Jagdish Dukre

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Most common intraocular malignancy of infants & children.

Third most common malignancy affecting children.

In India, retinoblastoma is the leading pediatric tumour after Wilm's tumour and lymphoma.

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Epidemiology The incidence of

retinoblastoma worldwide ranges from 1 in 14,000 live births to 1 in 34,000 .

No predisposition RaceGender

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India : 1 in 15,000

Developed

Developing

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The Retinoblastoma Gene and Gene ProductThe first human cancer

suppressor gene to be completely charted.

The retinoblastoma gene, located on the long arm of chromosome 13 (13q14).

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The Retinoblastoma Gene Product

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Knudson’s ‘two-hit’ hypothesis

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Pathology1. Histology

It is composed of small basophilic cells (retinoblasts) with large hyperchromatic nuclei and scanty cytoplasm.

Many retinoblastomas are undifferentiated but varying degree of differentiation,characterised by formation of rosettes which are of 3 types

a) Flexner -Wintersteiner rosettes: consists of central lumen surrounded by tall columnar cells, nuclei of which lie away from the lumen.

b) Homer-Wright rosettes (pseudo-rosettes) it has no lumen and cells form around a tangled mass of eosinophilic processes .

c) Fleurettes: cluster of cells with long cytoplasmic processes, projecting through a fenestrating membrane and appearance resembles the bouquet of flowers.

Pattern of tumour spread1. Growth pattern: It may be endophytic (into the

vitreous) with seeding of tumour cells throughout the eye or exophytic (into the sub-retinal space) causing retinal detachment.

2. Optic nerve invasion: with spread of tumour along the sub-arachnoid space to the brain

3. Metastatic Spread: Regional lymph nodes, lungs and bone.

Growth pattern ENDOPHYTICInto vitreous cavityNo overlying retinal vesselsSimulate endophthalmitisPresent as pseudohypopyon,

nodules at pupillary border.

EXOPHYTIC Grows outwards into

subretinal spaceRetinal vessels seen over itRetinal detachmentSimulate coats disease

ASSOCIATED PRIMARY MALIGNANCIES

Leukemia

Neuroblastoma

Chondrosarcoma

Osteosarcoma

Rhabdomyosarcoma13

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1. Quiescent stage : Last for 6 month to 1 year.

(a) Leukocoria or Amaurotic cat’s eye appearance.

- Commonest presentation

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Pseudoglioma :

disease presenting as leucokoria other than retinoblastoma

- congenital cataract

- persistant hyperplastic primary vitreous

- coat’s disease

- toxocariasis

- retinopathy of prematurity

- organised vitreous haemorrhage.

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b. Squint :

Second most common presentation

Usually convergent

Fundus examination mandatory in childhood stabismus

c. Nystagmus : in bilateral cases

d. Defective vision : when tumour arise late.

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I. Glaucomatous stage :

a. Severe pain, redness, watering, corneal clouding

Mass effect or blockage of angle of anterior chamber

b. Tumour induced uveitis, iris nodules, pseudohypopyon

c. Orbital inflammation — resembling orbital or perseptal cellulitis.

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III. Stage of extraocular extension

Globe burst at limbus followed by rapid fungation and involvement of extraocular tissues resulting in marked proptosis

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Reese-Ellsworth Classification Group Ia. Solitary tumor, less than 4 DD in size, at or behind the equator.b. Multiple size tumors, none over 4 DD in size, all at or behind the

equator.Group IIa. Solitary tumor, 4 to 10 DD in size, at or behind the equator.b. Multiple size tumors, 4 to 10 DD in size, all at or behind the equator.Group IIIa. Any lesion anterior to the equator.b. Solitary tumors larger than 10 DD behind the equator.Group IVa. Multiple tumors, some larger than 10DD.b. Any lesion extending anteriorly to the ora serrata.Group Va. Massive tumors involving over half the retina.b. Vitreous seeding.

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The Grabowski-Abramson Classification Scheme for Extraocular Retinoblastoma

1. Intraocular diseasea. Retinal tumoursb. Extension into choroidc. Extension up to lamina cribrosa2. Orbital diseasea. Orbital tumour1. Suspicious (pathology of scattered episcleral cells)2. Proven (biopsy proven orbital tumor)b. Local nodal involvement3. Optic nerve diseasea. Tumour beyond lamina but not up to cut sectionb. Tumour at cut section of optic nerve4. Intracranial metastasisa. Positive CSF onlyb. Mass CNS section5. Hematogenous metastasisa. Positive marrow/bone lesionsb. Other organ involvement 21

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USG objective assessment of

tumor dimensionpresence of calcium, a high

reflective echoes are seen.but if the tumor has

extended in to the optic nerve, then the presence of calcium blocks the ultrasound penetration

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MRI

CT scan

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Metastatic work upCases with

Suspected extrascleral spread.Optic nerve invasion on imaging studies.Presentation with glaucoma/ orbital cellulitis.Anterior chamber seeding.Gross choroidal invasion.Suspected metastasis.

Blood investigation (count,LFT, RFT) .Lumber puncture.Bone marrow biopsy.

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Objective in order of priority Survival of the patient. Preservation of the globe. Focus on visual acuity. Therapy is tailored to each individual case:

based on the overall situation. including threat of metastatic disease. risks for second cancers. systemic status. laterality of the disease. size and location of the tumour(s).

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Modalities

Cryotherapy.Laser photocoagulation.Thermotherapy.Plaque therapy.Chemotherapy.Enucleation.

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Cryotherapy

Indicationprimary treatment of small tumours (4 mm in

diameter & 3 mm in height).located anterior to the equator near the ora

serrata.

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Triple-freeze-thaw

technique.

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Laser photocoagulationIndication

Tumors smaller than 4.5 mm in diameter that are confined to the retina with no evidence of seeding.

Not involving OD or macula.Photocoagulation using low energy 532nm argon

or 810 nm diode laser achieve focal consolidation after chemotherapy.

At least 3 sessions are required36

Usually performed using an indirect ophthalmoscope delivery system and relatively long exposure durations (1 second or more up to a continuous exposure).

First an intense confluent white chorioretinal coagulation approximately 1–2 mm wide entirely around the retinal tumor is created.

Any feeding retinal blood vessels are treated until they appear to be occluded.

Finally, the tumor is treated directly until it also appears homogeneously and intensely white.

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Transpupillary thermotherapyIndication

Tumours 2 mm thick & 3 mm diameter & confined to retina.

For tumours adjacent to fovea or optic nerve

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Tumour heating using a diode infrared laser(810 nm)

Thermochemotherapy.Temp – 42 – 60 °C (below coagulative

threshold)

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External beam radiotherapy

Method of delivering whole eye irradiation to treat advanced retinoblastoma, particularly when there is diffuse vitreous seeding

total dose of 35–40 Gy is given in fractionated doses over a period of 4–5 weeks.

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Complications

Temporal bone suppression.Cataract.Radiation retinopathy.Optic neuropathy.Keratopathy.Secondary cancers in the field of irradiation

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Plaque therapyIndicationTumour <15 mm in base & 6 – 8 mm in thicknessAt least 2 mm from OD or fovea.Failed with chemoreduction, laser photocoagulation or

cryotherapy.principal isotopes used in radioactive eye plaques are iodine-

125 and ruthenium-106.

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Schipper Technique

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Complications

Maculopathy.Papillopathy.Transient mild vitreous haemorrhage.Cataract.Iris neovascularisation.

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Chemotherapy - Vincristine : also known as Oncovin or VCR. blocks mitosis in metaphase

- Carboplatin : also known as Paraplatin. inhibits both DNA & RNA synthesis

- Etoposide : also known as VP-16 or VePesid. blocks cell cycle in late S-G2 phase

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Primary chemotherapy with i.v. carboplatin, etoposide & vincristine given in 3 - 6 cycles

Single agent chemoreduction with carboplatinSubtenon carboplatin injectionObjective – reduce tumour size so that focal treatment can

be applied to a smaller tumour volume in order to preserve more vision

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Chemoreduction

Enucleation

Indication advanced disease with no

hope of useful vision Concern of invasion of

tumour into optic nerve, choroid or orbit

Secondary glaucoma, pars plana seeding or anterior chamber invasion

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Technique Long section of optic nerve

should be removedGentle removal without seeding

into orbitFresh tissue is harvested for DNA

analysisSurgeon must change the sterile

gloves after this step to avoid the risk of tumour contamination into the child’s orbit

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Genetic counselingTo identify individuals with heritable mutation in

RB1 gene and to inform families of the implication of this finding.

The test results allow us to focus on high risk screening on those who carry a heritable mutation and provide reassurance to individuals with sporadic, non heritable retinoblastoma.

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