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病

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.