Retinoblastoma

What is retinoblastoma?

Retinoblastoma is a rare cancer affecting the retina, the thin layer of light- and color-sensing tissue that lines the back of the eye. This tumor typically develops in childhood, almost always before the age of 5 and usually before the child is 2. It can affect one or both eyes.

Retinoblastoma can cause blindness and is life-threatening if it spreads to other parts of the body. Fortunately, thanks to earlier diagnosis and improved treatment, survival rates for children with retinoblastoma are now about 95%.

Causes of retinoblastoma

Most cases of retinoblastoma are caused by a mutation in the RB1 gene, which normally suppresses tumors by regulating cell growth. The mutation allows retinal cells to divide uncontrollably, forming tumors that damage surrounding tissues.

About one-third of cases are hereditary: The gene mutation is either inherited from a parent or occurs while the fetus is developing. The mutated gene is present in every cell of the child’s body, including eggs or sperm, which means it can be passed on to their children.

But most cases are caused by a spontaneous gene mutation in the eye's cells. This won't be passed on to the next generation.

Children with the hereditary form of the disease tend to develop multiple retinoblastomas, usually in both eyes. They're also at risk for tumors of the brain, bone, lungs and other parts of the body. The nonhereditary form of the disease usually affects just one eye and doesn't carry the same risk for other cancers.

Signs & symptoms of retinoblastoma

Retinoblastoma is typically discovered when someone notices that the child’s pupil looks white or pale rather than black. Often this happens when light catches the pupil from a certain direction or a photograph is taken using a flash. Sometimes the problem is detected because the child’s eyes seem to be looking in different directions, a condition called strabismus.

Other signs and symptoms of retinoblastoma include:

• Change in color of the iris (the colored part of the eye)
• Eye pain
• Loss of vision
• Red, sore or swollen eyelid
• Swelling or bulging of the eye

Diagnosis of retinoblastoma

If your child's doctor is concerned about retinoblastoma, you'll be referred to a pediatric ophthalmologist (a doctor who specializes in conditions of the eyes). To check for this problem, the ophthalmologist has to look directly inside the eye, either by using special drops that dilate the pupil or by performing an eye exam with your child under anesthesia.

If a tumor is detected, additional tests are needed to get more information about it. These may include:

• Ultrasound. This painless imaging exam uses high-frequency sound waves to generate images that doctors use to measure the size of the tumor.
• MRI scan. This imaging technique uses magnetic fields and radio waves to produce detailed images, allowing doctors to check for tumors growing in the brain.
• Genetic tests. These are done to identify the gene mutation responsible for the retinoblastoma and to determine whether it’s hereditary (present in cells throughout the body) or only in the tumor cells. The result can help guide treatment decisions. To run the test, we take either a blood sample or buccal smear (gentle scraping of the mouth's lining) from your child. If the test shows hereditary retinoblastoma, the parents will undergo genetic testing, too.

   

Treatment of retinoblastoma

How retinoblastoma is treated depends on several factors, including the tumor's size and location, whether one or both eyes are affected, how the cancer is affecting the child's vision, and whether the cancer has spread beyond the eyes.

Focal therapies

A small tumor may be treated using focal therapy, so-called because either extreme heat or cold is focused directly on the cancer cells. Retinoblastomas located toward the back of the eye are treated with a laser that delivers heat. Those located toward the front of the eye are destroyed by cryotherapy (freezing). In either approach, the treatment is repeated several times to ensure the tumor is completely destroyed.

Chemotherapy

If the tumor is too large to be removed with lasers or cryotherapy, chemotherapy is used. There are several methods of administering chemotherapy.

• Systemic chemotherapy. Drugs to kill the cancer cells are delivered through an intravenous (IV) infusion. This method is systemic because the bloodstream carries the drugs to the entire body. That means it can cause system-wide side effects and damage to healthy tissue in many parts of the body, but it may be appropriate if there are tumors in both eyes or other parts of the body.
• Intra-arterial chemotherapy. This method delivers the chemo drug directly to the eye, allowing use of a more powerful dose with less impact on healthy tissue. A catheter (a thin, flexible tube) is inserted into a small incision in the groin and guided through blood vessels to a tiny artery behind the eye, where the medication is then released. Children are under general anesthesia (completely asleep) during the treatment. Intra-arterial therapy is used to treat retinoblastoma affecting only one eye.
• Intravitreal chemotherapy. The chemo drug is injected into the middle of the eye with a needle. Again, children are under general anesthesia for the procedure. This method is used if the tumor has scattered cancer cells into the vitreous cavity (the space between the lens and the retina) or when other treatments have failed.

All of these chemotherapy methods require several sessions, usually at monthly intervals.

Surgery

Surgical removal of the affected eye may be needed if the retinoblastoma doesn't respond to other treatments or if the chances of saving the eye are too poor to justify exposing the child to chemotherapy and anesthesia.

The operation to remove the eye is called enucleation. During the procedure, the eye is replaced with a ball implant, and the surgeon attaches the ocular muscles to this artificial eye so it can move normally. Then a contact lens-like prosthesis is custom-made to match the color of the remaining eye. The prosthesis is fitted to the implant approximately six weeks after surgery.

Although enucleation may sound frightening, babies and young children typically adapt well to the prosthetic eye.

After the cancerous eye is removed, the tumor is examined to estimate the risk of metastasis (spread of the cancer to other body parts). The risk is higher if the tumor extends into the optic nerve, the choroid (tissue between the white of the eye and the retina) or tissues beyond the eye. Children with increased risk of metastatic disease receive systemic chemotherapy as a precaution.

Radiation therapy

This treatment destroys cancer cells with high doses of radiation. The methods most commonly used are:

• Plaque radiotherapy. A small metal disc (called a plaque) containing tiny radioactive seeds is attached to the eye. The seeds emit radiation that kills the tumor cells. Treatment lasts a few days, after which the plaque is removed.
• External beam radiation therapy (EBRT). Radiation is delivered by a machine that directs high-energy beams at the tumor. Treatments are typically administered daily for several weeks. Compared with plaque radiotherapy, EBRT is less precisely focused and therefore carries a greater risk of damage to healthy tissue.

Follow-up care for retinoblastoma

With treatment, most children survive retinoblastoma, though the outlook is best when the cancer is caught before it spreads. Once treatment is complete, your child will need regular eye exams – monthly at first, then tapering to every six months. After age 9, children need only an annual exam. The aim of these checkups is to detect new or recurring tumors when they are small and easier to treat.

The care team

Through the Pediatric Retinoblastoma Program, patients receive care from a large team that includes ocular oncologists, pediatric oncologists, interventional radiologists, nurse specialists, social workers and other experts. We strive to ensure parents have the knowledge and support they need to achieve the best possible outcomes for their children.