Retinoblastoma

What is retinoblastoma?

Retinoblastoma is a cancer of the eye. It occurs most often in young children, usually before age 3. It rarely develops in children older than 5. 

Retinoblastoma forms in the retina, a thin layer of nerve tissue in the back of the eye. Retina cells detect light and color. Unilateral retinoblastoma affects 1 eye. It is the most common form of the disease. Bilateral retinoblastoma affects both eyes.

Symptoms of retinoblastoma

A doctor may find retinoblastoma during a routine eye exam. More often, a parent or relative notices that a child’s eye looks different from normal. Some retinoblastoma symptoms are common to other eye problems. It is important to see a children’s eye doctor for evaluation.

Symptoms of retinoblastoma include:

• A white glow in the pupil: This may be easier to see in a photo. The pupil is the black center part of the eye. In a child with retinoblastoma, a camera flash can cause a white pupil reflex (cat’s eye) instead of a red reflex (red eye). This is known as leukocoria. It is the most common sign of retinoblastoma.
• A “lazy eye”: 1 eye may turn outward or inward when the child looks straight ahead. This is known as strabismus. It is the second most common sign of retinoblastoma.
• Vision problems
• Red or irritated eyes
• Eye pain: Added pressure may cause eye pain as the tumor grows. This may also cause nausea and vomiting.

Risk factors for retinoblastoma

Retinoblastoma usually comes from a mutation in the RB1 gene. This mutation causes cells to grow and divide abnormally.

There are 2 types of retinoblastoma: non-hereditary (sporadic) and hereditary.

Non-hereditary retinoblastoma

The most common form of retinoblastoma is sporadic, or non-hereditary:

• It is not passed down in families.
• It is caused by a change in the RB1 gene in a single cell in the retina of 1 eye. These cells divide and form a tumor.
• Most patients with retinoblastoma in 1 eye (unilateral) have this form of the disease.

Hereditary retinoblastoma

Retinoblastoma is hereditary in about 25–30% of patients.

• This form is caused by a change in the RB1 gene in every cell in the body.
• About 10–15% of patients with retinoblastoma in 1 eye (unilateral) and all patients with disease in both eyes (bilateral) have the hereditary form.
• Children with hereditary retinoblastoma are at higher risk for other cancers.

Genetic testing is important in retinoblastoma. Both forms of retinoblastoma can affect risk of future cancers.

Learn more about hereditary retinoblastoma.

Diagnosis of retinoblastoma

If a child shows signs of retinoblastoma, they should see a pediatric ophthalmologist, or children’s eye doctor. The eye doctor will screen your child to see if more tests are needed.

Eye exam under anesthesia

An eye exam under anesthesia (EUA) helps doctors diagnose retinoblastoma. In this test, a doctor looks closely at the eye using a magnifying lens after the eyes are dilated. A special camera takes digital pictures of the eye and tumor. The child is asleep during this test.

A biopsy is not used to diagnose retinoblastoma because it could cause cancer cells to spread.

Other tests used to help diagnose retinoblastoma include:

• A physical exam and health history
• Blood test to find out if the child has an inherited form of retinoblastoma
• Imaging tests such as ultrasound or magnetic resonance imaging (MRI)

If the disease seems to have spread beyond the eye, doctors will take samples of bone marrow and cerebrospinal fluid. They may perform other imaging tests to look at the brain and spinal cord.

Eye tumors are classified from Group A to Group E. 

The group is based on tumor size, location, and extent of spread inside the eye. If both eyes are affected, each eye is classed separately.

Group A tumors are small and away from the center of vision. Patients with Group A tumors have a good chance of maintaining normal eye function and vision during and after treatment.

Group E tumors are large and have broken apart inside the eye (vitreous seeding). These tumors are more likely to spread outside the eye. Children with Group E tumors likely have reduced or complete loss of vision. They have a high risk of losing the eye, even with treatment.

The stage of cancer refers to whether it has spread outside the eye. Stages 1 and 2 mean the tumor is only in the eye. Stages 3 and 4 mean the tumor has spread to tissues around the eye or to other parts of the body.

Treatment of retinoblastoma

Treatment of retinoblastoma depends on whether the tumor affects 1 eye or both eyes, the extent of disease, and whether the tumor has spread. Doctors also consider:

• The child’s age
• Family history and genetics
• Whether the tumor affects the center of vision
• Whether the tumor has broken apart into vitreous seeds
• Number of tumors

Treatments may include:

• Surgery
• Focal therapy
• Chemotherapy
• Radiation therapy

Usually, doctors use a combination of treatments. Before starting therapy, you should discuss the treatment plan with your child’s doctors to understand the short- and long-term risks and benefits.

Treatments for localized retinoblastoma

Chemotherapy

Chemotherapy, or chemo, uses strong medicines to kill cancer cells or stop them from growing. Chemo might use 1 medicine or more than 1 medicine.

Chemotherapy for retinoblastoma might include:

• Vincristine
• Carboplatin
• Etoposide
• Topotecan
• Cyclophosphamide
• Doxorubicin
• Melphalan

Chemotherapy alone cannot cure retinoblastoma. It is used along with other treatments.

Chemo for retinoblastoma might be given:

• Through the vein (intravenous)
• Near the eye (periocular)
• Directly in the eye (intravitreal)
• Through the ophthalmic artery, either by ophthalmic artery chemosurgery (OAC) or intra-arterial chemotherapy

OAC should only be done by a medical team with experience in this technique to lower the risk of damage to the eye.

Focal therapy

Focal therapy treats the tumor directly. If the tumor is very small, focal therapy alone may be enough to treat the cancer. It is done while the child is asleep under anesthesia. There are 3 types:

• Laser therapy: This therapy uses high intensity light or heat to kill cancer cells.
• Cryotherapy: This therapy uses freezing and thawing to shrink the tumor and kill the cancer cells.
• Plaque radiotherapy (brachytherapy): Surgeons place a small device made of radioactive material on the eye directly above the tumor. The device remains in place for a few days. Surgery with anesthesia is required to place and remove the device. After the device is removed, no radioactivity is left in the eye.

Surgery

Surgery is used to remove the eye if necessary. This surgery is called enucleation.

• Unilateral retinoblastoma: Most patients (70–90%) with only 1 affected eye do not need more treatment after the eye is removed. If the tumor has spread into tissues around the eye or eye socket, tests including bone marrow aspirates and biopsies and lumbar puncture are used to stage the disease. In these cases, patients need chemo because of a higher risk that the tumor will spread.
• Bilateral retinoblastoma: If 1 eye is removed, treatment focuses on saving the other eye. Doctors also consider the risk of tumor spread.

Radiation therapy

Radiation therapy may be used for advanced retinoblastoma. External beam radiation uses a machine to deliver radiation to the entire eye. This is the most aggressive treatment for retinoblastoma. It is used to help the child keep their vision and to prevent the cancer from spreading. Because of the risk of long-term effects and second cancers, radiation is usually only used for patients whose cancer:

• Has spread beyond the eye
• Has not responded to other therapies
• Has come back

Treatments for metastatic retinoblastoma

Very rarely, retinoblastoma spreads to the brain or cerebrospinal fluid. It can also spread to the liver, bones, bone marrow, or lymph nodes. Intensive chemo followed by autologous bone marrow transplant may be needed in these cases. Some patients may also need radiation therapy.

Prognosis for retinoblastoma

Most children with retinoblastoma can be cured. The main factor that affects survival is whether the tumor has spread beyond the eye. If it is only in the eye, the chance for survival is excellent. If it has spread to other parts of the body, the cancer becomes harder to treat.

Other factors that can affect recovery include:

• Whether the cancer is in 1 or both eyes
• Whether it is hereditary or non-hereditary
• Tumor size and location
• Number of smaller tumors, or vitreous seeds
• Patient age
• Tumor’s effect on vision or eye function

The survival rate for children with cancer only in the eye is higher than 95% with treatment.

The survival rate for cancer that has spread to the eye socket, lymph nodes, bone marrow, bones, or liver is about 80% with intensive chemotherapy, autologous stem cell rescue, and radiation therapy.

The survival rate for cancer that has spread to the brain or cerebrospinal fluid at the time of diagnosis is less than 10%.

Support for retinoblastoma patients

Monitor for recurrence

Children will need regular eye exams under anesthesia throughout treatment and for a period after treatment. Recurrence can be managed with focal therapy if caught early. The medical team will suggest specific tests and their schedule.

Promote eye health

Lifelong follow-up care for eye health is important for all retinoblastoma survivors. Eye exams by an ophthalmologist every 6–12 months (based on age) are a part of routine health care. Protective glasses help prevent eye injury.

Patients with eyesight loss may need glasses or other vision assistance. A low-vision specialist can help patients who have significant eyesight loss. Early introduction to braille also may be helpful.

Tips for good eye health:

• Get regular eye exams.
• Wear sunglasses with UV protection outdoors.
• Wear protective glasses, especially when playing sports, doing yard work, or using machines or chemicals.
• Avoid objects and activities that put eyes at risk, such as sharp toys or fireworks.
• Seek medical care for any eye injury or infection.

Artificial eye after surgery

When an eye is removed by surgery (enucleation), the surgeon will replace it with an orbital implant. After the eye socket heals, the child can be fitted for an artificial eye. This prosthetic eye is custom-made for the patient to look and feel as natural as possible. Most children who need eye removal adapt to vision changes before surgery. Children with a prosthetic eye can do their normal activities, including sports and swimming. Learn more about living with 1 eye.

Proper care of the prosthetic eye is important. The prosthetic is adjusted as the child grows, usually every 6 months. A patient with a prosthetic should have an eye exam every 6–12 months. These visits involve cleaning the prosthetic eye, making sure the fit is correct, and addressing any problems.

Eye problems after retinoblastoma treatment

Common eye problems after retinoblastoma include:

• Dry eye
• Lid lag or change in eyelid appearance
• Issues with the prosthetic eye or implant
• Low vision in eyes that have been treated
• Late effects of chemotherapy or radiation therapy

Patients treated with external beam radiation therapy are at risk for certain late effects of therapy. These may include:

• Cataracts
• Dry eyes
• Watery eyes
• Swollen cornea
• Eye and eye socket do not develop as they should
• Eye sinks within the eye socket
• Higher risk for second cancers

Hereditary retinoblastoma and future cancer risk

Hereditary retinoblastoma survivors have a greater risk of other cancers later in life. Young patients have routine brain MRIs until age 5 to screen for pineoblastoma. After age 5, there is no standard guideline on screening for second cancers. Your child should tell their primary health care providers about their medical history.

Life after cancer

All cancer survivors should adopt healthy lifestyle habits. These include getting regular medical checkups by a primary care physician. Survivors who were treated with systemic chemotherapy or radiation should be monitored for late effects of therapy.

Your child’s care team should give you a survivorship care plan after treatment ends. This report will include needed tests and tips for a healthful lifestyle.

Questions to ask your care team

• Is my child’s retinoblastoma hereditary or non-hereditary?
  
• What are our treatment options?
• What are the possible side effects of each treatment?
• What can be done to manage side effects?
• Will my child need to be in the hospital for treatment?
• Where is the treatment available? Is it close to home or will we have to travel?