Glaucoma Drainage Device and Endothelial Cell Density Loss Compare (DECLARE) Trial

项目摘要/摘要 青光眼引流装置(GDD)手术在治疗内科青光眼患者中越来越受欢迎 失控的青光眼。然而，GDD的主要长期并发症之一是进行性角膜。 内皮细胞丢失(ECL)导致角膜失代偿，需要复杂的护理。虽然是外科手术 已对技术进行了改进，将导管插入睫状沟以解决前房这个问题 (Ac)导管放置仍然是首选位置，因为缺乏令人信服的数据来验证 沟放置的优势。例如，(1)直接比较沟槽后内皮细胞丢失(ECL) 与AC管放置的对比仅限于三项回顾研究；(2)研究不一致 插管后的眼压和其他手术结果是否相似 (3)沟管是否因以下原因引起更多交流微环境改变的问题仍然存在 与AC管相比，慢性虹膜管接触的几率更高，从而危及内皮细胞健康，眼压 控制，或其他手术结果的沟管。 为了回答这些问题，我们提出了一项多中心、结果掩盖的临床试验，随机选择240名 受试者接受沟管与交流管的放置。在这项试验中，我们将比较ECL(特异靶1)、IOP GDD植入置管后的对照(特指2)和交流微环境(特指3) 在睫状沟和前房。在更多使用GDDS的背景下，我们建议的试验将 寻找更好的方法来减少其角膜并发症对角膜和 青光眼专家。 旧金山加州大学(UCSF)眼科，弗朗西斯·I·普罗科特 加州大学旧金山分校、宾夕法尼亚大学(UPenn)的基金会和4个GDD植入的大容量中心将 共同执行这场审判。加州大学旧金山分校的眼科将作为临床协调中心。 宾夕法尼亚大学将成为数据协调中心。弗朗西斯·I·普罗科特基金会将成为成像阅读中心 和元基因组RNA深度测序分析(MDS)中心。 这项试验具有创新性的原因有很多，包括手术(沟管)的随机化 与AC管相比)和新型MDS分析(检查术后AC微环境)的应用 在此之前已经有过前瞻性的研究。它与NEI的优先事项保持一致，研究高- 分辨率成像技术，如内皮细胞成像和前段光学相干 指导术后治疗，并在未来的试验中作为潜在的替代试验终点。这支世界级的球队 的合作者在执行NEI资助的大型眼科试验方面有经过证明的记录，并且表现良好 能够回答这项提案中提出的重要问题。

PROJECT SUMMARY/ABSTRACT Glaucoma drainage device (GDD) surgery has gained popularity in managing patients with medically uncontrolled glaucoma. However, one of the major long-term complications of GDD is progressive corneal endothelial cell loss (ECL) leading to corneal decompensation, which requires complex care. Although surgical techniques have been modified to insert the tube into the ciliary sulcus to address this issue, anterior chamber (AC) tube placement remains the preferred location, as there is a lack of convincing data to validate the advantages of sulcus placement. For example, (1) Direct comparison of endothelial cell loss (ECL) after sulcus versus AC tube placement is limited to three retrospective studies; (2) Studies are inconsistent regarding whether intraocular pressure (IOP) and other surgical outcomes are similar after sulcus tube or AC tube placement; (3) Question remains whether a sulcus tube cause more AC microenvironment change due to higher chance of having chronic tube-iris touch than an AC tube, jeopardizing endothelial cell health, IOP control, or other surgical outcomes of the sulcus tube. To answer these questions, we propose a multi-center, outcome-masked clinical trial randomizing 240 subjects to sulcus tube versus AC tube placement. In this trial, we will compare ECL (specific aim 1), IOP control (specific aim 2) and AC microenvironment (specific aim 3) after GDD implantation with tube placement in the ciliary sulcus versus the anterior chamber. In the setting of increased use of GDDs, our proposed trial to identify better approaches to decrease its corneal complications is of substantial interest to both corneal and glaucoma specialists. Department of Ophthalmology at University of California San Francisco (UCSF), Francis I. Proctor Foundation at UCSF, University of Pennsylvania (UPenn), and 4 high-volume centers for GDD implantation will jointly execute this trial. The Department of Ophthalmology at UCSF will serve as Clinical Coordinating Center. UPenn will be the Data Coordinating Center. Francis I. Proctor Foundation will be the imaging reading center and metagenomic RNA deep sequencing analysis (MDS) center. This trial is innovative for a number of reasons including the randomization of surgery (sulcus tube versus AC tube) and application of novel MDS analysis (examining postoperative AC microenvironment), none of which has been prospectively studied before. It is aligned with the priorities of the NEI, studying high- resolution imaging techniques such as endothelial cell imaging and anterior-segment optical coherence to guide post-operative treatment and as potential surrogate trial endpoints in future trials. This world class team of collaborators have a proven track record for executing large NEI-funded trials in ophthalmology, and are well positioned to answer the important questions presented in this proposal.