Overview
Definition:
Retinoblastoma is the most common primary intraocular malignancy of childhood, arising from primitive neuroectodermal cells of the retina
It is a malignant tumor that affects infants and young children, typically diagnosed before age 5.
Epidemiology:
The incidence is approximately 1 in 15,000 to 20,000 live births worldwide
Bilateral retinoblastoma accounts for approximately 25-30% of cases and is often hereditary, linked to germline mutations in the RB1 gene
Unilateral cases are more commonly sporadic.
Clinical Significance:
Early diagnosis and prompt management are crucial for salvaging vision, preserving the eye, and improving survival rates
Retinoblastoma can metastasize and if left untreated, has a high mortality rate
Understanding its presentation, diagnosis, and treatment is vital for pediatricians and ophthalmologists.
Clinical Presentation
Symptoms:
The most common presenting sign is leukocoria, also known as the "white reflex" or "cat's eye reflex"
Other symptoms include strabismus (crossed or wandering eye), poor vision, red or inflamed eye, and sometimes hyphema or vitreous seeding
In advanced stages, orbital cellulitis or proptosis may occur.
Signs:
On examination, leukocoria is a prominent sign
Tumors can appear as whitish or yellowish masses within the retina
They may be endophytic (growing into the vitreous) or exophytic (growing into the subretinal space)
Other signs include retinal detachment, neovascularization, and seeding into the anterior chamber.
Diagnostic Criteria:
Diagnosis is primarily clinical, confirmed by ophthalmic examination and imaging
In suspicious cases, a thorough ophthalmologic evaluation including dilated fundus examination under anesthesia (if necessary) is performed
Biopsy is generally avoided due to the risk of tumor dissemination.
Diagnostic Approach
History Taking:
Key history includes age of onset, presence and duration of leukocoria or strabismus, family history of retinoblastoma or other cancers, and any prior eye trauma
Ask about developmental milestones, as delayed development might indicate neurological involvement in advanced cases.
Physical Examination:
A complete ophthalmic examination is essential, including visual acuity assessment, pupillary light reflexes, extraocular movements, and detailed fundus examination
In infants and young children, a dilated fundus examination may require sedation or general anesthesia
Evaluate for proptosis, orbital mass, and signs of metastatic disease.
Investigations:
Ophthalmic ultrasound (B-scan) is useful for visualizing intraocular masses and calcification
CT scan of the orbits and brain can detect orbital invasion and CNS metastasis
MRI is preferred for assessing optic nerve and orbital soft tissue involvement
Genetic testing for RB1 mutations is important for hereditary cases
Blood counts and liver function tests may be done to rule out metastasis.
Differential Diagnosis:
Leukocoria can be caused by other conditions, including persistent hyperplastic primary vitreous (PHPV), Coats' disease, toxocariasis, retinal detachment, uveitis, cataract, and orbital cellulitis
Differentiating these from retinoblastoma is critical for appropriate management.
Management
Initial Management:
Management strategies depend on the stage and laterality of the disease, aiming to preserve vision and the globe, and prevent metastasis
For small, peripheral tumors, focal therapies like cryotherapy, laser photocoagulation, or transpupillary thermotherapy (TTT) may be used.
Medical Management:
Systemic chemotherapy is the mainstay for most cases, especially bilateral disease or larger unilateral tumors, and for controlling metastatic disease
Common regimens include vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, and doxorubicin
Localized chemotherapy via intra-arterial infusion (e.g., melphalan, topotecan) offers targeted delivery and reduced systemic toxicity for select cases.
Surgical Management:
Enucleation (surgical removal of the eyeball) is indicated for eyes with advanced disease (e.g., extensive retinal detachment, vitreous seeding, optic nerve involvement beyond the lamina cribrosa, or when vision cannot be salvaged)
It is a definitive treatment for the affected eye and is crucial for preventing systemic spread.
Supportive Care:
Supportive care includes regular ophthalmic and oncological follow-up to monitor for tumor recurrence, new tumor development, and treatment-related toxicities
Psychosocial support for the child and family is paramount, especially in cases of enucleation
Prosthetic eyes are fitted after enucleation once healing is complete.
Complications
Early Complications:
Complications of treatment can include post-enucleation hemorrhage, infection, or inadequate tumor removal
Chemotherapy can cause myelosuppression, nausea, vomiting, and alopecia
Localized treatments may lead to retinal necrosis or scarring.
Late Complications:
Late complications include secondary cancers (especially in heritable retinoblastoma), impaired vision in treated eyes, strabismus, refractive errors, and cosmetic issues related to enucleation
Risk of infertility and other long-term effects of chemotherapy should be monitored.
Prevention Strategies:
Preventing metastasis involves prompt and adequate treatment
Genetic counseling and screening are crucial for families with a history of retinoblastoma to identify at-risk individuals and facilitate early detection
Careful monitoring for treatment-related toxicities is also important.
Prognosis
Factors Affecting Prognosis:
Favorable prognostic factors include early diagnosis, smaller tumor size, unilateral disease, and absence of optic nerve or choroidal invasion
Factors associated with a poorer prognosis include bilateral disease, larger tumors, high-risk histology, and optic nerve or orbital involvement.
Outcomes:
With modern multimodal therapy, survival rates for retinoblastoma are excellent, often exceeding 95% for localized disease
However, the visual outcome varies significantly, depending on the extent of the tumor and the treatment modality used
Enucleation offers a high cure rate for localized intraocular disease.
Follow Up:
Long-term follow-up is essential
Patients require regular ophthalmic examinations to monitor for recurrence or new tumors in the fellow eye
Survivors of heritable retinoblastoma are at increased risk for other cancers and require ongoing surveillance throughout their lives, including regular physical examinations and age-appropriate cancer screening.
Key Points
Exam Focus:
Leukocoria is the hallmark sign of retinoblastoma
Differentiate between heritable (often bilateral) and sporadic (often unilateral) forms
Understand the role of RB1 gene
Recognize indications for enucleation vs
conservative management (chemotherapy, local therapies)
Know common chemotherapy regimens (VEC) and intra-arterial chemotherapy.
Clinical Pearls:
Always consider retinoblastoma in any infant with leukocoria or strabismus, even if the fundus appears normal on initial inspection
A thorough family history is crucial
Remember that treated eyes can still develop secondary cancers, necessitating long-term follow-up.
Common Mistakes:
Delayed diagnosis due to misinterpreting leukocoria as a benign condition like persistent pupillary membrane or strabismus
Failure to perform a dilated fundus examination or repeat examinations when suspicious
Inadequate treatment of larger or higher-risk tumors
Not considering genetic counseling for suspected heritable forms.