RETINOBLASTOMA

1. RETINOBLASTOMA
DR.CHRISTINA SAMUEL

2. Overview
•Retinoblastoma is the most common primary intraocular malignancy of
childhood and infancy with a cumulative life time incidence of 1 in 3,300 to 1 in
20,000 live births world wide.
• Indian studies have shown the incidence of the tumor in 1:15000 live births.
• Retinoblastoma is a highly malignant tumor that arises from an accumulation of
proliferating embryonic retinal cells.
• Early diagnosis and treatment of the tumor is essential for child survival and
salvaging the eye to give useful vision.

3. Genetics
Retinoblastoma represents the phenotypic expression of an abnormal tumor
suppressor gene known as retinoblastoma gene RB1.
Normally a gene will cause expression of a cell proliferation, but RB1 gene
acts by suppressing the phenotypic characteristics.
The gene is activated in hypophosphorylated state, (pRB)4, which is
responsible for the inhibition of cell proliferation.
After the mutation, the gene is not converted to pRB form which leads
to uncontrolled cell growth.
In order for retinoblastoma to develop; both copies of the gene at the 13q14
locus must be lost, deleted, mutated, or inactivated.

4. ‘two hit’ hypothesis
• Alfred Knudson in 1971, stated that two complementary chromosomal mutations are
required in the same retinal cell to develop retinoblastoma.
• The “first hit” is a germ line mutation that is found in all or most of the cells of the
body and hence inherited.
• The second hit occurs sometime during development, and if it occurs in a somatic
cell such as a retinal cell then retinoblastoma develops.
• The likely retinoblastomas which are heritable are:
• All familial tumors
• 15- 20 % of sporadic tumors caused by germ line mutation
• Bilateral tumors
• Unilateral tumors with multi-focal lesions

5. HISTOLOGY
• Retinoblasts- Basophilic cells, Increases N:C ratio
• Flexner Wintersteiner rosettes
• Homer Wright Pseudo rosettes
• Fleurettes

6. Age at diagnosis
• Average age at diagnosis – 18 months
• Unilateral – a 23 months
• Bilateral – 12 months
• 90% of cases – diagnosed before 5yrs

7. PRESENTATION
-Leukocoria (Amaurotic cat’s eye)
-Strabismus ( convergent)
- Secondary glaucoma ( Buphthalmos)
-Pseudohypopyon, hyphema
-Tumour seedings on Iris, tumor induced uveitis
-Iris neovascularisation
-Orbital inflammation, Orbital invasion with proptosis
- Bony involvement, metastasis in regional lymph nodes and brain

8. --- Thorough slit lamp examination
IDO under sedation- with 360 degree scleral depression –mandatory
(diagnostic in 90% of RB)
GROWTH PATTERN:-
• ENDOPHYTIC- seeds into the vitreous as a white mass
• EXOPHYTIC- subretinal, multilobular white mass causing RD
- O.N invasion
- Choroidal invasion

12. Special presentation
• Spontaneous hyphema
posterior segment ischemia- causes new vessels
to develop in iris- bleed.
any child with spontaneous hyphema, without trauma
- B scan to rule out RB

13. • Phthisis bulbi
undergo severe inflammation-spontaneous
regress-phthisis
RB to considered in any child with phthisical eye of
uncertain origin

15. Exophytic lesions

16. CUT SECTION

17. Investigations
• TC,DC,ESR-to exclude inflammatory/other causes simulating RB
• Aqueous humor-assay of LDH
aqueous:blood LDH ratio
>1 – in RB
<1 – in other causes
• X-rays of orbit – not help in diagnosis, but can show
calcifications
• Genetic analysis – blood samples from patient and parents

18. B - Scan
Round irregular intraocular mass, V-Y pattern.
Numerous highly reflective echoes-representing typical
intralesional calcification.
A-Scan- high internal echoes with tumor & rapid attenuation of
orbital pattern

20. Irregular soft tissue density with
Heavy calcification- CT ORBIT

21. • Calcific mass
• Posterior wall of the globe

22. TRILATERAL RETINOBLASTOMA
Retinoblastoma + Pinealoblastoma

23. QUADRILATERAL RETINOBLASTOMA
• Bilateral Retinoblastoma
• Pinealoblastoma
• Suprasellar mass

24. FFA-
Large tumors-dilated feeding vessels & veins
Small tumors-minimally dilated feeding vessels in the arterial phase, mild
hypervascularity in venous phase& late staining of mass
METASTATIC WORK UP:-
Only if evidence of local/systemic extension
Bone marrow aspiration/biopsy
CSF analysis

25. Reese – Ellsworth Classification Of Retinoblastoma
Older
Gr I A. Solitary tumours < 4D
B. Multiple tumour < 4D
Gr II A. Solitary tumour 4-10 D
B. Multiple tumour 4-10D
Gr III A. tumour anterior to equator
B. Solitary tumour larger than 10d.
Gr IV A. Multiple tumours > than 10d
B. Lesion extending to ora
Gr V Massive tumours involving half retina
Vitreous seeding

26. Newer Classification
Group A
• 3 mm or less – in greatest diameter
• Not touching optic nerve or foveal avascular zone
• no vitreous seeding
Rx-
• Local treatment only
• Cryotherapy for peripheral ds
• Laser photocoagulation for posterior ds

27. Group B
• Multiple smaller tumour not larger than 10 mm
• Solitary tumour not larger than 10 mm
• No vitreous seeding ; no RD
Rx
Primary brachytherapy – single site. If multiple sites are needed, to
treat like C

28. Group C
• Tumours less than 15 mm
• No vitreous seeding or RD
• Small tumours < 3mm touching optic nerve or involving
fovea
Rx
-Three drug chemoreduction
Local consolidation – cryotherapy laser or plaque
Lens sparing External Beam Radiotherapy for tumours not
responding to chemo
< 1 yr – consider plaque therapy

29. Group D
• Dispersed, disseminated or diffuse
• Vitreous seeding or RD or both
• Volume of tumour does not exceed half the volume of the eye
Rx
Four drug chemoreduction with prechemotherapy cryo
Whole Eye EBR – Intensified chemo
Enucleation for unilateral lesions

30. Group E
Extra retinal
• Volume of tumour greater than half the volume of eye
• Antr. seg - glaucoma, hyphaema
• total detachment
• Fixed retinal folds
Rx
Enucleation

31. Group F
Metastatic ds –
Massive choroidal involvement/ involvement of Optic Nerve
Posterior to lamina cribrosa
Rx
Adjuvant. Chemotherapy before and after enucleation
Orbital radiation therapy if
- orbit
- optic nerve is involved

32. Treatment Methods andTechniques
Focal treatment
• Direct tumour Hyperthermia and Photocoagulation
• Argon Laser – frequency doubled YAG –
• Diode laser (532mm or 810mm)

34. Technique
Hyperthermia using Iris medical 810nm diode laser
Spot size upto 2mm
Duration – 9 sec
Tumour is covered over 10-15 mts.
Hyperthermia – given on same day as IV carboplatin
Hyperthermia useful in smaller tumour not responding to chemotherapy

35. Photocoagulation
In darkly pigmented eye
- long wavelength laser
Lightly pigmented
- shorter wavelength
Power 250-300 mw
Duration 400-600 msec increased till blanching of tumour occurs

36. Cryotherapy
Destruction by cryo – (ice crystals directly destroy tumour cells
rupturing cellular memb)
Done in Gr. A Ds – anterior to equator
In lesion – 2.5mm in diameter and 1mm thickness in sensory retina
If 3.5mm in diameter and 2mm thickness, more than one treatment is
necessary.
Contraindication – vitreous seeding and Tumour greater than 5mm

37. Radioactive Plaque (Brachytherapy)
•Primary brachytherapy – is the treatment in
Group B
•Iodine 125 Isotope is used
•Other radioactive plaques are –
Cobalt 60, Ruthenium 106, Iridium 192 and
Palladium 103

39. Chemotherapy
1) Primary Neoadjuvant chemotherapy
2)Adjuvant chemotherapy
3) Thermo chemotherapy

41. New Drugs used are –
Carboplatin
VP-16 (Etoposide)
VM-26 teniposide
CyclosporinA
Older Drugs used
Cyclophoshamide – (Cytoxan)
Vincristin and Adriamycin – do not penetrate into eye

42. Group C and D –
have been treated by initially by
Chemoreduction (Neoadjuvant
therapy) followed by focal therapy

43. Day Chemotherapeutic agent
0 C E V
1 E
2 E
7 V
14 V

44. i. Carboplastin 560 mg/m2/close or
18.7mg/kg
IV over 1 hr in 100 ml of NS
ii. Etoposide
150m/m2/dose or 5mg/kg/IV in 1 hr in
100 ml of NS
iii.Vincristine 1.5mg/m2/dose or
.05mg/kg/dose

45. •Group C - 3 - 4 cycles of CT
•Group D - 7 - 9 cycles

46. Adjuvant chemotherapy – given to
1) Prevent metastasis in patients with risk for
- extra ocular spread
- tumour extension to optic nerve past lamina cribrosa
- massive choroidal invasion
Dose – 6-12 cycles of 3 drugs
Carboplatin, etoposide and vincristine

47. Thermochemotherapy
•Done for group C tumour – with 3 drugs
•Smaller than 8mm in diameter & 5mm in thickness
•Cured withTCT –
continuous heat for 20-30mins after 2-3 hrs after
chemotherapy infusion

48. Hyperthermia due
1. Continuous wave diode laser – small
& portable. Power 110v
2.Argon laser

49. External Beam Radiotherapy
EBR – Retinoblastoma – radiosensitive tumour
However, incidence of second malignant neoplasm (SMN) following EBR has
increased
35% of patient 40 yrs after treatmemt – pt died –SMN
Only 6% of not treated – patient died

50. Complications
•Radiation – Cataract
•Radiation retinopathy
•Dry eye syndrome & loss of eye lash

51. Dose – 15 Gy given by Antr approach
30 by – Lateral approach
Total dose 45 Gy – or daily 2Gy or alt.
day 4Gy.
Wedge is used to block lens

52. Lens sparing Electron beam
approach
•Done under sedation or short anesthesia
•Eye fixed with beam defining collimater
•Using low – vacuum contact lens – held in place
by magnetic slide.

53. Enucleation
1. Major treatment since 100 years
2.Initial treatment for advanced I.O.Retinoblastoma
3. In massive tumours where no vision is salvageable
4.Diffuse vitreous seeding – Enucleation done

55. FOLLOW UP
• Every 4 months- 3-4yrs
• 6 months - 6yrs
• Every year
• Examine under GA
• Unilateral 20% risk
• Rpt CT
• Secondary tumours in hereditary cases