Retinoblastoma (RB) is the most common primary intraocular malignancy with an incidence of approximately 1:15,000 births. The tumor suppressor RB1 gene is known to be key in the development of the disease. Most cases (60%) result from a somatic nonhereditary mutation; however, 40% arise from germline hereditary mutations that may occur spontaneously. There is no gender or racial predilection. Most RBs are diagnosed in children younger than 5 years; because of the lack of early symptoms, most children are diagnosed late in the disease process. The mean time of diagnosis in bilateral RB is 11 months. Solitary RB typically is diagnosed after 2 years of age. However, RB has been described in adults. Special attention to prior family history should be undertaken during the initial encounter. Historically, RB has been associated with poor survival and visual outcomes. Currently, survival in industrialized countries is close to 100%. Developing nations continue to report significant mortality associated with this disease entity mainly due to late diagnosis. The most common presenting signs are leukocoria, strabismus, and decreased visual acuity. Early diagnosis and treatment is the most important limitation associated with morbidity and mortality. Referral to a tertiary center could significantly reduce the mortality discrepancy.
Differential diagnoses include Coat’s disease, persistent fetal vasculature (PFV), familial exudative vitreoretinopathy, retinal astrocytoma, osteoma, pediatric cataracts, retinopathy of prematurity, coloboma of the choroid, uveitis, vitreous hemorrhage, retinal dysplasia, retinal detachment, corneal opacities, myelinated nerve fiber, and parasitic infections. Expertise in the complete RB differential diagnosis is critically important at the time of diagnosis.
97.1.1 Common Symptoms
Mostly asymptomatic; pain may be present in advanced cases.
97.1.2 Exam Findings
RB is characterized by a creamy white retinal mass, unilateral or bilateral (▶ Fig. 97.1). In unilateral cases, it is important to determine if multifocal tumor burden is present. Different growth patterns may be present. Endophytic tumors grow toward the vitreous and develop vitreous seeding. Exophytic tumors grow toward the subretinal, choroidal, and scleral space and are associated with exudative retinal detachments. Diffuse tumors may thicken the retina and might be confused with other etiologies.
The most common physical exam finding is leukocoria, especially in large or macular tumors (▶ Fig. 97.2). However, in early or peripheral posterior segment disease, leukocoria might not be present. Strabismus secondary to central visual loss is the second most common sign at initial presentation. Less common presentations include uveitis, orbital cellulitis, hyphema, vitreous hemorrhage, cataract, glaucoma, pseudo-hypopyon, and proptosis. Any child younger than 5 years with a white or yellow posterior segment lesion should be evaluated under anesthesia for RB.
Fig. 97.1 Bilateral retinoblastoma. (a) Fundus photograph demonstrating small macular retinoblastoma. (b) Fundus photography of large macular retinoblastoma with associated epiretinal hemorrhage.
Fig. 97.2 Child with bilateral asymmetrical retinoblastoma with obvious leukocoria in the left eye.
97.2 Key Diagnostic Tests and Findings
97.2.1 Optical Coherence Tomography
Most recently, spectral domain optical coherence tomography (SD-OCT) has become available in the operating room. It can help detect microscopic changes that are not clearly visible during indirect ophthalmoscopy such as intraretinal and subretinal fluid. It can be used to guide management decisions; however, lack of fixation during examination under anesthesia (EUA) may limit the comparison of images over time. OCT may also help with prognostication based on evaluation of foveal anatomic structure and may potentially have a role in the identification of subclinical tumors that manifest as retinal layer alterations (e.g., thickening of the middle retinal layers).
97.2.2 Fluorescein Angiography or Ultra-Widefield Fluorescein Angiography
Fluorescein angiography (FA) or near ultra-widefield fluorescein angiography (UWFA) during EUA has become available to large centers during the last decade. UWFA allows localization areas of vascular ectasia, capillary drop-off, and/or compromised vascular permeability that may be associated with tumoral activity. It may also aid in differentiation from other retinovascular diseases.
97.2.3 Fundus Autofluorescence
Autofluorescence may help detect intraocular calcifications. Autofluorescence of RB generally shows bright hyper-autofluorescence of the calcified portion and variable autofluorescence of the noncalcified portion. The presence, location, and progression of intraocular calcifications facilitate in the diagnosis and management of RB.
97.2.4 Fundus Photography
Widefield fundus photography is extremely important during evaluation and follow-up of RB. Although it does not aid in diagnosis, it remains a vital tool for follow-up to detect subtle changes in time that may otherwise be unrecognized (▶ Fig. 97.3). These images can be tracked longitudinally over time to assess progression or arrest of RB. New ultra-widefield photography technologies allow documentation of the retinal periphery and better assessment during management.
Fig. 97.3 Fundus photography demonstrates vitreous seeding, an ominous sign of advanced disease.