Ocular Manifestations of von Hippel-Lindau Disease.

Misty D Ruppert,Kelly T Mitchell,Alan N Peiris,Meredith Gavin

doi:10.7759/cureus.5319

Abstract

In this review article, we aimed to analyze the available data on the ocular manifestations of von Hippel-Lindau (VHL) disease. In this disease, the VHL protein becomes inactivated by germline mutations of the VHL tumor suppressor gene on chromosome 3p25-26, resulting in an overproduction of VEGF in non-hypoxic conditions. Ocular manifestations are expected in roughly half of VHL patients. Retinal capillary hemangioblastomas (RCHs) are the most commonly observed tumors in VHL and are often the initial manifestation of the disease. Ablative therapy, surgical resection, and pharmacotherapy have been implemented to control tumors. Left untreated, RCHs will often enlarge, emphasizing the importance of early diagnosis and treatment to preserve vision. Complications of enlarging peripheral or optic nerve tumors may be severe. Large RCHs may disrupt normal retinal architecture, eventually leading to exudative retinal detachment. Rarely, non-retinal manifestations, such as neovascularization of the iris or cornea, may progress to neovascular glaucoma and vision loss. Ablative therapy of larger tumors carries increasing risks and offers limited success, often necessitating surgical resection. Because this life-threatening disease is not routinely encountered in clinical practice, clinicians will benefit from our review which brings awareness to the ocular presentation of VHL and lifelong screening recommendations for diagnosed patients.

Highlights

BackgroundVon Hippel-Lindau (VHL) disease, known as familial cerebello-retinal angiomatosis, is one of the neurocutaneous syndromes or phakomatoses
Type 1 is characterized by retinal angiomas, central nervous system (CNS) hemangioblastomas, renal cell carcinomas, pancreatic cysts, and neuroendocrine tumors, whereas type 2 is characterized by pheochromocytomas, retinal angiomas, and CNS hemangioblastomas [2]
We describe the ocular manifestations of von Hippel-Lindau (VHL), which can be viewed as a progressive neurodegenerative disease [4]

Summary

Introduction

Von Hippel-Lindau (VHL) disease, known as familial cerebello-retinal angiomatosis, is one of the neurocutaneous syndromes or phakomatoses. Clusterin was suggested as a potential biomarker of ocular VHL disease after clusterin immunoreactivity was found to be decreased in retinal and the optic nerve hemangioblastomas [14]. A large crosssectional study reported that 42% of RCHs presented unilaterally and 58% presented bilaterally in VHL patients, with no association of age, gender, or laterality of involvement [21] These tumors are often detected in the peripheral retina but may occur in the juxtapapillary area [21]. External beam radiation may be considered in refractory cases Patients treated with this therapy have reportedly experienced improved vision, decreased RCH volume and retinal detachment stabilization [37]. Photodynamic therapy of these lesions has shown poor success [40]. Begin MRI scans (no less than a 1.5T MRI performed with and without contrast) every 2 to 3 years of the brain, cervical, thoracic, and lumbar spine with visualization of the posterior fossa and inner ear/petrous temporal bone to rule out endolymphatic sac tumors and neuraxis hemangioblastomas

Conclusions

Disclosures

Findings

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