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: 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
• 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' 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.

项目摘要 这项提案解决了一个重要的公共卫生问题：糖尿病， 美国（US）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眼库的建立， 数据表明，糖尿病供体现在占角膜供体的30- 35 在短短十多年的时间里，增长了50-72%。糖尿病对角膜移植术的影响 结果仍然未知，来自次要或回顾性研究的证据相互矛盾 多项临床研究的分析。以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术和后弹力层的影响 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， 后弹力层剥脱自动内皮角膜移植术（DSAEK）。虽然目前的 护理标准是将糖尿病供体角膜用于所有类型的角膜成形术， 眼库和外科医生越来越避免使用DMEK。作为糖尿病患者 供体人群和DMEK需求增加，一项明确的优效性研究评估了 供体糖尿病状态对移植结果的影响将减轻和/或确定这些担忧。 糖尿病内皮角膜移植术研究（DEKS）将解决这些重要的问题。 通过一项前瞻性设盲临床试验，招募1420名参与者， 美国30个临床中心和15个眼库。DEKS将决定3年 使用来自无糖尿病供体的角膜进行DMEK后的移植成功率 上级于糖尿病供体角膜的移植成功率。它还将 确定DMEK后3年的中央内皮细胞损失（ECL）是否与来自 无糖尿病的供体的角膜小于中心ECL， 糖尿病使用。最后，DEKS将探讨供体糖尿病的关系 严重程度，通过眼库确定的糖尿病风险分类评分测量， 尸检HbA 1c和皮肤晚期糖基化终产物和氧化标志物， 糖尿病供体角膜术后3年DMEK移植物结局。的 DEKS可能对角膜的靶向使用产生重大影响， 供体库中具有一系列疾病严重程度的糖尿病供体数量， 必须继续扩大，以满足人口老龄化和DMEK的临床需求 增长