A Letter from Dr. Schefler
Hearing that your baby has cancer is one of the scariest moments in a parent’s life.
Retinoblastoma is a rare disease, with only 250 to 350 new patients diagnosed per year in the United States. We at Retina Consultants of Houston along with Children’s Memorial Hermann Hospital are one of the only centers in the nation that specialize in the care of children with this disease. We take care of patients with this problem every day and are engaged in cutting-edge research to try to help find better treatments and a cure for this rare cancer. Our doctors attend national and international meetings every year to present their research findings with other experts around the world. We pride ourselves on outstanding care for children and for their families. You will find that our team is accessible and kind, and treats your child as if he/she were our own.
We are honored to take care of your child.
Carly RCH Testimonial Video
Retinoblastoma is the most common eye cancer in children. However, among the general population, the disease is actually very rare. In fact, it occurs in only 250 to 350 new children in the U.S. per year; an average of one in every 15,000 to 20,000 births. Worldwide, the disease affects about 8,000 children per year (0.006 percent of all births). We know from years of working with retinoblastoma families that receiving this diagnosis can be terribly distressing. The good news is that it is highly curable in places like the U.S., where modern treatment is available. Although the untreated disease continues to claim many lives in developing areas of the world, retinoblastoma has the highest survival rate among all pediatric cancers in the United States.
With all of the advances in treatment options over the past few decades, up to 98 percent of patients diagnosed with retinoblastoma in the U.S. survive the initial cancer. In addition, over 90 percent of those retinoblastoma patients will be able to retain good vision in at least one and possibly both eyes.
Before you can truly understand what retinoblastoma is, it helps to have a basic understanding of what cancer is in general. Cancers are diseases characterized by large masses of cells (tumors) that develop when healthy cells do not develop properly or become damaged and begin to divide uncontrollably. These masses, which can develop in any part of the body, are usually considered either benign (stable) or malignant (actively growing/spreading). Although benign tumors can become cancerous over time, the term “cancer” refers specifically to malignant tumors that are capable of invading surrounding healthy tissues.
Malignant tumors are dangerous, because they deprive normal cells of resources, and can eventu- ally cause the cells, and even entire organs, to stop functioning. If left undetected or untreated, the tumors can continue to grow, and can eventually metastasize (spread) to other parts of the body. Therefore, early detection and treatment is essential in combatting these cancer.
Retinoblastoma is a malignant cancer of the eye that is typically diagnosed in children before the age of five. Specifically, the cancer involves the formation of one or multiple tumors in the neurosensory retina. These tumors form when retinoblasts (cells) involved in normal retinal development don’t develop correctly during embryo- genesis. Instead of giving rise to mature retinal cells, the faulty retinoblasts begin reproducing rapidly and form tumors.
Tumors can damage or alter the structure of the retina, and can therefore impact vision. If left untreated, cancer cells can spread throughout the eye, and eventually exit the eye. Once outside of the eye, cancer cells can spread to other areas including the orbit (soft tissue spaces around the eye), brain, and bone marrow. As with most cancers, patient survival rates are significantly worse when children develop metastases. Therefore, the primary goal of our treatment regimens are to maximize vision in the affected eye while minimizing the risk for metastases.
Current evidence suggests that retinoblastoma affects children of all ethnicities, nationalities, genders, and socioeconomic statuses equally. There aren’t any known environmental risk factors that have been associated with retinoblastoma, so there are very few lifestyle measures that can be taken to prevent the disease.
However, retinoblastoma has been linked to certain genetic changes (mutations) that can be acquired randomly or from a parent. Understanding what specific kind of retinoblastoma your child plays a critical role in the management of your child.
There are two forms of retinoblastoma: somatic, which affects only a single cell in the body, and germline, which affects many (mosaicism) or all cells in the body. In the somatic form of the disease, a single mutation in the key gene con- trolling retinal development occurs in just one retinal cell in one eye. As such, these patients only develop a tumor in that one location. Somatic mutations are always randomly acquired in children who have no family history of the disease. Fortunately, somatic mutations cannot be passed on to offspring.
The average age at diagnosis for retinoblastoma varies depending on the type (somatic or germline), laterality (unilateral or bilateral), and extent of the disease. Generally, patients with the germline form of the disease will develop more tumors and at younger ages. Often times, these patients can already have tumors in their eyes at birth. As a result, germline patients are usually diag- nosed sooner than those with the somatic form of the disease, which usually develops later.
Retinoblastoma can affect only one eye (unilateral) or both eyes (bilateral), depending on the type of mutation a patient has. On average, 60 percent of patients will have the unilateral form of the disease, and the remaining 40 percent will have bilateral disease. Children with somatic mutation will always develop a unilateral disease. Those with a germline mutation can also develop unilateral retinoblastoma, but in about 85 percent of cases, they will develop bilateral disease.
Retinoblastoma almost never affects individuals above the age of seven. If you did not develop symptoms of retinoblastoma in childhood, it is highly unlikely that you have the mutation responsible for the disease.
Retinoblastoma can be a very aggressive disease, and every child tends to respond to treatment differently. Some children can be cured after a single treatment, but most may have to undergo multiple cycles of treatment before they are considered cured. Fortunately, with the advent of intra-arterial chemotherapy and intra-vitreal chemotherapy, children are being treated with fewer cycles and are experiencing fewer side effects.
During treatment, it is common for tumors to regrow very quickly. It is important to monitor these tumors for any signs of growth in order to catch any recurrences early. Dr. Schefler, and the members of the retinoblastoma team are highly trained to perform diagnostic techniques that can be used to detect the slightest changes in tumor size.
Dr. Schefler monitors all of her retinoblastoma patients very closely. Toward the beginning of a treatment regimen, she performs examinations frequently to ensure there aren’t any new tumors in the eye. As a child begins to stop experiencing recurrence of tumors, she begins to extend the intervals between examinations. Once a child has been recurrence-free for a period of 18 months, or reached the age of seven, they are usually considered cured of retinoblastoma.
These children are unlikely to develop more tumors in the eye due to retinoblastoma, but those with a germline mutation may be at risk of developing second cancers elsewhere in the body, including the brain. As a result, these children will have to undergo routine screenings for other cancers going forward.
Common Signs / Symptoms
Retinoblastoma may be detected by a pediatrician via routine pediatric eye exams. Typically, however, parents are the first to notice signs of the disease in their children. If any of the following symptoms are observed in a child, especially below the age of 5, a comprehensive eye examination should be performed in order to confirm or rule out the diagnosis of retinoblastoma.
The most common presenting symptom of retinoblastoma is leukocoria, a white pupillary response commonly seen in flash photographs or eye exams. You may be familiar with the appearance of red eyes in photographs. This is actually caused by light being reflected off the surface of the retina, which has a red color, and is completely normal. Leukocoria refers to the appearance of a white pupillary reflex, usually resulting from light being reflected off the surface of a white tumor or other white structure within the eye, rather than normal retina. This is commonly referred to as cat’s eye reflex.
The second most common sign of retinoblastoma is strabismus (crossed eyes). Retinoblastoma can cause a cross-eyed appearance in which one or both eyes tend to be more esotropic (pointed inward) or exotropic (pointed outward) than average.
Usually, persistent redness and pain in the eye are indicative of diseases such as eye infections, but rarely these symptoms can also be a sign of retinoblas- toma. In particular, these symptoms can be related to neovascular glaucoma (increased intraocular pressure) or orbital inflammatory/tumor necrosis syndrome, findings common in advanced retinoblastoma cases.
In some instances, retinoblastoma patients can present with associated symptoms including developmental delay, and altered facial features. This occurs in patients who have a complete deletion of the long arm of the 13th chromosome that includes the entire RB1 gene. This condition is known as 13q Deletion Syndrome.
The treatment of retinoblastoma is complex and tailored specifically to the needs of each child. It differs from other pediatric cancers in that there is no single standardized protocol.
Reasons for lack of standardization are:
- The rare nature of the disease makes it difficult for centers around the country to perform large, multicenter prospective standardized trials, which is the gold standard in medicine.
- The variability of the disease. Some patients have disease in one eye; some have it in both eyes. Some patients have the disease at birth, and some patients don’t develop the disease until they are much older, at which time their bodies can handle much stronger treatments. Some patients respond well to only one or two treatments, and some patients require many sessions of treatment.
Intra-arterial (or ophthalmic artery) chemotherapy is a groundbreaking new form of treatment in which a small dose of chemotherapeutic agent(s) is delivered directly to the blood vessels that feed the eyes (ophthalmic artery). This allows for a more potent and targeted treatment of the cancer cells while avoiding many of the side effects commonly associated with intravenous chemotherapy (chemo delivered throughout the entire body). With the advent of this technique, many eyes with advanced disease that were once considered unsalvageable are now routinely being saved.
Our center was the first in Texas to perform this therapy, and we are currently the only hospital in Texas performing these surgeries weekly for children with retinoblastoma.
This form of treatment, which was first introduced in Japan thirty years ago, has been performed by leading retinoblastoma centers in the U.S. since 2006. The procedure is performed by an interventional neurosurgeon who inserts a catheter into the femoral artery (the artery in the groin, at the top of the leg). The catheter is then carefully threaded through the arteries in the abdomen, then through the arteries in the chest, then through the artery in the neck, and finally, to the ophthalmic artery.
A tiny dosage of chemotherapy is injected into the beginning (called ostium) of the ophthalmic artery, from which the tumor receives nutrients for growth. Intraarterial chemotherapy allows us to deliver higher doses of chemotherapy to the tumor while using a fraction of the total amount of drug required in systemic chemotherapy.
As a result, patients almost never have low white blood cell counts after treatment, require hospitalization, lose hair or weight, which are all common side effects of traditional intravenous chemotherapy. Although there are fewer systemic side effects, the administration of a more concentrated dose to the eye can result in more localized side effects in and around the eye. Rare reported side effects include: loss of blood flow to the choroid and retina (ischemia), bleeding in the eye (hemorrhage), and retinal toxicity that can damage the retina and lead to poor vision. Additionally, since the ophthalmic artery supplies blood to the area around the eye and forehead too, the chemotherapy can cause redness and inflammation in those areas. These side effects are rare and occur most commonly in centers that have less experience, or in patients who have already undergone (and failed) other forms of treatment.
Some children are not good candidates for intra-arterial chemotherapy, such as very, very small babies (less than 13 pounds), children who have metastatic retinoblastoma (retinoblastoma that has traveled to other parts of the body), children who cannot finish a long-term treatment program (sometimes lasting one to two years) because of travel or financial limitations, children who have certain unusual changes in the anatomy of the blood vessels around the eye, or children with certain bleeding disorders.
Some recent reports have claimed that more children undergoing intra-arterial chemotherapy develop metastatic disease (retinoblastoma that travels to other parts of the body) than children undergoing traditional chemotherapy. These claims are controversial. Rarely, children who receive intra-arterial chemotherapy or traditional intravenous chemotherapy can develop metastatic disease and can even die from retinoblastoma. Causes for this include: a very late presentation to the doctor, very aggressive bilateral disease, a delay in time to eye removal when a certain treatment approach is failing, and infrequent follow up with the ocular oncologist or discontinuing follow up visits. The most important aspect of retinoblastoma care is choosing a center in which the ocular oncologist has excellent clinical judgment as to when eye removal is necessary to prevent metastatic disease. When performed correctly, intra-arterial chemotherapy does not lead to an increased rate of death from retinoblastoma.
The goal of intra-arterial chemotherapy is usually to shrink tumors so that they can be treated with focal therapies such as laser and cryotherapy. Therefore, children who undergo intra-arterial chemotherapy require regular examinations under anesthesia in order to monitor the progress of the disease and perform these additional therapies.
Intravenous chemotherapy is a traditional approach in which chemotherapy is delivered intravenously to the whole body. This treatment has been used for retinoblastoma since the 1990, and remains the standard treatment at many centers around the U.S. The main advantage of systemic chemotherapy is that it provides a less concentrated dose to the eye that does not result in ocular side effects.
While systemic chemotherapy prevents ocular side effects, it also limits the efficacy of the drugs in treating tumors. As a result, systemic chemotherapy has a lower rate of saving eyes with advanced retinoblastoma than intraarterial chemotherapy. In addition, this form of treatment exposes all cells in the body to the drug. The chemotherapeutic agents are designed specifically to target cancer cells that are rapidly dividing, but they will also target healthy cells that divide regularly such as those in the hair follicles and gastrointestinal (GI) tract. Therefore, patients who undergo systemic chemotherapy may experience side effects including neutropenia (depressed immune system requiring hospitalization), loss of hair, and difficulty with weight gain. In addition, the patient will tend to be less responsive to other treatments if the tumor(s) have failed to respond to intravenous chemotherapy first.
As with intra-arterial chemotherapy, the goal of systemic chemotherapy is usually to shrink tumors so that they can be treated with focal therapies such as laser and cryotherapy. Therefore, children who undergo systemic chemotherapy also require regular examinations under anesthesia in order to monitor the progress of the disease and perform these additional therapies.
Intravitreal chemotherapy is a new type of treatment for retinoblastoma that involves the injection of minute amounts of chemotherapy directly into the eye with a small needle. This procedure is performed in the operating room during the examination under anesthesia. It is fast, minimally painful, and highly effective in treating residual vitreous seeds (pieces of non-cohesive tumor floating in the vitreous) that are present, typically after treatment with another form of chemotherapy.
Intravitreal chemotherapy is usually not used as primary treatment, but more as a supplement to other therapies (adjuvant therapy). Most often, it is administered in patients who just only need a small additional dose of chemotherapy to treat several stubborn vitreous seeds after tumors are almost completely treated with intra-arterial or intravenous chemotherapy. Intravitreal chemotherapy is performed until Dr. Schefler confirms drastic regression of the vitreous seeds.
In the past, vitreous seeds have been particularly difficult to treat. Since the seeds are loosely floating in the vitreous, they do not have blood vessels. As a result, traditional forms of chemotherapy have been ineffective at reaching the seeds. Before intra-arterial chemotherapy, radiation or enucleation (surgical removal of the eye) were the primary methods of treatment for eyes with vitreous seeding. With the introduction of intravitreal and intra-arterial chemotherapy, many of these eyes that would have been removed or radiated are now being saved and fully cured.
Dr. Schefler has performed thousands of these types of injections in both, adults (for diseases such as macular degeneration) and in children, and is highly skilled in the procedure. In order to prevent any cancer cells from exiting the eye, Dr. Schefler freezes the needle to -80oC as it is pulled out of the eye. This seals the injection site, and kills any retinoblastoma cells that may be stuck to the needle or needle tract.
Most types of treatment such as chemotherapy require additional local therapy like laser or cryotherapy to kill small remaining remnants of tumors. These treatments can be performed during the examination under anesthesia and can serve as standalone primary treatment for tumors that are classified as ICRB A or B.
In cryotherapy, a small probe is applied to the white of the eye (sclera) directly above the site of the tumor. Liquid nitrogen, upon touching the sclera, freezes the tumor instantly. The tumor cells are cooled to -80 °C and die instantly. Afterwards, children are left with a flat scar in the periphery of the retina that typically does not affect central vision. This therapy can only be used for small tumors located near the front of the eye or for the remaining tumor cells after chemotherapy.
On the other hand, laser ablation is performed using indirect ophthalmoscope. Dr. Schefler views the tumor and guides the laser through a dilated pupil toward the retina via careful head movements. The tumor absorbs the laser and turns into a scar. This therapy is generally used for small tumors located toward the back of the eye.
Plaque brachytherapy is a form of localized radiation treatment in which a radioactive device is surgically attached to the surface of the eye directly above the tumor. The plaque completely covers the tumor margin and is left implanted for up to a week and then surgically removed. Each plaque is designed specifi cally based on the shape, size and location of the tumor. Radiation exposure to surrounding healthy tissues is minimal with this treatment. However, plaques can only be used for patients with a single tumor and is therefore not recommended for those with germline mutations and multiple lesions.
Side effects of radiation include: cataracts (clouding of the lens), damage to the healthy retina (radiation retinopathy), and optic nerve (radiation optic neuropathy), and dry eyes. For these reasons, plaques are generally performed as a last resort after other treatments have failed.
Until the 1990’s, external beam radiation was the primary form of treatment for retinoblastoma. The procedure involves the application of radiation to the eye and orbit (area surrounding the eye) from an external source. EBRT often requires several short sessions of radiation spread across multiple weeks. EBRT kills cancer cells but also damages healthy tissues around the tumor.
Many patients with retinoblastoma are at risk for developing other cancers in the soft tissues and bones of the face due to radiation. EBRT is particularly harmful to patients with germline mutations, as the radiation can increase the risk of recurrence of retinoblastoma as well as secondary cancers. Consequently, external beam radiation is only performed as a last resort after other treatments have failed.
Similar to plaque brachytherapy, the side effects of EBRT include: cataracts (clouding of the lens), dry eyes, and damage to the healthy retina (radiation retinopathy), and optic nerve (radiation optic neuropathy). In addition, serious complications including facial and developmental deformities have been associated with radiation treatments when administered to patients below the age of one-year-old.
Enucleation is surgical removal of the eye. The procedure is very safe and only takes about an hour. The treatment is curative for retinoblastoma if the cancer cells have not already spread beyond the eye. Enucleation is generally reserved for severe cancers that have not responded to other treatments or are so advanced that they will not respond to currently available treatments. The primary benefit of this treatment option is that it can eliminate the risk for extraocular spread, and the need for further treatment. When the eye is removed, the eye muscles, eyelids, eyelashes, and face are kept intact. An implant is placed in the orbit where the eye was, and the muscles are reattached so that the implant can move like a normal eye. About one month after the surgery, patients are fitted with a prosthesis (a hard contact lens that is hand-painted by a special artist called an ocularist). The prosthesis will match the other eye in appearance and movement. However, the prosthesis is only cosmetic, and will not be able to produce vision.
When removing an eye, there are many caveats that must be considered. When one eye is removed, you lose the ability to perceive depth. We use both eyes to detect relative distances in the visual fi eld. This may result in difficulty in performing tasks such as reaching out and grabbing an object. Secondly, when one eye is removed, the other eye becomes the sole source for vision. For this reason, we encourage all retinoblastoma patients who have undergone an enucleation to wear protective glasses at all times.
Patients with a history of retinoblastoma can have highly productive, completely normal lives after an enucleation. There are very few activities or jobs that a patient with one eye cannot do. They can go to school, drive, work, play sports, read, and enjoy life to the fullest.
Life After Retinoblastoma
Most children with retinoblastoma will go on to live completely normal lives. Based on where the tumor was located prior to treatment, visual field may or may not be significantly affected. Unilateral patients will have one, and possibly two eyes with good vision. Bilateral patients typically have one and sometimes two eyes with good vision. Retinoblastoma patients usually require frequent examinations under anesthesia while the disease is actively recurring. Once the disease has stabilized (no recurrences) for a period of roughly 18 to 24 months, eye examinations can be performed less frequently. The disease has rarely presented in children above the age of seven. If there is a germline mutation, closer monitoring is required for potential secondary cancers. Any signs of cancer such as suspicious lumps or unexplained changes in weight or health should be immediately reported to the ocular oncologist.