Saving the Eye, Counting the Cost: Rethinking Treatment Burden in Unilateral Retinoblastoma

The management of retinoblastoma has changed profoundly over recent decades. In high-income countries, survival now exceeds 95%, shifting therapeutic priorities from life preservation alone towards globe salvage and vision preservation [1, 2]. Advances such as intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy and focal consolidation have enabled many children to retain an eye that would previously have been enucleated. Yet as treatment options expand, an essential dimension of care warrants closer attention: the cumulative burden of treatment experienced by children and their families. In this issue of Clinical and Experimental Ophthalmology, Rolfe and colleagues present a detailed evaluation of treatment burden in children with sporadic unilateral retinoblastoma treated in Australia [3]. By quantifying examinations under anaesthesia (EUAs), total anaesthetics, hospital admissions, outpatient visits and total healthcare encounters, the authors move beyond traditional oncologic and ocular endpoints to capture the lived experience of contemporary retinoblastoma care and the cost to save an eye. Their findings are compelling. Children treated with globe-conserving therapies—whether IVC or IAC—experienced a substantially higher treatment burden than those undergoing primary enucleation, particularly within the first 12 months following diagnosis, with increased healthcare utilisation persisting beyond the first year. This work builds on prior studies using EUAs as a surrogate measure of disease burden. Fabian and colleagues demonstrated that children undergoing eye-salvaging therapy require approximately two to three times more EUAs than those treated with primary enucleation, even in unilateral disease [4, 5]. Rolfe et al. extend this concept by capturing a broader range of encounters, including oncology visits and admissions related to chemotherapy and its complications. Their data demonstrate a three- to four-fold increase in total hospital visits in the first year for children receiving globe-conserving therapy, with no significant difference between IVC and IAC during that period. These findings are particularly relevant in sporadic unilateral retinoblastoma, where cure rates are excellent regardless of primary treatment modality and therapeutic decisions are often guided by the preference of caregivers—who may not understand the full impact of the care needs especially early after diagnosis when these initial decisions are made. Globe salvage offers the potential for retained vision and avoids the lifelong cosmetic implications of eye loss. However, as this study clearly shows, it also entails a prolonged and intensive treatment course characterised by repeated anaesthetic administrations for EUAs, IAC, MRI, chemotherapy exposure and hospitalizations for both planned therapy and treatment-related complications. For children, this intensity of care raises important concerns. Repeated exposure to general anaesthesia during early childhood has prompted concern regarding potential neurodevelopmental effects and psychological trauma from caregiver separation and forced mask induction can occur. In addition, chemotherapy carries established systemic risks including ototoxicity, myelosuppression and febrile neutropenia [6]. In the cohort described by Rolfe et al., febrile neutropenia was a major contributor to unplanned admissions, underscoring the clinical and emotional toll of systemic therapy. Beyond physical morbidity, frequent hospital encounters may shape early childhood experiences in ways that influence emotional development and medical anxiety. The burden of care extends well beyond the patient. Caregivers of children with retinoblastoma consistently report significant psychological distress, driven not only by fear of mortality but by prolonged uncertainty regarding the status of the eye, treatment intensity and disruption to family life [7]. Qualitative studies have identified frequent hospital visits, repeated anaesthesia, and extended treatment timelines as major contributors to trauma and stress, affecting siblings as well as primary caregivers [7]. For families facing geographic, financial or social barriers, the cumulative impact of repeated hospital encounters may be particularly profound. Family and caregiver burden includes fatigue, high levels of anxiety, depression and guilt, particularly when trying to balance the demanding, long-term treatment schedule with daily life and other offspring. Additionally, the financial, medical and emotional strain can lead to significant stress on the parental relationship [8]. Importantly, a higher treatment burden should not be equated with poorer quality of life, nor should a lower burden be assumed to represent a superior outcome. Contradictory to previous findings, a recent study demonstrated that adolescent and young adult survivors of retinoblastoma report similar quality of life compared to their healthy peers regardless of treatment regimen (including enucleation) [9]. Enucleation itself carries lifelong consequences. Children with monocular vision may experience deficits in depth perception and motor coordination, and long-term neuroplastic changes following early enucleation have been described [10]. Issues related to cosmesis, prosthesis maintenance and social integration may also emerge over time. Nevertheless, many adult survivors and caregivers retrospectively view enucleation positively, valuing the oncologic certainty and avoidance of prolonged therapy it provides [7]. Together, these data highlight the need to broaden how success is defined in retinoblastoma care. Survival and globe salvage, while essential, are incomplete metrics when considered in isolation. Treatment burden—encompassing the frequency and duration of interventions, complications, psychosocial impact, and family burden—represents a meaningful outcome that directly shapes the lived experience of childhood cancer care. In unilateral disease, where multiple treatment pathways may offer equivalent survival, burden becomes a critical factor in shared decision-making. As eye-salvaging therapies become increasingly sophisticated and accessible, there is a risk that treatment intensity becomes normalised or underemphasized. Transparent counselling should include not only the potential benefits of globe salvage but also a realistic portrayal of the anticipated treatment course, including the psychosocial burden, the frequency of anaesthesia, hospital visits and the possibility of rescue therapy or secondary enucleation after failed attempts at globe salvage (not to mention that chemotherapy may be again needed after an enucleation). Families differ in their values, resources and tolerance for uncertainty, and treatment recommendations should reflect these differences and be openly discussed. The current findings by Rolfe and colleagues underscore that the treatment of unilateral sporadic retinoblastoma, particularly with globe-conserving modalities like IVC and IAC, is associated with a significantly higher burden of treatment—including more anaesthetics and hospital visits—compared to primary enucleation. Their work reminds us that preserving an eye is not synonymous with preserving childhood, and that the true cost of cure extends beyond the operating theatre. Rolfe and colleagues are to be commended for bringing treatment burden to the forefront of retinoblastoma discourse. Their work highlights that while eye preservation is a key objective, it comes with a high, often unrecognised, cost to the child's quality of life and the family, as the true burden extends beyond just the immediate, lifesaving or vision-sparing procedures. As therapeutic options continue to expand, integrating treatment burden into outcome assessment and clinical conversations will be essential to delivering patient-centered care for children with retinoblastoma and their families. The authors would like to acknowledge the tireless efforts of the entire CHLA retinoblastoma team in the compassionate care of patients with this disease. The authors have no funding directly related to this manuscript. Dr. Berry has grant support from National Cancer Institute of the National Institute of Health Award Number R01CA282759 Wright Foundation Children's Oncology Group/St. Baldrick's Foundation Alex's Lemonade Stand Foundation Grant # is 23-27881 Melanoma Research Association The Amy Elizabeth Corwin Aqueous Humor Liquid Biopsy Laboratory Danhakl Family Foundation The Knights Templar Eye Foundation A. Linn Murphree, MD, Chair in Ocular Oncology The Berle & Lucy Adams Chair in Cancer Research The Larry and Celia Moh Foundation An unrestricted departmental grant from Research to Prevent Blindness funds in honor of Rory Anne and her Papop. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.