Global Retinoblast 2020

Research
JAMA Oncology | Original Investigation
Global Retinoblastoma Presentation and Analysis

by National Income Level
Global Retinoblastoma Study Group
Supplemental content
IMPORTANCE Early diagnosis of retinoblastoma, the most common intraocular cancer, can
save both a child’s life and vision. However, anecdotal evidence suggests that many children
across the world are diagnosed late. To our knowledge, the clinical presentation of
retinoblastoma has never been assessed on a global scale.
OBJECTIVES To report the retinoblastoma stage at diagnosis in patients across the world
during a single year, to investigate associations between clinical variables and national income
level, and to investigate risk factors for advanced disease at diagnosis.
DESIGN, SETTING, AND PARTICIPANTS A total of 278 retinoblastoma treatment centers were
recruited from June 2017 through December 2018 to participate in a cross-sectional analysis
of treatment-naive patients with retinoblastoma who were diagnosed in 2017.
MAIN OUTCOMES AND MEASURES Age at presentation, proportion of familial history of

retinoblastoma, and tumor stage and metastasis.
RESULTS The cohort included 4351 new patients from 153 countries; the median age at
diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were
female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries
(LMICs). Globally, the most common indication for referral was leukocoria (n = 2638
[62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients
from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656
of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis.
Patients from low-income countries were diagnosed at a median age of 30.5 months, with
256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having
metastasis. Lower national income level was associated with older presentation age, higher
proportion of locally advanced disease and distant metastasis, and smaller proportion of
familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs
even after adjusting for age (odds ratio for low-income countries vs upper-middle–income
countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle–income countries vs
upper-middle–income countries and HICs, 5.74 [95% CI, 4.30-7.68]).
CONCLUSIONS AND RELEVANCE This study is estimated to have included more than half of
all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main
global retinoblastoma burden lies, presented at an older age with more advanced disease
and demonstrated a smaller proportion of familial history of retinoblastoma, likely because
many do not reach a childbearing age. Given that retinoblastoma is curable, these data are
concerning and mandate intervention at national and international levels. Further studies are
needed to investigate factors, other than age at presentation, that may be associated with
advanced disease in LMICs.
Group Information: The members

of the Global Retinoblastoma Study
Group appear at the end of this
article.
Corresponding Author: Ido Didi
Fabian, MD, London School of
Hygiene & Tropical Medicine,
Keppel Street, London WC1E 7HT,
JAMA Oncol. 2020;6(5):685-695. doi:10.1001/jamaoncol.2019.6716 United Kingdom
Published online February 27, 2020. Corrected on September 24, 2020. ([email protected]).
(Reprinted) 685
Downloaded From: https://jamanetwork.com/ on 02/06/2022

Research Original Investigation Global Retinoblastoma Presentation and Analysis by National Income Level
R
etinoblastoma, the most common eye cancer of child-
hood, is fatal if left untreated. Prognosis of patients with Key Points
retinoblastoma in high-income countries (HICs) has im-
Question Is the income level of a country of residence associated
proved over the past 50 years, now reaching a near 100% dis- with the clinical stage of presentation of patients with
ease-free survival rate.1-3 This is attributed to several factors, in- retinoblastoma?
cluding (1) creation of specialized referral centers, (2) decoding
Findings In this cross-sectional analysis that included 4351
of the genetic basis of the disease, (3) formation of screening pro-
patients with newly diagnosed retinoblastoma, approximately half
grams, and (4) the introduction of chemotherapy.4 In HICs, reti- of all new retinoblastoma cases worldwide in 2017, 49.1% of
noblastoma is a curable disease, and attention has now shifted patients from low-income countries had extraocular tumor at time
to eye salvage5,6 and improvement of quality of life.7 In low- and of diagnosis compared with 1.5% of patients from high-income
middle-income countries (LMICs), where more than 80% of countries.
global retinoblastoma cases arise, the prognosis is poor, and Meaning The clinical stage of presentation of retinoblastoma,
it is assumed that this is because of delayed diagnosis and which has a major influence on survival, significantly differs among
treatment.8-10 Publications from LMICs are scarce, and many patients from low-income and high-income countries, which may
countries do not report their retinoblastoma data.11 The stage warrant intervention on national and international levels.
of retinoblastoma at the time of diagnosis in low-income,
middle-income, and high-income countries has not been sur- eye with the more advanced disease was used for analysis. Com-
veyed globally. This information is important for policy and pleted forms were electronically uploaded onto a secure server,
health care planning at national and international levels. after which a data quality assurance process was performed
The objectives of this study are to (1) report the stage at (eMethods in the Supplement).
diagnosis in a large global sample of patients with retinoblas- The study was approved by the institutional review board
toma, (2) examine associations between clinical variables at at the London School of Hygiene & Tropical Medicine, which
presentation and national-income level, and (3) investigate risk granted a waiver of patient informed consent. Participating cen-
factors for advanced disease at diagnosis. ters applied for and received ethics clearance in their coun-
tries according to local institutional guidelines.
Statistical Analysis
Methods
All analyses were performed using R software, version 3.5.2
This study originated from a consortium of retinoblastoma (R Foundation for Statistical Computing), and IBM SPSS Sta-
treatment centers in 8 countries on 3 continents.12 From June tistics, version 25.0 (IBM Corp). The crude birth rate, country
2017 through December 2018, all known retinoblastoma treat- population size, and country classification by national in-
ment centers across the world were contacted by means of per- come level were obtained from the 2017 World Population
sonal communications, presentations at scientific confer- Prospects.16 The predicted number of new patients with reti-
ences, and linking to professional societies in the fields of noblastoma per country was calculated as follows: [country
ophthalmology and oncology to form a global network. All cen- population × crude birth rate/1000/17 000], and predicted
ters involved in the diagnosis and treatment of patients with number per national income level was the sum result of all
retinoblastoma, at least by means of enucleation, were eli- countries at the same level.
gible to participate. Unless otherwise indicated, summary statistics are pre-
sented as median and interquartile range (25%-75%). The t test
Study Design was used to compare means of normally distributed continu-
This study adheres to the Strengthening the Reporting of ous variables, Fisher exact and Pearson χ2 tests were used to
Observational Studies in Epidemiology (STROBE) reporting compare categorical variables, Spearman rank correlation test
guidelines.13 It was a 1-year cross-sectional analysis that included was used for nonnormal continuous and ordinal variables, and
all treatment-naive patients with retinoblastoma who present- the Cochran-Armitage test17,18 was used to test for trend in the
ed to participating centers from January 1, 2017, to December 31, proportions of patients with a given parameter across the in-
2017, and who were treated or offered treatment for retinoblas- come levels. Binomial logistic regression was used to model
toma. A predesigned form was used for data collection (eTable 1 the effect of income level (upper-middle–income level and
in the Supplement). The data collected included country of resi- high-income level combined), presentation age (grouped by
dence, sex, first ocular symptom as noted by parents, age at first tertiles), familial retinoblastoma history, sex, and bilaterality,
indication of symptom, age and ocular indication at presenta- on the likelihood of children having advanced disease (cT4)
tion to the retinoblastoma treatment center, laterality, familial at presentation. An α level of .05 and 2-tailed P values were
history of retinoblastoma, staging according to the American Joint used to determine statistical significance.
Committee on Cancer Staging Manual, Eighth Edition14 and the
International Retinoblastoma Staging System,15 and primary
treatment. Data on country of residence, sex, and laterality were
minimum criteria for patient enrollment. The staging classifica-
Results
tions were simplified to include only the major subcategories The study sample included 4351 treatment-naive patients
(eTable 2 in the Supplement). For the primary tumor site (cT), the with retinoblastoma residing in 153 countries (Figure). The data
686 JAMA Oncology May 2020 Volume 6, Number 5 (Reprinted) jamaoncology.com

Global Retinoblastoma Presentation and Analysis by National Income Level Original Investigation Research
analyzed by national income level are shown in Table 1.

Figure. Cohort Recruitment Flowchart
Country-level and continent-level data are shown at http://
globalretinoblastoma.org (password: Ret2017). 298 Retinoblastoma centers from
134 countries were contacted
Geographic and Socioeconomic Characteristics

6 Centers were excluded because they
More than half (2276 [52.3%]) of the patients were from Asia, had no patients with retinoblastoma
1024 (23.5%) were from Africa, 522 (12.0%) were from in 2017
Europe, 512 (11.8%) were from the Americas, and 17 (0.4%)
were from Oceania. Of all patients, 533 (12.3%) came from low- 6 Centers were excluded because they
income countries (LICs), 1940 (44.6%) from lower-middle, Center had new patients with retinoblastoma
recruitment in 2017 but did not report the patients
1212 (27.9%) from upper-middle, and 666 (15.3%) from HICs. to this study
Completeness of Data 8 Centers were excluded because they

For 4116 (94.6%) of the study patients, data were reported on each had no information available on patients
with retinoblastoma in 2017
study parameter, except for age at first ocular symptom of reti-
noblastoma (2175 [50.0%]; not included in the analysis). Analy-
sis by national income level showed that reporting was nearly 278 Retinoblastoma centers from
130 countries joined the study and
complete (≥98.5%) for patients from high-income and upper- reported 4395 new patients with
middle–income countries, and more than 94.1% and 89.1% for pa- retinoblastoma from 153 countriesa
tientsfromlower-middle–incomecountriesandLICs,respectively.
14 Patients were excluded owing to
duplicate reporting
Symptoms Leading to Referral Patient
The most common first symptom of disease was leukocoria enrollment
(n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]), 30 Patients were excluded because they
did not fulfill the inclusion criteriab
with a further 162 (3.9%) patients having a combination of leu-
kocoria and strabismus (eTable 3 in the Supplement). Propto-
4351 Patients from 153 countries
sis was reported in 309 (7.4%) patients. At least 1 symptom of were eligible
advanced disease (ie, proptosis, swollen eyelids, red eye) was
a
reported in 487 (11.7%) patients. A higher income level was as- Patients from 23 countries with no retinoblastoma centers were treated
outside of their country of residence.
sociated with a lower proportion of patients with symptoms
b
Inclusion criteria included reporting of country of residence, sex, and laterality.
of advanced disease (z score = 10.9, dim = 4; P < .001; addi-
Patients for whom 1 or more of these parameters were not available were not
tional analysis is provided in eTable 4 in the Supplement). included in the analytic sample.
Symptoms at Time of Diagnosis at Retinoblastoma Centers

Of all patients, 2998 (70.4%) presented with either leukoco- M0 (n = 3964 of 4275 [92.7%]) (Table 1). Extraocular retino-
ria, strabismus, or a combination of these symptoms (eTable 3 blastoma at time of diagnosis was reported in 926 of 4302
in the Supplement). In LICs, combinations of proptosis, red eye, (21.5%) patients (256 [49.1%] in LICs vs 10 [1.5%] in HICs).
orbital cellulitis, and extraocular retinoblastoma (ie, ad- Distant metastases were reported in 94 (18.9%), 157 (8.3%),
vanced disease) were present in 248 (46.7%) patients. Analy- 58 (4.8%), and 2 (0.3%) patients from low, lower-middle, upper-
sis of patients who had only leukocoria and/or strabismus middle, and high income–level countries, respectively
(ie, early disease) as the symptoms noticed by the parents, but (z score = 11.9, dim = 4; P < .001). Higher economic grouping
who presented to retinoblastoma treatment centers with symp- was associated with higher proportions of intraocular and
toms of advanced disease, showed a significantly larger pro- earlier stage disease at diagnosis (Table 1).
portion coming from LICs (z score = 18.4, dim = 4; P < .001; ad-
ditional analysis is provided in eTable 4 in the Supplement). Risk Factors for Advanced Disease
at Time of Diagnosis
Age at Diagnosis Sex (χ 21 = 1.016; P = .31), bilaterality (χ 21 = 0.830; P = .36) and
The overall median age at diagnosis was 23.5 months (interquar- familial history of retinoblastoma (χ 21 = 2.269; P = .13) were
tile range [IQR], 11.2-36.5 months; Table 1). The median age at di- found to be nonsignificant factors for the prediction of cT4 cat-
agnosis of patients from LICs was 30.5 months (IQR, 18.3-45.9 egory (extraocular retinoblastoma) and hence were removed
months) compared with 14.0 months (IQR, 6.2-26.6 months) for from the model. On logistic regression, low-income level and
patients from HICs. There was a significant association between older presentation age were found to be independent and
presentationageandnationalincomelevel,withchildreninLMICs significant predictive factors for advanced disease (Table 2).
presenting at an older age (eTable 5 in the Supplement).
Familial History and Bilateral Retinoblastoma
Tumor Staging Familial history of retinoblastoma was reported in 199 of 4215
Globally, the most common cTNM stages were cT3 (n = 1933 (4.7%) patients (15 [3.1%], 75 [4.0%], 54 [4.5%], and 55 [8.4%]
of 4114 [47.0%]), N0 (n = 3303 of 4281 [77.2%]), and patients from low, lower-middle, upper-middle, and high
jamaoncology.com (Reprinted) JAMA Oncology May 2020 Volume 6, Number 5 687

Table 1. Clinical Characteristics at Presentation of 4351 New Patients With Retinoblastoma Diagnosed in 2017
National Income Level, No. (% within the national income level)
[% within the evaluated parameter]
Signifi- P
Parameter Low Lower-Middle Upper-Middle High Total, No. (%) cance Value
Age at diagnosis,
median (IQR), mo
Total sample 30.5 (18.3-45.9) 24.4 (12.2-37.3) 20.7 (10.1-33.8) 14.0 (6.2-26.6) 23.5 (11.2-36.5)
Unilateral 35.0 (22.2-48.0) 29.1 (18.1-42.9) 25.5 (12.9-37.6) 19.7 (9.0-32.4) 27.1 (15.0-41.0)
ρ: −0.22 <.001a
Bilateral 22.9 (11.8-32.8) 14.4 (8.0-25.8) 11.4 (6.0-21.0) 8.1 (3.7-15.8) 12.3 (6.1-24.3)
Reported cases, No. (%) 524/533 (98.3) 1909/1940 (98.4) 1192/1212 (98.3) 664/666 (99.7) 4289/4351 (98.6)
Laterality at diagnosisb
Unilateral 408 (76.5) [13.6] 1325 (68.3) [44.0] 847 (69.9) [28.1] 430 (64.6) [14.3] 3010/4351 (69.2)
NA <.001c
Bilateral 125 (23.5) [9.3] 615 (31.7) [45.9] 365 (30.1) [27.2] 236 (35.4) [17.6] 1341/4351 (30.8)
Familial history of
retinoblastoma
No 467 (96.9) [11.6] 1805 (96.0) [44.9] 1141 (95.5) [28.4] 603 (91.6) [15.0] 4016/4215 (95.3)
z score:
Yes 15 (3.1) [7.5] 75 (4.0) [37.7] 54 (4.5) [27.1] 55 (8.4) [27.6] 199/4215 (4.7) −4.3, <.001d
dim: 4
Total, No. (%) 482/533 (90.4) 1880/1940 (96.9) 1195/1212 (98.6) 658/666 (98.8) 4215/4351 (96.9)
Primary tumor
cT1 5 (1.0) [1.8] 96 (5.1) [35.3] 67 (6.1) [24.6] 104 (15.9) [38.2] 272/4114 (6.7)
cT2 62 (12.6) [4.9] 406 (21.7) [31.8] 482 (44.1) [37.8] 326 (49.7) [25.5] 1276/4114 (31.0)
z score:
cT3 209 (42.6) [10.8] 1013 (54.1) [52.4] 488 (44.6) [25.2] 223 (34.0) [11.5] 1933/4114 (47.0) 22.3, <.001e
dim: 4
cT4 215 (43.8) [34.0] 359 (19.2) [56.7] 56 (5.1) [8.8] 3 (0.4) [0.4] 633/4114 (15.4)
Total, No. (%) 491/533 (92.1) 1874/1940 (96.6) 1093/1212 (90.2) 656/666 (98.5) 4114/4351 (94.6)
Regional lymph node
NX 105 (20.7) [12.6] 350 (18.4) [42.1] 267 (22.2) [32.1] 109 (16.4) [13.1] 831/4281 (19.4)
N0 360 (71.0) [10.9] 1475 (77.3) [44.7] 912 (75.9) [27.6] 556 (83.6) [16.8] 3303/4281 (77.2) z score:
8.3, dim: <.001f
N1 42 (8.3) [28.6] 82 (4.3) [55.8] 23 (1.9) [15.6] 0 147/4281 (3.4) 4
Total, No. (%) 507/533 (95.1) 1907/1940 (98.3) 1202/1212 (99.2) 665/666 (99.8) 4281/4352 (98.4)
Distant metastasis
M0 404 (81.1) [10.2] 1749 (91.8) [44.1] 1147 (95.2) [28.9] 664 (99.7) [16.8] 3964/4275 (92.7)
cM1 65 (13.1) [30.4] 110 (5.8) [51.4] 39 (3.2) [18.2] 0 214/4275 (5.0) z score:
11.9, <.001g
pM1 29 (5.8) [29.9] 47 (2.5) [48.5] 19 (1.6) [19.6] 2 (0.3) [2.1] 97/4275 (2.3) dim: 4
Total, No. (%) 498/533 (89.1) 1906/1940 (98.2) 1205/1212 (99.4) 666/666 (100) 4275/4351 (98.3)
Hereditary trait
HX 360 (72.7) [14.2] 1211 (63.8) [47.9] 736 (61.6) [29.1] 221 (33.4) [8.7] 2528/4250 (59.5)
H0 0 44 (2.3) [17.3] 59 (4.9) [23.2] 151 (22.8) [59.4] 254/4250 (6.0)
NA NA
H1 135 (27.3) [9.2] 643 (33.9) [43.8] 400 (33.5) [27.2] 290 (43.8) [19.8] 1468/4250 (34.5)
Total, No. (%) 495/533 (92.9) 1898/1940 (97.8) 1195/1212 (98.6) 662/666 (99.4) 4250/4351 (97.7)
Extraocular retinoblastoma
No 265 (50.9) [7.8] 1393 (73.0) [41.3] 1062 (88.0) [31.5] 656 (98.5) [19.4] 3376/4302 (78.5)
z score:
Yes 256 (49.1) [27.6] 515 (27.0) [55.6] 145 (12.0) [15.7] 10 (1.5) [1.1] 926/4302 (21.5) 21.8, <.001h
dim: 4
Total, No. (%) 521/533 (97.7) 1908/1940 (98.4) 1207/1212 (99.6) 666/666 (100) 4302/4351 (98.9)
International Retinoblastoma
Staging System
Stage 0 44 (8.7) [3.0] 459 (24.2) [31.3] 585 (48.8) [39.9] 378 (56.8) [25.8] 1466/4264 (34.4)
Stage I 170 (33.8) [1.0] 816 (43.0) [47.9] 444 (37.0) [26.1] 272 (40.8) [16.0] 1702/4264 (39.9)
Stage II 58 (11.5) [27.2] 111 (5.9) [52.1] 40 (3.3) [18.8] 4 (0.6) [1.9] 213/4264 (5.0)
Stage III 101 (20.1) [26.1] 242 (12.8) [62.5] 41 (3.4) [10.6] 3 (0.5) [0.7] 387/4264 (9.1) NA NA
Stage IV 94 (18.7) [29.9] 157 (8.3) [50.0] 60 (5.0) [19.1] 3 (0.5) [1.0] 314/4264 (7.4)
NA 36 (7.2) [19.8] 111 (5.9) [61.0] 29 (2.4) [15.9] 6 (0.9) [3.3] 182/4264 (4.3)
Total, No. (%) 503/533 (94.4) 1896/1940 (97.7) 1199/1212 (98.9) 666/666 (100) 4264/4351 (98.0)
e
Abbreviations: IQR, interquartile range; NA, not applicable. Cochran-Armitage test for proportion of cT3 or greater.
a f
Spearman rank correlation. Cochran-Armitage test for proportion of cases with lymph node involvement.
b g
Inclusion criteria: 100% reporting. Cochran-Armitage test for proportion of cases with distant metastasis.
c h
Fisher exact test for proportion of bilateral cases. Cochran-Armitage test for proportion of cases with extraocular disease.
d
Cochran-Armitage test for proportion of familial history of retinoblastoma.

Table 2. Logistic Regression Analysis: Predictors of Advanced Disease at Presentationa,b
Variable B (SE) Corrected P Value Odds Ratio (95% CI)

Income level
a
Low vs (upper-middle + high) 2.886 (0.166) <.001 17.92 (12.94-24.80) The logistic regression model was
statistically significant (χ 42 = 727.27;
Low-middle vs (upper-middle + high) 1.748 (0.148) <.001 5.74 (4.30-7.68)
P < .001). The model explained
Age at diagnosis 28.5% (Nagelkerke R2) of the
14.27-31.20 mo 1.343 (0.167) <.001 3.83 (2.76-5.31) variance and correctly classified
85.1% of cases. Area under the
>31.20 mo 2.026 (0.160) <.001 7.58 (5.54-10.38)
curve was 0.813.
Constant −4.602 (0.190) <.001 0.01 b
Advanced disease is defined as cT4.
income–level countries, respectively). Bilateral disease at time for retinoblastoma, which, if detected early, can be cured. These
of diagnosis was seen in 1341 of 4351 (30.8%) patients (125 findings are consistent with a recent study of global disease
[23.5%], 615 [31.7%], 365 [30.1%], and 236 [35.4%] patients from burden that found that cancer among 0- to 4-year-olds ac-
low, lower-middle, upper-middle, and high income–level coun- counts for 37% of the global disease-adjusted life year; this pro-
tries, respectively) (Table 1). Significantly more familial portional burden is greater in LMICs.26
(z score = −4.3, dim = 4; P < .001) and, independently, more The factors causing delay in retinoblastoma diagnosis and
bilateral cases were seen in HICs compared with LICs. treatment in LMICs are beyond the scope of this study. How-
ever, the findings here suggest that late recognition of signs
Diagnostic Facilities and Treatment Modalities of retinoblastoma, as well as delay in reaching a dedicated reti-
The available diagnostic and treatment modalities are shown noblastoma treatment center once ocular symptoms have been
in eTable 6 in the Supplement. The majority of patients (4201 detected, likely play a role, and both factors are associated with
[96.6%]) were diagnosed in a center that contained resources national income level. These findings indicate clinically sig-
for computed tomography and/or magnetic resonance imaging. nificant progression of signs between parental detection and
A histopathology service was available for 4236 (97.4%) par- presentation to a specialist center in LMICs. Earlier recogni-
ticipants, and intravenous chemotherapy for 4263 (98.0%). tion of leukocoria or strabismus and urgent referral for diag-
nosis is very important if children are to receive treatment
Global Magnitude of Retinoblastoma and before extraocular spread occurs.
Representativeness of the Study A familial history of retinoblastoma followed the same pat-
Given that the mean age at the time of diagnosis was approxi- tern, with relatively fewer cases in lower-income countries. A
mately 2 years old, the 2015 birth rate data were used for cal- possible explanation could be underreporting or inadequate
culation of the number of new retinoblastoma cases.16 Accord- medical record keeping in resource-limited settings. How-
ing to these data, the predicted annual number of new ever, a more plausible explanation would be that children with
retinoblastoma cases worldwide ranged from 7752 to 8914. familial history of disease are diagnosed and treated early in
Using an average incidence figure of 1 of 17 000 live births, cap- HICs so that they survive to childbearing age, whereas this may
ture rates were 88.2%, 56.5%, 48.7%, and 39.9% of expected not be the case in LMICs.
cases from high, upper-middle, lower-middle, and low- Nearly all essential diagnostic and therapeutic modali-
income countries, respectively. No data were received from 65 ties were available in most participating treatment centers.
countries and principalities, mainly with small populations; Enucleation surgery, which was available in all treatment cen-
the estimated number of missing cases from these countries ters, can save lives, and intravenous chemotherapy, which was
was 46. available for 98.0% of the patients in this study, can save lives
and also result in globe salvage if patients are diagnosed and
treated in time.27,28
The results of this study point to an urgent need to im-
Discussion prove retinoblastoma detection and access to treatment in
Findings of this study show a large disparity in the presenta- LMICs. Several initiatives are addressing this challenge by
tion patterns of retinoblastoma between HICs and LMICs. A implementing twinning programs that link centers from higher-
total of 666 children were from HICs, 99% of whom had at the resource and lower-resource countries.12,29-32 However, there
time of diagnosis a tumor confined to the eye and thus a fa- is a pressing need for coordinated action on a global level. In a
vorable prognosis. In comparison, of the 3685 patients from rare yet curable cancer such as retinoblastoma, with approxi-
LMICs, 25% were diagnosed with tumor spread beyond the mately 8000 new patients annually worldwide, such an ac-
globe, for which the prognosis is much worse.19,20 It is likely tion is feasible to make retinoblastoma a zero-death cancer.33
that the real gap in the pattern of retinoblastoma presenta- The World Health Organization Global Initiative for Child-
tion is even wider owing to unreported patients in LICs who hood Cancer aims to raise survival for key childhood cancers,
never arrived at a retinoblastoma treatment center and for including retinoblastoma, to 60% by the year 2030 by help-
whom death from metastatic disease is inevitable. ing health systems in LMICs integrate childhood cancer into
Late cancer diagnosis, also in the pediatric population, is their national strategies and improve their capacity to diag-
a major issue in LMICs.21-25 This study confirms this finding nose and deliver curative treatment.34 In this context, accu-

rate retinoblastoma-specific data are essential. The results of data collection was mostly retrospective, with the exception
this study serve as a report of the current retinoblastoma pre- of treatment centers that were recruited early in 2017. How-
sentation status, against which future interventions can be ever, the simplicity of the study design and quality assurance
measured, and demonstrate the need for a strong global part- process enabled the collection of almost complete data, also
nership to improve outcomes for patients with retinoblas- from LMICs. Third, the socioeconomic status of individual
toma everywhere. families was not included as a variable, and the national
Results of the present study showed that older age at pre- income level was used as a surrogate, an approach that as-
sentation and, independently, national income level were as- sumes that all families from the same country are of the same
sociated with advanced disease, which suggests that other fac- socioeconomic level.
tors besides age may be important in disease progression. It
has been suggested that infection by the human papillomavi-
rus, which is more prevalent in LMICs, is associated with the
development of nonhereditary retinoblastoma, and it is pos-
Conclusions
sible that this could be associated with more aggressive dis- The findings of this cross-sectional global analysis of retino-
ease behavior.35 Another possible explanation relates to the blastoma at the time of diagnosis revealed important differ-
genetic landscape of retinoblastoma and especially to cases ences in presentation among patients from different coun-
with no RB1 mutation but a high level of amplification of the tries, depending on their national income level. Patients with
oncogene MYCN.36 These cases are unilateral, develop at an retinoblastoma from HICs present with early disease and are,
early age, and show aggressive features. They were found only therefore, likely to survive. In contrast, patients from lower-
in 1.4% of unilateral retinoblastoma cases, all from cohorts in income settings present with late disease, many with extraocu-
HICs,36 but have not been evaluated in patients from LICs. No- lar extension and some already with metastasis, and their prog-
tably, in the present study, there were substantially more uni- nosis is poorer. A familial history of retinoblastoma is relatively
lateral cases in LICs as compared with other income levels, in uncommon in lower-income countries, likely owing to death
keeping with the above-mentioned hypotheses. However, related to late-disease presentation before childbearing years.
these speculations, warrant further studies. A surprise finding of this study is that more advanced disease
at presentation in lower-income countries is not entirely ex-
Limitations plained by older age. Further research is warranted to investi-
This study has several limitations. First, it included a conve- gate what factors other than age play a role in disease progres-
nience sample and therefore had an inherent potential bias. sion in low-income settings. Prompt action at national and
Nevertheless, to our knowledge, it is the largest and most geo- international levels is warranted to improve health education
graphically comprehensive study in the field of retinoblas- about retinoblastoma, as well as access to early diagnosis and
toma, and we believe its findings can be generalized. Second, treatment in retinoblastoma treatment centers in LMICs.
ARTICLE INFORMATION Al-Mafrachi, FIBMS; Argentino A. Almeida, MD; Codruta Comsa, MD; Zelia M. Correa, MD, PhD; Maria
Accepted for Publication: November 13, 2019. Khalifa M. Alsawidi, MD; Athar A. S. M. Al-Shaheen, G. Correa Llano, MD; Timothy W. Corson, PhD; Kristin
MD; Entissar H. Al-Shammary, MD; Primawita O. E. Cowan-Lyn, MD, MBBS; Monika Csóka, MD, PhD;
Open Access: This is an open access article Amiruddin, MD; Romanzo Antonino, MD; Nicholas J. Xuehao Cui, MS; Isac V. Da Gama, MD; Wantanee
distributed under the terms of the CC-BY License. Astbury, FRCS, FRCOphth; Hatice T. Atalay, MD; Dangboon, MD; Anirban Das, MD; Sima Das, MS;
© 2020 Global Retinoblastoma Study Group. La-ongsri Atchaneeyasakul, MD; Rose Atsiaya, OCO; Jacquelyn M. Davanzo, BSN, BSPH; Alan Davidson,
JAMA Oncology. Taweevat Attaseth, MD; Than H. Aung, MRCSEd; MBChB, MPhil; Patrick De Potter, MD, PhD; Karina Q.
Published Online: February 27, 2020. Silvia Ayala; Baglan Baizakova, MD; Julia Balaguer, Delgado, MD, PhD; Hakan Demirci, MD; Laurence
doi:10.1001/jamaoncol.2019.6716 MD, PhD; Ruhengiz Balayeva, PhD; Walentyna Desjardins; Rosdali Y. Diaz Coronado, MD; Helen
Correction: This article was corrected September Balwierz, MD; Honorio Barranco, MD, PhD; Dimaras, PhD; Andrew J. Dodgshun, MPhil; Craig
24, 2020, to fix an error in a coauthor’s name. Covadonga Bascaran, MD, MSc; Maja Beck Popovic, Donaldson, MD, FRANZCO; Carla R. Donato Macedo,
MD; Raquel Benavides, MD; Sarra Benmiloud, MD; MD; Monica D. Dragomir, MD, PhD; Yi Du, MD;
The Global Retinoblastoma Study Group Authors: Nissrine Bennani Guebessi, MD, PhD; Rokia C. Berete, Magritha Du Bruyn, MD; Kemala S. Edison, MD;
The following investigators take authorship MD, PhD; Jesse L. Berry, MD; Anirban Bhaduri, MS; I. Wayan Eka Sutyawan, MD; Asmaa El Kettani, MD;
responsibility for the study results: Ido Didi Fabian, Sunil Bhat, MD; Shelley J. Biddulph, FCOph; Eva M. Amal M. Elbahi, MD; James E. Elder, MBBS; Dina
MD; Elhassan Abdallah, MD; Shehu U. Abdullahi, MD; Biewald, MD; Nadia Bobrova, MD; Marianna Boehme; Elgalaly, BPh; Alaa M. Elhaddad, MD, PhD; Moawia M.
Rula A. Abdulqader, MD; Sahadatou Adamou H.C. Boldt, MD; Maria Teresa B. C. Bonanomi, MD, Ali Elhassan, MD; Mahmoud M. Elzembely, MD; Vera
Boubacar, MD; Dupe S. Ademola-Popoola, FMCOph, PhD; Norbert Bornfeld, MD; Gabrielle C. Bouda, MD; A. Essuman, FWACS; Ted Grimbert A. Evina, MD;
FWACS; Adedayo Adio, FWACS; Armin R. Afshar, MD; Hédi Bouguila, MD, PhD; Amaria Boumedane, MD; Zehra Fadoo, MBBS; Adriana C. Fandiño, MD;
Priyanka Aggarwal, MD; Ada E. Aghaji, MSc, FMCOph; Rachel C. Brennan, MD; Bénédicte G. Brichard, MD, Mohammad Faranoush, MD; Oluyemi Fasina, FWACS;
Alia Ahmad, MRCPCH; Marliyanti N. R. Akib, MD; PhD; Jassada Buaboonnam, MD; Patricia Delia D. P. G. Fernández, MSc; Ana Fernández-Teijeiro,
Lamis Al Harby, MD; Mouroge H. Al Ani, MD; Aygun Calderón-Sotelo, MD; Doris A. Calle Jara, MD; Jayne E. MD, PhD; Allen Foster, FRCOphth; Shahar Frenkel,
Alakbarova, MD; Silvia Alarcón Portabella, MD; Safaa Camuglia, FRANZCO; Miriam R. Cano, MD, MSc; MD, PhD; Ligia D. Fu, MD; Soad L. Fuentes-Alabi, MD,
A. F. Al-Badri, MD; Ana Patricia A. Alcasabas, MD; Michael Capra, FRCPI; Nathalie Cassoux, MD, PhD; MPH; Brenda L. Gallie, MD; Moira Gandiwa, MD; Juan
Saad A. Al-Dahmash, MD; Amanda Alejos, MD; Guilherme Castela, MD; Luis Castillo, MD; Jaume L. Garcia, MSc; David García Aldana, MD; Pascale Y.
Ernesto Alemany-Rubio, MD; Amadou I. Alfa Bio, MD; Català-Mora, MD, PhD; Guillermo L. Chantada, MD, Gassant, MD; Jennifer A. Geel, MBChB, MMed; Fariba
Yvania Alfonso Carreras, MD; Christiane Al-Haddad, PhD; Shabana Chaudhry, MD; Sonal S. Chaugule, MD; Ghassemi, MD; Ana V. Girón, MD; Zelalem Gizachew,
MD; Hamoud H. Y. Al-Hussaini, MD, MSc; Amany M. Argudit Chauhan, BA; Bhavna Chawla, MD; Violeta S. MD; Marco A. Goenz, MD; Aaron S. Gold, OD; Maya
Ali, MD; Donjeta B. Alia, MD; Mazin F. Al-Jadiry, MD; Chernodrinska, MD, PhD; Faraja S. Chiwanga, MSc; Goldberg-Lavid, MD; Glen A. Gole, MD, FRANZCO;
Usama Al-Jumaly, MD; Hind M. Alkatan, MD; Tsengelmaa Chuluunbat, MD, PhD; Krzysztof Cieslik, Nir Gomel, MD; Efren Gonzalez, MD; Graciela
Charlotta All-Eriksson, MD, PhD; Ali A. R. M. MD; Ruellyn L. Cockcroft, MB, ChB, MMedPaed; Gonzalez Perez, MD; Liudmira González-Rodríguez,

MD; Henry N. Garcia Pacheco, MD; Jaime Graells, MD; Ghislaine Obono-Obiang, MD; Ngozi C. Oguego, MB, Wiwatwongwana, MD; Damrong Wiwatwongwana,
Liz Green, MBA; Pernille A. Gregersen, MD; BS, FWASC, FAEH; Andrzej Olechowski, MD; Scott C. MD; Charlotte Wolley Dod, MD; Phanthipha
Nathalia D. A. K. Grigorovski, MD; Koffi M. Guedenon, N. Oliver, MD; Peter Osei-Bonsu, MD, FWACS; Diego Wongwai, MD, PhD; Daoman Xiang, MD, PhD;
MD; D. Sanjeeva Gunasekera, MD; Ahmet K. Gündüz, Ossandon, MD; Manuel A. Paez-Escamilla, MD; Yishuang Xiao, MSc; Jason C. Yam, FRCSEd;
MD; Himika Gupta, MD; Sanjiv Gupta, MS; Theodora Halimah Pagarra, MD, PhD; Sally L Painter, FRCOphth; Huasheng Yang, MD; Jenny M. Yanga, MD;
Hadjistilianou, MD; Patrick Hamel, MD; Syed A. Vivian Paintsil, FWACP; Luisa Paiva, MD; Bikramjit P. Muhammad A Yaqub, MD, FCPS, FRCSEd; Vera A.
Hamid, FCPS; Norhafizah Hamzah, MSc; Eric D. Pal, FECF, FICO; Mahesh Shanmugam Palanivelu, Yarovaya, MD; Andrey A. Yarovoy, MD, PhD; Huijing
Hansen, MD; J. William Harbour, MD; M. Elizabeth FRCSED; Ruzanna Papyan, MD; Raffaele Parrozzani, Ye, MD; Yacoub A. Yousef, MD; Putu Yuliawati, MD;
Hartnett, MD; Murat Hasanreisoglu, MD; Sadiq MD, PhD; Manoj Parulekar, MS, FRCOphth; Claudia R. Arturo M. Zapata López, MD; Ekhtelbenina Zein, MD;
Hassan, MD, FWACS; Shadab Hassan, FRCS, FCPS; Pascual Morales, MD; Katherine E. Paton, MD, FRCSC; Chengyue Zhang, MD; Yi Zhang, MD, PhD; Junyang
Stanislava Hederova, MD; Jose Hernandez, MD; Katarzyna Pawinska-Wasikowska, MD, PhD; Jacob Zhao, MD; Xiaoyu Zheng, MD; Katsiaryna Zhilyaeva,
Lorelay Marie Carcamo Hernandez, MD; Laila Pe'er, MD; Armando Peña, MD; Sanja Perić, MD, PhD; MD; Nida Zia, MBBS, MCPS; Othman A. O. Ziko, MD,
Hessissen, MD; Diriba F. Hordofa, MD; Laura C. Chau T. M. Pham, MD; Remezo Philbert, MD; David A. PhD; Marcia Zondervan, MBA; Richard Bowman,
Huang, MD; G. B. Hubbard, MD; Marlies Hummlen, Plager, MD; Pavel Pochop, MD, PhD; Rodrigo A. FRCOphth.
MD; Kristina Husakova, MD; Allawi N. Hussein Polania, MD; Vladimir G. Polyakov, MD; Manca T. Affiliations of The Global Retinoblastoma Study
Al-Janabi, MD; Russo Ida, MD; Vesna R. Ilic, MD; Pompe, MD, PhD; Jonathan J. Pons, MD; Daphna Group Authors: International Centre for Eye Health,
Vivekaraj Jairaj, DNB; Irfan Jeeva, FRCOphth; Helen Prat, MD; Vireak Prom, MD; Ignatius Purwanto, BS; London School of Hygiene & Tropical Medicine,
Jenkinson, MD, PhD; Xunda Ji, MD; Dong Hyun Jo, Ali O. Qadir, MD; Seema Qayyum, FCPS; Jiang Qian, London, United Kingdom (Fabian, Astbury, Bascaran,
MD, PhD; Kenneth P. Johnson, MD; William J. MD; Ardizal Rahman, MD; Salman Rahman, MD; Foster, Zondervan, Bowman); The Goldschleger Eye
Johnson, MD; Michael M. Jones, MD, PhD, FRANZCO; Jamalia Rahmat, MD; Purnima Rajkarnikar, MD; Institute, Sheba Medical Center, Tel Hashomer,
Theophile B. Amani Kabesha, MD, PhD; Rolande L. Rajesh Ramanjulu, MD; Aparna Ramasubramanian, Tel Aviv University, Tel Aviv, Israel (Fabian, Prat,
Kabore, MD; Swathi Kaliki, MD; Abubakar Kalinaki, MD; Marco A. Ramirez-Ortiz, MD, MPH; Léa Raobela, Vishnevskia-Dai); Ophthalmology Department of
MD; Mehmet Kantar, MD; Ling-Yuh Kao, MD; Tamar MD; Riffat Rashid, MS; M. Ashwin Reddy, FRCOphth; Rabat, Mohammed V University, Rabat, Morocco
Kardava, PhD; Rejin Kebudi, MD; Tomas Kepak, MD; Ehud Reich, MD; Lorna A. Renner, FRCPCH; David (Abdallah); Aminu Kano Teaching Hospital, Bayero
Naama Keren-Froim, BMedSc; Zohora J. Khan, MD; Reynders, MD; Dahiru Ribadu, FMCOph; Mussagy M. University, Kano, Nigeria (Abdullahi, Sadiq Hassan,
Hussain A. Khaqan, MD; Phara Khauv, MD; Wajiha J. Riheia, MD; Petra Ritter-Sovinz, MD; Duangnate Umar); Basra Children’s Specialty Hospital, Basra, Iraq
Kheir, MD; Vikas Khetan, FRCS; Alireza Khodabande, Rojanaporn, MD; Livia Romero, MD; Soma R. Roy, (Abdulqader, Al-Shaheen); National Hospital of
MD; Zaza Khotenashvili, MD; Jonathan W. Kim, MD; DCO; Raya H. Saab, MD; Svetlana Saakyan, MD, PhD; Niamey, Niamey, Niger (Adamou Boubacar);
Jeong Hun Kim, MD, PhD; Hayyam Kiratli, MD; Tero T. Ahmed H Sabhan, MD; Mandeep S. Sagoo, FRCS(Ed); University of Ilorin Teaching Hospital, University of
Kivelä, MD; Artur Klett, MD, PhD; Jess Elio Kosh Azza M. A. Said, MD; Rohit Saiju, MD; Beatriz Salas, Ilorin, Ilorin, Nigeria (Ademola-Popoola); Department
Komba Palet, MD; Dalia Krivaitiene, MD, PhD; MD; Sonsoles San Román Pacheco, MD; Gissela L. of Ophthalmology, University of Port Harcourt
Mariana Kruger, MMedPaed, PhD; Kittisak Kulvichit, Sánchez, MD; Phayvanh Sayalith, MD; Trish A. Teaching Hospital, Port Harcourt, Nigeria (Adio);
MD; Mayasari W. Kuntorini, MD; Alice Kyara, BA; Eva Scanlan, MRCPI, MSc; Amy C. Schefler, MD; Judy University of California, San Francisco (Afshar, S.
S. Lachmann, MD; Carol P. S. Lam, FCOphth; Geoffrey Schoeman, MSc; Ahad Sedaghat, MD; Stefan Rahman); Department of Pediatrics, Banaras Hindu
C. Lam, FRANZCO; Scott A. Larson, MD; Slobodanka Seregard, MD, PhD; Rachna Seth, DNB MNAMS; University, Varanasi, India (Aggarwal); Department of
Latinović, MD, PhD; Kelly D. Laurenti, MD; Bao Han A. Ankoor S. Shah, MD, PhD; Shawkat A. Shakoor, MS; Ophthalmology, College of Medicine, University of
Le, MD; Karin Lecuona, MD; Amy A. Leverant, MD; Manoj K. Sharma, MD; Sadik T. Sherief, MD; Nandan Nigeria, Enugu, Nigeria (Aghaji, Oguego); The
Cairui Li, MD; Ben Limbu, MD; Quah Boon Long, G. Shetye, MS; Carol L. Shields, MD; Sorath Noorani Children’s Hospital and the Institute of Child Health,
FRCS(Ed), MMedOphth; Juan P. López, MD; Robert Siddiqui, MD; Sidi Sidi Cheikh, MD, PhD; Sónia Silva, Lahore, Pakistan (Ahmad, Mushtaq, Qayyum);
M. Lukamba, MD; Livia Lumbroso, MD; Sandra MD; Arun D. Singh, MD; Niharika Singh, MS; Usha RS Dr Wahidin Sudirohusodo, Makassar, Indonesia
Luna-Fineman, MD; Delfitri Lutfi, MD; Lesia Lysytsia, Singh, MS; Penny Singha, MD; Rita S. Sitorus, MD, (Akib, Pagarra); The Royal London Hospital, Barts
MD; George N. Magrath, MD; Amita Mahajan, MD; PhD; Alison H. Skalet, MD, PhD; Hendrian D. Health NHS Trust, and Moorfields Eye Hospital NHS
Abdul Rahim Majeed, MPPA; Erika Maka, MD; Mayuri Soebagjo, MD, PhD; Tetyana Sorochynska, MD, PhD; Foundation Trust, London, United Kingdom (Al
Makan, MD; Emil K. Makimbetov, MD; Chatonda Grace Ssali, MD; Andrew W. Stacey, MD; Sandra E. Harby, Reddy); Hawler Medical University, Erbil, Iraq
Manda, MMedOphth; Nieves Martín Begue, MD, PhD; Staffieri, PhD; Erin D. Stahl, MD; Christina (Al Ani); Zarifa Aliyeva National Center of
Lauren Mason, MBA; John O. Mason III, MD; Ibrahim Stathopoulos, MD; Branka Stirn Kranjc, MD, PhD; Ophthalmology, Baku, Azerbaijan (Alakbarova,
O. Matende, MD, MMedOphth; Miguel Materin, MD; David K. Stones, MBChB, FCPaed; Caron Balayeva); Department of Pediatric Ophthalmology,
Clarissa C. D. S. Mattosinho, MD; Marchelo Matua, Strahlendorf, MD; Maria Estela Coleoni Suarez, MD; Hospital Vall d’Hebron, Barcelona, Spain (Portabella,
BAPH; Ismail Mayet, MD; Freddy B. Mbumba, MD, Sadia Sultana, FCPS; Xiantao Sun, MD; Meryl Sundy, Martín Begue, Wolley Dod); Pediatric Oncology Unit,
MMedPaed; John D. McKenzie, MD; Aurora MD; Rosanne Superstein, MD; Eddy Supriyadi, MD, Children Welfare Teaching Hospital, College of
Medina-Sanson, MD, PhD; Azim Mehrvar, MD; PhD; Supawan Surukrattanaskul, MD; Shigenobu Medicine, University of Baghdad, Baghdad, Iraq
Aemero A. Mengesha, MD; Vikas Menon, MD; Suzuki, MD, PhD; Karel Svojgr, MD, PhD; Fatoumata (Al-Badri, Al-Jadiry, Sabhan); Philippine General
Gary John V. D. Mercado, MD; Marilyn B. Mets, MD; Sylla, MD; Gevorg Tamamyan, MD, PhD; Deborah Tan, Hospital, University of the Philippines, Manila,
Edoardo Midena, MD, PhD; Divyansh K. C. Mishra, MBBS; Alketa Tandili, MD, PhD; Fanny F. Tarrillo Leiva, Philippines (Alcasabas, Mercado); College of
DNB; Furahini G. Mndeme, MD; Ahmed A. MD; Maryam Tashvighi, MD; Bekim Tateshi, MD, PhD; Medicine, King Saud University, Riyadh, Saudi Arabia
Mohamedani, FRCPath; Mona T. Mohammad, MD, Edi S. Tehuteru, MD; Luiz F. Teixeira, MD; Kok Hoi Teh, (Al-Dahmash, Alkatan); Unidad Nacional de
FRCS; Annette C. Moll, MD, PhD; Margarita M. MD; Tuyisabe Theophile, MSc; Helen Toledano, Oncología Pediátrica, Guatemala City, Guatemala
Montero, MD; Rosa A. Morales, MD; Claude Moreira, MBChB; Doan L. Trang, MD; Fousseyni Traoré, MD; (Alejos, Girón); Instituto Cubano de Oftalmología
MD, PhD; Prithvi Mruthyunjaya, MD, MHS; Mchikirwa Sumalin Trichaiyaporn, MD; Samuray Tuncer, MD; Ramón Pando Ferrer, Marianao, Havana, Cuba
S. Msina, MMedOphth; Gerald Msukwa, Harba Tyau-Tyau, MD; Ali B. Umar, MD, FMCPath; (Alemany-Rubio, González-Rodríguez); University of
MMedOphth; Sangeeta S. Mudaliar, DNBPediatric; Emel Unal, MD; Ogul E. Uner, BA; Steen F. Urbak, MD, Parakou, Parakou, Benin (Alfa Bio); St Damien
Kangwa I. Muma, MMedOphth, FCOphth; Francis L. PhD; Tatiana L. Ushakova, MD; Rustam H. Usmanov, Pediatric Hospital, Port-au-Prince, Haiti (Alfonso
Munier, MD; Gabriela Murgoi, MD; Timothy G. MD; Sandra Valeina, MD; Milo van Hoefen Wijsard, Carreras, Gassant); Department of Ophthalmology,
Murray, MD, MBA; Kareem O. Musa, FWACS, MD; Adisai Varadisai, MD; Liliana Vasquez, MD; Leon American University of Beirut Medical Center, Beirut,
FMCOphth, FICO; Asma Mushtaq, MD; Hamzah O. Vaughan, FRCS(Ed); Nevyana V. Veleva-Krasteva, Lebanon (Al-Haddad); Pediatric Oncology
Mustak, MD; Okwen M. Muyen, MD; Gita Naidu, MD, PhD; Nishant Verma, MD; Andi A. Victor, MD, Department, National Oncology Center, Sana’a,
MMedPaed, PhD; Akshay Gopinathan Nair, MD; PhD; Maris Viksnins, MD; Edwin G. Villacís Chafla, Yemen (Al-Hussaini); Pediatric Oncology
Larisa Naumenko, MD, PhD; Paule Aïda Ndoye Roth, MD; Vicktoria Vishnevskia-Dai, MD; Tushar Vora, MD; Department, South Egypt Cancer Institute, Assiut
MD, PhD; Yetty M. Nency, MD; Vladimir Neroev, MD, Antonio E. Wachtel, MD; Werner Wackernagel, MD; University, Assiut, Egypt (Ali, Elzembely); University
PhD; Hang Ngo, MD; Rosa M. Nieves, MD; Marina Keith Waddell, DM, FRCP, FRCS, FRCOphth; Patricia Hospital Center Mother Theresa, Tirana, Albania (Alia,
Nikitovic, MD, PhD; Elizabeth D. Nkanga, FMCOph; D. Wade, MBBS; Amina H. Wali, MD, FMCOph; Tandili); Imam Hussein Cancer Center, Karbala, Iraq
Henry Nkumbe, MD; Murtuza Nuruddin, FRCS; Yi-Zhuo Wang, MD; Avery Weiss, MD; Matthew W. (Al-Jumaily); St Erik Eye Hospital, Stockholn, Sweden
Mutale Nyaywa, MD, MMedOphth, FCOphth; Wilson, MD; Amelia D. C. Wime, MD; Atchareeya (All-Eriksson, Seregard); Ibn Al Haitham Teaching Eye

Hospital, Baghdad, Iraq (Al-Mafrachi); Beira Central (Castela, Silva); Hospital Pereira Rossell, Montevideo, A. Rahman); Department of Ophthalmology, Faculty
Hospital, Beira, Mozambique (Almeida); Tripoli Eye Uruguay (Castillo); Hospital Sant Joan de Déu, of Medicine, Udayana University, Sanglah Eye
Hospital, University of Tripoli, Tripoli, Libya (Alsawidi, Barcelona, Spain (Català-Mora, Chantada, Correa Hospital, Bali, Indonesia (Eka Sutyawan, Yuliawati);
Elbahi); Oncology Unit, Child’s Central Teaching Llano); Hospital Garrahan, Buenos Aires, Argentina Department of Ophthalmology, Royal Children’s
Hospital, Baghdad, Iraq (Al-Shammary); National Eye (Chantada, Fandiño); National Scientific and Technical Hospital, Parkville, Victoria, Australia (Elder,
Center, Cicendo Eye Hospital, Bandung, Indonesia Research Council, CONICET, Buenos Aires, Argentina McKenzie, Staffieri); Department of Paediatrics,
(Amiruddin, Kuntorini); Bambino Gesù IRCCS (Chantada); Paediatric Ophthalmology Department, Melbourne Medical School, University of Melbourne,
Children’s Hospital, Rome, Italy (Antonino, Ida); Mayo Hospital and College of Allied Visual Sciences, Parkville, Victoria, Australia (Elder); Children’s Cancer
Department of Ophthalmology, School of Medicine, King Edward Medical University, Lahore, Pakistan Hospital Egypt 57357, Cairo, Egypt (Elgalaly,
Gazi University, Ankara, Turkey (Atalay, (Chaudhry); Department of Ophthalmic Plastic Elhaddad); Department of Oncology, National Cancer
Hasanreisoglu); Siriraj Hospital, Mahidol University, Surgery, Orbit and Ocular Oncology, PBMA’s Institute, University of Gezira, Wadi Madani, Sudan
Bangkok, Thailand (Atchaneeyasakul, Buaboonnam); H. V. Desai Eye Hospital, Pune, Maharashtra, India (Elhassan); Ophthalmology Unit, Department of
Lighthouse For Christ Eye Centre, Mombasa, Kenya (Chaugule); University of Louisville, Louisville, Surgery, School of Medicine and Dentistry, University
(Atsiaya, Matende); Department of Ophthalmology, Kentucky (Chauhan, Ramasubramanian); Ocular of Ghana, Accra, Ghana (Essuman); Magrabi ICO
Faculty of Medicine, Ramathibodi Hospital, Mahidol Oncology Service, Dr Rajendra Prasad Centre for Cameroon Eye Institute, Yaounde, Cameroon (Evina,
University, Bangkok, Thailand (Attaseth, Rojanaporn); Ophthalmic Sciences, All India Institute of Medical Nkumbe); Aga Khan University, Karachi, Pakistan
Yangon Eye Hospital, University of Medicine 1, Sciences, New Delhi, India (Chawla); Eye Clinic, (Fadoo, Jeeva); Pediatric Growth and Development
Yangon, Myanmar (Aung); Retina Consultants of Department of Ophthalmology, University Hospital Research Center, Institute of Endocrinology and
Houston, Houston, Texas (Ayala, Schefler); Scientific Alexandrovska, Medical University, Sofia, Sofia, Metabolism, Iran University of Medical Sciences,
Center of Pediatrics and Pediatric Surgery, Almaty, Bulgaria (Chernodrinska, Veleva-Krasteva); Muhimbili Rasool Akram Hospital, Tehran, Iran (Faranoush);
Kazakhstan (Baizakova); Pediatric Oncology Unit, National Hospital, Dar es Salaam, Tanzania Department of Ophthalmology, University College
Hospital Universitario y Politécnico La Fe, Valencia, (Chiwanga, Kyara, Scanlan); National Center for Hospital, University of Ibadan, Ibadan, Nigeria
Spain (Balaguer, Barranco); Institute of Pediatrics, Maternal and Children Health of Mongolia, (Fasina); Mi Clinic, Ciudad del Este, Paraguay
Jagiellonian University Medical College, Children’s Ulaanbaatar, Mongolia (Chuluunbat); Department of (Fernández); Hospital Universitario Virgen Macarena,
University Hospital of Krakow, Krakow, Poland Ophthalmology, The Children’s Memorial Health Sevilla, Spain (Fernández-Teijeiro); Hadassah Medical
(Balwierz, Pawinska-Wasikowska); Pediatric Institute, Warsaw, Poland (Cieslik, Olechowski); Center, Hebrew University of Jerusalem, Jerusalem,
Hematology-Oncology Unit, Lausanne University Starship Children’s Health, Auckland, New Zealand Israel (Frenkel, Pe'er); Hospital Escuela, Tegucigalpa,
Hospital, Lausanne, Switzerland (Beck Popovic); (Cockcroft); Institute of Oncology, Prof. Dr Al. Honduras (Fu, Peña); Pediatric Oncology
Hospital Nacional de Niños Dr Carlos Sáenz Herrera, Trestioreanu, Bucharest, Romania (Comsa, Dragomir, Department, Benjamin Bloom National Children’s
San Jose, Costa Rica (Benavides); Department of Murgoi); Wilmer Eye Institute, Johns Hopkins Hospital, San Salvador, El Salvador (Fuentes-Alabi,
Pediatric Oncology, University Hassan II Fès, Fez, Medicine, Baltimore, Maryland, and University of Goenz); Lions Sight First Eye Hospital, Queen
Morocco (Benmiloud); Center Hospitalier et Cincinnati College of Medicine, Cincinnati, Ohio Elizabeth Central Hospital, Blantyre, Malawi
Universitaire Ibn Rochd, Casablanca, Morocco (Correa); Indiana University Medical Center, (Gandiwa, Manda, Msukwa); Clínica Anglo American,
(Bennani Guebessi, El Kettani); Ophthalmologic Indianapolis (Corson, Plager); Bustamante Hospital Lima, Perú (Garcia); Servicio Andaluz de Salud,
Department of the Teaching Hospital of Treichville, for Children, Kingston, Jamaica (Cowan-Lyn, Sevilla, Spain (García Aldana); Charlotte Maxeke
Abidjan, Côte d’Ivoire (Berete); Children’s Hospital Vaughan); Semmelweis University, Budapest, Johannesburg Academic Hospital, Johannesburg,
Los Angeles, Keck School of Medicine, University of Hungary (Csóka, Maka); Department of South Africa (Geel); Retina and Vitreous Service,
Southern California, Los Angeles (Berry, J. W. Kim); Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong Farabi Eye Hospital, Tehran University of Medical
The Calcutta Medical Research Institute, Kolkata, University School of Medicine, Shanghai, China Sciences, Tehran, Iran (Ghassemi, Khodabande);
India (Bhaduri); Department of Pediatric Hematology (Cui, Ji); Quelimane Central Hospital, Quelimane, Department of Ophthalmology, School of Medicine,
and Oncology, Narayana Health City, Bangalore, India Mozambique (Da Gama); Department of Addis Ababa University, Addis Ababa, Ethiopia
(Bhat); University of the Witwatersrand, Ophthalmology, Songklanagarind Hospital, Prince of (Gizachew, Sherief); Murray Ocular Oncology and
Johannesburg, South Africa (Biddulph, Mayet, Songkla University, Songkla, Thailand (Dangboon, Retina, Miami, Florida (Gold, Murray); Sackler Faculty
Naidu); Department of Ophthalmology, Essen Singha); Department of Pediatric of Medicine, Tel Aviv University, Tel Aviv, Israel
University Hospital, University Duisburg-Essen, Hematology-Oncology, Tata Medical Center, Kolkata, (Goldberg-Lavid, Keren-Froim); Department of
Essen, Germany (Biewald, Boehme, Bornfeld); The India (A. Das); Ocular Oncology Services, Dr Shroff’s Ophthalmology, Sourasky Medical Center Tel Aviv,
Filatov Institute of Eye Diseases and Tissue Therapy, Charity Eye Hospital, New Delhi, India (S. Das); Cole School of Medicine, Sackler Faculty of Medicine, Tel
Odessa, Ukraine (Bobrova, Sorochynska); Eye Institute, Cleveland Clinic, Cleveland, Ohio Aviv University, Tel Aviv, Israel (Gomel); Department
Department of Ophthalmology and Visual Sciences, (Davanzo, A. D. Singh); Red Cross War Memorial of Ophthalmology, Boston Children’s Hospital and
University of Iowa, Iowa City (Boldt, Larson); Hospital Children’s Hospital and the University of Cape Town, Harvard Medical School, Boston, Massachusetts
das Clínicas da FMUSP, São Paulo, Brazil (Bonanomi); Cape Town, South Africa (Davidson); National (Gonzalez, Shah); Hospital Civil de Guadalajara,
Centre Hospitalier Universitaire Yalgado Ouédraogo Children’s Hospital, Panama City, Panama (Delgado, Guadalajara, Mexico (Gonzalez Perez); Pediatric
de Ouagadougou, Ouagadougou, Burkina Faso L. M. C. Hernandez); Department of Ophthalmology, Oncology Unit, Instituto Regional de Enfermedades
(Bouda, Kabore); Institut Hédi Raïs d’Ophtalmologie, Kellogg Eye Center, University of Michigan, Ann Arbor Neoplásicas del Sur, Arequipa, Perú (Garcia Pacheco);
Faculté de Médecine, Université Tunis El Manar, (Demirci); Institut Curie, Paris, France (Desjardins, Unidad de Oncologia Ocular Hospital Oncologico
Tunis, Tunisia (Bouguila); Etablissement Hospitalière Lumbroso); Instituto Nacional de Enfermedades Luis Razzetti, Caracas, Venezuela (Graells, Romero);
Spécialise Emir Abdelkader CEA Service d’Oncologie Neoplasicas, Lima, Perú (Diaz Coronado, Wachtel, IAM NOOR Eye Care Programme, Afghanistan (Green,
Pédiatrique, Oran, Algeria (Boumedane); Solid Tumor Zapata López); The Hospital for Sick Children, Majeed); Department of Clinical Genetics and Center
Division, Department of Oncology, St. Jude Children’s Toronto, Ontario, Canada (Dimaras, Gallie); for Rare Disorders, Aarhus University Hospital,
Research Hospital, Memphis, Tennessee (Brennan); Department of Paediatrics, University of Otago, Aarhus, Denmark (Gregersen); National Cancer
Cliniques Universitaires Saint-Luc, Brussel, Belgium Christchurch, Children’s Haematology and Oncology Institute, Rio de Janeiro, Brazil (Grigorovski,
(Brichard, De Potter); Hospital Infantil Manuel de Center, Christchurch Hospital, Christchurch, New Mattosinho); Département de Pédiatrie, CHU
Jesús Rivera, Managua, Nicaragua (Calderón-Sotelo, Zealand (Dodgshun); The Children’s Hospital at Sylvanus Olympio, Université de Lomé, Lomé, Togo
Morales); Hospital del Niño Dr. Francisco De Icaza Westmead, Sydney, New South Wales, Australia (Guedenon); National Cancer Institute, Maharagama,
Bustamante, Guayaquil, Ecuador (Calle Jara, Villacís (Donaldson, Jones); Pediatric Oncology Institute, Sri Lanka (Gunasekera); Department of
Chafla); Department of Ophthalmology, Queensland Federal University of São Paulo, São Paulo, Brazil Ophthalmology, Ankara University School of
Children's Hospital, Brisbane, Queensland, Australia (Donato Macedo, Teixeira); Department of Medicine, Ankara, Turkey (Gündüz); Bai Jerbai Wadia
(Camuglia, Gole); Salud Ocular, Ministerio de Salud Ophthalmology, The First Affiliated Hospital of Hospital for Children, Mumbai, India (H. Gupta,
Publica, Asuncion, Paraguay (Cano); Our Lady’s Guangxi Medical University, Nanning, China (Du); Mudaliar); King George’s Medical University,
Children’s Hospital, Dublin, Ireland (Capra); Institut University of KwaZulu-Natal, Durban, South Africa Lucknow, India (S. Gupta, Verma); Retinoblastoma
Curie, Université de Paris Medicine Paris V Descartes, (Du Bruyn); Ophthalmology Department, Referral Center, University of Siena, Siena, Italy
Paris, France (Cassoux); Centro Hospital Universitário Dr M. Djamil General Hospital, Faculty of Medicine, (Hadjistilianou); Centre Hospitalier Universitaire
de Coimbra, University of Coimbra, Coimbra, Portugal Andalas University, West Sumatra, Indonesia (Edison, Sainte-Justine, University of Montreal, Montréal,

Quebec, Canada (Hamel, Superstein); The Indus (Klett); Oncologue Pédiatre Responsable d’Unité de Ophthalmology, Amsterdam UMC, Amsterdam, the
Hospital, Karachi, Pakistan (Hamid, Zia); Hospital Bangui, Bangui, Central African Republic (Komba Netherlands (Moll, van Hoefen Wijsard); Hospital
Kuala Lumpur, Kuala Lumpur, Malaysia (Hamzah, Palet); Children’s Ophthalmology Department, Infantil Dr Robert Reid Cabral, Santo Domingo,
Rahmat, Teh); John A. Moran Eye Center, University Children’s Hospital of Vilnius, University Hospital Dominican Republic (Montero, Nieves); Service
of Utah, Salt Lake City (Hansen, Hartnett); Bascom Santaros Clinic, Vilnius, Lithuania (Krivaitiene); d’Oncologie Pédiatrique de l’Hôpital Aristide le
Palmer Eye Institute, University of Miami Miller Department of Paediatrics and Child Health, Faculty Dantec, Dakar, Senegal (Moreira); Ministry of Health,
School of Medicine, Miami, Florida (Harbour, of Medicine and Health Sciences, Stellenbosch Lusaka, Zambia (Muma); Jules-Gonin Eye Hospital,
Paez-Escamilla); Department of Pediatric University, Stellenbosch, South Africa (Kruger); Fondation Asile de Aveugles, University of Lausanne,
Ophthalmology and Strabismus, Al Shifa Trust Eye Vitreo-Retina Research Unit, Department of Lausanne, Switzerland (Munier, Stathopoulos);
Hospital, Rawalpindi, Pakistan (Shadab Hassan, Ophthalmology, Chulalongkorn University, Bangkok, Department of Ophthalmology, Lagos University
Siddiqui); University Children’s Hospital, Bratislava, Thailand (Kulvichit, Varadisai); University Medical Teaching Hospital, College of Medicine of the
Slovakia (Hederova, Husakova); Hospital Nacional Center Hamburg-Eppendorf, Hamburg, Germany University of Lagos, Lagos, Nigeria (Musa); Abii
Guillermo Almenara Irigoyen, Lima, Perú (Lachmann); Hong Kong Eye Hospital, Chinese Specialists Hospital, Bamenda, Cameroon (Muyen);
(J. Hernandez, Pascual Morales); Pediatric University of Hong Kong, Hong Kong SAR, China Aditya Jyot Eye Hospital, Mumbai, India (Nair);
Hematology and Oncology Center, Mohammed V (C. P. S. Lam, Yam); Perth Children’s Hospital, Lokmanya Tilak Municipal General Hospital and
University, Rabat, Morocco (Hessissen); Department University of Western Australia, Perth, Western Medical College, Mumbai, India (Nair);
of Pediatrics and Child Health, Jimma University Australia, Australia (G. C. Lam); Clinical Center of N.N. Alexandrov National Cancer Centre of Belarus,
Medical Center, Jimma, Ethiopia (Hordofa); Byers Eye Vojvodina, University Eye Clinic, Eye Research Minsk, Belarus (Naumenko, Zhilyaeva); Cheikh Anta
Institute, Stanford University, Stanford, California Foundation Vidar–Latinović, Novi Sad, Serbia Diop University, Le Dantec Hospital, Dakar, Senegal
(Huang, Mruthyunjaya); Emory Eye Center, Atlanta, (Latinović); Division of Ophthalmology, Feinberg (Ndoye Roth); Child Health Department, Faculty of
Georgia (Hubbard, Uner); Department of School of Medicine, Northwestern University, and Medicine, Diponegoro University, Semarang,
Ophthalmology, Oslo University Hospital, Oslo, Ann & Robert H. Lurie Children’s Hospital of Chicago, Indonesia (Nency); Moscow Helmholtz Research
Norway (Hummlen); Oncology Unit, Child’s Central Chicago, Illinois (Laurenti, Mets); John A. Burns Institute of Eye Diseases, Moscow, Russia (Neroev,
Teaching Hospital, Baghdad, Iraq (Hussein Al-Janabi); School of Medicine, University of Hawaii, Honolulu, Saakyan); Ho Chi Minh Eye Hospital, Ho Chi Minh,
Institute for Oncology and Radiology of Serbia, and University of Southern California Roski Eye Vietnam (Ngo); Department of Ophthalmology,
Belgrade, Serbia (Ilic, Nikitovic); Pacific International Institute, Los Angeles (Le); Division of Calabar Children’s Eye Center, University of Calabar
Hospital, Port Moresby, Papua New Guinea (Jairaj); Ophthalmology, Faculty of Health Sciences, Teaching Hospital, Calabar Nigeria (Nkanga);
Eye Department, Birmingham Children’s Hospital, University of Cape Town, Cape Town, South Africa Chittagong Eye Infirmary and Training Complex,
Birmingham Women’s and Children’s NHS (Lecuona, Mustak); Phoenix Children’s Hospital, Chittagong, Bangladesh (Nuruddin, Roy); Arthur
Foundation Trust, Birmingham, United Kingdom Phoenix, Arizona (Leverant); Affiliated Hospital of Davison Children’s Hospital, Ndola, Zambia (Nyaywa);
(Jenkinson, Painter, Parulekar); Fight Against Dali University, Dali City, China (Li); Tilganga Institute CHU Angondje Cancerologie, Libreville, Gabon
Angiogenesis-Related Blindness Laboratory, of Ophthalmology, Kathmandu, Nepal (Limbu, (Obono-Obiang); Sue Anschutz-Rodgers Eye Center,
Biomedical Research Institute, Seoul National Rajkarnikar, Saiju); Singapore National Eye Center, University of Colorado School of Medicine, Aurora
University Hospital, Seoul, Republic of Korea (Jo); Singapore, Singapore (Long, Tan); Ophthalmology (Oliver); Komfo Anokye Teaching Hospital, Kumasi,
Clínica Oftalmológica Pasteur, Santiago, Chile Department, Faculty of Medicine, Universidad de Ghana (Osei-Bonsu, Paintsil); Clínica Alemana de
(K. P. Johnson); Storm Eye Institute, Medical Chile, Santiago, Chile (López); University Clinics of Santiago, Universidad del Desarrollo, Santiago, Chile
University of South Carolina, Charleston Lubumbashi, University of Lubumbashi, Lubumbashi, (Ossandon); National Ophthalmological Institute of
(W. J. Johnson, Magrath); Bukavu Eye Clinic, Bukavu Democratic Rrepublic of Congo (Lukamba); Pediatric Angola, Luanda, Angola (Paiva, Wime); H M Diwan
Official University, Bukavu, Democratic Republic of Hematology/Oncology/Stem Cell Transplantation, Eye Foundation, and Tata Medical Center, Kolkata,
the Congo (Kabesha); Operation Eyesight Universal Center for Global Health, Children’s Hospital India (Pal); Department of Oncology, Yerevan State
Institute for Eye Cancer, L V Prasad Eye Institute, Colorado, University of Colorado, Aurora Medical University, and Pediatric Cancer and Blood
Hyderabad, India (Kaliki); Department of (Luna-Fineman); Department of Ophthalmology, Disorders Center of Armenia, Hematology Center
Ophthalmology, Makerere University College of Dr Soetomo General Hospital, Airlangga University, after R. H. Yeolyan, Yerevan, Armenia (Papyan,
Health Sciences Kamplala, Uganda (Kalinaki); Division Surabaya, Indonesia (Lutfi, Soebagjo); Okhmatdyt Tamamyan); University of British Columbia,
of Pediatric Oncology, School of Medicine, Ege National Children’s Hospital, Kiev, Ukraine (Lysytsia); Vancouver, British Columbia, Canada (Paton);
University, Izmir, Turkey (Kantar); Chang Gung Pediatric Hematology-Oncology Unit, Apollo Center University Hospital Center Zagreb, Zagreb, Croatia
Memorial Hospital, Taipei, Taiwan (Kao); for Advanced Pediatrics, Indraprastha Apollo (Perić); Vietnam National Institute of Ophthalmology,
Ophthalmology Department, Central Children’s Hospital, New Delhi, India (Mahajan); Sekuru Kaguvi Ha Noi, Vietnam (Pham, Trang); Centre Hospitalier
Hospital of Georgia, Tbilisi, Georgia (Kardava, Eye Unit, Parirenyatwa Group of Hospitals, Harare, Universitaire de Kamenge, Bujumbura, Burundi
Khotenashvili); Division of Pediatric Zimbabwe (Makan); National Center of Oncology and (Philbert); Department of Ophthalmology for
Hematology-Oncology, Department of Pediatrics, Hematology, Bishkek, Kyrgyzstan (Makimbetov); Children and Adults, Second Faculty of Medicine,
Cerrahpaşa Faculty of Medicine and Oncology University of Alabama at Birmingham, Birmingham Charles University, and Motol University Hospital,
Institute, Istanbul University, Istanbul, Turkey (L. Mason, J. O. Mason III); Ruharo Eye Centre, Ruharo Prague, Czech Republic (Pochop); Fundacion Clinica
(Kebudi); St. Anne’s University Hospital Brno, Mission Hospital, Mbarara, Uganda (Matua, Waddell); Valle del Lili, Cali, Colombia (Polania); Head and Neck
Masaryk University, and International Clinical Scottish Livingstone Hospital, Molepolole, Botswana Tumors Department, SRI of Pediatric Oncology and
Research Center/St Anna University Hospital, Brno, (Mbumba); Department of Ocular Oncology, Royal Hematology, N.N. Blokhin Russian Cancer Research
Czech Republic (Kepak); Dhaka Medical College Victorian Eye and Ear Hospital, East Melbourne, Center, Moscow, Russia (Polyakov, Ushakova);
Hospital, Dhaka, Bangladesh (Khan); Department of Victoria, Australia (McKenzie); Department of Russian Medical Academy of Postgraduate Education,
Ophthalmology, Postgraduate Medical Institute, Oncology, Hospital Infantil de México Federico Moscow, Russia (Polyakov, Ushakova); University Eye
Ameer-Ud-Din Medical College, Lahore General Gómez, Mexico City, Mexico (Medina-Sanson); Hospital Ljubljana, University Medical Center
Hospital, Lahore, Pakistan (Khaqan); Angkor Hospital MAHAK Hematology Oncology Research Center, Ljubljana, Ljubljana, Slovenia (Pompe, Stirn Kranjc);
for Children, Krong Siem Reap, Cambodia (Khauv); Mahak Hospital, Tehran, Iran (Mehrvar, Tashvighi); Good Shepherd Hospital, Siteki, Swaziland (Pons);
Duke Eye Center, Duke University Hospital, Durham, Department of Ophthalmology, Jimma University, Sardjito Hospital, Faculty of Medicine, Universitas
North Carolina (Kheir, Materin); Sankara Nethralaya, Jimma, Ethiopia (Mengesha); Centre for Sight, New Gadjah Mada, Yogyakarta, Indonesia (Purwanto,
Chennai, India (Khetan, Prom, N. Singh); Department Delhi, India (Menon); Department of Ophthalmology, Supriyadi); Hiwa Cancer Hospital, Sulaymaniyah, Iraq
of Ophthalmology, Seoul National University University of Padova, Padova, Italy (Midena, (Qadir); Department of Ophthalmology, Eye and Ear,
Hospital, Seoul, Republic of Korea (J. H. Kim); Ocular Parrozzani); Sankara Eye Hospital, Bangalore, India Nose, and Throat Hospital of Fudan University,
Oncology Service, Department of Ophthalmology, (Mishra, Palanivelu, Ramanjulu); Kilimanjaro Christian Shanghai, China (Qian); Department of
Hacettepe University School of Medicine, Ankara, Medical Centre, Moshi, Tanzania (Mndeme, Msina); Ophthalmology, Hospital Infantil de Mexico Federico
Turkey (Kiratli); Ocular Oncology Service, Department of Pathology, Faculty of Medicine, Gómez, Mexico City, Mexico (Ramirez-Ortiz); Centre
Department of Ophthalmology, Helsinki University University of Gezira, Wad Medani, Sudan Hospitalier Universitaire Joseph Ravoahangy
Hospital, University of Helsinki, Helsinki, Finland (Mohamedani); King Hussein Cancer Center, Amman, Andrianavalona, Antananarivo, Madagascar
(Kivelä); East Tallinn Central Hospital, Tallinn, Estonia Jordan (Mohammad, Yousef); Department of (Raobela); Department of Oculoplasty and Ocular

Oncology, Ispahani Islamia Eye Institute and Hospital, Department, Federal University of São Paulo, São Cancer Trust, as well as nonfinancial support from
Dhaka, Bangladesh (Rashid, Sultana); Department of Paulo, Brazil (Teixeira); Kabgayi Eye Unit, Gitarama, Institute for Families, The Larry and Celia Moh
Ophthalmology, Davidoff Center for Oncology, Rabin Rwanda (Theophile); Department of Pediatric Foundation, and Research to Prevent Blindness.
Medical Center, Sackler School of Medicine, Tel Aviv Hematology-Oncology, Schneider Children’s Medical Dr Correa reports receiving personal fees from
University, Israel (Reich); School of Medicine and Center, Sackler School of Medicine, Tel Aviv Castle Biosciences and Immunocore. Dr Diaz
Dentistry, Korle-Bu Teaching Hospital, University of University, Tel Aviv, Israel (Toledano); Pediatric Coronado reports receiving support from Merck
Ghana, Accra, Ghana (Renner); University of Pretoria, Oncology Service, Gabriel Toure Hospital, Bamako, Sharp & Dohme. Dr Demirci reports receiving
Pretoria, South Africa (Reynders, Schoeman); Federal Mali (Traoré); Department of Ophthalmology, Faculty support Castle Biosciences and Immunocore.
Medical Center, Yola, Nigeria (Ribadu); Nampula of Medicine, Ocular Oncology Service, Istanbul Dr Foster reports receiving grants from the Queen
Central Hospital, Nampula, Mozambique (Riheia); University, Istanbul, Turkey (Tuncer); Université Elizabeth Diamond Jubilee Trust. Dr Gold reports
Division of Pediatric Hematology and Oncology, Adam Barka, Abeche, Chad (Tyau-Tyau); Division of receiving personal fees from Regeneron.
Department of Pediatrics and Adolescent Medicine, Pediatric Hematology-Oncology, Department of Dr Harbour reports receiving royalties and other
Medical University of Graz, Graz, Austria Pediatrics, Ankara University, Ankara, Turkey (Unal); support from Castle Biosciences. Dr Hartnett
(Ritter-Sovinz); Children’s Cancer Institute, American Department of Ophthalmology, Aarhus University reports receiving grants from the National Eye
University of Beirut Medical Center, Beirut, Lebanon Hospital, Aarhus, Denmark (Urbak); National Cancer Institute; having a patent issued and a patent
(Saab); NIHR Biomedical Research Centre for Center of Uzbekistan, Tashkent, Uzbekistan pending related to her work in eye care; receiving
Ophthalmology, Moorfields Eye Hospital, and UCL (Usmanov); Children’s Clinical University Hospital, honoraria from Wolters Kluwer as editor in chief of
Institute of Ophthalmology and London Riga, Latvia (Valeina, Viksnins); Department of the textbook Pediatric Retina Disease, Second
Retinoblastoma Service, Royal London Hospital, Ophthalmology, Medical University of Graz, Graz, Edition; receiving honoraria for academic lectures at
London, United Kingdom (Sagoo); Department of Austria (Wackernagel); Jos University Teaching the University of Alabama at Birmingham, Michigan
Ophthalmology, Faculty of Medicine, Ain Shams Hospital, Jos, Nigeria (Wade); National Eye Center State University, University of Florida, University of
University, Cairo, Egypt (Said, Ziko); Hospital Kaduna, Kaduna, Nigeria (Wali); Department of Iowa, Ohio State University, Indiana University, Cole
Dr Manuel Ascencio Villarroel, Cochabamba, Bolivia Paediatrics, Beijing Tongren Hospital, Capital Medical Eye Institute, Scheie Eye Institute, Massachusetts
(Salas); Pediatric Hemato-Oncology, Hospital University, Beijing, China (Wang, Y. Zhang); Eye and Ear, and University of Colorado; and
Universitario Infantil La Paz, Madrid, Spain Department of Surgery, St Jude Children’s Research receiving paid trips to consult for the National Eye
(San Román Pacheco); Hospital Solca Quito, Quito, Hospital, Memphis, Tennessee (Wilson); Department Institute’s National Advisory Eye Council and for
Ecuador (Sánchez); Mahosot Hospital, Vientiane, of Ophthalmology, Chiang Mai University, Chiang Mai, grant review for the Knights Templar Eye
Laos (Sayalith); Department of Ophthalmology, Thailand (A. Wiwatwongwana, D. Wiwatwongwana); Foundation. Dr Kivela reports receiving personal
Rasool Akram Hospital, Tehran, Iran (Sedaghat); Department of Ophthalmology, Faculty of Medicine, fees from Santen. Dr Materin reports receiving
Department of Pediatrics, All India Institute of Khon Kaen University, Khon Kaen, Thailand personal fees from IDEAYA Biosciences and Castle
Medical Sciences, New Delhi, India (Seth); National (Wongwai); Department of Pediatric Ophthalmology, Biosciences. Dr Nair reports receiving personal fees
Institute of Ophthalmology, Dhaka, Bangladesh Guangzhou Children’s Hospital and Guangzhou from HelpMeSee and Carl Zeiss Meditec. Dr Oliver
(Shakoor); East Timor Eye Program, Dili, Timor-Leste Women and Children’s Medical Center, Guangzhou reports receiving grants from Roche. Dr Skalet
(Sharma); Tata Memorial Hospital, Mumbai, India Medical University, Guangzhou, China (Xiang); reports receiving support as a consultant from
(Shetye, Vora); Ocular Oncology Service, Wills Eye Kunming Children’s Hospital, Kunming, China (Xiao); Castle Biosciences and Immunocore. Dr Soebagjo
Hospital, Thomas Jefferson University, Philadelphia, State Key Laboratory of Ophthalmology, Zhongshan reports rights to 2 licensed patents. Dr Stahl reports
Pennsylvania (Shields); Ophthalmology Department, Ophthalmic Center, Sun Yat-sen University, receiving personal fees from Avedro and
Nouakchott Medical University, Nouakchott, Guangzhou, China (Yang, Ye); Service nonfinancial support from Sydnexis.
Mauritania (Sidi Cheikh); Department of d’Ophtalmologie, Cliniques Universitaires de Funding/Support: This work was supported by
Ophthalmology, Postgraduate Institute of Medical Kinshasa, Université de Kinshasa, Kinshasa, the Queen Elizabeth Diamond Jubilee Trust.
Education and Research, Chandigarh, India (U. Singh); Democratic Republic of Congo (Yanga); Armed Forces
Department of Ophthalmology, Faculty of Medicine, Institute of Ophthalmology, Rawalpindi, Pakistan Role of the Funder/Sponsor: The funder had no
Universitas Indonesia, and Dr Cipto Mangunkusumo (Yaqub); S.Fyodorov Eye Microsurgery Federal State role in the design and conduct of the study;
National General Hospital, Jakarta, Indonesia (Sitorus, Institution, Moscow, Russia (Yarovaya, Yarovoy); collection, management, analysis, and
Victor); Casey Eye Institute, Oregon Health & Science Assistante Hospitalo Universitaire, Faculte de interpretation of the data; preparation, review, or
University, Portland (Skalet, Sundy); Mulago National Medecine de Nouakchott Medecin Oncopediatre, approval of the manuscript; and decision to submit
Referral Hospital, Kampala, Uganda (Ssali); Center National d’Oncologie, Nouakchott, Mauritania the manuscript for publication. The funder assisted
Department of Ophthalmology, University of (Zein); Department of Ophthalmology, Beijing in institutional review board application fees for
Washington, Seattle (Stacey, Weiss); Centre for Eye Children’s Hospital, Capital Medical University, selected retinoblastoma centers from low-income
Research Australia, University of Melbourne, East Beijing, China (C. Zhang, Zhao); Department of countries.
Melbourne, Victoria, Australia (Staffieri); Children’s Ophthalmology, Children’s Hospital, Zhejiang Additional Contributions: We thank the following
Mercy Hospital, Kansas City, Missouri (Stahl); University School of Medicine, Hangzhou, China contributors for assisting in the creation of the
Department of Paediatrics and Child Health, (Zheng); Ophthalmology Department, Great Ormond global network: Malakhova Alina, Yuriy Serov, and
University of the Free State, Bloemfontein, South Street Hospital, London, United Kingdom (Bowman). Olga Yugay from N. N. Blokhin National Medical
Africa (Stones); BC Children’s Hospital, Vancouver, Author Contributions: Dr Fabian had full access to Research Center of Oncology in Moscow, Russia;
British Columbia, Canada (Strahlendorf); Pediatra all of the data in the study and takes responsibility Syuzanna Tadevosyan from Helmholtz Moscow
Hemato-Oncologa, Instituto Oncologico del Oriente for the integrity of the data and the accuracy of the Research Institute of Eye Diseases in Moscow,
Boliviano, Santa Cruz de la Sierra, Bolivia (Suarez); data analysis. All coauthors approved the final Russia; George Ramappa from LV Prasad Eye
Henan Children’s Hospital, Affiliated Children’s version for publication. Institute in Hyderabad, India; Friska Mardianti from
Hospital of Zhengzhou University, Zhengzhou, China Study concept and design: Fabian, Foster, Bowman. Cicendo Eye Hospital in Bandung, Jawa Barat,
(Sun); Queen Sirikit National Institute of Child Health, Acquisition, analysis, or interpretation of data: Indonesia; Daniel Getaneh and Bethelhem Sileshi
Bangkok, Thailand (Surukrattanaskul, Trichaiyaporn); All authors. from Menelik II Hospital in Addis Ababa, Ethiopia;
Department of Ophthalmic Oncology, National Drafting of the manuscript: Fabian, Bascaran, Mostafizur Rahman and Mastura Khatun from
Cancer Center Hospital, Tokyo, Japan (Suzuki); Chantada, Dimaras, Foster, Khetan, Kivela, Reddy, Ispahani Islamia Eye Institute and Hospital in Dhaka,
Department of Pediatric Hematology and Oncology, Sagoo, Stacey, Zondervan, Bowman. Bangladesh; Alenka Lavric Groznik from University
Second Faculty of Medicine, Charles University, Motol Critical revision of the manuscript for important Eye Clinic, Ljubljana in Ljubljana, Slovenia; Layal
University Hospital, Prague, Czech Republic (Svojgr); intellectual content: All authors. Bayram from Children's Cancer Center of Lebanon
Africa Institute of Tropical Ophthalmology, Bamako, Statistical analysis: Stacey. in Beirut, Lebanon; Narjes Mehrvar from MAHAK
Mali (Sylla); Hospital Nacional Edgardo Rebagliati Children Hospital in Tehran, Iran; Chinsisi Myirenda,
Martins, Lima, Perú (Tarrillo Leiva, Vasquez); Conflict of Interest Disclosures: Dr Berry reports Catherine Lunduka, and George Chagaluka from
University Eye Clinic, Skopje, Macedonia (Tateshi); receiving grants from National Cancer Institute Lions Sight First Eye Hospital, Queen Elizabeth
National Cancer Center, Dharmais Cancer Hospital, (K08CA232344), Wright Foundation, Knights Central Hospital in Blantyre, Malawi; Suganeswari
Jakarta, Indonesia (Tehuteru); Ophthalmology Templar Eye Foundation, American Cancer Society, Ganesan and Pukhraj Rishi from Sankara Nethralaya
Hyundai Hope on Wheels, and Childhood Eye

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Research

JAMA Oncology | Original Investigation

Global Retinoblastoma Presentation and Analysis

MAIN OUTCOMES AND MEASURES Age at presentation, proportion of familial history of

Group Information: The members

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analyzed by national income level are shown in Table 1.

Geographic and Socioeconomic Characteristics

Completeness of Data 8 Centers were excluded because they

Symptoms at Time of Diagnosis at Retinoblastoma Centers

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Table 2. Logistic Regression Analysis: Predictors of Advanced Disease at Presentationa,b

Variable B (SE) Corrected P Value Odds Ratio (95% CI)

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