ORIGINAL ARTICLE

Clinical Course of Retinoblastoma

Farrah Islam1, Saemah Nuzhat Zafar2, Sorath Noorani Siddiqui2 and Ayesha Khan2

ABSTRACT

Objective: To determine the clinical manifestations and results of current treatment for patients with retinoblastoma (Rb)
in a tertiary care eye hospital in the north west of Pakistan.
Study Design: Case series.
Place and Duration of Study: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from January 2006 and December 2009.
Methodology: The data of 139 patients diagnosed as having retinoblastoma was collected. Gender, age at diagnosis,
laterality, presenting sign, classification of tumour, treatment modality and outcome were noted.
Results: The mean age of presentation in this patients ranged from 6 to 50 months (mean: 24.05 10.74 months). The
most common presenting sign was leucocoria in 78 eyes (44.1%). One hundred and one (72.7%) patients had unilateral
retinoblastoma. Using the International Classification of Retinoblastoma (ICRB), 135 (76.3%) eyes were placed in group-E.
one hundred and twenty four (77.5%) eyes were enucleated or exenterated while globe preservation was achieved by
chemoreduction and/or focal therapy in the rest of the treated eyes (n = 36, 22.5%). Twenty three (16.5%) cases were lost
to follow-up before one year. Ninety two (66.2%) patients survived, being free of tumour, at least one year after the
completion of treatment.
Conclusion: Most children with Rb showed an advanced stage of tumour at the time of diagnosis. Measures to improve
the rate of globe preservation and patient survival by early diagnosis and intervention are the need of the hour.
Key Words: Retinoblastoma. Enucleation. External beam radiation. Chemotherapy.

INTRODUCTION

Retinoblastoma is the most common primary ocular

malignancy of childhood. It is the most common
paediatric ocular tumour in Pakistan as well.1 Worldwide, about one case of retinoblastoma (Rb) is recorded
per 15,000 20,000 live births.2 With the advent of new
and better diagnostic and treatment modalities, the
outcome of retinoblastoma has improved tremendously
in developed countries. In contrast to the previous
management protocols, where enucleation and external
beam radiation was considered pivotal in management
of Rb, more emphasis is now being paid to focal
therapies and chemotherapy. This has led to improved
outcomes in terms of globe survival and patient
survival. Over the last decade, the documented survival
rate of Rb patients has reached to above 87 99% in
developed countries.3

In this era of improvised therapies, the underdeveloped

countries are still facing many challenges in the
management of retinoblastoma. Data on pattern of
presentation and metastasis,4,5 epidemiological aspects6-8
and Rb among histopathological audits are available in
literature from Pakistan. However, the assessment of
results of current therapeutic methods in the Pakistani
population has not been presented earlier.
Department of Retina1 / Paediatric Ophthalmology2, Al-Shifa
Trust Eye Hospital, Rawalpindi.
Correspondence: Dr. Saemah Nuzhat Zafar, M-223,
Abdul Habib Khan Road, Lalkurti, Rawalpindi.
E-mail: saemahsaqib@yahoo.co.uk

Received: October 27, 2011; Accepted: April 27, 2013.

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The aim of this study was, therefore, to determine the

clinical presentation and outcome of prevalent
management for retinoblastoma at the tertiary care eye
hospital in Rawalpindi, Pakistan.

METHODOLOGY

This study was conducted prospectively at a tertiary

care eye hospital in Pakistan. Consecutive patients,
diagnosed with retinoblastoma were enrolled between
January 2006 and December 2009. All demographic
details including age at presentation, gender, age at the
onset of symptoms, laterality, presenting symptoms
and family history of retinoblastoma were recorded.
Following initial ocular examination in the clinic,
complete ophthalmic examination under anaesthesia
including fundus photography by Ret Cam (Massie
Labs) was done. Ophthalmic ultrasound and computerized tomography of the brain and orbit was done
for every patient.

The involved eye was classified according to International Classification for Retinoblastoma (ICRB).
Treatment modalities included focal therapy with
cryotherapy or laser photocoagulation, chemotherapy
with or without focal therapy, enucleation, and exenteration. Patients were referred to paediatric oncologists
for chemotherapy. Chemoreduction (CRD) involved
systemic administration of vincristine, etoposide and
carboplatin. CRD cycles were given every 3 4 weeks
to a total of six cycles. Some advanced or bilateral
cases received 8 cycles of chemotherapy. During
chemotherapy, patients were examined under anaes-

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (8): 566-569

Clinical course of retinoblastoma

thesia every month. External beam radiotherapy

(EBRT) was given in the cases where after maximum
chemotherapy and focal treatment the tumour did not
fully regress or there was optic nerve involvement or
extrascleral extension of the tumour.

In the eyes with ICRB group-A and B cryotherapy or

indirect laser photocoagulation was performed,
depending on the tumour location. In patients having
bilateral involvement, Group-A tumours also received
chemotherapy along with focal treatment in specific
cases having worse ICRB staging in the fellow eye.
Group-B eyes with macular retinoblastoma also
received chemotherapy in addition to focal treatment.
All group-E eyes were offered primary enucleation. In
the presence of adverse histopathological features like
invasion of anterior segment, retrolaminar invasion of
optic nerve, invasion of choroid greater than 2 mm,
scleral or orbital invasion, 6 cycles of chemotherapy
were continued postoperatively to prevent metastasis.
Exenteration was done in the cases where there was
extra ocular extension of the tumour.

Data was analysed with the help of Statistical Package

for Social Sciences (SPSS) for windows software.
Descriptive statistics were obtained as mean SD for
time in months and age, frequencies in percentages
were presented for sex, unilateral or bilateral disease,
number of case per year, mode of presentation, number
of eyes having different classification of retinoblastoma,
mode of treatment used for each involved eye and the
outcome of treatment described in terms of globe
survival and patient survival. Globe survival was
defined as globe salvaged compared to enucleation or
exenteration of the globe. Kaplan-Meier test was applied
for globe survival analysis across different ICRB groups.
Patient survival was taken as a minimum of one year of
tumour-free survival.

RESULTS

One hundred and seventy-seven eyes of 139 patients

were enrolled in this study. The number of eyes with Rb
that presented in each year were 57 (32.2%) in 2006, 48
(27.1%) in 2007, 37 (20.9%) in 2008 and 35 (19.8%) in
2009. There were on an average 34.75 new cases with
Rb each year (2.9 cases per month).
One hundred and one (72.7%) cases had unilateral
involvement and the remaining 38 (27.3%) patients had
Table I: Treatment modalities used in different ICRB groups.
ICRB group

bilateral tumours. Among the patients with bilateral

disease, 24 (63.2%) were males and 14 (36.8%) were
females, while among unilateral cases, there were 44
(43.6%) males and 57 (56.4%) females. The mean age
of presentation was 24.05 10.74 months (ranging from
6 to 50 months). It was 25.78 10.66 months (ranging
from 9 to 50 months) in unilateral cases and 19.47
9.67 months (ranging from 6 to 45 months) for bilateral
cases.
Family history for retinoblastoma was positive in 7 (5%)
patients. Among these 5 (13.15%) children had bilateral
Rb and 2 patients (1.98%) had unilateral tumours. In
addition, parents of 3 patients with bilateral Rb were
diagnosed with retinomas. The mean follow-up duration
was 18.96 18.40 months.
Leucocoria was the most common presenting sign in 78
(44.1%) eyes, followed by fungating mass, enlarged or
ruptured globe seen in 38 (21.5%). Strabismus was
seen in 22 (12.4%), uveitis in 18 (10.2%) and
buphthalmos in 8 (4.5%) eyes. Eight (4.5%) eyes
presented with decreased vision and 5 (2.8%) eyes with
phthisis bulbi.

Group-A tumour was diagnosed in 6 eyes of patients

with bilateral involvement, group-B in 14 eyes of patients
with bilateral tumours, group-C in 2 unilateral cases and
10 eyes of patients with bilateral lesions, group-D in 8
unilateral cases and 2 eyes of cases with bilateral Rb,
while group-E tumours were seen in 91 unilaterally
involved eyes and 44 eyes of patients with bilateral
involvement.

Different treatment modalities were used in 160 eyes

(Table I). Among 17 eyes that did not receive treatment
for different reasons, one belonged to ICRB group-A,
2 to group-C and 14 were group-E eyes. Enucleation
was done in 112 (70%) of the treated 160 eyes.
Among them in 19 (16.96%) eyes only enucleation
without adjuvant therapy was performed. Exenteration
was carried out in 12 (7.5%) of the 160 eyes that
received treatment. All of them were given adjuvant
chemotherapy, while 2 (16.66%) of the post-exenteration
orbital sockets also received radiotherapy.
The patient survival was 66.2% (n = 92) who were
tumour-free for at least one year after completion of
treatment. Out of the 92 surviving patients, 64 (69.57%)
had unilateral and 28 (30.43%) had bilateral retinoblastoma. Twenty four patients died during the study

Focal

Focal +chemotherapy

Enucleation

Enucleation+ adjuvant therapy

Exenteration + adjuvant therapy

Total No. of eyes

14

14

Total

A
B

C
E

1
0
0

10

35

0
0

19
19

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (8): 566-569

0
9

84
93

0
0

12
12

10
9

122
160

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Farrah Islam, Saemah Nuzhat Zafar, Sorath Noorani Siddiqui and Ayesha Khan

period and 23 patients were lost before one year of

follow-up.

Seventeen (70.8%) out of the 24 cases that died had

advanced retinoblastoma with optic nerve and or
anterior segment involvement and extensive metastasis
at initial presentation. Four (16.7%) patients initially
presented with small tumours but soon defaulted and
went for alternative medicines or visited quacks. They
later came back with fungating mass and extensive
metastasis with eventual fatal outcome. Two (8.3%) of
the patients died during chemotherapy due to
disseminated intravascular coagulation or other
chemotherapy related complications. One (4.2%) patient
of unilateral retinoblastoma presented with orbital
tumour in the enucleated socket 3 months after the
completion of chemotherapy and died shortly because
of metastasis.
The mean time lag between the age of presentation and
the time when parents first noticed the symptoms was
5.63 3.79 months in those who eventually showed
tumour-free survival. It was 13.79 6.91 months in those
who eventually died during the study duration.

Two eyes of 2 patients developed retinal detachment

after completion of treatment for which vitrectomy with
silicon oil was done. One patient remained well with
ambulatory vision while the other developed repeated
retinal detachment due to tumour progression, for which
secondary enucleation was done. At the end of study
period, the globe was salvaged in 36 (22.5%) of the 160
eyes that received treatment, mostly belonging to
group-A and B. Among the 36 salvaged globes, 28
(77.8%) were the other eye of the bilateral Rb cases and
8 (22.2%) eyes had unilateral retinoblastoma. KaplanMeier curve showing globe survival in different ICRB
groups as shown in Figure 1.

DISCUSSION

Although retinoblastoma has been mentioned in studies

analyzing histopathology data.9-11 This study reports the
outcome of current treatment, which has not been
documented before from our part of the world.

The mean age of presentation in these patients was

24.05 10.74 months. This is comparable to that
reported by Naseripour et al.12 In this study, it was
25.7810.66 months in unilateral cases and 19.47
9.67 months for bilateral cases. Another report by Lee
et al. mentions19.65 months as age at presentation
which is less than that noted in the present study.13 The
mean lag time between first noticing the symptoms and
initiation of treatment was much greater in these patients
and this might be the reason for lesser globe survival
and patient survival in this study. Twenty three (16.5%)
patients who were lost to follow-up before one year of
age, may also have contributed to the lesser patient
survival. The diagnostic delay is associated with greater
risk of local tumour spread.14 In this study, patients born
to educated parents and those having a positive family
history reported early. This reflects the need for better
health education in our community.

In this study, the number of new cases of retinoblastoma, who presented each year in a single institute,
was greater than many of previous studies. It was 9.33
according to Bonanomi et al.,15 Naseripour et al.
reported 16.57, Chantada et al. documented 31.67,12,16
while Shanmugam et al.17 recorded 25.36 new cases
each year compared to 34.75 new cases each year
according to this study.
The most common presenting symptom in this study
was leucocoria. Frequency of leucocoria as the
commonest presenting feature is much less in a
published report where proptosis is the second
commonest sign.17 Badhu et al. reported proptosis
to be most common mode of presentation in Nepal
(90.70%).19 According to Menon et al. it was the
second most common presentation in Malaysian (22%)
children.20

Among the 101 unilateral cases, 91 eyes (90.1%)

presented with advanced stage of disease (ICRB-E)
while 44 (57.9%) eyes of bilateral cases presented with
advanced disease in at least one eye and variable stage
tumour in the other eye. This is consistent with reports
from other developing countries.21

Figure 1: Kaplan-Meier plot of globe survival in eyes having different tumour

groups according to International Classification of Retinoblastoma (ICRB).

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The news of cancer itself brings in great stress for

parents of children with retinoblastoma, be it a
developed or underdeveloped country. To avoid the
physical and cosmetic deformity of enucleation, parents
in underdeveloped countries revert to quacks. When
they finally come back to the hospital, the patients
have advanced disease that greatly increases the
morbidity and mortality associated with it. Enucleation
or exenteration and subsequent chemotherapy require
repeated inpatient stays with consequent disruption to

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (8): 566-569

Clinical course of retinoblastoma

normal domestic and working life. This problem has also

been narrated by other researchers.13,22

In developed countries, there is an increased trend

towards globe salvaging treatments of retinoblastoma,
as reported by Dondey et al.,23 Lee et al.13 and Sheilds
et al.24 In underdeveloped countries, the globe survival
rates are considerably lower. In this study, the globe
survival rate was only 22.5% at the end of study
duration. Globe survival was 44.2% in an Iranian study,12
and 32% in a Malaysian study.20 This again is attributable to late presentation and poor health education in
developing countries. One patient in the present study
was diagnosed with a new retinoblastoma lesion in the
fellow eye, 9 years after one eye was enucleated in
infancy.25 The need for strict adherence to follow-up
should be highlighted to detect such rare cases of late
bilateralization. Most of the patients in this study were
from the north and central parts of the country.

We believe that incidence of Rb in this area of Pakistan

is much higher than reported worldwide but due to lack
of good health services and referral system, it is
impossible to know the true scenario. The need of the
hour is to work in a cooperative group and develop an
intensified national early detection program as well as a
treatment protocol. Educating parents and physicians is
required to improve clinical outcome with less morbidity
and mortality as survival in retinoblastoma patients
will be increased only by earlier diagnosis and better
treatment adherence.26

CONCLUSION

Most children with retinoblastoma showed an advanced

stage of tumour at the time of diagnosis in this study.
Although they were treated with an updated therapeutic
approach, the rate of globe preservation did not reach
that of developed countries.

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