Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

What is Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)?

Retinal vascular anomalies are uncommon conditions that can be inherited or sporadic. They affect the retina (the innermost layer of the eye) and several other parts of the body. These can include vascular tumors (abnormal growths of blood vessels) and telangiectasias (tiny, widened blood vessels on the skin or other surface). Specific types of these tumors found in the retina are retinal capillary hemangiomas, cavernous hemangiomas, racemose hemangiomas, and retinal vasoproliferative tumors. Retinal telangiectasias can occur in conditions like Coats disease, Leber’s miliary aneurysms, and idiopathic juxtafoveal telangiectasias.

The first case of capillary hemangiomas of the retina was reported by Vigla in 1864 in a patient who also showed brain (Central Nervous System) abnormalities. These hemangiomas are harmless vascular tumors that can originate from the sensory part of the retina or the optic disc. Sometimes, they can be linked to a disorder called Von Hippel-Lindau (VHL) syndrome. VHL syndrome is an inherited disorder leading to vascular tumors and cysts in different parts of the body. Some conditions connected with VHL syndrome include brain and retinal hemangioblastomas, kidney cancer, pheochromocytoma, pancreatic islet tumors, endolymphatic sac tumors, and epididymal, renal, and pancreatic cystadenomas. These retinal tumors usually appear as reddish-orange masses in the retinal periphery and can cause vision loss due to retinal leakage, detachment, vitreous hemorrhage, and neovascular glaucoma.

The retinal cavernous hemangiomas, also known as retinal cavernomas, were first described as angiomatosis retinae by Niccol and Moore in 1934. These are rare, non-progressive retinal vascular hamartomas (non-cancerous tissue growths). In some cases, these can involve the Central Nervous System and can cause significant health issues if not identified and managed promptly.

Retinal capillary hemangiomas may appear as a single lesion or as a part of a rare congenital disorder known as Wyburn-Mason syndrome or Bonnet-Dechaume-Blanc syndrome. This disorder results in arteriovenous malformations (abnormal connections between arteries and veins) in the retina, visual pathways, and areas like the midbrain, maxilla, and mandible. This can be observed during an eye examination as dilated and twisted vessels from the optic disc to the retinal periphery. Patients’ visual acuity (clarity of vision) can vary from normal to poor, depending on the complications associated.

What Causes Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)?

Retinal capillary hemangiomas, also known as retinal hemangioblastomas, can exist alone or as part of a condition known as VHL syndrome. This syndrome is linked to a change in the VHL gene, found on the 3rd pair of our 23 pairs of chromosomes. The VHL gene makes a protein that helps break down another protein that reacts to low oxygen levels (HIF). If the VHL gene is changed, this can lead to a buildup of HIF proteins, which in turn promotes the growth of new blood vessels and tumors in the retina.

Another type of growth, called retinal cavernous hemangiomas, can occur randomly or can be inherited. When inherited, this condition often comes with changes in the brain and skin. In cases where both the retina and brain are involved, researchers have identified changes in several genes, located on different chromosomes. A change in the PIK3CA gene, specifically, has been linked to randomly occurring cases of cerebral cavernous malformation, a condition that can affect the brain.

Racemose hemangiomas, which are seen with a condition known as Wyburn-Mason syndrome, are caused by a development issue impacting a structure called the vascular mesoderm. This structure is shared by the developing eye and a part of the brain called the anterior neural tube and plays a role in forming blood vessels in the eye and brain.

Risk Factors and Frequency for Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

Retinal capillary hemangiomas, a common symptom of VHL syndrome, tend to appear first and are most common in Europeans. If you have a solitary retinal hemangioma, there is a 30% to 46% chance you may develop VHL syndrome later in life. These hemangiomas typically show up around the age of 25, equally in both men and women, and can become more severe in each generation. Patients with VHL syndrome usually live between 40 and 52 years, most often passing away due to Central Nervous System hemangioblastomas.

Cavernous hemangiomas of the retina, on the other hand, are more common in white patients and usually present at a median age of 21. There’s a familial type of these malformations that are dominant and can highly likely be passed down from parents to their children. The frequency of patients with familial cerebral cavernous hemangiomas also having retinal cavernous hemangiomas is projected to be 5%.

Racemose hemangiomas are rare and their exact count is not known. They can appear in any racial or gender group before the third decade of life. Changes in high-flow arteriovenous malformations can lead to retinal or choroidal damage. Such malformations can remain undetected or without any symptoms if they are small, and hence could be diagnosed at a later stage of life.

Signs and Symptoms of Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

Retinal capillary hemangiomas, which are types of eye tumors, can have different symptoms depending on their size and location. A family history can sometimes point to Von Hippel-Lindau syndrome, which is often associated with these tumors. Usually, patients notice a gradual loss of vision. Other types of tumors like cerebellar hemangioblastomas can cause symptoms like headaches, vomiting, unsteady gait, and issues with sensation and movement. Endolymphatic sac tumors, although rare, can cause feelings of fullness in the ear, balance problems, and hearing loss. Pancreatic and kidney cysts generally don’t cause symptoms, while adrenal pheochromocytomas can lead to perspiration, fast heartbeat, high blood pressure, paleness, headaches, or nausea. A lot of these conditions are found during regular eye exams or check-ups. Cystadenomas of the epididymis, which are cysts in the testes, can occasionally cause infertility when they occur on both sides.

Meanwhile, cavernous hemangiomas, another type of eye tumor, usually don’t have symptoms but may cause a slight to moderate decline in sharpness of vision. If these spread to the central nervous system (CNS), they may cause headaches, seizures, and vision disturbances. Retinal hemangiomas, especially the smaller ones, can show up without symptoms and are often found during routine exams. However, larger ones can lead to serious vision loss and various symptoms like bleeding in the eye’s jelly-like interior; detached retinas; blocked veins; swelling and damage of the optic disc, which connects the eye to the brain. Neurological symptoms could include headaches, seizures, muscle weakness on one side of the body, nerve problems in the head, and a buildup of cerebrospinal fluid in the brain (hydrocephalus).

Testing for Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

When a doctor suspects that a person may have retinal capillary hemangiomas (small, benign, blood vessel tumors on the retina), there are several ways they can make a diagnosis.

One method is by a clinical examination using a tool to widen the patient’s pupils and examine the retina. This can lead the doctor to observe a reddish-orange mass with some twisted blood vessels at its base, usually found in the outer side of the retina, near the temporal bone. However, there are instances where these can be found near the papilla (where the optic nerve enters the eye). There are also cases where these masses may be found on the optic nerve itself, making them harder to notice and diagnose due to the absence of the feeding artery and draining vein observed in retinal hemangioblastomas.

There are three types of optic nerve hemangioblastomas: endophytic, exophytic, and sessile. Endophytic tumors appear as round, reddened lesions that project into the vitreous, the clear, gel-like substance in the eye. Exophytic lesions extend from the edge of the optic disc into the space beneath the retina and appear as a yellow, nodular tumor. Conversely, sessile types are harder to detect due to their appearance as localized thickening at the neuroretinal rim, without prominent coloration.

Further diagnostic tools include Fundus Fluorescein Angiography (FFA), which is used to highlight the blood vessels in the retina and helps detect even tiny tumors. Ultrasonography can help show the presence of a solid intraocular tumor and possible surrounding fluid. Optical Coherence Tomography (OCT) can show tumors affecting the entire retinal thickness, and medical imaging technologies like OCT Angiography (OCTA) can be used to measure the dimensions of the tumor and monitor its response to treatment.

Magnetic Resonance Imaging (MRI) of the brain can be used to diagnose other types of hemangioblastomas that might occur in the cerebellum, spinal cord, and brainstem, as well as optic pathways and the choroidal plexus.

In addition to these imaging methods, genetic testing can also be useful to identify mutations in genes associated with these conditions. These tests can be beneficial to other family members in terms of knowing their potential risk of experiencing similar conditions.

As well, dilated fundoscopy (dilation of the pupils to examine the back of the eye) can be used to diagnose cavernous vascular hemangioma, where dark, grape-like clusters of dilated blood vessels are seen along the retinal vein or on the optic disc. Along with dilated fundoscopy, doctors may also use FFA, OCT, and ultrasonography as diagnostic tools for cavernous vascular hemangiomas.

Lastly, in diagnosing a condition called retinal racemose angiomas, ophthalmoscopic examination is conducted where unusually large and twisted retinal arteries and veins are seen extending from the optic disc. Depending on the symptom characteristics, doctors can classify this condition into three groups to accurately diagnose and treat. In addition, vascular lesions in the central nervous system can be diagnosed using imaging technology such as computed tomography (CT), MRI, and magnetic resonance angiography (MRA).

Treatment Options for Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

Capillary hemangiomas are small, benign blood vessel tumors that can appear on the skin or in the body. The decision to treat them depends on the location of the tumor, how many there are, their size, and how they are affecting the person.

Sometimes, inactive fibrotic lesions (scars that have developed over time) don’t need any treatment. However, small capillary hemangiomas (that are up to 4 mm across) can be effectively treated with laser photocoagulation, a technique that uses laser light to destroy the tumor.

In case of larger tumors, up to 5mm, cryotherapy (a treatment that uses freezing temperatures to destroy tissue) can work, but they typically need more than one treatment to get the best results. In some cases, cryotherapy could cause a temporary increase in exudative or tractional vitreoretinopathy (vision problems due to damage to the retina).

For even larger tumors, techniques like external beam radiotherapy (using radiation to destroy the tumor), plaque brachytherapy (a type of radiation treatment), or proton beam therapy (another type of radiation treatment) might be needed. For severe cases with retinal detachment (when the retina pulls away from the back of the eye), surgery may be required.

In cases where the tumor is affecting the eye, surgical removal of the tumor can potentially minimize any secondary effects and improve vision outcomes. Techniques like endodiathermy (using electric currents to heat and destroy the tumor) or feeder vessel ligation (tying off the blood vessels feeding the tumor) can help prevent excessive bleeding during the surgery and provide better control over the tumor.

Another type of hemangioma known as a retinal cavernous hemangioma typically doesn’t cause any symptoms and remains stable, so treatment isn’t usually needed. But if there’s severe bleeding, cryotherapy and laser photocoagulation may be recommended as potential treatments.

Retinal arteriovenous malformations are a different kind of issue where the blood vessels in the retina are improperly connected. If these malformations aren’t causing any symptoms, treatment may not be necessary. But if symptoms or complications occur, laser photocoagulation, surgery, or treatments to destroy the malfunctioning part of the eye might be needed.

Certain medication treatments have shown promise for some cases, such as combinations of anti-vascular endothelial growth factor (anti-VEGF) agents and photodynamic therapy. However, the side effects of some of these treatments can vary greatly, and these need to be discussed with your doctor before starting any new treatments.

What else can Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason) be?

When trying to diagnose a condition known as retinal capillary hemangiomas, it’s important to consider and rule out other similar conditions. These might include cavernous hemangiomas, retinal hemangiomas, retinal macroaneurysms, and retinal vasoproliferative tumors.

Retinal vasoproliferative tumors are benign and often a reaction to an injury or lack of blood supply to the retina. They are usually not associated with other inherited conditions or diseases, but can occur alongside certain eye conditions such as retinitis pigmentosa, Coats disease, uveitis, and retinal detachment. These tumors can be differentiated from capillary hemangiomas by their location in the outermost parts of the lower part of the retina and the lack of significant blood supply.

Treatment largely depends on the size of the tumor and whether it’s causing vision problems. Smaller tumors located on the outer edges of the retina often only require monitoring. Depending on the complications, treatment options can include laser therapy, heat therapy, cryotherapy, injections to prevent blood vessel growth, or eye surgery.

Distinguishing cavernous hemangiomas from other similar conditions, such as Coats disease and Leber’s miliary aneurysm, is typically less challenging. These conditions cause widening of the blood vessels, leading to fluid-leakage within and beneath the retina. It is possible to detect early signs of these conditions and help with diagnosis by using a test that involves injecting a special dye into the bloodstream which can be traced using a camera to show the blood vessels in the retina.

A condition called retinal arteriovenous malformations, which pairs up with facial arteriovenous malformations, needs to be differentiated from a condition called Sturge-Weber Syndrome, especially if there are birthmarks on the face or if it’s associated with a form of congenital glaucoma.

Additional conditions to consider during the diagnosis include:

• Inflammatory granuloma related to tuberculosis and sarcoidosis
• Exudative vascular anomalous complex or retinal capillary macroaneurysm
• Perifoveal exudative vascular anomalous complex
• Macroaneurysm
• Congenital retinal macrovessel

What to expect with Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

The future vision of a person with retinal capillary hemangiomas, which are blood vessel growths in the eye, depends on several factors. These include the size and location of the growth, how many there are, and the amount of fluid that leaks from them. Patients with multiple growths have a higher risk of developing new ones, so they need regular check-ups.

Around 25% of these cases may result in permanent loss of vision, and about 20% of patients may experience a decrease in vision quality. The kind of mutations in the VHL gene, which is related to this condition, can affect the vision outcome. People with a specific type of mutation known as truncated VHL proteins tend to have less vision loss compared to those with another type of mutation known as missense mutations. These individuals usually develop more aggressive eye growths with higher rates of complications.

Retinal cavernous hemangiomas, another type of blood vessel growth, usually don’t cause symptoms and don’t worsen with time. In rare cases, patients may experience bleeding into the jelly-like substance inside the eye, which typically resolves on its own. However, similar growths in the brain can lead to severe complications, like seizures, brain bleeding, and even death. Regular brain imaging tests are recommended for early detection and management of this condition.

The general outcome for most people with these retinal growths is good unless they develop complications such as swelling in the central part of the retina, internal eye bleeding or a type of high eye pressure called neovascular glaucoma. Vision loss can occur due to abnormal blood vessel connections between arteries and veins causing pressure damage to the optic nerve, which transmits images to the brain. If these abnormal blood vessel connections occur in the brain, around the area where the optic nerves cross, they can have poor outcomes after surgical removal.

Possible Complications When Diagnosed with Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

Retinal capillary hemangiomas can often lead to the formation of an epiretinal membrane and subretinal fluid, as the most common complications. Impaired vision in around half of those affected is majorly caused by retinal exudation and proliferative gliosis. In a review of 18 patients’ cases, it was found that eyes with retinal detachment due to contraction or exudation had poor eyesight later on. Numerous factors lead to vision loss in cases of retinal capillary hemangioma including retinal exudation, fibrovascular proliferation, rhegmatogenous or tractional retinal detachment, macular hole, and glaucoma.

Common Complications of Retinal Capillary Hemangiomas:

• Formation of an epiretinal membrane
• Subretinal fluid
• Retinal exudation
• Proliferative gliosis
• Retinal detachment
• Macular hole
• Glaucoma

Meanwhile, retinal cavernous hemangiomas typically do not worsen and have fewer complications, with vitreous hemorrhage being the most frequent. Exudation is rare, but fibroglial tissue may grow on the tumor surface, and this can interfere with vision if the tumor is located at the macula.

Potential Complications of Retinal Cavernous Hemangiomas:

• Vitreous hemorrhage
• Fibroglial tissue development on the tumor surface

Retinal arteriovenous malformations, seen in cases of Wyburn-Mason syndrome, can lead to various complications such as macular edema, retinal ischemia, retinal vein occlusion, vitreous hemorrhage, and neovascular glaucoma. If such arteriovenous malformations appear in the maxillary and mandibular region, they can cause heavy bleeding during dental or maxillofacial surgical procedures.

Possible Complications of Retinal Arteriovenous Malformations:

• Macular edema
• Retinal ischemia
• Retinal vein occlusion
• Vitreous hemorrhage
• Neovascular glaucoma

Preventing Retinal Vascular Anomalies (VHL, Cavernous Hemangioma, Wyburn-Mason)

It’s very important to spot changes in the blood vessels in the retina of the eye early and keep a regular check on them to prevent serious problems. People who either have a known VHL mutation (changes in a specific gene) or a family history of this condition should be checked every year for any changes in blood pressure, vision, hearing, and brain function, starting from one year old. Tests for a specific substance found in urine or blood, called metanephrines, should be done every year starting at age 5 to look out for a certain type of tumor called pheochromocytomas.

Starting from 16 years old, it’s suggested to have a brain and spine MRI and an ultrasound of the abdomen every two years. If a person starts showing symptoms, an MRI of the inner part of the ear can help find a type of tumor called an endolymphatic sac tumor.

Examinations of the eye should be done every 6 to 12 months until the age of 30, from then on they should be yearly. If these eye tumors, known as cavernous hemangiomas of the retina, run in the family, they usually affect both eyes and can be related to similar skin and brain conditions. Therefore, it would be necessary for at-risk family members to be checked for brain tumors using a brain MRI.