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Dr. Mahziba Rahman
MCPS, FCPS
Eye Specialist & Surgeon
Bangladesh Eye Hospital Ltd.
• The most common primary intraocular malignancy of childhood
• 3% of all childhood cancer
• Occurs due to malignant transformation of primitive retinal cells
before final differentiation
• Seldom seen after 3 yrs of age
• Incidence : 1/14000 – 1/20,000 live birth.
• 90% of case present before 3 yrs of age.
• Occurs equally in male & female.
• No racial predilection.
• 60% - 70% unilateral
• 30% – 40% bilateral
• Prevents cellular replication
• Disrupton of this gene leads to growth of cancer cells
• Retinoblastoma occurs due to mutation of RB1 gene, located at
13q14
• Both alleles of RB1 must be mutated for a tumour to form.
.
• Two mutations requred to produce retinoblastoma
• The‘two hit hypothesis on’ was proposed by
Knudson.
Hereditary case-
• First hit –one mutated allele is inherited & present in
all somatic cells.
• Second hit – Further mutagenic event effects the
second allele during the person’s lifetime.
In non- hereditary cases
• Affected individuals are born with two normal alleles
• Both the mutations (hits) occur somatically with in
the single retinal cell.
Heritable
retinoblastoma
Non-Heritable
retinoblastoma
Occurrence 40% 60%
Family History Positive Negative
Age 1 year 2 years
Predisposition to other
malignancies
Present Absent
Tumour Bilateral, multifocal Unilateral
Risk to sibling 2%- healthy parents
40%-affected parents
1%
• LeukocoriaLeukocoria (white pupillary reflex)- 60%
• Commonest presentation
• Often first noticed in family photograph
• Strabismus (20%)
•
• Secondary glaucoma
occasionally associated with Buphthalmos
• Red eye due to tumour induced uveitis & iris nodule ,
pseudohypopyon (5%)
• Orbital inflammation
mimicking orbital or preseptal cellulitis
• Orbital invasion with proptosis
• Metastatic disease involving
regional lymph node & brain.
• Raised ICP due to trilateral
retinoblastoma.
• Bilateral retinoblastoma with intracranial
retinoblastoma
• Usually present in pineal gland or parasellar region
• Present in 5% of children with hereditary type
• Visual function
• Slit lamp biomicroscopy
• Indirect Ophthalmoscopy
with scleral indentation
• EUA
Corneal diameters
IOP
Ophthalmoscopy
Intraretinal tumour -
• Dome shaped,
• Gray to white ,
• Fed & drained by dilated & tortuous vessels,
• Developing foci of calcification - chalky white appearance.
 They may grow in 3 types
Subretinal, multilobular white masses
Retinal detachment may occur
Projects into vitreous as white mass
May seed into vitreous
• Rare
• Unilateral
• Detected in later age ( >5 years)
• Difficult to detect
• B-scan ultrasonography
 To assess tumour size
• CT scan
 Detect calcification
 Not preferred as radiation can lead to second tumour
• MRI
 Superior for ON evaluation, extra ocular extension or to detect
pinealoblastoma
 Used for follow up
• Systemic investigations
• Genetic studies
• Cells have round, oval or spindle-shaped nuclei ,
twice the size of lymphocyte
• Nuclei are hyper-chromatic with scanty cytoplasm.
• High mitotic activity
• Calcification with necrosis
Many retinoblastoma are undifferentiated but varying degree of
differentiation are characterized by the formation of Rosettes
1.Flexner-Wintersteiner rosettes,
2.Homer-Wright rosettes,
3.Fleurettes.
Undifferentiated tumour
 Tall columnar cell surrounding a central lumen
 Nuclei lie away from lumen
 Cells have undergone retinal differentiation
• Less common
• The lumen of a H W rosette is filled with a tangle of
eosinophilic cytoplasmic processes
• Also be found in other neuroblastic tumour
• These cells exhibit photoreceptor differentiation.
• Cluster of cells with long cytoplasmic process project
through a fenestrated membrane.
• Appearance resembles a bouquet of flower.
• Congenital cataract
• Retinopathy of prematurity
• Persistent fetal vasculature
• Coats disease
• Toxocariasis
• Uveitis
• Retinal dysplasia
• Retinoma (retinocytoma)
• Retinal astrocytoma
Table: Reese-Ellsworth Classification of Retinoblastoma
Group Quick Reference Description Treatment
A Tumors≤3 mm
Small discrete tumors away from 
critical structures      
•Confined to the retina
• >3 mm from the foveola
• >1.5 mm from the optic 
nerve
Focal therapy
B Discrete retinal tumor of any size 
or location
•Tumors not in group A
•No vitreous or subretinal 
seeding
•Subretinal fluid >3 mm 
from the base of the tumor
Small number of 
chemotherapy 
cycles
Focal therapy
C Minimal vitreous or subretinal 
seeding 
•Subretinal fluid involves 
¼ retina
•Subretinal  & vitreous 
seeds ≤3 mm from the 
tumor
Chemotherapy
Focal therapy
Group Quick Reference Description Treatment
 D Diffuse vitreous or subretinal 
seeding 
•Massive and/or diffuse 
intraocular tumour
•More than one quadrant of 
retinal detachment
Fine greasy vitreous seeding 
or avascular masses
Subretinal seeding include 
plaques
Chemotherapy
Focal therapy
E •Eyes that have been destroyed 
anatomically or functionally by 
the tumor
• Eyes with one or more than the 
following
•Tumor touching the lens
• Neovascular glaucoma
•Tumor anterior to vitreous 
•Diffuse infiltrating 
retinoblastoma
•Massive intraocular 
hemorrhage
•Aseptic orbital cellulitis
•Phthisis bulbi
Enucleation
• When treating retinoblastoma, it is first & foremost 
important to understand that it is a malignancy
•  In deciding on a treatment strategy, the first goal 
must be -
Saving lifeSaving life,
then saving the sight
• Primary health care providers
• Pediatrician
• Ophthalmologist
• Paediatric oncologist
• Geneticist
• Important 
                                  Cause & prognosis of disease
                                  Treatment options
                                   Follow up
                                   Genetic counselling 
•  Parents must be examined prior to treatment
• Photocoagulation
• Cryotherapy
• Plaque radiotherapy / Brachytherapy
• Transpupillary thermotheapy
•  External beam radiotherapy
•  Post-equatorial tumour  for (IIRC group A,B,C,D)
• Tissue temperature raised > 60°c using a argon or diode laser
                    Encircling tumour double row of laser burns
                                              
                               
                    Destruction of blood supply
                 
                                          Regression                               
                                                                                       
                                                               
• Diode laser (810nm) is used over tumour surface
  Temperature raised above 45°c for 1 min
Tumour cell death occurs by hyperthermia
 
• Pre-equatorial tumour (IIRC group A & B)
• Triple freeze thaw technique
               Tumour cells killed while thawing
               Full minute thaw before freezing again
• Repeated 4 weeks apart
•  Solitary tumours <15mm, not near disc or macula
• Commonly used isotopes are iodine 125 & ruthenium 106
•  The tumour is localized
       Plaque sutured to sclera                          Before treatment
                                                                                                                                                      Before treatment    
       Left in situ for 3-5 days
                                                                                                                  Cottage-cheese appearance after   
                                                                                                                                 treatment
• Drugs used:
     Carboplatin 
     Vincristin                                          
     Etoposide                                                 Before treatment
     Cyclosporine
• Cycles:  
     4- 9 cycles every 3 to 4 weeks
                                                                                       
                                                                                 6 months later after treatment
• Dose of 4000-4500 cGy in divided fractions over 3-4 weeks
• Indication-
Bilateral disease not responsive to laser or cryotherapy
• Should be avoided -
- Second tumour risk - Radiation retinopathy
- Cataract formation - Mid face hypoplasia
- Radiation optic
neuropathy
• IIRC Group E , recurrent tumour & failure of other
treatment
• Minimum manipulation of the globe
• Important to obtain a long optic nerve stump (8-12mm)
• Sent for histopathological examination & genetic studies
• Placement of orbital implant within muscle cone to
allow orbital growth
• Local orbital recurrence :
External beam radiation and systemic
chemotherapy
• Metastatic RB:
Intensive chemotherapy with cyclosporine
• Meningeal spread of RB:
Intrathecal or intra ventricular chemotherapy
• Intravitreal chemotherapy
Administration of melphalan has been used for vitreous
seeding
High success rate
Needle might create hole and allow tumour spread
• Intra-arterial chemotherapy
Chemotherapy directly injected in ophthalmic artery
Low dose required
Reduce systemic side-effects
• Periocular chemotherapy injection
Increases intraocular level
• Complete and spontaneous necrosis
• Following treatment
-Cottage-cheese calcified mass
-Translucent fish-flesh mass Fig: Cottage-cheese mass
-Mixture
-Flat atrophic scar
Fig: Before and after 2 cycles of chemotherapy
• Risk of secondary malignancies
• Detection of recurrence & new tumour growth
• Management of the complications of therapy
• Genetic counseling
• EUA every 2-8 wks until the age of 3 yrs
• Every 6 months until the age of 5 yrs
• Annually until the age of 10 yrs
Fig: Recurrent RB
Pictures courtesy of the department of Oculoplasty
Parent Affected child Siblings
Bilateral RB
survivor
45%
Unilateral RB
survivor
7%
Healthy Bilateral RB 5%
Healthy Unilateral RB 1%
• Survival rate
-95% , 5 year survival (intraocular tumour)
- 5%, 5 year survival (extraocular)
• Poor prognostic factors
-Size of timour
- Optic nerve involvement
- Extraocular spread
- Older age at presentation
• Extraocular extension
• Trilateral retinoblastoma
• Second malignancies
• Over the last decade dramatic improvement in
management
• In the developed countries due to advancement in
management protocol treatment now focuses on
vision saving
• In developing countries much advancement still
required
Retinoblastoma

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