RETINOBLASTOMA: EYE CANCER IN CHILDREN

Retinoblastoma is an uncommon type of eye cancer that can affect young children, especially those under the age of 5.

As a parent, the fact that your little child may have cancer is an impossible situation to be in. You may experience sadness, fear, anger, and uncertainty.

However, you must know that retinoblastoma has a strong survival rate of over 96% if caught in time and treated. Hence, your allies in this situation are an early diagnosis and proper treatment.

The retinoblastoma’s cure rate at Sant Joan de Déu Children’s Hospital in Barcelona is over 95%. So you can rest assured that if you choose us, your child will get the best medical attention possible to guarantee a great outcome.

Also, considering that knowledge is power and an early diagnosis is of utmost importance, we are here to give you a few important details about this rare disease.

Written by Dr Osama Bahsas Zaky
Updated on September 8, 2021

What is Retinoblastoma?

What Causes Retinoblastoma?

Retinoblastoma Prevention.

Signs and Symptoms.

How Is Retinoblastoma Diagnosed?

Treatment Options.

Intraocular Retinoblastomas.

Intra-Arterial and Intra-Vitreous Chemotherapy.

Extraocular Retinoblastoma.

Oncolytic Virus Vcn-01 In Severe Retinoblastoma.

Side Effects of Treatment and Follow-Up.

What is Retinoblastoma?

The retina is the light-sensitive lining at the back of the eye. It is made up of nerve cells that send signals through the optic nerve at the back of the eyeball in response to the pattern of light.

Then, the optic nerve sends this information to an area of the brain called the visual cortex, allowing us to “see.” Hence, the pattern of light is translated into images.

Retinoblastoma represents about 4 % of all cancers in children younger than 15 years. Also, it is the most common type of eye cancer in children, mainly under the age of 5.

It may occur in one or both eyes. However, one out of three children presents with cancer in both eyes.

In the early stages of development, the eyes cells called retinoblasts multiply to fill the retina. Later, these cells stop multiplying and turn into mature retinal cells.

Retinoblastoma is secondary to genetic mutations in the nerve cells in the retina.

These mutations cause the cells to keep growing and multiplying uncontrollably. Then, this accumulating mass of cells ends up forming a tumor.

With time, retinoblastoma cells can also invade deeper structures into the eye and the surroundings. It can also spread to other parts of the body (metastasis).

What Causes Retinoblastoma?

The events inside cells that lead to retinoblastoma are complex, but it always starts with a change (mutation) in a gene called RB1.

In about 1 out of 3 (40%) cases, retinoblastoma is caused by an inherited faulty gene, which often affects both eyes (bilateral) and is present in all the body cells.

This faulty RB1 gene can be inherited from a parent, or more commonly, a change to the gene (mutation) may occur during the child’s development in the womb- with no family history of this cancer.

Hereditary retinoblastoma can be passed from parents to children in an autosomal dominant pattern, which means that if one parent carries a mutated gene, each child has a 50% chance of inheriting that gene.

Children with the inherited form of retinoblastoma develop the disease at an earlier age.

Also, they have more chances of developing other types of cancers in any part of the body, especially pineoblastoma (a type of brain tumor), osteosarcoma (bone cancer), sarcomas (cancers of soft tissues), and melanomas.

For this reason, children with this inherited retinoblastoma should have regular exams to screen for other cancers.

Conversely, in about 2 out of 3 children with this disease, the abnormality in the RB1 gene is not inherited and only affects a single cell in one eye.

This sporadic (non-heritable) type of retinoblastoma is diagnosed when the child is slightly older. Also, children with this disease do not have an increased risk of other cancers.

Retinoblastoma Prevention

If there is a family history of this disease, genetic testing lets parents know whether their children could have an increased risk of retinoblastoma. Hence, medical care is planned with time.

For example, eye exams and check-ups may begin soon after birth or even before a baby is born.

Therefore, retinoblastoma may be diagnosed early on when the tumor is small, increasing the chances for cure and vision preservation.

Signs and Symptoms of Retinoblastoma

Because retinoblastoma generally affects infants and small children, symptoms aren’t common. Most children seem well and don’t complain of any pain. But signs you may notice as a parent are:

An unusual white reflection in the pupil: This is also known as “cat’s eye reflex” or leukocoria. This unusual whiteness is evident in dim light or photographs with flash. Actually, the presence of the photographic red-eye in only one eye may be a sign of retinoblastoma.
Crossed eyes or eyes that point to different directions (strabismus): they can cause squinting.
A change in the color of the colored part of the eye called iris.
A red or inflamed eye.
Uncontrollable movement of the eye from side to side (nystagmus).
Poor vision: You may notice that your child doesn’t focus or follow objects like other children of the same age.
Faltering growth or delayed development in older children.

If you see any of these signs, you should get your child’s eyes checked urgently to be sure. Although, you should remember that retinoblastoma is a rare disease, and all of these signs can be due to other reasons.

However, if it turns out to be a retinoblastoma, it can be curable up to six months after the initial signs are detected, as long as the tumor is intraocular.

How Is Retinoblastoma Diagnosed?

Retinoblastoma is curable when it is diagnosed in time. So, many advocate that testing for retinoblastoma must be included in the “well-baby” screening for newborns.

Children with bilateral retinoblastoma are diagnosed in the first year of life. Those children with one affected eye tend to be diagnosed later, between 2 and 3 years.

An ophthalmologist (eye specialist) must perform eye examinations. This is done under sedation (so your child is asleep) to have a better look at the retina.

Eyedrops are used to increase the size of your child’s pupils, allowing a clear view of the retina at the back of the eye.

Red reflex test: An eye specialist examines the eye while shining a light into it with an ophthalmoscope. In a dimly lit or darkroom, the goal is to check for a normal reddish-orange reflection from the eye’s retina.

Additionally, an ultrasound scan is also sometimes used to help diagnose retinoblastoma.

The doctor will glide a wand-like probe over gel that is placed on top of your child’s eyelid.

The probe uses sounds waves to create a picture of the eye’s structure. Hence, ultrasound can help determine the height and thickness of the tumor.

If the eye examination results are abnormal, further testing may include imaging studies, such as computerized tomography (CT) and magnetic resonance imaging (MRI). Also, blood tests and genetic testing may be necessary.

These studies help to check the exact position and size of the tumor, and whether it has spread. This is known as staging.

Unlike other types of cancer, retinoblastomas can be diagnosed just by examination and imaging– a biopsy is not usually necessary.

Treatment Options for Retinoblastoma

If retinoblastoma tumors are left untreated, they can grow and fill the eyeball.

Then, cancer cells might break away from the main tumor on the retina and reach surrounding areas, where they can block the flow of fluid inside the eye. This leads to a build-up of pressure and can cause loss of vision.

Ultimately, the cancer cells can migrate to anywhere in the body, including the brain, bones, and lymph nodes, forming more tumors and causing metastasis.

In consequence, staging is essential when choosing the type of treatment. This includes the position, size, and quantity of tumors.

The priority of treatment is to preserve the child’s life, preserve vision, and minimize complications or side effects of treatment.

The exact course of treatment is decided by the ophthalmologist and the pediatric oncologist, depending on the individual case.

In the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with up to 90% of children surviving into adulthood.

Intraocular Retinoblastoma

For smaller tumors (contained within the eye), treatment is given to the eye itself (local therapy) while your child is asleep and under general anesthetic.

There are several possible treatment options for small tumors:

Laser treatment to the eye (photocoagulation): Laser energy is targeted to blood vessels around the tumor, causing tiny blood clots and depriving the cancerous tissue of nutrients it needs.
Freezing the tumor (cryotherapy): Liquid nitrogen is used to freeze and destroy cancer cells.
Radioactive plaques: radioactive material (little plaques) is stitched over the tumor on the outside of the eye to deliver radiation beams. This form of treatment limits the damage to surrounding healthy tissue.

Intra-Arterial and Intra-Vitreous Chemotherapy

For larger tumors, there are other treatment options available, including newer techniques, such as:

Intra-arterial chemotherapy: Chemotherapy medicines are injected right into the small artery (a blood vessel) that goes to the eye. This helps the medication go straight to the tumor.

The Hospital Sant Joan de Deu has been a pioneer in Europe in introducing intra-arterial chemotherapy to treat retinoblastoma. To date, all centers have offered conservative intravenous chemotherapy treatments.

Intra-vitreous chemotherapy: Chemotherapy is injected into the central gelatinous part that fills the eyeball to treat small tumors that float in the vitreous humor.

Retinoblastoma Treatment - Retina Cancer

Extraocular Retinoblastoma

Retinoblastoma that has spread from the eye to surrounding tissues or other parts of the body is called extraocular. This is rare but can affect the brain, spinal cord, bone marrow, or lymph nodes.

Extraocular retinoblastoma may need aggressive treatment, such as radiation, chemotherapy, and a bone marrow transplant.

Oncolytic Virus Vcn-01 In Severe Retinoblastoma

In nearly 30% of cases, intra-arterial or intra-vitreous chemotherapy fails to treat retinoblastoma. The only remaining solution to date was enucleation of the affected eye.

However, this is a radical and mutilating approach for some patients. Therefore, it was necessary to develop a new line of research for treating aggressive cases.

The Sant Joan de Déu Children’s Hospital was the first center to treat retinoblastoma with an oncolytic virus. The ideal candidates are children who do not respond to conventional therapy.

This new viral therapy is the result of 5 years of research. The first patients treated demonstrated the therapeutic efficacy of the oncolytic virus VCN-01 showing promising results.

This new treatment involves injecting a genetically modified virus into the eye affected by retinal cancer. The oncolytic virus VCN-01 can identify and selectively target cancer cells and leave healthy body cells unharmed.

The work was published in January 2019 in the prestigious journal Science Translational Medicine.

Side Effects of Treatment and Follow-Up

The side effects will depend on the particular treatment used, including sight loss.

Sometimes side effects can occur years later, called late effects. The treating physician will discuss the risks before choosing the treatment.

Surgery and radiotherapy are related to functional and cosmetic problems. Chemotherapy may impact heart and kidney function or cause fertility problems in the future.

Children treated for retinoblastoma have a greater risk of cancer recurrence in and around the treated eye. Hence, following treatment, the eye specialist will frequently examine your child’s eyes under general anesthesia to check that the retina is healthy.

Also, children with heritable retinoblastoma will receive genetic counseling when they grow up.

The heritable form of retinoblastoma includes an increased risk of developing other types of cancer later in life. Hence, your child will be followed up closely into adulthood.

RETINOBLASTOMA SPECIALISTS AT SANT JOAN DE DÉU CHILDREN’S HOSPITAL (BARCELONA, SPAIN)

Doctor Jaume Català Mora

Specialist in anterior and posterior segment surgery, retinoblastoma, surgical retina, vitreous.

More information:

Pediatric ophthalmologist with over 20 years of experience.

Degree in medicine (University of Navarre, 1997).

Stay at Moorfields Eye Hospital (London, 2002).

Training in retina and pediatric retinoblastoma at the Casey Eye Institute and the Denvers Eye Institute in Portland (United States, 2007).

Languages: Spanish, English, French.

Doctor Jaume Mora Graupera

Specialist in developmental tumors: retinoblastoma, neuroblastoma, Ewing’s sarcoma, Wilms tumor, brainstem glioma. Scientific Director of the Oncology and Hematology Department

More information:

Pediatric oncologist with over 25 years of experience.

Degree in medicine (University of Barcelona, 1990).

Doctorate in Medicine (Autonomous University of Barcelona, 2003)

Since 2000, he has received numerous awards in recognition of his research work.

Scientific Director of the Oncology and Hematology Department of Sant Joan de Déu Hospital.

Stay at New York Hospital Cornell University and Memorial Sloan-Kettering Cancer Center (USA, 1996-1999)

Stay at Memorial Sloan-Kettering Cancer Center (USA, 1999 – 2001).

Languages: Spanish, English, French.