Improving patient-centered outcomes in Fuchs endothelial corneal dystrophy with reliable assessment of preoperative disease severity and corneal morphology

富氏内皮性角膜营养不良是角膜移植最常见的适应症。内皮角膜移植术只需要更换病变的内皮细胞，从而减少手术的侵入性。目前，尚不清楚何时进行内皮移植。在疾病的早期，角膜重塑开始于所有的角膜层，而不仅仅是病变的内皮细胞被手术取代。这种重塑会导致特征性的视觉障碍。本项目旨在提高对Fuchs营养不良早期变化的诊断，预测内皮角膜移植术后患者相关的预后，了解角膜重塑的细胞基础。可靠的诊断。富克斯营养不良症患者的特点是早上视力浑浊，随着时间的推移视力逐渐消失。本研究将量化富氏营养不良和正常眼睛在一天中角膜形态和视力的变化。该研究旨在确定日变化对常规临床诊断的影响，以及在疾病分期中是否需要考虑一天中的时间。这些结果将有助于提高诊断可靠性和理解富克斯营养不良患者的主观日变化。2. 内皮角膜移植术前后的视力障碍。这项前瞻性研究将探讨哪些临床和光学因素可预测内皮角膜移植术后的视力障碍。我们为富氏营养不良症专门开发的V-FUCHS问卷将用于评估视力障碍。这些结果将改善术前对疾病严重程度的评估，并有助于在角膜内皮角膜移植术无法成功改善视力之前找到手术干预的最佳时机。功能失调的周围内皮细胞在fuchs营养不良。实验性治疗方法是测试疾病中心内皮细胞的移除，依赖于剩余的外周内皮细胞的功能。该项目将评估是否可以通过术前疾病分期来预测外周内皮细胞的功能损伤。这些数据将阐明Fuchs营养不良患者周围内皮细胞改变的程度，以及去除中心内皮细胞后哪些角膜不太可能清除。结果本项目将改进Fuchs营养不良的常规诊断，优化手术干预时机，阐明个体间变异的功能基础，并可能为Fuchs营养不良的诊断和治疗提供新的基于机制的方法。

Fuchs endothelial corneal dystrophy is the most common indication for corneal transplantation. Endothelial keratoplasty allows for less invasive surgery by replacing the diseased endothelium only. Currently, it is not clear when to perform endothelial transplantation. Early in the course of the disease, corneal remolding starts in all corneal layers, not only the diseased endothelium that is replaced by surgery. This remodeling causes characteristic visual disability.This project aims at improving diagnosis of early changes in Fuchs dystrophy, predicting patient-relevant outcomes after endothelial keratoplasty, and understanding the cellular basis of corneal remodeling.1. RELIABLE DIAGNOSIS. Patients with Fuchs dystrophy characteristically report on cloudy vision in the morning that clears up as the day progresses. This study will quantify changes in the corneal morphology and in vision over the course of the day in Fuchs dystrophy and normal eyes. The study aims at identifying the impact of diurnal variation on routine clinical diagnostics and whether the time of the day needs to be considered in disease staging. These results will help improving diagnostic reliability and understanding subjective diurnal variation in Fuchs dystrophy patients. 2. VISUAL DISABILITY BEFORE AND AFTER ENDOTHELIAL KERATOPLASTY. This prospective study will investigate which clinical and optical factors predict visual disability after endothelial keratoplasty. V-FUCHS, our newly developed questionnaire specific for Fuchs dystrophy, will be used to assess visual disability. These results will improve preoperative assessment of disease severity and help find the optimal timing for surgical intervention before the cornea is too altered for endothelial keratoplasty to successfully improve vision.3. DYSFUNCTIONAL PERIPHERAL ENDOTHELIAL CELLS IN FUCHS DYSTROPHY. Experimental therapeutic approaches are testing the removal of disease central endothelial cells, relying on the function of the remaining peripheral endothelial cells. This project will assess if functional impairment of peripheral endothelial cells can be predicted using preoperative measures of disease stage. The data will elucidate to what degree peripheral endothelial cells are altered in Fuchs dystrophy and which corneas are unlikely to clear after removal of central endothelial cells.RESULTS FROM THIS PROJECT will improve routine diagnostic of Fuchs dystrophy, optimize the timing of surgical intervention, and elucidate the functional basis of inter-individual variability and may point to novel mechanism-based approaches to Fuchs dystrophy diagnosis and treatment.