What is retinoblastoma?

Retinoblastoma is a rare cancer of the eye, which typically develops in early childhood, before the age of 5. Each year 250-350 children in the US are diagnosed with retinoblastoma. In this disease, malignant (cancerous) cells form in the retina, the specialized nerve tissue lining the back of the eye; this tissue detects light and color and sends images to the brain via the optic nerve. Two-thirds of children with retinoblastoma develop a tumor in only one eye (unilateral). The other third develop cancer in both eyes.


What causes retinoblastoma?

Every cell in the body contains a gene called RB1, which provides instructions for making a protein called pRB. This protein acts as a tumor suppressor, which means that it regulates cell growth and keeps cells from dividing too quickly or in an uncontrolled way. Children who develop retinoblastoma have one or more mutations in the RB1 gene in cells in the retina. Cells that contain a mutated gene are unable to produce functional pRB protein, and they therefore divide in an unregulated manner, forming a tumor. In a small percentage of children with retinoblastoma a larger section of genetic material is missing, and the chromosomal changes involve several genes in addition to RB1. Affected children usually also have intellectual disability, slow growth, and distinctive facial features (such as prominent eyebrows, a short nose with a broad nasal bridge, and ear abnormalities).


What is the difference between heritable and non-heritable retinoblastoma?

Retinoblastoma that occurs in people with no history of the disorder in their family is called non-germinal or non-heritable retinoblastoma. Children with this form of retinoblastoma are born with two normal copies of the RB1 gene. Then, usually in early childhood, both copies of the gene in retinal cells acquire mutations. In non-heritable retinoblastoma the RB1 mutations occur only in the eye, and the disease cannot be passed on to the patient’s children. Two-thirds of cases of retinoblastoma are this non-heritable form. When retinoblastoma is associated with a gene mutation that occurs in all of the body's cells, it is known as heritable or germinal retinoblastoma. The mutation in the RB1 gene may be passed from a parent to child or it may occur in the egg or sperm before conception or soon after conception. Children with heritable or germinal retinoblastoma usually have a family history of the disease. They are also at an increased risk of several types of cancer that develop in tissues outside the eye, including cancer of the pineal gland in the brain (pinealoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues such as muscle, and the aggressive form of skin cancer called melanoma.


What are the symptoms of retinoblastoma?

The most common first sign of retinoblastoma is a visible whiteness in the pupil called "cat's eye reflex" or leukocoria. This unusual whiteness is particularly noticeable in photographs taken with a flash. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus); persistent eye pain, redness, or irritation; and blindness or poor vision in the affected eye(s).


How is retinoblastoma diagnosed?

Ophthalmologists use a number of tests to examine the retina to diagnose retinoblastoma. These include one or more eye exams performed when the pupil is dilated (opened wider than normal) with medicated eye drops, which enables the doctor to look through the lens and pupil to the retina and use a light to examine the inside of the eye, the retina, and the optic nerve. Depending on the age of the child, this exam may be done under anesthesia.

  • Ophthalmoscopy: An exam of the inside of the eye using a magnifying lens and light.
  • Slit-lamp biomicroscopy: An exam of the inside of the eye using a strong beam of light and a microscope.
  • Fluorescein angiography: A procedure looking at the blood vessels and the flow of blood inside the eye.

Ophthalmologists use a specialized test of blood or tissue in a child suspected of having retinoblastoma to detect mutations in the mRB1 gene.

Ophthalmologists may use one or more imaging tests including:

  • Ultrasound, which uses high-energy sound waves to create a picture (sonogram) of the inside of the eye
  • MRI (magnetic resonance imaging) or nuclear magnetic resonance imaging (NMRI), which uses a magnet and radio waves to make a series of detailed pictures of the inside of the eye
  • Computed tomography (CT) scan, which takes x-ray pictures of the inside of the head and neck as the child slides through the CT scanner while lying on a table.


How is retinoblastoma treated?

Cancer that is entirely within the eye and has not spread is called intraocular retinoblastoma. Most children are diagnosed when the disease is in this localized stage, and 90% are cured. When the tumor has spread beyond the eye and into the tissues surrounding it or to another part of the body, it is called extraocular retinoblastoma. Retinoblastoma is often curable when it is diagnosed early, but becomes more difficult to treat if not found and treated in the early stages. Whenever possible, ophthalmologists design treatments with the aim of preserving a child’s sight.

Ophthalmologists determine a course of treatment for the disease based on the size and location of the tumor.

For small, localized tumors treatment may include:

  • Laser surgery
  • Cryotherapy (the localized use of extreme cold produced by liquid nitrogen or argon gas)
  • Radiation (see below)

Larger tumors may be treated with:

  • Radiotherapy: Ophthalmologists may use a type of internal radiotherapy called brachytherapy, in which surgeons stitch small radioactive plates (plaques) in place directly over the tumor, then leave these in place for a few days. If a tumor is large or has not responded to other treatments, ophthalmologists may treat the whole eye with radiotherapy.
  • Surgery: In some cases surgeons may have to remove the eye, a procedure called enucleation.
  • Chemotherapy: Doctors may use chemotherapy drugs to shrink a tumor before they use more targeted treatments. The chemotherapy may be introduced into the affected eye through a nearby blood vessel (artery); this is called intra-arterial chemotherapy.

Doctors sometimes devise a course of treatment that includes a combination of these approaches.


What is the recommended follow-up for a child with retinoblastoma?

Children who have been diagnosed and treated for heritable retinoblastoma may develop new tumors for a few years, so ophthalmologists schedule regular eye exams every 2 to 4 months for at least 28 months after the completion of treatment. A child who has retinoblastoma in one eye and a family history of the disease may be screened regularly using MRI.

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 they are known not to have a RB1 gene mutation.