The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, China; Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
Ophthalmol Retina. 2021 Nov;5(11):1085-1096. doi: 10.1016/j.oret.2021.01.012. Epub 2021 Feb 2.
Macular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with antiangiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histologic analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD.
Case study and clinicopathologic correlation.
A White woman in whom age-related macular degeneration (AMD) findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and OCT, with no detectable subretinal fluid or other recurrent exudation and no intravitreal injections before her death at age 90 years.
The right eye was preserved 6.25 hours after death, postfixed in osmium tannic acid paraphenylenediamine, and prepared for submicrometer epoxy resin sections (n = 115), with 19 matched to clinical OCT B-scans.
Light microscopic morphology of a hyperautofluorescent (hyperFAF) area due to prior exudation ("floodplain" hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF.
Floodplain hyperFAF was visible throughout the 9 years of follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete RPE and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer.
This direct clinicopathologic correlation for FAF imaging is the first for nAMD. Fundus autofluorescence is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. Hyperautofluorescence due to an exudative floodplain signifies loss of photoreceptors over continuous RPE. Hypoautofluorescence in MA signifies loss of both cell layers. For maximal value, fundus autofluorescence imaging should be interpreted with the multilayer perspective provided by OCT. Prevention of exudation in nAMD may preserve photoreceptors.
视网膜色素上皮（RPE）和光感受器的黄斑萎缩（MA）导致新生血管性年龄相关性黄斑变性（nAMD）患者视力丧失，尽管抗血管生成药物治疗取得了成功。为了增强对 MA 的理解，加强眼底自发荧光（FAF）成像的细胞基础，并为 nAMD 的治疗提供信息，我们对一只眼睛进行了组织学分析，该眼睛进行了多模态临床成像，并因 nAMD 而出现明显的先前渗出。
病例研究和临床病理相关性。
一名白人女性，在 9 年的时间里，右眼因年龄相关性黄斑变性（AMD）而出现无活性的视网膜下纤维化（右眼），使用 FAF 和 OCT 进行随访，在她 90 岁去世前，没有检测到视网膜下液或其他复发性渗出物，也没有进行玻璃体内注射。
在她去世后 6.25 小时，将右眼保存下来，用锇酸单宁酸对苯二胺后固定，并制备用于亚微米环氧树脂切片（n = 115），其中 19 个与临床 OCT B 扫描相匹配。
先前渗出物引起的高自发荧光（高 FAF）区域的光镜形态（“泛滥平原”高 FAF）、MA 的低自发荧光（低 FAF）点和无明显 FAF 的区域。
泛滥平原高 FAF 在 9 年的随访中均可见，随着时间的推移，其中几个低 FAF 萎缩点在其中扩大。高 FAF 模式与 OCT 上的外视网膜萎缩（ORA）和组织学上的形态异常但连续的 RPE 上的光感受器丧失相对应。泛滥平原内的低 FAF 点与 OCT 上的完全 RPE 和外视网膜萎缩（cRORA）以及组织学上的光感受器和 RPE 均丧失相对应。相比之下，无明显 FAF 的区域显示连续的 RPE 伴有全长光感受器和厚厚的外核层。
这是 nAMD 的第一个直接临床病理相关性 FAF 成像。眼底自发荧光是一种投影图像，涉及光感受器的光学信号调制以及 RPE 中的发射信号源。渗出性泛滥平原的高自发荧光表示在连续的 RPE 上光感受器的丧失。MA 中的低自发荧光表示两个细胞层的丧失。为了获得最大价值，眼底自发荧光成像应该结合 OCT 提供的多层视角进行解释。预防 nAMD 中的渗出物可能会保留光感受器。
