Boyer David S, Hopkins J Jill, Sorof Jonathan, Ehrlich Jason S
Retina Vitreous Associates Medical Group, 1127 Wilshire Boulevard, Suite 1620, Los Angeles, CA 90017, USA.
Ther Adv Endocrinol Metab. 2013 Dec;4(6):151-69. doi: 10.1177/2042018813512360.
Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients.
糖尿病是一个严重的健康问题，全球有超过3.5亿人受其影响。糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症，是工作年龄成年人失明新病例的主要原因。糖尿病性黄斑水肿（DME）是DR的一种晚期、限制视力的并发症，影响近30%患有糖尿病至少20年的患者，并且是导致DR所致视力丧失的主要原因。DME的传统治疗标准是黄斑激光光凝术，已证明该方法可稳定视力，并将进一步视力丧失的发生率降低50%；然而，黄斑激光光凝术仅能使15%的治疗患者实现显著的视力恢复。导致DR和DME微血管损伤的机制包括高血糖的直接毒性作用、细胞信号通路的持续改变以及白细胞介导损伤的慢性微血管炎症。慢性视网膜微血管损伤导致眼内血管内皮生长因子A（VEGF）水平升高，VEGF是一种强效、可扩散的内皮特异性有丝分裂原，介导许多重要的生理过程，包括但不限于血管系统的发育和通透性。VEGF被确定为DME的重要病理生理介质，这表明向眼内递送抗VEGF疗法可能会改善该疾病的视力结果。迄今为止，四种不同的VEGF抑制剂，均通过眼内注射给药，已在DME患者的前瞻性、随机II期或III期临床试验中进行了测试。这些试验的结果表明，与激光光凝术相比，抗VEGF药物治疗可显著改善视力和解剖学结果，并避免与激光治疗相关的眼部副作用。因此，抗VEGF疗法已成为许多患者治疗DME的首选治疗方案。
