Diagnosis and Treatment of Retinoblastoma

No screening tests are in practice for retinoblastoma, namely because it is so rare. However, if retinoblastoma is suspected, Sheba’s doctors may perform the following tests:

• Blood tests: an initial blood test can be done to look for an RB1 gene mutation in cells outside the eye. This test can usually tell if the child has the inherited form of retinoblastoma.
• Eye exam: A full eye examination consists of an external examination, followed by specific tests for visual acuity, pupil function, extraocular muscle motility, visual fields, intraocular pressure and ophthalmoscopy through a dilated pupil.
• Genetic testing (multiple) / RB1 gene test (multiple): When a diagnosis of retinoblastoma is confirmed, genetic testing is helpful for determining if the disease is the congenital form or the non-heritable form. Knowing which form of the disease a child has is significant, because it can provide information about their risk of developing other cancers in the future.
• Retinal imaging: Also referred to as a retinal photograph, this is a surgery-free technique of taking pictures of the back of your eye or retina. The technique allows your eye doctor to have a closer look at your retina, blood vessels, and optic nerve, helping to determine whether retinoblastoma has grown to affect other structures around the eye.
• Orbit CT scan: A CT scan of the eye socket.
• Orbit MRI: An MRI scan uses magnets and radio waves to capture images of the orbits, surrounding nerves, muscles and tissue.
• Ultrasound of the eye: An eye and orbit ultrasound is a test that examines the eye as well as measures the size and structures of the eye.
• Electroretinography: A test to measure the electrical response of the eye’s light-sensitive cells, called rods and cones. These cells are part of the retina (the back part of the eye). The electroretinography (ERG) test measures the electrical response of the retina to light.

• Intraocular retinoblastoma: This means that cancer occurs in one or both eyes, but has not spread into surrounding tissues or other parts of the body.
• Extraocular retinoblastoma: The cancer has spread beyond the eye. Orbital retinoblastomas refer to when cancer has only moved into the eye socket, versus metastatic retinoblastomas, which have spread to other distant organs.
• Recurrent retinoblastoma: The cancer has returned, either in the eye or to other body parts.

The stage of retinoblastoma is strongly associated with the prognosis for children who have this cancer. Staging is also crucial for designing the most effective treatment program.

The most common symptoms features are the following:

• Leukocoria (whitish pupillary reflex): It is the most common presenting feature and accounts for 60% of cases.
• Strabismus: It is the second common presenting feature, and it is therefore important to perform fundus examination in all patients of childhood squint.
• Painful red eye: Painful red along with secondary glaucoma and associated buphthalmos can be present.
• Inflammation: Orbital inflammation resembling pre-septal or orbital cellulitis can also be a presenting feature.
• Visible extraocular growth
• Decreased vision
• Restriction of extraocular movements
• Metastatic disease: Metastatic disease involving lymph nodes, liver, lungs, brain, and bones is rare before ocular involvement.

While pediatric retinoblastoma is the most common intraocular malignancy in children, retinoblastoma is still a relatively rare malignancy, as according to the latest estimations only 8,000 new cases of retinoblastoma are diagnosed every year.

If retinoblastoma is left untreated the patient is likely to develop the following complications:

• Retinal detachment
• Retinal necrosis
• Orbital invasion
• Optic nerve invasion
• Blindness
• Intracranial extension
• Secondary neoplasms
• Metastasis
• Tumor recurrence
• Temporal bone hypoplasia
• Cataract
• Radiation neuropathy
• Radiation retinopathy

Retinoblastoma can be fatal if left untreated, so early diagnosis can save both a child’s life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late.

Fortunately, the cure rate is very high due to the development of precise, modern diagnostics and state-of-the-art medical treatments. A treatment plan for retinoblastoma must take into consideration the tumor’s type, size, and location, and may include laser therapy (photocoagulation or thermotherapy), chemotherapy, radiation therapy, and surgery.

Our team of ocular specialists evaluates each patient’s unique case to design the most effective, personalized treatment program. The goals of retinoblastoma treatment are to destroy the cancer, preserve as much vision as possible, limit the long-term effects that can result from cancer therapies, and save the patient’s life.

Treatment options may include:

• Photocoagulation: Laser beams are used to target and destroy the blood vessels that feed the tumor.
• Chemotherapy: To treat retinoblastoma, chemotherapy drugs may be delivered via oral medications, intra-arterial delivery (injection into the ophthalmic artery), or intravitreal delivery (injection into the vitreous humor).
• Laser therapy: Laser therapy may be used to treat small retinoblastoma tumors.
• Transpupillary thermotherapy (TTT): Thermotherapy uses a different type of laser than photocoagulation to apply infrared light directly to the tumor. This laser heats and kills the tumor cells directly. TTT may be used alone for small tumors or along with chemotherapy or radiation to treat larger tumors.
• Radiotherapy: The high-energy rays employed during radiotherapy can eliminate tumor cells, reducing or even curing cancer. Radiotherapy is often combined with other treatment modalities, such as chemotherapy and surgery, to effectively address patients’ cancer.
• Surgery (enucleation): If the tumor has grown large before it is detected or after other treatments fail, there may already be irreversible vision damage and enucleation (surgery to remove the entire eye) may be necessary.

Significant advancements in treatment over the past few decades have greatly improved the prognosis for children with retinoblastoma, enabling them to lead normal lives with normal lifespans. However, certain treatments required to eradicate the cancer can have long-term consequences on a child’s health. Consequently, monitoring potential health effects as they grow older has become an increasing concern in recent years.

Similar to the specialized approach needed for childhood cancer treatment, post-treatment care and follow-up also require specific attention. The earlier any issues are identified, the greater the likelihood of effective treatment.

Children and young individuals who have undergone treatment for retinoblastoma face varying degrees of risk for potential late side effects resulting from their cancer treatment. It is crucial to have discussions with your child’s medical team regarding these potential effects.

The risk of late effects is influenced by several factors, including the specific treatments administered, the dosage of treatment, the type of retinoblastoma (heritable or non-heritable), and the age at which the child received treatment.

These late effects may encompass:

• Reduction or loss of vision in the affected eye(s)
• Swelling around the eye
• Flushing of the skin around the eye and forehead
• Droopiness of the eyelid
• Minor drop in blood count
• Drop in the vision in the treated eye which may be temporary or, in some cases, permanent
• Deformities in the bones surrounding the eye (particularly following surgery or external radiation)
• Decreased kidney function
• Heart problems arising from specific chemotherapy drugs
• Slowed or delayed growth and development
• Alterations in sexual development and fertility
• Elevated risk of other cancers (especially in children with hereditary retinoblastoma, as explained below)

Additionally, there are other potential complications that may arise from the treatment.

Late effects of chemotherapy for retinoblastoma

Side effects from chemotherapy treatment are reassuringly low and most patients can expect very few late effects. The drugs used to treat retinoblastoma (carboplatin, etoposide and vincristine) are very well tolerated. However, a small number of patients may develop complications specific to the drug and tend to occur with greater frequency the higher the dose received. Occasionally, if first line drugs have not been successful or if treatment was given many years ago, additional or alternative chemotherapy drugs will be used to treat retinoblastoma. The side effects of these will be discussed with the patient on an individual basis.

Complications from chemotherapy can include:

• Hearing problems: These are uncommon but may occur with certain drugs and after radiotherapy to the head, in the region of the ear. Carboplatin very infrequently may cause hearing impairment (i.e., partial deafness) and can be detected by sensitive hearing tests. Hearing problems due to carboplatin do not get worse after treatment has finished but once hearing problems are present, they usually remain.
• Kidney problems: Kidney problems can occur after carboplatin, but they are rare and not usually severe. The main job of the kidney is to get rid of waste products from the bloodstream into the urine. It is also involved in controlling blood pressure. Carboplatin can reduce the efficiency with which the kidneys ‘clean’ the blood, and may make the kidneys ‘leaky’. This means that the body loses too much of certain substances, e.g. some salts such as phosphate. These substances may need to be replaced by medicines or tablets taken regularly to supplement the losses from the kidneys. Kidney damage is always evident at or within a few months of finishing treatment.
• Second malignancies: Acute myeloid leukemia is a rare second malignancy amongst retinoblastoma patients. This may be linked to the use of chemotherapy, particularly etoposide, but the underlying risk factors are unclear.
• Intra-arterial chemotherapy for retinoblastoma: Intra-arterial chemotherapy enables a higher dose of chemotherapy to be given to the eye and results in fewer general side effects associated with conventional chemotherapy.

Late effects of radiotherapy for retinoblastoma

• Cataracts: After whole eye radiotherapy, most children will develop a cataract. A method of radiotherapy called lens sparing radiotherapy has been devised, which is suitable for many children requiring external beam radiotherapy, and cataracts do not occur with this technique. If a cataract does develop after whole eye radiotherapy, it can be removed by a simple operation, and the child will then be given special glasses to correct their vision. Following removal of a cataract, the eye can be sensitive to bright light.
• Dry eye: After whole eye radiotherapy damage to the lacrimal glands, which produce tears, can lead to dry eye. A dry eye is more susceptible to infection, to damage from dust and air pollution, and to extremes of temperature. Artificial tears or eye drops can keep the eye moist on a long-term basis. This problem is much less evident after “lens-sparing” radiotherapy.
• Facial asymmetry: Radiotherapy can reduce the growth of the bones around the eye socket. If the radiotherapy beam has exited through the jaw, dental problems may also occur, and for this reason, children should be monitored regularly by an orthodontist.
• Retinal detachment: Very rarely, the retina may become detached some months or possibly years after successful treatment for retinoblastoma. This tends to occur in eyes treated for large tumors and where cryotherapy has been used. Any sudden deterioration in vision should be taken seriously, and people are advised to make an urgent appointment to see the ophthalmologist.

At the Ocular Oncology Center at Sheba Medical Center, we offer advanced retinoblastoma treatment in Israel. Our center is a national and international referral center for the diagnosis and treatment of various ocular tumors and associated conditions. Working in collaboration with the experts at our Goldschleger Eye Institute, the largest facility for ocular medicine in Israel, we strive to preserve the overall health and vision of adult and pediatric patients with retinoblastoma.

Sheba Medical Center, the largest and most prominent medical center in the Middle East, continues to set the standard for excellence in care. For the fifth year in a row, Newsweek included Sheba on their list of the world’s best hospitals, in addition to naming it as one of the best smart hospitals and a leader in gastroenterology, neurology, and cardiology. Sheba’s vision for global healthcare combines clinical excellence and medical innovation alongside international collaboration, and we employ these powerful resources to help patients worldwide.