Lecture on Retinoblastoma For 4th Year MBBS Undergraduate Students By Prof. Dr. Hussain Ahmad Khaqan

1. Retinoblastoma
Prof. Dr. Hussain Ahmad Khaqan
 MD
 FRCS(Glasgow)
 FCPS(Ophth.)
 FCPS(Vitreo Retina)
 MHPE (KMU)
 CICO(UK)
 CMT(UOL)
 Fellowship in Medical Retina (LMU, Munich)
 Fellowship in Vitreo Retinal Surgery (LMU, Munich)
 Consultant Ophthalmologist & Retinal Surgeon
Professor of Ophthalmology
Lahore General Hospital, Lahore
Ameer Ud Din Medical College, Lahore
Post Graduate Medical Institute, Lahore
Shaukat Khanum Memorial Cancer Hospital & Research Centre ,Lahore

2. DEFINITION
• Retinoblastoma (RB) is a primary malignant
intraocular neoplasm that arises from primitive
retinoblasts of the developing retina, with loss of
function of the RB tumour suppressor gene.

3. TYPES
• Heritable Retinoblastoma (Germline):
• Accounts for 40% of cases.
• 85% of heritable retinoblastoma present as bilateral
disease while 15% presents as unilateral disease.
• Non Heritable Retinoblastoma(Somatic):
• Accounts for 60% of cases.
• 85% of non heritable retinoblastoma present as unilateral
disease while 15% presents as bilateral disease.

4. SYMPTOMS CONTINUE
1. Leukocoria (white pupillary reflex)- 60%
2. Strabismus - (20%).
3. Painful red eye with secondary glaucoma, which
may occasionally be associated with buphthalmos.
4. Poor vision.

6. 5. Inflammation or pseudo inflammation
6. Orbital inflammation mimicking orbital or
preseptal cellulitis may occur with necrotic
tumours
SYMPTOMS CONTINUE

7. 7. Orbital invasion or visible extraocular growth
may occur in neglected cases
8. Metastatic disease involving regional lymph
nodes and brain before the detection of
ocular involvement is rare.
SYMPTOMS

8. SIGNS Continue..
1. An intraretinal tumour is a homogeneous, dome-
shaped white lesion that becomes irregular, often
with white flecks of calcification.
2. An endophytic tumour projects into the vitreous as
a white mass that may ‘seed’ into the gel.

9. 3. An exophytic tumour forms multilobular subretinal
white masses and causes overlying retinal
detachment .
4. Mixed or diffuse infiltrating (generalized retinal
thickening) ± visible calcification.
SIGNS Continue..

10. Growth Pattern of Retinoblastoma:
Endophytic: Tumour grows inwards towards the
vitreous projecting from the retinal surface.
Exophytic: Tumour grows outwards as subretinal
white mass and detaches the retina.

11. 5. Congestive ocular signs: acute red eye, orbital
inflammation, excess watering.
6. Anterior segment involvement: glaucoma ±
buphthalmos/corneal oedema, iris invasion
manifesting as heterochromia, phthisis bulbi ±
pseudohypopyon, rubeosis ± hyphaema.
SIGNS

12. INTERNATIONAL CLASSIFICATION OF
RETINOBLASTOMA (ICRB) CONTINUE
1. Group A: small intraretinal tumors (<3 mm ) away
from foveola and disc.
2. Group B: tumors > 3 mm macular or juxtapapillary
location or with subretinal fluid
3. Group C: Tumor with focal subretinal

13. 4. Group D: tumor with diffuse subretinal
5. Group E: extensive retinoblastoma occupying >50%
of the globe with or without neovascular glaucoma,
hemorrhage, extension of tumor to optic nerve or
anterior chamber.
INTERNATIONAL CLASSIFICATION OF
RETINOBLASTOMA (ICRB)

14. A
B
C
D
E

15. DIFFERENTIAL DIAGNOSIS CONTINUE
1. Persistent anterior fetal vasculature
2. Persistent posterior fetal vasculature
3. Coats disease
4. Retinopathy of prematurity

16. 5. Toxocariasis.
6. Uveitis
7. Vitreoretinal dysplasia
8. Other tumours: Retinoma (retinocytoma), Retinal
astrocytoma
DIFFERENTIAL DIAGNOSIS

17. INVESTIGATION continue..
1. Red reflex testing with a direct ophthalmoscope
2. Examination under anaesthesia (EUA) includes the
following:
• General examination for congenital
abnormalities of the face and hands.
• Tonometry.

18. • Measurement of the corneal diameter.
• Anterior chamber examination with a hand-held slit
lamp.
• Ophthalmoscopy, documenting all findings with
colour drawings or photography.
• Cycloplegic refraction.
INVESTIGATION continue..

19. 3. Ultrasound (USG-B scan) is used mainly to assess
tumour size. It also detects calcification (Fig.
20.39E) within the tumour
4. RETCAM
5. Wide-field photography
INVESTIGATION continue..

20. 6. CT also detects calcification but entails a significant
dose of radiation so is avoided by many
practitioners. Plain X-rays may be used to detect
calcification in resource poor regions.
INVESTIGATION continue..

21. 7. MRI brain and orbit does not detect calcification
but is useful for optic nerve evaluation, detection of
extraocular extension and pinealoblastoma
INVESTIGATION continue..

22. 8. OCT
9. Systemic assessment: physical examination, bone
scans, bone marrow aspiration and lumbar
puncture
10. Genetic studies
INVESTIGATION

23. B Scan showing calcification in
retinoblastoma lesion

24. MRI showing Right eye RB

25. TREATMENT CONTINUE
• Treatment Modalities for Retinoblastoma
1. Systemic Chemotherapy
2. Intra-Arterial Chemotherapy
3. Intra-vitreal Chemotherapy
4. Peri-ocular Chemotherapy

26. 5. Laser Therapy
6. Cryotherapy
7. Radiotherapy
8. Enucleation
TREATMENT CONTINUE

27. 1. Systemic Chemotherapy
• Retinoblastoma Tumors are very sensitive to
chemotherapy. Chemotherapy is used to shrink
tumor to a size at which laser treatment is
effective.
TREATMENT CONTINUE

28. • It is effective against solid tumors as well as sub-
retinal and vitreous disease. It may be given as first
line treatment in patient with intraocular
Retinoblastoma group B, C, D.
TREATMENT CONTINUE

29. • First Line Chemotherapy:
• The most common used regime is JOE or CEV
including Carboplatin, Etoposide, and
Vincristine.
• It is delivered via central line systemically.
• It involves 4 to 6 cycles at 3 to 4 weeks interval.
TREATMENT CONTINUE

30. • Second line Chemotherapy:
• It is used in recurrent cases after first line
chemotherapy.
• It includes Topotecan, Vincristine and
Doxorubicin.
TREATMENT CONTINUE

31. 2. Intra Arterial Chemotherapy:
• It includes:
1. One drug regimen-Melphalan.
2. Two drug regimen-Melphalan and Topotecan.
3. Three drug regimen-Melphalan, Toptecan and
carboplatin.
• Cycles:
1. It is given every three weeks over 2-4 cycles.
TREATMENT CONTINUE

36. 3. Intravitreal Chemotherapy:
• Drugs used are:
1. Melphalan (25µg/0.125ml;30µg/0.15ml)
2. Topotecan hydrochloride (20µg/0.1ml
with 0.9% normal saline)
TREATMENT CONTINUE

37. • Number of injections:
1. Six injections are delivered on weekly or
biweekly schedule if only one injection is being
used.
2. Only one or two injections are used if
combination of Melphalan and Topotecan is
used.
TREATMENT CONTINUE

38. 4. Peri-ocular chemotherapy:
• Drugs used are:
1. Carboplatin (2ml at concentration of 10mg/ml)
2. Topotecan (0.09-0.27mg/kg)
TREATMENT CONTINUE

39. 5. Laser Therapy:
• Laser is applied directly on the tumor or in a
ring like manner around the tumor to coagulate
feeding blood vessels leading to ischemic
necrosis of tumor.
• In the next2-3 sessions laser is applied
consecutively at 4-6 weeks intervals
TREATMENT CONTINUE

40. • Laser Approaches:
• Photocoagulation
• Thermotherapy
TREATMENT CONTINUE

41. 6. Cryotherapy:
• It is used for anterior and small tumors.
• It involves application of below freezing
temperature (below -90◦) directly to the tumor
mass.
• Triple freeze thaw technique is used through
the conjunctiva in two sessions with three
week interval.
TREATMENT CONTINUE

42. 7. Radiotherapy:
A. Radioactive Plaque brachytherapy:
• Gold plaques carrying radio-active seeds used are
sutured to the base of the tumor, to provide 40 Gray
(Gy) to the tumor apex over a period of 2–4 days, and
the plaque is then removed.
Radioisotopes used are:
• Iodine (I 125)
• Ruthenium (Ru 106)
TREATMENT CONTINUE

43. B. External Beam Radiation Therapy:
• Six weeks after surgery, external beam
radiation (45 to 50 Gy) is delivered to the orbit.
• The radiation field should include the regional
lymph nodes if the patient had regional lymph
node involvement at presentation.
TREATMENT CONTINUE

44. 8. Enucleation:
• Primary Enucleation is the preferred treatment
in eyes with advanced unilateral intraocular
retinoblastoma (where globe salvage is not
desired or possible) corresponding to Group E
in the International Intraocular Retinoblastoma
Classification.
TREATMENT CONTINUE

45. • Secondary Enucleation is performed in:
a. Eyes that have failed conservative treatment
strategies
b. Phthisical eyes after-high-dose chemotherapy
TREATMENT

46. Types of Regression

47. Type I
Figure A and C is before Chemotherapy
and B is after Chemotherapy showing
completely calcified lesions
A B
C D
. , .

48. Type II
• In figure A and C lesions are before Chemo-
reduction and figure B and D shows type II
Regression pattern after Chemotherapy
A B
C D
, , ,

49. Type III
In figure A and C lesions are before
Chemo-reduction and figure B and D
shows type III Regression pattern after
Chemotherapy

50. Type IV
In figure A and C lesions
are before Chemo-
reduction and figure B and
D shows type IV
Regression pattern after
Chemotherapy

51. THANK YOU