Retinoblastoma
Retinoblastoma is a malignant, cancerous tumor that originates in the retina inside the eye. It develops almost exclusively in children less than five years old.
If left untreated, retinoblastoma almost always grows, making the eye blind and painful.
The tumor can also spread to other parts of the body to cause fatal illness.
Some patients with retinoblastoma are also at risk of developing cancers in other parts of the body later in life; such patients can also pass on the disease to their children.
If left untreated, retinoblastoma almost always grows, making the eye blind and painful.
The tumor can also spread to other parts of the body to cause fatal illness.
Some patients with retinoblastoma are also at risk of developing cancers in other parts of the body later in life; such patients can also pass on the disease to their children.
Retinoblastoma growth and spread
Retinoblastoma tends to grow in front of the retina into the vitreous cavity (‘endophytic growth’) and/or under the retina (‘exophytic growth’) or in both directions.
Rarely, retinoblastoma remains very thin, spreading mostly within the retina (‘diffuse growth’).
Many retinoblastomas scatter seeds into the vitreous cavity and/or under the retina.
Large tumors under the retina cause a buildup of fluid under the retina (‘retinal detachment’).
Advanced tumors can seed into the anterior chamber of the eye and can cause new vessels to form on the iris (‘neovascularization’).
Retinoblastoma can invade the uvea, from where they can enter the blood circulation and disseminate to other parts of the body.
Retinoblastomas can also invade the optic disc and nerve and can spread along the nerve to the brain.
Retinoblastomas can also grow through the wall of the eye (the 'sclera') into the tissues behind the eye (‘extraocular spread’), pushing the eye forward (‘proptosis’).
Rarely, retinoblastoma remains very thin, spreading mostly within the retina (‘diffuse growth’).
Many retinoblastomas scatter seeds into the vitreous cavity and/or under the retina.
Large tumors under the retina cause a buildup of fluid under the retina (‘retinal detachment’).
Advanced tumors can seed into the anterior chamber of the eye and can cause new vessels to form on the iris (‘neovascularization’).
Retinoblastoma can invade the uvea, from where they can enter the blood circulation and disseminate to other parts of the body.
Retinoblastomas can also invade the optic disc and nerve and can spread along the nerve to the brain.
Retinoblastomas can also grow through the wall of the eye (the 'sclera') into the tissues behind the eye (‘extraocular spread’), pushing the eye forward (‘proptosis’).
Spread to Other Parts of the Body
Retinoblastoma can disseminate through the blood system to other parts of the body (i.e., they can 'metastasize'). This is more likely to happen if the tumor invades the uvea, the optic nerve (particularly the optic nerve outside the eye, beyond the lamina cribrosa) or the orbit.
It can also extend along the optic nerve to the brain.
Patients with germinal retinoblastoma can develop brain tumors known as pinealoblastoma, as well as cancers in bone (‘osteosarcomas’) and other parts of the body.
It can also extend along the optic nerve to the brain.
Patients with germinal retinoblastoma can develop brain tumors known as pinealoblastoma, as well as cancers in bone (‘osteosarcomas’) and other parts of the body.
Cause of Retinoblastoma
Either by chance or by inheritance…
The body is made up of organs, which consist of tissues, which are composed of cells. For example, the eyes are visual organs, which contain tissues such as the cornea, the sclera, the lens, the uvea, the vitreous gel - and the retina.
The retina is composed of many types of cell, including those that are sensitive to light (i.e., receptor cells, consisting of color-sensitive cones and brightness-sensitive rods).
The behavior of cells is regulated by genes. Genes control what cells do, where they go, what they produce, when they proliferate, and, importantly, when they stop multiplying.
Each gene exists in duplicate, with one inherited from the father and the other from the mother. With many genes, if one gene stops working because of a mutation, the other gene in the pair compensates, so that the cell continues to behave normally. Disease occurs only when both genes in the pair are defective.
The type of disease that develops will depend on the activity regulated by the gene. Some mutations cause retinitis pigmentosa, with night-blindness, tunnel vision and eventually total blindness. Other mutations, such as those affecting the RB1 gene, result in uncontrolled cell replication, that is, cancer.
When both maternal and paternal copies of the same RB1 gene are mutated in the same cell, then the cell proliferates uncontrollably to form a cancer. If this ‘double-hit’ happens in a retinal cell, then retinoblastoma arises. If it occurs in a bone cell, then a bone cancer occurs and this is known as 'osteosarcoma'. If the second mutation occurs in a cell in the pineal gland, then pinealoblastoma forms, and so on.
It is very rare more than one cell in the body to develop the same mutation in both RB1 genes so that patients with such ‘sporadic’ disease have only one tumor.
If an RB1 mutation is inherited from a parent, then all cells in the body have that mutation so that the chances of a mutation in the second RB1 gene are quite high. Patients with such ‘heritable’ disease tend to have several retinoblastomas, usually affecting both eyes. They can also develop a malignant tumor in or near the pineal gland in the brain and this tumor is known as 'pinealoblastoma'. They are also at increased risk of developing osteosarcomas and other cancers later in life. They may also pass on this mutation to any of their children.
In some patients, the first RB1 mutation occurs in the baby before birth. If this happens in the first few days of fetal development, then many but not all cells in the body carry that mutation (so-called ‘mosaicism’).
The body is made up of organs, which consist of tissues, which are composed of cells. For example, the eyes are visual organs, which contain tissues such as the cornea, the sclera, the lens, the uvea, the vitreous gel - and the retina.
The retina is composed of many types of cell, including those that are sensitive to light (i.e., receptor cells, consisting of color-sensitive cones and brightness-sensitive rods).
The behavior of cells is regulated by genes. Genes control what cells do, where they go, what they produce, when they proliferate, and, importantly, when they stop multiplying.
Each gene exists in duplicate, with one inherited from the father and the other from the mother. With many genes, if one gene stops working because of a mutation, the other gene in the pair compensates, so that the cell continues to behave normally. Disease occurs only when both genes in the pair are defective.
The type of disease that develops will depend on the activity regulated by the gene. Some mutations cause retinitis pigmentosa, with night-blindness, tunnel vision and eventually total blindness. Other mutations, such as those affecting the RB1 gene, result in uncontrolled cell replication, that is, cancer.
When both maternal and paternal copies of the same RB1 gene are mutated in the same cell, then the cell proliferates uncontrollably to form a cancer. If this ‘double-hit’ happens in a retinal cell, then retinoblastoma arises. If it occurs in a bone cell, then a bone cancer occurs and this is known as 'osteosarcoma'. If the second mutation occurs in a cell in the pineal gland, then pinealoblastoma forms, and so on.
It is very rare more than one cell in the body to develop the same mutation in both RB1 genes so that patients with such ‘sporadic’ disease have only one tumor.
If an RB1 mutation is inherited from a parent, then all cells in the body have that mutation so that the chances of a mutation in the second RB1 gene are quite high. Patients with such ‘heritable’ disease tend to have several retinoblastomas, usually affecting both eyes. They can also develop a malignant tumor in or near the pineal gland in the brain and this tumor is known as 'pinealoblastoma'. They are also at increased risk of developing osteosarcomas and other cancers later in life. They may also pass on this mutation to any of their children.
In some patients, the first RB1 mutation occurs in the baby before birth. If this happens in the first few days of fetal development, then many but not all cells in the body carry that mutation (so-called ‘mosaicism’).
Chances of Relatives having the Retinoblastoma Mutation
The chances of an RB1 mutation being present in a brother or sister depend on whether or not a parent's germ cells (i.e., eggs or sperm) have the mutation. If the germ cells are affected, the disease is described as ‘germline’ whereas if the germ cells are unaffected, the disease is ‘somatic’.
With germline retinoblastoma, every egg or sperm cell has a mutation in one of the two RB1 genes. The chances of passing on the gene to the next generation are therefore one in two (i.e., 50%, or ‘five-in-ten’ or ‘fifty-fifty’). When this RB1 mutation is inherited, the chances of developing retinoblastoma are approximately 90% (or ‘nine-in-ten’). If a patient as germinal retinoblastoma, therefore, the chances of retinoblastoma are approximately 45% in every child of that patient.
If the parents of a child with germline retinoblastoma are apparently healthy, there is approximately a 10% chance that one of them has the mutation in the germ cells. This equates to a 5% (‘one-in-twenty’) chance of the patient’s brother or sister having the mutation. The chances of developing retinoblastoma lessen with age so that tumors are less likely to appear in older brothers and sisters than in younger siblings.
If the mutation is somatic (i.e., not affecting germ cells) then the disease is not transmitted to the patient’s children.
With germline retinoblastoma, every egg or sperm cell has a mutation in one of the two RB1 genes. The chances of passing on the gene to the next generation are therefore one in two (i.e., 50%, or ‘five-in-ten’ or ‘fifty-fifty’). When this RB1 mutation is inherited, the chances of developing retinoblastoma are approximately 90% (or ‘nine-in-ten’). If a patient as germinal retinoblastoma, therefore, the chances of retinoblastoma are approximately 45% in every child of that patient.
If the parents of a child with germline retinoblastoma are apparently healthy, there is approximately a 10% chance that one of them has the mutation in the germ cells. This equates to a 5% (‘one-in-twenty’) chance of the patient’s brother or sister having the mutation. The chances of developing retinoblastoma lessen with age so that tumors are less likely to appear in older brothers and sisters than in younger siblings.
If the mutation is somatic (i.e., not affecting germ cells) then the disease is not transmitted to the patient’s children.
Finding out whether or not Retinoblastoma is Germline
If there is more than one retinoblastoma, affecting one or both eyes and/or if any other relatives have had this disease, the chances of germline disease are 100%.
When there is only one retinoblastoma in only one eye, and when no other family members have had this disease, the chances of germline disease are approximately 12% (i.e., ‘one-in-eight’).
The first step is therefore to list all the relatives and find out whether any have had retinoblastoma and, if so, who has had the disease.
The next step is to examine the parents as well as any brothers and sisters for retinal tumors and tumors in other parts of the body. Some retinoblastomas die or stop growing without ever causing any symptoms (i.e., retinoctyomas or retinomas).
Genetic tests can be performed to determine whether a retinoblastoma mutation is present and to identify the gene that is mutated. There are many genes that can result in retinoblastoma if mutated.
If the eye is removed, a sample can be obtained from the tumor itself. If the eye is not removed, a blood sample or a buccal scraping (from the inside of the mouth) can be taken.
Each family with germline retinoblastoma has a mutation that is particular to that family. In other words, different families have different mutations. Once the mutation particular to an individual patient is identified, it becomes easier to test brothers, sisters and other relatives for the same mutation. This makes it possible to identify which relatives are at risk of retinoblastoma so that they can receive special examinations to detect and treat any tumors as early as possible.
Genetic tests and genetic counseling are provided by the geneticist, who has special expertise in this aspect of care.
When there is only one retinoblastoma in only one eye, and when no other family members have had this disease, the chances of germline disease are approximately 12% (i.e., ‘one-in-eight’).
The first step is therefore to list all the relatives and find out whether any have had retinoblastoma and, if so, who has had the disease.
The next step is to examine the parents as well as any brothers and sisters for retinal tumors and tumors in other parts of the body. Some retinoblastomas die or stop growing without ever causing any symptoms (i.e., retinoctyomas or retinomas).
Genetic tests can be performed to determine whether a retinoblastoma mutation is present and to identify the gene that is mutated. There are many genes that can result in retinoblastoma if mutated.
If the eye is removed, a sample can be obtained from the tumor itself. If the eye is not removed, a blood sample or a buccal scraping (from the inside of the mouth) can be taken.
Each family with germline retinoblastoma has a mutation that is particular to that family. In other words, different families have different mutations. Once the mutation particular to an individual patient is identified, it becomes easier to test brothers, sisters and other relatives for the same mutation. This makes it possible to identify which relatives are at risk of retinoblastoma so that they can receive special examinations to detect and treat any tumors as early as possible.
Genetic tests and genetic counseling are provided by the geneticist, who has special expertise in this aspect of care.
Treatment of Retinoblastoma
The main priority is to save life. The next objective is to conserve as much vision as possible, as long as it is safe to do so. As a last resort, if the risks outweigh the benefits, it may be necessary to remove one or both eye.
Small retinoblastomas can effectively be treated with binocular indirect laser therapy if located towards the back of the eye or with cryotherapy (i.e., ‘freezing treatment’) if they are placed nearer the front of the eye. The treatment usually needs to be repeated several times, even after the tumor appears to have gone completely.
Retinoblastomas that are too large for such ‘focal’ therapy can first be treated with chemotherapy until they are small enough for laser or cryotherapy. The chemotherapy can be administered intravenously (i.e., 'intra-venous chemotherapy') or into an artery behind the eye (i.e., 'intra-arterial chemotherapy'). If the retinoblastoma has scattered seeds into the jelly of the eye (i.e., ‘vitreous gel’), it may be necessary to inject the chemotherapy drug directly into the eye itself (i.e., ‘intra-vitreal chemotherapy’). Chemotherapy needs to be repeated every 3-4 weeks for several weeks or months to achieve tumor control.
Radiotherapy can be administered by placing a temporary radioactive implant known as a plaque behind the eye for a few days (i.e., ‘brachytherapy’) or by directing a beam of radiation at the eye from an external source (i.e., ‘external beam radiotherapy’). Radiotherapy is avoided, especially in patients with germinal retinoblastoma and in babies less than a year old. This is because of the risks involved (particularly new cancers and facial deformity).
If the retinoblastoma is very advanced, the best treatment may be eye removal and this operation is known as 'enucleation'. Babies and young children cope with this remarkably well and better than what the parents might expect.
Treatment is selected on an individual basis, according to tumor size, number and location. It involves close collaboration between ocular oncologists, pediatric oncologists and pediatric ophthalmologists as well as other specialists and support staff.
Small retinoblastomas can effectively be treated with binocular indirect laser therapy if located towards the back of the eye or with cryotherapy (i.e., ‘freezing treatment’) if they are placed nearer the front of the eye. The treatment usually needs to be repeated several times, even after the tumor appears to have gone completely.
Retinoblastomas that are too large for such ‘focal’ therapy can first be treated with chemotherapy until they are small enough for laser or cryotherapy. The chemotherapy can be administered intravenously (i.e., 'intra-venous chemotherapy') or into an artery behind the eye (i.e., 'intra-arterial chemotherapy'). If the retinoblastoma has scattered seeds into the jelly of the eye (i.e., ‘vitreous gel’), it may be necessary to inject the chemotherapy drug directly into the eye itself (i.e., ‘intra-vitreal chemotherapy’). Chemotherapy needs to be repeated every 3-4 weeks for several weeks or months to achieve tumor control.
Radiotherapy can be administered by placing a temporary radioactive implant known as a plaque behind the eye for a few days (i.e., ‘brachytherapy’) or by directing a beam of radiation at the eye from an external source (i.e., ‘external beam radiotherapy’). Radiotherapy is avoided, especially in patients with germinal retinoblastoma and in babies less than a year old. This is because of the risks involved (particularly new cancers and facial deformity).
If the retinoblastoma is very advanced, the best treatment may be eye removal and this operation is known as 'enucleation'. Babies and young children cope with this remarkably well and better than what the parents might expect.
Treatment is selected on an individual basis, according to tumor size, number and location. It involves close collaboration between ocular oncologists, pediatric oncologists and pediatric ophthalmologists as well as other specialists and support staff.
Aftercare following Retinoblastoma Treatment
Frequent ocular examinations are needed in case any tumors persist or return after treatment or if new retinoblastomas arise. This is so that any active disease is treated promptly before the chances of success diminish.
Ocular examinations are also necessary to identify any ocular disturbance cause by the tumor or by treatment and to administer further care as appropriate. An example of such disturbance is cataract, which can be removed once there has been no active retinoblastoma for more than a year.
Patients with germline retinoblastoma need regular brain scans to detect any brain tumor as early as possible. The preferred type of scan is magnetic resonance imaging (MRI), which is sensitive and which avoids radiation exposure.
Patients with an increased risk of tumor dissemination to other parts of the body require regular exams to detect tumor without delay. These exams consist of special scans, lumbar punctures (sampling fluid from the spine) and bone marrow biopsies (sampling bone in the hip).
Patients who have had systemic/intravenous chemotherapy need regular hearing tests in case any of the therapeutic agents have impaired hearing.
Patients also need regular sight tests to ensure that they can see as well as possible, if necessary with the aid of glasses.
If an eye has been removed, patients will need to remain under the care of an ocularist, who will fit a prosthesis (artificial eye) and who will replace the prosthesis with a new one whenever necessary.
Eventually, all patients should attend a survivorship clinic so that they can receive appropriate counseling and advice on how to reduce the chances of developing new tumors (eg, avoiding smoking, alcohol, excessive sunlight).
Ocular examinations are also necessary to identify any ocular disturbance cause by the tumor or by treatment and to administer further care as appropriate. An example of such disturbance is cataract, which can be removed once there has been no active retinoblastoma for more than a year.
Patients with germline retinoblastoma need regular brain scans to detect any brain tumor as early as possible. The preferred type of scan is magnetic resonance imaging (MRI), which is sensitive and which avoids radiation exposure.
Patients with an increased risk of tumor dissemination to other parts of the body require regular exams to detect tumor without delay. These exams consist of special scans, lumbar punctures (sampling fluid from the spine) and bone marrow biopsies (sampling bone in the hip).
Patients who have had systemic/intravenous chemotherapy need regular hearing tests in case any of the therapeutic agents have impaired hearing.
Patients also need regular sight tests to ensure that they can see as well as possible, if necessary with the aid of glasses.
If an eye has been removed, patients will need to remain under the care of an ocularist, who will fit a prosthesis (artificial eye) and who will replace the prosthesis with a new one whenever necessary.
Eventually, all patients should attend a survivorship clinic so that they can receive appropriate counseling and advice on how to reduce the chances of developing new tumors (eg, avoiding smoking, alcohol, excessive sunlight).
Ocular Oncology Nurse
The Ocular Oncology Nurse works directly with the Attending Ocular Oncologist and has significant experience speaking with children and families affected by retinoblastoma. She may be reached during regular business hours by:
Office phone: 415-514-8957
Email: jami.manning@ucsfmedctr.org
Office phone: 415-514-8957
Email: jami.manning@ucsfmedctr.org
Retinoblastoma Team at UCSF
Many specialists across different disciplines at UCSF come together to create the retinoblastoma team. If your child is diagnosed with retinoblastoma, you will come to meet the members of the team relevant to your case.
Ophthalmology Team
Bertil Damato, PhD, MD
Director of the retinoblastoma service and the Ocular Oncology service at UCSF.
Jami Manning, RN
Specialty Ocular Oncology nurse.
Antionette Gutierrez
Surgical scheduler, the primary contact for families in terms scheduling examinations under anesthesia at UCSF.
Michael Seider, MD
Fellow in Ocular Oncology.
Pediatric Oncology Team
Katherine Matthay, MD
Division Chief of the Pediatric Hematology/Oncology service at UCSF.
Sheila Thampi, MD
Fellow in Pediatric Oncology.
Ilana Withop, NP
Pediatric Oncology Nurse Practitioner.
Pediatric Ophthalmology
Alejandra de Alba Campomanes, MPH, MD
Pediatric Ophthalmologist
Genetics
Robert Nussbaum, MD
Chief of the Division of Medical Genetics at UCSF.
Ophthalmology Team
Bertil Damato, PhD, MD
Director of the retinoblastoma service and the Ocular Oncology service at UCSF.
Jami Manning, RN
Specialty Ocular Oncology nurse.
Antionette Gutierrez
Surgical scheduler, the primary contact for families in terms scheduling examinations under anesthesia at UCSF.
Michael Seider, MD
Fellow in Ocular Oncology.
Pediatric Oncology Team
Katherine Matthay, MD
Division Chief of the Pediatric Hematology/Oncology service at UCSF.
Sheila Thampi, MD
Fellow in Pediatric Oncology.
Ilana Withop, NP
Pediatric Oncology Nurse Practitioner.
Pediatric Ophthalmology
Alejandra de Alba Campomanes, MPH, MD
Pediatric Ophthalmologist
Genetics
Robert Nussbaum, MD
Chief of the Division of Medical Genetics at UCSF.
Ocular Oncology Clinic at UCSF
8 Koret Way, U525
San Francisco CA 94143
Main Office: 415-514-6918
24HR Main: 415-353-2800
Fax: 415-514-6919
San Francisco CA 94143
Main Office: 415-514-6918
24HR Main: 415-353-2800
Fax: 415-514-6919
UCSF Ambulatory Care Center
400 Parnassus, Level B1
San Francisco, CA 94143
San Francisco, CA 94143
Further Information
A Parent’s Guide to Understanding Retinoblastoma
www.retinoblastoma.com
American Childhood Cancer Organization
http://www.acco.org/Information/AboutChildhoodCancer/TypesofChildhoodCancer/retino.aspx
National Cancer Institute, Young People with Cancer: A Handbook for Parents
http://www.cancer.gov/cancertopics/coping/youngpeople
National Federation of the Blind
https://nfb.org
www.retinoblastoma.com
American Childhood Cancer Organization
http://www.acco.org/Information/AboutChildhoodCancer/TypesofChildhoodCancer/retino.aspx
National Cancer Institute, Young People with Cancer: A Handbook for Parents
http://www.cancer.gov/cancertopics/coping/youngpeople
National Federation of the Blind
https://nfb.org
