Saturday May 7, 2022
Prompt investigation of signs and symptoms is vital to diagnose retinoblastoma early. Timely diagnosis provides the best opportunity to save a child’s life and sight. For Retinoblastoma Awareness Week 2022, Rb Care Coordinator Sandra Staffieri explores the signs and symptoms that may lead to a diagnosis of childhood eye cancer.
This child has one healthy red reflex, and white pupil reflex in the other eye.
Signs are simply physical evidence that can be seen by an individual or third party, such as a parent, caregiver or healthcare professional. The presence or occurrence of signs indicates the presence or occurrence of something else.
Symptoms on the other hand, are more subjective, for example pain. It is felt by the affected person, and their response to the pain is what draws attention that something is amiss.
A diagnosis of retinoblastoma can follow either the observation of signs, or obvious symptoms. Usually, the symptoms may occur after some weeks, months, or even years of an otherwise ‘silent sign’.
Ultimately, a child will always rely on someone else recognising and acting on the signs, or responding to the symptoms. Read on…
Globally, the most commonly reported presenting sign of retinoblastoma is leukocoria (white pupil). This ominous sign is taught to medical professionals during their training as one not to be missed or ignored. Because it is rare, and unlikely to be encountered, it is readily forgotten. This is a story for another time.
Unfortunately, leukocoria is not a sign regularly taught to parents to look out for. Awareness campaigns using posters, stories in the media, and increasingly through social media, we are seeing more promotion of this sign. However, it is silent, may not be present all the time, and even difficult to elicit in the doctor’s office.
Leukocoria occurs only in certain lighting – when the pupil dilates, and light bounces off the tumour nestled within the eye. So this sign can be easily ignored or dismissed because the child does not have obvious ‘symptoms’ that they are unwell or cannot see. The extra symptoms may be what prompts a parent or caregiver to seek health advice
And of course, not all leukocoria is caused by retinoblastoma. Many other eye conditions can affect a child’s vision that may present with leukocoria, or it may even be an artefact caused by the camera or the direction the child is looking in. But no condition is more important than retinoblastoma, and it must be excluded as a possible cause.
White reflex often does not appear in every photograph. This depends on the size, number and location of tumours, and the angle at which the flash enters the eye. The child in these three photos was diagnosed with cancer in both eyes.
In a newborn, strabismus can be part of normal eye development as the brain and the eyes learn to work together. Beyond approximately 4 months of age, the eyes should be straight (pointing in the same direction) all the time. Any strabismus – whether it is observed some or all of the time, is small or large, drifts in any direction (up, down, in or out) – should be assessed by a health professional familiar with examining children’s eyes.
There are many reasons why the eyes may not be aligned. When the cause is due to an eye muscle or nerve problem, the strabismus can result in the vision not developing properly – amblyopia. With early diagnosis and treatment, the poor vision resulting from the strabismus can be improved.
Sometimes however, it is poor vision that causes the strabismus in the first place. Since the eye cannot see properly, it drifts in towards the nose, or outwards to the temple. The reason for the poor vision MUST be investigated. It could be caused by cataracts or other significant problems with the eye – including retinoblastoma.
Research has shown that compared to children who present with leukocoria, children who present with strabismus are less likely to require enucleation (removal of the eye). So, if you notice any strabismus in your child, seek health advice promptly, and ensure your child has a dilated eye examination.
Outward turn (exotropia)
Inward turn (esotropia)
Upward turn (hypertropia)
Apart from leukocoria and strabismus, there are many other signs and symptoms of retinoblastoma. What they are may depend on how advanced the disease is. When we compare presenting signs of children diagnosed with retinoblastoma in upper-middle income (UMIC) and lower-middle income countries (LMIC), we find that children in LMIC often present with signs and symptoms of more advanced disease. This is largely because of limited awareness, resources, and access to health care.
Advanced retinoblastoma can break free from the eyeball and spread into the socket (the bony structure in which it sits). The tumour can grow rapidly behind the eye and push the eyeball forward, giving the appearance of a bulging eye (proptosis). This is a very serious situation and requires urgent treatment. This sign would be accompanied by the symptom of pain.
When a child has only a white pupil glow or turned eye, and appears otherwise well, a family with severely limited financial resources and no awareness of childhood eye cancer will be unlikely to seek a medical explanation. By the time signs and symptoms like proptosis and pain develop, the need for care is emergent, but poverty and limited professional awareness of retinoblastoma creates many barriers to healthcare, leading to more delays.
Sadly, many children in LMIC present with very advanced cancer because of this poor access to appropriate medical care.
Eye infections in children are very common. “Pink eye” (conjunctivitis) occurs frequently in both children and adults, when the conjunctiva (very thin, translucent layer of tissue that covers the eye ball and inside of the eye lids) becomes inflamed and infected. The inflammation makes the white of the eye appear “pink”, hence the term “pink eye”. There is often a yellow-green discharge, and the eyelids may get stuck together. Because it is highly infectious, it usually affects one eye, then the other.
Along with other eye problems, sometimes retinoblastoma can present as an eye infection similar to “pink eye”, but it persists in one eye only. That only one eye appears infected should be a red flag to all that something more sinister may be occurring.
Any child with only one “pink” or infected eye should be examined promptly. It may not be retinoblastoma, but one of many other eye problems. Whilst not quite as serious, it is still important infections are diagnosed and treated promptly.
Some eye infections present with pus that appears as yellowish-white fluid that collects in front of the iris – the coloured part of the eye. This is called a hypopyon and indicates there is infection or inflammation INSIDE the eye. The source of the always needs to be determined.
In retinoblastoma, when tumour cells collect in front of the iris, it can look exactly like hypopyon (pseudohypopyon).
Some eye infections will be present in the eye socket. This is called orbital cellulitis. Again, not always retinoblastoma, but still a very important eye disease to treat urgently as it can cause irreversible blindness.
Retinoblastoma presenting as pseudohypopyon. Source: Science Direct.
Pupils are like the shutter of a camera; they narrow or widen depending on how much light is entering the eye. The brighter the lighting, the smaller the pupil. This protects the eye from being over stimulated. Conversely, under low lighting conditions, the pupil dilates, stimulating the light-sensing cells in the eye that work best in dim lighting.
Our pupils should be the same size. Some eye problems can cause the pupils to appear a different size. Although rare, retinoblastoma is one of them. Pupils that are not the same size should be investigated by a healthcare professional to make sure it is not a sign of a more serious eye or health problem.
In children with very dark eyes, the pupils may be very hard to see, so pupil size may only be obvious in children with light-coloured eyes.
The iris is the coloured part of the eye. With close-up examination, the iris can have the most spectacular appearance. As with pupils though, the iris should look much the same in both eyes.
Any change or difference between the colour of the iris should be investigated promptly as it could be a sign of several eye conditions, including retinoblastoma.
Again, in children with very dark eyes, any change may be difficult to see.
This child’s heterochromia (different coloured irises) prompted her mother to seek an eye exam, leading to her retinoblastoma diagnosis.
Two components within the eye help to maintain its shape. The largest space within the eye is filled with jelly (vitreous). The remaining space is filled with fluid (aqueous) that is produced by a structure sitting behind the iris. The fluid then flows through the pupil and drains away through a sieve-like structure at the front of the eye. Not only does this fluid keep the eye nourished, it also keeps the pressure in the eye stable.
Glaucoma develops when the pressure in the eye is too high and can cause irreversible vision loss. The most common type of glaucoma in ADULTS is painless. In children, it is quite different.
The trio of symptoms of eye pain, light sensitivity, and a watering eye are often associated with acutely raised pressure in the eye. In children, these symptoms are more commonly associated with childhood glaucoma.
Glaucoma can be the only problem (primary) or it can be caused by other problems (secondary). When a retinoblastoma tumour becomes large enough that it interferes with the circulation of aqueous fluid within the eye, the eye pressure also rises. This is an example of secondary glaucoma.
The onset of secondary glaucoma is usually rather rapid. It is very painful and difficult to ignore. The child may rub their eye to protect it from light or in response to the watering eye. They can be very difficult to examine because of the light sensitivity. Glaucoma should always be suspected in any child who cowers their head and cannot be examined. Sometimes, sedating the child may be required to examine them adequately. This is essential to confirm the cause of the glaucoma and ensure it is not secondary to retinoblastoma.
Unlike adults, children don’t know how well they should be seeing, so we rely on their visual behaviour to alert us there might be a vision problem. Observing a child bumping into objects, being hesitant to walk or negotiate steps independently, holding toys or books close to their face, or getting close to the television can all be signs of poor vision.
These observations are more common when both eyes have poor vision, because from a vision point of view, people can manage very well with just one eye. When the deterioration is slow, it may be difficult to notice until the vision is very poor. Also, young children are very adaptable.
Obviously, there are many causes for poor vision, but since a child’s vision is constantly developing, it is important they are examined and treated promptly so their vision can develop normally.
Although not the most common presentation, a child with retinoblastoma can present with poor vision. It is usually when both eyes are affected, but it can also be the presenting sign when one eye is affected and they lose their depth perception (3D vision).
In a very young baby, when vision is very poor, the eyes can move uncontrollably as they ‘try to see’. This is called nystagmus, and appears as a slow, side-to-side movement of the eyes. Even though it can be benign, any child with any type of nystagmus requires urgent assessment to rule out a sinister cause for this condition.
Vision screening programs are common, but vary from country to country, or even state to state within the same country. Taking note of your child’s visual behaviour might raise the alarm that vision is not developing, before a screening opportunity arises.
A child does not need to know their alphabet letters to have a vision test. Any concerns about your child’s vision, or a change in their visual behaviour should be promptly assessed by a health professional who is experienced in examining vision in pre-verbal children.
Having a family history of retinoblastoma (or any unexplained eye removal surgery) is a very important consideration. Genetic testing is not available to most people in the world, and does not always definitively confirm whether the individual’s retinoblastoma is the type that can be inherited.
Therefore, all children with a family history of retinoblastoma should undergo screening and surveillance so that any tumours can be detected at the earliest possible time. We know that screening high-risk babies from birth results in fewer children requiring an enucleation, or even losing their life.
As a parent, it can be overwhelming to feel like you have so much to remember.
When it comes to eyes, all you need to commit to your memory is what normal eyes look like. Anything that does not look normal – or has changed – is a good enough reason to seek advice from a healthcare professional.
Your child’s eyes should be:
- Black pupils when looking at your child.
- Red pupils in a photo taken with a flash camera.
- Straight eyes (pointing in the same direction).
- Eyes not bulging or appearing swollen.
- Whites of the eyes are white.
- Pupils are equal in size.
- Iris (coloured part of the eye) should be the same between the two eyes.
- No eye watering, light sensitivity, or complaining of pain.
- Normal visual behaviour
This is what healthy eyes should look like.
About the Author
Sandra Staffieri is the Retinoblastoma Care Co-ordinator at the Royal Children’s Hospital (RCH) Melbourne, Australia. Working at the RCH and in private clinics, she has over 35 years’ experience in children’s eye health and disease.
As a Research Fellow and Clinical Orthoptist at the Centre for Eye Research Australia, Sandra completed her PhD on delayed diagnosis of retinoblastoma. Her prime focus was to develop and evaluate an information pamphlet for new parents to raise awareness of the important signs of childhood eye disease – particularly strabismus and leukocoria – in the hope this could lead to earlier diagnosis.