Moorfields Eye Hospital NHS Foundation Trust, London, UK; Department of Ophthalmology, University of Bonn, Bonn, Germany; Center for Rare Diseases, University of Bonn, Bonn, Germany; Institute of Ophthalmology, University College London, London, UK.
Moorfields Eye Hospital NHS Foundation Trust, London, UK; Department of Ophthalmology, University of Basel, Basel, Switzerland; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
Am J Ophthalmol. 2020 Oct;218:136-147. doi: 10.1016/j.ajo.2020.05.023. Epub 2020 May 22.
To investigate the development and progression of retinal pigment epithelial and outer retinal atrophy (RORA) secondary to maternally inherited diabetes and deafness (MIDD).
Retrospective observational case series.
Thirty-six eyes of 18 patients (age range, 22.4-71.6 years) with genetically proven MIDD and serial optical coherence tomography (OCT) images were included. As proposed reference standard to diagnose and stage atrophy, OCT images were longitudinally evaluated and analyzed for presence and precursors of RORA. RORA was defined as an area of (1) hypertransmission, (2) disruption of the retinal pigment epithelium, (3) photoreceptor degeneration, and (4) absence of other signs of a retinal pigment epithelial tear.
The majority of patients revealed areas of RORA in a circular area around the fovea of between 5° and 15° eccentricity. Over the observation time (range, 0.5-8.5 years), evidence for a consistent sequence of OCT features from earlier disease stages to the end stage of RORA could be found, starting with loss of ellipsoid zone and subretinal deposits, followed by loss of external limiting membrane and loss of retinal pigment epithelium with hypertransmission of OCT signal into the choroid, and leading to loss of the outer nuclear layer bordered by hyporeflective wedges. Outer retinal tabulations seemed to develop in regions of coalescent areas of RORA.
The development and progression of RORA could be tracked in MIDD patients using OCT images, allowing potential definition of novel surrogate markers. Similarities to OCT features in age-related macular degeneration, where mitochondrial dysfunction has been implicated in the pathogenesis, support wide-ranging benefits from proof-of-concept studies in MIDD.
研究母系遗传性糖尿病和耳聋（MIDD）继发的视网膜色素上皮和外层视网膜萎缩（RORA）的发展和进展。
回顾性观察性病例系列。
纳入了 18 名患者（年龄 22.4-71.6 岁）的 36 只眼，这些患者均具有遗传性 MIDD 且具有连续的光学相干断层扫描（OCT）图像。作为诊断和分期萎缩的参考标准，对 OCT 图像进行了纵向评估和分析，以确定 RORA 的存在和前兆。RORA 定义为（1）高透过区、（2）视网膜色素上皮破裂、（3）光感受器变性和（4）无其他视网膜色素上皮撕裂迹象的区域。
大多数患者在 5°至 15°偏心度的黄斑周围呈现 RORA 区域。在观察时间（0.5-8.5 年）内，可以发现从早期疾病阶段到 RORA 终末期的 OCT 特征的一致序列，首先是椭圆带和视网膜下沉积物的丧失，随后是外部限制膜的丧失和视网膜色素上皮的丧失，OCT 信号高透过脉络膜，导致外层核层边界呈低反射楔形缺失。外层视网膜表格似乎在 RORA 融合区域发展。
使用 OCT 图像可以在 MIDD 患者中跟踪 RORA 的发展和进展，从而有可能定义新的替代标志物。与年龄相关性黄斑变性的 OCT 特征相似，其中线粒体功能障碍被认为是发病机制的一部分，支持从 MIDD 的概念验证研究中获得广泛的益处。
