Retinoblastoma

What is retinoblastoma?

Retinoblastoma is a rare cancer of the retina (the innermost layer of the eye, located at the back of the eye, which receives light and images necessary for vision). About 300 children will be diagnosed with retinoblastoma in the United States this year. It accounts for 3 percent of childhood cancers. Nearly all children with retinoblastoma can be cured of the disease if it has been diagnosed early enough, and 90 percent will have normal vision in at least one eye after treatment.

More information about retinoblastoma

• Retinoblastoma is the most common malignancy of the eye in children
• It can affect one eye or both eyes at the same time
• Retinoblastoma is suspected when the child develops whitish discoloration of the pupil of the eye or when the eyes are not aligned.
• Most often there is no parental history of eye cancer in childhood.
• This disease results from specific genetic defects in one of the chromosomes in the cell.
• Retinoblastoma can be hereditary.
• If one parent had retinoblastoma (usually in both eyes as a child) and then passed on the genetic mutation to the child, then the child can develop retinoblastoma and should be monitored closely from birth.
• Retinoblastoma usually occurs in children less than 3 years of age. It is very rare beyond the age of 6.
• Any child can get retinoblastoma regardless of their sex or age.
• Almost 90 percent of children with retinoblastomas are cured. When retinoblastoma spreads beyond the eye, a child usually has a very poor outcome.
• Early detection of retinoblastoma is extremely important.
• In a child with one eye involved, the disease is usually advanced. In this situation, the eye is surgically removed, which results in the loss of the eye and in more than 90 percent of patients, a permanent cure.
• If both eyes are involved, then chemotherapy, consisting of anti-tumor drugs is used first to shrink the tumors in both eyes. Eventually, the eye that is most affected is removed and the other eye may receive radiation treatment.
• Ophthalmologists also treat small tumors if necessary by using laser therapy or cryotherapy.

What causes retinoblastoma?

Retinoblastoma occurs due to mutations in a tumor suppressor gene (called RB1) located on chromosome #13. Two mutations (or gene changes) are necessary to "knock-out" this gene, and cause uncontrolled cell growth. In inherited retinoblastoma (40 percent of the cases), the first mutation is inherited from a parent, while the second occurs during the development of the retina. In sporadic retinoblastoma (60 percent of the cases), both mutations occur during development of the retina. Sporadic means occurs by chance. Alterations in the RB1 gene have also been found in other tumors, including osteosarcoma and breast cancer.

Most children with inherited retinoblastoma have tumors involving both eyes. Consider the following statistics:

• 60 percent to 75 percent of retinoblastoma cases involve one eye (unilateral), and the majority of these are not inherited.
• 25 percent of retinoblastoma cases are bilateral (both eyes) and hereditary (inherited from a parent).
• 15 percent of retinoblastoma cases are unilateral (one eye) and hereditary.

Any individual with a positive family history of retinoblastoma may want to seek genetic counseling to identify the specific risks of passing the gene or disease to their children.

What are the symptoms of retinoblastoma?

The following are the most common symptoms of retinoblastoma. However, each child may experience symptoms differently. Symptoms may include:

• Leukocoria. A white light reflex that occurs at certain angles when a light is shined into the pupil.
• Strabismus (also called wandering eye or lazy-eye). A misalignment of the eyes; when one or both eyes do not appear to be "looking" in the same direction.
• Pain, redness, or swelling around or in the eye(s)
• Poor vision or change in child's vision

Often the symptoms may not appear if the disease is diagnosed early. The symptoms of retinoblastoma may resemble other conditions or medical problems. Always consult your child's doctor for a diagnosis.

How is retinoblastoma diagnosed?

In addition to a complete medical and physical examination, diagnostic procedures for retinoblastoma may include:

• Complete eye examination and medical history
• Funduscopic examination. With the child under anesthesia, the pupils are dilated so the entire retina can be viewed and examined.
• Ultrasound exam of the eye. This is one of the most commonly used tests to confirm diagnosis, using sound waves to create images of tissues. 
• Computed tomography scan (also called a CT or CAT scan). A diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce horizontal, or axial, images (often called slices) of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general X-rays.
• Magnetic resonance imaging (MRI). A diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body without the use of X-rays.
• Lumbar puncture (spinal tap)
• Bone marrow aspiration and biopsy
• Blood tests
• Genetic and/or DNA testing

A diagnosis may be made before symptoms are present. If a family history is positive for retinoblastoma, frequent eye examinations may be necessary at many stages of the child's development to determine the presence of any tumor. When retinoblastoma is diagnosed, tests will be performed to determine the size of the tumor, and if the tumors have spread to the other parts of the body. This is called staging and is an important step toward planning a treatment program.

What are the stages of retinoblastoma?

There are various staging systems that can be used for retinoblastoma. Always consult your child's physician for more information on staging.

The newest staging method is called The International Classification for Intraocular Retinoblastoma and groups tumors into five categories--groups A through E--based on the likelihood of saving the eye.

The more traditional method of staging is the Reese-Ellsworth stages of retinoblastoma (this staging system is only for tumors that have not spread beyond the eye):

• Group I. One or more tumors that are less than 4 disc diameters (DD) in size and are all located at or behind the equator*.
• Group II. Either one or more tumors that are 4 to 10 DD in size located at or behind the equator.
• Group III. Any lesion in front of the equator or one tumor larger than 10 DD behind the equator.
• Group IV. Multiple tumors with some or all greater than 10 DD in size, or any lesions that extend forward to the ora serrata (front edge of the retina).
• Group V. Very large tumors involving more than half of the retina or that have spread into the vitreous (the gelatinous material that fills the eye).

*The "equator" is an imaginary line that divides the eye into two equal parts: a front half and a back half.

Treatment for retinoblastoma

Specific treatment for retinoblastoma will be determined by your child's doctor based on:

• Your child's age, health, and medical history
• Extent of the disease
• Your child's tolerance for specific medications, procedures, or therapies
• Expectations for the course of the disease
• Your opinion or preference

The primary goal of treatment is to remove the tumor and prevent metastasis (spreading) of the cancer to other parts of the body.

Treatment may include one or more of the following:

• Enucleation (surgical removal of the eye or eyes involved with the tumor)
• Chemotherapy - given either through the child's vein (intravenous, or IV) or directly into the artery behind the eye (intra-arterial, or IA)
• Radiation therapy
• Laser therapy or photocoagulation
• Cryotherapy (uses a freezing process to destroy the tumor)

Long-term outlook for a child with retinoblastoma

Prognosis greatly depends on the following:

• The extent of the disease
• The size and location of the tumor
• Presence or absence of metastasis
• The tumor's response to therapy
• The age and overall health of your child
• Your child's tolerance of specific medications, procedures, or therapies
• New developments in treatment

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Every child is unique and treatment and prognosis is structured around the child's needs. Prompt medical attention and aggressive therapy are important for the best prognosis.

Continuous follow-up care is essential for a child diagnosed with retinoblastoma. In hereditary retinoblastoma, new tumors may form in either eye until the child is 3 to 4 years old. Children will need very close follow-up by an ophthalmologist. Children with hereditary retinoblastoma and those treated with some chemotherapies, radiation therapies, and some other therapies, are at higher risk for new cancers later in life and should have regular medical and eye exams.