What is von Hippel-Lindau syndrome?
Von Hippel-Lindau syndrome (VHL) is a rare inherited disorder that causes tumors and cysts to grow in many parts of the body, including the eyes. The tumors often appear in early adulthood and can occur throughout life. Prompt detection and treatment are critical to preserving health and vision.
Von Hippel-Lindau disease affects about 1 in 36,000 people at birth. It’s caused by a mutation in the VHL gene. This gene is responsible for a protein that helps regulate and control cell growth and prevents tumor formation. When the VHL gene doesn’t work properly, blood vessels can grow uncontrollably. This uncontrolled growth forms tumors called hemangioblastomas.
People with von Hippel-Lindau syndrome need lifelong monitoring because tumors can develop at any age, often starting in early adulthood. While these tumors are usually noncancerous, they can still damage organs like the eyes, brain, kidneys and spinal cord. This can cause serious health issues.
Retinal hemangioblastomas are the most common tumors seen in the eye in VHL. They are growths made of new, abnormal blood vessels that occur in the back of the eye. Though usually not cancerous, the growths can lead to vision loss. This makes regular monitoring and proper management very important.
How does VHL affect the eyes?
The most common eye-related issue in VHL is the development of retinal hemangioblastomas. It is often one of the earliest signs that someone has von Hippel-Lindau disease. Because of this, eye doctors play a key role in diagnosing and caring for individuals with VHL.
It is not known how often retinal hemangioblastomas occur without VHL. These “sporadic” tumors are usually discovered when people are in their 20s or 30s, but they can be found at any age, from birth to 80 years old.
People with inherited VHL tend to develop tumors earlier, around 18 years old. In comparison, people without a family history of VHL are typically around 30 when they develop tumors. These tumors are more common in Caucasians and affect men and women equally.
Retinal hemangioblastomas
Hemangioblastomas can occur in the retina. This is the light-sensitive tissue at the back of the eye that is responsible for vision. Studies show that 60% of individuals with von Hippel-Lindau syndrome will develop these retinal tumors, also called retinal capillary hemangioblastomas (RCHs).
If left untreated, retinal hemangioblastomas can cause serious vision problems. Large tumors can:
- Disrupt the normal structure of the retina
- Cause the retina to leak fluid and blood
- Cause retinal swelling and scarring
- Result in permanent vision loss
If these tumors progress to severe stages, the abnormal blood vessel growth may lead to:
- Retinal detachment – A separation of the retina from the back of the eye
- Macular edema – A buildup of fluid in the central retina (the macula)
- Uveitis – Inflammation of the middle layer of the eye (the uvea)
- Cataracts – A clouding of the crystalline lens inside the eye
- Glaucoma – A group of eye diseases that damage the optic nerve
A large study by the National Eye Institute looked at over 300 people with von Hippel-Lindau disease. It found that:
- In about 40% of cases, the tumors were in only one eye.
- In about 60% of the cases, tumors were in both eyes.
The location of tumors and other complications impacted how vision was affected:
Peripheral tumors
Most RCHs are found in the peripheral retina (the area outside the macula). These tumors are typically small, but as they grow, they become more noticeable with bigger blood vessels. They can lead to swelling and deposits in the retina, which might affect the macula (the center part of the retina that helps you see clearly). These affect about 85% of VHL patients.
Juxtapapillary tumors
These are near the optic nerve and occur in about 10% to 15% of cases. They can cause swelling around the optic nerve.
Rare complications
Bleeding in the retina or vitreous (the gel inside the eye) happens very rarely, in less than 3% of cases.
Symptoms of retinal hemangioblastomas
Small tumors might not cause symptoms at first. In fact, most patients with retinal hemangioblastomas are asymptomatic. Monitoring with regular eye exams and imaging techniques is very important for individuals with von Hippel-Lindau syndrome to detect these tumors early.
When retinal tumors cause symptoms, they do so by disrupting the retina’s structure. They can also cause bleeding, fluid leakage and swelling. Symptoms of retinal hemangioblastomas include:
- Blurred or decreased vision – When tumors near the center of the retina (the macula) distort sharp vision
- Floaters – If the tumor bleeds into the vitreous gel inside the eye, these dark spots or squiggly lines may appear
- Blind spots – When large tumors block parts of the visual field (also called scotomas)
Diagnosing eye involvement in VHL
Regular comprehensive eye exams are key for detecting eye issues early in individuals with von Hippel-Lindau disease. These exams include a thorough evaluation and imaging of the retina. Imaging techniques play an important role in detecting and monitoring hemangiomas in the eye.
A comprehensive eye exam for someone with VHL usually includes:
- Dilated fundus evaluation – Eye drops are used to widen the pupil, allowing the doctor to check the back of the eye (the fundus) for abnormal blood vessels.
- Fluorescein angiography – A special dye is injected into the patient’s arm. This dye highlights blood vessels in the retina to reveal leaks and blockages. Pictures of the retina are taken to detect abnormalities in the blood vessels.
- Optical coherence tomography (OCT) – This non-invasive imaging technique provides detailed cross-sectional images of the retina. OCT is helpful for measuring tumor size and tracking changes.
Treatment options for retinal hemangioblastomas
Managing VHL disease is complex because it can affect many parts of the body, including the eyes. Eye treatments are especially challenging because there can be multiple tumors in both eyes, and new ones can form at any time.
Tumors that are near the central retina or the optic nerve are more difficult to treat because they can cause more vision problems. Doctors must decide the best treatment based on:
- The patient's symptoms
- The size and location of their tumors
- Any other relevant factors
Current treatments include:
Laser photocoagulation
Laser photocoagulation uses a focused laser beam to seal off abnormal blood vessels. This procedure can be used to treat small tumors on the outer (peripheral) parts of the retina. It works well for most people and has few complications.
Cryotherapy
Cryotherapy involves using extreme cold to freeze and destroy tumor tissue. It can be used for tumors surrounded by fluid or those that can’t be reached by a laser. It can be used for larger tumors.
Vitrectomy
Vitrectomy is performed for serious complications like bleeding or retinal detachment. It involves removing the clear gel inside the eye (the vitreous humor) to access and treat retinal tumors.
Radiation therapy
In some cases, small amounts of radiation may be used to try and reduce the size of large tumors. This may be done when other treatments don't work, or in combination with other therapies.
Living with VHL: Eye care recommendations
Working closely with an eye doctor and a VHL specialist gives patients the best chance to protect their sight. People with this condition should regularly monitor their eyesight and report any new visual symptoms to their eye doctor. Early treatment can reduce the risk of vision impairment.
Since von Hippel-Lindau syndrome is inherited, families should consider genetic testing. It can help patients understand the disease's inheritance pattern and the risk for other family members. Genetic testing helps doctors understand how gene mutations affect the body and eyes. This can help doctors predict:
- Which parts of the body might be affected
- The age of symptom onset
- The severity of the condition
Vision loss from von Hippel-Lindau disease can often be prevented with routine comprehensive eye exams. For those who have experienced vision impairment due to VHL, low vision support services can be beneficial.
Even if you have no symptoms, screenings can catch tumors early. Tell your eye doctor about new floaters, flashes of light or vision changes immediately.
