HISTOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Multilayer Approach.
HISTOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Multilayer Approach.
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DOI：
10.1097/iae.0000000000002182
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发表时间：
2018-10
期刊：
影响因子：
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通讯作者：
Curcio CA
中科院分区：
文献类型：
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作者：
Li M;Huisingh C;Messinger J;Dolz-Marco R;Ferrara D;Freund KB;Curcio CA
补充数字内容在文本中可用。继发于年龄相关性黄斑变性的地图状萎缩（或完整的视网膜色素上皮和外部视网膜萎缩）边缘的高分辨率组织学显示明显的神经胶质增生和几乎全部的感光细胞耗竭，丰富的细胞外沉积物，以及布鲁赫膜和脉络膜毛细血管的长期异常，表明在疾病的这个阶段存在严重的和潜在的不可逆的组织损伤。系统描述继发于年龄相关性黄斑变性的地图状萎缩或完全视网膜色素上皮（RPE）和外视网膜萎缩的眼睛中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;并将这些变化与基础RPE-Bruch膜-脉络膜毛细血管复合体和相关细胞外沉积物中的变化进行比较。地图样萎缩由外界膜（ELM）下降到Bruch膜界定。在13只眼中，评估了ELM下降的非萎缩侧和萎缩侧的四个定义位置的Henle纤维层、外核层、下层支持组织和细胞外沉积物的组织学表型和/或厚度，并与其他组织层进行了比较，采用广义估计方程和logit模型。在ELM下降的非萎缩侧，明显的Henle纤维层和外核层变得分层障碍，视锥细胞内节肌样变短，感光细胞核和线粒体向内移位，RPE变形。在ELM下降的萎缩侧，感光细胞健康的所有措施下降到零。在没有光感受器的情况下，汉勒纤维层/外核层厚度减半，仅剩下Müller细胞。视网膜色素上皮下沉积物残留，Bruch膜变薄，脉络膜毛细血管密度降低。ELM下降明显界定了明显的神经胶质增生和临床上定义为地图状萎缩（或外视网膜萎缩）的几乎全部光感受器耗竭的区域，表明严重且可能不可逆的组织损伤。跨越该边界的支持组织的退化是渐进的，与稳定的年龄相关变化一致，并表明RPE和Müller细胞随后对应力阈值作出反应。在严重的胶质增生和厚的沉积物阻碍治疗干预之前，应在年龄相关性黄斑变性阶段寻找新的临床试验终点。
Supplemental Digital Content is Available in the Text. High-resolution histology at the border of geographic atrophy (or complete retinal pigment epithelium and outer retinal atrophy) secondary to age-related macular degeneration reveals marked gliosis and near-total photoreceptor depletion, abundant extracellular deposits, and long-standing abnormalities of Bruch membrane and choriocapillaris, indicating severe and potentially irreversible tissue damage at this stage of the disease. 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.