Retinoblastoma

What is retinoblastoma?

Retinoblastoma is a type of eye cancer that starts in your retina, the light-sensing layer of cells at the back of your eye. It’s the most common childhood eye cancer.

Retinoblastoma can happen in one or both eyes. About 1 in 4 cases affect both eyes. Experts suspect it happens because of a malfunction in young, developing retinal cells. Diagnosis occurs before age 3 in 4 out of 5 cases. In rare cases, adults can also develop the condition after a pause in the tumor’s early development.

Types of retinoblastoma

There are three types of retinoblastoma:

• Unilateral: This means “one-sided,” so it affects one eye only.
• Bilateral: This means “two-sided,” so it affects both eyes.
• Trilateral: This means you have cancer in three places. Each eye reflects one of those places. The third place is in the pineal gland inside your brain. (Cancer affecting that gland is called pineoblastoma.)

About 60% of retinoblastoma cases are one-sided. Bilateral and trilateral cases make up the other 40%.

How common is retinoblastoma?

Retinoblastoma is rare. There are about 3.3 cases per 1 million people under age 20. In that age group, there are a little over 300 new cases annually in the U.S. and slightly under 9,000 new cases worldwide.

What are the symptoms of retinoblastoma?

Because the condition is typically diagnosed before age 3, children often can’t describe their symptoms or what they’re experiencing. Instead, the symptoms are visible changes in eye appearance or differences in how your child behaves.

Leukocoria

The earliest and most common symptom of retinoblastoma is the pupil of your eye appearing white (leukocoria) or pale-colored in certain settings, especially seen in photos taken in dim places that also use a flash for illumination. It can happen in one or both eyes.

Other symptoms of retinoblastoma

While retinoblastoma commonly happens in children before they can talk, there are also other signs and symptoms that can signal its development, including:

• Eyes that have trouble following movement or don’t follow it at all.
• Misaligned eyes (strabismus).
• Pain (it may cause your child to cry more or be fussier than usual, or they might have trouble sleeping or feeding).
• Enlarged eye (buphthalmos).
• Bulging eye (proptosis).
• Blood in the front chamber of your eye (hyphema).
• Infection, swelling or inflammation of your eye or surrounding tissue (orbital cellulitis).

What causes retinoblastoma?

Retinoblastoma is a type of cancer where retinal cells malfunction and start to multiply uncontrollably. As they do, they can form tumors and damage surrounding tissues. If they keep growing unchecked, eventually, those malfunctioning cells spread (metastasize) beyond the original tumor, and cancer appears in other places in your body.

The malfunction that causes healthy cells to turn into retinoblastoma starts in your DNA.

Your cells use DNA like a cookbook. You inherit DNA from both of your biological parents, so it’s like they each give you part of their cookbook, so you can make a full cookbook of your own.

But sometimes, you can have an error in your DNA. Your cells only know how to follow the recipes in the book exactly, so a DNA error means your cells only know how to make the recipe incorrectly. That can cause those cells to grow and multiply uncontrollably.

Experts recommend genetic testing and counseling for children with retinoblastoma regardless of whether or not it was inherited. They also recommend testing for biological siblings and other family members.

The mutation that causes retinoblastoma affects RB1, a tumor suppressor gene. Tumor suppressor genes are responsible for normal development of the tissues (retina). They act like brakes and control cell reproduction and growth processes. A mutation in RB1 means your retinal cells can grow uncontrolled into a tumor. Retinoblastoma can also happen with “deletion” of chromosome 13p, which is the location of the RB1 gene.

In rare instances, people can have a benign retinal growth called a retinoma. These are like precursors to retinoblastoma, but they stop growing for some reason. Later in life, a retinoma may start growing again and turn into retinoblastoma.

There are two main ways that DNA errors that cause retinoblastoma can happen:

• Sporadic: This is when an error happens while your cells copy a parent’s DNA. It’s like accidentally introducing a typo while hand-copying a recipe. The recipe you copied from was sound, but the new error means your recipe is now incorrect. Sporadic cases of retinoblastoma affect one eye only.
• Inherited: This is when one or both biological parents have DNA with the error. Your cells copy their DNA correctly, but that also includes the pre-existing typo. Retinoblastoma has autosomal dominant inheritance. That means you have roughly a 50% chance of inheriting the gene if one parent has it and a 75% chance if both parents have it. But biological parents may not have retinoblastoma even if their child has the inherited form. That’s because some people are carriers, meaning they have the mutation without it causing them to have the condition.

Inheriting a gene mutation also determines what form of retinoblastoma your child has. Inherited cases are usually bilateral and less often unilateral.

A sibling of a child with retinoblastoma also has an increased chance of developing it. When both parents are unaffected by retinoblastoma, biological siblings of the affected child have a 4% to 7% risk of having retinoblastoma, too.

What are the complications of retinoblastoma?

Retinoblastoma can damage surrounding tissues. It can cause partial or total blindness in the affected eye(s).

Because it’s a type of cancer, there’s also a risk of retinoblastoma spreading (metastasizing) to other parts of your body. Once it does, it becomes even more dangerous, so preventing that spread is a key part of treatment. One dangerous way it can spread is through the optic nerve to your brain, where it becomes a new brain cancer tumor.

The genetic mutations that can cause retinoblastoma also increase your risk of developing other types of cancer. There’s a 1% cumulative risk per year of developing another cancer (for example, about 20% at 20 years).

The most likely cancers are:

• Sarcomas: These affect bones and connective tissues.
• Melanomas: These affect your skin, eyes and mucus membranes, like those inside of your mouth and nose.
• Lung cancers: Because of the intricate blood vessel connections in the lungs, cancers here can easily spread anywhere else in your body.

How is retinoblastoma diagnosed?

Parents (or caregivers) may be the first to see leukocoria and tell their child’s pediatrician, who can then also look for it. A pediatrician (or another healthcare provider with a similar role) can confirm leukocoria during an exam, or they might see leukocoria during routine physical exams that monitor child development.

Once a pediatrician sees leukocoria, the next step is usually an urgent referral to an ophthalmologist or other eye care specialist. An eye specialist will try to see retinoblastoma directly by looking at the eye’s interior. For young children, that may involve using medicated drops to dilate their pupils or doing an eye exam under anesthesia.

Imaging scans are likely, as these can look for harder-to-see tumors in the other eye or corresponding tumors in the brain (like pineoblastoma).

Imaging scans they might use include:

• Ultrasound: This scan can show calcium accumulations that are common with retinoblastoma.
• Computed tomography (CT) scan: Retinoblastoma often involves calcium accumulations, which are also visible on CT scans.
• Magnetic resonance imaging (MRI) scan: This is the best scan for detailed images of the different tissues and structures inside your body. It takes longer and is costlier, so it’s often not the first test. Still, it’s a vital way to see just how far a tumor has spread or detect tumors elsewhere in the other eye or brain.
• Positron emission tomography (PET) scan: This test may happen early in the diagnosis and treatment process or long after. It’s especially useful for detecting if the tumor has metastasized to other places or if other tumors have developed elsewhere.

How is retinoblastoma treated?

There are multiple ways to treat retinoblastoma. Often, treatment involves a combination of methods. They can happen simultaneously or in sequence. The treatment methods include (but aren’t limited to):

• Chemotherapy: This approach uses drugs that attack cancerous cells’ weaknesses directly. That can help avoid surgery that might involve a loss of vision. It can also cause tumors to shrink enough that other treatments can destroy the remaining cancerous cells. It can be local, meaning it happens via targeted injections or infusions through the artery (intraarterial). It can also be systemic, meaning it happens via a standard intravenous (IV) infusion. The method of administration varies depending on your specific case and needs.
• Radiation therapy: This involves using high-frequency energy to destroy tumor cells. That can happen from outside your body with treatments like external beam radiation therapy (EBRT) or inside your body with methods like brachytherapy. However, treatment usually avoids this because of long-term complication risks.
• Focal therapies (cryotherapy, thermotherapy, laser therapy, etc.): Focal treatments get their name because they “focus” on destroying tumor cells directly. That can involve thermotherapy or laser therapy, which use intense heat energy to destroy the cells, or cryotherapy, which uses intense cold to destroy the cells instead of heat.
• Surgery: Surgery is most likely when there’s a risk of retinoblastoma spreading. This usually involves a surgery like enucleation, which means removing your eye. This prevents the cancer from spreading further. By the time this surgery is necessary, the cancer likely has already damaged your affected eye enough to cause vision loss.
• Other therapies and treatments: These can vary widely and usually help with the side effects of other treatments. One example of treatments like this would be medications that can help with nausea and vomiting, which are common with chemotherapy. Because there are so many support treatments like this, your provider is the best person to tell you what they recommend for your specific case and needs.

Can retinoblastoma be prevented?

Retinoblastoma happens because of genetic mutations, so there’s no way to prevent it entirely. If you have a family history of retinoblastoma or know you carry a genetic mutation that causes it, genetic counseling can help you understand the risk of passing it on to a biological child.

What can I expect if I have (or my child has) this condition?

The outlook for retinoblastoma depends strongly on how long it takes to diagnose and treat it, but the odds, in general, are very good. The overall survival rate for pediatric retinoblastoma is 95%. The odds of a good outcome — including avoiding loss of vision — are best with a diagnosis before age 2.

People who survive retinoblastoma will need lifelong surveillance for new cancers. This usually involves yearly scans or other tests that can detect new tumors. Your provider can tell you what surveillance measures they recommend for your case.

When should I call my healthcare provider about retinoblastoma?

Call your provider if you notice any signs of retinoblastoma or changes in your child’s eyes or vision. Talk to your provider if you or your partner has a family history of retinoblastoma or you know you have the RB1 gene mutation. You may want to consider genetic counseling before having children.

What do I need to know if I have a family history of retinoblastoma?

If you have a family history of retinoblastoma, be sure to schedule regular eye exams for your child and other family members. The RB1 gene that causes retinoblastoma can also cause retinocytoma, a benign (noncancerous) eye tumor. Retinocytoma can develop in people of all ages.