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.

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.
  

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. 
  

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)

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.

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.

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.

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.