Retinoblastoma: Meaning, Causes, Symptoms, Treatment

Written by Medicover Team and Medically Reviewed by Dr Sarita Shrivastva , Oncologists

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Retinoblastoma is a rare type of eye cancer that develops in the retina, the light-sensitive tissue at the back of the eye. It primarily affects young children, before the age of 5 but in very rare cases, it can also occur in newborns like neonatal retinoblastoma or adults.

The disease occurs when the nerve cells in the retina change, grow uncontrollably and form tumors. If detected and treated early, retinoblastoma has a very high cure rate and most children can be saved with their vision preserved. However, advanced cases may lead to loss of vision or spread of cancer beyond the eye.

The condition can occur in one or both eyes and may be hereditary or non-hereditary. Hereditary retinoblastoma is linked to mutations in the RB1 gene, which controls cell growth. In non-hereditary cases, the transformation occurs spontaneously in retinoblast cells.

Different Types of Retinoblastoma

Retinoblastoma can appear in different forms depending on whether one or both eyes are affected and in rare cases, it can involve other parts of the brain. Following are the types of retinoblastoma:

Unilateral Retinoblastoma

This form affects only one eye and is the most common type. In most cases, it develops randomly or sporadically and is not linked to inherited genetic mutations.

Bilateral Retinoblastoma

This type occurs when both eyes are affected. It is associated with inherited RB1 gene mutations and may appear at a younger age compared to unilateral cases.

Trilateral Retinoblastoma

A very rare type in which another tumor develops in the pineal gland or other parts of the brain. Children with inherited retinoblastoma are at greater risk of developing this form.

Neonatal Retinoblastoma

This refers to cases diagnosed in newborns or very young infants. It is almost always related to inherited RB1 mutations passed down from a parent.

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Retinoblastoma Symptoms

The symptoms of retinoblastoma vary depending on the size and stage of the tumor. Parents are the first to notice unusual signs, sometimes even before the child complains of vision problems. Here are some common symptoms of retinoblastoma:

• Leukocoria or white reflection in the pupil: This is also called the cat's eye reflex, which appears as a white glow in the centre of the pupil when light shines on it such as in flash photos.
• Strabismus or crossed eyes: The eyes may not look in the same direction and signalling that one eye is not focusing properly.
• Vision problems: The child may have poor vision, blurred vision or difficulty tracking objects.
• Redness or swelling of the eye: When the tumor grows larger, it can cause irritation and visible swelling.
• Eye pain: More common in advanced cases due to pressure inside the eye.
• Different-colored irises: In some cases, one iris may appear a different shade than the other.

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What are the Causes of Retinoblastoma?

Retinoblastoma develops when there are mutations in a specific gene called RB1, which normally controls cell growth in the retina. When this gene stops working properly, retinal cells begin to grow and divide uncontrollably, eventually forming a tumor.

There are two main ways these gene changes can occur:

Inherited Retinoblastoma

This form is passed down from parents through the RB1 gene. Children with inherited retinoblastoma are more likely to have tumors in both eyes, called bilateral retinoblastoma. If one parent carries the faulty gene, there is about a 50% chance of passing it on to their child. Inherited cases appear at a very young age and sometimes even in newborns.

Sporadic Retinoblastoma

In most cases, the gene change occurs sporadically during early development in the child. This usually affects only one eye, called unilateral retinoblastoma and is not passed on to future generations.

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Retinoblastoma Classification

To guide treatment, doctors use the International Classification of Retinoblastoma (ICRB), which categorises the cancer based on the size of the tumor, its location in the retina, and whether it has spread within the eye. This system ranges from Group A (least severe) to Group E (most advanced).

• Group A: Very small tumours up to 3 mm and located away from the optic nerve and fovea. These tumors are treatable with local therapies and vision can be preserved.
• Group B: Larger tumors of more than 3 mm or tumors closer to vital structures in the retina. They are still confined to the eye and can be treated successfully.
• Group C: Tumours with small amounts of seeding, meaning tiny cancer cells have spread into nearby parts of the eye. These require more intensive treatment.
• Group D: Tumours with extensive seeding throughout the eye. At this stage, saving vision is very difficult but treatments may still preserve the eye itself in some cases.
• Group E: In most cases, the affected eye cannot be saved and removal may be recommended to prevent the cancer from spreading. It is very advanced tumors that fill much of the eye or cause severe damage.

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Retinoblastoma Staging and Progression

Staging describes how far retinoblastoma has progressed, whether it is confined to the eye or has spread to other parts of the body. Here is how retinoblastoma progresses:

• Stage 0: The cancer is present only inside the eye and can be treated successfully with local therapies such as laser, cryotherapy or chemotherapy. Surgery is not needed at this stage and vision can be preserved.
• Stage I: The affected eye has been removed, called enucleation and no cancer cells are found outside the eye. The risk of recurrence is very low at this stage.
• Stage II: Cancer cells have extended beyond the eye into surrounding tissues but it has not spread to other organs. Additional treatment such as chemotherapy or radiation can be required.
• Stage III: The tumor has spread into nearby structures such as the orbit or eye socket or lymph nodes around the eye. This stage carries a higher risk of progression and requires advanced treatment.
• Stage IV: The cancer has metastasised to other parts of the body such as the brain, bone marrow or other organs. This is the most advanced stage and usually requires an intensive, combined treatment plan.

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What are the Side Effects or Complications of Retinoblastoma?

If retinoblastoma is not detected and treated early, it can cause several complications that affect both health and quality of life. These complications may arise from the disease itself or as side effects of treatment.

• Loss of vision in one or both eyes.
• Spread of cancer to the brain, bone marrow or other parts of the body.
• Secondary cancers later in life, especially in inherited cases.
• Emotional and psychological stress for the child and family.
• Side effects of retinoblastoma treatments like vision impairment, cataracts or dry eyes.

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When to See a Doctor

Parents should consult an eye specialist if they notice:

• A white glow in their child's pupil in photos.
• Frequent eye crossing or strabismus.
• Unclear vision problems or poor eye tracking in infants.
• Redness, swelling or pain in the eye.
• Family history of retinoblastoma or RB1 gene mutation.

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How to Diagnose Retinoblastoma?

Retinoblastoma is usually suspected when a child shows early warning signs like a white reflection in the pupil or crossed eyes. Doctors use many specialised examinations and imaging tests to confirm the diagnosis as these symptoms can also occur in other eye conditions.p>

Eye examination

An ophthalmologist carefully examines the inside of the child's eye using a special instrument called an ophthalmoscope. This is done under anesthesia to keep the child still and ensure accurate results.

Retinoblastoma MRI

MRI scans are used to determine the exact size and location of the tumor inside the eye and to check if cancer has spread to nearby structures such as the brain or optic nerve.

Ultrasound of the eye

High-frequency sound waves help detect calcifications within the tumor, which are a sign of retinoblastoma.

CT scan

CT scans are less commonly used today because of radiation exposure risks in children.

Genetic testing

Since retinoblastoma can be inherited, doctors recommend genetic testing to identify mutations in the RB1 gene.

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Advanced Retinoblastoma Treatment

The goal of retinoblastoma treatment is to save the child's life, to preserve the affected eye and to maintain as much vision as possible. The choice of treatment depends on whether one or both eyes are involved, the size of the tumor and the stage of cancer. Here are some of the effective treatments:

1. Local Treatments

These treatments target the tumor directly within the eye and are used for small or medium-sized tumors.

• Laser therapy (photocoagulation): Uses a focused laser beam to destroy the tumor's blood supply and stop its growth.
• Cryotherapy: Involves freezing small tumours with extreme cold to kill cancer cells.
• Thermotherapy: Uses infrared or microwave energy to shrink and destroy cancerous tissue.

2. Chemotherapy

• Systemic chemotherapy: Specific medicines are delivered through the bloodstream to shrink tumors, which makes them easier to treat with local therapies.
• Intra-arterial chemotherapy: Medicine is delivered directly into the artery supplying the eye, which allows higher medicine concentration in the tumor with fewer body-wide side effects.
• Intravitreal chemotherapy: Injection of chemotherapy directly into the eye may be used if tumor seeds are floating inside the vitreous fluid.

3. Radiation Therapy

• External beam radiation therapy (EBRT): Uses high-energy rays from outside the body but it is now used less frequently in children due to long-term side effects.
• Plaque brachytherapy: A small radioactive disc is temporarily placed on the outside of the eye, close to the tumour to deliver radiation precisely to the cancer cells.

4. Surgery

• Enucleation or eye removal: In advanced cases where the eye cannot be saved, the entire eye may need to be removed to prevent the cancer from spreading. After healing, an artificial eye can be fitted for cosmetic appearance and confidence.

5. Supportive and Rehabilitation Care

• Counselling and family support: Emotional support is important for both the child and parents during treatment.
• Low vision aids such as glasses and magnifiers can help children adapt to changes in their vision.
• Rehabilitation services: Special programs help children with reduced vision develop independence and coping skills.

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Conclusion

Retinoblastoma is a rare but highly treatable childhood eye cancer. Early diagnosis and treatment are very important to save both life and vision of children. Advances in treatment like chemotherapy, laser therapy and supportive care have dramatically improved outcomes and offer a successful life to many children. Retinoblastoma has a very high survival rate of above 95%. Most children can be cured if the disease is limited to the eye.

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