Retinoblastoma

Retinoblastoma is a rare eye cancer that develops in the retina, the light-sensing layer at the back of the eye. Though uncommon, it is the most common eye cancer in childhood, typically affecting children under age 5. With early detection and modern treatment, survival rates are very high, often exceeding 95% in specialized care centers.

Table of contents

• What is retinoblastoma?
• Signs and symptoms
• What causes retinoblastoma?
• Types of retinoblastoma
• How is retinoblastoma diagnosed?
• Treatment options
• Outlook and survival
• Living with retinoblastoma

What is retinoblastoma?

Retinoblastoma is a type of cancer that develops in the retina, which is the light-sensitive tissue lining the inside of the eye^[1]. The retina is made up of nerve tissue that senses light as it enters through the front of the eye. When light hits the retina, it sends signals to the brain, which interprets these signals as images^[1].

This cancer happens when cells in the retina start to grow uncontrollably^[2]. It is the most common eye cancer in children and accounts for about 3% of all childhood cancers^[4][6]. About 300 children are diagnosed with retinoblastoma in the United States each year^[6]. Globally, there are approximately 3.3 cases per 1 million people under age 20^[2].

• Eye
• Retina
• Optic nerve

Signs and symptoms

Because retinoblastoma most often affects very young children, they usually cannot describe what they are experiencing. Instead, parents or doctors notice visible changes in the child’s eyes or behavior^[2].

The most common and earliest sign is called leukocoria, also known as “white pupil” or “cat’s eye reflex”^[5][2]. This appears as a white, pale, or yellowish color in the center circle of the eye (the pupil) when light shines into it^[1]. Parents often first notice this unusual white reflection in flash photographs of their child^[2][6].

Other signs and symptoms of retinoblastoma include^[1][2][6]:

• Eyes that appear to be looking in different directions, also called crossed eyes or strabismus
• Eye redness or swelling
• Poor vision or change in vision
• Pain around the eye (which may cause a baby to cry more than usual or have trouble sleeping or feeding)
• An enlarged or bulging eye
• Eyes that have trouble following movement

What causes retinoblastoma?

Retinoblastoma is caused by changes, called mutations, in a gene called RB1^[4][8]. This gene normally helps control how cells grow. When both copies of the RB1 gene in a cell are changed, the cell can no longer control its growth properly, and cancer can develop^[8].

The RB1 gene is located on chromosome 13^[5]. Your cells use DNA like a cookbook with recipes for how to function. Sometimes there can be an error in the DNA, which means cells only know how to follow the incorrect recipe. This can cause cells to grow and multiply when they shouldn’t^[2].

While the RB1 gene is the primary cause of retinoblastoma, in rare cases, the cancer can be caused by changes in a different gene called MYCN^[4].

Types of retinoblastoma

There are different ways to classify retinoblastoma based on which eye or eyes are affected and whether the condition is inherited.

Based on number of eyes affected

About 60% of retinoblastoma cases affect only one eye, which is called unilateral retinoblastoma^[2][6]. The remaining 40% of cases affect both eyes, called bilateral retinoblastoma^[2].

In rare cases, children can develop trilateral retinoblastoma, which means cancer appears in both eyes and also in the pineal gland inside the brain^[2][9].

Based on inheritance pattern

About 60% of retinoblastoma cases are non-hereditary (also called sporadic)^[8]. In these cases, children are born with two normal copies of the RB1 gene. The mutations happen by chance in the retinal cells after birth. Non-hereditary retinoblastoma usually affects only one eye and will not be passed on to the child’s future children^[8][9].

About 40% of cases are hereditary retinoblastoma^[8]. This happens when a child is born with one copy of the RB1 gene already mutated in all cells of the body. The mutation may have been inherited from a parent or may have occurred in the egg or sperm before the baby was conceived^[9]. Children with hereditary retinoblastoma are more likely to have tumors in both eyes and can develop more than one tumor^[7][8]. They can pass the mutation on to their future children and have a higher risk of developing other types of cancer later in life^[7][9].

How is retinoblastoma diagnosed?

Retinoblastoma is often first detected during a routine well-baby examination by a pediatrician^[6]. If a doctor or parent notices concerning changes in a child’s eyes, the child will be referred to an eye specialist called an ophthalmologist^[6].

Eye examination

Diagnosis begins with a careful examination of the eyes^[10]. During this exam, the doctor uses a special light to look inside the eye and examine the retina. Because very young children often find it hard to stay still for a thorough eye exam, the doctor may use medicine to put the child in a sleep-like state during the examination^[10].

A doctor may perform a red reflex test, in which light from an instrument called an ophthalmoscope goes through the transparent parts of the eye and reflects off the back of the eye. If retinoblastoma is present, it may block this light path, resulting in an abnormal reflection or the white pupil appearance^[5].

Imaging tests

Imaging tests create pictures of the inside of the body. For retinoblastoma, doctors use imaging tests to look at the eye and surrounding area, to see the size of the cancer and whether it has spread beyond the eye^[10]. Common imaging tests include ultrasound, MRI (magnetic resonance imaging), and CT (computed tomography) scans^[1][10].

Genetic testing

Genetic testing uses a sample of blood or saliva to look for changes in the RB1 gene^[10]. All children with retinoblastoma have RB1 gene changes in their cancer cells. However, genetic testing can determine whether a child has the mutation in all cells of the body, which indicates hereditary retinoblastoma^[10]. This information helps doctors plan treatment and determine if the child has a higher risk of other cancers. It also helps families understand if future children might be at risk^[7].

Other tests

Unlike many other cancers, doctors usually do not perform a biopsy (removing a small piece of the tumor to examine under a microscope) for retinoblastoma. This is because a biopsy presents a high risk of damaging the eye or spreading cancer cells^[21]. Most of the time, examination under an ophthalmoscope is enough to confirm the diagnosis^[21].

Treatment options

The goals of treating retinoblastoma are to save the child’s life, preserve as much vision as possible, and reduce the risk of long-term side effects^[14]. Treatment depends on several factors, including whether one or both eyes are affected, the size and location of the tumor, and whether the cancer has spread outside the eye^[14].

For most children, treatment does not require removing the eye to get rid of the cancer^[1]. A team of specialists works together to create a treatment plan tailored to each child’s needs^[14].

Chemotherapy

Chemotherapy uses drugs to treat cancer. It is the most common treatment for retinoblastoma and is often the first treatment doctors try^[12]. Chemotherapy drugs work to shrink the tumor.

There are different ways to deliver chemotherapy for retinoblastoma^[12]:

• Systemic chemotherapy: The medicine is injected into a vein and travels through the whole body to reach cancer cells
• Intra-arterial chemotherapy: A specialist inserts a thin, flexible tube into an artery near the hip and guides it to the artery that supplies blood to the eye. The medicine goes directly to the eye through this tube. This approach delivers chemotherapy only where it is needed, largely sparing children from side effects^[18]
• Intraocular chemotherapy: Doctors inject the medicine directly inside the eye. This is often used when tumor cells are floating inside the eye^[12]

Focal therapies

Focal therapies are treatments that target the tumor directly. These include^[12]:

• Cryotherapy (freeze therapy): Doctors use a very cold tool to freeze and kill tumor cells
• Laser therapy: Doctors use different types of lasers to heat and destroy cancer cells or to cut off the blood supply to the tumor

Radiation therapy

Radiation therapy uses high-energy rays to kill cancer cells. There are two main types^[12]:

• Internal radiation (also called plaque brachytherapy): Doctors implant a small disc-shaped device behind the eye near the tumor. This device sends radiation to kill tumor cells. The implant is usually removed after about 7 days^[12]
• External radiation: A machine sends radiation into the body from outside. This is not commonly used for retinoblastoma because of potential long-term consequences in young children^[18]

Surgery

In some cases, doctors may recommend surgery to remove the eye, a procedure called enucleation^[12]. This may be necessary if the tumor is too large to save the eye, if the cancer could spread outside the eye, or if the tumor doesn’t respond to other treatments^[12].

After surgery, doctors will place a special shield in the eye socket to protect it while it heals. After about 6 weeks, doctors will replace the shield with an artificial eye^[12].

Outlook and survival

The outlook for children with retinoblastoma is generally very good. Thanks to advances in diagnosis and treatment, more than 95% of children with retinoblastoma that is contained within the eye can now be cured^[7]. In specialized care centers, survival rates reach 95%, with vision preserved in most cases^[4].

Early detection is crucial for a good outcome and increases the chances of a better quality of life^[21]. Children diagnosed before age 2 often have better outcomes than those diagnosed later^[6].

The outlook depends on several factors, including whether the cancer is in one or both eyes, the size and location of the tumor, whether it has spread outside the eye, and how well the cancer responds to treatment^[14].

Children with hereditary retinoblastoma have a higher risk of developing other types of cancer later in life, including brain tumors, bone cancer, and soft tissue cancers^[7][9]. Regular screening and follow-up care throughout life are important for these children.

Living with retinoblastoma

Life after retinoblastoma treatment can present ongoing challenges for children and their families. Many survivors must adapt to vision loss caused by tumors or treatment, and some children require ongoing eye care^[16][19].

Children who have had one eye removed can often excel in school and achieve great things throughout their lives with appropriate support^[19]. Even with bilateral disease affecting both eyes, many children adapt well and lead full, active lives^[20].

Raising a child with cancer places increased pressure on family life. Communication skills, understanding, patience, and flexibility become more important than ever for parents, siblings, and extended family members^[19].

Children with hereditary retinoblastoma require lifelong monitoring for potential second cancers. Regular screening helps detect any new cancers early when they are most treatable^[9][10].

While the physical and emotional impacts of retinoblastoma can be significant, survivors often describe their lives as richly blessed and full of living, with the right knowledge, understanding, and support^[19]. Believing in a better tomorrow is vital throughout the cancer journey, motivating and sustaining families through difficult times^[19].