Surgery in Fuchs Endothelial Dystrophy (FED): evaluation of current approaches and exploration of next-generation techniques.

OBJECTIVE: This project focuses on the in depth evaluation of the functional outcome of currently used cornea transplantation techniques (PKP, DSAEK and UT-DSAEK for surgical treatment of Fuchs Endothelial Dystrophy (FED). The outcome of this study is a reference standard for the exploration of next-generation techniques for surgical treatment, e.g. DMEK.. In addition, we will develop a better quantification of corneal endothelial cells is required to improve one of the main endpoints of clinical studies in cornea transplantation. HYPOTHESIS: Among the available techniques for corneal transplantation in FED of the last decades, a technique can be selected that is superior with respect to clinical outcome, patient care and efficiency. STUDY DESIGN: Prospective and retrospective clinical observational studies and structured registry of the learning curve for a new surgical procedure. 1. Building a clinical outcome reference of the currently used surgical technique PLK and DSAEK with a foloow-up period up to ten years (sub-study 1) 2. A study on the effect of the thickness of the cornea graft for DSAEK surgical procedures on clinical outcome. (sub-study 2) 3. The work out of the exploration phase of the new surgical intervention DMEK in order to be prepared for a justified randomized clinical trial comparing two surgical techniques. The final objective is to prepare the protocol and other study requirements to start a RCT to compare the two surgical techniques for FED: DMEK and DSAEK. (sub-study 3) 4. Development of a novel accurate and robust image analysis methods for the segmentation and subsequent quantification of the corneal endothelial cells. Better quantification of corneal endothelial cells is required to improve one of the main endpoints of clinical studies in cornea transplantation. STUDY POPULATION/DATASET: Fuchs’ endothelial dystrophy patients eligible for cornea transplantation surgery for visual rehabilitation who are operated in the REH. INTERVENTION:No study interventions according to the criteria of the WMO. OUTCOME MEASURES: Sub-study 1: Primary outcome parameter: Postoperative astigmatism Sub-study 2: Primary outcome parameter: Corneal graft thickness as measured by AS-OCT Sub-study 3: Primary outcome parameter: Non donor related primary graft failure SAMPLE SIZE: This is a retrospective and prospective observational study to assess the natural history of disease progression, and each subject’s data will be assessed on a case-by-case basis and by descriptive analysis, thus there is no specific sample size requirement. Number of study subjects: Sub-study 1: 500 patients in the Netherlands Organ Transplantation Registry (NOTR) and in addition 100 patients long term follow-up DSAEK. Sub-study 2: 75 patients who are scheduled for (UT)DSAEK cornea transplantation because of FED Sub-study 3: 30 patients who will be scheduled for DMEK cornea transplantation because of FED DATA ANALYSIS: Sub-study 1 Vector analysis for changes of astigmatism and angle of axis at 24 months will be calculated according to Holladay[5]. Visual acuity will be expressed as logMAR before statistical analysis. One-Way ANOVA post hoc Tukey for differences and changes of BSCVA and astigmatism between techniques. The Log rank test will be used for graft survival analysis. The independent-samples Kruskal-Wallis test and the independent-samples Mann-Whitney U test will be used for surgical induced astigmatism change. COLLABORATION/CONNECTION: - Rotterdam Ophthalmic Institute (R.O.I.) and Rotterdam Eye Hospital (REH): Subjects participating in this study will be recruited from FED patients visiting the cornea department of the REH who need a keratoplasty for visual rehabilitation. - R.O.I., REH and Euro Tissue Bank (ETB) Sub-study 2 will be conducted in collaboration with the Euro Tissue Bank (ETB) in Beverwijk, The Netherlands. - REH cornea department and Netherlands Transplantation Foundation (NTS): the principal investigator is responsible for the ophthalmological support of the NOTR follow-up database, from which data will be extracted for study 1. - REH and Dutch Ophthalmological Society Experience derived from this study will be implemented directly in patient care in the REH, and will be shared with other corneal surgeons in the Netherlands participating in the cornea work group of the Dutch Ophthalmological Society and with corneal surgeons abroad and cornea fellows who are trained in the REH. TIME SCHEDULE:Start date: July 2016 Sub-study 1: July 1 2016 – March 31 2017 Sub-study 2: July 1 2016 – June 30 2017: inclusion of 75 patients; June 30 2018: Last Patient Last Visit and final analysis Sub-study 3: September 1 2016 – August 31 2017: Surgical procedures; September 1, 2017 – October 30, 2018: description of surgical procedure and final protocol and other study documents for RCT.