Retinoblastoma

UT Southwestern’s ocular oncology team has extensive training and experience in diagnosing and treating retinoblastoma, a rare eye cancer that commonly occurs in young children.

UT Southwestern provides individualized care using the latest technology to successfully treat retinoblastoma while preserving the eye and vision whenever possible.

What Is Retinoblastoma?

Retinoblastoma is a rare eye cancer that begins in the retina, the light-sensitive layer of tissue lining the inside of the eye. This cancer most commonly affects children under the age of 2. It is rare to see cases in children over age 5.

When it is promptly diagnosed and treated, retinoblastoma is often curable. However, if it is not caught early, this eye cancer can spread to other parts of the body and become life-threatening.

What Are the Types of Retinoblastoma?

There are two types of this eye cancer, based on when and where the genetic mutation occurs.

Hereditary Retinoblastoma

In about 40 percent of children with retinoblastoma, the gene mutation is present in most or all cells in the body, either as a result of inheriting the mutation from a parent or developing the mutation very early in fetal development.

Children with this type of retinoblastoma tend to develop the disease at an earlier age and often develop multiple tumors in both eyes.

Later in life, these individuals can pass on the mutation to their children, and they are at increased risk of developing other types of cancer, including:

• Pineoblastoma, a brain cancer that arises in or around the pineal gland, which usually arises by age 5 or 6.
• Melanoma, an aggressive form of skin cancer usually seen in younger adults
• Osteosarcoma, a type of bone cancer that arises in the teenage years
• Soft tissue sarcomas, cancers of soft tissues such as muscle, which usually appear in the teenage years

Non-Hereditary (Somatic) Retinoblastoma

In about 60 percent of children with retinoblastoma, the gene mutation develops in only one cell of one eye and is not present in any other cells in the body. In most cases, this mutation is thought to arise as a random mistake made by the cell while copying the DNA.

A child who has somatic retinoblastoma develops only one tumor in one eye, is not at increased risk for other cancers, and does not pass on this mutation to their children. Non-hereditary retinoblastoma is often found in slightly older children.

What Are the Signs and Symptoms of Retinoblastoma?

Because retinoblastoma mostly affects infants and small children, symptoms such as pain are rare, and young children rarely complain of vision loss. Retinoblastoma is almost always discovered when the child’s caregiver or pediatrician notices unusual changes in a child’s eye.

The most common first symptom of retinoblastoma is a visible whiteness in the pupil called leukocoria, meaning “white pupil” and sometimes known as “cat's eye reflex.” It is most noticeable in dim light or in photographs taken with a flash.

The second most common symptom of retinoblastoma is the drifting in or out of an eye, a condition called strabismus, or crossed eyes. While retinoblastoma is a rare cause of strabismus, it needs to be ruled out in children presenting with this condition.

Uncommon signs and symptoms of retinoblastoma include:

• A different color in each iris, the colored part of the eye
• A pupil that doesn’t get smaller when exposed to bright light
• Bleeding in the front part of the eye
• Bulging of the eye
• Eye pain
• Redness of the white part of the eye
• Redness, soreness, or swelling of the eyelids
• Vision loss in older children where vision can be measured

Many of these signs and symptoms are more likely to be caused by something other than retinoblastoma, but it’s important for parents to be aware of any unusual symptoms and to make an appointment to see a pediatrician if they have any concerns about their child’s health.

How Is Retinoblastoma Diagnosed?

After performing a thorough medical history, the ocular oncologist will perform an examination while the child is under anesthesia, using a variety of equipment to diagnose retinoblastoma. To diagnose retinoblastoma, we may use:

• Retinal examination: Using an indirect ophthalmoscope, the ocular oncologist will examine the entire retina while the patient’s eyes are dilated. This is a very important part of the diagnostic work-up, as an experienced ocular oncologist can diagnose retinoblastoma simply by looking at the tumor.

• Retinal photography: UT Southwestern and Children’s Medical Center use state-of-the-art retinal fundus cameras to document and measure all retinoblastomas in each eye and monitor their size over time after treatment is administered.
• Ultrasonography: This is a test that uses sound waves to produce detailed images of the inside of the eye and eye socket. This test is critical for measuring the size of tumors and detecting retinal detachment, calcium deposits, tumor seeding, and other features that are important in diagnosing and staging retinoblastoma.
• Optical coherence tomography (OCT): This test uses lightwaves to create a high-resolution image of the retina, which can be very useful in detecting small retinoblastomas.
• Fluorescein angiography: This test involves injecting a nonradioactive fluorescent dye into a vein in the arm or hand, then photographing the retina as the dye passes through the retinal blood vessels to detect changes in their structure or function. It can help to distinguish retinoblastoma from other abnormalities in the eye and assess response to therapy.
• Electroretinogram (ERG): This test is rarely needed but in select patients can be used to assess the health and visual potential of the retina by measuring electrical responses of the light-sensitive retinal cells.
• Magnetic resonance imaging (MRI): This is a test performed in the radiology unit to evaluate the eye, eye sockets, and brain. MRI is very important as an initial baseline examination; it is used periodically thereafter to determine the extent of retinoblastoma and assess response to therapy.
• Genetic testing: Depending on the family history and other circumstances, genetic testing may be recommended to assess for a germline mutation in the RB1 gene to determine if the retinoblastoma is hereditary or non-hereditary.

Biopsies are rarely performed to diagnose this disease, due to the risk of spreading cancer cells.

What Are the Stages of Retinoblastoma?

The International Intraocular Retinoblastoma Classification (IIRC) is the staging system that most ocular oncologists now use. It divides retinoblastomas into five groups based on the extent of the cancer within the eye and on the chances the eye can be saved using current chemotherapy.

Group stages of retinoblastoma are as follows:

• Group A: Small tumors, no more than 3 millimeters (mm) across, confined to the retina and not near important structures of the eye
• Group B: Tumors that are still confined to the retina and larger than 3 mm or close to important structures
• Group C: Tumors with localized spread of tumor clumps or “seeds” into the jellylike vitreous gel or under the retina
• Group D: Tumors with more extensive seeding into the vitreous or under the retina. The retina may have become detached from the back of the eye
• Group E: Tumors that are very large, extend to the front of the eye, cause bleeding or glaucoma (high pressure inside the eye), or have high-risk features that indicate a risk of spread outside of the eye

After retinoblastoma has been diagnosed and staged, UT Southwestern ocular oncologists work with the family to customize a treatment plan for each patient.

How Is Retinoblastoma Treated?

UT Southwestern ocular oncologists use the entire range of leading-edge treatments to cure retinoblastoma. The treatment plan for each patient is individually designed to account for numerous factors, including:

• Tumor number, size, and location
• Tumor seeding, retinal detachment, bleeding, glaucoma, and tissue invasion
• Involvement of one or both eyes
• Spread of the cancer outside of the eye
• The general health of the child
• The family’s preferences

Treatment options include:

Laser Therapy

A laser emits certain wavelengths of light, some of which can be used to destroy retinoblastoma cancer cells. Laser therapy is especially useful for treating small tumors near sensitive structures of the eye.

Cryotherapy

This is a freezing treatment that employs a small probe with a very cold tip to directly kill cancer cells. Cryotherapy is less commonly used than laser therapy but can be useful for treating slightly larger retinoblastoma tumors near the front part of the retina.

Chemotherapy

For many years, chemotherapy has been used to shrink retinoblastomas, but the tumors invariably grow back without further treatment. In the 1990s, research showed that chemotherapy could be successful if followed up by laser or cryotherapy to kill off any remaining cancer cells after tumor shrinkage. Since then, there have been continued improvements in the use of chemotherapy for successfully treating retinoblastoma and avoiding eye removal.

Methods of delivering chemotherapy that are commonly used for retinoblastoma include:

Radiation Therapy

External beam radiation therapy (EBRT), in which a large machine outside the body delivers high-powered beams of radiation, was commonly used for treating retinoblastoma until the 1990s. However, EBRT has been largely replaced by chemotherapy due to the concerns of secondary cancers, arrested bone growth, and other side effects of radiation. Currently, EBRT is used only in very rare circumstances to save certain eyes for which other therapies have failed.

Another form of radiation therapy is called plaque brachytherapy, a surgical procedure in which a small disclike plaque made of gold and carrying tiny radioactive pellets is temporarily attached to the outside of the eye near the tumor. Plaque brachytherapy has fewer side effects than EBRT and can be highly effective for treating select tumors that have not begun to shed tumor seeds and are too large to treat with laser or cryotherapy but small enough to be covered by the plaque.

Enucleation

Despite the availability of advanced treatment options, surgical removal of the eye (enucleation) is still the safest option for some children.

Enucleation is usually recommended when the cancer fills most of the eye, invades the optic nerve or other structures, causes bleeding or high pressure (glaucoma) inside the eye, or otherwise creates a danger of cancer spreading if the eye is not removed.

Enucleation is performed under general anesthesia by an ophthalmic surgeon skilled in performing such procedures in young children. The surgeons will disconnect the eyeball from the muscles that control eye movement and from the optic nerve. They will then insert a ball-shaped implant into the eye socket and attach it to the muscles, so the implant will move with the other eye. Children usually recover quickly from this procedure.

About six weeks after surgery, an ocularist will make a customized prosthesis (artificial eye) to match the color and appearance of the remaining natural eye. The prosthesis is a shell-like device that fits over the eye socket implant that was placed at surgery. The ocularist needs to check and clean the prosthesis periodically and may need to replace the prosthesis every few years, especially as the child grows.

Retinoblastoma Treatment Success Rates

When retinoblastoma is diagnosed and treated promptly, over 95 percent of children with the disease in the United States can be saved. Most children can be successfully treated without removal of the eye, and many retain useful vision.

UT Southwestern pediatric oncologists are highly experienced in treating young children with retinoblastoma, and they work closely with our ocular oncologists to coordinate the care of each patient.