Retinoblastoma
Description
Retinoblastoma is the most common intraocular malignant tumour of childhood, arising from the retina. It may arise from single or multiple foci in one or both eyes and is caused by biallelic inactivation of the RB1 tumour-suppressor gene.
Referral Requirement:
Any child presenting with leukocoria or any associated signs must be urgently referred to an ophthalmologist for examination under anaesthesia (EUA) for diagnosis, staging, and visual prognosis assessment.
Signs and Symptoms
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Leukocoria (white pupillary reflex)
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Strabismus
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Red, painful eye
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Intraocular eye tumour mass
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Creamy-pink mass projecting into the vitreous
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White avascular tumour
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Retinal detachment
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Vitreous haemorrhage
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Clouding of the anterior chamber
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Local eye pain
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Loss of vision
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Anaemia
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CNS involvement: seizures, altered consciousness
Advanced disease features
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Buphthalmos
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Glaucoma
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Periorbital cellulitis
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Proptosis
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Lymph node enlargement
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Distant metastases (brain, bone, bone marrow, other sites)
Investigations
A. Intraocular Disease Assessment
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Intraocular extent assessment
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Indirect ophthalmoscopy
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Ultrasonography of the globe
B. Orbital Extent Assessment
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Plain X-ray: optic foramen, orbit, skull
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CT scan of the orbit
C. Metastatic Evaluation
| Investigation | Purpose |
|---|---|
| Lumbar puncture + CSF cytology | CNS metastatic assessment |
| Full blood count | Systemic involvement |
| Liver function tests | Baseline and staging |
| Ferritin | Supportive tumour markers |
| Neuron-Specific Enolase (NSE) | Additional tumour marker |
| Bilateral bone marrow aspiration & biopsy | Bone marrow involvement |
| Abdominal ultrasound (liver/spleen) | Abdominal metastases |
| CT scan: brain, head, abdomen | Distant metastases |
| Bone scan | Bone metastases |
| Biopsy of extraocular masses | Confirm metastatic disease |
| Globe + optic nerve stump histopathology (if enucleated) | Local invasion, margin status |
D. Additional Investigations
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Genetic testing for RB1 mutation
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FISH
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Methylation studies for epigenetic analysis
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Multiplex ligation-dependent probe amplification (MLPA)
Treatment Overview
Primary goal: Save life
Secondary goal: Preserve vision where possible
Metastatic disease outside CNS (liver, bone, bone marrow):
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Treatable with platinum-based chemotherapy,
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Followed by autologous haematopoietic stem cell transplant and irradiation.
CNS metastatic disease:
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Poor prognosis
Treatment Approach Based on Laterality
Table 72: Treatment Approach Based on Laterality of Disease
| Extent of Disease | Features | Recommended Treatment |
|---|---|---|
| Unilateral or bilateral retinoblastoma | Each eye staged independently (Groups A–E) | Groups A, B, C: Eye-conserving therapy (chemo + laser, cryotherapy, and/or radiotherapy in equipped centres) |
| Group D, E without buphthalmos | — | Non-eye-conserving therapy |
| Post-laminar invasion OR invasion of surgical optic nerve margin OR scleral/orbital extension | Pathological high-risk features | 6 cycles of VJE after enucleation |
| Presence of buphthalmos | — | 2 cycles of VJE → enucleation → 4 cycles of VJE |
| Orbital retinoblastoma with MRI/CT evidence of optic nerve or extrascleral invasion | — | 2–3 cycles VJE → enucleation → 5–6 cycles VJE (total 8 cycles) + Orbital radiotherapy |
| Overt orbital-metastatic retinoblastoma (IRSS Stage III–IV) | — | Palliative therapy: Standard-dose VJE, Metronomic therapy, ± Palliative radiotherapy |
Drug Regimen: VJE
VJE Chemotherapy Regimen
| Drug | ≥3 years / >10 kg Dose | <3 years / <10 kg Dose | Route & Frequency |
|---|---|---|---|
| Vincristine | 1.5 mg/m² IV push over 5 min day 1 | 0.05 mg/kg IV push over 5–10 min day 1 | Every 3–4 weeks |
| Etoposide | 150 mg/m² IV infusion over 1 hr on days 1 and 2 | 5 mg/kg IV infusion over 1 hr on days 1 and 2 | Every 3–4 weeks |
| Carboplatin | 600 mg/m² IV infusion over 1 hr day 1 | 18.6 mg/kg IV infusion over 1 hr day 1 | Every 3–4 weeks |
Total duration: 6–12 cycles depending on disease stage.