Retinoblastoma is a rare type of ocular cancer that develops in the retina of the eye. It is a type of blastoma, which are cancers that develop in precursor cells, most often in children. It can occur in one eye (unilateral retinoblastoma, usually non-hereditary), or in both eyes (bilateral retinoblastoma, often hereditary).
The eye is a sensory organ that allows us to see by reacting to light. Light passes through the cornea (the clear, front layer of the eye) and enters the eye through an opening called the pupil (the black centre of the eye). The amount of light received by the pupil is controlled by the iris (the coloured portion of the eye). This light is then passed through the lens (the clear, inner portion of the eye) and works together with the cornea to focus light onto the retina (a layer of tissue at the back of the eye that is sensitive to light). The retina then activates photoreceptors (image forming cells) to convert the light to electrical impulses that travel to the brain via the optic nerve, which is then converted into an image.
Retinoblastomas are generally found equally between the genders, and is usually diagnosed before the age of five. However, anyone can develop this disease.
Types of Retinoblastomas
Retinoblastomas can be classified in a few different ways.
Hereditary (Bilateral) Retinoblastomas
Hereditary retinoblastomas, also known as familial retinoblastomas, are tumours that have developed in patients with a family history of the disease. In most cases, this is due to a genetic mutation in the retinoblastoma tumour suppressor gene (RB1). Hereditary retinoblastomas are generally bilateral (affect both eyes).
Hereditary retinoblastomas are classified as familial cancer syndromes. Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutattions in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal.
Non-Hereditary (Unilateral) Retinoblastomas
Non-hereditary retinoblastomas are the most common subtype of this disease. They are non-hereditary, and may be the result of a random genetic mutation. In most cases, non-hereditary retinoblastomas are unilateral (only affect one eye), and are diagnosed at a later stage than hereditary retinoblastomas.
Intraocular Retinoblastomas
Intraocular retinoblastomas are cancers that are solely located in one or both of the eyes, and have not metastasized (spread).
Extraocular Retinoblastomas
Extraocular retinoblastomas are cancers that have spread beyond the eye into nearby tissues and organs.
Treatment
If a retinoblastoma is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.
There are two primary staging and grading systems used in the classification of retinoblastomas – The International retinoblastoma staging system and the TMN system.
The International Classification for Intraocular Retinoblastoma (ICIR)
The international classification for intraocular retinoblastoma (ICIR) divides intraocular cancer into five groups based on the characteristics of the tumour. These groups include:
- Group A: very low risk, very small tumours not located near critical structures, confined to retina.
- Group B: low risk, small tumours close to critical structures, confined to retina.
- Group C: moderate risk, well-defined tumours with small amounts of spread under the retina (subretinal seeding) or into the vitreous (gel-like substance in the eye) (vitreous seeding).
- Group D: High risk, large tumours with widespread subretinal and/or vitreous seeding, retina may become detached from the back of the eye.
- Group E: Very high risk, very large tumours extending near the front of the eye, may cause bleeding or glaucoma (high intraocular pressure).
TNM Staging System
The TNM system can also be used to classify a retinoblastoma. This system is beneficial for all types of retinoblastomas, including extraocular tumours. The TNM system is comprised of:
- T (tumour) indicates the size and depth of the tumour.
- N (nodes) indicates whether the cancer has spread to nearby lymph nodes.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Treatment options
Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for retinoblastomas may include:
- Chemotherapy, potentially including:
- Ophthalmic artery infusion chemotherapy.
- Intravitreal chemotherapy.
- Intrathecal chemotherapy.
- Radiation therapy.
- Laser therapy (transpupillary thermotherapy).
- Laser therapy (photocoagulation).
- Cryotherapy.
- Surgery, specifically enucleation (removal of the eye and attached optic nerve).
- Targeted therapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.
Risk factors
Because of how rare retinoblastomas are, there has been limited research into the risk factors of this disease. However, few potential factors have been identified:
- Family history of retinoblastomas.
- Genetic mutation in the RB1 (retinoblastoma protein 1) gene.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
The symptoms of retinoblastoma may include:
- The pupil (the black portion in the middle of the eye) appears white instead of red when light is shone into it (e.g., in photographs)
- Pain and/or redness in the eye.
- Eyes that suddenly start looking in different directions (crossed eyes or lazy eyes).
- Infection around the eye.
- Abnormally large eyeball.
- Cloudiness in the iris and pupil.
Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.
Some of the information regarding symptoms was obtained from the Retinoblastoma treatment (PDQ) page published by the National Cancer Institute.
Diagnosis/diagnosing
If your doctor suspects you have an ocular melanoma, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.
Imaging & blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), and/or ultrasound, depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Eye tests
Your doctor may request a variety of eye tests to check for abnormalities in your eye. One of these tests is called an ophthalmoscopy (fundoscopy), which involves using eye drops to widen your pupil and then looking into a large microscope. This option is beneficial as you may not require a biopsy after this test.
Another test, called a fluorescein angiography, examines the blood vessels and blood flow in the eye. This procedure is done by injecting a fluorescent dye into the bloodstream, which travels to the eye. A special camera is used to determine if there are any blocked or leaking vessels in the eye.
The doctor may also request an electroretinography, which measures small electrical signals given off by the eye when exposed to different types of light. This test can be used to measure the effectiveness of the retina during and/or after treatment.
Biopsy
In few instances, a biopsy may be required if the previous measures have come back inconclusive. In a biopsy, a tissue sample will be removed using a needle, and is then sent to a lab for analysis.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage retinoblastomas have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.