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HomemifeatureRetinoblastoma: Photos Catch the Cancer

Retinoblastoma: Photos Catch the Cancer

Retinoblastoma occurs in one in every 13-15,000 births each year in the western world.

The disease, which develops in the retina, is a cancer that usually only affects one eye, however one out of three children with the disease will develop the cancer in both eyes. While retinoblastoma accounts for approximately 11 per cent of cancers developing in the first year of life, it accounts for just three per cent of cancers developing among children younger than 15 years of age.1

The disease was drawn to the attention of the Australian public in a segment on Network Seven’s show Today Tonight, which told the story of a two-year old girl, Airlia, whose condition was first noticed by her day-carer. When her story went to air last November, the little girl’s eye had been removed and she was undergoing further treatment.

Dr. Geoff Lam, a West Australian ophthalmologist treated the child and told mivision that her prognosis is now good. “Airlia’s diagnosis at the age of two was relatively late – most children with retinoblastoma are diagnosed between the ages of nine and 18 months – so her cancer had extended into the optic nerve. She is now undergoing chemotherapy to minimise the risk of the cancer spreading beyond the eye, but she is doing well.

Knowing what is ‘normal’ is easy, everything else should be referred for further examination

“Barring anything happening to her other eye, Airlia will be fine,” he added.

First Signs

According to the experts, the most common first sign of retinoblastoma is a visible whiteness in the pupil called cats eye reflex or leukocoria.1 The discolouration is especially obvious in photographs taken with a

digital camera when using a flash without red eye reduction.

However Dr. Lam said people shouldn’t jump to the conclusion of a tumour in the retina just because of a visual difference between the eyes in a digital photograph.

“It could be retinoblastoma or it could be one of a number of conditions such as a squint, cataracts or an infection – regardless though, if there is a difference it’s well worth looking further.”

Further Investigation Essential

Sandra Staffieri, Retinoblastoma Care Co-ordinator at the Royal Children’s Hospital, Melbourne and Research Orthoptist at the Clinical Genetics Unit at the Centre for Eye Research Australia (CERA) agrees that despite retinoblastoma being uncommon, further investigation of symptoms is essential.

“While it would be important not to ‘over-concern’ parents in the community with regards to abnormalities identified in photographs, it is important to educate them to seek appropriate advice and examination of their child when there is ANY concern regarding their eyes,” said Ms. Staffieri.

“Additionally, the clinicians coming into contact with children – GPs, optometrists, maternal child health nurses – should be aware of the possibility of retinoblastoma, the importance of its prompt diagnosis and where to seek further urgent advice if they are unsure or unable to adequately examine the child.”

Other symptoms of retinoblastoma can include strabismus (crossed eyes), a family history of the disease and, if both eyes are affected, poor vision. In rare cases, when retinoblastoma masquerades as an intra ocular eye infection, the eye(s) can appear red and irritated.

“Knowing what is ‘normal’ is easy, everything else should be referred for further examination by a suitably qualified paediatric ophthalmologist,” said Ms. Staffieri.

She added that many children present with retinoblastoma late, even in Australia simply because of misinformation regarding what is ‘normal’ for children. “They think that symptoms like strabismus will go away. And indeed, often baby’s eyes do turn from the age of 0 to four months as the brain develops and the eyes ‘learn’ to work together.”

“However when the condition continues past this age, it’s incredibly important to have these symptoms checked – it’s not often a tumour, but if it is and you’re the practitioner having to explain the diagnosis to the family, it’s no fun. The family goes through so much guilt because they’ve ‘allowed’ the condition to escalate, and then there is the long, intense period of treatment, followed by
a permanent disability.”

Digital Photography

There’s no doubt that the digital photograph taken of Airlia saved her life and that digital photographs are a

useful screening tool for GPs, optometrists and parents as well.

However Dr. Lam warns that the child must be looking straight at the camera when the photo is taken. “If the camera is held at an angle there will often appear to be a difference between the eyes, but that difference is most likely to be due to an optical illusion.”

Ms. Staffieri recommends that all practitioners examining children should conduct the red reflex test using an ophthalmoscope – it should be part of any eye examination in a child presenting for any suspicious eye condition.

Family History Vital

Ms. Staffieri told mivision that family history is extremely important when diagnosing retinoblastoma. “In my research, I’ve been looking at the incidence of retinoblastoma and it would seem to be increasing slightly year on year. The increase is mostly coming from children with a family history of the disease.”

She said that’s because people born in the 60s and 70s who were treated with retinoblastoma are now at the stage of having their own children.

“Retinoblastoma can be a fatal cancer – people born with it prior to the 60s and 70s were less likely to survive, but early survivors are now having children and those with the heritable form of retinoblastoma are also adding to the pool of children with this condition. The number of children presenting each year without a family history has stayed much the same whereas those with a family history is increasing.”

She said that survivors of retinoblastoma who are considering having children should be made aware of the risks before pregnancy. “It’s important that individuals make informed choices and understand the genetic testing technology available to either ensure their child doesn’t have the disease or is able to receive earlier treatment.

Ms. Staffieri continued, “We can now conduct pre-natal testing to determine whether the baby has the gene that causes retinoblastoma to develop, as well as consider pre-natal MRIs to look for tumours. Then if necessary, we can induce the baby – at around 36 weeks – to begin treatment.”

High Cure Rates

Treatment of retinoblastoma achieves a good success rate compared to other childhood cancers (95–98 per cent).2 However, it must be diagnosed in the early stages. If left untreated the cancer can spread to other

organs and be fatal.

Treatment is determined by the size of the tumour and the spread of the disease and may include surgery, chemotherapy, cryotherapy and/or laser. Dr. Lam said if the condition is diagnosed early, laser can be used for small tumours at the back of the eye or cryotherapy for small tumours in the periphery of the retina. Larger tumours can be reduced in size using chemotherapy before being treated with laser or cryotherapy.

Ms. Staffieri added that intense monthly treatment, particularly in the early months, is most effective. “When a baby is five months old, it is growing fast – and so is the disease. As the child reaches the 12 month mark, the growth slows.”

She said treatment is very much tailored to the patient. “A child born with a genetic mutation will usually be screened and if necessary, treated with laser or cryotherapy under anaesthetic once a month for at least 12 months or until the condition is under control.”

Often the disease results in blindness or the loss of one or both eyes. Additionally, according to some reports, there have been cases of retinoblastoma metastasizing to the brain and bones.

According to Ms. Staffieri, some specialists overseas are now using intra-arterial chemotherapy to treat retinoblastoma in an effort to save the eyes. “You could argue that saving the eye means the eye socket will grow normally, however this does not necessarily save vision. It is a relatively new treatment and not all patients are suitable candidates.”

Poorer Prognosis in Undeveloped Countries

Despite being a curable condition, many children in undeveloped countries die from retinoblastoma. According to research, in low income countries, cure rates for retinoblastoma are <50 per cent and vision preservation is minimal, primarily because by the time a child is diagnosed with retinoblastoma the disease is in its advanced stages.3

A review of presentations at the 2007 One World One Vision Symposium in published online in the US journal Pediatrics, highlighted the significant disparity in cure rates between developed and undeveloped countries. Researchers said the disparity could be explained by a “lack of access to care, scarcity of human resources, unavailability of essential medications, inadequate infrastructure, lack of support from government and international nongovernmental organisations and a lack of cancer registries” in developing nations.3

Discussions highlighted the benefit of, and need for more, consumer education to create awareness of the disease and to overcome socio-economic and cultural barriers.

Researchers also discussed strategies to improve outcomes for global retinoblastoma that ‘twinning’ between centres in developing nations and mentor institutions in high-income countries.3

In Australia the National Health and Medical Research Council (NHMRC) has recently funded a Centre for Clinical Research Excellence grant to Translate Genetic Eye Research. “Retinoblastoma will be one of the genetic eye diseases we aim to improve with clinical care utilising genetic information,” says Professor David Mackey from the Lions Eye Institute at the University of Western Australia. He is also President of the International Society for Genetic Eye Diseases and Retinoblastoma.


1. seer.cancer.gov/publications/childhood/retinoblastoma.pdf

2. www.cancer-aware.com/eye-cancer-retinoblastoma.html#axzz1fEtAvErO

3. http://pediatrics.aappublications.org/content

Incidence of Retinoblastoma

• Retinoblastoma accounts for approximately 11 per cent of cancers developing in the first year of life, but for only three per cent of the cancers developing among children younger than 15 years of age

.• In the US, approximately 300 children and adolescents younger than 20 years of age are diagnosed with retinoblastomas each year.

• The vast majority of cases of retinoblastoma occur among young children, with almost two-thirds (63 per cent) of all retinoblastomas occurring before the age of two years and 95 per cent occurring before the age of five years.

• The incidence of bilateral tumors is strongly age dependent with 42 per cent of the retinoblastomas occurring in children less than one year of age being bilateral compared to 21 per cent of those among children aged one year, and only nine per cent among older children.


Reason for Rapidity in Retinoblastoma Identified

Researchers have known for decades that loss of a tumour suppressor gene named RB1 launches retinoblastoma during foetal development. However, until recently, the other steps involved in the rapid transformation from a normal cell to a malignant tumour cell that occurs in this cancer were unknown.

The new findings from the St. Jude Children’s Research Hospital – Washington University Paediatric Cancer Genome Project (PCGP) explain why the tumour develops so rapidly while other cancers can take years or even decades to form.

The finding also led investigators to a new treatment target and possible therapy. The study appeared in the 11 January advance online edition of the scientific journal Nature.

The study linked the RB1 mutation to abnormal activity of other genes linked to cancer without changing the makeup of the genes themselves. Evidence suggests that epigenetic factors, including reversible chemical changes that influence how genes are switched on and off in tumour cells, are altered when RB1 is mutated.

“The dogma in the field has been that once RB1 is mutated, the genome of the affected cell becomes unstable, chromosomes begin to break and recombine, and mutations quickly develop in the pathways that are essential for cancer progression,” said Michael Dyer, Ph.D., member of the St. Jude Department of Developmental Neurobiology, a Howard Hughes Medical Institute Early Career Scientist and one of the research paper’s corresponding authors. “What we found through the Paediatric Cancer Genome Project was exactly the opposite. These tumours contain very few mutations or chromosomal rearrangements.”

For this study, the researchers sequenced the complete normal and cancer genomes of four St. Jude patients with retinoblastoma. The human genome is the complete set of instructions needed to assemble and sustain an individual.

The effort, a first for retinoblastoma, was part of the Paediatric Cancer Genome Project (PCGP) that St. Jude and Washington University officials launched in 2010. The three-year project aims to complete whole-genome sequencing of normal and tumour DNA from 600 children and adolescents battling some of the most challenging cancers. Organisers believe the results will provide the foundation for the next generation of clinical care.

The retinoblastoma tumours sequenced contained about 15-fold fewer mutations than have been found in nearly all other cancers sequenced so far. In one patient’s tumour, RB1 was the only mutation.

The findings prompted Prof. Dyer to integrate the whole-genome sequencing results with additional tests that looked at differences in the patterns of gene activity in tumour and normal tissue. In particular, researchers focused on genes that, when mutated, promote cancer development. “To our surprise and excitement, what we found was that instead of cancer genes having genetic mutations, they were being epigenetically regulated differently than normal cells,” said Prof. Dyer.

The genes included SYK, which is required for normal blood development and has been linked to other cancers. Drugs targeting the SYK protein are already in clinical trials for adults with leukaemia and rheumatoid arthritis.

SYK has no role in normal eye development. When researchers checked SYK protein levels in normal and retinoblastoma tissue, they found high levels of the protein in 82 tumour samples and absent in normal tissue. “We see changes in the SYK gene in retinoblastoma that probably give the cancer cell a growth advantage or provide other key factors with regard to how retinoblastoma is initiated,” said Prof. Richard Wilson, director of The Genome Institute at Washington University in St. Louis.

When researchers used the experimental drugs to block SYK in human retinoblastoma cells growing in the laboratory or in the eye of a mouse, the cells died. Prof. Dyer said work is now underway to reformulate one of the experimental drugs, a SYK-inhibitor called R406, so it can be delivered directly into the eye. If successful, those efforts are expected to lead to a Phase One trial in retinoblastoma patients.