Effect of Corneal Preservation Time on Long-Term Graft Success (CPTS)

描述（由申请人提供）：2004年至2006年间，美国角膜移植术的数量下降了12%，而在过去的两年里，角膜移植术的数量增加了37%，2009年进行了近6万例。与10年前的角膜供体研究（CDS）一样，关于供体池未来是否充足的公共卫生问题再次被提出。这一增长是由内皮角膜移植术（EK）的出现所推动的，EK已经成为内皮衰竭的首选手术，在2006- 2009年间增加了两倍，去年角膜移植术的30%。与穿透性角膜移植术（PKP）相比，原发性供体失败率更高，人口老龄化，病理更多，角膜评估过程随着法规的增加而改变，对新发感染的检测要求更多，以及这些感染对供体池的威胁，除了使用较老的供体组织外，还需要其他手段来扩大供体池。一个主要的机会是将供体组织的使用延长到FDA批准的在4oC （Optisol GS和Life 4oC）的中间储存介质中保存14天的时间。在美国，保存超过7天的角膜很少用于PKP或EK，但经常出口到国际上成功使用。虽然现有数据不支持这种偏见，但需要一项基于证据的研究来改变这种实践模式。本研究的主要目的是通过一项随机、前瞻性、隐蔽性临床试验设计，确定保存7天或更短时间的供体角膜与保存8 - 14天的供体角膜在术后3年是否具有可比性，这是EK成功的两个最佳指标。已经提交了两份单独的拨款申请。指导CDS的Jaeb健康研究中心的数据管理和分析中心将监督眼库参与研究、多功能网站开发、统计计划、数据管理和分析以及DSMC协调的各个方面。CWRU的协调中心和UH眼科研究所由PI和主任领导，将为临床站点提供科学指导和协调，并监督角膜图像分析阅读中心。相关性：如果更长的保存时间达到FDA限制的14天，可以证明不会对移植成功和内皮细胞损失产生不利影响，那么在美国所有角膜移植手术中，将有更多的供体组织可以有效地分配，对于疑似新发感染的延长测试将有更大的灵活性，并且由于超过7天的存储限制，将有更少的组织出口

DESCRIPTION (provided by applicant): After a 12% decline in keratoplasties in the USA between 2004 and 2006, a 37% increase has occurred in the last 2 years with nearly 60,000 cases performed in 2009. As with the Cornea Donor Study (CDS) 10 years ago, a public health issue is again raised regarding the future adequacy of the donor pool. This increase has been driven by the emergence of endothelial keratoplasty (EK) which has become the procedure of choice for endothelial failure conditions, tripling in cases between 2006-09, and 30% of the keratoplasties last year. With a higher primary donor failure than penetrating keratoplasty (PKP), an aging population with more pathology, changes in the cornea evaluation process with increased regulations and more testing requirements for emerging infections and the threat to the donor pool from these infections, additional means to expand the donor pool besides the use of older donor tissue are needed. One major opportunity is to extend the use of donor tissue to the FDA approved preservation time of 14 days for intermediate storage media at 4oC (Optisol GS and Life 4oC). Corneas preserved beyond 7 days are rarely used for PKP or EK in the United States, but are regularly exported for successful use internationally. While existing data do not support this bias, an evidence based study is needed to change this practice pattern. The primary objectives of our study are to determine whether recipient corneal stroma clarity and endothelial cell loss, the two best measures for EK success, are comparable 3 years postoperatively for donor corneas preserved for 7 days or less compared to those preserved for between 8 and 14 days utilizing a randomized, prospective, masked clinical trial design. Two separate grant applications have been submitted. The Data Management and Analysis Center at the Jaeb Center for Health Research, which directed the CDS, will oversee all aspects of eye bank participation in the study, multi-functional website development, statistical plan, data management and analysis, and coordination of the DSMC. The Coordinating Center at CWRU and the UH Eye Institute, directed by the PI and Director, will provide scientific direction and coordination of the clinical sites, as well as oversee the Cornea Image Analysis Reading Center. RELEVANCE: If longer preservation time up to the FDA limit of 14 days can be shown to not adversely impact graft success and endothelial cell loss at 3 years, more donor tissue will be available to be efficiently distributed within the United States for all keratoplasty procedures, there will be more flexibility in time for extended testing for a suspected emerging infection, and less tissue will be exported due to exceeding a perceived limit of seven days in storage