Retinoblastoma: Overview and More

Retinoblastoma is cancer of the eye that begins in the retina, a layer of tissue near the optic nerve. It occurs most often in infants and children, but sometimes in older children and adults. Ninety-five percent of all cases are diagnosed in children under the age of 5.

The most common type of eye cancer, retinoblastoma, is often first detected by parents who notice a white pupil or other abnormalities of the eye, such as crossed eyes, bulging, or vision difficulty. Retinoblastoma may occur in one or both eyes and may have few or no symptoms at first.

Retinoblastoma affects both sexes and all races and ethnicities equally. There are fewer than 20,000 cases per year in the United States.

(Retinoblastoma Symptoms) A young child with a white pupil in their left eye.

Verywell / Mira Norian

Types of Retinoblastoma

Retinoblastoma can occur in one eye or both eyes, with an equal frequency between the left and the right. There are three types of retinoblastoma, as well as three retinal subtypes. The types are:

  • Unilateral retinoblastoma: Cancer is found in only one eye. This is the most common type of retinoblastoma, making up 60% to 75% of all cases. Unilateral retinoblastoma has no known cause 85% of the time.
  • Bilateral retinoblastoma: This affects both eyes, making up 20% to 35% of all retinoblastoma cases, and is almost always inherited from one or both parents.
  • Trilateral retinoblastoma: This is known as primitive neuroectodermal tumors (PNET). It refers to a combination of retinoblastoma and pineoblastoma, an aggressive cancer that starts in the brain’s pineal gland and then spreads to the retina. This type of cancer almost always affects both eyes, is always hereditary, and accounts for 5% of all people with retinoblastoma.

The retinal subtypes are:

  • Subtype 1: A single tumor is clearly distinct from the rest of the retina
  • Subtype 2: More of the retina is affected, and the primary tumor blends into the surrounding retina.
  • Subtype 3: The tumor has spread throughout the retina.

Retinoblastoma Symptoms

Because retinoblastoma most often appears in infants and toddlers, parents usually first notice that something is not quite right with their child's eye. The eye may appear deformed or irritated, or their vision may seem impaired.

Symptoms of retinoblastoma include:

  • A pupil that appears white instead of black (this is called leukocoria and occurs when light reflects against the tumor's white surface).
  • A crossed eye (an eye looking either towards the nose or the ear), also known as strabismus
  • Poor vision or vision loss
  • A red, irritated eye
  • Eye pain
  • A bulging pupil (proptosis)
  • An enlarged pupil or eyeball (buphthalmos)
  • Two different-colored irises

If cancer is not detected when it is still limited to the eye, it may spread (metastasize) to the other eye, other areas of the head or brain, the spine, or distant parts of the body.

Symptoms of metastasized retinoblastoma include:

  • Unintended weight loss or failure to grow as expected (failure to thrive)
  • Vomiting
  • Headaches
  • Neurological impairment
  • Pain syndromes
  • Mood disorders; crankiness
  • Fatigue

Causes

Retinoblastoma occurs when a tumor develops in some of the brain’s primitive nerve cells. Nearly 85% of unilateral (affecting one eye) retinoblastoma cases are referred to as “sporadic,” meaning that doctors do not know what caused them. In the other 15% of cases, the genetic predisposition has been inherited from one or both parents, even if they never had it themselves.

Bilateral retinoblastoma (affecting both eyes) is usually hereditary. Trilateral retinoblastoma (affecting both eyes and pineal gland) is always hereditary.

Gene mutations that cause retinoblastoma include:

  • Germline mutation: Some 1 in 3 children who have retinoblastoma have a germline mutation in one of their RB1 genes, and this mutated RB1 gene is in every cell of the body. In 75% of these children, this mutation occurred spontaneously in the womb very early in development. In the other 25%, the mutation is inherited from one of the parents.
  • Non-heritable sporadic: Of the remaining 2 out of 3 children with retinoblastoma, most do not have an RB1 gene mutation in all of their cells. In a tiny minority of people, no RB1 gene mutation is found at all. In some of these children, the retinoblastomas may be caused by mutations in a different gene, MYCN.

The Cause of Mutation Is Currently Unknown

Whether mutations are inherited or sporadic, scientists do not know what causes them. Instead, they suspect random errors in gene transcription and have not identified any environmental or lifestyle causes.

Diagnosis

People with bilateral retinoblastoma tend to be diagnosed before they are 1 year old, typically earlier than those with unilateral retinoblastoma.

The most accurate way to diagnose retinoblastoma is through an ophthalmic examination, ideally performed under general anesthesia. During this exam, the ophthalmologist (a medical doctor that diagnoses and treats eye diseases):

  • Uses metal clips to keep the eye open and a magnifying light to scan the retina for tumors.
  • Manipulates portions of the retina into view to examine, using either a cotton swab or a tool that looks like a flat-tipped pen (a metal scleral indenter).
  • A team member will create drawings of the eye or take photographs to evaluate afterward.

Other Labs and Tests

In addition to an ophthalmic examination, the ophthalmologist may order or perform the following tests:

  • MRI of the head: This is to confirm the diagnosis and check the brain to make sure tumors have not spread to that region.
  • Ultrasound: Using sound waves to visualize the entire eye, ultrasound can also confirm whether retinoblastoma is present and the size and thickness of any tumors. The doctor may take photos of the ultrasound images to have those examined.
  • Electroretinogram: This may replace vision tests by measuring electrical activity within the retina.
  • Genetic testing: This will be performed to establish whether a mutation caused cancer. 

Assessing Spread

To make sure cancer has not spread anywhere else, a pediatric oncologist will also conduct a physical exam, blood tests, a spinal tap, and testing of bone marrow tissue.

Treatment

Most people will have a combination of treatments that may extend over months or years. The most important factors that guide treatment protocol include type, subtype, and staging.

In the case of some small tumors, focal treatments (noninvasive techniques) might be sufficient for treatment and removal. These include:

  • Laser therapy (photocoagulation or thermotherapy)
  • Cryotherapy (freezing)
  • Brachytherapy (plaque radiotherapy)

In most cases, tumors are larger or difficult to access, so the care plan consists of both focal treatments and chemotherapy.

Chemotherapy and Radiation

When systemic (whole body) chemotherapy is part of the treatment plan, it ordinarily continues for six months. In recent years, many oncologists have instead ordered targeted chemotherapy, delivered directly into the artery that supplies blood to the eye (intra-arterial chemotherapy).

When retinoblastoma has spread throughout the eye, another strategy is direct chemo injection into the eye (intravitreal chemotherapy). Usually, this entails several treatments, each a few weeks apart.

When chemotherapy concludes, external radiation therapy might be added to the regimen, especially if you have hereditary retinoblastoma, making recurrence more likely. 

When there are large tumors in both eyes, chemotherapy can be used to shrink the tumors and potentially prevent surgery or save vision in at least one eye.

Removal of the Eye

If these treatment combinations cannot control cancer, the eye may need to be removed. If the eye has already lost vision, the tumor is extremely advanced, or there is painful, increasing pressure in the eye due to glaucomas, the eye is removed and replaced with an orbital implant (glass eye).

If retinoblastoma has spread to distant sites, the prognosis is more concerning and requires more aggressive treatment, such as higher doses of chemotherapy and a stem cell transplant. Enrolling in clinical trials to take advantage of newer treatments may be a promising option for later stage cancers.

Prognosis

Early diagnosis and treatment are crucial to prevent vision loss and the metastasis of retinoblastoma beyond the eye. All genders have similar outcomes with the treatment of the disease. Children from underserved or minority communities are often diagnosed later and therefore have less favorable outcomes. This is purely socioeconomic; there is no genetic influence on outcome based on race or ethnicity.

Almost all children who are treated for retinoblastoma live for five years or more after finishing treatment. Those who are cancer-free after five years are considered cured. 

Out of every 10 children with retinoblastoma, 9 are cured. The chances of being cured are dramatically improved if cancer is caught in its early stages. Left untreated, though, retinoblastoma is nearly always fatal.

Risk of Other Cancers

Due to the same genetic mutations that led to retinoblastoma, and to the effects of chemotherapy and radiation, people who had cancer do have an increased risk of other cancers later on in life. For this reason, the person who had cancer, their families, and providers will want to remain vigilant in order to catch any subsequent cancers early.

Coping

A cancer diagnosis can create a sense of helplessness, despair, depression, anger, or fear. Parents of a child with retinoblastoma need to remember that they did not cause the disease. Children with cancer and their parents need to practice self-care, including adequate rest, healthy eating, and exercise. Talking to family and friends can be helpful, and therapy or support groups might help a lot as well.

Tips for Parents

If you are parenting a child with retinoblastoma, help your child to get familiar with smells, sounds, textures, and surface changes to make up for any vision deficiencies. Start using your voice to convey directives or emotions that would normally be conveyed through facial expressions.

Summary

Retinoblastoma is cancer of the eye that begins in the retina. A majority of all cases are diagnosed in children under the age of 5. Retinoblastoma can occur in one eye (unilateral) or both eyes (bilateral). It is caused by a gene mutation that can be hereditary or sporadic (no known cause).

Symptoms of retinoblastoma include redness, blurry vision, a crossed eye or eyes, white pupil(s), pain, and more. It is most often diagnosed with an ophthalmic examination, but may also include an ultrasound, MRI, electroretinogram, and/or genetic testing.

Retinoblastoma can be treated with noninvasive techniques such as laser therapy, cryotherapy, and brachytherapy. Sometimes these therapies are combined with chemotherapy and/or radiation. If cancer is in only one eye, removal of the eye may be considered. Early diagnosis and treatment are crucial to prevent vision loss and the metastasis of retinoblastoma beyond the eye.

A Word From Verywell

A cancer diagnosis and the prospect of vision impairment in your child, another loved one, or yourself can be scary and overwhelming. It can disrupt your daily routine, your future plans, and your finances. It can test your faith or your sense of security, but knowledge is power. The more information you have from credible sources, the more questions you can ask, and the more decisions you can actively participate in.

You may find that you have strength and wisdom you never knew you had. We encourage you to talk to your care team about all your options, including existing and experimental treatments and clinical trials, as well as mental health resources and support groups. 

Frequently Asked Questions

  • What is retinoblastoma?

    Retinoblastoma is a rare eye cancer that begins in the retina, a sliver of light-sensitive tissue at the back of the eye. This disease runs in families and most often appears in children under the age of 2, but older children and adults can get the disease. 

  • What causes retinoblastoma?

    Retinoblastoma is caused by a mutation in a gene that is involved in eye development. A child can inherit this mutation from a parent, or it can appear spontaneously on its own.

  • What are the symptoms of retinoblastoma?

    Symptoms include:

    • A pupil that is white instead of black
    • Cross eyes (eyes that look in different directions, or strabismus) 
    • In the case of large retinoblastomas, vision trouble may occur

    If cancer spreads, symptoms can include appetite loss, headache, and vomiting.

  • How can doctors tell if someone has retinoblastoma?

    If a doctor sees outward signs of retinoblastoma, the next steps will be an eye exam under general anesthesia, CT scan, ultrasound, or MRI of the retina.

    Once a diagnosis of retinoblastoma is made, doctors will conduct more tests to determine whether cancer has spread, including, possibly a bone scan, a bone marrow biopsy, or a spinal tap. Doctors will also do genetic testing to see if your child's retinoblastoma is the type that can be passed down in a family.

  • How do doctors treat retinoblastoma?

    Treatment varies depending on tumor location, size, and whether it has spread. Doctors will make treatment decisions with survival as the top priority, and saving vision, the second.
    When retinoblastoma is in one eye, the eye is usually removed. When it is in both eyes, doctors will use chemotherapy, radiation, and focal therapies. Regular eye exams will be an important part of the care plan, to monitor for recurrence or spread. 

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. American Cancer Society. Signs and symptoms of retinoblastoma.

  3. National Organization for Rare Disorders. Retinoblastoma.

  4. El Zomor, H, Nour, R, Saad, A. et al. Unilateral retinoblastoma; natural history and an age-based protocol in 248 patientsEye. 2021;35(9):2564–2572. doi:10.1038/s41433-020-01275-2

  5. Wang YZ, Zhang Y, Huang DS, et al. Clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma and intracranial segment of Retrobulbar optic nerve invasionBMC Ophthalmol. 2021;21(1):38. doi:10.1186/s12886-020-01768-4

  6. Ancona-Lezama D, Dalvin LA, Shields CL. Modern treatment of retinoblastoma: a 2020 reviewIndian J Ophthalmol. 2020;68(11):2356-2365. doi:10.4103/ijo.IJO_721_20

By Jennifer Leavitt
Jennifer Leavitt, MS, is a health advocate, award-winning writer, and editor who empowers readers with evidence-based information.