170	P. Imbach

15.5Clinical Manifestations

•Leukokoria or leucocoria (“cat’s eye” reflex) shows whitish clouding of the pupil and loss of bright red spot normally seen there when light is shined on the eye; this is the first symptom in the majority of patients

•Strabismus

•Anisocoria

•Loss of vision

•In examination of the fundi following chemical dilatation, often under general anesthesia in young children, tumor mostly present in the area of ora serrata retinae, frequently with vitreous hemorrhages and detachment of the retina

•Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) for detection of extension within the orbit, the optical nerve, and the intracranial area

•Diagnosis of metastases: cerebrospinal fluid analysis by lumbar puncture, bone marrow analysis, bone scintigraphy, and chest X-ray

•Occasionally there is a high level of serum a-fetoprotein or carcinoembryonic antigen (CEA)

15.6Differential Diagnosis

•Granuloma caused by Toxocara infection (with or without eosinophilia in WBC)

•Retinal astrocytoma is rare

•Leukokoria in hyperplasia of the vitreous body

•Detached retina: retinopathy in the preterm infant, Coats syndrome (usually shows a yellow rather than whitish pupil area), congenital retinal detachment, the juvenile form of retinoschisis, von Hippel–Lindau syndrome

•Vitreous hemorrhage: traumatic, neonatal bleeding

•CT and/or MRI allow differentiation and assessment of extension of the pathological process

15.7Therapy

•Treatment of retinoblastoma should be delegated to a specialized oncoophthalmological center in cooperation with pediatric oncologist

•The objective is to maintain vision without endangering the life of the child

•In most advanced stages (groups 3–5) and in unilateral retinoblastoma, enucleation of the eye is necessary; in bilateral retinoblastoma, the eye with the more extensive tumor/loss of vision may need to be enucleated, while the remaining eye can be treated with other therapeutic options; some eyes with group 3 disease can be saved with chemotherapy treatment

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•In extraocular and metastatic retinoblastoma of the CNS, craniospinal irradiation and high-dose chemotherapy with or without autologous transplantation in children above the age of 2–3 years may be considered

•For survivors and families of a child with retinoblastoma genetic counseling and screening is recommended

•Future approaches aimed at avoiding enucleation have included direct to gene therapy using adenoviral vectors containing the thymidine kinase gene that produces an apoptotic response when exposed to ganciclovir

15.7.1 Surgical Management

• Enucleation: in patients with no rupture of the ocular globe and if the ocular nerve has sufficient length. Early prosthetic implant for promoting growth of the orbit and to improve the cosmetic outcome is often necessary

15.7.2 Chemotherapy

•Reduction of the tumor by combination of vincristine, etoposide, and carboplatin, and eventually cyclophosphamide or anthracycline followed by other treatment modalities (see below)

•Chemotherapy is the first therapeutic option in bilateral retinoblastoma, reducing the need for radiotherapy and the risk of secondary tumors

•In extraocular retinoblastoma and/or metastatic retinoblastoma: combination chemotherapy followed by autologous stem-cell transplantation

•In palliative care: vincristine, cyclophosphamide, or vincristine combined with doxorubicin may be helpful

15.7.3 Chemothermotherapy

• Chemotherapy may be augmented by a combination of ultrasound, microwaves, and/or infrared treatments, which increase the temperature of the tissue to 42–60°C and result in excellent outcomes, especially in multiple, small retinal tumors

15.7.4 Radiotherapy

•Retinoblastoma is highly radiosensitive

•Irradiation (linear accelerator) is used most commonly

•Dosage: 35–45 Gy depending of the tumor size (Reese–Ellsworth group 1–2, less than 10 disc diameter)

•Sedation of the child and use of a plaster cast may be necessary