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.