Sivaprasad Sobha
Laser and Retinal Research Unit, King's College Hospital, Denmark Hill, London, UK.
Clin Ophthalmol. 2008 Jun;2(2):339-46. doi: 10.2147/opth.s2617.
Age-related macular degeneration (AMD) is responsible for more than half the blind registration in the United Kingdom. Retinal manifestations of AMD can be categorized as either atrophic or neovascular. The hallmark of AMD is the development of choroidal neovascularization (CNV). Until recently, there have been few, limited treatment modalities (eg, photodynamic therapy [PDT]) for this condition and the mainstay of treatment has comprised social and lifestyle support. However, increased understanding of the molecular processes at work in neovascular AMD and CNV in recent years has led to the introduction of new anti-angiogenic agents that target vascular endothelial growth factor (VEGF). These agents either inhibit a selected VEGF isoform (eg, VEGF(165) inhibition by pegaptanib sodium) or inhibit all forms of the VEGF isoform (eg, non-selective VEGF blockade by ranibizumab). The trial data suggest that non-selective inhibition of VEGF offers better treatment outcomes in neovascular AMD. As a result, agents that inhibit all VEGF isoforms are now widely used as first-line therapy for this condition. However, it is known that VEGF plays an important role in maintaining the intergrity of the cardiovascular system and, particularly as the age of patients with AMD places them at an elevated risk of thromboembolic events, long-term post-marketing surveillance data are essential to determining whether non-selective VEGF blockade confers any increased risk. Theoretically, selective VEGF inhibition may reduce any risk associated with pan-VEGF blockade, yet on the basis of initial trials, their use remains more limited at this time. However, clinical practice suggests that initial trials may have under-estimated the efficacy of selective-VEGF inhibition. Observational studies also indicate that better treatment outcomes may be possible by combining VEGF inhibitors sequentially with each other, or with existing therapies (eg, photodynamic therapy [PDT]). The optimum role and indications of anti-VEGF agents will come through careful consideration of the available efficacy and safety data, from the outcomes of long-term follow-up studies, and through assessment of the relative merits of the two approaches to VEGF inhibition in clinical practice. At this time, further head-to-head trials, and economic evaluations, comparing the treatment alternatives are needed.
年龄相关性黄斑变性（AMD）导致了英国半数以上的失明登记病例。AMD的视网膜表现可分为萎缩性或新生血管性。AMD的标志是脉络膜新生血管（CNV）的形成。直到最近，针对这种疾病的治疗方式很少且有限（例如光动力疗法[PDT]），治疗的主要内容包括社会和生活方式支持。然而，近年来对新生血管性AMD和CNV中起作用的分子过程的深入了解，促使了针对血管内皮生长因子（VEGF）的新型抗血管生成药物的引入。这些药物要么抑制特定的VEGF异构体（例如，培加尼布钠抑制VEGF(165)），要么抑制所有形式的VEGF异构体（例如，雷珠单抗进行非选择性VEGF阻断）。试验数据表明，非选择性抑制VEGF在新生血管性AMD中能提供更好的治疗效果。因此，抑制所有VEGF异构体的药物现在被广泛用作这种疾病的一线治疗药物。然而，已知VEGF在维持心血管系统的完整性方面起着重要作用，特别是由于AMD患者的年龄使他们发生血栓栓塞事件的风险升高，长期的上市后监测数据对于确定非选择性VEGF阻断是否会带来任何增加的风险至关重要。从理论上讲，选择性VEGF抑制可能会降低与泛VEGF阻断相关的任何风险，但基于初步试验，目前它们的使用仍然更为有限。然而，临床实践表明，初步试验可能低估了选择性VEGF抑制的疗效。观察性研究还表明，通过将VEGF抑制剂相互序贯联合使用，或与现有疗法（例如光动力疗法[PDT]）联合使用，可能会获得更好的治疗效果。抗VEGF药物的最佳作用和适应症将通过仔细考虑现有的疗效和安全性数据、长期随访研究的结果，以及通过评估临床实践中两种VEGF抑制方法的相对优点来确定。此时，需要进一步进行对比治疗方案的直接比较试验和经济学评估。
