Ranibizumab (rhuFAB V2) for Advanced Ocular Disease of V

Von Hippel-Lindau综合征（VHL）是一种常染色体显性遗传性疾病，其中在肾脏、肾上腺、胰腺、脑、脊髓、眼、内耳、附睾和阔韧带中发生具有特定组织病理学的多种良性和恶性肿瘤和囊肿。视网膜血管瘤可能是VHL疾病的最早表现之一，并可能导致受影响个体的视力显著下降。这些肿瘤很少自发消退。视力丧失的主要原因是视网膜水肿，特别是继发于周围视网膜血管瘤或在视盘上或周围发现的血管瘤的扩大的黄斑水肿。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，对于视神经上或周围的VHL眼部病变或外周视网膜中的病变太大而对传统疗法没有反应，还没有被证明有效的治疗方法。在VHL疾病中发现的基因突变上调了血管内皮生长因子（VEGF）的产生。VHL眼部病变的免疫化学研究，以及其他发现在身体其他地方显示VEGF显着增加。这项开放标签研究将在5名受试者中试用抗VEGF疗法雷珠单抗（rhuFab V2），以研究其作为VHL相关视网膜血管瘤治疗的潜在疗效。受试者将在6个月内接受7次玻璃体内注射研究药物，并可选择在治疗开始后1年的随访期间以相同剂量和时间表进行最多7次额外注射。主要结局将是1年时最佳矫正视力变化15个字母或更多。次要结果将是一年时视网膜增厚和渗漏的减少，以及包括局部和全身毒性在内的不良事件。招募工作仍在继续。

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, ranibizumab (rhuFab V2) in 5 participants to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Participants will receive 7 intravitreal injections of study drug over a 6-month period, with the option of up to seven additional injections at the same dose and schedule during follow-up for a period of 1 year after the initiation of treatment. The primary outcome will be a change in the best-corrected visual acuity of 15 letters or more at 1 year. The secondary outcomes will be a reduction in retinal thickening and leakage at one year, and adverse events including local and systemic toxicities. Recruitment continues.