Retinoblastoma is the most common primary intraocular malignancy of childhood. Even so, it is rare, occurring in about 1:20,000 live births and accounts for about 3% of all childhood cancers. It develops from the immature cells of retina, the light detecting tissue of the eye. Though most children survive this cancer, they may lose their vision in the affected eye or need to remove the eye. Retinoblastoma results from malignant transformation of primitive retinal cells before final differentiation. Because these cells disappear within the first few years of life, the tumour is seldom seen after 3 years of age. Almost half of children with retinoblastoma have a hereditary genetic defect associated with retinoblastoma. In other cases, it is caused by a congenital mutation in the chromosome 13. The predisposing gene (RPE1) is at 13q14.
The most common sign of retinoblastoma is an abnormal appearance of the retina viewed through pupil called leukocoria also known as amaurotic cat’s eye reflex. Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop squint. Retinoblastoma presents with advanced disease in developing countries and eye enlargement is common finding. Leukocoria is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats’ disease. The presence of the photographic fault red eye in only one eye and not in the other eye may be a sign of retinoblastoma.
Heritable or Germline retinoblastoma accounts for about 40%. In these patients one allele of the RPE1 (a tumour suppressor gene) has mutated in all body cells. When a further mutogenic event (second hit) affects the second allele, the cell undergoes malignant transformation. This is bilateral condition and may also develop another non ocular cancer like pinealoblastoma (trilateral retinoblastoma) and osteosarcoma.
Non-heritable or Somatic retinoblastoma accounts for about 60% of cases. The tumour is unilateral, not transmissible and does not predispose the patient to an increased risk of second non ocular cancers.
Intra-Arterial Chemotherapy(IAC) for retinoblastoma
Intra-arterial chemotherapy for the treatment of retinoblastoma was first performed by Algeron B. Reese with direct internal carotid artery injection of the alkylating agent triethylene melamine (TEM) in 1954. The idea of local delivery of chemotherapy for retinoblastoma was later revised by Yamane & Kaneko in 2004 when they described the technique of selective ophthalmic artery infusion (SOAI) where a micro-balloon catheter is positioned by a trans femoral artery approach at the cervical segment of the internal carotid artery just distal to the orifice for the ophthalmic artery. At this point, the balloon catheter is inflated, and chemotherapy is injected with flow thereby directed into the ophthalmic artery. It is important to note intra-arterial treatment is indicated only for intraocular retinoblastoma and not for disease with extra-ocular involvement which requires consultation with pediatric oncologist.
There is intense interest in the use of intra-arterial chemotherapy for retinoblastoma. The main reason is for this is because the technique is theoretically focused to provide chemotherapy directly to the eye via ophthalmic artery with minimal escape of chemotherapy for the rest of the body. This is achieved by catheterization of the femoral artery, through the aorta, into the internal carotid artery and slipping into the ophthalmic artery with subsequent pulsatile chemotherapy flush. The good news is that it works and the bad news is that there are potential complications of vascular obstruction of the choroidal or retinal vessels leading to blindness and more seriously, there is a risk of spasm of obstruction of larger vessels in the brain leading to stroke or death. But most of the researches show that there has been no case of stroke or death till now. Initially, retinal or choroidal flow reduction was noted but this feature has nearly disappeared now with better technique. We do not enter the ophthalmic artery, as initially discussed. We just prick into the ostium of the artery, so that there is no obstruction to flow and the chemotherapy is flushed to the eye admixed with blood.
Most of authors have shown that only 1 or 2 sessions of IAC are necessary to complete control of retinoblastoma in some instances. This is an important observation as most centers plan 3 sessions or more. However, with less advanced tumours that show minimal seeding, only 1 or 2 sessions are needed. This allows for reduction in complications. A complete blood count with platelets is recommended for all patients 7-10 days after the IAC procedure to monitor for myelosupression. Complete ophthalmic examinations should be performed every 3-4 weeks after treatment.
Retinoblastoma is a dangerous, life-threatening malignancy of the eye, classically found in children. This cancer grows rapidly and can lead to metastasis and death if not appropriately managed with time. The use of IAC has allowed rapid control of this cancer with minimal systemic toxicity. Long term data are not available regarding IAC, but hopefully the tumour control is lasting and the complications remain minimal. Intra-arterial chemotherapy is an emerging therapy and represents a significant advance in the treatment of intraocular retinoblastoma, particularly for advanced cases. Its preliminary success is recognized worldwide, and it is currently being performed in over 31 countries.
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Author Sarbind Kumar Yadav, M.Optom Senior Consultant Optometrist Ramlal Golchha Eye Hospital Foundation Biratnagar,Nepal