Ophthalmology Volume 130, Number 3, March 2023
2. Tomar AS, Finger PT, Gallie B, et al. American Joint Committee
on Cancer Ophthalmic Oncology Task Force. Metastatic death
based on presenting features and treatment for advanced intra-
ocular retinoblastoma: a multicenter registry-based study.
Ophthalmology. 2022;129:933e945.
3. Abramson DH, Francis JH, Gobin YP. What’s new in intra-arterial
chemotherapy for retinoblastoma? Int Ophthalmol Clin. 2019;59:
87e94.
4. Lu JE, Francis JH, Dunkel IJ, et al. Metastases and death rates
after primary enucleation of unilateral retinoblastoma in the
USA 2007-2017. Br J Ophthalmol. 2019;103:1272e1277.
REPLY: Drs Abramson and Shields’ letter addresses our 2
American Joint Committee on Cancer Ophthalmic Oncology
Task Force (AJCC-OOTF) publications. Our research aimed
to answer the question: can high-risk clinical factors uniquely stratified
within the AJCC staging system predict high-risk pathology features
and thus the risk for metastatic retinoblastoma (RB)?
Their letter and our reply can be used to contrast the 2 worlds of
RB.
One is the high-resource world of Abramson and Shields, where
every possible primary and rescue treatment is available no matter
the cost. The second is our results, derived from 41 centers in 18
countries on 6 continents, that more accurately represents what
happens to children with RB around the world.1 Ours includes high-,
middle-, and low-resource environments where attempts emulating
Abramson and Shields’ published eye-saving methods are per-
formed without available rescue therapies. This may result in a
greater incidence of metastatic RB and death. As reflected in our
research, it is under those circumstances where primary enucleation
of AJCC staged high-risk eyes is more likely to save the lives of most
of the world’s children with RB. On the one hand, Abramson and
Shields are quick to decry our conclusions because they might cause
the loss of eyes, but they do not consider that they might just save
lives. Perhaps high-resource centers promoting results commonly
unattainable in the rest of the world are the real “danger.”
Abramson and Shields criticize our 2 publications for including
many different treatments. Quite the contrary, we consider this a
foundational element of our conclusions because it comprises the
best available local care, selected based on the clinical, socioeco-
nomic, and parental considerations in each individual case from
centers around the world, where most cases of RB occur. Consider
that the incidence of RB depends on population size and birth rate.2
Because of the lack of national registries, mathematical estimates
have been used to predict trends in the incidence of RB. One
such report used an RB incidence of 1 in 16 642 live births per
year and found an annual incidence of 264 new RB children in
North America, 464 in Europe, 615 in Latin America, 2293 in
Africa, and 4258 in Asia.3 Clearly, Asia and Africa carry the
highest RB burden (83%). There, advanced RB is the most
common presentation, and primary enucleation of AJCC high-risk
eyes will most likely save lives.1,3
In addition, high-risk pathological features are seen in > 50%
of children in moderate- and low-resource countries, compared with <
20% of enucleated eyes in high-resource countries.4 Our prior global
RB outcome analysis showed that enucleated eyes with high-risk pa-
thology (pT3 and pT4) from high-resource countries were more likely
to survive than low-resource ones.1 This was attributed to the relative
lack of stem cell treatment facilities, external beam radiation therapy,
e12
and salvage techniques in the latter. To make matters worse,
pathology results can be delayed, incomplete, or absent. The lack of
ophthalmic pathology services places emphasis on identifying high-
risk clinical features that predict high-risk pathology features and
thus facilitate potentially life-saving clinical decisions.
Although our findings most likely have their maximum effect in
Africa and Asia, they also apply to high-risk RB children in
high-resource countries. Although resource-rich centers are more
likely to detect intraocular recurrence and metastatic disease promptly
and apply life-saving measures, the risks of eye-sparing treatments
remain. To be clear, RB specialists even in high-resource countries
have voiced their concerns about the costs (physical, emotional, and
financial) of multiple, sequential therapies to save eyes that may never
provide useful vision and increase the risk for metastatic disease. Our
results show that clinical findings uniquely stratified in AJCC RB
staging predict the presence of high-risk pathology and, thus, risk for
metastatic disease no matter where the child might live.
Drs Abramson and Shields’ concern that massive choroidal inva-
sion, extension into the optic nerve beyond the lamina cribrosa, and
scleral invasion can rarely be detected before enucleation is also un-
warranted; these features are not needed to assign high-risk AJCC
clinical RB stages that were used to predict such pathology findings in
our studies. In addition, our finding is particularly important where
ophthalmic pathology services are lacking and where a clinical deci-
sion to attempt to save a high-risk, poor prognosis eye may sacrifice a
child’s life.4,5
Our registry studies showed that identifying high-risk clinical fea-
tures and viewing them through the lens of a universal staging system,
here the AJCC clinical RB staging, is best performed at initial tumor
staging. Failure to identify high-risk pathology can deprive the child of
necessary follow-up and adjuvant treatment to avoid local tumor
recurrence, and it risks metastatic disease and death.
Although Abramson and Shields agreed with our stratification of
metastatic risk based on clinical features, they considered our
conclusion, “primary enucleation offered the highest survival rates for
patients with advanced intraocular RB,” as potentially dangerous.
They use a rationale of a lack of treatment standardization between
centers, the nonrandomized study design, variations in local treat-
ments, experience, resources, cultures, and selection bias. However,
they omit that no uniform treatment protocol or equitable resource
distribution exists to offer every child a similar RB treatment outcome
across the globe. Furthermore, they do not address that outcomes are
confounded by factors beyond any physician’s control, including
parents’ religious beliefs, social stigma, gender bias, abandonment of
treatment, and other economic factors. For example, our authors have
witnessed parent pressure based on unrealistic hope for eye salvage
fed by high-resource center “marketing” to the underprivileged world,
where up to 100% local control and survival are not achievable.6,7 This
results in unnecessary treatments, delay of definitive cure, metastasis,
and financial collapse of the family. Such outcomes would not be seen
in high-resource countries, where timely follow-up and aggressive
local therapies are feasible, even for the smallest recurrences.
Clearly this letter and reply contrast the 2 worlds of RB. The
incredible advancements seen in the management of RB are not
accessible uniformly in the foreseeable future. Many unserved
countries and large regions with no trained ophthalmic oncologists or
pathologists exist. Our statement, “enucleation is the best treatment
for advanced RB eyes” must be considered both in the context of our
registry experience and in specific clinical situations.1,8-10 We
consider every child with RB unique, requiring shared clinical and
 Correspondence
social decision-making by eye cancer specialists, and family mem-
bers. Further, decisions are based on presenting features, socioeco-
nomic constraints, and available technology.
Drs Abramson and Shields conclude by pointing out that
intravenous and intra-arterial chemotherapy “can be particularly
effective at saving eyes with more advanced RB.” This may be true,
but there exists a danger in their statement. Abramson and Shields
have revealed no multicenter, international evidence that these
treatments are equal to enucleation for saving life. In contrast, our
research revealed statistically significant clinical evidence to show
that enucleation of high-risk eyes is, globally, more likely to save
life. With this letter, the AJCC-OOTF and The Eye Cancer Foun-
dation invite Drs Abramson and Shields to join our efforts to
address the inequities in RB care. Because, as a medical commu-
nity, we must unite and ensure that the tide raises all boats to bring
the world’s RB children to safety.
PAUL T. FINGER, MD1
ANKIT S. TOMAR, MD1
BRENDA GALLIE, MD2
TERO T. KIVELÄ, MD3
FOR THE AMERICAN JOINT COMMITTEE ON CANCER
OPHTHALMIC ONCOLOGY TASK FORCE
1
The Department of Ocular Tumor, Orbital Disease, and Ophthalmic
Radiation Therapy, The New York Eye Cancer Center, New York, New
York; 2The Eye Cancer Clinic, Princess Margaret Cancer Centre, and
Department of Ophthalmology and Vision Sciences, Hospital for Sick
Children, Toronto, Canada; 3Ocular Oncology Service, Department of
Ophthalmology, University of Helsinki and Helsinki University Hospital,
Helsinki, Finland
Disclosures:
All authors have completed and submitted the ICMJE disclosures form.
The authors have no proprietary or commercial interest in any materials
discussed in this article.
Available online: November 25, 2022.
Correspondence:
Paul T. Finger, MD, The New York Eye Cancer Center, 115 East 61st
Street, Fifth Floor, New York, NY 10065. E-mail: pfinger@eyecancer.
com.
References
1. Tomar AS, Finger PT, Gallie B, et al. Global retinoblastoma
treatment outcomes: association with national income level.
Ophthalmology. 2021;128:740e753.
2. Kivelä T. The epidemiological challenge of the most frequent
eye cancer: retinoblastoma, an issue of birth and death. Br J
Ophthalmol. 2009;93:1129e1131.
3. Munier FL, Beck-Popovic M, Chantada GL, et al. Conservative
management of retinoblastoma: challenging orthodoxy without
compromising the state of metastatic grace. “Alive, with good
vision and no comorbidity.” Prog Retin Eye Res. 2019;73:100764.
4. Chantada GL, Qaddoumi I, Canturk S, et al. Strategies to
manage retinoblastoma in developing countries. Pediatric
Blood Cancer. 2011;56:341e348.
5. Zhao J, Feng ZX, Wei M, et al. Impact of systemic chemo-
therapy and delayed enucleation on survival of children with
advanced intraocular retinoblastoma. Ophthalmol Retina.
2020;4:630e639.
6. Lu JE, Francis JH, Dunkel IJ, et al. Metastases and death rates
after primary enucleation of unilateral retinoblastoma in the
USA 2007-2017. Br J Ophthalmol. 2019;103:1272e1277.
7. Shields CL, Dockery PW, Yaghy A, et al. Intra-arterial
chemotherapy for retinoblastoma in 341 consecutive eyes (1,
292 infusions): comparative analysis of outcomes based on
patient age, race, and sex. J AAPOS. 2021;25:150.e1e150.e9.
8. Tomar AS, Finger PT, Gallie B, et al. A multicenter, interna-
tional collaborative study for American Joint Committee on
Cancer staging of retinoblastoma: part II: treatment success and
globe salvage. Ophthalmology. 2020;127:1733e1746.
9. Finger PT, Tomar AS. Retinoblastoma outcomes: a global
perspective. Lancet Glob Health. 2022;10:e307ee308.
10. Tomar AS, Finger PT, Gallie B, et al. A multicenter, interna-
tional collaborative study for American Joint Committee on
Cancer staging of retinoblastoma: part I: metastasis-associated
mortality. Ophthalmology. 2020;127:1719e1732.
Re: Oke et al.: Adjustable suture
technique is associated with fewer
strabismus reoperations in the
Intelligent Research in Sight
Registry
(Ophthalmology. 2022;129:1028e1033)
TO THE EDITOR: Oke et al1 found that strabismus surgery with the
adjustable suture technique had a 2.1% lower reoperation rate
than without adjustable suture in adults.
Thirty-five percent of the adjustable suture patients had prior stra-
bismus surgery, but only 19% of the nonadjustable procedure patients
underwent repeat surgery (P < 0.001). What were the reoperation rates
in the 27 125 patients without prior strabismus surgery?
The abstract’s conclusions section states, “the adjustable
suture technique was associated with a significantly lower
reoperation rate.” Do the authors mean “the adjustable suture
technique was associated with a statistically significant lower
reoperation rate” (P < 0.001), or is the 2.1% “modest decrease”
also a clinically significant difference? A statistically significant
difference would not be uncommon given the very large com-
parison groups of 28 580 and 6292.
EDSEL ING, MD, PHD
University of Toronto, Toronto Ontario, Canada
The author has completed and submitted the ICMJE disclosures form.
The author has no proprietary or commercial interest in any materials
discussed in this article.
Available online: November 25, 2022.
Correspondence:
Edsel Ing, MD, PhD, Michael Garron Hospital, 650 Sammon Ave, K306
Toronto, ON, M2P 1E5 Canada. E-mail: edsel.ing@tehn.ca.
Reference
1. Oke I, Hall N, Elze T, et al. IRIS Data Analytics Committees.
Adjustable suture technique is associated with fewer strabismus
reoperations in the Intelligent Research in Sight Registry.
Ophthalmology. 2022;129:1028e1033.
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