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

• 批准号: 10395917
• 负责人: Colleen Bauza
• 金额: $ 113.86万
• 依托单位: JAEB CENTER FOR HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 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/10395917
• 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' 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

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.

项目总结 这项提案解决了一个重要的公共卫生问题：糖尿病、 美国第三大死因：影响供体角膜适合性 用于移植的组织？随着最近的眼库，这个问题变得越来越紧迫 数据显示，目前糖尿病患者的捐赠者约占角膜捐赠者的30-35%。 泳池，在短短十多年的时间里增长了50%-72%。糖尿病对角膜移植的影响 结果仍然未知，来自二手或回顾的相互矛盾的证据 对多项临床研究的分析。之前的大型临床研究没有显示出 糖尿病供体对穿透性角膜移植及后弹力膜的影响 内皮角膜移植(DMEK)成功，但我们最近的角膜保存时间 研究(CPTS)发现糖尿病供者对以下移植结果产生不利影响 Descemet剥离自动内皮角膜移植(DSAEK)。虽然是当前的 护理的标准是将糖尿病供体角膜用于所有类型的角膜成形术，一些 眼库和外科医生越来越多地避免使用DMEK。因为糖尿病患者 捐赠者群体和DMEK需求增加，一项明确的优势研究评估 供者糖尿病状况对移植结果的影响将缓解和/或定义这些担忧。 糖尿病内皮性角膜移植研究(DEKS)将解决这些重要问题 通过一项有1420名参与者参加的前瞻性临床试验提出问题-眼睛在 全美30个临床站点和15个眼库。Deks将决定是否将3年期 非糖尿病供体角膜行DMEK术后移植成功率 比糖尿病捐赠者的角膜移植成功率更高。它还将 确定DMEK术后3年的中央内皮细胞丢失(ECL)是否来自 无糖尿病的供者的角膜低于中央ECL 糖尿病被用来治疗。最后，Deks将探讨捐赠者糖尿病之间的关系。 严重程度，由眼库确定的糖尿病风险分类评分衡量，术后 死亡的HbA1c和皮肤晚期糖基化终末产物和氧化标记物， 糖尿病供者术后3年的DMEK角膜移植结果。这个 DEK可能会对角膜的靶向使用产生重大影响，因为 捐赠者库中有一系列疾病严重程度的糖尿病捐赠者的数量 必须继续扩展以满足老龄化人口和DMEK的临床需求 成长。