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老年黄斑变性的药物治疗

     

摘要

在美国等发达国家中,老年黄斑变性(AMD)是65岁以上人群最主要的致盲原因.迄今为止,老年黄斑变性的治疗方法很有限.目前的治疗方法可以分为两大类:物理治疗和药物治疗.前者曾受到广泛关注却效果不显著,而后者近来发展迅速.药物治疗包括:光动力学治疗、激素、血管内皮生长因子VEGF的抑制药物、细胞外间质的修饰药物、基因治疗、营养补充和脉络膜血流促进药物等.光动力学治疗是某些特定类型的新生血管型AMD唯一有效的治疗方法.Anecortave acetate(一种人工合成的激素)球旁注射可以稳定患者的视力达6mo.玻璃体腔注射VEGF的拮抗药物,也能稳定患者的视力3mo.在AMD的早期就可发现脉络膜血流的改变.血管压力的增加是AMD重要的血流动力学改变,它导致了脉络膜毛细血管血流减少.经过一系列反应,最终导致视网膜色素上皮细胞变性、Bruch膜断裂、脉络膜新生血管形成、老年黄斑变性、失明.因此改善脉络膜血流的药物可能阻止AMD的发展和恶化.虽然这些药物还多处于试验阶段,但还是很有希望来发现治疗AMD的药物,从而阻止其发展.%· Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals aged over 65 in the United States and other industrialized nations. Till now, we have limited choices of treatment for this kind of disease. Treatment available can be grouped into two major categories: physical and pharmacological therapies. The former received extensive attention with little success whereas the latter attract new attention with great hope of success. The pharmacological therapies indude photodynamic therapy (PDT), steroids, vascular endothelial growth factor (VEGF) inhibitors, extracellular matrix (ECM) modifiers, gene therapy, nutrition supplements, choroidal blood flow facilitators and the like. PDT treatment is the only available effective treatment for certain forms of neovascular AMD. Anecortave acetate,as a synthetic derivative of cortisol, might stabilize vision in patients with predominantly classic subfoveal choroidal neovascularization (CNV) for up to 6mo through subtenon juxtascleral depot application. Intravitreous injection of VEGF aptamer stabilized or improved vision in 87.5% of patients with subfoveal CNV 3mo after treatment. Malfunction of choroidal blood flow is found in early stage of AMD. Elevation of intravascular pressure is the crucial hemodynamic factor in age-related macular degeneration, resulting in a decrease of the blood flow of choriocapillaries. Chain reactions are triggered which lead to retinal pigment epithelium (RPE) degeneration,Bruch's membrane breakdown, CNV formation, AMD and blindness in the end. Therefore, specific drugs that can increase the choroidal blood flow could be very useful to prevent the AMD from developing and worsening. Although most of them are still in the experimental stage,it is hopeful to find a way to treat AMD at the early stage and to prevent the disease to be triggered and developed.

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