Retinal capillary hemangioma in von Hippel-Lindau disease.

von Hippel-Lindau (VHL) disease is caused by a mutation in the VHL gene, resulting in the functional disorder in VHL-encoded protein (pVHL). Recent advances in experimental and clinical studies on VHL gene/protein and VHL disease have provided novel concepts in molecular pathology and clinical managements. pVHL plays a critical role in the regulation of hypoxia inducible factor (HIF)-dependent as well as HIF-independent signaling pathways. These mechanisms should underlie the pathogenesis of VHL-related retinal vascular tumors. It is still controversial whether the histological term “hemangioma” vs “hemangioblastoma” should be appropriate in calling retinal vascular tumors of VHL disease. Recent clinical studies have proved efficacy of various therapeutic options depending on the location of retinal tumors between peripheral and optic disc/juxtapapillary hemangioma. Long-term follow-up observation can be achieved in VHL disease patients, showing favorable outcomes of conventional standard treatments. However, there still exists a population suffering from irreversible severe visual disturbance even though the conventional treatments had been performed enough. Further challenging of molecular targeting therapy as well as development of vitreoretinal surgeries and gene/protein transfer technique may contribute to preservation of the patients’ vision in the future.