What Is Retinoblastoma?

Retinoblastoma is the most frequently diagnosed eye cancer in children. It’s a life threatening cancer of the retina within the back of the eye. Retinoblastoma is usually discovered in babies between the ages of 6 and 24 months, even though it can be seen at earlier or later ages.

How Common Is Retinoblastoma?

Retinoblastoma occurs in about 1 in 15,000 live births, and it’s estimated to affect approximately 250 to 300 children every year in the USA. Worldwide, about 5,000 children develop retinoblastoma every year.

What Are the Symptoms of Retinoblastoma?

The parents of the affected child may notice white reflex in the centre of the eye. This finding is present in 60% of children having retinoblastoma.

In 20% of cases, the eye may be deviated/squinted caused by tumor in the central part of retina.

In the remaining cases, the eye may become large in size because of secondary glaucoma. It may become red with poor vision. In advanced cases, the tumor may become so big that the normal structures of the eye are not identifiable.

EXAMINATION

Once a child is suspected of having retinoblastoma, a complete eye and systemic examination is required.

Eye examination for Retinoblastoma

Intraocular retinoblastomaThe ophthalmologist who suspects retinoblastoma typically refers the child relatively urgently (within one or two days or a week) to a retinoblastoma expert. The retinoblastoma specialist evaluates the child’s medical and family history, examines parents and family members and then specifically focuses on the child’s eye examination.

The eyes are checked with the pupils dilated. The doctor wears a headlight, called an indirect ophthalmoscope, and she/he uses a focusing lens to see all of the details in the back of the eye. It is generally necessary to restrain the child to steady the head and body so that a reliable examination can be performed.

Numbing eyedrops are placed on the child’s eyes for comfort. The child’s eyelids are held open by a lid speculum and soft cotton applicators are used to gently rotate the eyes to allow maximal visualization of the back of the eye. This is generally not painful to the child, but the child may cry.

Systemic examination

The pediatric examination is performed by a pediatrician or a pediatric oncologist. The examination of other organs of the body is based on the size and extent of tumor and the type of treatment planned. It might include:

  • Physical examination
  • CT or MRI scans of brain and orbits
  • Blood tests
  • Bone marrow analysis
  • Hearing and kidney tests

If on chemotherapy, the hearing and brain tests are important. The brain CT and MRI are usually performed twice yearly until age 5 years. These tests are done to evaluate for possible spread of the tumor as well as other related cancers.

MRI scan of retinoblastoma

DIAGNOSIS (How to Detect Retinoblastoma)

How do we know it is retinoblastoma?

The diagnosis of retinoblastoma depends primarily on findings seen on eye examination. The child with retinoblastoma may be found to have a crossed eye or a white pupil by the parents or a pediatrician and then referred to an eye specialist for an eye examination.

On examination, retinoblastoma has a relatively white appearance with noticeable blood vessels. It is rarely necessary to biopsy the tumor for confirmation.

To better assess the tumor, an examination with sedation of the child in the operating room, called an examination under anesthesia or EUA, is usually necessary. During EUA, a complete eye examination with a detailed drawing of all tumors and related findings is performed.

Other confirmatory tests like photography, ultrasonography and fluorescein angiography are performed. These tests assist in planning the treatment strategy for the child. Fluorescein angiography uses an intravenous dye that discolors the child’s urine to a green-yellow color for one day.

Ultrasound scan of retinoblastoma

If treatment is necessary, it is usually performed while the child is under anesthesia. Later, the doctors discuss the findings and treatment with the family. When the child recovers, the eyes might appear somewhat swollen and red for about 2 or 3 weeks.

Future appointments are scheduled. If the child is in the midst of treatment, appointments are about 1 month apart. If the child is stable, then appointments are usually 2 to 6 months apart. Lifelong, all children with retinoblastoma should have an eye examination once or twice yearly.

GOALS OF TREATMENT

The goals of treatment for a child with retinoblastoma are threefold

  1. To save the child’s life
  2. To save at least one eye
  3. To protect the vision

How is retinoblastoma treated? There are several ways to treat retinoblastoma depending on the size, location and multiplicity of tumors as well as the child’s age, status of the opposite eye and systemic condition.

The treatment modalities include chemoreduction, laser photocoagulation, cryotherapy, thermotherapy, plaque radiotherapy, external beam radiotherapy (EBRT) and complete removal of the eye (enucleation). These are often used in combination.

CHEMOREDUCTION

Chemoreduction is a method of using intravenous chemotherapy to reduce retinoblastoma to a small size so that the residual tumors can be eradicated with focal treatment methods like thermotherapy or cryotherapy.

Chemoreduction is used in almost all children who have bilateral (involving both eyes) retinoblastoma and about 25 percent of children with unilateral (involving one eye) retinoblastoma.

This technique involves delivery of intravenous chemotherapy each month for 6 months. Each chemotherapy session is coupled with an examination under anesthesia so that treatment of the tumor scars can be done the same day.

THERMOTHERAPY

Thermotherapy is a laser method in which the residual tumor is heated for 5 to 15 minutes to a temperature that kills the cells. It is focal so that the surrounding tissue is unaffected. It typically leaves no external scars on the eye, but some children might show an irregular pupil after treatment.

LASER PHOTOCOAGULATION

Laser photocoagulation is a method to treat a small retinoblastoma by closing the blood vessels to the tumor with heat. This causes no external scars on the eye, but leaves a small scar on the retina.

CRYOTHERAPY

Cryotherapy involves the use of a probe the size of a pencil placed on the eye to deliver a focal freeze for about 1 minute through the wall of the eye into a tumor inside the eye.

Surrounding tissue is usually unaffected from this treatment. It typically leaves no external scars on the eye, but the eye is often swollen for 2 or 3 weeks.

PLAQUE RADIOTHERAPY

Plaque radiotherapy is a method of giving focal radiation treatment to a small part of the eye by using a piece of metal, called a plaque. The plaque has radiation incorporated in it and is attached temporarily outside the eye directly over and in vicinity of retinoblastoma.

The child stays in the hospital for several days (usually 3 to 7 days) while the radiation plaque is in place. The radiation dose to the retinoblastoma is quite focal and limited to the eye itself with little radiation elsewhere to the body. After the correct dose is given, the plaque is removed in the operating room and the child is discharged.

Eye drops will be prescribed to be used 3 times a day for 3 weeks. The eye heals well over a few weeks. Long term concerns include vision loss from cataract or retinal swelling. We have not seen radiation related second cancers following plaque treatment.

EXTERNAL BEAM RADIOTHERAPY

External beam radiotherapy is a method of treatment to the entire eye by a radiation machine. This is available at only a few experienced centers worldwide. It takes about 4 weeks in which small doses of radiation are given to achieve the final dose.

External beam radiotherapy can cause the eye to feel irritated, dry, look red and the patient might loose the eyelashes temporarily. This generally resolves, but the child is also at risk for long term problems like vision loss from cataract or retinal swelling.

There is also a risk for radiation related second cancers, especially in children with bilateral retinoblastoma.

ENUCLEATION

Enucleation is a method of removing the entire eyeball. The eyelids and muscles of the eye remain. This is used for eyes that have large tumors or eyes that have developed painful glaucoma.

All other methods of treatment are considered before advising enucleation, but many patients have life-threatening large tumors that necessitate enucleation. Following enucleation, an implant is placed in the empty orbit and allowed to heal for 1 or 2 months.

Then, an artificial eye (prosthesis) is made to match the remaining eye. The cosmetic appearance is generally outstanding with a natural appearance and comfortable fit as well as some movement of the eye. Protective glasses or goggles are advised to be worn at all times during the day especially during activities or sports.

What is a prosthesis?

When an eye is removed (enucleation), the surgeon places an implant into the socket that remains buried in the tissue for life. About 6 weeks after surgery when the tissue is healed without swelling, an ocular prosthesis (artificial plastic eye) is fitted by an ocularist (an artist who specializes in making the artificial eye) to conceal the implant underneath.

The prosthesis is a removable device and resembles a thick contact lens. The prosthesis fits comfortably and provides a natural appearing eye that matches the opposite eye.

How long can a prosthesis be worn?

A prosthesis can remain in the socket for life, but it should generally be cleaned daily while bathing or showering by rinsing the surface using clean warm water. A warm washcloth can be used to wipe off debris without removing the eye.

Occasionally, it should be removed to clean off mucous or debris. Most parents remove a child’s prosthesis at home for cleaning every 1 to 3 months. Sometimes a prosthesis feels dry and teardrops are necessary for lubrication.

Should the prosthesis be replaced?

During the child’s lifetime, the eye socket will grow and the prosthesis may need to be reshaped or even completely replaced to better fit the socket. This will be determined by the ophthalmologist or ocularist. In general, the prosthesis should be checked annually by the ocularist.

We recommend a book entitled “A Singular View: The Art Of Seeing With One Eye“ by Frank Brady for those with one functional eye.

What Is the Prognosis?

Fortunately, most children with retinoblastoma survive and lead good long and productive lives. In the United States, nearly 98% of children survive, but not so in less advanced countries where about 50% of children die from tumor spread. Long term ocular and pediatric examinations are advised for the child.

Who Is at Risk for Metastasis and Death?

The prognosis of a child with retinoblastoma depends on several factors, most importantly the results of pathology.

Children with retinoblastoma that has invaded into the optic nerve, choroid, sclera, orbit or anterior chamber require chemotherapy as they are at greatest risk for metastasis (spread) and death. Those without invasion do not require chemotherapy.

Important Life-Threatening Concerns for Children With Bilateral or Hereditary Retinoblastoma

Metastasis

This can occur, usually within one year from diagnosis, and primarily depends on the pathology findings. Fortunately, only 2% of patients develop metastasis. If the tumor invades into the optic nerve or choroid then chemotherapy is advised to prevent metastasis.

Pinealoblastoma

This is a brain cancer that can occur in 8% to 10% of children with bilateral or familial retinoblastoma. MRI scan or CT scan of the brain is crucial to find this tumor. This is important up to age five years as most pinealoblastoma tumors are found before this age.

Second Cancers

Children with bilateral or familial retinoblastoma have an increased risk for second cancers elsewhere in the body such as in the bone, soft tissue and skin. Lifelong monitoring for second cancers is advised.

What Causes Retinoblastoma

There are several important aspects of the genetics of retinoblastoma. Retinoblastoma is classified into hereditary or nonhereditary types. Hereditary retinoblastoma patients are at increased risk for pinealoblastoma, second cancers and transmission of the genetic trait to their children.

Hereditary retinoblastoma includes:

  • 100% of children with bilateral retinoblastoma
  • 100% of children with familial retinoblastoma
  • 10% of children with unilateral retinoblastoma

Nonhereditary retinoblastoma includes:

90% of children with unilateral retinoblastoma

The chance of having another child with retinoblastoma depends on two factors:

  1. If the affected child has the tumor in one or both eyes and
  2. If there is another family member with retinoblastoma.

How is retinoblastoma inherited? Generally, if there is another family member with retinoblastoma, the parents have a higher chance of carrying the gene (trait) to pass on to future babies. If there is no family history of retinoblastoma and the child has the tumor in only one eye, then the chances of passing on the trait to future generations is much less.

Frequently Asked Questions About Retinoblastoma

1. What is retinoblastoma?

Retinoblastoma is a childhood eye cancer arising from immature retinal cells in one or both eyes. The tumor can develop in the human fetus, newborns, infants, or young children.

2. How is retinoblastoma found?

It causes a yellow-white glow in the pupil or a crossed eye.

3. What does the white pupil indicate?

This is called leukocoria and it is actually the tumor that is visualized inside the eye through the pupil.

4. Why does the eye drift?

Retinoblastoma can decrease vision especially if it is located in the center of retina, and this will cause the eye to drift or become “lazy”.

5. Can retinoblastoma cause pain?

No, retinoblastoma is usually painless, but some patients with secondary glaucoma develop pain.

6. What causes retinoblastoma?

It is caused by a mutation in chromosome.

7. Who is at risk for retinoblastoma?

Those with a known family history of retinoblastoma are at risk to have children with it. However, most new cases of retinoblastoma have no family history.

8. Is retinoblastoma hereditary?

It can be, especially if the child has bilateral retinoblastoma.

9. Can something in pregnancy cause retinoblastoma?

No, the process of pregnancy as such is not known to cause retinoblastoma.

10. Is there something in the environment that causes retinoblastoma?

No, there are no known environmental causes for retinoblastoma.

11. Can retinoblastoma be detected with amniocentesis?

Sometimes, but the genetic mutation is not always visible.

12. If a child has retinoblastoma in one eye, can it develop in the other eye?

Yes, if there is a family history of retinoblastoma or if the tumor in one eye is multiple.

13. What are the side effects of treatment?

This depends on the treatment. Some children have hair loss with chemotherapy, others have redness around the eyes with radiation, and others have eye swelling with cryotherapy.

14. Do I need to see a pediatric oncologist instead of my regular pediatrician?

It is important to follow with both physicians.

15. How can we afford the treatment?

Most insurances cover the costs of treatment.

16. Can this cancer spread to other parts of the body?

Possibly it can spread to the brain and rest of the body, but this happens only in advanced retinoblastoma.

17. What might the vision be?

The vision depends on many factors, but most children can see enough to walk and play without great difficulty. But remember, the goals of treatment are to first save the child’s life, then save the eye and vision.

18. Will my child have delayed development?

Some children with hereditary retinoblastoma are delayed in walking, speech and other facets of development. However, most children are not delayed.

19. Will my child be socially withdrawn?

No, most children adapt well to the diagnosis and the visual handicap, especially with family support and education.

20. Why must retinoblastoma children wear protective glasses?

Eye protection at all times is advised for all children with retinoblastoma to shield the eye(s) from injury, especially during sports. This is particularly important for children with one remaining eye.

21. Can a child with retinoblastoma attend a regular school?

Yes, but if both eyes are affected and the vision is reduced, the child might need a visual assistant during school. Public schools provide this service for visually handicapped children, but it is important to ask your school system about this in advance.

22. Can an eye transplant be done after the eye is removed?

No, transplantation of the whole eye is not currently possible.

23. Is there research for retinoblastoma?

Yes, much research is being conducted worldwide for retinoblastoma. Newer and better ways to detect and treat it are being investigated. Studies into the gene that causes retinoblastoma (RB1) are underway.

Images Courtesy: Wikimedia Commons

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