Imaging endpoints for clinical trials in MacTel type 2.

Macular Telangiectasia type 2 (MacTel) is a bilateral neurodegenerative disease associated with dysfunction in the serine and lipid metabolism resulting in loss of Muller cells and photoreceptors. Typical structural changes include vascular abnormalities, loss of retinal transparency, redistribution of macular pigment and thinning of the central retina with photoreceptor loss. The presence and extent of photoreceptor loss, as visible on Optical Coherence Tomography (OCT) (“disease severity scale”), correlate with functional loss and the limitation of photoreceptor loss appears to be the most promising therapeutic approach. Ongoing clinical trials of ciliary neurotrophic factor (CNTF) implants for the treatment of MacTel are using this outcome to evaluate efficacy. An ideal outcome measure provides the ability to quantify the extent of the disease progression with precision and reproducibility. This review describes the changes and findings on different imaging techniques including fluorescein- and OCT angiography, blue light reflectance, 1- and 2-wavelength autofluorescence and OCT. The possibilities of objective quantification of the severity of MacTel and correlation with functional characteristics such as best-corrected visual acuity (BCVA) and microperimetry and their applications as quantitative imaging endpoints for clinical treatment trials are discussed. OCT and especially en face OCT could be demonstrated as precise and reproducible methods to quantify the area of photoreceptor loss, which correlated highly significantly with functional loss in microperimetry. The analysis of the area of photoreceptor loss on en face OCT is the most reliable imaging endpoint for treatment trials in MacTel. This method is already being used in ongoing randomized trials. 简介: 2型黄斑毛细区血管扩张症 (MacTel) 为双侧神经元退行性疾病, 伴有丝氨酸和脂质代谢紊乱, 并导致Muller细胞和光感受器的消失。典型的结构改变包括血管异常、视网膜透明度丧失、黄斑色素再分布、视网膜中央变薄和光感受器的消失。光感受器消失的发生以及程度, 如光学相干断层扫描 (OCT) (“疾病严重程度分级”) 所示, 与功能的丧失有关, 并且阻止光感受器的结构退行似乎是最有希望的治疗方法。目前正在进行的睫状神经营养因子 (CNTF) 植入物治疗MacTel的临床试验正利用这一结果来评估疗效。一个理想的结果测量可以精确地和可重复地量化疾病的进展程度。 方法: 本文综述了不同成像技术的发现的病理变化以及体征, 包括荧光血管造影和OCT血管造影、蓝光反射检查、1型及2型波长自体荧光和OCT。 结果: 本文探讨了客观量化MacTel严重程度的可能性, 其与最佳矫正视力(BCVA)和显微视野检查等功能特征的相关性, 以及它们作为临床治疗试验定量成像终点的应用。OCT, 特别是en face OCT证明是一种精确的和可重复的方法来量化光感受器损失的面积, 这与显微视野检查的功能损失高度相关。 结论: 在MacTel治疗试验中, 利用en face OCT进行光感受器损失面积的分析是最可靠的成像方法。这种方法已经被用于正在进行的随机试验当中。