45  Retinoblastoma

45.1 Introduction

Retinoblastoma is the most common primary intraocular malignancy of childhood, arising from the retina. It typically presents before the age of 5 years and carries major implications for vision, survival, and quality of life. The disease has become a paradigm for cancer genetics, as the RB1 tumour suppressor gene was the first tumour gene identified in humans.

Early diagnosis and treatment are critical: retinoblastoma is highly curable if detected early, but advanced disease can be fatal. In high-income countries, survival exceeds 95%, while in many low- and middle-income countries—including Ghana—delayed diagnosis often results in poorer outcomes.

45.2 Incidence and Prevalence

• Global incidence: about 1 in 15,000–20,000 live births.
• Accounts for 3–4% of all childhood cancers.
• Peak age:
  • Unilateral disease: 2–3 years.
  • Bilateral disease: diagnosed earlier, often before 1 year.
• No sex predilection.
• In Ghana and other sub-Saharan countries, children frequently present late, often with extraocular spread, which worsens survival rates.

45.3 Aetiology

The development of retinoblastoma is intimately linked to the RB1 gene on chromosome 13q14.

• Heritable form (40% of cases):
  • Germline mutation in one allele of RB1 gene is inherited.
  • Second hit occurs somatically in retinal cells.
  • Usually bilateral and multifocal.
  • Associated with increased risk of secondary malignancies (e.g., osteosarcoma).
• Non-heritable form (60% of cases):
  • Both RB1 mutations occur somatically.
  • Usually unilateral and unifocal.

Rarely, retinoblastoma may arise from MYCN amplification even without RB1 mutation.

45.4 Pathophysiology

The RB1 gene product regulates the G1–S checkpoint of the cell cycle. Loss of both functional RB1 alleles leads to uncontrolled retinal cell proliferation.

• Tumours originate from retinal progenitor cells.
• Can grow in various patterns:
  • Endophytic: growing into the vitreous.
  • Exophytic: growing beneath the retina, leading to retinal detachment.
  • Diffuse infiltrating: rare, spreading through the retina without forming a discrete mass.
• Spread:
  • Local invasion (into optic nerve, choroid, sclera).
  • Extraocular spread (orbit, brain via optic nerve, systemic metastasis to bone marrow, liver).

45.5 Clinical Features

Presentation varies depending on stage and extent of disease.

• Most common presenting sign:
  • Leukocoria (white pupillary reflex), often noticed in photographs with flash.
• Other features:
  • Strabismus (misalignment of eyes).
  • Red, painful eye (from secondary glaucoma, uveitis, or tumour necrosis).
  • Poor vision or blindness.
  • Hyphema (blood in anterior chamber).
  • Orbital swelling or proptosis (extraocular disease).
  • Rare systemic symptoms in metastatic disease (bone pain, weight loss, fever).

45.6 Differential Diagnosis

• Coats’ disease (retinal telangiectasia with exudation).
• Persistent hyperplastic primary vitreous.
• Congenital cataract.
• Toxocariasis.
• Retinal detachment.
• Medulloepithelioma of the ciliary body.

45.7 Investigations

• Ocular examination:
  • Indirect ophthalmoscopy under anaesthesia (definitive for diagnosis).
• Imaging:
  • Ultrasound B-scan: reveals intraocular mass with calcification.
  • CT scan: useful for calcifications but limited due to radiation risk.
  • MRI of orbits and brain: preferred for local extension (optic nerve, CNS).
• Laboratory tests: not diagnostic, but baseline bloods useful before chemotherapy.
• Genetic testing:
  • Detects RB1 mutation.
  • Guides family counselling and screening of siblings.

Biopsy of the eye is avoided due to risk of tumour spread.

45.8 Staging

Two main systems:

1. International Intraocular Retinoblastoma Classification (IIRC) – based on disease extent within the eye (Groups A–E).
2. International Retinoblastoma Staging System (IRSS) – for post-enucleation staging, including extraocular spread and metastasis.

45.9 Treatment

Treatment depends on whether the disease is unilateral or bilateral, intraocular or extraocular, and the aim (life preservation, eye salvage, vision preservation).

45.9.1 Emergency Care

• Treat secondary glaucoma for pain relief.
• Manage raised intracranial pressure in cases of optic nerve invasion.

45.9.2 Definitive and Ongoing Management

• Enucleation: removal of the affected eye. Standard for unilateral advanced disease.
• Focal therapies (for small tumours):
  • Laser photocoagulation.
  • Cryotherapy.
  • Thermotherapy.
• Chemotherapy:
  • Systemic chemotherapy (vincristine, carboplatin, etoposide) for chemoreduction.
  • Intra-arterial chemotherapy (direct to ophthalmic artery).
  • Intravitreal chemotherapy (for vitreous seeds).
• Radiotherapy:
  • External beam (rare now, due to risk of secondary tumours in heritable cases).
  • Plaque brachytherapy for selected cases.
• Bilateral disease: efforts made to preserve at least one eye with useful vision.

45.9.3 Preparation for Discharge

• Educate parents on prosthesis care after enucleation.
• Importance of follow-up for recurrence detection.
• Genetic counselling for families with heritable disease.

45.9.4 Long-Term Management

• Regular ophthalmologic examinations under anaesthesia.
• Screening for second malignancies in heritable cases.
• Monitoring growth, vision development, and psychosocial adjustment.

45.10 Complications

• Local recurrence within the eye or orbit.
• Extraocular spread with poor prognosis.
• Metastases to CNS, bone marrow, or distant organs.
• Vision loss, especially in bilateral disease.
• Cosmetic issues after enucleation.
• Secondary malignancies in heritable retinoblastoma, particularly osteosarcoma and soft tissue sarcomas (especially after radiotherapy).

45.11 Prognosis

• In high-income countries: >95% survival.
• In sub-Saharan Africa: survival often <40%, mainly due to late presentation, extraocular disease, and limited treatment resources.
• Prognosis is best with early detection, small intraocular tumours, and access to multimodal therapy.

45.12 Prevention

• No known prevention for sporadic cases.
• Genetic counselling and testing: vital in families with heritable retinoblastoma.
• Screening of at-risk infants (regular eye exams from birth to 5 years).
• Avoid unnecessary exposure to ionising radiation in heritable cases.

45.13 Conclusion

Retinoblastoma is a highly curable childhood malignancy when detected early. The disease highlights the importance of integrating clinical suspicion, imaging, genetic counselling, and multimodal therapy in management. In Ghana and similar settings, community education to recognise leukocoria early, improved access to ophthalmic oncology, and support for families can dramatically improve survival and quality of life.