Introduction:
Retinoblastoma is a rare type of cancer that affects the retina of the eye. It usually develops in early childhood, especially in children below five years of age. The retina is located at the back of the eye, which coordinates with the brain and perceives light and color. Retinoblastoma generally affects only one eye, and in some rare instances, both eyes are affected. The initial sign of retinoblastoma is the white appearance of the pupil of the eye. It is referred to as Cat’s eye reflex or leukocoria. Although retinoblastoma is a malignant tumor, it can be treated and cured if diagnosed early. It can also be life-threatening if it spreads to other parts of the body. They may be associated with some hereditary conditions where both eyes are affected.
What Is the Retina?
The retina is a layer of cells attached to the back wall at the inner aspect of the eye. The retina serves as the sensitive layer of the eye located close to the optic nerve. Its function is to sense the light and color signals and send them to the brain through nerve impulses. The brain decodes the signals and sends them back to the retina for visual recognition.
What Is the Incidence of Retinoblastoma?
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Retinoblastoma is very rare, with an incidence of 1 in 18,000 to 20,000 births.
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It is the second most commonly occurring cancer in children after uveal melanoma.
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There is no gender predilection.
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The highest incidence is seen in India and Africa.
How Do They Progress as Cancer Cells?
The development of the eye begins during the intrauterine stage from the seventh week of gestation onwards. During the seventh week, the cornea, pupil, iris, and retina start developing. At this stage, the eyes will have retinoblast cells that multiply and fill the entire retina. When the development is complete, they receive signals to stop the multiplication and begin with the maturation of retinal cells. In the case of retinoblastoma, the cells continue to multiply in an uncontrolled manner and turn into cancer cells.
What Causes Retinoblastoma?
Retinoblastoma is caused due to mutations of the RB1 gene. The RB1 gene is the tumor suppressor gene located on the long arm of chromosome 13. They regulate cell growth and division and prevent cancer cell formation. The mutation of the RB1 gene prevents the formation of functional proteins that checks the formation of tumor cells in the body. In some cases, there occurs deletion of the chromosome that contains the RB1 gene.
What Are the Types of Retinoblastoma?
There are two types of retinoblastoma. They are:
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Type 1 Heritable Retinoblastoma: About 40 % of retinoblastoma cases are inherited conditions that run in families and get passed on from their parents. Inheritable retinoblastoma, both eyes are affected, and the condition is often diagnosed during the first year of life.
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Type 2 Non-heritable Retinoblastoma: 60 % of the cases of retinoblastoma are sporadic without familial history. They are diagnosed before the age of five.
What Are the Stages of Retinoblastoma?
Depending on the location of the tumor cells, they are categorized into five stages through a process called staging. This staging method may help the clinicians render the correct treatment plan depending on the severity.
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Stage 0: The tumor cells are present only in the eye and are often treated without surgery.
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Stage 1: The tumor cells are seen in the eyes, but the cancer cells and the eyes are removed surgically.
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Stage 2: The cancerous cells are present in the eye, and some tumor cells remain even after the surgical removal of the eye.
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Stage 3: Stage three is subdivided into 3a and 3b.
- Stage 3a: The tumor cells begin to spread to the adjacent tissues, and the eyeball socket is affected.
- Stage 3b: Tumor cells spread to the adjacent lymph nodes of the neck and ear. The lymph nodes are specialized glands that help the body resist infections.
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Stage 4: Like stage 3, stage 4 is subdivided into 4a and 4b.
- Stage 4a: Cancer cells proliferate and attack the bones, liver, and other vital structures.
- Stage 4b: The final stage and the cancerous growth occur rapidly, affecting the brain and spinal cord.
What Are the Signs and Symptoms?
The symptoms are noticeable during the first year of age in the case of bilateral retinoblastoma. In the case of unilateral retinoblastoma, the symptoms become evident by three years of age.
However, the common presentations of retinoblastoma are:
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The pupil appears white (called leukocoria) and is seen in 60 % of the cases.
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The eyes do not lie on a similar line, and they appear to be crossed. This condition is called strabismus.
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The eyes appear red, inflamed, and often painful.
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Extraocular growths are present that interfere with the eyesight of the child.
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Decreased ocular movements and vision.
What Is the Differential Diagnosis of Retinoblastoma?
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Coats Disease - Abnormal dilation of the blood vessels of the capillaries of the retina, mostly affecting the unilateral eye of young males.
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Toxocariasis - It is an infection transmitted from animals to humans caused by the parasitic roundworms commonly found in the intestine of dogs.
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Uveitis - Inflammation of the eye.
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Coloboma of the Choroid and Disk - Due to the failure or incomplete closure of the embryonic fissure during development.
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Cataract - Cloudy lens.
What Are the Possible Complications?
The complications that occur if the condition is not treated early are:
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Blindness.
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Detachment and necrosis of the retina.
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Invasion of the orbit and optic nerve.
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Cataracts and glaucoma.
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Recurrence of tumor cells.
How to Diagnose Retinoblastoma?
Retinoblastoma is usually diagnosed by a physical examination of the eye. Ophthalmologists may use the ophthalmoscope for the examination of the inner aspects of the eye. In some cases, the child is sedated with general anesthesia, and the medicines are administered through an intravenous route to get a detailed report of the condition.
Other diagnostic procedures for the diagnosis of retinoblastoma are:
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Ultrasound: The ultrasound uses sound waves to produce the internal picture of the eye and detects any abnormal changes.
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Magnetic Resonance Imaging (MRI): The MRI of the eye and brain is indicated if more information is required to establish the diagnosis. They produce more precise and accurate information than ultrasound.
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Spinal Tap: Spinal tap is also called lumbar puncture, which detects the presence of cancer cells in the brain and cerebrospinal fluid.
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Bone Marrow Biopsy: It is an investigative procedure where a small portion of the affected part is taken and viewed under the microscope. It helps to rule out any abnormal changes in the tissues.
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Wide Field Photography: They are specialized retinal imaging techniques that help to determine the retinoblastoma in the child.
Can Retinoblastoma Be Prevented?
Retinoblastoma, especially the non-heritable forms, is not preventable. However, if there is a known familial history, the child may require a regular eye examination to assess any problems in the eye. If any signs are suspected, then an appropriate and immediate diagnosis, followed by the initiation of treatment, is necessary to prevent serious complications.
How Are Retinoblastomas Treated?
Despite being malignant, retinoblastomas are successfully treated with a good prognosis. The treatment modalities followed are:
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Chemotherapy: This is the initial approach to managing any malignant tumor. The chemotherapeutic agents are used to regulate abnormal cell growth and rapid division. These medications are given through the intravenous route. However, one major drawback is that the normal and healthy cells are also destroyed along with the cancer cells.
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Cryotherapy: It is a minimally invasive technique where the tissues are subjected to extreme cold and frozen. The abnormal tissues are then removed from the body. This technique reduces the blood flow to the affected part, thus reducing inflammation.
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Laser Therapy: The cancer cells are subjected to heat and destroyed.
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Radiation Therapy: High doses of radiation are used to kill and shrink cancer cells, thus reducing their multiplication.
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Enucleation: It is a surgical approach indicated if there is a failed chemotherapy and the tumor size is large. In this procedure, the eye and a portion of the optic nerve are removed.
Conclusion:
Although the diagnosis of retinoblastoma is challenging and the cancer is a rare one, it generally has a good prognosis with early detection. Regular eye examinations are required in children with a familial history of retinoblastoma. Advanced treatment modalities are available that improve the quality of life for the survival of the child. Parents and other family members are given counseling regarding the treatment plan and are requested to cooperate with the healthcare professionals in treating the child. Regular follow-ups are essential and mandatory to check for the recurrence of the tumor.
