Presented by-Dr.Puneet Sharma
Post graduate student ( 2nd yr )
Department of Ophthalmology
Pawius described retinoblastoma in 1597.
In 1809, wardop referred to tumor as fungus
haematodes as suggested enucleation as primary
mode of management.
Discovery of ophthalmoscope in 1851 facilitated
reconginition of clinical features of retinoblastoma.
Thought to be derived from glial cells, was called
glioma of retina by virchow (1864).
Flexner (1891) and wintersteiner (1897) believed it to
be a neuroepithelioma because of presence of rosettes.
Later, consensus was that tumor originated from
retinoblasts and officially american ophthalmological
society (1926) accepted the term retinoblastoma.
Most common intraocular malignancy in
children ( 1 in 15,000 to 1 in 18,000 live births).
No racial or gender predisposition.
Bilateral in 25 to 35% cases.
Age of diagnosis is 18 months.
Unilateral cases around 24 months & bilateral
before 12 months.
RB gene is located on long arm of chromosome
13 (13q14) containing 27 exons & 26 introns.
2 normal copies of RB gene present in most
human cells. RB gene product is 928 AA
phosphoprotein whose normal func. is to
suppress cell growth.
RB represents phenotypic expression of
abnormal or absent tumour suppressor gene aka
Most RB1 mutations are minute deletions,
Out of newly diagnosed cases
Bilateral RB involve germinal mutations
Approx. 15% unilateral sporadic RB caused by
germinal mutation, affecting one eye , 85%
Imp. Aspect in management of RB
Pts, positive family history, 40% siblings would
be at risk & 40% offspring of affected patient may
Pts, no family history, if affected child has
unilateral RB, 1% of sibilings are at risk & 8% of
offspring may develop RB
Bilateral RB, no family history 6% siblings & 40%
offspring have chance of developing RB
On low magnification, basophilic areas of
tumor are seen along with eosinophilic areas of
necrosis & more basophilic areas of
calcification within the tumor.
Poorly differentiated tumors consist of small
to medium sized round cells with large
hyperchromatic nuclei & scanty cytoplasm
with mitotic figures.
Flexner-wintersteiner rosettes consist of
columnar cells arranged around a central
lumen,highly characteristic of retinoblastoma,
also seen in medulloepithelioma.
Homer wright rosettes, cells arranged
around central neuromuscular tangle
(neuroblastomas, medulloblastomas &
Arrangement of tumor cells around blood
Fleurettes -eosinophilic structures, composed
of tumor cells with pear shaped eosinophilic
processes, projecting through fenestrated
Basophilic deposits,precipitated DNA
(released from tumor necrosis) can be found in
walls of lumen of blood vessels.
Reese-Ellsworth classification (1960)
Was designed for treatment with EBRT. Was in
use till 1980
Now not used as EBRT has been replaced by
chemotherapy as preferred mode of treatment
Group A Small tumor
R.B < 3 mm in basal dimension/thickness
Group B Larger tumor
R.B > 3 mm in basal dimension/thickness
Macula location ( < 3 mm to foveola)
Juxtapapillary location ( < 1.5 mm to disc)
Clear subretinal fluid < 3 mm from margin
Group C Focal seeds
C1 Subretinal seeds < 3 mm from R.B
C2 Vitreous seeds < 3 mm from R.B
C3 Subretinal & vitreous seeds < 3 mm from
Group D Diffuse seeds
D1 Subretinal seeds > 3 mm
D2 Vitreous seeds > 3mm
D3 Subretinal & vitreous seeds > 3
Group E Extensive R.B
Occupying > 50% globe
Opague media from haemorrhage in A.C &
vitreous or subretinal space.
Invasion of postlaminar optic nerve, choroid (>
2 mm), sclera, orbit, A.C
Detailed Anterior segment examination
I O P
Indirect Ophthalmoscopy with Scleral
Fundus drawing denoting site & extent
Gross systemic examination
Fully Dilated fundus examination
Bilateral with 360 degree scleral depression
Indirect ophthalmoscopy (diagnostic in 90%
Wide angle fundus camera ( Retcam)
rounded or irregular intraocular mass
representing typical intralesional calcification
delineates extraocular extension, can detect
asso. Pinealoblastoma Cases with atypical
Diagnostic dilemma Extraocular &intracranial
tumor extension is suspected
optic nerve invasion or intracranial extension
Not required in routine work up.
Can be used to differentiate viable tumour
from an avascular residue following
radiotherapy or spontaneously regressed
Active lesion shows hypervascularity,dilated
feeders and late staining
AQUEOUS HUMOUR ENZYME ASSAY
normal aqueous to plasma LDH >1.0
increased phosphoglucoisomerase levels
increased neuron specific enolase levels
Rarely done, invasive procedure
Approach through peripheral cornea, A/C,
zonules, vitreous is recommended
potential of needle track dissemination of
Useful in ruling out intracranial or distant spread
as primary mode of spread of RB is
EXAMINATION OF SIBLINGS/PARENTS
To detect small lesions which may otherwise go
undetected in siblings.
Parents may harbour regressed RB lesions.
Blood specimens of patient/parents/siblings
should be taken for DNA analysis which could aid
in genetic counselling.
10% of all vision loss in children world
prevalence of 1 to 6 cases per 10,000 live
cataract resulting from congenital rubella
rare congenital developmental
purely anterior (persistent tunica
vasculosa lentis and persistent posterior
fetal fibrovascular sheath of the lens)
purely posterior (falciform retinal
septum) and a combination of both
Genetic disorder (inherited X link
shrinkage of globe
wasting of the iris
30-50%have developmental delay/mental
Psychotic like features
Very rare, congenital non hereditary eye
6-8 years of age
range ( 5 mnths to 71 yrs )
Blood leaks from abnormal vessels in back
of the eye, leaving cholesterol deposits
& damaging retina
RD, Glaucoma, Atrophy, Cataracts
secondary to Coat’s.
Special considerations for enucleation in R.B
Avoid perforation of eye
Harvest long ( >15 mm) optic nerve stump
Inspect the enucleated eye for macroscopic
extraocular extension & optic nerve
Harvest fresh tissue for genetic studies
Place a primary implant
Avoid biointegrated implant if postoperative
radiotherapy is necessary
Equatorial & Peripheral retinal tumors upto 4
mm in diameter & 2 mm in thickness.
Triple freeze thaw cryotherapy at 4-6 week
interval until complete tumor regression.
Small post. tumors 4 mm basal diameter & 2
mm in thickness.
Idea is too
Restrict blood supply to tumor by
surrounding it with 2 rows of overlapping
Transient serous R.D
Retinal vascular occlusion
Large visual field defect ( tumor in juxtapapillary
Pt on active chemoreduction protocol, restricts
blood supply to tumor & reduces intraocular
concentration of chemotherapeutic agent
Day 1: vincristine + Etoposide + Carboplatin
Day 2: Etoposide
Standard dose: (3 weekly, 6 cycles): Vincristine 1.5
mg/m2 (0.05 mg/kg for children < 36 mnths of
age & maximum dose < 2 mg), Etoposide 150
mg/m2 (5 mg/kg for children < 36 mnths of age ),
Carboplatin 560 mg/m2 (18.6 mg/kg for children
< 36 mnths of age)
High – dose (3 weekly, 6-12 cycles) : Vincristine 0.025
mg/kg, Etoposide 12 mg/kg, Carboplatin 28
Focused heat generated by infrared radiation,
applied to tissues at subphotocoagulation
levels to induce tumor cell apoptosis.
Achieve slow & sustained ( 40 to 60 degree C)
within tumor, sparing retinal vessels.
Transpupillary thermotherapy using infrared
radiation from semiconductor diode laser
delivered (1300 micron large spot indirect
ophthalmoscope, operating microscope,
transscleral route with diopexy probe).
Tumor heated till it turns gray
Satisfactory control for small tumors(4 mm
basal diam. & 2 mm thickness).
Complete tumor regression 85% (3-4 sessions)
Focal iris atrophy
Focal paraxial lens opacity (minimised using
1300 micron indirect ophthalmoscope, duration
5 mins in single session)
Placement of radioactive implant on sclera
corresponding to base of tumor,transsclerally
Radioactive materials – Ruthenium 106 &
Tumors < 16mm basal diameter & < 8 mm
Primary or Secondary
Primary- chemotherapy is contraindicated,
secondary treatment in eyes that fail to
respond to chemoreduction & external beam
radiotherapy or tumor recurrences.
Tumor thickness measured by ultrasonography
Plaque design depending on basal tumor
dimensions, its location & configuration e.g
notched plaque used to protect optic nerve (
tumors peripapillary in location)
Dose – 4000 – 5000 cGy
Plaque sutured to sclera after tumor centration
& left for duration of exposure (ranging 36 to
90% tumor control
Focal delivering of radiation, minimal damage to
surrounding normal structures
Minimal periorbital tissue damage
Cosmetic abnormality absent, retarded bone
growth in field of irradiation ( as in external beam
Reduced risk of second malignant neoplasm
Shorter duration of treatment
Used less often, newer chemotherapy
Indicated- primary chemotherapy & local
therapy has failed or rarely chemotherapy is
Delivered using Cobalt 60 (gamma rays) or
linear accelerator ( X-rays)
Linear accelerator with multi-beam technique,
image guided radiotherapy & stereotactic
radiotherapy, better treatment accuracy.
Stunting of orbital growth
Second malignant neoplasms (hereditary form
30% chance of another malignancy by 30 yrs
Risk of second malignant neoplasm greater in
children under 12 mnths
Non- buried implants
have problems of -
Rare in developed countries
Common in developing countries
In Mexico, 18% of 500 pts presented with
Taiwanese group, 36% (42 of 116) pts
manifested orbital RB
In Nepal, incidence is higher 40% (19 of 43)
with proptosis being most common
manifestation of RB
Primary orbital RB- clinical or
detected orbital extension of intraocular RB at
initial clinical presentation with or without
proptosis or fungating mass.
Silent proptosis without orbital & periocular
inflammation in pt will manifest intraocular
tumour,with inflammation indicates reactive
sterile orbital cellulitis sec. to intraocular
Secondary orbital RB-
recurrence following uncomplicated enucleation
for intraocular RB.
Unexplained displacement, bulge or extrusion
of previously well fitting conformer or
prosthesis is an ominous finding sugg. of
Accidental orbital RB-
Fine-needle aspiration biopsy
Intraocular surgery with unsuspected
Overt orbital RB
Unrecognized extrascleral or optic n. extension
discovered during enucleation.
Pale pink to cherry red episcleral nodule
(juxtapapillary location or at site of vortex v.)
Enlarged and inelastic optic n. with or without
nodular optic n. sheath is an indicator of optic
Microscopic orbital RB
Detection of full thickness scleral infiltration,
extra scleral extension & invasion of optic n.
on histopathologic evaluation on enucleated
Tumor cells in choroidal & scleral emissaria &
optic n. sheath indicates orbital extension.
General physical examination- includes
regional lymph nodes palpation
MRI or CT Scan of orbit & brain (axial &
Bone marrow biopsy
Combination therapy more effective
Vincristine, Etoposide, Carboplatin high dose
chemotherapy (3-6 cycles or even 12 cycles)
followed by enucleation, extended
enucleation or orbital exenteration