Overview
Definition:
Retinoblastoma is the most common primary intraocular malignancy of childhood, arising from photoreceptor precursor cells
Red reflex screening is a simple, non-invasive method to detect potential abnormalities in the ocular media, particularly leukocoria (white pupillary reflex), which is a classic sign of retinoblastoma.
Epidemiology:
Incidence is approximately 1 in 15,000 to 20,000 live births worldwide
It accounts for about 3-5% of all childhood cancers
Bilateral cases are more common in heritable forms (germline mutation), while unilateral cases are more frequent in sporadic forms
Peak age of diagnosis is around 18-24 months.
Clinical Significance:
Early detection of retinoblastoma through red reflex screening is crucial for successful treatment and preservation of vision
Delayed diagnosis significantly worsens the prognosis, increasing the risk of enucleation, metastasis, and mortality
This screening is a fundamental skill for pediatricians and ophthalmologists.
Clinical Presentation
Symptoms:
The most common presenting sign is leukocoria (a white or yellowish reflex in the pupil)
Other symptoms may include strabismus (crossed or wandering eyes), decreased visual acuity, eye pain, redness, or a visible mass
In advanced stages, exophthalmos may be present.
Signs:
A normal red reflex appears as a symmetric, symmetrical reddish-orange glow in both pupils when illuminated by an ophthalmoscope or penlight
An abnormal reflex can be white, yellow, or absent
Other signs include visible tumors within the eye, vitreous seeds, or retinal detachment
Strabismus can be a primary observation.
Diagnostic Criteria:
Diagnosis is primarily clinical and confirmed by ocular imaging
Definitive diagnosis relies on ophthalmoscopic visualization of a retinoblastoma tumor
Histopathological confirmation after enucleation or biopsy (less common) is the gold standard, but usually not required for initial diagnosis when typical findings are present.
Diagnostic Approach
History Taking:
Inquire about any noticed abnormalities in the child's eyes, especially a white or unusual reflex
Ask about family history of retinoblastoma or other cancers
Note the age of onset of symptoms and any associated visual complaints or neurological symptoms.
Physical Examination:
Perform a thorough ophthalmic examination including visual acuity assessment (age-appropriately)
Assess for strabismus
Crucially, perform the red reflex test using an ophthalmoscope or penlight from a distance of about 30 cm, observing the pupillary reflex in each eye
Follow with a funduscopic examination to visualize the retina and any intraocular lesions.
Investigations:
Ocular ultrasound (B-scan) is vital for assessing tumor size, calcification, and calcification extent
MRI of the orbits and brain is essential for staging, assessing optic nerve and orbital involvement, and ruling out intracranial extension
CT scans can also be used, but MRI is preferred due to better soft tissue contrast and avoidance of radiation
Genetic testing may be indicated for suspected hereditary retinoblastoma.
Differential Diagnosis:
Conditions mimicking leukocoria include persistent hyperplastic primary vitreous (PHPV), Coats disease, toxocariasis, retinopathy of prematurity (ROP), congenital cataracts, vitreous hemorrhage, and ocular inflammatory conditions
Strabismus can be due to refractive errors, accommodative excess, or other cranial nerve palsies.
Management
Initial Management:
Management is multidisciplinary, involving ophthalmologists, pediatric oncologists, and radiation oncologists
The primary goal is to preserve the eye and vision, while eradicating the tumor and preventing metastasis
Staging of the tumor is critical for treatment planning.
Medical Management:
Systemic chemotherapy is the mainstay for many cases, particularly for bilateral disease or larger tumors
Common agents include carboplatin, etoposide, and vincristine
Localized chemotherapy delivery via intra-arterial infusion (IA chemotherapy) offers a targeted approach with reduced systemic toxicity
Intravitreal chemotherapy may be used for vitreous seeding.
Surgical Management:
Enucleation (surgical removal of the eye) is indicated for eyes with advanced tumors, extensive optic nerve involvement, or when other therapeutic modalities have failed
It is the definitive treatment to prevent spread
Cryotherapy and thermotherapy are used for focal, peripheral tumors, often in conjunction with chemotherapy.
Supportive Care:
Supportive care includes managing treatment-related side effects like myelosuppression, nausea, and alopecia
Psychological support for the child and family is paramount
Prosthetic eyes are fitted after enucleation to maintain cosmetic appearance.
Complications
Early Complications:
Chemotherapy side effects (neutropenia, anemia, thrombocytopenia, nausea, vomiting, alopecia)
Surgical complications of enucleation include infection, hemorrhage, and anesthetic risks
Ocular complications from local treatment include inflammation, cataract formation, and retinal detachment.
Late Complications:
Secondary malignancies (in heritable retinoblastoma), impaired vision or blindness in the affected eye, cosmetic disfigurement from enucleation, recurrence of tumor, and psychological distress
Long-term effects of chemotherapy can include infertility and cardiac issues.
Prevention Strategies:
Regular and thorough red reflex screening in infancy and early childhood
Prompt referral for any suspicious findings
Accurate staging and appropriate treatment selection based on consensus guidelines (e.g., International Classification of Retinoblastoma)
Close follow-up to monitor for recurrence or complications.
Prognosis
Factors Affecting Prognosis:
Tumor size and location, presence of optic nerve or uveal involvement, vitreous seeding, bilaterality, and the specific treatment received
Early diagnosis and treatment significantly improve outcomes.
Outcomes:
With modern multimodal therapy, the cure rate for retinoblastoma is over 90%
Vision can often be preserved in many cases, especially with early detection and focal treatments
However, enucleation may be necessary for advanced disease
Metastasis and death are rare with timely and appropriate care.
Follow Up:
Lifelong surveillance is recommended for survivors, particularly those with heritable retinoblastoma, due to the increased risk of secondary malignancies
Regular ophthalmic examinations are required to monitor for tumor recurrence, assess vision, and detect any complications
Screening for other cancers may also be advised.
Key Points
Exam Focus:
Leukocoria is the cardinal sign of retinoblastoma
Differentiate retinoblastoma from other causes of leukocoria
Understand the role of red reflex screening in early detection
Know the main chemotherapeutic agents and local treatment modalities
Recognize the importance of genetic counseling in heritable forms.
Clinical Pearls:
Never assume leukocoria is benign
Always perform a thorough ophthalmic examination and consider retinoblastoma in any child with leukocoria or strabismus
Remember that a normal red reflex is bright red and symmetrical
Early referral to a pediatric ophthalmologist is paramount.
Common Mistakes:
Failing to perform red reflex screening in all infants and young children
Delaying referral for suspected leukocoria or strabismus
Misinterpreting benign conditions as retinoblastoma or vice versa
Inadequate staging leading to suboptimal treatment
Not considering the possibility of hereditary retinoblastoma.