Case presentation

Dr. Ashish Dubey

History

A case of 18 months old boy whose parents

noticed a white reflex in R eye few months
after birth .The parents had shown to some
general practitioner who advised them to
come for a regular follow up. Parents
noticed an increase in the white reflex in a
few months and were referred to R.P.C.

History

On detailed history it is a case of FTNVD

No H/O birth asphyxia,birth trauma,oxygen
administration
No H/o any similar illness in any family members
No H/o any familial predisposition to develop
cancers in body
No C/o any pain,redness,watering,
The patient has 1 sibling{1month old}

General examination
Vitals : PR 85/min, RR 16/min
Oral Hygiene N
Systemic examination:
Abdomen - No organomegaly, no ascites
CVS NAD,
Respiratory system - NAD
Mild nasal discharge +

Ocular Examination
R

Visual
acuity

Does not fixate or

follow light

Fixates and follows

light

Eye balls

RDS + , no
nystagmus

Normal

Movement N
s
Palpebral
aperture

Slight prominence N
of eye ball

Ocular examination
Eye lids

Lacrimal system No regurgitation Noregurgitation

Conjuctiva

NAD

NAD

Cornea

NAD

NAD

Sclera

NAD

NAD

A.C

No cells,flare

No cells; flare

Iris

Brown,no
nodules

Brown,no
nodules

Pupil

3mm,round,cent 3mm,round,cent
ral,nosyn,C+,D+ ral,C+D+

Lens

Clear

Clear

I.O.P

DTN

DTN

Fundus

Whitish
reflex,total
Rd,a mass
lesion seen

Red glow,C:d.
.3:1,NRRN,superiorly
located mass
seen

Investigations
Hb 13.5gm%
Urine protein, sugar nil
USG R - Soft tissue intraocular mass
height 7.6mm, base 10.6mm with total
exudative RD. The mass shows presence of
calcification
USG L Superiorly located intraocular
mass with calcification. Height 5mm, base
6.3mm. No RD+

Investigations
CT scan R-shows soft tissue density filling
posterior segment with multiple
calcifications, optic nerve extension absent
N brain parenchyma
CT scan L a small soft tissue posterior
chamber mass present superiorly ,with
presence of calcification . Mass appear
localised, no involvement of optic nerve or
CNS seen

Differential Diagnosis
RETINOBLASTOMA
PHPV
ROP
COATS DISEASE
COLOBOMA OF CHOROID /DISC
CONGENITAL CATARACT
TOXOCARA GRANULOMA
RETINAL DYSPLASIA

Clinical Significance
Retinoblastoma (RB) is most common
intraocular malignancy in children
Untreated it is uniformly fatal
Confused and misdiagnosed with other
conditions simulating it
It is the only cause which can prove fatal
Any child presenting with leucocoria should
be considered as RB unless proved
otherwise

Retinoblastoma
Incidence 1:18000- 1:20,000
No sex predeliction
Peak age 18 months
Familial tumours present earlier
Inheritance 60% non hereditary{85% U/L}
40%germline mutation

Inheritance
Unaffected parent with 1 affected child 5%
risk
With 2 or more affected child 50% risk
Survivor of hereditary RB has 50% risk of
having a child with RB.

Pathogenesis

Mutation in RB 1 gene Chr 13 band 14

Tumor suppressor gene
Deletion of both genes necessary
Cell affected is primitive retinal precursor of photo
receptor elements in outer retinal layer
Growth can be Endophytic or Exophytic
Most common is endophytic
It can vary from well differentiated to
undifferentiated

Classification

Rees Ellsworth classification :

1. <4D.D at or posterior to equator, multiple upto
4D.D at or posterior to equator
2. Solitary 4-10 D.D at or posterior toequator,
multiple 4-10 D.D
3. Tumor extending anterior to equator,or solitary
tumor >10D.D behind equator
4. Anterior to ora serrata, multiple tumour >10D.D
5. >1/2 retina involved , vitreous seedings present

RPC - IRCH
1. Or more lesion <4D.D,<4m.m height
1 or more lesion 4-6D.D,4-8m.mheight
1 or more lesion >6D.D > 8m.m height
Extraocular extension to orbit
Distant metastasis

Investigations
History
Family History
Clinical examination[ EUA]
USG - Estimate presence, dimension,
associated RD
CT- confirm presence, detect calcification,
estimate dimension, invasion of orbit, gross
involvement of optic nerve, CNS extension

Investigations
MRI is not routinely required ,only for
better delineation of optic nerve involvment
and cns soft tissue involvment
MRI useful in differentiating Rb. From
simulating lesions
Metastatic workup not routinely required
unless signs of spread present
Metastatic workup includes CSF , bone
marrow examination,LFT ,bone scans

Treatment
Enucleation
Indication ->1/2 globe involved, ant.
Segment involvment, total R.D , absence of
useful vision, glaucoma
Removal of entire eyeball intact along with
a long stump of optic nerve
Meticulous surgical technique

Enucleation

Enucleation

Placement of superior fornix traction

suture[10 m.m above]{5-0 silk}
During peritomy preserve as much
conjuctiva and tenons
Avoid tear of of posterior tenons and
intermuscular septa
Adeuate hemostasis

Avoid excess traction on globe ,damage to

chiasm can occur
Temporal traction on medial recti
accentuate the medial location of optic
nerve,facilitating neurectomy from nasal
side
Metzenbaum scissor should be introduced
in orbit in closed state

First confirm the position and then open and

cut the nerve with a stump of 8-10mm
After removal of globe adequate hemostasis
is must to prevent hematoma,infection and
implant migration

Place a adequate size implant behind

posterior tenons
Attach recti muscles to posterior tenons
Do not imbricate muscles on the implant
Close anterior tenons and conjuctiva in 2
layers
Place a transparent conformer with drainage
pores to maintain cul de sac

CHEMOTHERAPY
Indications
Focal lesions involving macula and optic nerve
Along with cryo or laser if lesion not totally
regressed or presence of significant vitreous
seedings
Metastatic disease,extra ocular spread
High risk cases with more chance of metastasis
Neoadjuvant chemotherapy for advanced
stages as primary modality

CHEMOTHERAPY
Regimens
4 week regimen :
Week 0 Carboplatin 560mg/m2, Etoposide
200mg/m2 I.V.,
Week 3 Vincristine1.5 mg/m2,
cyclophosphamide150mg/m2 oral for 7 days
VAC regimen :
Vincristine 1.5mg/m2, Cyclophosphamide
150mg/m2; Adriamycin25 mg/m2 all given on day
1 repeated every 3 weeks

CHEMOTHERAPY
Side effects
Cyclophosphamide bone marrow toxicity,
cystitis, case report of bladder carcinoma
Carboplatin nausea , vomiting ,renal
toxicity
Vincristine- vesicant,neurologic,marrow,
Adriamycin- cardiac toxicity

Other treatment modalities

EBRT
Indications involvment of orbital bones,
progression during chemotherapy,extension
beyond cut margins of optic nerve
Side effects secondary tumours, facial
hypoplasia, radiation retinopathy, optic
neuropathy, cataract,

Plaque brachy therapy

Focal delivery of radiation, small or med.
sized tumors,
CO60, I125
Disadvantges : incomplete treatment,high
dose to sclera, difficult for posterior lesions,
retinal detachment

PHOTOCOAGULATION
Direct treatment of tumour with
argon/diode/laser
Destroy blood vessels supplying tumour
Small size, posteriorly located tumours
250-300 mw ,400-600msec

CRYOTHERAPY
Lesion anterior to equator,confined to
sensory retina, <2.5mm diameter, <1mm
thickness
3 freeze thaw cycles
Side effects : retinal hole , R.D, SRF,
Vitreous hemorrhage

Other treatment modalities

Thermochemo therapy
TTT
Subconjuctival chemotherapy : carboplatin,
excess fibrosis, later enucleation difficult
Hyperfractionation radiotherapy[Archives
opthalmology 2002]

NEW MODALITIES
GENE replacement therapy
Phase 1 clinical trial of gene therapy
altered adeno virus with thymidine kinase
with ganciclovir injected in tumour cells ;
ONYX_O15
Discovery of vitamin D receptors in Rb.has
lead to use of 1 alpha hydroxy D2 and other
analogues ,increase p53 expression
[2002]Wisconsin ,USA

BJO SEP, 1994 ;Rb. Patients with +F/Hwill

develop new I/o tumour within
6months,Total 6%will develop new
tumour , out of which 24%after EBRT,none
developed new tumour after 7.5 years

Recent Dutch study reported 5 case reports

of Rb. In babies born after IVF,though
scandinavian and other centre studies have
refuted it.