacin plus topical 0.05% difluprednate plus CXL This approach is innovative for a number of reasons including its testing of novel treatments such as topical difluprednate 0.05% and corneal cross-linking. It is also aligned with the priorities of the NEI including the study of infectious processes, as well as studying new high-resolution imaging techniques such as confocal microscopy, anterior-segment optical coherence and Pentacam Scheimflug imaging to guide treatment of corneal ulceration and as potential surrogate trial endpoints in future trials. Proctor has a proven track record of studying the optimal treatment of corneal ulceration with large NEI-funded trials. Corneal opacity remains one of the leading causing of blindness worldwide and we anticipate that this research will guide clinicians on the best management of cornea infection to reduce the morbidity associated with this condition.