Retinoblastoma is the most common primary intraocular malignancy in pediatrics. This type of cancer can either affect one or both eyes. Leukocoria and strabismus are the two most common changes that a parent or caregiver might notice. The child then will then undergo an ophthalmologic exam and imaging studies to best characterize the disease. Several different treatment modalities exist, including cryotherapy, thermotherapy, brachytherapy, EBR, enucleation and chemotherapy.
Retinoblastoma accounts for 4% of pediatric malignancies. It is the most common primary intraocular cancer in childhood; with an incidence of 1 in 15,000 to 1 in 20,000 live births.1, 2, 3 In 2003, retinoblastoma was designated the pediatric cancer with the highest survival rate. In medically developed nations, over 95% of children survive this malignancy.4
Where Does Retinoblastoma Come From?
Retinoblastoma is a tumor that arises from precursors of retinal sensory cells. It is currently believed that a mutation affecting both of the alleles of the retinoblastoma susceptibility gene, RB1, are a prerequisite to developing this tumor. 5
Retinoblastoma can either affect one or both of a patient’s eyes. It is believed that tumors affecting one eye typically arise from spontaneous mutations in the RB1 gene. This change is assumed not be inherited from a patient’s mother or father.6
Bilateral disease is more likely to be inherited from a child’s parents in an autosomal dominant fashion via the RB1 gene, which has been mapped to chromosome 13q14. Patients with heritable disease have one germline mutation such that all cells have one normal and one affected allele. A tumor develops when the normal allele is lost, or if the normal allele becomes mutated.7
Clinically, What do we see?
The most common presentation (50-60% of cases) of retinoblastoma in the developed world is leukocoria- an abnormal white discoloration of one or both pupils. The discoloration is caused by the absence of a red reflex in the eye and usually becomes visible when a large tumor is present. The tumor is reflecting light, and blocking view of the red retina. However, sometimes a whitish pupil is also seen when there is a smaller tumor associated with a retinal detachment. Typically, a child’s family member notices this change first.
The second most common (20-25%) physical finding that leads to the diagnosis of retinoblastoma is strabismus (misalignment of the eye). In the case of retinoblastoma, the eye becomes misaligned due to a tumor causing a loss of central vision, and the eye trying to compensate.8,9
- Other (less common) symptoms include:
- Swelling or inflammation of the eye (6-10%)
- Heterochromia – a difference in color between the two pupils
- Hyphema – blood in the anterior chamber of the eye
- Glaucoma – increase intraocular pressure
How is Retinoblastoma Diagnosed?
The diagnosis of retinoblastoma is based on an exam by an ophthalmologist. Physical findings are then correlated with imaging studies.
Fundoscopy typically shows a large white or cream-colored tumor, frequently with satellite lesions (scattered, smaller lesions) in the retina, subretinal space, and/or vitreous. To confirm the presence of a tumor, examination under anesthesia is preformed after dilating the pupils.6
Ultrasonography of the eyes is often performed to get a better understanding of the characteristics of the tumor. Calcifications and heterogeneity of the tissue seen provide strong evidence for the presence of retinoblastoma. Ultrasonography is not as sensitive as Computed Tomography (CT), which is the ideal imaging modality for detecting calcifications. There is however, a concern of exposing children with germline mutations to radiation at such a young age. Magnetic resonance imaging (MRI) is the most sensitive way to see if the tumor as grown outside of the eye.8
How is Retinoblastoma Treated?
The treatment of retinoblastoma usually involves a multidisciplinary team to help optimize outcomes. Several factors must be considered, including patient age, prognosis of vision, size and location of the tumor and the presence or absence of vitreous or subretinal seeding6.
Focal and Local Treatment Modalities: 8,10,11
Cryotherapy is done for small tumors. This method causes the tumor to quickly freeze, resulting in damage to the blood supply. Without a blood supply, the tissue making up the tumor dies.
Thermotherapy involves the application of heat directly to small tumors, usually by using infrared radiation. The goal of this is to cause death of the tumor tissue, but sparing the blood vessels.
Plaque brachytherapy involves placing a radioactive plaque on the sclera adjacent to the base of the tumor. Commonly used radioactive materials include Ruthenium 106 and Iodine 125. This plaque delivers radiotherapy directly to the tumor, with minimal impact on surrounding tissues and structures.
External beam radiotherapy (EBR) is used in children with bilateral retinoblastoma with active or recurrent disease after completion of chemotherapy and local therapies. The major problem with this treatment is the side effects. These include: stunted eye growth, dry eyes, cataracts, radiation retinopathy and optic neuropathy.
Enucleation is the removal of the entire eye, leaving the muscles intact. Enucleation is curative in more than 95% of patients with unilateral disease. In bilateral retinoblastoma, the more diseased eye is removed, and the lesser is treated aggressively by focal and local techniques.
(the following was added March 2015)
An up-and-coming treatment option for RB is intra-arterial chemotherapy (IAC). It is done by highly selective catheterization of the ophthalmic artery via a catheter inserted through the iliac artery. This allows for higher concentration locally of chemotherapy within the eye than would be achieved with traditional systemic chemotherapy options. The downside, however, is that this increased concentration comes with the risk of added toxicity to the structures within the eye.
Little information is available at the present time with respect to exact indications, advantages and risks as it is primarily used at major referral centers. It should also be noted that a team of extremely specialized personal is needed for the successful administration of IAC. 12
Systemic Treatment: 8,10,11
Chemotherapy is the mainstay of systemic treatment. Chemotherapy is used to reduce the size of the tumor. It is important to note that chemotherapy alone is not considered a curative treatment; it must be combined with intensive focal and/or local therapies to be most effective.Debra-Meghan Sanft
References:1/ ZA K, TH Orbital tumors—diagnosis and treatment. Springer. 2004. 2/ Mahoney MC, Burnett WS, Majerovics A, Tanenbaum H. The epidemiology of ophthalmic malignancies in New York State. Ophthalmology. Sep 1990;97(9):1143-1147. 3/ Shields CL, Shields JA. Diagnosis and management of retinoblastoma. Cancer control : journal of the Moffitt Cancer Center. Sep-Oct 2004;11(5):317-327. 4/ Abramson DH. Retinoblastoma in the 20th century: past success and future challenges the Weisenfeld lecture. Investigative ophthalmology & visual science. Aug 2005;46(8):2683-2691. 5/ Lohmann, DR. RB1 Gene Mutations in Retinoblastoma. Human Mutation. 1999 14: 283-288. 6/ Ray A, Gombos DS. Symposium on Pediatric Oncology: Malignant Solid Tumors. Retinoblastoma: An Overview. Indian Journal of Pediatrics. March 2012. 7/ Becker AJ, Dunn JM, Gallie BL, Phillips RA. Identification of Germline and Somatic Mutations Affecting the Retinoblastoma Gene. Science. Sep 1988; p1797. 8/ Chintagumpala M, Chevez-Barrios P, Evelyn AP, Plon SE, Hurwitz R. Retinoblastoma: Review of Current Management. The Oncologist. 2007; 12:1237-1246. 9/ Abramson DH, Beaverson K, Sangani P, Vora RA, Lee TC, Hochberg HM, Kirszrot J, Ranjithan M. Screening for Retinoblastoma: Presenting Signs as Prognosticators of Patient and Ocular Survival. Pediatrics. Dec 2003; Vol 112 No 6. 10/ Reddy VAP, Honavar SG. Retinoblastoma- Advances in Management. Apollo Medicine. Sept 2008, Vol. 5 No. 3. 11/ Gambos, DS. Retinoblastoma in the perinatal and neonatal child. Seminars in Fetal and Neonatal Medicine. 17 (2012); 239-242.
12/ Chantada, G Schaiquevich P. Management of Retinoblastoma in Children: Current Status. Pediatr Drugs. Published online March 6th 2015.