Anti-VEGF Pegylated Aptamer for Advanced Ocular Disease

Von Hippel-Lindau综合征(VHL)是一种常染色体显性遗传性疾病 多发性良、恶性肿瘤和特定组织病理学的囊肿发生在 肾，肾上腺，胰腺，脑，脊髓，眼，内耳，附睾体，和宽 韧带。视网膜血管瘤可能是VHL病的最早表现之一，并可能 导致受影响个体的视力显著下降。这些肿瘤很少发生 自发地倒退。视力丧失的主要原因是视网膜水肿，特别是黄斑。 继发于视网膜周围血管瘤或周围血管瘤增大的水肿 光碟。视网膜血管瘤的治疗取决于病变的位置和大小，但 通常包括光凝或冷冻治疗。然而，目前还没有被证明有效的方法 视神经或视神经周围VHL眼部病变的治疗 外周视网膜太大，对传统疗法不起作用。发现的基因突变 在VHL疾病中，上调血管内皮生长因子(VEGF)的产生。 VHL眼部损害的免疫化学研究，以及在其他地方发现的 体表血管内皮生长因子明显升高。这项开放标签研究将试行抗血管内皮生长因子的使用 EYE001治疗视网膜潜在疗效观察5例 与VHL相关的血管瘤。患者将在一年内接受6次玻璃体内注射研究药物 30周，然后在开始注射一年后返回进行随访。初级阶段 结果是1年后最佳矫正视力提高15个字母或更多， 一年后视网膜增厚和渗漏减少，ERG波幅和隐含 时间和不良事件，包括局部和全身毒性。

Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis, and broad ligament. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of an anti-VEGF therapy (EYE001) in 5 patients to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Patients will receive 6 intravitreal injections of study drug over a 30-week period, then return for a follow-up visit 1 year after initiating injections. The primary outcomes will be improvement in best corrected visual acuity of 15 letters or more at 1 year, reduction in retinal thickening and leakage at one year, changes in ERG amplitude and implicit time, and adverse events including local and systemic toxicities.