seminar presented by Dr.Puneet Sharma ( P.G 2nd yr ) Department of Ophthalmology, MMIMSR , Mullana ( Ambala )

1. Presented by-Dr.Puneet Sharma
Post graduate student ( 2nd yr )
Department of Ophthalmology
MMIMSR,Mullana
Ambala

2.  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.

3.  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.

4.  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
RB1.
 Most RB1 mutations are minute deletions,

6.  Out of newly diagnosed cases
 6% familial
 94% sporadic
 Bilateral RB involve germinal mutations
 Approx. 15% unilateral sporadic RB caused by
germinal mutation, affecting one eye , 85%
sporadic

7.  Imp. Aspect in management of RB
 Pts, positive family history, 40% siblings would
be at risk & 40% offspring of affected patient may
develop RB
 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

8.  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.

10. Rosettes
 Flexner-wintersteiner rosettes consist of
columnar cells arranged around a central
lumen,highly characteristic of retinoblastoma,
also seen in medulloepithelioma.

11.  Homer wright rosettes, cells arranged
around central neuromuscular tangle
(neuroblastomas, medulloblastomas &
medulloepitheliomas)

12.  Arrangement of tumor cells around blood
vessels.

13. Fleurettes
 Fleurettes -eosinophilic structures, composed
of tumor cells with pear shaped eosinophilic
processes, projecting through fenestrated
membrane.
 Basophilic deposits,precipitated DNA
(released from tumor necrosis) can be found in
walls of lumen of blood vessels.

14. 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

15. 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

16. 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
R.B

17. Group D Diffuse seeds
 D1 Subretinal seeds > 3 mm
 D2 Vitreous seeds > 3mm
 D3 Subretinal & vitreous seeds > 3
mm

18. Group E Extensive R.B
 Occupying > 50% globe
 Neovascular glaucoma
 Opague media from haemorrhage in A.C &
vitreous or subretinal space.
 Invasion of postlaminar optic nerve, choroid (>
2 mm), sclera, orbit, A.C

19.  Leucocoria 56%
 Strabismus 20%
 Red painful eye 7%
 Poor vision 5%
 Asymptomatic 3%
 Orbital cellulitis 3%
 Unilateral mydriasis 2%
 Heterochromia iridis 1%
 Hyphema 1%

20.  Endophytic
 Exophytic
 Diffuse infiltrating tumor

21.  Tumor grows into vitreous cavity
 yellow white mass
 Progressively fills vitreous cavity & vitreous
seeds occur
 Retinal vessels not seen on tumor surface

24.  Tumor grows towards sclera
 Solid R.D usually occurs
 Retinal vessels seen on tumor surface

25.  Tumor diffusely involves retina causing
placoid thickness of retina (not mass)
 Seen in older children

26.  Grade 1
superficial involvement of optic nerve head only
 Grade 2
Involvement upto or involving lamina cribrosa

27.  Grade 3
Involvement beyond lamina cribrosa
 Grade 4
Involvement upto surgical margin

28.  History
 Prenatal/natal/postnatal
Maternal rubella ( cong. Cat.)
Gestation period or delivery ( ROP )
Oxygen therapy ( ROP )
 Family history
6% of RB pts have positive family history

29.  Physical examination
Rule out tuberous sclerosis, cong. defects asso.
with trisomy 13-15, rubella syndrome
 Ocular examination
Squint, leukocoria, heterochromia, proptosis,
lymphadenopathy ( adv. cases )
pseudohypopyon, rubeosis iridis

30.  Detailed Anterior segment examination
 I O P
 Indirect Ophthalmoscopy with Scleral
indentation
 Fundus drawing denoting site & extent
 Gross systemic examination

32.  Fully Dilated fundus examination
Bilateral with 360 degree scleral depression
Indirect ophthalmoscopy (diagnostic in 90%
cases)
Wide angle fundus camera ( Retcam)

34. rounded or irregular intraocular mass
representing typical intralesional calcification

36.  delineates extraocular extension, can detect
asso. Pinealoblastoma Cases with atypical
manisfestations
Diagnostic dilemma Extraocular &intracranial
tumor extension is suspected

38. optic nerve invasion or intracranial extension

40.  Not required in routine work up.
 Can be used to differentiate viable tumour
from an avascular residue following
radiotherapy or spontaneously regressed
retinoblastoma.
 Active lesion shows hypervascularity,dilated
feeders and late staining

41.  AQUEOUS HUMOUR ENZYME ASSAY
normal aqueous to plasma LDH >1.0
increased phosphoglucoisomerase levels
increased neuron specific enolase levels

42.  Rarely done, invasive procedure
 Approach through peripheral cornea, A/C,
zonules, vitreous is recommended
 Complication
potential of needle track dissemination of
tumor cells

43.  Useful in ruling out intracranial or distant spread
as primary mode of spread of RB is
hematogenous.
 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.

45.  Congenital cataract
10% of all vision loss in children world
wide
prevalence of 1 to 6 cases per 10,000 live
births
cataract resulting from congenital rubella
syndrome

46.  PHPV
rare congenital developmental
anomaly
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

47.  Norrie disease
Genetic disorder (inherited X link
recessive)
Features –
shrinkage of globe
wasting of the iris
30-50%have developmental delay/mental
retardation
Psychotic like features
Behavioral abnormalities

48.  Coat’s disease
Very rare, congenital non hereditary eye
disorder
Unilateral
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.

49.  ROP
Oxygen toxicity, relative hypoxia
Disorganized growth of retinal blood
vessels ( scarring & RD )

50. Stage 1 is a faint
demarcation line
Stage 2 is an elevated
ridge
Stage 3 is extraretinal
fibrovascular tissue
Stage 4 is sub-total
retinal detachment
Stage 5 is total retinal
detachment.

51.  Toxocariasis
 Uveitis
 Endophthalmitis
 Retinal dysplasia
 Retinoma

52. Special considerations for enucleation in R.B
 Minimal manipulation
 Avoid perforation of eye
 Harvest long ( >15 mm) optic nerve stump
 Inspect the enucleated eye for macroscopic
extraocular extension & optic nerve
involvement
 Harvest fresh tissue for genetic studies
 Place a primary implant
 Avoid biointegrated implant if postoperative
radiotherapy is necessary

55. 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.

56.  Transient serous R.D
 Retinal tear
 Rhegmatogenous R.D

57.  Small post. tumors 4 mm basal diameter & 2
mm in thickness.
Idea is too
 Delimit tumor
 Restrict blood supply to tumor by
surrounding it with 2 rows of overlapping
laser burns

59.  Transient serous R.D
 Retinal vascular occlusion
 Retinal hole
 Retinal traction
 Preretinal fibrosis
 Large visual field defect ( tumor in juxtapapillary
area)

60.  Pt on active chemoreduction protocol, restricts
blood supply to tumor & reduces intraocular
concentration of chemotherapeutic agent

61.  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
mg/kg

65.  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).

66.  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)

67.  Focal iris atrophy
 Focal paraxial lens opacity (minimised using
1300 micron indirect ophthalmoscope, duration
5 mins in single session)
 Retinal traction
 Serous R.D

68.  Placement of radioactive implant on sclera
corresponding to base of tumor,transsclerally
irradiate tumor.
 Radioactive materials – Ruthenium 106 &
Iodine 125
 Tumors < 16mm basal diameter & < 8 mm
thickness
Primary or Secondary
 Primary- chemotherapy is contraindicated,
secondary treatment in eyes that fail to
respond to chemoreduction & external beam
radiotherapy or tumor recurrences.

70.  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
72 hrs)
 90% tumor control

73.  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
radiotherapy )
 Reduced risk of second malignant neoplasm
 Shorter duration of treatment

74.  Radiation papillopathy
 Radiation retinopathy

75.  Used less often, newer chemotherapy
protocols
 Indicated- primary chemotherapy & local
therapy has failed or rarely chemotherapy is
contraindicated.
 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.

79.  Stunting of orbital growth
 Dry eye
 Cataract
 Radiation retinopathy
 Optic neuropathy
 Second malignant neoplasms (hereditary form
of retinoblastoma)
 30% chance of another malignancy by 30 yrs
 Risk of second malignant neoplasm greater in
children under 12 mnths

80.  Buried
 Non-buried

81.  Buried implants
Better cosmosis & safety
Materials used- plastic, silicone &
hydroxyappatite ( currently recommended )

82.  Non- buried implants
have problems of -
migration
extention
infection

83.  Rare in developed countries
 Common in developing countries
 In Mexico, 18% of 500 pts presented with
orbital RB
 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

84.  Primary orbital RB- clinical or
radiologically
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
tumor necrosis.

85.  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
orbital recurrence

87.  Accidental orbital RB-
Inadvertent perforation
Fine-needle aspiration biopsy
Intraocular surgery with unsuspected
intraocular RB

89.  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
n. extension.

90.  Microscopic orbital RB
Detection of full thickness scleral infiltration,
extra scleral extension & invasion of optic n.
on histopathologic evaluation on enucleated
eye
Tumor cells in choroidal & scleral emissaria &
optic n. sheath indicates orbital extension.

91.  General physical examination- includes
regional lymph nodes palpation
 MRI or CT Scan of orbit & brain (axial &
coronal orientation)
 FNAC
 Chest X-RAY
 USG abdomen
 Bone marrow biopsy
 CSF cytology

92.  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