Abstract
Retinoblastoma, the most common intraocular tumor in childhood, still
faces challenges in diagnosis and treatment, particularly in low- and
middle-income countries. Identifying strategies to improve the time to
diagnosis and access to treatment is crucial to enhance survival rates
and preserve ocular health. We conducted a systematic review to identify
interventions that have demonstrated potential in addressing these
challenges. We performed a comprehensive search across databases until
March 2023. Out of the studies reviewed, twenty-one met the inclusion
criteria and were categorized into five main areas: surveillance
strategies, genetic counseling, education, public assistance and
international partnership. Despite the obstacles faced, the initiatives
identified in this review present acts towards improving the time to
diagnosis and access to treatment for retinoblastoma. Based on the
extracted data, we propose a comprehensive chain of initiatives. We
firmly believe that implementing this chain of initiatives can lead to
improved clinical outcomes for retinoblastoma patients.
INTRODUCTION
Retinoblastoma (RB) is the most common intraocular tumor in children,
constituting 10-15% of all cancers diagnosed in the first year of
life1. It
is an aggressive cancer developing rapidly in the retina, before age
five years. Epidemiological estimates suggest 7000–8000 children
develop RB globally annually with approximately 3000–4000 succumbing to
it each year2.
RB management must prioritize saving lives, although eye salvage and
vision preservation are also crucial clinical outcomes. Clinical
decisions should be risk-adapted and supported by a multidisciplinary
team.
Prevalence and mortality rates vary worldwide, being higher in low- and
middle-income countries (LMICs). In Africa and Asia, 40% to 70% of
children with RB die, compared with 3% to 5% of children in Europe and
North
America3.
Disease extension and prognosis strongly correlates with a long
prediagnostic symptoms
interval4–7. In LMICs, RB diagnosis often occurs at advanced stages
due to delayed diagnosis, cost barriers, and a lack of specialized
personnel and equipment8.
An efficient RB screening and diagnostic model could cut healthcare
costs, enhance time to diagnosis, and expedite treatment referral9. Early
diagnosis can increase not only the rate of survival but also very
important vision preservation2.
Although there are many studies evaluating risk factors for diagnostic
delay, few of them report interventions for its reduction. The present
study systematically reviewed the literature to identify strategies that
can contribute to earlier diagnosis and access to treatment.
METHODS
2.1. Protocol registration
A comprehensive systematic review (PROSPERO CRD42023403511) of the
literature, conduced according to the preferred reporting items for
systematic reviews and meta-analyses (PRISMA) guidelines, was performed
to map the scope, quality, and efficacy of interventions aiming to
improve the time to diagnosis and access to treatment of childhood
RB10.
2.2. Study selection
Pubmed, BVS (Biblioteca Virtual em Saúde ), Scielo and Scopus
searches were concluded in March 2023. The MeSH descriptors used were
retinoblastoma; developing countries; diagnosis; health services; and
accessibility, and the search strategies adapted to each database.
Detailed search strategies are included in Appendix I. All searches,
title and abstract screening, full-text evaluation, and data extraction
were conducted by two independent authors (B.S.R. and K.A.F.A.). Any
disagreements were resolved by discussion until consensus.
Quantitative and qualitative
studies employing either interventional or observational approaches to
assess the effects of strategies aimed at improving the diagnosis of RB
or enhancing access to treatment in LMICs were considered for inclusion.
No restrictions were imposed on language or publication date.
We excluded review articles, book excerpts, and studies that did not
report intervention results and articles reporting interventions
conducted in developed countries (Appendix II).
2.3. Data collection and
analysis
Using a data extraction form, relevant data was acquired from each
study, including study location and design, population, intervention,
comparisons made, and outcomes. Studies were categorized based on the
intervention type: surveillance strategies, international partnership,
telemedicine, education, public assistance, and genetic counseling. A
summary table was assembled to describe the results. The heterogeneity
of designs, types of interventions, and outcomes prevented quantitative
synthesis.
2.4. Quality appraisal
To evaluate the methodological quality of the studies, the Joanna Briggs
Institute’s critical appraisal instruments were employed11,
12. Both reviewers (B.S.R.
and K.A.F.A.) independently assessed the quality of all studies, using a
specific form tailored to each study design: cohort, case series, and
cross-sectional. Any discrepancies were discussed and resolved through
consensus. Four articles were excluded from the analysis: Joseph et.
al., 2006, because it is a diagnostic model proposal13, and
Chantada et al., 2016, Howard et al., 2018, and Wilimas et al., 2009
that are public policy studies14–16.
In total, 17 studies underwent analysis. Concerning the quality of the
study, the included articles were categorized as ”high”, ”moderate”, and
”low ” based on the percentage of ”yes” answers within the domains: 70%
or more, 50-69%, and 0-49%, respectively.
RESULTS
The search yielded 870 records. Thirty-two reports were selected after
title/abstract screening and assessment for eligibility, and twenty-one
studies included (Fig. 1). Publications were further classified into 5
categories: surveillance strategies3,17–22,
genetic counseling9,13,23,
education24–27,
public
assistance28and international partnership8,14–16,29,30.
Table 1 describes the extracted data.