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 cellsthe basic structural and functional unit of all living things, most often in children.
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 tissuea group of cells that work together to perform a function 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 tumoura tissue mass that forms from groups of unhealthy cells suppressor gene (RB1). Hereditary retinoblastomas are generally bilateralaffecting both sides.
Hereditary retinoblastomas are classified as familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes. Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen 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 unilateralaffecting one side, 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 metastasised (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, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid.
- 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 localisedaffecting only one area of body 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 advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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:
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, potentially including:
- Ophthalmic artery infusion chemotherapya type of chemotherapy that involves delivering chemotherapy medication directly to the eye via infusion into the ophthalmic artery.
- Intravitreal chemotherapya type of chemotherapy that involves delivering chemotherapy medication directly into the vitreous humor (gel-like fluid inside the eye).
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Laser therapya procedure that uses an infrared laser to raise the temperature of the tumour to shrink and damage cancer cells.
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, specifically enucleationremoval of the eye and attached optic nerve.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
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.
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).
- Infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body 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
If your doctor suspects you have an retinoblastoma,they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
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- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- Eye tests, potentially including:
- Ophthalmoscopyan examination of the back of the eye (fundus) to visualise the retina, optic disc and/or blood vessels; also known as a fundoscopy.
- Fluorescein angiographyan eye test that involves using a special dye and camera to examine blood flow in the retina and choroid.
- Electroretinographyan eye test that measures small electrical signals given off by the eye when exposed to different types of light.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
- Imagingtests that create detailed images of areas inside the body tests, potentially including: