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PiretMettälä

JohannaRehunen

Retinoblastoma

Retinoblastoma is a disease of young children. In the early stages, it causes a white pupillary reflex (leukocoria) or strabismus (squint), which is often noticed by the parents (picture 1).
Early detection is vital to save the vision.
Every child who is noted to have a white reflection in the pupillary aperture should always be referred to an ophthalmologist on the next working day as should any child who, after having developed straight eyes, begins to squint.

The global incidence of retinoblastoma is about 1/15-20 000 children born.
Retinoblastoma may already develop during foetal life.
The majority of patients are under 3 years of age; patients aged over 8 are rare.
Over half of all children with retinoblastoma have tumours in both eyes.
Approximately half of retinoblastomas are inherited as an autosomal dominant trait.
- However, in most cases hereditary retinoblastomas are due to new germ line gene defect in the RB1 gene and there are, therefore, no other affected relatives.
- The patients' children have a 50% risk of inheriting the gene defect causing the disease.
- A gene test on a blood sample detects the mutation in 98% of the cases.
Unless treated promptly, the tumour will rapidly blind the eye and in extreme cases prove to be fatal.

The most common symptom is leukocoria, a white reflex seen in the pupillary aperture (picture 1).
Leukocoria is usually noticed by the parents at home in dim light when the pupil is dilated.
- The reflex is often obvious in photographs taken with a flash.
Leukocoria suspected by parents is always an indication for consultation with an ophthalmologist on the next working day, even if the examining physician cannot confirm any abnormality within the eye. Unit for eye diseases should be consulted in order to arrange the appointment as smoothly as possible.
In a typical case, an abnormal white area may be seen in the fundus reflex.
Manifest strabismus in the affected eye is the second most common finding, and it occurs before leukocoria.
Strabismus typically develops in a child whose eyes have already been aligned for some time.
Regardless of the age of the child, a child who develops manifest strabismus should always be referred to an ophthalmologist as an emergency case. Unit for eye diseases should be consulted before referral.
The outward appearance of the affected eye is usually normal.

Treatment methods that preserve both the eye and vision have advanced significantly.
- The most common first-line treatment is chemoreduction which involves the reduction of the tumour volume with cytotoxic drugs.
- After the tumour has been shrunk, or if the tumour is initially small, it can be destroyed with laser therapy, cryocoagulation or plaque radiotherapy.
- External beam radiotherapy is reserved only for special cases.
Advanced tumours necessitate the enucleation of the affected eye.
Treatment is usually centralised at specialist centres.

If a couple with a family or personal history of retinoblastoma plans pregnancy, they should be referred for genetic counselling Genetic Counselling.
- If a RB1 gene defect has been identified in the family, gene testing can, if the family so wishes, reveal already during pregnancy whether the child has inherited it.
- With preimplantation genetic testing done in association with in vitro fertilization, it may be possible to choose a healthy embryo.
Screening is essential if a child has inherited the RB1 gene defect, or if the parents or siblings have a history of the disease and the inheritance status is not known.
- An ultrasound examination can detect tumours in the foetus several weeks before the expected date of delivery. In such cases, the delivery can be induced earlier and treatment started.
- If a gene defect has been determined in the family earlier, gene test done from a blood test taken right after birth will provide a result within 1-2 weeks.
- The fundi of the newborn must be examined without general anaesthesia during the first 24 hours after birth followed by an examination under general anaesthesia within the first week of life and regularly thereafter.
- If the gene test result is negative, screening may be discontinued.
In hereditary retinoblastoma, there is an increased risk of sarcoma and some other cancers later in life, and this should be taken into account in health status follow-up.

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MacCarthy A, Bayne AM, Draper GJ, et al. Non-ocular tumours following retinoblastoma in Great Britain 1951 to 2004. Br J Ophthalmol 2009;93(9):1159-62. [PubMed]