Diabetes Endothelial Keratoplasty Study: Impact of Diabetes on Corneal Transplant Success and Cell Loss

糖尿病内皮角膜移植术研究：糖尿病对角膜移植成功和细胞损失的影响

基本信息

批准号：
9933642
负责人：
Colleen Bauza
金额：
$ 83.13万
依托单位：
JAEB CENTER FOR HEALTH RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9933642
关键词：
Address Adherence Advanced Glycosylation End Products Affect Applications Grants Autopsy Categories Cause of Death Cell Density Cells Clinical Clinical Management Clinical Research Clinical Trials Communication Communities Companions Confidence Intervals Conflict (Psychology)Cornea Data Analyses Data Management Resources Descemet&apos s membrane Diabetes Mellitus Donor person Drug or chemical Tissue Distribution Effectiveness Endothelial Cells Endothelium Enrollment Equilibrium Eye Eye Banks Eye Surgeon Failure Fructose Funding Glycosylated hemoglobin A Goals Grant Growth Health Individual Institutional Review Boards Keratoplasty Lysine Masks Measures Modeling Monitor Operative Surgical Procedures Outcome Participant Patient Participation Patients Penetrating Keratoplasty Population Postoperative Period Procedures Process Protocols documentation Public Health Research Resources Safety Sample Size Severities Severity of illness Side Site Skin Statistical Data Interpretation Statistical Methods Surgeon System Time Study Tissue Donors Tissue Transplantation Tissues Transplantation United States United States National Institutes of Health Universities Variant aging population base clinical research site data integrity data management data repository design diabetes risk diabetic follow-up glycemic control human subject non-diabetic oxidation participant safety preservation prospective quality assurance recruit secondary analysis sound standard of care success web site

项目摘要

PROJECT SUMMARY This proposal addresses a significant public health question: Does diabetes, the 3rd leading cause of death in the United States (US), impact suitability of donor corneal tissue for transplantation? This question takes on increasing urgency as recent eye bank data suggests donors with diabetes now comprise about 30-35% of the cornea donor pool, a 50-72% increase in just over a decade. The impact of diabetes on keratoplasty outcomes remains unknown, with conflicting evidence from secondary or retrospective analyses of multiple clinical studies. Previous large clinical studies did not show a diabetic donor effect on penetrating keratoplasty (PKP) and Descemet membrane endothelial keratoplasty (DMEK) graft success, yet our recent Cornea Preservation Time Study (CPTS) found the diabetic donor adversely affected graft outcomes following Descemet stripping automated endothelial keratoplasty (DSAEK). Although current standard of care is to use diabetic donor corneas for all types of keratoplasties, some eye banks and surgeons are increasingly avoiding them for DMEK. As both the diabetic donor population and DMEK demand increases, a definitive superiority study evaluating effect of donor diabetes status on graft outcomes will allay and/or define these concerns. The Diabetes Endothelial Keratoplasty Study (DEKS) will address these important questions through a prospective masked clinical trial enrolling 1420 participant-eyes at 30 clinical sites and 15 eye banks across the US. The DEKS will determine if the 3-year graft success rate following DMEK performed with corneas from donors without diabetes is superior to the graft success rate with corneas from donors with diabetes. It will also determine if the 3-year central endothelial cell loss (ECL) after DMEK with corneas from donors without diabetes is less than the central ECL when corneas from donors with diabetes are used. Lastly, the DEKS will explore the relationship of donor diabetes severity, as measured by eye bank-determined diabetes risk categorization scores, post- mortem HbA1c, and skin advanced glycation endproducts and oxidation markers, with DMEK graft outcomes 3 years postoperatively in corneas from diabetic donors. The DEKS could have a major impact on the targeted use of corneas from an increasing number of donors with diabetes with a range of disease severity in a donor pool that must continue to expand to meet the clinical demands of an aging population and DMEK growth.

项目概要该提案解决了一个重要的公共卫生问题：糖尿病是否会导致美国第三大死亡原因，影响供体角膜的适用性用于移植的组织？随着最近的眼库的出现，这个问题变得越来越紧迫数据显示，目前角膜捐献者中约有 30-35% 患有糖尿病池，在短短十年内增加了 50-72%。糖尿病对角膜移植术的影响结果仍然未知，二次或回顾性证据相互矛盾多项临床研究的分析。之前的大型临床研究并未显示糖尿病供体对穿透性角膜移植术（PKP）和后弹力层的影响内皮角膜移植术（DMEK）移植成功，但我们最近的角膜保存时间研究 (CPTS) 发现糖尿病供体对移植结果产生不利影响后弹力层剥离自动内皮角膜移植术（DSAEK）。虽然目前护理标准是使用糖尿病供体角膜进行所有类型的角膜移植术，其中一些眼库和外科医生越来越多地避免使用 DMEK。作为一名糖尿病患者供体人口和 DMEK 需求增加，一项明确的优势研究评估供体糖尿病状况对移植结果的影响将减轻和/或明确这些担忧。糖尿病内皮角膜移植术研究 (DEKS) 将解决这些重要问题通过一项前瞻性屏蔽临床试验提出的问题，该试验招募了 1420 名参与者全美有 30 个临床中心和 15 个眼库。 DEKS 将确定 3 年期是否使用非糖尿病捐献者的角膜进行 DMEK 后的移植成功率优于糖尿病捐献者的角膜移植成功率。它还将确定角膜 DMEK 后 3 年中央内皮细胞损失 (ECL) 是否来自当来自患有糖尿病的捐献者的角膜时，没有糖尿病的捐献者的中央ECL要低糖尿病被使用。最后，DEKS 将探讨捐赠者糖尿病的关系严重程度，通过眼库确定的糖尿病风险分类评分来衡量，尸检 HbA1c、皮肤高级糖基化终产物和氧化标记物，糖尿病供体角膜术后 3 年的 DMEK 移植结果。这 DEKS 可能会对角膜的针对性使用产生重大影响，因为角膜的使用量不断增加捐献者库中患有各种疾病严重程度的糖尿病捐献者的数量必须继续扩大以满足人口老龄化和 DMEK 的临床需求生长。