Delay in Retinoblastoma Detection in LMICs: A Call to Action for Global Pediatric Health

Retinoblastoma is an aggressive intraocular pediatric malignancy that is life-threatening if left untreated. Early detection and prompt treatment offer an excellent chance for a favorable prognosis and vision preservation. The global incidence of retinoblastoma ranges from 1 in 16 000 to 24 000 live births.1 However, in low and middle income countries (LMICs), the incidence is notably higher, estimated at 1 in 10 000 to 13 000 live births.1 Retinoblastoma typically manifests before the age of 5, with the peak incidence occurring between 1 and 2 years of age.1 According to the Global Burden of Disease Study 2021, the burden of retinoblastoma remains higher in low sociodemographic index regions, where delayed diagnosis is common, reflecting underlying disparities.2 A 2020 cohort study involving 278 retinoblastoma treatment centers reported that advanced disease at diagnosis (Stages 3/extraocular and 4/metastatic, per the International Retinoblastoma Staging System)3,4 was more common in LMICs.5 As a result of this higher proportion of advanced-stage presentations, enucleation rates among all children diagnosed with retinoblastoma in LMICs are also higher, with 60% to 70% undergoing eye removal compared with less than 60% in HICs.1,2,5 Although early detection of retinoblastoma and prompt intervention can lead to survival rates exceeding 95% as seen in high-income countries (HICs), survival rates in LMICs remain substantially lower, ranging from 50% to 80%.1,5The Bright Futures/American Academy of Pediatrics (AAP) Recommendations for Preventive Pediatric Health Care/Periodicity Schedule recommends a schedule of screenings and assessments with 31 well-child visits from infancy through adolescence (including 15 visits before the age of 5).6 Many LMICs lack the infrastructure to support regular pediatric well-child visits because of under-resourced public health systems.7 Therefore, routine immunizations and sick visits often represent a child’s only interaction with the health system. Immunization visits are conducted in diverse settings such as public health facilities, including public health centers, immunization camps, or schools, which are typically staffed by nurses or other nonphysician health care providers without training in ocular examination, limiting opportunities for early screening.7–9Even when seen by primary care physicians, children seldom receive vision screening like red reflex tests (RRTs), primarily because of limited access to essential equipment like a direct ophthalmoscope.7,10,11 Other systemic challenges include a low physician-patient ratio, poor referral networks, and limited access to trained optometrists, pediatric ophthalmologists, and pediatric oncologists in rural and suburban areas.7,12Inconsistent use of RRTs, a standard ocular screening technique essential for early detection, is another challenge in LMICs. In HICs, RRTs using an ophthalmoscope are a standard procedure during every well-child visit, enabling early identification of retinoblastoma and other vision-threatening conditions.13 This screening is essential because young children often cannot articulate vision difficulties. Despite its effectiveness, many pediatricians and primary care physicians in LMICs do not routinely perform RRTs.11,14A 2011 study from an LMIC found that only 54% of final-year medical students had knowledge that RRTs can clinically aid in screening retinoblastoma. This highlights a critical gap in undergraduate medical training.14 This is compounded by limited training in recognizing the early ocular signs leading to diagnostic delays, particularly in rural and underserved areas where access to specialists is minimal.7,10Multiple sociocultural factors play a major role in the delayed diagnosis of retinoblastoma in LMICs. Key barriers include reliance on nonevidence-based traditional remedies, often chosen because of cultural beliefs, spiritual or religious factors, community influence, low cost of traditional practices, fear and misconceptions regarding allopathic treatment, distrust in hospitals, easy accessibility, and the perception of being less invasive,15 as well as low perceived severity, stigma, and misinformation about treatment costs and outcomes.3,7,12 All these factors delay access to formal medical care.These challenges are compounded by sex inequities, rural residence, transportation challenges, and limited awareness of the importance of routine well-child visits.7,12,16 Although literature specifically examining these barriers is limited, a 2014 retrospective cohort study from Mexico observed that lower maternal education was associated with delayed diagnosis.16 This association may stem from low health literacy among many parents and caregivers in LMICs, which may limit their ability to recognize early warning signs, navigate health care systems, or make informed medical decisions, all of which contribute to diagnostic delays.7For instance, many parents and caregivers have limited awareness regarding the early signs of retinoblastoma, such as leukocoria (white pupillary reflex), strabismus (misaligned eyes) and poor visual tracking.3,7,12,16 Parents may occasionally notice these early warning signs and should seek prompt medical evaluation if they are observed. However, such signs are often subtle to individuals without clinical expertise and specialized training. Therefore, relying solely on parental observation is insufficient; systematic routine screening by trained health care providers remains essential for timely diagnosis.3,16Delayed diagnosis of retinoblastoma leads to poor outcomes, including higher rates of enucleation, increased risk of metastasis, and high mortality rates.3 In LMICs, nearly half of children are diagnosed at an advanced stage, with 19% to 43% presenting with extraocular metastasis, thus limiting eye-salvaging treatment options and reducing survival odds.1,2,5 However, poor outcomes in LMICs are not solely due to delayed diagnosis; they are also driven by limited access to timely and efficient treatment, as well as treatment abandonment and refusal.3,7,12Improving early diagnosis of retinoblastoma in LMICs hinges on integrating routine ocular assessments into primary care workflows. The following multilevel strategies are proposed to address the systemic, provider-level, and sociocultural barriers previously outlined and offer scalable solutions for resource-limited settings (Figure 1).The most important step to early diagnosis is increasing the accessibility of vision screening tools at the primary care level. The Arclight ophthalmoscope is a low-cost, portable, solar-powered, light-emitting diode, miniature direct ophthalmoscope used for performing RRTs that offers a practical alternative in primary care settings.17A 2020 cross-sectional diagnostic accuracy and feasibility study from Tanzania compared 4 screening methods: torchlight, Arclight, PEEK Retina, and CatCam. Among these, Arclight demonstrated higher sensitivity than torchlight (estimated at 92.7%). Although PEEK Retina and CatCam (smartphone-based tools requiring additional hardware or software setup) showed promising results, they were considered less practical in low-resource primary care settings because of higher costs and greater operational complexity. This study also reported that community nurses trained to use Arclight devices found the tool simpler to use than other conventional methods like the direct ophthalmoscope, highlighting its feasibility in resource-limited environments.17,18Addressing the critical gap in equipment availability, including scaling up alternative tools like Arclight, will require financial planning, budget prioritization, and secure procurement. National Health authorities and global health agencies should explore collaborations to support procurement and distribution, particularly in rural and underserved areas.Technological advancements, such as the CRADLE and MDEyeDetector apps (user-friendly tools capable of analyzing captured images for leukocoria), offer promising solutions for community screening.17 Training nonphysician health care workers to use these tools may improve early detection substantially, particularly where access to traditional equipment remains limited.2Training primary care physicians, nurses, and midwives to perform ocular screening during neonatal examinations, immunization appointments, and school health visits can substantially improve detection rates. Additionally, inclusion of ocular examinations as part of standard pediatric care within national pediatric screening guidelines can help standardize training for primary care providers, ensuring consistent early screening practices. Several freely available, open-access training tools can support capacity building among primary health workers. Two notable examples are the World Health Organization’s (WHO’s) Primary Eye Care Training Manual and Orbis International’s Cybersight Platform, both of which provide multilingual, competency-based modules, webinars, instructional videos, and online courses focused on pediatric eye screening and the early recognition of ocular conditions.19,20A 2017 Nigerian study demonstrated that community health workers trained in vision screening effectively screened children aged 0 to 2 years presenting for routine immunization over a six-month period, with prompt referrals for suspected vision abnormalities.21 Adapting such models locally could improve outcomes in LMICs.Overcoming sociocultural barriers requires the development and implementation of country-specific policy-driven systemic reforms and strategic educational programs. Caregiver education on early warning signs, delivered through visual symptom cards and awareness videos, may be tailored to local languages and contexts to effectively acknowledge cultural sensitivity. In Honduras, a national vaccination campaign with educational materials designed for broad accessibility (posters and flyers on retinoblastoma) significantly reduced extraocular retinoblastoma cases (P = .002) through effectively improving early detection.22Several nonprofit organizations, like Know The Glow and World Eye Cancer Hope, provide free, culturally adaptable educational resources aimed at empowering families in LMICs.23 Global organizations like International Agency for the Prevention of Blindness (IAPB) Knowledge Hub offer toolkits, videos, and print materials that can be used in public health campaigns to promote awareness of pediatric eye diseases, including retinoblastoma.24International partnerships with organizations like the WHO, United Nations International Children’s Emergency Fund, AAP, and IAPB can support global campaigns and screening programs, including prenatal genetic screening for families with a history of retinoblastoma. These organizations are well-positioned to collaborate with national governments in developing and implementing evidence-based screening policies. In parallel, initiatives by One Retinoblastoma World, World Eye Cancer Hope, and the Retinoblastoma Network have already been contributing by raising awareness and expanding access through shared care models and telemedicine.5,23The Retinoblastoma Network (Rb-NET), launched in 2017, is one example of a successful shared care model. Through collaborative initiatives and a multidisciplinary approach, it delivers integrated retinoblastoma care in LMICs. This facilitated the development of the Global Retinoblastoma Study Group, which brought together many experts around the world to improve outcomes globally.5 By adapting elements of these shared care models, national governments can enhance local capacity, establish strong referral networks, and improve timely access to specialized retinoblastoma care.National governments can further strengthen early detection by integrating ocular screening into newborn and child health policies, securing supply chains for diagnostic tools, and mandating RRT training in undergraduate medical curricula.11,14,18 Aligning these efforts with Sustainable Development Goal 3 (Good Health and Well-Being) can bring equity to pediatric oncology care.Strengthening early detection by training frontline providers, providing community education, embracing cost-effective technologies, and integrating eye screening into existing child health programs offers a crucial opportunity for the timely diagnosis and treatment of retinoblastoma in LMICs. Such efforts, coupled with improved access to care and strategies to reduce treatment refusal or abandonment, can contribute to advancing equity in pediatric cancer care globally, and also help to reduce preventable blindness and mortality.