年龄相关性黄斑变性(age-related macular degeneration, AMD)是导致老年人失明的主要原因之一，其特征为光感受器的死亡和视网膜色素上皮细胞的变性。该病的发病机制复杂，涉及遗传、环境和代谢等多种因素。细胞衰老是AMD的重要危险因素，表现为细胞在经历有限次数的分裂后进入永久性细胞周期停滞状态。随着年龄增长，衰老细胞的数量增加，并与多种年龄相关的慢性疾病密切相关。细胞衰老的潜在机制包括氧化应激、DNA损伤、线粒体功能障碍、自噬/线粒体自噬缺陷以及表观遗传改变等。在AMD中，色素上皮细胞、血管内皮细胞、Bruch膜、感光细胞和小胶质细胞等不同类型的细胞均表现出衰老及其相关变化。细胞衰老在AMD的发病机制中起着关键作用，涉及多种视网膜细胞类型和血管系统的退化。通过深入研究这些机制，期望能开发出更有效的治疗方法，以帮助患者恢复和保护视力。本文回顾了细胞衰老的生物学机制及其在AMD中的作用，深入探讨了不同细胞衰老引发AMD发病的具体机制，旨在为AMD的发病机制和治疗研究提供新思路。
Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly, characterized by the degeneration of retinal pigment epithelial cells and the death of photoreceptors. The pathogenesis of AMD is complex, involving a multitude of factors, including genetic, environmental, and metabolic influences. Cellular senescence serves as a significant risk factor for AMD, where cells enter a permanent state of cell cycle arrest after a limited number of divisions. As age increases, the accumulation of senescent cells is closely associated with various age-related chronic diseases. Key mechanisms underlying cellular senescence include oxidative stress, DNA damage, mitochondrial dysfunction, defects in autophagy and mitophagy, and epigenetic alterations. In the context of AMD, various cell types-including pigment epithelial cells, vascular endothelial cells, cells of Bruch's membrane, photoreceptors, and microglia-exhibit signs of senescence and related changes. Cellular senescence plays a pivotal role in the pathogenesis of AMD, contributing to the degeneration of different retinal cell types and supporting vascular systems. By thoroughly investigating these mechanisms, there is hope for the development of more effective therapies aimed at restoring and protecting vision in affected patients. This article reviews the biological mechanisms of cellular senescence and its role in AMD, exploring how different cell types contribute to the disease's onset, with the goal of providing new insights into the pathogenesis and treatment of AMD.
年龄相关性黄斑变性(age-related macular degeneration,AMD)是一种发生在黄斑区的退行性变，其中湿性年龄相关性黄斑变性(wet age-related macular degeneration,wAMD)以黄斑区新生血管为主要病理特征，是导致老年人视力受损甚至失明的重要原因，视网膜下纤维化是wAMD最常见的自然后遗症，可导致光感受器、视网膜色素上皮(retinal pigment epithelial,RPE)和脉络膜毛细血管受损，导致不可逆转的中心视力丧失。多种基线特征被发现是视网膜下纤维化的危险因素，可用于预测早期视网膜下纤维化的发生。迄今为止，还没有有效的抗纤维化治疗方法，抗血管内皮生长因子(anti-vascular endothelia growth factor, anti-VEGF)治疗是wAMD的一线治疗方案，该治疗方法不能改善视网膜下纤维化，但及时启动治疗可能有助于预防或延缓纤维化的进展，目前多种靶向分子药物正被研发用于抗纤维化的治疗。该文综述了wAMD视网膜下纤维化的临床表现及意义、预测纤维化形成的基线特征、基本发病机制及潜在的抗纤维化治疗方法，旨在为临床诊治工作提供参考。
Age-related macular degeneration (AMD) is a degenerative disease of the macular, and wet age-related macular degeneration(wAMD) is mainly characterized by macular neovascularization, which is an important reason of visual impairment or even blindness in the elderly. Subretinal fibrosis is the most common natural sequelae of wAMD, which can lead to irreversible central vision loss by damaging photoreceptors, RPE, and choroidal capillaries. Multiple baseline features have been identified as the risk factors for subretinal fibrosis, which can be used to predict the early subretinal fibrosis. Heretofore, no anti fibrotic treatment method is effective. Anti vascular endothelial growth factor (anti VEGF) treatment is the first-line treatment for wAMD. This therapy cannot improve subretinal fibrosis, but timely initiation of treatment may help prevent or delay the progression of fibrosis. Currently, multiple targeted molecular drugs are being developed for anti fibrotic treatment. This article reviews the clinical manifestations and significance of subretinal fibrosis in wet age-related macular degeneration, baseline features for predicting the formation of fibrosis, basic pathogenesis, and potential anti-fibrosis treatment methods,aiming to provide reference for clinical diagnosis and treatment.
目的：调查抗VEGF药物治疗湿性年龄相关性黄斑变性(wet age-related macular degeneration, wAMD)5年的疗效。方法：2011年至2021年于北京医院眼科诊断为wAMD的患者共84人103只眼进行回顾性分析。抗VEGF治疗采用3+PRN方案。观察5年来的最佳矫正视力(best-corrected visual acuity，BCVA)、玻璃体腔注射次数、随访次数和病灶的解剖学变化。结果：治疗5年后平均BCVA为38.1个字母，与基线相比下降9.4个字母，差异有统计学意义(P<0.001)。23.3%的患眼5年后可维持初始视力。5年内平均注射次数为13.8次，第1年注射次数最多，平均为4.3次。5年内平均随访次数为24.3次，仅有34.0%的患眼可遵循每次随访间隔≤3个月。5年后有68.0%的患眼出现纤维瘢痕，27.2%的患眼出现地图样萎缩，69.0%(71/103)的患眼存在持续的色素上皮脱离(pigment epithelial detachment，PED)。年龄、基线BCVA、是否初始治疗、随访年限、注射次数、中心视网膜厚度 (central retina thickness，CRT)、地图样萎缩等对BCVA有显著影响。结论：多数患者在抗VEGF治疗1年内可维持视力，但5年以上维持效果不佳。早期诊治、提高注射频率，可能是未来改善预后的研究方向。
Objective:To investigate the efficacy of anti-VEGF injection in the treatment of wet age-related macular degeneration (wAMD) for 5 years. Methods: A total of 84 patients (103 eyes) wAMD diagnosed in Department of Ophthalmology in Beijing Hospital from 2011 to 2021 were analyzed retrospectively. 3 + PRN regimen was applied for anti-VEGF treatment. The changes of best corrected visual acuity (BCVA), the number of intravitreal injections and the number of follow-up visits, and the anatomical changes of the lesions in the past 5 years were collected. Results: The average BCVA after 5 years was 38.1 letters, indicating a decrease of 9.4 letters comparing to baseline, which was statistically significant (P<0.001). 23.3% of the eyes could maintain the baseline BCVA after 5 years. The average injection times within 5 years was 13.8, and the injection was concentrated in the first year, with an average of 4.3. The average number of follow-up visits within 5 years was 24.3, and only 34.0% of the affected eyes could keep the follow-up interval ≤3 months. After 5 years, 68.0% of the eyes developed fibrous scar, 27.2% developed geographic atrophy, and 69.0% (71/103) had consistent pigment epithelial detachment. Factors significantly affect BCVA include: age, baseline BCVA, initial treatment, follow-up time, injection times, central retinal thickness, geographic atrophy and so on. Conclusion: Most patients can maintain vision within the first year after anti-VEGF treatment, but the efficacy is poor for more than 5 years. Early diagnosis and treatment, and increased injection frequency may be the research direction for improving prognosis in the future.
