Retinoblastoma

What is retinoblastoma?

Retinoblastoma is a rare type of eye cancer that begins in the retina, the light-sensitive layer of the eye. During the very early stages of eye development that occur when the baby is in the womb, the eyes contain fast-growing cells called retinoblasts.

At a certain point, these cells stop growing and become mature retinal cells. But very rarely, something goes wrong with this process. Instead of maturing, some retinoblasts continue to grow out of control and develop into a cancerous tumour called retinoblastoma.

This type of cancer usually develops in early childhood, typically affecting children under the age of five. One in 20,000 children in the UK are affected by retinoblastoma, with approximately 40 to 50 new cases diagnosed each year.

In nearly all cases, retinoblastoma is curable when it is diagnosed early.

Treatment is very effective and 99 out of 100 children with the condition will be successfully treated. However, if it is not treated promptly, the cancer can spread beyond the eye to other parts of the body. At this advanced stage, the disease can be life-threatening.

Does retinoblastoma run in families?

Retinoblastoma is either heritable (germline or genetic) or non-heritable (somatic or non-genetic).

It can affect one (unilateral) or both eyes (bilateral).

Around four out of ten (40%) children have the heritable form, which often affects both eyes, but can occasionally be unilateral.

The gene mutation in such cases is present in every or most cells in the body, and can result in multiple tumours in both eyes.

The remaining 60% of retinoblastomas are the non-heritable form, which is not passed through families and where the gene mutation only occurs in one retinal cell in one eye.

This form always affects only one eye.

Who is at risk of retinoblastoma?

Retinoblastoma most commonly affects children under the age of five. Around 40% of cases are diagnosed in the first year of life.

The risk of developing retinoblastoma is much higher for a child with a parent who had the heritable form of the disease themselves.

Inheritance from a parent is referred to as familial retinoblastoma.

However, most affected children will have no family history of retinoblastoma, and it has occurred for the first time in that family- this is referred to as sporadic.

This is regardless of whether they have the heritable or non-heritable form of the disease.

What causes retinoblastoma?

In almost all cases, retinoblastoma starts with a change (or mutation) in the RB1 gene. This gene makes a protein that normally helps keep cells from growing out of control.

Each cell normally has two copies of the RB1 gene. As long as a retinal cell has one of copy of the gene that is working properly, it will not form a tumour.

But when there are mutations in both copies of  RB1, it stops the RB1 protein from working in the way it should. As a result, the cell may start to grow out of control and form a cancerous tumour.

Hereditary retinoblastoma

In children with the hereditary form of retinoblastoma, a mutation in one copy of RB1 gene is present at birth and occurs in all cells of the body, including  both retinas. For retinoblastoma to develop, they must acquire another mutation in the other copy of the RB1 gene in a retinal cell.

About 9 out of 10 children born with an RB1 mutation in all cells of their body will go on to develop retinoblastoma. This usually occurs in childhood and often leads to the development of retinoblastoma in both eyes – and there are often several tumours within the eye (which is known as multifocal retinoblastoma).

However, sometimes it is found early enough that it has so far only occurred in one eye.

People with heritable retinoblastoma may have a family history of the disease. The majority of affected individuals with heritable retinoblastoma have a 1 in 2 (50%) chance of passing on a faulty copy of the RB1 gene to each child. However, most children will have no family history of the disease, and the RB1 mutation is not inherited from a parent. In these cases, the faulty gene is the result of a new mutation (sporadic) that occurred in an egg or sperm cell or just after fertilisation. Only a small proportion of children born with an RB1 mutation will have inherited it from a parent.

Non-hereditary retinoblastoma

In children with non-hereditary (or sporadic) retinoblastoma, only one eye is affected and they have no family history of the disease. In these cases, both copies of the RB1 gene acquire mutations early in life. These gene changes arise only in a single retinal cell in one eye. It’s unclear what causes these mutations, but they may result from random errors that sometimes occur during cell division.

This type of retinoblastoma often develops when the child is slightly older compared with those with the heritable form. People with non-hereditary retinoblastoma are not at risk of passing on the faulty RB1 gene to their children.

Is it possible for adults to get retinoblastoma?

Retinoblastoma can sometimes occur in adults, but this is extremely rare. One possibility is these cancers arise after a pause in the tumour’s early development.

What are the signs and symptoms of retinoblastoma?

Most children with retinoblastoma will seem well. Because the condition typically affects children at a very young age, they may not be able to describe any symptoms. The signs and symptoms of retinoblastoma may be related to other less serious conditions so it is important to have your child’s eyes tested if you have any concerns.

Signs and symptoms of retinoblastoma may include:

• An unusual white reflection or glow in the centre of their eye (pupil) – the first sign of retinoblastoma is often a white pupil that doesn’t reflect the light. This is called leukocoria and may be particularly noticeable in photographs taken with a flash and the pupil appears white rather than the typical red colour.
• Squint – their eyes may appear to be looking in different directions (crossed eyes). This is also known as strabismus.
• Colour change – there may be a change in the colour of the coloured part of their eye (iris).
• Poor vision – they may experience a deterioration in their sight, typically when both eyes are affected.
• Red or inflamed eye – their eye may appear red, sore or swollen.

How is retinoblastoma diagnosed?

There are a number of tests used to diagnose retinoblastoma. For some of these tests, the child may need to be drowsy (sedated) or asleep (general anaesthetic).

Tests for diagnosing retinoblastoma include:

• Red reflex test – this test will take place in a darkened room using a magnifying instrument with a light at one end (ophthalmoscope). The light will be shone into the child’s eyes to check the retina at the back of both of their eyes. The doctor will be looking for a red reflection, which is normal. If there is a white reflection, the child will be referred to a specialist eye doctor (ophthalmologist) for further investigation. The ophthalmologist will repeat the test using eye drops that increase the size of the pupil, which will give them a clearer view of the retina.
• Ultrasound scan – an ultrasound scan may help to confirm whether or not a child has retinoblastoma. This imaging test uses high-energy sound waves to create images inside the body, such as the inner parts of the eye. A gel is rubbed on the outside of the eyelid and a small ultrasound probe, which scans the eye, is gently placed on the outside of the eyelid. This probe emits sound waves and detects echoes that bounce from the internal tissues of the eye, which are then converted by a computer into an image on a screen.
• Optical coherence tomography (OCT) – this imaging test uses light waves instead of sound waves to build detailed images of the back of the eye.
• Magnetic resonance imaging (MRI) scan – this is a type of scan that creates detailed images using radio waves and strong magnets. It can provide detailed images of the inside of the eye. Most children with retinoblastoma will have an MRI scan as part of initial investigations.
• Genetic testing – this is a laboratory test where a sample of blood or tissue is tested to look for changes in the RB1 It is important to find out whether a child’s retinoblastoma is the heritable or non-heritable form of the disease. This is because children with heritable retinoblastoma have an increased risk of developing some other types of cancer later in life.

If retinoblastoma is suspected, the ophthalmologist will refer your child to one of the two specialist retinoblastoma treatment centres (Birmingham Womens and Children’s Hospital or The Royal London Hospital).

What are the stages of retinoblastoma?

The stages of cancer are used to describe the size of a tumour and whether it has spread to other parts of the body. Doctors use staging systems to predict the outlook for saving a child’s vision, as well as for guidance in choosing treatment.

Retinoblastoma has two main stages:

• Intraocular retinoblastoma: the cancer is still entirely within the eye and has not spread. This group can then be further classified into five subgroups (A to E), with A the lowest risk group and E the highest risk group. Most children are diagnosed with intraocular disease – and almost all can be cured if they are properly treated, regardless of its stage. However, the stage may impact on whether the affected eye (or the sight in the eye) can be saved – and help with decisions on which treatment is best.

• Extraocular retinoblastoma: the cancer has spread beyond the eye and into the surrounding tissues or to other parts of the body, such as the brain or bone marrow. In the UK, this is rare.

How is retinoblastoma treated?

There are several treatment options for children with retinoblastoma – and the most appropriate treatments will depend on each child’s individual needs. There are several factors to consider, including where the cancer is, whether it is in one or both eyes, its size, how far it has spread – and how many tumours are present in the eye. The main goal of treatment is to eradicate the cancer. Unfortunately, some patients may lose some or all of their sight as a result, although every effort is made to preserve their vision.

What are possible treatments for retinoblastoma?

Some of the treatments for retinoblastoma include:

Laser treatments

There are two types of laser treatment for retinoblastoma: photocoagulation and thermotherapy (or heat therapy). They both involve the use of a thin, focused beam of light (a laser beam), which is directed through the pupil while the child is under general anaesthetic. They differ because the laser delivers light at different wavelengths.

Laser therapy is usually used for small tumours which are located towards the back of the eye. This treatment can either be used alone or in combination with chemotherapy. It will require a series of treatments at regular intervals and may continue even after the chemotherapy courses have been completed.

Cryotherapy 

A technique used to freeze small tumours located at the outer edge of the retina. This treatment may be needed more than once.

It is performed under general anaesthetic so your child will not feel any pain during the procedure. An instrument called a cryoprobe is carefully positioned on the outer surface of the eye, overlying the base of the tumour. The cancer cells are destroyed by freezing them.

Surgery (enucleation)

If the tumour is extremely large and the eye is no longer working, it may be recommended for your child to have surgery to remove the eye and part of the optic nerve.

This operation is called an enucleation. It is only recommended when other treatments are unlikely to work and/or would put the child’s life at risk. When the eye is removed, a prosthesis (artificial eye) will be fitted a few weeks after surgery.

See Katie's story, below.

Chemotherapy

Chemotherapy (drug treatment) may be required to shrink larger tumours. However, it may also be used for small tumours. It can be given to the whole body (systemic), to the eye via a blood vessel (intra-arterial) or injected into the eye (intravitreal).

Systemic chemotherapy may also be required after an eye has been removed by surgery (enucleation) if there are signs that the cancer has spread to surrounding tissues.

Radiotherapy

Radiotherapy uses high-energy X-rays or radioactive particles to kill the cancer cells. There are two main types of radiotherapy: external beam radiation therapy and brachytherapy.

External beam radiation therapy (EBRT) is where a machine is used to directly aim beams of radiation (protons or photons) at the cancer. Proton beam therapy is a type of external radiotherapy that uses a high-energy beam of protons to precisely deliver a dose of radiotherapy to the cancer. As the proton beams stop once they hit the tumour (unlike photons where there is scatter radiation), it reduces the risk of side effects in surrounding health tissues.

This treatment is currently only available at specialist facilities in Manchester and London.  

External beam radiotherapy (protons or photons) is very rarely used nowadays.

Brachytherapy

Brachytherapy (also known as plaque radiotherapy) is where a small radioactive disc (known as a plaque) is attached to the outside of the eye near the site of the tumour for up to four days. It works by delivering a high amount of radiation for a defined period of time to kill the cancer cells.

Are there any long-term complications after treatment for retinoblastoma?

Once their treatment is finished, a child with retinoblastoma will have regular follow-up examinations. This is important for monitoring for any signs of retinoblastoma recurrence (or new cancers), as well as identifying any potential treatment-related complications.

Nearly all children with retinoblastoma will survive without the cancer returning. However, there is risk of relapse – and so it’s very important to attend regular follow-up appointments.

Children with the heritable (germline or genetic) form of retinoblastoma also face a small risk of developing a tumour in their pineal gland in the brain within a few years. For this reason, doctors may advise regular MRI scans for several years after treatment to try and detect these tumours as early as possible.

A small subset of children may experience long-term complications due to their cancer treatment. The risk of these late effects will depend on the specific treatments they received, the doses of treatment, the type of retinoblastoma (heritable or non-inheritable), and the age of the child when treated. They can include:

• Reduced or loss of vision in the affected eye(s)
• Changes to shape and size of the bones around the eye
• Kidney problems
• Heart problems
• Hearing problems
• Slowed or delayed growth and development
• Fertility issues

Children with the heritable form of retinoblastoma also have a higher risk of developing other types of cancer (such as lung cancer, bladder cancer, sarcoma or melanoma skin cancer) throughout their lives. The risk of these tumours is even higher in any tissues exposed to radiation during treatment for retinoblastoma. Most of these cancers can be successfully treated if spotted early, which is why it is important they continue to be monitored into adulthood. They will also be encouraged to get any new symptoms checked early and to follow a healthy lifestyle to help reduce the risk of cancer.

Is it possible to prevent retinoblastoma?

Unfortunately, it’s not possible to prevent retinoblastoma. However, screening tests can detect it early when treatment is more likely to be successful.

If a child is at increased risk of retinoblastoma – for example, because one of their parents had the disease – they may be offered regular screening from birth.

What research is underway for retinoblastoma?

In recent decades, research on retinoblastoma has led to significant advances in the diagnosis and treatment of the disease. This has led to greatly improved cure rates and fewer side effects. However, not all children are cured, and even those who do may experience long-term treatment-related side effects, so more research is needed.

Fight for Sight is funding groundbreaking research projects into retinoblastoma. For example:

• A team at Newcastle University recently developed a new model of the disease using patient stem cells. The researchers intend to use this model to help accelerate work to identify and test the effectiveness of potential new treatments in the lab, before moving into human trials.
• Researchers at Birmingham’s Children’s Hospital are aiming to develop a safer and less invasive test to reliably diagnose retinoblastoma using small quantities of DNA in eye fluid. As a result, fewer young children would need to undergo a general anaesthetic, which is required for full eye examinations.

Kalli had retinoblastoma as a child and now her ten month old daughter is being treated for the condition. Read Kalli's full story. She said:

Find out how the retinoblastoma research we fund will have a huge impact for people like Kalli and Autumn who are living with the condition.

Last updated January 2024

Approved by Amy Gerrish, PhD, Research and Development Scientist at Birmingham Women’s and Children’s NHS Foundation Trust and

Manoj Parulekar, Consultant Ophthalmologist at the Birmingham Children's Hospital