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 该提案解决了一个重要的公共卫生问题：糖尿病是否存在 美国第三大死亡原因（美国），捐赠者角膜的影响 组织进行移植？随着最近的眼睛银行，这个问题逐渐增加 数据表明，现在患有糖尿病的捐助者约占角膜供体的30-35％ 泳池，十年来，增长了50-72％。糖尿病对角化膜成形术的影响 结果仍然未知，有次要或回顾性的证据相互矛盾 多个临床研究的分析。以前的大型临床研究未显示 糖尿病供体对穿透性角膜生成形术（PKP）和descemet膜的影响 内皮角膜置换术（DMEK）移植物成功，但我们最近的角膜保存时间 研究（CPTS）发现糖尿病供体不利影响的移植结果 descemet剥离自动内皮角膜成形术（DSAEK）。虽然是最新的 护理标准是将糖尿病供体角膜用于所有类型的角膜体，有些 眼库和外科医生越来越避免使用DMEK。作为糖尿病患者 捐助者人口和DMEK需求增加，这是一项评估的最终优势研究 供体糖尿病状况对移植结果的影响将减轻和/或定义这些问题。 糖尿病内皮角化膜成形术研究（DEK）将解决这些重要的 通过预期蒙面的临床试验招募1420名参与者眼 全美30个临床站点和13个眼库。迪克斯将确定是否三年 DMEK与无糖尿病的捐助者进行角膜后的移植成功率 糖尿病供体的角膜的移植成功率优于移植成功率。它也会 确定DMEK与Corneas后的3年中央内皮细胞损失（ECL）是否来自 当没有糖尿病的捐助者小于中央ECL。 使用糖尿病。最后，迪克斯将探索供体糖尿病的关系 严重程度，如眼库确定的糖尿病风险分类得分， Mortem HBA1C和皮肤晚期糖基化最终产物和氧化标记物，带有带有 DMEK移植物在糖尿病供体的角膜术后3年。这 迪克斯可能会对越来越多的目标使用角膜产生重大影响 患有糖尿病疾病严重程度范围的供体严重程度的供体的供体数量 必须继续扩展以满足人口老龄化和DMEK的临床需求 生长。