Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Dis Primers. 2021 May 6;7(1):31. doi: 10.1038/s41572-021-00265-2.
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the industrialized world. AMD is characterized by accumulation of extracellular deposits, namely drusen, along with progressive degeneration of photoreceptors and adjacent tissues. AMD is a multifactorial disease encompassing a complex interplay between ageing, environmental risk factors and genetic susceptibility. Chronic inflammation, lipid deposition, oxidative stress and impaired extracellular matrix maintenance are strongly implicated in AMD pathogenesis. However, the exact interactions of pathophysiological events that culminate in drusen formation and the associated degeneration processes remain to be elucidated. Despite tremendous advances in clinical care and in unravelling pathophysiological mechanisms, the unmet medical need related to AMD remains substantial. Although there have been major breakthroughs in the treatment of exudative AMD, no efficacious treatment is yet available to prevent progressive irreversible photoreceptor degeneration, which leads to central vision loss. Compelling progress in high-resolution retinal imaging has enabled refined phenotyping of AMD in vivo. These insights, in combination with clinicopathological and genetic correlations, have underscored the heterogeneity of AMD. Hence, our current understanding promotes the view that AMD represents a disease spectrum comprising distinct phenotypes with different mechanisms of pathogenesis. Hence, tailoring therapeutics to specific phenotypes and stages may, in the future, be the key to preventing irreversible vision loss.
年龄相关性黄斑变性（AMD）是工业化世界中导致法定失明的主要原因。AMD 的特征是细胞外沉积物（即玻璃膜疣）的积累，以及光感受器和相邻组织的进行性退化。AMD 是一种多因素疾病，包含衰老、环境风险因素和遗传易感性之间的复杂相互作用。慢性炎症、脂质沉积、氧化应激和细胞外基质维持受损在 AMD 的发病机制中被强烈牵连。然而，导致玻璃膜疣形成和相关退化过程的病理生理事件的确切相互作用仍有待阐明。尽管在临床护理和揭示病理生理机制方面取得了巨大进展，但与 AMD 相关的未满足的医疗需求仍然很大。尽管在治疗渗出性 AMD 方面取得了重大突破，但尚无有效的治疗方法可预防进行性不可逆转的光感受器退化，从而导致中心视力丧失。高分辨率视网膜成像的引人注目的进展使我们能够在体内对 AMD 进行精细的表型分析。这些见解，结合临床病理和遗传相关性，强调了 AMD 的异质性。因此，我们目前的理解认为 AMD 代表了一种疾病谱，包含具有不同发病机制的不同表型。因此，未来针对特定表型和阶段进行治疗可能是预防不可逆转视力丧失的关键。
