Understanding Retinoblastoma

Symptoms, Diagnosis, Treatments, and Prognosis

baby with blue eyes
 Istockphoto.com/Stock Photo©bvb1981

Retinoblastoma is a cancer of the eye and makes up around 3 to 4 percent of childhood cancers. It is found most often in young children and babies, and though the prognosis was poor in the past, the majority of children now survive the disease.

Retinoblastoma Overview

Retinoblastoma is a rare childhood cancer that occurs in roughly one in 20,000 children. It begins in the light-detecting nerve tissues in the back of the eye (the retina) and 80 percent of cases occur in children under the age of 3 years. The cancer is only very rarely found in children over the age of 5.

While retinoblastoma once had a very poor prognosis, around 9 out of 10 children now survive, with many having their sight preserved as well. That said, treatment can be intense for parents facing this condition in their children, and support is greatly needed.

Let's take a look at the common symptoms and how retinoblastoma is treated. Since the condition is sometimes hereditary, we will also talk about the genetics of retinoblastoma and what you should know if a child in your family has been diagnosed.

Anatomy of the Eye and Retina

Understanding the symptoms of retinoblastoma is easier to understand if you consider the anatomy of the eye.

The retina comprises the inner layer of the back of the eye and is made up of light-detecting nerve cells (photoreceptors) called rods and cones. The retina is very thin, around 1/5th of a millimeter thick, and around the size of a quarter.

When you observe an image, the image is directed through your pupil and focused on the retina. These nerve cells then transmit an electrical signal of that image to the part of the brain which processes vision (the occipital lobes).

Symptoms of Retinoblastoma

Retinoblastoma is often diagnosed during well-child visits with your pediatrician, or even after one of the diagnostic signs is noted on a photograph. Symptoms may include:

  • White pupillary reflex (leukocoria): When a pediatrician shines a light and looks into your child’s eyes she sees something called a “red reflex.” The retina is loaded with blood vessels which makes the area observed beyond the pupil look red. When a retinoblastoma is present, this area may appear white instead. Sometimes the condition is suspected if a photograph of a child's eyes reveals a white reflex.
  • Lazy eye (strabismus): A child’s eyes may appear to be looking in different directions or have a cross-eyed appearance. Keep in mind that a cross-eyed look in newborns can be normal up until the age of 3 or 4 months. Some children with retinoblastoma also appear to squint excessively.
  • Absent light reflex: Your pediatrician will shine a light on your baby’s pupils to see if they contract. If a retinoblastoma is present, this reflex may be absent in one eye.
  • Bulging of the eye, redness, pain, or swelling
  • Glaucoma (increased pressure in the eye): Glaucoma may occur when tumor cells block the normal drainage paths of the eye.

Diagnosis of Retinoblastoma

A diagnosis of retinoblastoma is usually first suspected based on a white pupillary reflex during a well-child exam. (For babies who carry the mutation, see below). As noted above, parents sometimes suspect something is wrong when they see a white pupil reflex on a photograph of the child. There is even a smartphone app available which designed to screen for this reflex.

Imaging studies are often done next. An ultrasound or OCT (optical coherence tomography) is often the first test and can give important information on the thickness of a tumor. This study also spares the baby the risk of radiation. An MRI is often recommended as well, to further examine the area, and is an excellent test for visualizing soft tissue abnormalities such as a retinoblastoma. Sometimes a CT is needed as calcifications are easier to detect on a CT, but it exposes a child to the risk of radiation, so is usually not the primary test for follow-up.

Unlike many cancers, a biopsy of the tumor is usually not needed as the examination findings alone most often make the diagnosis (there are very few conditions that are similar in appearance). The risk of a biopsy can include damage to the eye and optic nerve as well as the chance that cancer cells may be seeded, resulting in the spread of the cancer.

If there is concern that the cancer has spread beyond the eye, tests designed to look for metastatic disease may be done. These may include a lumbar puncture (to look for cancer cells in spinal fluid), a bone marrow study (to look for evidence of cancer cells in bone marrow), or a bone scan (to look for bone metastases).

Some children also have pineal gland tumors (trilateral retinoblastoma), so imaging studies to evaluate this part of the brain (such as MRI) can be important.

Differential Diagnosis—What Else Could It Be?

There are actually very few conditions that are similar to retinoblastoma, making it easier to make the diagnosis based on an exam and imaging studies alone. Other conditions which may appear similar include:

  • Coates disease: Coates disease is a rare congenital (but not hereditary) disorder characterized by abnormal blood vessels behind the retina. The abnormal vessels cause blood to leak in the back of the eye. The leakage of blood can cause fatty tissue to build up (which has a whitish yellow appearance) that may be mistaken for a retinoblastoma.
  • Toxocara Canis: Toxocara Canis is a dog roundworm that is sometimes transmitted to humans from infected dogs. The parasite tends to grow in the back of the eye (as well as other places) and may lead to retinal detachment.
  • Retinopathy of prematurity: Retinopathy of prematurity is a condition related to the overgrowth of blood vessels in the eye and is most often found in children born prior to 31 weeks gestation.
  • Persistent hyperplastic primary vitreous (PHPV): PHPV is a rare congenital problem in babies caused by abnormal fetal blood vessels in the eye.
  • Intraocular epithelioma: Intraocular medulloepithelioma is a rare congenital tumor that begins in the ciliary body rather than the retina.

Causes and Risk Factors

It's not certain what causes the mutations responsible for the development of retinoblastoma. With many cancers, diet, exercise, and environmental exposures play a role, but since retinoblastoma usually develops shortly after, or even before birth, these factors likely play a much smaller role. We do know that genetics play a role in a significant percentage of these tumors.

Genetics of Retinoblastoma

Retinoblastoma may occur due to a gene mutation in a gene known as RB1 found on the 13th chromosome. This gene is a tumor suppressor gene, which codes for proteins that limit the growth of cells. This is inherited in an autosomal dominant fashion and the abnormal gene may be inherited from either the mother or father. There are also other mutations, such as those in MYCN that are associated with the disease.

With RB1 mutations it's thought that around 25 percent are germ-line mutations (inherited from one parent) and the other 75 percent acquired (mutations which occur during fetal development). For children who have the mutation in RB1 (either inherited from a parent or when the mutation occurs early in gestation) the chance of developing retinoblastoma (penetrance) is 90 percent.

Hereditary retinoblastoma is often bilateral and occurs at a younger age than sporadic retinoblastoma. Hereditary retinoblastoma may also be multifocal, with several tumors developing at the same time. Children who have hereditary retinoblastoma are also at risk of developing other cancers in the future.

Staging Retinoblastoma

The stages of retinoblastoma can be divided into stages I to IV as other cancers, but different classification systems are often used. (Stage I refers to cancers in which the eye can be preserved, and stage II to IV are cancers in which an eye is removed). Since the disease is usually caught earlier in developed countries, other staging systems are often used.

There are two main stages of the disease:

  • Intraocular—Tumors that are within the eye
  • Extraocular—Tumors that extend beyond the eye. These are further broken down into orbital extraocular tumors in which there is spread throughout the region of the eye (the orbit) and metastatic extraocular tumors that have spread to the brain, bone marrow, bones, or other regions.

In the United States and other developed countries, retinoblastoma is usually diagnosed in the intraocular stage.

Intraocular tumors are further classified into the following stages:

  • A—Includes tumors that are less than 3 mm (millimeters) in diameter and do not involve the optic disc (the center of vision)
  • B—Greater than 3 mm in diameter
  • C—Any small and well-defined tumor that has spread under the retina or into the vitreous humor
  • D—Any large or poorly defined tumor which has spread under the retina or into the vitreous humor
  • E—Large tumors that have spread to the front of the eye, are complicated by glaucoma, or retinal detachment. With these tumors it may be difficult to save the eye.

When retinoblastoma spreads, it may invade the remaining areas of the eye (the globe). The most common sites of distant metastases include the lymph nodes, brain and spinal cord, liver, bone marrow, and bones.

Retinoblastoma Treatment Options

The ideal treatments for retinoblastoma depend on the stage of the cancer, the location of the tumor, whether the tumor is unilateral or bilateral, and other factors. For smaller tumors, chemotherapy along with focal treatments is often used.

The goals of treatment include:

  • Saving the child’s life
  • Saving the eye (or eyes) if possible
  • Preserving as much vision as possible
  • Reducing long-term side effects related to treatment

Treatment options include:

  • Chemotherapy: Chemotherapy may be used alone or to decrease the size of the tumor before surgery. Different types of chemotherapy may be used with intra-arteriolar chemotherapy commonly used. In this technique, the chemotherapy drug is delivered directly to an artery that supplies the eye, reducing the effect of the drugs on other tissues. Intravenous chemotherapy may also be used. For larger tumors or those which have metastasized or recurred, high-dose chemotherapy with stem cell rescue may be used.
  • Local treatments: There are several different types of local treatments that may be used to treat retinoblastoma. These result in the removal of cancer cells but are less invasive than surgery to remove the eye. These include cryotherapy (freezing the tumor) thermography (heating the tumor), laser surgery (photocoagulation), and others.
  • Radiation therapy: Radiation therapy may be used externally (external radiation therapy), or internal (brachytherapy) in which radiation is placed inside the body near the tumor. Proton beam therapy is being evaluated as an alternative to traditional radiation therapy as it may have less potential for causing secondary cancers.
  • Surgery (enucleation): For smaller tumors, chemotherapy and local procedures are usually done in hopes of preserving the eye. For larger tumors, or those that progress or recur, removal of the eye and part of the optic nerve (enucleation) may be needed. An eye implant is often installed at the time of surgery, with an artificial eye placed on top of the implant at a later date.
  • Clinical trials: There are a number of different treatment methods being researched in clinical trials, ranging from nanoparticulate chemotherapy to newer types of local treatments.

Follow-up After Treatment

Many retinoblastomas can be cured with treatment, but follow-up is very important. These tumors may sometimes recur, and follow-up MRIs are often used. Evaluation and follow-up of vision, if preserved, also requires special attention. In addition, developmental delays are not uncommon. Follow-up is also extremely important with special attention given to the late effects of treatment. The Children's Oncology Group (COG) Survivor Guidelines outline many of these concerns.

Late Effects and Second Cancers

Late effects of cancer treatment refer to conditions caused by cancer treatments that may develop years to decades after treatment. We are learning that childhood cancer survivors have an increased risk of medical conditions ranging from heart disease (often related to chemotherapy), to infertility, to secondary cancers.

In a study looking at long-term outcomes of children with retinoblastoma, it was found that decades later (average age was 42 in the study), 87 percent of children who had survived retinoblastoma had at least one medical condition related to treatment. While this can be discouraging to discuss, this information highlights how important it is for childhood cancer survivors to have long-term follow-up with a physician well-versed in detecting and treating long-term outcomes of treatment.

Children who have survived retinoblastoma have an increased risk of developing secondary cancers (new primary cancers) down the road. With hereditary retinoblastoma, part of this increase is due to the dysfunction of the tumor suppressor gene in other tissues. With non-hereditary retinoblastoma, these second cancers may occur as a side effect of either chemotherapy or radiation therapy. The most common second cancers include osteosarcoma (bone cancer), soft tissue sarcomas, melanoma, lung cancer, and lymphoma.

In addition to second cancers, long-term side effects of chemotherapy and long-term side effects of radiation therapy are of significant importance since many of these children will be living with these late effects or at risk for late effects for nearly a lifetime.


Most children diagnosed with retinoblastoma now will be cured. The 5-year overall survival rate for retinoblastoma in the United States was 97.3 percent looking at the period between 2000 and 2012, and treatments continue to improve. Even children with metastases to regions outside of the brain (such as bone marrow) are often cured. That said, spread within the brain (intracranial disease) is associated with a poor outcome.

Other poor prognostic factors include developing the cancer in a developing country (where there are more HPV-related cancers). Trilateral retinoblastoma is responsible for much of the mortality from retinoblastoma in developed countries.

Early Detection for Children Who Have a Germ-Line Mutation

We currently don’t have any way to prevent the development of retinoblastoma, but children who are at an increased risk due to a known germ-line mutation or a family history of the disease can be examined with hopes of catching the tumor as early as possible. Funduscopic exam (an eye exam looking at the retina) under general anesthesia as soon as possible after birth and monthly for the first year of life is often recommended. The gene can be detected in amniotic fluid, and affected children can also be monitored and delivered early if signs of cancer are noted.

If a child develops retinoblastoma, other children and family members may also be screened to see if they have the suspect gene.

Coping and Support

As a parent, knowledge is truly power, and it is helpful to learn all you can.

Support is also paramount. Due to the rarity of the tumor, most communities do not have retinoblastoma support groups, but there are excellent support communities online and via Facebook. Getting involved in these communities not only provides support as you cope with the in and outs of being a parent of a child with cancer, but can be an excellent place to learn about the latest research regarding retinoblastoma. Nobody is more motivated to learn about and share new discoveries than parents who are coping with this disease in their child.

As children grow older there are now many opportunities for support for children. There are cancer survivor support groups designed specifically for young people with cancer, and camps and retreats are also available.

A Word From Verywell

Retinoblastoma is a rare tumor involving the nerve tissue in the retina. It occurs most often in very young children. Since it is rare, it is usually important for children to be seen at a larger cancer clinic or children’s hospital, which has specialists who are very familiar with the best treatments for the disease. The overall prognosis is excellent, but getting there can be emotionally, physically, and financially draining for parents and children. If your child has been diagnosed, reach out for the support that is available.

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