Retinoblastoma is a rare, malignant intraocular tumor of childhood that arises from embryonic retinal cells. It can occur as either a hereditary or non-hereditary form. The hereditary form is caused by a germline mutation in the RB1 gene and accounts for around 40% of cases. It presents at a younger age and is typically bilateral and multifocal. The non-hereditary form occurs due to two somatic mutations and presents later with a unilateral, unifocal tumor. Treatment aims to cure the cancer while preserving vision and the eye depending on the type and stage of disease. Management may involve various local therapies, chemotherapy, and enucleation depending on the classification and extent of involvement.

1. RETINOBLASTOMA

2. ●M/C malignant intraocular tumor of childhood
●Malignant tumor of the embryonic neural retina
●2.5-4% of all childhood malignancies
●2/3 cases are diagnosed before 2 yrs of age, 95% before 5
yrs
●Discovery of retinoblastoma beyond the age of 6 years is
rare
●Unifocal/multifocal
● Unilateral (70%) or bilateral (30%).
●Sporadic (94%) or familial (6%).
●Non hereditary (50-60%) or hereditary (40- 50%)
INTRODUCTION

3. HISTORY
● First mentioned by Petras Pawius in
Amsterdam -1597.
● James Wardrop - Scottish surgeon first
recommended enucleation for saving lives -
1809.
● Verhoeff -origin from undifferentiated retinal
cells, named retinoblastoma in 1900’s.
● American Ophthalmology Society first adopted
the term retinoblastoma in 1926.

4. EPIDEMIOLOGY
⮚ No racial or gender diff for hereditary
Retinoblastoma
⮚ Non hereditary RB : increased frequency
in poorer, tropical regions, 50 fold
increase frequency in African countries
⮚ Human Papilloma infection
⮚ Diet deficient in fruits and veg

5. GENETICS
⮚ Autosomal dominant inheritance
⮚ RB gene- first human cancer suppressor gene to be completely charted
⮚ Deletion 13q14, which is a tumor
suppressor gene termed as RB
gene
⮚ 2 clinical forms:
❖ Bilateral or multifocal form
(25%)
❖ Unilateral or unifocal (75%)
❖ Sporadic form of Retinoblastoma
are affected unilaterally.
 Wild type RB1 with MYCN amplification (2.7%)

6. “In the dominantly inherited form of RB, one
mutation is inherited via the germ line and the
second occurs in somatic cells. In the non inherited
form, both mutations occur in the somatic cells”

7. Younger age
Bilaterality
Multifocality
Hereditary RB
Hereditary RB
⮚ 40% of all RB is hereditary
⮚ Only 10% have Family
history

8. Non Hereditary RB
⮚ Accounts for 60%
of cases
⮚ U/L and unifocal
“All bilateral cases are positive for
germline mutation, whereas only
10–15% patients with unilateral.”

9. Germline Mutation Somatic Mutation
Mutations in germ cells Mutations in any tissue other than
germ cell (retinal precursor cells)
Heritable form transferred to 50%
of offspring as (RB+/-)trait
Never inherited as somatic cells
are not passed to offspring
45% 53%
All cells of offsprings carry an
inactive allele of RB1 from the
parent and need one more “hit”.
Early presentation (12 months)
Multifocal and Bilateral
Susceptible to secondary
tumour development
First “hit” during embryogenesis
or preimplantation and second
‘hit” occurs in the same
retinoblast later in life
Later presentation (1-2Y)
Single, Unilateral
No risk of secondary cancers.

10. Genetic Counselling
➢ Heritable retinoblastoma is inherited in an autosomal
dominant manner.
➢ Individuals with heritable retinoblastoma (H1) have a
heterozygous de novo or inherited germline RB1
pathogenic variant.
➢ Offspring of H1 individuals have a 50% chance of inheriting
the pathogenic variant.
➢ Prenatal testing for pregnancies at increased risk is possible
if the RB1 pathogenic variant has been identified in an
affected family member.
: Lohmann DR, Gallie BL. Retinoblastoma. 2000 Jul 18 [Updated 2018 Nov 21]. In: Adam MP, Ardinger HH, Pagon RA, et al.,
editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.

11. CLINICAL FEATURES
Xiaolian Fang, Huanmin Wang, Xiaoli Ma, Yongli Guo, Wei Yang, Shoulong Hu, Yue Qiu, Junyang Zhao, Xin Ni, "Clinical Features of Children with
Retinoblastoma and Neuroblastoma", Journal of Ophthalmology, vol. 2020, Article
ID 9315784, 8 pages, 2020. https://doi.org/10.1155/2020/9315784
INTRAOCULAR
Leukocoria (65-75%)
Strabismus (10-15%)
Nystagmus (5-10%)
ADVANCED
INTRAOCULAR
Buphthalmos
Glaucoma
Periorbital cellulitis
EXTRAOCULAR
Proptosis
Lymphadenopathy
Metastases

12. Endophytic: grows
in to vitreous
cavity.
Vitreous seeds.
Retinal vessels –not
seen on the surface.
Exophytic:
tumor towards
subretinal space.
Retinal
detachment,
retinal vessels are
seen over tumor.
Diffuse infiltrating
tumor: grows diffusely
and insidiously in the
retina without forming
a detectable mass.
Older children,
Delay in diagnosis.
Mixed endophytic and
exophytic tumours
PATHOLOGY - Morphology

13. Microscopy
 Densely packed small hyperchromatic cells with scant
cytoplasm with background of necrosis and calcification.
 The retinoblasts -large basophilic nucleus and scanty
cytoplasm.
 Cellular necrosis & intralesional calcification- larger tumors.
 Small blue round cell neoplasm

14. Histology
Flexner Wintersteiner rosettes -columnar cells around a
central lumen -also seen in medulloepithelioma
Homer Wright rosettes around a central neuromuscular
core -neuroblastoma, medulloepithelioma,
medulloblastomas
Fleurettes Tumor cells with pear shaped eosinophilic
processes projecting through a fenestrated membrane

15. ROUTES OF SPREAD
▪ Optic Nerve:
⮚ Most common route of spread
⮚ Reaches the CNS via the subarachnoid space
▪ Choroid:
⮚ Next common route
⮚ Highly vascular structure, so risk of hematogenous spread
▪ Scleral Vessels:
⮚ Intraocular fluid filters into venous channels
⮚ risk of both hematogenous and lymphatic spread
▪ Orbital soft tissues:
⮚ Highly vascular

16. WORK-UP
1) Initial evaluation of the disease
Detailed & complete history
Positive family history +
Genetic testing is advisable in all cases of
retinoblastoma, both for the patient and for the rest
of his/her nuclear family if germline disease is
confirmed.
2) Ophthalmology Evaluation—Leukocoria, strabismus,
features of inflammation, secondary glaucoma,
proptosis, associated pinealoblastoma.

17. 3) Indirect Ophthalmoscopy
⮚ Creamy white color
⮚ Tortuous vessels may be
seen feeding the tumor
⮚ Serous RD
⮚ Examination under
anesthesia (with
microscope) essential to
fully evaluate the retina
since RB may be
multifocal
⮚ B/L fundus examination
with 360 degree scleral
depression

18. 4) USG
⮚ Rounded or irregular intraocular mass
⮚ Highly reflective calcifications
⮚ Confirms presence, relationship, size and shape of tumors
⮚ Recommended when retina cannot be visualized
● Vitreous hemorrhage
● Vitreous seeding
● Hazy cornea

19. 6) MRI
⮚ Involvement of optic nerve, orbit
⮚ Better than CT as no radiation exposure
⮚ Most useful for evaluating sellar/ parasellar
⮚ Evaluation of CNS ( trilateral RB & CNS mets)

20. 5) CT Scan
⮚ Dense heterogenous lesion with hyperdense foci
corresponding to calcification.
⮚ Assessing extraocular extension and invasion of the optic
nerve.
⮚ Try to avoid !!

21. 7) Biopsy
⮚ Not required for diagnosis
⮚ Not recommended due to risk of intraocular seeding
and extra ocular spread
8) Molecular Genetic testing
To identify individuals with heritable retinoblastoma
single gene testing and chromosomal microarray
(CMA)

22. 9) Metastatic Workup
⮚ For patients who present with small tumors,
o Metastatic work-up not required
⮚ More extensive metastatic work-up is required for
children with optic nerve extension or extensive
choroidal invasion
o Lumbar puncture to obtain CSF cytology
o Bone marrow examination or bone scan is required
only if suspicious of systemic involvement

23. DIFFERENTIAL DIAGNOSIS
 Coats’ disease
 Persistent hyperplastic primary vitreous
 Ocular toxocariasis
 Retinopathy of prematurity
 Congenital retinal folds
 Astrocytic Hamartoma (Tuberous Sclerosis)
 Congenital Cataract
 Ocular Tuberculosis

24. Two commonly used classification systems
Reese Ellsworth classification system
International Classification of Retinoblastoma
❏ In 1950s the Reese Ellsworth classification system was
developed to predict the prognosis after treatment with
radiation.
❏ In 1990s, clinicians found the Reese Ellsworth
classification system no longer accurately reflect the
prognosis with newer treatment modalities and also
increased risk of secondary tumors following radiation
❏ Thus, the International Classification of Retinoblastoma
was developed to better predict the need for enucleation
or EBRT.
CLASSIFICATION & STAGING

25. REESE ELLSWORTH CLASSIFICATION
TYPE DESCRIPTION
Group I Very favourable
A Solitary tumour <4 disc diameter in size, at or posterior to
the equator
B Multiple tumours none over 4DD in size, all at or posterior to
the equator
Group II Favourable
A Solitary tumour 4-10DD in size, at or posterior to the equator
B Multiple tumours 4-10DD insize, all posterior to the equator
Group III Doubtful
A Any lesion anterior to the equator
B Solitary tumor larger than 10DD posterior to the equator
Group IV Unfavourable
A Multiple tumours some larger than 10DD
B Any lesion extending to the ora serrata
Group V Very unfavourable
A Massive tumours involving over half the retina
B Vitreous seeding

26. Group Quick Reference Features
A Small tumor Rb <_ 3mm in size
B Large tumor
Macula
Juxtapapillary
Subretinal fluid
Rb > 3mm in size OR
● Macular Rb location (<_ 3mm to foveola)
● Juxtapapillary Rb location (<_ 1.5mm to disc)
● Clear subretinal fluid (<_ 3mm from margin)
C Focal seeds Rb with
● Subretinal seeds (<_3mm from Rb)
● Vitreous seeds ( <_ 3mm from Rb)
● Both subretinal + Vitreous seeds (<_3mm from Rb)
D Diffuse seeds Rb with
● Subretinal seeds (>3mm from Rb)
● Vitreous seeds ( > 3mm from Rb)
● Both subretinal + Vitreous seeds (>3mm from Rb)
E Extensive Rb Extensive Rb occupying > 50% globe OR
● Neovascular glaucoma
● Opaque media from hemorrhage in AC, vitreous or subretinal
space
● Invasion of postlaminar optic nerve, choroid (>2mm), sclera, orbit,
AC
INTERNATIONAL CLASSIFICATION OF RETINOBLASTOMA (ICRB)

27. INTERNATIONAL RETINOBLASTOMA STAGING
SYSTEM (IRSS)
Stage 0 No enucleation, treated conservatively (1 or both eyes may have
intraocular disease)
Stage I Enucleation, tumour completely resected
Stage II Enucleation with microscopic residual tumour
Stage III Regional extension
❖ Overt orbital disease
❖ Preauricular or cervical lymph node extension
Stage IV Metastatic disease
❖ Hematogenous metastasis
❖ Single lesion
❖ Multiple lesion
CNS Extension
❖ Prechiasmatic lesion
❖ CNS mass
❖ Leptomeningeal disease

28. MANAGEMENT
Goals of treatment
Primary goal-save life
Salvage of the organ and function-Secondary
Tertiary -Decrease the risk of late sequelae from
treatment, particularly subsequent neoplasms
Multidisciplinary approach
Individualized –depending on
• ICRB Classification
• Age
• +_ Extraocular factors
• Germline testing results
• Family Psychosocial
situation
• Institutional resources
Laterality
• Location
• Systemic condition
• Overall progression
• Cost effectiveness

29. General Principles
Tumours Treatment options
Small tumours Local ablative therapy
Small tumors near optic disc/ fovea Chemotherapy followed by local
ablative therapy or Radiotherapy
Medium tumors
Large tumors Chemotherapy followed by
radiotherapy
Vitreous seeding Systemic chemotherapy / intravitreal
chemotherapy…Severe seeding –
Sub Tenon chemotherapy
Persistent / Recurrent tumour after
chemotherapy
Radiotherapy
Persistent / Recurrent tumour after
radiotherapy
Local ablative therapy
No chance of saving vision Enucleation

30. Treatment Options
1. Local Ablative Therapy
● Photocoagulation
● Thermotherapy
● Cryotherapy
2. Radiotherapy
● EBRT
● Brachytherapy
● SBRT
● Proton Therapy
3. Chemotherapy
● Systemic
● Periocular
● Intra-arterial
● Intravitreal
● Intracameral
4. Enucleation/ Exenteration
LOCAL ABLATIVE THERAPIES
● Used to treat small tumors 3-6mm
● Classically in patients with B/L disease
● Combined with chemotherapy
● Breaks down the blood ocular barrier and
increases penetration of chemotherapeutic
agents into the eye.

31. PHOTOCOAGULATION
● Indication:
➢ Tumors at or posterior to equator of the eye
➢ Small tumors <4.5mm in base and not >2.5mm away from OD or
macula
● Technique
❖ An argon green laser of wavelength 532nm is used
❖ An indirect ophthalmoscope delivery system
❖ Relatively long exposure durations (up to a continuous exposure).
❖ Chorioretinal coagulation 1–2 mm wide entirely around the retinal
tumor.
❖ Photocoagulates the retinal feeding vessels white retinal burn
surrounding the tumor by 1mm -interrupt the blood supply.
❖ Beam should not be directed at the tumor due to risk of tumor
seeding.

32. ⮚ Contraindication
● When patient is on chemo
● Vitreous seeding
⮚ Complications
● Transient serous R.D
● Retinal vascular occlusion
● Retinal hole
● Retinal traction
● Preretinal fibrosis
● Large visual field defect

33. THERMOTHERAPY CRYOTHERAPY
⮚ Indication
● Small tumors 4mm in diameter
and 2mm in thickness
⮚ Technique
● Infrared rays to induce tumor
cell apoptosis
● Slow and sustained rise of
temperature (40-60 degree C)
within tumor thus sparing retinal
vessels
● Transpupillary route—mainly
● Transcleral route is also used
⮚ Complete regression in 85 % of
tumors using 3-4 sessions
⮚ Complications – focal iris atrophy
and focal paraxial lens atrophy
⮚ Indications:
● Tumors anterior to the equator
without vitreous seeding, which can
be reached with the cryoprobe
● Size not more than 3.5mm base and
no more than 2mm height
● Local recurrence
● Tumor persistence after irradiation
● In conjunction with chemotherapy
⮚ Technique:
● Nitrous oxide probe (-80 C), freeze
thaw cycle repeated 3 times.
● Disruption of the retina by
cryotherapy may increase
intravitreal penetration of systemic
chemotherapy.
⮚ Side effects:
● Acute retinal edema
● Accumulation of subretinal fluid.

34. Group A retinoblastoma
managed with transpupillary
thermotherapy (TTT). (a)
Subtle tumor (black arrow)
temporal to the macula, with
(b) regression 1 month after
treatment
Cryotherapy

35. ⮚ Indications
● To shrink tumors so that they may be amenable to
local ablative therapy
● Following enucleation with histopathological features
of high risk disease
● Extra ocular disease should be treated first with
chemo
● Localized bulky disease or large orbital recurrence
● Palliation in metastatic disease
CHEMOTHERAPY

36. ⮚ Systemic Chemotherapy
● Chemotherapy + focal therapy is the most widespread treatment
● VEC chemotherapy (6 cycles Q 28 days)
Inj VCR 0.05 mg/kg IV on Day1
Inj Carboplatin 18.6mg/kg IV infusion on Day1
Inj Etoposide 5mg/kg/IV infusion on Day1 and Day2
● Most successful for tumors without associated subretinal fluid or
vitreous seeding
A 4-month-old patient was
diagnosed with a (a) Group B
retinoblastoma in the right eye, and
was treated with 6 cycles of
standard-dose IVC, (b) achieving a
complete regression of the tumor

37. ⮚ Intra-vitreal chemotherapy
⮚ Used to salvage eyes with vitreous seeding
⮚ Melphalan – 20-30 microgram/0.1mL
⮚ Topotecan also
⮚ Precautions to avoid extra ocular spread of tumor
⮚ Side effects:
● Salt and pepper retinopathy
● Transient intraocular haemorrhage
● Hypotonia
● Phthisis bulbi
Melphalan dose > 50 ug

38. ⮚ Intra-arterial chemotherapy
● Direct delivery of chemotherapy into the eye via cannulation of the
ophthalmic artery
● Drugs: Melphalan is the most commonly used
● Topotecan and carboplatin are also being tested
● Ocular salvage rates >80% as first-line therapy in patients with intraocular
unilateral RB
● 16% cases alternate route needed – orbital branch of middle meningeal
artery
● Adverse effects
▪ Potential blindness from stenosis or occlusion of the ophthalmic
artery, central retinal artery, or branch retinal artery
▪ Chorioretinal atrophy
▪ Vasculopathy in ophthalmic, choroidal, and retinal vessels
▪ Exposure to radiation (from fluoroscopy)
▪ Systemic side effects include iodine allergy, the risk for ischemia and
hemorrhagic stroke

40. • Intra-cameral chemotherapy
• 2017 - Munier et al.
• To provide sufficient drug availability in the anterior chamber.
• Oral acetazolamide 5 mg/kg
• Aqueous humor aspirated from the anterior and posterior chambers
through a transcorneal approach with a 34-gauge long needle.
• A syringe exchange to replace aqueous with Melphalan (15-20 µg/0.05
mL) or Topotecan (7.5 µg/0.015 mL).
• The dose was fragmented 1/3 to Anterior Chamber & 2/3 to Posterior
Chamber
• Following the injection, cryotherapy was applied to the entry site at the
time of needle removal
• Side effects iris heterochromia and cataract

41. ⮚ Periocular Chemotherapy
● Periocular Topotecan or Carboplatin achieves rapid levels
within the vitreous in 30 min which lasts for hours, and
attains doses that are six to ten times higher than that
achieved by IVC
● Used for advanced groups D or E with diffuse vitreous seeds
in which a higher local dose of chemotherapy is desired
● Administered by posterior sub-tenon injection in the
quadrant closest to the location of the vitreous seeds.

42. EVIDENCES…
Treatment outcomes of Chemoreduction
103 patients
158 eyes-364 tumors
Between June 1994 to August 1999

43. Purpose
To report the results of chemoreduction and focal
therapy for retinoblastoma with determination of
factors predictive of the need for treatment with EBRT
or enucleation
Treatment -six planned cycles of chemoreduction
using Vincristine, Etoposide and Carboplatin + focal
treatments (cryo-
therapy, thermotherapy, or plaque radiotherapy).
Outcome measured Need for EBRT and enucleation.
Conclusions
Chemoreduction offers satisfactory retinoblastoma
control for groups I–IV eyes, with treatment failure
necessitating additional EBRT in only 10% of eyes

44. Purpose: To evaluate the reliability of the International Classification of
Retinoblastoma (ICRB) for predicting treatment success with chemoreduction
Methods
All eyes were treated with CRD and were classified according to the ICRB
The CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus
local consolidation with thermotherapy or cryotherapy.
Outcome measured: Chemoreduction success, defined as avoidance of external
beam radiotherapy or enucleation.
Conclusions: The ICRB can be of assistance in predicting CRD success for
retinoblastoma. Additional treatment methods are necessary to salvage more group
D eyes.

45. Purpose To assess a new chemoreduction protocol using intravenous
cyclophosphamide with reduced dose of carboplatin on eye retention in patients with
retinoblastoma.
Treatment
The 6-cycle chemotherapy used Vincristine, Etoposide, Carboplatin and
Cyclophosphamide. Most patients received additional hyperthermia, some received
local treatment with laser coagulation, cryotherapy and/or β-ray brachytherapy.
Conclusions Chemoreduction, including Cyclophosphamide, with or without focal
treatment, effectively controlled retinoblastoma progression without requiring
enucleation or EBRT. Addition of cyclophosphamide is safe, and allows reduction of
Carboplatin.

46. RADIOTHERAPY
Goal of EBRT :
To provide a homogenous and tumoricidal dose to the entire
retina and vitreous
⮚ All retinal cells may have a genetic neoplastic potential
⮚ Vitreous seeding may occur
⮚ Multiple tumors may arise from a primary RB
⮚ Tumor may spread via the subretinal space
The use of EBRT for RB has declined from 30% of treatments
in the period from 1973 to 1976 to 2% in the period from 2005
to 2008.
The use of EBRT is now generally reserved for patients with
persistent or relapsed diffuse disease after chemotherapy and
focal therapies

48. Indications
• Following enucleation
⮚ Tumors involving cut end of optic nerve
⮚ Tumors with scleral breach
• In a preserved eyeball
⮚ Multifocal RB or close to the macula or optic nerve with preserved
vision not amenable for focal therapy
⮚ Large tumors not amenable to focal therapies
⮚ Secondary therapy to salvage chemoreduction and focal therapy
failures
• To palliate or consolidate the systemic therapy of metastatic disease
Positioning
Proper immobilization
Thermoplastic shell with patient supine and chin in neutral position
Treatment preferably done under GA

49. Energy
4-6 MV photons
Dose
⮚ 40-45 Gy in 1.8-2 Gy/ fraction
Radiation Techniques
1. Whole Eye Radiotherapy
2. Lens Sparing Technique
3. 3DCRT
4. IMRT
5. SBRT
6. Brachytherapy
7. Proton therapy

50. WHOLE EYE TECHNIQUE
In 1930s----
Temporal and
Nasal portals, with
nasal portal angled
at 24-30 degrees
to save the lens.
Mainly for tumors
located posteriorly
Disadvantage
High dose to bones
leading to saddle
nose and temporal
bone depression

51. LATERAL BEAM MEGAVOLTAGE
TECHNIQUE (Cassadys et al) LATERAL FIELD
⮚ Borders :-
● Ant border: at
lateral edge of bony
orbit
● Posterior border: at
apex of orbit
● Superior border: at
superior bony ridge
● Inferior border: at
inferior bony ridge.

52. ⮚ Direct lateral field if opposite eye is enucleated.
⮚ If opposite eye is present then beam slightly angled
posteriorly to avoid exit radiation to other eye.
Advantage Disadvantage
‘D’ shaped field produced after
shielding pituitary and alveolar
processes, saves tooth buds and
pituitary.
May lead to recurrences at Ora
serrata.
Modified lateral beam technique-Two lateral opposed D
shaped fields are used.

53. DIRECT ANTERIOR FIELD (McCormick et al)
Borders
● Superior:
superior orbital
margin
● Inferior:
inferior orbital
margin
● Lateral: lateral
bony canthus
● Medial : medial
canthus

54. Advantages Disadvantages
❖ Treats entire eye
❖ Saves opposite eye
❖ Easy to set up,
reproducible
❖ Homogenous dose to
entire retina and
vitreous.
❖ Cataract almost
inevitable
❖ Lacrimal gland
dosage produces
impaired tear
production
❖ Exit beam through
brain.

55. ANTERIOR LENS SPARING TECHNIQUE (Abramson et al)
Lateral D shaped field Day 1-14 by photons
Anterior electron beam field with central circular contact lens as lens
shaped field on Day 5
Unilateral disease
1 lateral field & 2 oblique portals (superior and inferior)
LENS SPARING TECHNIQUES

56. Bilateral disease : parallel opposed lateral fields
The anterior beam edge is placed at the bony
canthus and the beam is angled posteriorly if the
contralateral eye remains in place.

57. HALF BEAM BLOCKED LATERAL TECHNIQUE
(Schipper et al)
⮚ Borders:
● Ant border kept at halfway between the bone and the
limbus.
⮚ Advantages:
● Sharp beam edge to save lens and treat Ora serrata.
⮚ Variations to save opposite eye:
● Superior oblique fields : exit beam through maxilla
● Inferior oblique fields: exit beam through frontal lobe.
SCHIPPERS PRECISION LATERAL TECHNIQUE
A contact lens with an attached rod and scale measuring system
allows accurate placement of the beam behind the lens.

58. Between 1979 to 1991
182 eyes in 123 children (104 Bilateral Retinoblastoma)
67 eyes- Ant lens sparing technique
113 eyes- Modified lateral technique
The doses used in this series ranged from 38 to 46 Gy in 2–2.5 Gy fractions.
Conclusion - 8-year local control for Reese–Ellsworth group I–III was
significantly better with a modified lateral beam technique compared to the
anterior lens-sparing technique, 84% versus 38%, p < 0.0001.
The long-term rate of cataract was 22% and no eyes required enucleation for
ocular complications.

59. Contra-indications of lens sparing radiotherapy
⮚ Untreated tumor anterior to equator
⮚ Retinal detachment extending to Ora Serrata
⮚ Vitreous seeding
3DCRT
● Based on 3D CT planning
● In unilateral RB, 4 non-coplanar fields are used
● Fields:
❖ Anterior oblique
❖ Superior
❖ Inferior
❖ Lateral

60. ● Bilateral disease
❖ 2 lateral opposing
❖ 2 anterior oblique field to each eye
● Entire retina should be treated, including 5 to 8mm of proximal
optic nerve
● Critical structure - opposite eye, optic chiasm, pituitary gland,
brainstem, posterior most upper teeth.

61. IMRT
⮚ Better dose distribution than 3DCRT
⮚ While delivering therapeutic dose to the entire retina helps in
greater sparing of
o Surrounding bony orbit
o Lacrimal gland
o Lens
o Cornea
⮚ Dose constraints
o Lacrimal Gland 30 Gy -Dry Eye Syndrome
o Optic Nerve 54 Gy -Radiation optic neuropathy
o Cornea 50 Gy
o Lens 10 Gy , -most radiosensitive-- Cataract

62. SBRT
⮚ Alternative to plaque radiotherapy
⮚ Treatment of locally progressive disease or as focal consolidative
therapy
⮚ Advantage
o Noninvasive treatment
o Dose within the target volume is more homogeneous
o Dose to the external sclera is lower
o Reduces the risk of optic nerve damage for tumors close to the
optic nerve
⮚ Target volume PTV=GTV+2-3mm margin

63. Complications of EBRT
ACUTE ONSET
Skin reaction
Fatigue
Burning sensation
Discharge from eyes
Pain and irritation
LATE ONSET
❖ Cataract
● Clinically significant posterior pole cataract
⮚ Anterior field – 85%
⮚ Lens sparing – 28%
● Radiation induced cataract can be removed successfully and vision corrected
with IOL.
● The complications of cataract removal after RT are
⮚ Risk of tumor dissemination if RB was not controlled with irradiation.
⮚ Retinal detachment
⮚ Amblyopia

64. ❖ Orbital maldevelopment
● EBRT (>35Gy) ,to < 6 month old children accentuates the risk.
● Mid facial anomalies:
⮚ Hypotelorism
⮚ Enophthalmos
⮚ Depressed temporal bones
⮚ Atrophy of temporal muscle
⮚ Narrow and deep orbits
⮚ Depressed nasion.
❖ Lacrimal gland - decreased tear film production
❖ Vascular : retinal vasculitis-- hemorrhage and vitreous
opacity
❖ Bone and soft tissue- temporal bone hypoplasia, molar
tooth abnormalities
❖ Radiation neuropathy
❖ Neovascular glaucoma

65. ❖ Common second malignancies

66. Kleinerman, R. A. et al. J Clin Oncol; 23:2272-2279 2005
Incidence of Second Malignancies in
Retinoblastoma Survivors

67. Kleinerman, R. A. et al. J Clin Oncol; 23:2272-2279 2005
Incidence of Second Neoplasms in Patients with Bilateral
Retinoblastoma is Radiation-Dependent

68. BRACHYTHERAPY
Plaque Brachytherapy
❏ Brachytherapy with insertion of Radon seeds was prescribed for treatment
of RB in 1930
❏ Refinement in techniques led to development of curved discs or plaques
loaded with radioactive isotopes and placed on outer sclera overlying the
tumor.
Episcleral Plaque Brachytherapy
● Indications
▪ Unilateral
▪ Small 2-16mm basal diameter ICRB Group B
▪ >3mm from OD/fovea
▪ <10mm high
▪ Single lesion or 2 lesions small enough or close enough to be
covered by one plaque
▪ For local recurrence ( too large for other local therapy )
▪ Absent vitreous seeding over tumor apex
▪ Tumors anterior to equator

69. ● Radiation Source Cobalt 60 Iodine 125 Iridium 192
Ruthenium 109 Gold 198
● Procedure
❖ 1st USG of eye done for tumour dimensions -
Maximum basal diameter, Maximum height
❖ Peritomy : open the conjunctiva
❖ Rotate the eyeball
❖ Trans illuminate over pupil : shadow cast
by the tumor is marked
❖ Applicators are applied over sclera
overlying tumour
❖ Place a dummy plaque
❖ Place the live plaque, rotate the eyeball
back into place, close sutures
❖ Remove the plaques after dose delivery

70. ● Advantages
❖ Better dose localization
❖ Lesser risk of cataract
❖ Minimal risk of bone hypoplasia
❖ Lesser risk of second malignancies
● Dose
❖ 40-50 Gy to the tumor apex
❖ Duration generally ranging from 36 to 72 hours
● Side effects
● Cataract
● Retinopathy
● Maculopathy
● Papillopathy
● Glaucoma

72. Treatment
Modality
Chemoreduction
alone
Chemoreduction +
RT
Chemoreduction +
lower dose
prophylactic RT
Pros Avoid or delay
enucleation or RT
Higher tumor
control than
chemoreduction
alone or lower
dose RT
Less recurrence
than
chemoreduction
alone
Lower risk of RT
related toxicity
Cons 30-50% eventually
required RT for
globe salvage
Late complication
of radiation –
orbital bone
hypoplasia or 2nd
malignancy
Exact risk of lower
dose of RT is not
known
Prospective study
may be needed

73. PROTON THERAPY
Advantages
● Superior dose distribution
● Sparing of other eye because of stopping characteristics
● In B/L cases tissue lying in between two eyes can be saved
● Lowering the risk of radiation induced malignancies.
Delivery techniques -Single lateral beam or Anterior oblique
beam.
Anterior oblique beam spares the orbital bone while fully
covering the retina.
At the National Cancer Center, Korea
A silicon suction contact lens with a radio-opaque ring marker
is placed on the cornea
Eyeball is rotated to the nasal or temporal side, depending on
the location of the tumor

74. A single scattering mode is used to treat the
retina
The status of eye fixation can be viewed in real-
time on the computer monitor in the treatment
control room so that any deviation from the
initial set-up can be immediately corrected.
The video image is transferred from a small
closed-circuit camera attached to the periphery
of the aperture attached to the snout.

76. ENUCLEATION
Removal of globe after severing the rectus muscles,
optic nerve is cut (10-20 mm) near its exit from the
socket.
Indications
● U/L or B/L Rb when eye is blind.
● Presence of neovascular glaucoma.
● When disease cannot be controlled by chemo or local treatment.
● Phthisis bulbi
● In B/L RB: Eye with RD, Vitreous hemorrhage, glaucoma, painful
blind eye should be enucleated and other eye should be treated
as per the disease status

77. Special Considerations
A Minimal manipulation
B Avoid perforation of eye
C Harvest long >15mm optic nerve stump
D Inspect the enucleated eye for macroscopic
extraocular extension and optic nerve involvement
E Harvest fresh tissue for genetic studies
F Place a primary implant
G Avoid bio integrated implant if postoperative RT
is necessary

78. Orbital Implant
Promotes orbital growth
Provides better cosmesis
Enhances prosthesis motility
Non integrated (PMMA/ Silicon)
OR Bio integrated (hydroxyapetite)
Myoconjunctival technique

79. EXENTERATION
➢ Indications:
▪ Extensive local tumor breaching the globe
(followed by postoperative radiotherapy and
chemotherapy)
▪ Recurrence of tumor in the socket after
enucleation.
❖ Structures removed:
▪ The globe
▪ Extraocular muscles
▪ Lids
▪ Optic nerve
▪ Orbital fat

80. Observation
/ Radiotherapy

83. TRILATERAL RETINOBLASTOMA
Bilateral retinoblastoma associated with ectopic tumor of the pineal or the
suprasellar region.
Incidence
⮚ Most cases in patients with B/L RB
⮚ Most cases diagnosed within 3-4 yrs of RB diagnosis.
⮚ Decreased incidence in patients treated with chemotherapy
Clinical features:
⮚ Intracranial lesion causes signs of raised ICT like anorexia, lethargy, vomiting,
ataxia, Diabetes insipidus.
Treatment
⮚ Treatment strategy followed: orbital radiation---chemo----CSI
⮚ Poor results with surgery alone or in combination with EBRT
⮚ Orbital fields must be set up with understanding that further CSI has to be
given
⮚ Conformal RT planning can be used to give a boost to intracranial tumor.
⮚ Chemo: systemic CTX, Carboplatin, Etoposide, Vincristine and intrathecal
MTx, Hydrocortisone and Cytarabine.

84. METASTATIC RETINOBLASTOMA
⮚ Whole brain irradiation or CSI is used for brain
metastases or leptomeningeal dissemination.
⮚ Bone and nodal metastases treated with involved field
radiation.
⮚ High dose chemotherapy with autologous stem cell
rescue is an option for treating advanced disease.
⮚ Widespread metastatic disease outside the CNS, treated
with HDC, local irradiation and stem cell rescue maybe
curable in about one half to one fourth of cases.

85. FOLLOW UP
⮚ First post treatment follow up with EUA +/- USG at 4 weeks
after photocoagulation or cryotherapy and 4-6 weeks after
completion of EBRT.
⮚ First six months after initial treatment are the most critical
with respect both to tumors in the second eye of unilateral
cases and to recurrences or new tumors not treated with
enucleation.
⮚ Second eye develops RB in 19 % cases during FU and risk
greater in children < 18 months at diagnosis.

86. o A retinoblastoma survivor should ideally be
monitored for life.
o Mainly for patients with germline mutation.
o Follow up with frequent ophthalmology examination
until age 7, and then less frequently throughout the
rest of their lives.
o Recurrences mostly occur within 3 years after
treatment.
o Rare-- 11years after initial treatment.
o Therefore, visits every 1-2 years with the pediatric
oncologist are warranted.
LONG-TERM MONITORING OF
CANCER FREE PATIENT

87. Ophthalmology visits should be focused on
• monitoring long-term effects secondary to
the cancer treatment (e.g. amblyopia,
glaucoma, cataract, vitreous hemorrhage,
retinal detachment, etc.)
• preservation of the fellow unaffected eye
• correction of refractive errors

91. THANK YOU
!!!!!