Retinoblastoma | Description | Prevention | Causes and symptoms | Treatment
Definition
Retinoblastoma is a cancer affecting one or both eyes. It occurs mainly in children under the age of four. Its name is derived from the area of the eye that is affected, the retina. The retina is the part of the eye that captures the images of the outside world and transfers these images to the brain. If the eye is thought of as a camera, the retina can be thought of as the film in the camera.
Description
Retinoblastoma is the most common primary eye tumor of infancy and childhood, accounting for about one percent of all pediatric tumors. In about 75% of cases, retinoblastoma only affects one eye; when this occurs, it is referred to as unilateral retinoblastoma. In 25% of cases, it affects both eyes, and is referred to as bilateral retinoblastoma. Approximately 90% of children who present with retinoblastoma have no previous family history of the disease. However, in about 10% of cases, there is a definite family history of retinoblastoma.
Many of the early symptoms of retinoblastoma, such as intermittent pain of the eye, inflammation of the eye, and poor vision, are often overlooked. It is often a parent who notices the most visible sign ofretinoblastoma, that being a whitish appearing pupil, known as leukocoria. If retinoblastoma is detected early enough, treatment such as surgery or radiation can result in a 95% cure and survival rate.
Genetic profile
The are two main types of retinoblastoma, called hereditary and nonhereditary. The vast majority of cases, approximately 90%, are nonhereditary, meaning that the children who develop retinoblastoma are the first ones in their family to have cancer of the eye. Ten percent of the cases are hereditary, meaning that someone in the immediate family, usually a parent, grandparent, aunt, uncle, brother or sister, also has the condition. In hereditary retinoblastoma, both eyes are usually affected. In non-hereditary retinoblastoma, usually only one eye is affected.
In 1986, after years of research, it was found that an abnormal gene on chromosome 13 is responsible for retinoblastoma. Part of chromosome 13 is responsible for normal growth and cellular division in the retina; in retinoblastoma, this growth and division is uncontrolled, leading to cancer of one or both eyes.
In 40% of children who present with retinoblastoma, there will be an abnormality of chromosome 13 in every cell in that child's body, including the affected eye(s). In 60% of the children who have retinoblastoma, the abnormal chromosome will only be found in the eye.
As stated earlier, retinoblastoma can occur spontaneously (nonhereditary) or be seen in families (hereditary). If neither parent had retinoblastoma, then the chances of having a child with retinoblastoma is approximately one in 20,000. However, parents with a child having the condition should have a detailed retinal exam to see if they perhaps had retinoblastoma and were not aware of it. One percent of the time, this exam will reveal that one of the parents had a limited form of retinoblastoma that was never diagnosed. In this case, a full 45% of the parent's children will have the chance of developing retinoblastoma. In even rarer cases, the parent could have the gene for retinoblastoma without any evidence of the disease in their eyes. This is called a carrier state, and again, 45% of the parent's children will have the chance of developing retinoblastoma. There are now genetic tests to determine if a parent is a carrier of the condition. However, the current test is only 80% accurate, and costs between $2,500.00 and $4,000.00.
In hereditary retinoblastoma, if a parent has bilateral (seen in both eyes) retinoblastoma and decides to have children, then with each pregnancy, there is a 45% chance his or her children will develop retinoblastoma. Many of these children will also have tumors spread from their retinas into their brains at the time of birth. Other children will not develop tumors until they are two to three years of age. Most children born to a parent with bilateral retinoblastoma will also have the condition in both eyes. Fifteen percent of these children will have retinoblastoma in only one eye.
There is also hereditary retinoblastoma in which the parent has unilateral (in one eye) retinoblastoma. In this case, 7–15% of the children of these parents will develop retinoblastoma. Like the children born to a parent with bilateral retinoblastoma, most of the children (approximately 85%) born to parents with unilateral retinoblastoma will have bilateral retinoblastoma.
Demographics
Retinoblastoma is the most common type of eye cancer in children. It occurs in approximately one in 20,000 births, which means that each year about 200–300 children are affected in the United States. The incidence of retinoblastoma in other areas of the world is thought to be approximately the same. As more and more children survive this condition and grow into adulthood and have their own families, the frequency of the condition in the population will probably increase.Retinoblastoma affects children of all races and is seen equally in both boys and girls.
Signs and symptoms
Since the successful management of retinoblastoma depends on detecting it early, the recognition of the signs and symptoms of the condition is critical. This is especially true for primary care physicians, who are often the first medical personnel to see infants or children with retinoblastoma.
There are many ways that retinoblastoma can present itself in infants and children. More than half of all patients with the condition will have a white pupil reflex, called leukocoria. In healthy infants and children, their pupils will appear black, or, when photographed, red. However, patients with retinoblastoma will often have a pupil that appears gray or white.
The second most common presenting sign of retinoblastoma, occurring about 25% of the time, is a crossed eye, a medical condition referred to as strabismus. The child's eye may appear to be looking out towards the ear, called exotropia, or inward towards the nose, called esotropia. It should be noted that three to four percent of all American children present with some form of strabismus, but not all of these children have retinoblastoma. However, since 25% of children with retinoblastoma have strabismus, any child with this condition should have a detailed eye exam to rule outretinoblastoma.
While leukocoria and strabismus are the two most common presenting signs of retinoblastoma, there are other ways the condition may present itself. Other symptoms may include a red, painful eye, poor vision, orbital cellultis (inflammation of the skin and tissue around the eye), and amblyopia, or "lazy eye." Heterochromia, which is different colored irises (the colored part in the center of the eye surrounding the pupil), may also be the first signs of retinoblastoma.
Diagnosis
The diagnosis of retinoblastoma is frequently made by the parents of an infant or child with the condition. Often, the parents will tell the physician that they have noticed that their child's eye looks "white," or that the child's eye or eyes seem to drift to one side or the other.
When a child is born into a family that has a history of retinoblastoma, diagnosis of the condition can often be made before the baby leaves the hospital by an eye specialist, or ophthalmologist. If there is no family history, and the initial diagnosis is made by the parents or family physician, then the child can be sent to an ophthalmologist for a more thorough eye exam.
To examine a child for retinoblastoma, dilating drops are placed in both eyes to dilate (enlarge) the pupils and allow the ophthalmologist to view the retina. If a tumor is seen or suspected, an ultrasound examination, which uses sound waves to penetrate and outline structures in the eye, is used to confirm the presence of a tumor. A specialized x ray, called a CAT scan, which uses computers to take very detailed pictures of the inside of the body, can be used to see if there are tumors in other parts of the body.
Treatment and management
Treatment options for retinoblastoma have significantly increased over the past twenty years. The earliest form of treatment for retinoblastoma was enucleation, the removal of the major portion of the affected eye. This led to total loss of vision in that eye. While enucleation is still used, especially when the tumor is very large, newer, more sophisticated treatments have emerged that offer the chance to save at least some vision in the affected eye.
Lasers can be used in a treatment known as photocoagulation. This treatment is best used when the tumor is small and confined to the retina. The laser is actually used to burn and destroy blood vessels that feed the tumor, rather then directly on the tumor itself. The treatment can be repeated one or two times, and in some studies complete remission of the retinoblastoma was achieved in 70% of patients.
Another modality that works well with tumors that are confined to the retina is cryotherapy. It may be used as either the primary mode of treatment or in conjunction with other treatment modalities. Like photocogulation, cryotherapy has its highest success rates with smaller tumors. Unlike photocoagulation, cryotherapy uses extreme cold to destroy the tumor itself.
Thermotherapy uses heat generated from ultrasound or microwaves to destroy the retinoblastoma tumor. While thermotherapy works well on its own with small tumors, it is even more effective when used with chemotherapy or radiation therapy, which are thought to make the tumor more susceptible to the heat generated by thermotherapy.
The use of conventional external beam radiation is still used for retinoblastoma, especially for tumors that are larger and have spread outside the retina. While radiation is applied directly to the tumor, with careful application the eye itself can be saved from destruction in about 75% of patients. In 35% of patients who receive external beam radiation, there is an increased risk for aretinoblastoma tumor to develop in the other eye within a 30-year time frame. Therefore, external beam radiation is generally only used when other conservative measures, such as cryotherapy or photocoagulation fail or cannot be used due to large tumor size.
Probably the most significant advancement in the treatment and management of retinoblastoma has come about in the use of chemotherapy. While in the past chemotherapy was only used to treat patients whose tumors had spread outside the eye, newer chemotherapy agents such as carboplatin and etoposide, along with older agents such as vincristine, are being used to treat tumors that are confined to the eye with significant success. Using these chemotherapeautic agents, it has been shown that tumors typically decrease in size 30–45%. This then allows more conservative and eye-sparing therapy such as cryotherapy and photocoagulation to be used much more effectively.
Prognosis
The prognosis for the vast majority of patients with retinoblastoma is excellent. In the United States, over 95% of children with retinoblastoma survive and lead healthy, productive lives.
Children who have unilateral retinoblastoma have at least one normal eye and can lead normal childhood lives, and even drive cars as they get older. The majority of children with bilateral retinoblastoma retain some vision in one eye, and sometimes both eyes. However, all children affected with bilateral retinoblastoma and 15% of children with familial unilateral retinoblastoma have a higher risk of developing other cancers throughout their lives. Therefore, children in these categories need to have regular medical checkups throughout their lives to watch for any signs of secondary cancers in areas such as bone, muscle, skin, and brain.
Resources
BOOKS
Gelehrter, T., F. Collins, and D. Ginsburg. Principles of Medical Genetics. Baltimore, MD: Williams and Wilkins, 1998.
PERIODICALS
Benz, Matthew, Ingrid Scott, Timothy Murray, Deborah Kramer, and Stuart Toledano. "Complications of Systemic Chemotherapy as Treatment of Retinoblastoma." Archives of Ophthalmology 118 (April 2000): 577-578.
MacDonald, Deborah, and Mira Lessick. "Hereditary Cancers in Children and Ethical and Psychosocial Implications." Journal of Pediatric Nursing 15, no. 4 (August 2000): 217-220.
Zhao, Da-You, Carol Shields, Jerry Shields, and Kann Gunduz. "New Developments in the Management of Retinoblastoma." Journal of Ophthalmic Nursing and Technology 17, no. 1 (1998): 13-18.
ORGANIZATIONS
Eye Cancer Network. 115 East 61st St., New York, NY 10021. (212) 832-8170.<http://www.eyecancer.com>.
National Eye Institute. Bldg. 31 Rm 6A32, 31 Center Dr., MSC 2510, Bethesda, MD 20892-2510. (301) 496-5248. 2020@nei.nih.gov. <http://www.nei.nih.gov>.
National Retinoblastoma Research and Support Foundation. PO Box 016880, 900 NW 17th St., Room 257, Miami, FL 33101-6880. (800) 226-2734.
University of Pennsylvania Cancer Center. 3400 Spruce St., Philadelphia, PN 19104. (215) 662-4000.<www.oncolink.upenn.edu>.
Edward R. Rosick, DO, MPH, MS
