Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Retina. 2018 Oct;38(10):1937-1953. doi: 10.1097/IAE.0000000000002182.
To systematically characterize histologic features of multiple chorioretinal layers in eyes with geographic atrophy, or complete retinal pigment epithelium (RPE) and outer retinal atrophy, secondary to age-related macular degeneration, including Henle fiber layer and outer nuclear layer; and to compare these changes to those in the underlying RPE-Bruch membrane-choriocapillaris complex and associated extracellular deposits.
Geographic atrophy was delimited by the external limiting membrane (ELM) descent towards Bruch membrane. In 13 eyes, histologic phenotypes and/or thicknesses of Henle fiber layer, outer nuclear layer, underlying supporting tissues, and extracellular deposits at four defined locations on the non-atrophic and atrophic sides of the ELM descent were assessed and compared across other tissue layers, with generalized estimating equations and logit models.
On the non-atrophic side of the ELM descent, distinct Henle fiber layer and outer nuclear layer became dyslaminated, cone photoreceptor inner segment myoids shortened, photoreceptor nuclei and mitochondria translocated inward, and RPE was dysmorphic. On the atrophic side of the ELM descent, all measures of photoreceptor health declined to zero. Henle fiber layer/outer nuclear layer thickness halved, and only Müller cells remained, in the absence of photoreceptors. Sub-RPE deposits remained, Bruch membrane thinned, and choriocapillaris density decreased.
The ELM descent sharply delimits an area of marked gliosis and near-total photoreceptor depletion clinically defined as Geographic atrophy (or outer retinal atrophy), indicating severe and potentially irreversible tissue damage. Degeneration of supporting tissues across this boundary is gradual, consistent with steady age-related change and suggesting that RPE and Müller cells subsequently respond to a threshold of stress. Novel clinical trial endpoints should be sought at age-related macular degeneration stages before intense gliosis and thick deposits impede therapeutic intervention.
系统描述与年龄相关性黄斑变性相关的地图样萎缩（完全性视网膜色素上皮[RPE]和外层视网膜萎缩）患者的多个脉络膜视网膜层的组织学特征，包括 Henle 纤维层和外核层；并将这些变化与下方的 RPE-布鲁赫膜-脉络膜毛细血管复合体及相关细胞外沉积物的变化进行比较。
地图样萎缩通过外界膜（ELM）向布鲁赫膜的下降来界定。在 13 只眼中，在 ELM 下降的非萎缩侧和萎缩侧的四个特定位置上评估并比较了 Henle 纤维层、外核层、下方支持组织以及细胞外沉积物的组织表型和/或厚度，并使用广义估计方程和对数模型进行比较。
在 ELM 下降的非萎缩侧，Henle 纤维层和外核层明显分层，圆锥内节肌缩短，视锥细胞核和线粒体向内移位，RPE 形态异常。在 ELM 下降的萎缩侧，所有与视锥细胞健康相关的指标均降至零。Henle 纤维层/外核层厚度减半，在没有视锥细胞的情况下，仅剩余 Müller 细胞。在 RPE 下方仍有沉积物，布鲁赫膜变薄，脉络膜毛细血管密度降低。
ELM 下降明显界定了一个区域，该区域有明显的神经胶质增生和接近完全的光感受器缺失，临床上定义为地图样萎缩（或外层视网膜萎缩），表明存在严重且潜在不可逆的组织损伤。在这个边界处支持组织的变性是逐渐发生的，与稳定的年龄相关性变化一致，并表明 RPE 和 Müller 细胞随后对压力阈值做出反应。在强烈的神经胶质增生和厚沉积物阻碍治疗干预之前，应在年龄相关性黄斑变性的阶段寻找新的临床试验终点。
