Atrophy of the macula in the context of its wet, age-related degeneration. An inescapable consequence of anti-VEGF therapy?
Atrophy of the macula in the context of its wet, age-related degeneration. An inescapable consequence of anti-VEGF therapy?
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DOI：
10.1007/s00347-016-0306-9
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发表时间：
2016-12-01
期刊：
影响因子：
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通讯作者：
Garweg, J. G.
中科院分区：
文献类型：
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作者：
Garweg, J. G.
背景目前对湿性年龄相关性黄斑变性（AMD）抗VEGF治疗的长期后果的机制的理解很差。在这里，这种治疗对黄斑萎缩（MA）的发展的影响进行了讨论，根据我们目前的病理生理学的理解。本综述基于PubMed文献调查，使用MeSH术语“湿性AMD”和“黄斑萎缩”（151次点击），仅限于2013年以来的出版物（n = 90）。排除了关注诊断和临床过程而不是治疗背景的出版物。黄斑萎缩在本文中定义为影响功能相关的光感受器、视网膜色素上皮（RPE）、布鲁赫膜和脉络膜毛细血管复合体的萎缩。实验上，局部VEGF的原发性完全抑制导致脉络膜毛细血管的明显变化，而其不完全抑制加剧了RPE和光感受器的细胞死亡。由于在诊断时已经存在先前存在的萎缩性改变，抗VEGF治疗的作用不能与AMD的自发进展分开。雷珠单抗组MA的进展似乎比贝伐单抗组更快，同样每月一次而不是按需治疗。虽然MA在后续治疗下进展更快，但视觉功能仍然更好。因此，在治疗的前五年，功能相关的萎缩进展仅在预先存在的晚期MA中预期。尽管抗VEGF治疗的长期安全性存在疑问，但作者认为这是稳定视功能的唯一选择。治疗引起的损伤对AMD自发进展和老年个体的生物学状态的影响无法明确评估。
Background. Current understanding of the mechanisms that underlie the long-term consequences of anti-VEGF therapy in wet, age-related macular degeneration (AMD) is poor. Here, the impact of this treatment on the development of macular atrophy (MA) is discussed based on our current pathophysiological understanding.Methods. This review is based on a PubMed literature survey using the MeSH terms "wet AMD" and "macular atrophy" (151 hits) and limited to publications since 2013 (n = 90). Publications focussing on diagnostics and clinical course not in the context of therapy were excluded. Macular atrophy is defined herein as atrophy affecting the functionally relevant complex of photoreceptors, retinal pigmented epithelium (RPE), Bruch's membrane and choriocapillaris.Results. Experimentally, a primary complete suppression of local VEGF leads to evident changes in the choriocapillaris, whereas its incomplete suppression exacerbates cell death of RPE and photoreceptors. Since preexisting atrophic changes are already present at diagnosis, the role of anti-VEGF treatment cannot be separated from the spontaneous progression of AMD. The progression of MA appears to be faster under ranibizumab than bevacizumab, and likewise on a monthly rather than as-needed basis. Although MA progresses more rapidly under consequent therapy, visual function remains better. Hence, a functionally relevant progression of atrophy during the first five years of treatment would only be expected in pre-existing advanced MA.Conclusions. Despite doubts regarding the long-term safety of anti-VEGF therapy, it is the author's view that this is the only option to stabilise visual function. The impact of therapy-induced damage on the spontaneous progression of AMD and the biological status of the aging individual cannot be unequivocally assessed.