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

项目摘要/摘要 研究减轻感染的炎症反应的因素可能对 细菌性角膜炎的临床结果。设计良好的随机对照试验比较不同的局部 抗生素一直无法确定治疗成功率的任何显著差异。激活的免疫细胞 导致角膜组织破坏的秘密细胞因子和胶原酶。同时治疗多发性硬化 炎症可以减少角膜散光和混浊，从而提高视力。这个 类固醇治疗角膜溃疡试验(SCUT)无法确定使用辅助性类固醇的益处或危害 然而，在细菌性溃疡的整体治疗中，假设生成亚组分析是一致的 提示早期使用类固醇治疗严重的非诺卡氏菌溃疡是有益的。 在这里，我们建议类固醇和交联剂治疗溃疡II(SCUT II)，一个国际， 随机、双盲、临床试验，旨在评估辅助角膜交联术的益处 CXL和早期类固醇治疗细菌性溃疡。患者出现在其中一只阿拉文德眼前 印度的医院或加州大学旧金山分校的典型(即非诺卡菌或分枝杆菌)细菌角膜涂片阳性 溃疡和中度至重度视力丧失，定义为Snellen视力20/40或更差，将符合条件 包容性。同意参与的人将被随机分为三个治疗组之一： 第1组：标准治疗组，外用0.5%莫西沙星+外用安慰剂+假CXL 第2组：早期类固醇组，外用0.5%莫西沙星+0.05%二氟泼尼特+假CXL 第3组：CXL组，外用0.5%莫西沙星+0.05%双氟泼尼特+CXL 这种方法是创新的，原因有很多，包括它对新疗法的测试，如局部用药 0.05%敌敌畏与角膜交联剂。它还与NEI的优先事项保持一致，包括这项研究 以及研究新的高分辨率成像技术，如共焦 显微镜、眼前段光学相干和Pentacam Scheimflg成像指导治疗 角膜溃疡和作为未来试验的潜在替代试验终点。普华永道在以下方面有着良好的业绩记录 通过NEI资助的大型试验研究角膜溃疡的最佳治疗方法。角膜混浊仍是一种 是世界范围内导致失明的主要原因，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.