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Ophthalmology > PHAKOMATOSES
von Hippel-Lindau Disease
Article Last Updated: Apr 4, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Arun Gulani, MD, Director, Gulani Vision Institute
Arun Gulani is a member of the following medical societies: American Academy of Ophthalmology
Editors: Michael J Bartiss, OD, MD, Medical Director, Ophthalmology, Family Eye Care of the Carolinas; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
von Hippel disease, retinal angiomatosis, capillary hemangiomas of the retina, benign capillary hamartoma, retinal capillary hemangioma
Background
von Hippel disease exhibits the characteristics of congenital capillary angiomatous hamartomas of the retina and the optic nerve.
Pathophysiology
This condition is a benign capillary hamartoma with autosomal dominant inheritance with variable penetrance. The responsible gene is on chromosome 3 (3p25-p26). This gene behaves as a typical tumor suppressor gene as defined in Knudson's theory of carcinogenesis. A nonhereditary form also exists.
Retinal capillary hemangiomas (von Hippel disease) are seen in 50% of patients. Similar tumors in the CNS (hemangioblastomas in the cerebellum [ie, von Hippel-Lindau disease]) and other organs of the body are present in 25% of patients. Cysts of the pancreas and kidneys may coexist. Pheochromocytoma and hypernephroma also are known to occur.
Retinal capillary hemangiomas, usually supplied by large dilated feeder vessels, may occur in any part of the retina. Serum leakage from these vessels and hemangiomas leads to retinal exudates. Organized fibroglial bands with traction retinal detachment and vitreous hemorrhage may occur with their own secondary sequelae.
On the microscopic level, the basic component is a capillary hemangioma comprised of endothelial cells and pericytes. The foamy stromal cells between the capillaries stain positive for glial fibrillary acid protein and neuron specific enolase.
Frequency
United States
This condition is uncommon in the general population.
Mortality/Morbidity
Untreated von Hippel-Lindau disease can cause serious visual impairment.
Sex
No known gender predilection exists.
Age
von Hippel-Lindau disease usually presents in the second to third decade of life.
History
- Patients may note a decrease in visual acuity.
- Have a high index of suspicion of ocular lesion if a patient presents with diagnosis of von Hippel-Lindau disease.
Physical
- Occasional lesions are noted on routine examination.
- Loss of vision usually is caused by lipid exudate in the macula area. If left untreated, this exudation can lead to retinal detachment. Vitreous hemorrhage, secondary iris neovascularization with glaucoma, and cataract formation may follow.
- Angiomas are the most common presenting signs and symptoms of this disease syndrome.
Causes
See Pathophysiology.
Other Problems to be Considered
Choroidal mass (tumor/metastasis)
Retinal telangiectasis
Retinal macroaneurysms
Lab Studies
- Vanillylmandelic acid levels in urine
- Genetic study analysis
Imaging Studies
- CT scan of brain with contrast
- MRI of brain (posterior fossa emphasis)
- Abdominal CT scan (to look for pheochromocytoma)
- Ophthalmic ultrasound
- Ocular color Doppler sonography
- In clinically diagnosed cases of angiomatosis retinae, applied color Doppler sonography is used to delineate the dilated, enlarged, and closely running feeder vessels on the retinal surface. The opposing directions of flow may indicate an artery or a vein. The angioma is not imaged because of to a low flow system. The above findings may be highly suggestive of angiomatosis retinae.
- Affected patients can be diagnosed clinically using ophthalmoscopy with its pathognomic appearance. The fundus shows the presence of an angioma in the temporal retinal periphery. Vessels will appear.
- A 7.5 MHz linear array transducer (Acuson 128XP) is used to examine the eyes of von Hippel disease. The real-time, gray scale image and color Doppler images are obtained. Pulsed Doppler analysis also can be used to evaluate vascular dynamics.
- On application of color Doppler sonography, the feeder vessels appear to be a pair of dilated, tortuous blood vessels coursing to the angioma from the optic disc. The color image depicts the flow in these vessels to be in opposite directions. No flow can be appreciated in the angioma. These findings are of value in diagnosing this condition in cases where the visualization of the fundus is not possible with an ophthalmoscope due to opaque media, which may be a complication of the disease.
- The regression of the disease (angioma) can be followed and monitored by repeated studies, after treatment with various modalities (ie, cryotherapy, diathermy, irradiation, laser photocoagulation). It is common to see new angiomas appearing or growing in the region of treated angiomas.
- Color Doppler sonography provides a simultaneous morphologic and vascular image of the disease entity, enabling diagnosis and monitoring the effectiveness of treatment.
- Ocular color Doppler sonography is a safe, noninvasive, relatively inexpensive investigative modality in diagnostic ophthalmology.
Surgical Care
von Hippel disease usually is a progressive disease. Therapy should begin as soon as the diagnosis is made. Surgical treatment may consist of argon laser photocoagulation, cryotherapy, fluid drainage, scleral buckling, penetrating diathermy, vitreous surgery, or endodiathermy.
- Argon laser photocoagulation is effective in treating angiomatosis retinae. Treatment consists of a large spot size, with low-intensity, long-duration burns directed at the angioma.
- Repeated laser treatment is required, except for small tumors. Obliteration of the tumor is confirmed by clinical observation and fluorescein angiography.
- If the tumor turns yellowish, photocoagulation becomes difficult because of the poor penetration of laser light.
- Cryotherapy, a repetitive freeze/thaw technique, may be used to treat anterior angiomas and larger posterior angiomas.
- To minimize the risk of hemorrhage, no more than 2 or 3 freeze/thaw cycles should be used per session. Multiple sessions generally are needed to arrest tumors.
- Resolution of the macula edema and improved visual acuity are common results of tumor eradication by cryotherapy.
- Scleral buckle and fluid drainage methods may be needed to treat larger tumors, tumors associated with retinal detachment, angiomas resistant to cryotherapy, or tumors involving subretinal exudation. Large tumors may develop surface membranes and vitreous traction, leading to vitreous hemorrhage or rhegmatogenous retinal detachment. Such complications may require treatment by vitreous surgery, endodiathermy, or scleral buckling techniques.
- Penetrating diathermy under a lamellar scleral bed is an effective treatment for larger angiomas.
- Endodiathermy may be used, instead of vitreous surgical techniques or scleral buckling procedures, to treat vitreous hemorrhage or retinal detachment.
Consultations
The ophthalmologist has a critical role to play in the management of this disease.
Further Outpatient Care
- Long-term follow-up care is important to detect any additional lesions.
Deterrence/Prevention
- Lifelong follow-up care is indicated when family history is positive, since systemic manifestation can occur years after retinal hemangiomas are noted.
Complications
- Visual complications of retinal angiomas include the following:
- Macular exudation
- Retinal detachment
- Vitreous hemorrhage
- Cataract
- Glaucoma
- Nerve damage
- Iatrogenic complications from argon laser photocoagulation, cryotherapy, or irradiation
Prognosis
- Early diagnosis is essential, since angiomas have a poor prognosis unless they are treated.
- Of those patients with retinal angiomas, 25% have associated cerebellar hemangioblastomas.
Medical/Legal Pitfalls
- Early detection and treatment of retinal lesions can help reduce the limitation of vision.
| Media file 1:
von Hippel-Lindau disease. Clinical picture of the retina, showing a pair of dilated and tortuous feeder vessels coursing on the surface of the retina from the optic nerve head toward the angioma (which is not seen in this image because it is in the extreme periphery). |
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Media type: Photo
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| Media file 2:
von Hippel-Lindau disease. Color Doppler image of the dilated feeder vessels with flow patterns in opposite directions as indicated by red for the artery and blue for the vein. The abbreviation ON designates the optic nerve with its blood vessels. |
 | View Full Size Image | |
Media type: Graph
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| Media file 3:
von Hippel-Lindau disease. Spectral display of the aberrant feeder vessels. |
 | View Full Size Image | |
Media type: Photo
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- Maher ER, Bentley E, Yates JR, et al. Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic linkage analysis. J Neurol Sci. Dec 1990;100(1-2):27-30. [Medline].
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von Hippel-Lindau Disease excerpt Article Last Updated: Apr 4, 2006
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