- Facts on Retinoblastoma (Eye Cancer)
- What Is Retinoblastoma and What Are the Risk Factors?
- What Are the Signs and Symptoms of Retinoblastoma?
- How Is Retinoblastoma Diagnosed?
- What Are the Stages of Retinoblastoma?
- What Are the Treatment Options for Retinoblastoma?
- What Are the Treatments by Type and Stage for Retinoblastoma?
- What Is the Prognosis for Retinoblastoma?
- Retinoblastoma (Eye Cancer) Topic Guide
Facts on Retinoblastoma (Eye Cancer)
- Retinoblastoma is a disease in which malignant (cancer) cells form in the tissues of the retina.
- Retinoblastoma occurs in heritable and nonheritable forms.
- Treatment for both forms of retinoblastoma should include genetic counseling.
- Children with a family history of retinoblastoma should have eye exams to check for retinoblastoma.
- A child who has heritable retinoblastoma has an increased risk of trilateral retinoblastoma and other cancers.
- Signs and symptoms of retinoblastoma include "white pupil" and eye pain or redness.
- Tests that examine the retina are used to detect (find) and diagnose retinoblastoma.
- Certain factors affect prognosis (chance of recovery) and treatment options.
What Is Retinoblastoma and What Are the Risk Factors?
Retinoblastoma is a disease in which malignant (cancer) cells form in the tissues of the retina.
The retina is the nerve tissue that lines the inside of the back of the eye. The retina senses light and sends images to the brain by way of the optic nerve.
Although retinoblastoma may occur at any age, it occurs most often in children younger than 2 years. The cancer may be in one eye (unilateral) or in both eyes (bilateral). Retinoblastoma rarely spreads from the eye to nearby tissue or other parts of the body.
Cavitary retinoblastoma is a rare type of retinoblastoma in which cavities (hollow spaces) form within the tumor.
Retinoblastoma occurs in heritable and nonheritable forms.
A child is thought to have the heritable form of retinoblastoma when one of the following is true:
- There is a family history of retinoblastoma.
- There is a certain mutation (change) in the RB1 gene. The mutation in the RB1 gene may be passed from the parent to the child or it may occur in the egg or sperm before conception or soon after conception.
- There is more than one tumor in the eye or there is a tumor in both eyes.
- There is a tumor in one eye and the child is younger than 1 year.
After heritable retinoblastoma has been diagnosed and treated, new tumors may continue to form for a few years. Regular eye exams to check for new tumors are usually done every 2 to 4 months for at least 28 months. Nonheritable retinoblastoma is retinoblastoma that is not the heritable form. Most cases of retinoblastoma are the nonheritable form.
Treatment for both forms of retinoblastoma should include genetic counseling. Parents should receive genetic counseling (a discussion with a trained professional about the risk of genetic diseases) to discuss genetic testing to check for a mutation (change) in the RB1 gene. Genetic counseling also includes a discussion of the risk of retinoblastoma for the child and the child's brothers or sisters.
Children with a family history of retinoblastoma should have eye exams to check for retinoblastoma.
A child with a family history of retinoblastoma should have regular eye exams beginning early in life to check for retinoblastoma, unless it is known that the child does not have the RB1 gene change. Early diagnosis of retinoblastoma may mean the child will need less intense treatment. Brothers or sisters of a child with retinoblastoma should have regular eye exams by an ophthalmologist until age 3 to 5 years, unless it is known that the brother or sister does not have the RB1 gene change.
A child who has heritable retinoblastoma has an increased risk of trilateral retinoblastoma and other cancers.
A child with heritable retinoblastoma has an increased risk of a pineal tumor in the brain. When retinoblastoma and a brain tumor occur at the same time, it is called trilateral retinoblastoma. The brain tumor is usually diagnosed between 20 and 36 months of age. Regular screening using MRI (magnetic resonance imaging) may be done for a child thought to have heritable retinoblastoma or for a child with retinoblastoma in one eye and a family history of the disease. CT (computerized tomography) scans are usually not used for routine screening in order to avoid exposing the child to ionizing radiation.
What Are the Signs and Symptoms of Retinoblastoma?
Signs and symptoms of retinoblastoma include "white pupil" and eye pain or redness.
These and other signs and symptoms may be caused by retinoblastoma or by other conditions. Check with a doctor if your child has any of the following:
- Pupil of the eye appears white instead of red when light shines into it. This may be seen in flash photographs of the child.
- Eyes appear to be looking in different directions (lazy eye).
- Pain or redness in the eye.
- Infection around the eye.
- Eyeball is larger than normal.
- Colored part of the eye and pupil look cloudy.
How Is Retinoblastoma Diagnosed?
Tests that examine the retina are used to detect (find) and diagnose retinoblastoma.
The following tests and procedures may be used:
Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken. The doctor will ask if there is a family history of retinoblastoma.
Eye exam with dilated pupil: An exam of the eye in which the pupil is dilated (opened wider) with medicated eye drops to allow the doctor to look through the lens and pupil to the retina. The inside of the eye, including the retina and the optic nerve, is examined with a light. Depending on the age of the child, this exam may be done under anesthesia.
There are several types of eye exams that are done with the pupil dilated:
Ophthalmoscopy: An exam of the inside of the back of the eye to check the retina and optic nerve using a small magnifying lens and a light.
Slit-lamp biomicroscopy: An exam of the inside of the eye to check the retina, optic nerve, and other parts of the eye using a strong beam of light and a microscope.
Fluorescein angiography: A procedure to look at blood vessels and the flow of blood inside the eye. An orange fluorescent dye called fluorescein is injected into a blood vessel in the arm and goes into the bloodstream. As the dye travels through blood vessels of the eye, a special camera takes pictures of the retina and choroid to find any blood vessels that are blocked or leaking.
RB1 gene test: A laboratory test in which a sample of blood or tissue is tested for a change in the RB1 gene. Ultrasound exam of the eye: A procedure in which high-energy sound waves (ultrasound) are bounced off the internal tissues of the eye to make echoes. Eye drops are used to numb the eye and a small probe that sends and receives sound waves is placed gently on the surface of the eye. The echoes make a picture of the inside of the eye and the distance from the cornea to the retina is measured. The picture, called a sonogram, shows on the screen of the ultrasound monitor. The picture can be printed to be looked at later. MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the eye. This procedure is also called nuclear magnetic resonance imaging (NMRI).
CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the eye, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
Retinoblastoma can usually be diagnosed without a biopsy. When retinoblastoma is in one eye, it sometimes forms in the other eye. Exams of the unaffected eye are done until it is known if the retinoblastoma is the heritable form.
What Are the Stages of Retinoblastoma?
The International Retinoblastoma Staging System (IRSS) may be used for staging retinoblastoma. There are several staging systems for retinoblastoma. The IRSS stages are based on how much cancer remains after surgery to remove the tumor and whether the cancer has spread.
The tumor is in the eye only. The eye has not been removed and the tumor was treated without surgery.
The tumor is in the eye only. The eye has been removed and no cancer cells remain.
The tumor is in the eye only. The eye has been removed and there are cancer cells left that can be seen only with a microscope.
Stage III is divided into stages IIIa and IIIb:
- In stage IIIa, cancer has spread from the eye to tissues around the eye socket.
- In stage IIIb, cancer has spread from the eye to lymph nodes near the ear or in the neck.
Stage IV is divided into stages IVa and IVb:
- In stage IVa, cancer has spread to the blood but not to the brain or spinal cord. One or more tumors may have spread to other parts of the body such as the bone or liver.
- In stage IVb, cancer has spread to the brain or spinal cord. It also may have spread to other parts of the body.
There are three ways that cancer spreads in the body. Cancer can spread through tissue, the lymph system, and the blood:
- Tissue. The cancer spreads from where it began by growing into nearby areas.
- Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
- Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.
Cancer may spread from where it began to other parts of the body.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if retinoblastoma spreads to the bone, the cancer cells in the bone are actually retinoblastoma cells. The disease is metastatic retinoblastoma, not bone cancer.
Treatment for retinoblastoma depends on whether it is intraocular (within the eye) or extraocular (outside the eye).
In intraocular retinoblastoma, cancer is found in one or both eyes and may be in the retina only or may also be in other parts of the eye such as the choroid, ciliary body, or part of the optic nerve. Cancer has not spread to tissues around the outside of the eye or to other parts of the body.
Extraocular retinoblastoma (metastatic)
In extraocular retinoblastoma, cancer has spread beyond the eye. It may be found in tissues around the eye (orbital retinoblastoma) or it may have spread to the central nervous system (brain and spinal cord) or to other parts of the body such as the liver, bones, bone marrow, or lymph nodes.
Progressive and Recurrent Retinoblastoma
Progressive retinoblastoma is retinoblastoma that does not respond to treatment. Instead, the cancer grows, spreads, or gets worse.
Recurrent retinoblastoma is cancer that has recurred (come back) after it has been treated. The cancer may recur in the eye, in tissues around the eye, or in other places in the body.
What Are the Treatment Options for Retinoblastoma?
Different types of treatment are available for patients with retinoblastoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.
Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.
Children with retinoblastoma should have their treatment planned by a team of health care providers who are experts in treating cancer in children.
The goals of treatment are to save the child's life, to save vision and the eye, and to prevent serious side effects. Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other health care providers who are experts in treating children with eye cancer and who specialize in certain areas of medicine. These may include a pediatric ophthalmologist (children's eye doctor) who has a lot of experience in treating retinoblastoma and the following specialists:
- Pediatric surgeon.
- Radiation oncologist.
- Pediatric nurse specialist.
- Rehabilitation specialist.
- Social worker.
- Geneticist or genetic counselor.
Treatment for retinoblastoma may cause side effects. Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Late effects of treatment for retinoblastoma may include the following:
- Physical problems such as seeing or hearing problems or, if the eye is removed, a change in the shape and size of the bone around the eye.
- Changes in mood, feelings, thinking, learning, or memory.
- Second cancers (new types of cancer), such as lung and bladder cancers, osteosarcoma, soft tissue sarcoma, or melanoma.
- The following risk factors may increase the risk of having another cancer:
- Having the heritable form of retinoblastoma.
- Past treatment with radiation therapy, especially before age 1 year.
- Having already had a previous second cancer.
It is important to talk with your child's doctors about the effects cancer treatment can have on your child. Regular follow-up by health professionals who are experts in diagnosing and treating late effects is important.
Six types of standard treatment are used:
Cryotherapy is a treatment that uses an instrument to freeze and destroy abnormal tissue. This type of treatment is also called cryosurgery.
Thermotherapy is the use of heat to destroy cancer cells. Thermotherapy may be given using a laser beam aimed through the dilated pupil or onto the outside of the eyeball. Thermotherapy may be used alone for small tumors or combined with chemotherapy for larger tumors. This treatment is a type of laser therapy.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. The way the chemotherapy is given depends on the stage of the cancer and where the cancer is in the body.
There are different types of chemotherapy:
Systemic chemotherapy: When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body. Systemic chemotherapy is given to shrink the tumor (chemoreduction) and avoid surgery to remove the eye. After chemoreduction, other treatments may include radiation therapy, cryotherapy, laser therapy, or regional chemotherapy.
Systemic chemotherapy may also be given to kill any cancer cells that are left after the initial treatment or to patients with retinoblastoma that occurs outside the eye. Treatment given after the initial treatment, to lower the risk that the cancer will come back, is called adjuvant therapy.
Regional chemotherapy: When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ (such as the eye), or a body cavity, the drugs mainly affect cancer cells in those areas. Several types of regional chemotherapy are used to treat retinoblastoma.
Ophthalmic artery infusion chemotherapy: Ophthalmic artery infusion chemotherapy carries anticancer drugs directly to the eye. A catheter is put into an artery that leads to the eye and the anticancer drug is given through the catheter. After the drug is given, a small balloon may be inserted into the artery to block it and keep most of the anticancer drug trapped near the tumor. This type of chemotherapy may be given as the initial treatment when the tumor is in the eye only or when the tumor has not responded to other types of treatment. Ophthalmic artery infusion chemotherapy is given at special retinoblastoma treatment centers.
Intravitreal chemotherapy: Intravitreal chemotherapy is the injection of anticancer drugs directly into the vitreous humor (jelly-like substance) inside of the eye. It is used to treat cancer that has spread to the vitreous humor and has not responded to treatment or has come back after treatment.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:
External-beam radiation therapy uses a machine outside the body to send radiation toward the cancer. Certain ways of giving radiation therapy can help keep radiation from damaging nearby healthy tissue.
These types of radiation therapy include the following:
Intensity-modulated radiation therapy (IMRT): IMRT is a type of 3-dimensional (3-D) external radiation therapy that uses a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of different intensities (strengths) are aimed at the tumor from many angles.
Proton-beam radiation therapy: Proton-beam therapy is a type of high-energy, external radiation therapy. A radiation therapy machine aims streams of protons (tiny, invisible, positively-charged particles) at the cancer cells to kill them. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. Certain ways of giving radiation therapy can help keep radiation from damaging nearby healthy tissue.
This type of internal radiation therapy may include the following:
Plaque radiotherapy: Radioactive seeds are attached to one side of a disk, called a plaque, and placed directly on the outside wall of the eye near the tumor. The side of the plaque with the seeds on it faces the eyeball, aiming radiation at the tumor. The plaque helps protect other nearby tissue from the radiation.
The way the radiation therapy is given depends on the type and stage of the cancer being treated and how the cancer responded to other treatments. External and internal radiation therapy are used to treat retinoblastoma.
High-dose chemotherapy with stem cell rescue
High-dose chemotherapy with stem cell rescue is a way of giving high doses of chemotherapy and replacing blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Enucleation is surgery to remove the eye and part of the optic nerve. A sample of the eye tissue that is removed will be checked under a microscope to see if there are any signs that the cancer is likely to spread to other parts of the body. This should be done by an experienced pathologist, who is familiar with retinoblastoma and other diseases of the eye. Enucleation is done if there is little or no chance that vision can be saved and when the tumor is large, did not respond to treatment, or comes back after treatment. The patient will be fitted for an artificial eye.
Close follow-up is needed for 2 years or more to check for signs of recurrence in the area around the affected eye and to check the other eye.
New types of treatment are being tested in clinical trials. This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI website.
Targeted therapy is a type of treatment that uses drugs or other substances to attack cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. Targeted therapy is being studied for the treatment of retinoblastoma that has recurred (come back).
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated.
Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
What Are the Treatments by Type and Stage for Retinoblastoma?
Treatment of Unilateral, Bilateral, and Cavitary Retinoblastoma
If it is likely that the eye can be saved, treatment may include the following:
- Systemic chemotherapy or ophthalmic artery infusion chemotherapy, with or without intravitreal chemotherapy, to shrink the tumor.
This may be followed by one or more of the following:
- Plaque radiotherapy.
- External-beam radiation therapy for bilateral intraocular retinoblastoma that does not respond to other treatments.
If the tumor is large and it is not likely that the eye can be saved, treatment may include the following:
- Surgery (enucleation). After surgery, systemic chemotherapy may be given to lower the risk that the cancer will spread to other parts of the body.
When retinoblastoma is in both eyes, the treatment for each eye may be different, depending on the size of the tumor and whether it is likely that the eye can be saved. The dose of systemic chemotherapy is usually based on the eye that has more cancer.
Treatment for cavitary retinoblastoma, a type of intraocular retinoblastoma, may include the following:
- Systemic chemotherapy or ophthalmic artery infusion chemotherapy.
Treatment of Extraocular Retinoblastoma
Treatment for extraocular retinoblastoma that has spread to the area around the eye may include the following:
- Systemic chemotherapy and external-beam radiation therapy.
- Systemic chemotherapy followed by surgery (enucleation). External-beam radiation therapy and more
- chemotherapy may be given after surgery.
- Treatment for extraocular retinoblastoma that has spread to the brain may include the following:
- Systemic or intrathecal chemotherapy.
- External-beam radiation therapy to the brain and spinal cord.
- Chemotherapy followed by high-dose chemotherapy with stem cell rescue.
It is not clear whether treatment with chemotherapy, radiation therapy, or high-dose chemotherapy with stem cell rescue helps patients with extraocular retinoblastoma live longer.
For trilateral retinoblastoma, treatment may include the following:
Systemic chemotherapy followed by high-dose chemotherapy with stem cell rescue. Systemic chemotherapy followed by surgery and external-beam radiation therapy.
For retinoblastoma that has spread to other parts of the body, but not the brain, treatment may include the following:
- Chemotherapy followed by high-dose chemotherapy with stem cell rescue and external-beam radiation therapy.
Treatment of Progressive or Recurrent Retinoblastoma
Treatment of progressive or recurrent intraocular retinoblastoma may include the following:
- External-beam radiation therapy or plaque radiotherapy.
- Systemic chemotherapy or ophthalmic artery infusion chemotherapy.
- Intravitreal chemotherapy.
- Surgery (enucleation).
A clinical trial that checks a sample of the patient's tumor for certain gene changes. The type of targeted therapy that will be given to the patient depends on the type of gene change.
Treatment of progressive or recurrent extraocular retinoblastoma may include the following:
Systemic chemotherapy and external-beam radiation therapy for retinoblastoma that comes back after surgery to remove the eye.
Systemic chemotherapy followed by high-dose chemotherapy with stem cell rescue and external-beam radiation therapy.
A clinical trial that checks a sample of the patient's tumor for certain gene changes. The type of targeted therapy that will be given to the patient depends on the type of gene change.
What Is the Prognosis for Retinoblastoma?
Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery) and treatment options depend on the following:
- Whether the cancer is in one or both eyes.
- The size and number of tumors.
- Whether the tumor has spread to the area around the eye, to the brain, or to other parts of the body.
- Whether there are symptoms at the time of diagnosis, for trilateral retinoblastoma.
- The age of the child.
- How likely it is that vision can be saved in one or both eyes.