From darkness to autonomy: The social and economic return of treating Retinopathy of Prematurity (ROP)

From darkness to autonomy: The social and economic return of treating Retinopathy of Prematurity (ROP) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article From darkness to autonomy: The social and economic return of treating Retinopathy of Prematurity (ROP) María José Barragán, Ellery Lopez-Star, Benjamin Aleman-Castilla, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8634905/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Retinopathy of Prematurity (ROP) is the leading cause of childhood blindness worldwide. Although effective treatments exist, their success depends on early diagnosis. In Mexico, limited public healthcare resources restrict adequate ROP screening, leaving many at-risk infants vulnerable to preventable blindness. Nonprofit organizations, such as the Mexican Institute of Ophthalmology (IMO), help bridge these gaps by providing accessible early detection and treatment. This study aims to evaluate the social and economic impact of treating ROP in Queretaro, Mexico, using a Social Return on Investment (SROI) framework. Methods Using the SROI methodology, the analysis draws on data from 342 infants to assess the costs and benefits of IMO’s screening program. Infant benefits are estimated through utility valuations based on visual acuity and weighted by the Value per Statistical Life (VSL). Caregiver benefits reflect reduced opportunity costs, as timely treatment enables earlier workforce reentry. Costs include medical resources, equipment depreciation, human resources, and caregivers’ time, food, and travel expenses. Results Among all screened infants, 9.6% required and received treatment for ROP. When accounting for all program costs, including those for infants not requiring treatment, and considering only the benefits of treated cases, findings show an average return of 48 Mexican pesos in well-being for every peso invested (a 48:1 ratio). When focusing exclusively on the beneficiaries, the average SROI rises to 493:1. Conclusions These findings offer valuable insights for policymakers, healthcare providers, and nonprofits to support early screening and treatment programs that prevent childhood blindness and improve long-term quality of life. Health sciences/Health care/Quality of life Health sciences/Diseases/Eye diseases/Retinal diseases Health sciences/Health care/Health care economics Health sciences/Health care/Public health Health sciences/Risk factors ROP cost-benefit analysis SROI nonprofit organizations Mexico Figures Figure 1 Figure 2 Figure 3 1. Introduction The rise in premature births, along with improved survival rates due to advances in neonatal care, has led to a growing number of infants at risk of developing preterm-related morbidities ( 1 ). A study analyzing cause-specific vision loss data from the Global Health Data Exchange reports that between 1990 and 2019, prevalence of moderate/severe vision impairment and blindness due to neonatal disorders increased from 13.73% to 33.53%, with retinopathy of prematurity (ROP) being the leading cause of vision loss related to these conditions ( 2 ). ROP is a condition that affects the development of retinal blood vessels in premature infants, potentially leading to severe visual impairment or blindness if left untreated. In the International Classification of Retinopathy of Prematurity, ROP is classified into five stages based on disease severity. Stage 1 is characterized by a demarcation line separating the vascularized and avascular retina. Stage 2 involves the formation of a ridge at this boundary. Stage 3 is marked by extraretinal neovascularization. Stage 4 involves partial retinal detachment, and Stage 5 represents total retinal detachment ( 3 ). Its causes are multifactorial, with lower gestational age, low birth weight, and hyperoxia being the most frequently associated factors ( 4 ) . Effective treatments for ROP, which significantly reduce the risk of poor visual outcomes and blindness, have been available for decades. Currently, the primary treatment options include laser photocoagulation therapy and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections ( 5 , 6 ). However, despite being a preventable condition, ROP remains the leading cause of childhood blindness worldwide ( 1 , 7 , 8 ). In 2019 alone, ROP accounted for 49.1 thousand cases of moderate vision loss, 27.5 thousand cases of severe vision loss, and 25.0 thousand cases of blindness ( 2 ). Furthermore, a recent systematic review analyzing global trends in ROP prevalence from 1985 to 2021 reported a pooled prevalence of 31.9%, with severe ROP occurring in 7.5% of cases ( 4 ), highlighting the significant burden this condition continues to pose worldwide. While effective treatments exist, their success depends on early and timely diagnosis, as interventions must occur within a critical four-week window after birth. A robust ROP screening program is essential to identify at-risk infants who could benefit from intervention while recognizing that not all cases require treatment. Timely screening is critical, as undiagnosed or delayed treatment can lead to irreversible blindness. These programs ensure that vision-threatening conditions are detected early, enabling successful interventions that preserve vision and enhance long-term quality of life for both premature infants and their caregivers ( 4 ). Despite legislation mandating eye examinations for preterm infants, Mexico’s public healthcare system struggles to provide adequate ROP screening programs due to limited resources. As a result, many at-risk infants face preventable blindness due to delayed or missed diagnoses within the critical four-week window. Evidence of these shortcomings is highlighted in a study by Zepeda C. and Gilbert C. ( 9 ), which found that 34.4% of surveyed Neonatal Intensive Care Units (NICUs) lacked a ROP program, while another 34.4% operated noncompliant programs, leaving a significant proportion of premature infants without proper eye care ( 10 ). Furthermore, Mexico’s health system is characterized by significant inequalities in financing and service delivery. Public health investment amounts to only half of the minimum level recommended by the World Health Organization and lags behind other countries in Latin America ( 11 ). Despite this, the 2025 budget for public health has been reduced by approximately 20%. Moreover, the public health system provides unequal resources and care based on individuals’ employment status, exacerbating disparities. According to the latest multidimensional poverty estimates published by the National Council for the Evaluation of Social Development Policy (CONEVAL), more than one-third of the Mexican population lacks access to public health services ( 12 ). Nonprofit organizations play a crucial role in addressing these gaps by offering vital complementary or supplementary roles to deliver accessible and affordable eye care. The Mexican Institute of Ophthalmology (IMO), a nonprofit healthcare institution based in Querétaro, central Mexico, is a key player in this effort. Established in 1997, its primary mission is to provide comprehensive diagnosis, treatment, and prevention of eye diseases for the low-income population. It boasts a multidisciplinary team of professionals, including ophthalmologists, anesthesiologists, internists, optometrists, assistants, nurses, and administrative staff, all dedicated to improving patients’ eyesight and overall quality of life. When public sector efforts are insufficient and require complementary action from the private sector, assessing the costs and benefits of nonprofit activities becomes particularly important. This evaluation serves several key purposes. First, it ensures transparency and accountability to stakeholders ( 13 ). Second, by distinguishing between high-impact initiatives and those with greater financial demands, nonprofits can make better strategic decisions, allocate resources more effectively, and enhance their chances of obtaining external funding ( 14 ). Third, cost-benefit analysis supports performance benchmarking, enabling organizations to compare their operations with sector norms and identify both exemplary practices and areas needing improvement ( 15 ). Additionally, systematically measuring and sharing these outcomes contributes to organizational learning and generates knowledge about the social value and impact of nonprofit interventions. By providing timely ROP interventions for vulnerable populations, IMO exemplifies how nonprofits can bridge disparities in neonatal ocular health, improve access to critical services, and reduce the burden of preventable blindness among underserved communities. In this context, the present study aims to evaluate the social and economic impact of the ROP screening program implemented by IMO in Querétaro, Mexico, using a Social Return on Investment (SROI) framework. While there is growing interest in the cost-effectiveness of early interventions in neonatal care, empirical research on the long-term social value of ROP screening programs in Mexico remains scarce, particularly in terms of quality-of-life improvements for both premature infants and their caregivers. By addressing this gap, the study contributes new evidence to support informed decision-making in public health policy. The paper is structured as follows: it begins with a description of the methodology and the SROI approach, followed by the Theory of Change used to map the expected pathways of impact. It then presents the data sources and descriptive analysis of the screened population, outlines the inputs and costs associated with program implementation, and details the outcomes considered in the valuation of benefits. Finally, the results of the SROI analysis are presented, followed by a discussion of their implications for healthcare policy, resource allocation, and the design of early screening programs. 2. Methods The present study employs the Social Return on Investment (SROI) methodology, to evaluate the costs and benefits of the screening program for early detection of ROP at IMO. SROI is a recognized framework for evaluating a broad range of non-financial outcomes and values, such as social well-being, environmental sustainability, and community development ( 16 ). Organizations frequently adopt SROI to assess and communicate their social and environmental contributions beyond standard financial metrics. This tool offers a clear perspective on the social value generated relative to costs, supporting investments in preventive and treatment programs. It quantifies social benefits in monetary terms, demonstrates long-term cost savings, and measures improvements such as enhanced quality of life and reduced visual impairments. 2.1 Theory of Change Figure 1 illustrates the theory of change for IMO's screening program for early ROP, mapping how inputs lead to outputs and outcomes, and how these outcomes translate into impacts in the life of beneficiaries ( 16 ). The primary stakeholders directly impacted by the intervention are patients and their caregivers. Figure 1 here 2.2 Data and Statistical Analysis Data for the analysis was collected from 342 infants who participated in the IMO's screening program for early ROP detection between October 2021 and July 2023. Among the total sample, only 9.6% required and received treatment for ROP. Table 1 here As shown in Table 1, and following WHO guidelines, preterm infants treated for ROP present, on average, low birth weight, as their mean birth weight is below 2 500 g. Likewise, the mean gestational age of treated infants places them in the very preterm category (born between 28 and < 32 weeks), in contrast with infants without a ROP diagnosis, whose mean gestational age falls within the moderate to late preterm range (32–37 weeks) ( 17 ). The overall sample means for birth weight and gestational age are displayed in Figs. 2 (a) and (b). As shown in Fig. 2 (c), among infants requiring treatment, 60.6% were female, whereas the proportion of females among those not requiring treatment was lower, at 45.7%. Figure 2 (d) illustrates medical conditions at birth. On average, 87.9% of infants treated for ROP experienced respiratory distress syndrome, 19 percentage points higher than infants not treated for ROP (68.8%). In this context, 90.9% of treated infants had received oxygen therapy (vs. 80.6% among non-treated infants), and 75.8% received pulmonary surfactant, a lipoprotein complex that prevents alveolar collapse and improves lung compliance, approximately 30 percentage points higher than the mean for infants not treated for ROP. Additionally, 78.8% of mothers of infants treated for ROP experienced maternal sepsis (vs. 66.7% among non-treated), and 69.7% of treated infants presented hyperbilirubinemia, 23 percentage points lower than those not treated for ROP. Given the observed differences between the means of treated and non-treated preterm infants, we conducted equality-of-means tests using Wilks’ lambda, Pillai’s trace, the Lawley–Hotelling trace, and Roy’s largest root ( 18 ). At the 95% confidence level, all tests rejected the null hypothesis that the means of all variables presented in Table 1 are equal between infants treated and not treated for ROP. We also performed the analysis using a dummy variable indicating treatment status (1 = treated, 0 = not treated). The results similarly provide statistically significant evidence that the groups defined by this variable do not share the same joint combination of means. Notably, 75.8% of the patients were diagnosed in public hospital NICUs, thanks to the ophthalmological visits conducted by IMO specialists to these facilities. Figure 2 here 2.3 Inputs We evaluate both direct and indirect costs associated with diagnosis and treatment. The intervention begins with an ophthalmological examination of premature infants conducted by IMO specialists through two modalities: either at Neonatal Intensive Care Units (NICUs) in public hospitals or at the IMO facility, where infants are accompanied by their primary caregiver, assumed in this study to be the mother. If ROP is diagnosed and the patient is eligible, treatment continues with ranibizumab injections and follow-up consultations, as shown in Fig. 3 . Figure 3 here Mothers contribute both time and money to the intervention, estimated as follows: Time : The value of the mother’s time is estimated using the 2024 general minimum wage of 248.93 Mexican pesos per day (approximately 13.6 US dollars), as set by the National Minimum Wage Commission ( 19 ). This wage serves as a proxy for the opportunity cost of time, representing the baseline income forgone by the mother while engaged in the intervention. Travel expenses : Travel costs were estimated using the methodology proposed by the Mexican Institute of Transport (IMT) for calculating the Generalized Travel Cost (GTC), which represents both monetary and non-monetary costs of a trip ( 20 ). The IMT calculates the GTC using two variables: Vehicle Operating Costs (VOC) and the Value of Time for Road Users for work-related trips (VT). VOC: Calculated based on the expenses incurred by the user of driving a specific vehicle on a given road. It considers factors such as geometric alignment, pavement surface conditions, and their impact on vehicle operating costs, such as fuel, lubricants, maintenance costs, and tire wear ( 21 ). VT: Estimated using the average general minimum wage, the weighted income factor of the population and the weekly average of hours worked by the population ( 22 ). The GTC is then calculated using the following formula: $$\:GTC=\:\left(distance\:\times\:\:VOC\right)+(travel\:time\times\:\:VT)$$ 1 Where distance and travel time are both determined based on the patients’ places of residence. The GTC is then multiplied by the number of visits required for the full two-eye intervention. Food expenses : These are calculated based on the cost of one meal per visit for the mother and one baby formula for the infant at IMO facilities. For IMO, costs include travel expenses, medical resources, depreciation of specialized equipment, human resources, and professional staff. Table 2 presents the summary statistics of these inputs. Table 2 here 2.4 Outcomes To estimate the intervention’s impact on infants’ well-being, outcomes are quantified using utility valuations based on visual acuity. Treated infants with good visual function were assigned a utility value of 0.88, while untreated infants with severe ROP were assigned a value of 0.40, based on Knauer C. and Pfeiffer N. ( 23 ). The difference in visual acuity between untreated and treated patients is then weighted by the Value per Statistical Life (VSL) for newborns in Querétaro, reflecting the economic value of life years gained due to treatment. VSL reflects people’s willingness to trade or sacrifice other resources for reductions in mortality risk. It is calculated as the marginal rate of substitution between money and mortality risk within a specific timeframe. In this study, we use the VSL estimates provided by Becerra-Pérez et al. ( 24 ), who calculated the VSL for Querétaro at $ 1.3 million US dollars, which we converted to Mexican pesos using the average exchange rate for 2021 (20.3 Mexican pesos per U.S. dollar) ( 25 ). Their study followed the OECD’s guidelines outlined in the Mortality Risk Valuation in Environment, Health, and Transport Policies manual ( 26 ). It is important to note that the authors used GDP data from the National Institute of Geography and Statistics (INEGI) for 2021, a year in which the country's economic growth was significantly impacted by the COVID pandemic. As a result, this VSL may be somewhat underestimated. The VSL was used to derive the Value per Statistical Life Year (VSLY), which accounts for the annual value of outcomes from timely treatment. The present value of these outcomes was then computed as a decreasing annuity ( 27 ). Thus, for each infant i , the total benefits derived from the treatment are calculated as: $$\:{Benefit}_{i}={Outcomes}_{i}^{0}[\frac{1}{r-g}-\:\frac{1}{r-g}\:\times\:{\left(\frac{1+g}{1+r}\right)}^{T}]$$ 2 Here, \(\:{Outcomes}_{i}^{0}\) is the VSLY for Querétaro, \(\:g\) is the negative drop-off rate, assumed to be equal to the mortality rate per 1 000 inhabitants obtained from World Development Indicators ( 28 ), \(\:T\) is the life expectancy at birth in Querétaro ( 29 ), and \(\:r\) is the discount rate, which in our baseline scenario is equal to the social discount rate of 10% fixed by the Mexican Ministry of Finance and Public Credit for evaluation of investment programs and projects ( 30 ). The analysis also considers the benefits for primary caregivers, the infants’ mothers, by estimating the reduction in opportunity costs. Without treatment, mothers were assumed to remain out of the labor market until the child reached adulthood (18 years). With treatment, this period was reduced to five years. This opportunity cost was monetized using the net present value of the mother's estimated average annual income (approximately 96 000 Mexican pesos per year, equivalent to 5 400 US dollars), multiplied by the probability of returning to work, which was assessed using Mexico’s female labor force participation rate. Both data points were sourced from the International Labour Organization ( 31 ). 3. Results 3.1 SROI ratio The benefits and costs incurred by the patient, primary caregiver, and IMO, as described earlier, were used to calculate the SROI ratio. This metric provides a comprehensive assessment of the program’s social and economic impact for each patient–caregiver pair \(\:i\) : $$\:{SROI\:ratio}_{i}=\:\frac{\sum\:{Benefit}_{i}}{\sum\:{Cost}_{i}}$$ 3 Among the total sample of 342 screened premature infants, only 9.6% required and received ranibizumab treatment for ROP. For this subset of infants diagnosed with ROP, on average, treatment was effectively managed with a single injection, complemented by 8 follow-up consultations. When considering all costs associated with the ROP screening program, including those related to cases that did not require treatment, and accounting solely for the benefits of treated cases, findings reveal that, on average, for every peso invested, treated patients and their caregivers gain 48 Mexican pesos in well-being, a 48:1 ratio (95% CI: 30–65), with a range of 46:1 to 997:1. If the analysis focuses exclusively on the costs and benefits for program beneficiaries, the average SROI ratio increases significantly to 493:1 (95% CI: 576 − 410). 3.2 Sensitivity analysis To assess the robustness of these results and explore how changes in key assumptions might affect the estimated benefits and costs, we conduct the following sensitivity analysis, as shown in Table 3. This approach provides a more nuanced understanding of the intervention’s impact and supports more informed decision-making in the future. Years that mothers remain out of the labor market : In our baseline scenario, we assume that if the patient receives timely treatment, the mother remains out of the workforce for only five years. We now adjust this value to 0, 10, and 18 years, reporting the corresponding results in case (a) of Table 3. The SROI ratios change on average by + 5.1%, -3.0% and − 5.6%, respectively. Mother's opportunity cost : As previously mentioned, the opportunity cost of the infant’s mother was monetized using the estimated average annual income for women in 2023. To determine the sensitivity of our estimates to this parameter, we first double this amount. In a second scenario, we replace it with the 2024 minimum annual wage of 59,743 Mexican pesos (approximately 3,258 USD). The results are shown in case (b) of Table 3. Modifying the opportunity cost of time induces average changes in SROI ratios of 5.6% and − 2.1%, respectively, compared to the baseline scenario. Visual acuity utility valuations : As described in the Outcomes section, the baseline scenario relies on utility valuations based on visual acuity reported by Knauer and Pfeiffer ( 23 ). In case (c) of the sensitivity analysis, we first vary the utility value assigned to untreated infants with ROP to 0.61, corresponding to visual acuity ranging from 20/200 to no light perception, and to 0.72, corresponding to visual acuity between 20/60 and 20/100, as reported in the same study. These changes result in average SROI variations of -41.3% and − 63.0%, respectively; however, the SROI remains positive under both scenarios. We then modify the utility valuation for treated infants with good visual acuity to 0.81, based on the estimates associated with visual acuity of 20/30–20/50. Under this assumption, the SROI ratio changes by -13.8%. IMO’s total costs : To assess the sensitivity of the results to the total costs incurred by IMO for diagnosis and treatment, we increase these costs by 50% and 75%, and then double and triple them. These adjustments reduce the average SROI ratio by -23.4%, -31.3%, -37.7%, and − 54.3%, respectively; however, the SROI remains positive across all scenarios. The corresponding results are presented in case (d) of Table 3. Discount rate : Finally, we also evaluate the effect of changing the discount rate. Under the baseline scenario it is set at 10 percent, in line with the rate for socioeconomic evaluation of investment programs and projects established by SHCP. We now change it to 0, 5, and 15 percent, reporting the results in case (e). The average changes in SROI ratios are 437.6%, 79.9% and – 31.6%, respectively. Table 3 here 4. Discussion ROP treatment is a quick and effective procedure with minimal complications, offering significant improvements in visual function, quality of life, and psychosocial well-being. However, timely diagnosis is imperative to ensure the treatment's effectiveness. This study conducted a comprehensive analysis of the Social Return on Investment (SROI) of the ROP screening program implemented by IMO, a Mexican nonprofit organization. The aim was to evaluate the potential social value generated by this intervention and provide valuable insights for practitioners and policymakers in the nonprofit sector. Investing in ROP treatment generates significant social and economic benefits, as it not only improves the quality of life for affected children and their families but also reduces long-term societal costs associated with untreated visual impairments. The findings underscore the pivotal role that nonprofit organizations play in addressing gaps in healthcare delivery, particularly in underserved and resource-limited regions where public health systems may fall short. By providing timely interventions and specialized care, these organizations help mitigate the far-reaching consequences of ROP, including developmental delays, educational challenges, and financial burdens on families and the healthcare system. To maximize the impact of such efforts, scaling up neonatal ocular health programs is imperative. This requires not only increased funding and resource allocation but also the development of robust frameworks for early diagnosis, treatment, and follow-up care. Promoting cross-sector collaboration among governments, nonprofits, private entities, and international organizations is equally essential. Nonetheless the limitations of the study must be addressed, such as sample representativeness. This study focused on the ROP screening program implemented by IMO, a specific intervention within a defined context, and while it provides valuable insights, generalizing these results to broader nonprofit initiatives necessitates caution. Future research should consider larger samples and diverse contexts to further enhance the robustness and applicability of results. Declarations Institutional Review Board Statement The study was conducted in accordance with the Declara-tion of Helsinki, ensuring compliance with ethical principles for medical research involving human subjects and approved by the Ethics Committee of Instituto Mexicano de Oftalmología I.A.P (IMO) . It is classified as a no-risk study, as the research methods did not involve any interventions that could affect the physiology, psychology, or social variables of the participants. Conflicts of Interest: The authors declare no conflicts of interest. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Data Availability Statement: The data are not publicly available due to ethical, legal, or other concerns. References Gyllensten H, Humayun J, Sjöbom U, Hellström A, Löfqvist C. Costs associated with retinopathy of prematurity: a systematic review and meta-analysis. BMJ Open. 2022;12(11):e057864. Zhang RH, Liu YM, Dong L, Li HY, Li YF, Zhou WD, et al. Prevalence, Years Lived With Disability, and Time Trends for 16 Causes of Blindness and Vision Impairment: Findings Highlight Retinopathy of Prematurity. Front Pediatr [Internet]. 2022;10. Available from: https://www.frontiersin.org/journals/pediatrics/articles/ 10.3389/fped.2022.735335 Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Paul Chan R V, Berrocal A, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology [Internet]. 2021;128(10):e51–68. 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World Development Indicators [Internet]. 2023 [cited 2025 Mar 30]. Available from: https://databank.worldbank.org/source/world-development-indicators INEGI. Esperanza de vida al nacimiento por entidad federativa según sexo, serie anual de 2010 a 2025 [Internet]. 2023 [cited 2025 Mar 30]. Available from: https://www.inegi.org.mx/app/tabulados/interactivos/?pxq=Mortalidad_Mortalidad_09_25171f46-857b-4d3a-aeae-c61235598f32 SHCP. Oficio No. 400.1.410.22.234. 2022 [cited 2023 May 9]. Determinación de la Tasa Social de Descuento aplicable a programas y proyectos de inversión. Available from: https://www.gob.mx/shcp/documentos/tasa-social-de-descuento-tsd . ILO. ILOSTAT. 2023. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations There is no conflict of interest Supplementary Files Table1.DescriptivestatisticsofpreterminfantsscreenedbyIMO.xlsx Table 1 Table3.Sensitivityanalysis.xlsx Table 3 Table2.SummarystatisticsofthevalueofinputsbystakeholdersandIMO.xlsx Table 2 Cite Share Download PDF Status: Under Review Version 1 posted Reviewer # 1 agreed at journal 07 May, 2026 Reviewers invited by journal 11 Feb, 2026 Editor assigned by journal 05 Feb, 2026 Submission checks completed at journal 19 Jan, 2026 First submitted to journal 18 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8634905","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":589440511,"identity":"b2af2ced-2b68-499f-8436-f4a7e2969a14","order_by":0,"name":"María José Barragán","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYDACCWTOBwMgcYAELYyNM0jW0szDQIQW3dnNzz5X1NTKm7P3mD+2Kbgjz3e8gXUzDx4tZneOGc88c+y44c6eY4nNOQbPDGeeOcB2cwY+LTcSjBkb2I4xbriRfBCo5TCQkcB24wNeLemfGRv+HbPfcP9hY7OFwWEg4wHbjQS8WnKMGRvbahI33GA+2MxgcBjIYCBgy50zxYyNfQeSN5xJS5zZY/AseeaZxDb8frndvpmx4Vud7YbjZww+/Phzx7bv+OFjt/GFGBQchjEOADFjA2ENDAx1yFpGwSgYBaNgFKACAIZOYBONmtjJAAAAAElFTkSuQmCC","orcid":"","institution":"IPADE Business School (IPADE)","correspondingAuthor":true,"prefix":"","firstName":"María","middleName":"José","lastName":"Barragán","suffix":""},{"id":589440512,"identity":"86d44df9-d851-4ede-ae14-990f580a37a2","order_by":1,"name":"Ellery Lopez-Star","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ellery","middleName":"","lastName":"Lopez-Star","suffix":""},{"id":589440513,"identity":"ac82be6a-204f-4a19-a52e-89cab81bacf2","order_by":2,"name":"Benjamin Aleman-Castilla","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Benjamin","middleName":"","lastName":"Aleman-Castilla","suffix":""},{"id":589440514,"identity":"2eef759b-eff9-42dc-aa92-56d57f33e4e0","order_by":3,"name":"Marlon García-Roa","email":"","orcid":"https://orcid.org/0000-0003-1970-799X","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Marlon","middleName":"","lastName":"García-Roa","suffix":""},{"id":589440515,"identity":"c84abb34-4ffc-40a9-8100-40d6362e995c","order_by":4,"name":"Luis Ochoa Ramírez","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Luis","middleName":"Ochoa","lastName":"Ramírez","suffix":""}],"badges":[],"createdAt":"2026-01-19 04:20:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8634905/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8634905/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102761007,"identity":"e99182c1-897e-4f54-9e27-bf1da906e04d","added_by":"auto","created_at":"2026-02-16 10:33:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73934,"visible":true,"origin":"","legend":"\u003cp\u003eTheory of change for the timely treatment of ROP\u003c/p\u003e","description":"","filename":"Figure1.TheoryofchangeforthetimelytreatmentofROP.png","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/5e396202ad8d3212cd5b0fa9.png"},{"id":102962688,"identity":"620db1a5-0d02-4084-977b-ae2b20d1b468","added_by":"auto","created_at":"2026-02-19 04:10:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":154399,"visible":true,"origin":"","legend":"\u003cp\u003eGeneral profile of infants screened for ROP at IMO\u003c/p\u003e","description":"","filename":"Figure2.GeneralprofileofinfantsscreenedforROPatIMO.png","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/a94907188a5a997d98b8f0f8.png"},{"id":102761002,"identity":"8c7108b1-c694-4fd1-936f-8da0db8eacaf","added_by":"auto","created_at":"2026-02-16 10:33:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":70705,"visible":true,"origin":"","legend":"\u003cp\u003eDiagnostic flowchart for ROP in IMO’s screening program\u003c/p\u003e","description":"","filename":"Figure3.DiagnosticflowchartforROPinIMOXXXsscreeningprogram.png","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/77ae3ac5c2f5d2ad907f7455.png"},{"id":102964934,"identity":"29328669-c770-4946-ab32-9558921af6b3","added_by":"auto","created_at":"2026-02-19 04:29:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":915139,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/7c12319d-0bef-4e65-9c35-ab6d30d17249.pdf"},{"id":102761005,"identity":"75f5dff4-608e-4b2a-a1a5-b13b8f37975a","added_by":"auto","created_at":"2026-02-16 10:33:51","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13967,"visible":true,"origin":"","legend":"Table 1","description":"","filename":"Table1.DescriptivestatisticsofpreterminfantsscreenedbyIMO.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/f24708dcac7710497c5f4ccc.xlsx"},{"id":102761006,"identity":"e787966f-6fec-4470-98e6-8ec2131afb73","added_by":"auto","created_at":"2026-02-16 10:33:51","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":12799,"visible":true,"origin":"","legend":"Table 3","description":"","filename":"Table3.Sensitivityanalysis.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/45cd50998a649aecd2c644c6.xlsx"},{"id":102761003,"identity":"89cb25ef-36fa-4f98-925a-98d62b54d658","added_by":"auto","created_at":"2026-02-16 10:33:51","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":11924,"visible":true,"origin":"","legend":"Table 2","description":"","filename":"Table2.SummarystatisticsofthevalueofinputsbystakeholdersandIMO.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8634905/v1/8b0caec2d020a43c22386779.xlsx"}],"financialInterests":"There is no conflict of interest","formattedTitle":"From darkness to autonomy: The social and economic return of treating Retinopathy of Prematurity (ROP)","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe rise in premature births, along with improved survival rates due to advances in neonatal care, has led to a growing number of infants at risk of developing preterm-related morbidities (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). A study analyzing cause-specific vision loss data from the Global Health Data Exchange reports that between 1990 and 2019, prevalence of moderate/severe vision impairment and blindness due to neonatal disorders increased from 13.73% to 33.53%, with retinopathy of prematurity (ROP) being the leading cause of vision loss related to these conditions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eROP is a condition that affects the development of retinal blood vessels in premature infants, potentially leading to severe visual impairment or blindness if left untreated. In the International Classification of Retinopathy of Prematurity, ROP is classified into five stages based on disease severity. Stage 1 is characterized by a demarcation line separating the vascularized and avascular retina. Stage 2 involves the formation of a ridge at this boundary. Stage 3 is marked by extraretinal neovascularization. Stage 4 involves partial retinal detachment, and Stage 5 represents total retinal detachment (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Its causes are multifactorial, with lower gestational age, low birth weight, and hyperoxia being the most frequently associated factors (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003eEffective treatments for ROP, which significantly reduce the risk of poor visual outcomes and blindness, have been available for decades. Currently, the primary treatment options include laser photocoagulation therapy and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, despite being a preventable condition, ROP remains the leading cause of childhood blindness worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In 2019 alone, ROP accounted for 49.1 thousand cases of moderate vision loss, 27.5 thousand cases of severe vision loss, and 25.0 thousand cases of blindness (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Furthermore, a recent systematic review analyzing global trends in ROP prevalence from 1985 to 2021 reported a pooled prevalence of 31.9%, with severe ROP occurring in 7.5% of cases (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), highlighting the significant burden this condition continues to pose worldwide.\u003c/p\u003e \u003cp\u003eWhile effective treatments exist, their success depends on early and timely diagnosis, as interventions must occur within a critical four-week window after birth. A robust ROP screening program is essential to identify at-risk infants who could benefit from intervention while recognizing that not all cases require treatment. Timely screening is critical, as undiagnosed or delayed treatment can lead to irreversible blindness. These programs ensure that vision-threatening conditions are detected early, enabling successful interventions that preserve vision and enhance long-term quality of life for both premature infants and their caregivers (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite legislation mandating eye examinations for preterm infants, Mexico\u0026rsquo;s public healthcare system struggles to provide adequate ROP screening programs due to limited resources. As a result, many at-risk infants face preventable blindness due to delayed or missed diagnoses within the critical four-week window. Evidence of these shortcomings is highlighted in a study by Zepeda C. and Gilbert C. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), which found that 34.4% of surveyed Neonatal Intensive Care Units (NICUs) lacked a ROP program, while another 34.4% operated noncompliant programs, leaving a significant proportion of premature infants without proper eye care (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, Mexico\u0026rsquo;s health system is characterized by significant inequalities in financing and service delivery. Public health investment amounts to only half of the minimum level recommended by the World Health Organization and lags behind other countries in Latin America (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Despite this, the 2025 budget for public health has been reduced by approximately 20%. Moreover, the public health system provides unequal resources and care based on individuals\u0026rsquo; employment status, exacerbating disparities. According to the latest multidimensional poverty estimates published by the National Council for the Evaluation of Social Development Policy (CONEVAL), more than one-third of the Mexican population lacks access to public health services (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNonprofit organizations play a crucial role in addressing these gaps by offering vital complementary or supplementary roles to deliver accessible and affordable eye care. The Mexican Institute of Ophthalmology (IMO), a nonprofit healthcare institution based in Quer\u0026eacute;taro, central Mexico, is a key player in this effort. Established in 1997, its primary mission is to provide comprehensive diagnosis, treatment, and prevention of eye diseases for the low-income population. It boasts a multidisciplinary team of professionals, including ophthalmologists, anesthesiologists, internists, optometrists, assistants, nurses, and administrative staff, all dedicated to improving patients\u0026rsquo; eyesight and overall quality of life.\u003c/p\u003e \u003cp\u003eWhen public sector efforts are insufficient and require complementary action from the private sector, assessing the costs and benefits of nonprofit activities becomes particularly important. This evaluation serves several key purposes. First, it ensures transparency and accountability to stakeholders (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Second, by distinguishing between high-impact initiatives and those with greater financial demands, nonprofits can make better strategic decisions, allocate resources more effectively, and enhance their chances of obtaining external funding (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Third, cost-benefit analysis supports performance benchmarking, enabling organizations to compare their operations with sector norms and identify both exemplary practices and areas needing improvement (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Additionally, systematically measuring and sharing these outcomes contributes to organizational learning and generates knowledge about the social value and impact of nonprofit interventions.\u003c/p\u003e \u003cp\u003eBy providing timely ROP interventions for vulnerable populations, IMO exemplifies how nonprofits can bridge disparities in neonatal ocular health, improve access to critical services, and reduce the burden of preventable blindness among underserved communities.\u003c/p\u003e \u003cp\u003eIn this context, the present study aims to evaluate the social and economic impact of the ROP screening program implemented by IMO in Quer\u0026eacute;taro, Mexico, using a Social Return on Investment (SROI) framework. While there is growing interest in the cost-effectiveness of early interventions in neonatal care, empirical research on the long-term social value of ROP screening programs in Mexico remains scarce, particularly in terms of quality-of-life improvements for both premature infants and their caregivers. By addressing this gap, the study contributes new evidence to support informed decision-making in public health policy.\u003c/p\u003e \u003cp\u003eThe paper is structured as follows: it begins with a description of the methodology and the SROI approach, followed by the Theory of Change used to map the expected pathways of impact. It then presents the data sources and descriptive analysis of the screened population, outlines the inputs and costs associated with program implementation, and details the outcomes considered in the valuation of benefits. Finally, the results of the SROI analysis are presented, followed by a discussion of their implications for healthcare policy, resource allocation, and the design of early screening programs.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThe present study employs the Social Return on Investment (SROI) methodology, to evaluate the costs and benefits of the screening program for early detection of ROP at IMO. SROI is a recognized framework for evaluating a broad range of non-financial outcomes and values, such as social well-being, environmental sustainability, and community development (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOrganizations frequently adopt SROI to assess and communicate their social and environmental contributions beyond standard financial metrics. This tool offers a clear perspective on the social value generated relative to costs, supporting investments in preventive and treatment programs. It quantifies social benefits in monetary terms, demonstrates long-term cost savings, and measures improvements such as enhanced quality of life and reduced visual impairments.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Theory of Change\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the theory of change for IMO's screening program for early ROP, mapping how inputs lead to outputs and outcomes, and how these outcomes translate into impacts in the life of beneficiaries (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The primary stakeholders directly impacted by the intervention are patients and their caregivers.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data and Statistical Analysis\u003c/h2\u003e \u003cp\u003eData for the analysis was collected from 342 infants who participated in the IMO's screening program for early ROP detection between October 2021 and July 2023. Among the total sample, only 9.6% required and received treatment for ROP.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;1 here\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAs shown in Table\u0026nbsp;1, and following WHO guidelines, preterm infants treated for ROP present, on average, low birth weight, as their mean birth weight is below 2 500 g. Likewise, the mean gestational age of treated infants places them in the very preterm category (born between 28 and \u0026lt;\u0026thinsp;32 weeks), in contrast with infants without a ROP diagnosis, whose mean gestational age falls within the moderate to late preterm range (32\u0026ndash;37 weeks) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The overall sample means for birth weight and gestational age are displayed in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e (a) and (b).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e (c), among infants requiring treatment, 60.6% were female, whereas the proportion of females among those not requiring treatment was lower, at 45.7%.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e (d) illustrates medical conditions at birth. On average, 87.9% of infants treated for ROP experienced respiratory distress syndrome, 19 percentage points higher than infants not treated for ROP (68.8%). In this context, 90.9% of treated infants had received oxygen therapy (vs. 80.6% among non-treated infants), and 75.8% received pulmonary surfactant, a lipoprotein complex that prevents alveolar collapse and improves lung compliance, approximately 30 percentage points higher than the mean for infants not treated for ROP. Additionally, 78.8% of mothers of infants treated for ROP experienced maternal sepsis (vs. 66.7% among non-treated), and 69.7% of treated infants presented hyperbilirubinemia, 23 percentage points lower than those not treated for ROP.\u003c/p\u003e \u003cp\u003eGiven the observed differences between the means of treated and non-treated preterm infants, we conducted equality-of-means tests using Wilks\u0026rsquo; lambda, Pillai\u0026rsquo;s trace, the Lawley\u0026ndash;Hotelling trace, and Roy\u0026rsquo;s largest root (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). At the 95% confidence level, all tests rejected the null hypothesis that the means of all variables presented in Table\u0026nbsp;1 are equal between infants treated and not treated for ROP. We also performed the analysis using a dummy variable indicating treatment status (1\u0026thinsp;=\u0026thinsp;treated, 0\u0026thinsp;=\u0026thinsp;not treated). The results similarly provide statistically significant evidence that the groups defined by this variable do not share the same joint combination of means.\u003c/p\u003e \u003cp\u003eNotably, 75.8% of the patients were diagnosed in public hospital NICUs, thanks to the ophthalmological visits conducted by IMO specialists to these facilities.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Inputs\u003c/h2\u003e \u003cp\u003eWe evaluate both direct and indirect costs associated with diagnosis and treatment. The intervention begins with an ophthalmological examination of premature infants conducted by IMO specialists through two modalities: either at Neonatal Intensive Care Units (NICUs) in public hospitals or at the IMO facility, where infants are accompanied by their primary caregiver, assumed in this study to be the mother. If ROP is diagnosed and the patient is eligible, treatment continues with ranibizumab injections and follow-up consultations, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMothers contribute both time and money to the intervention, estimated as follows:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eTime\u003c/b\u003e: The value of the mother\u0026rsquo;s time is estimated using the 2024 general minimum wage of 248.93 Mexican pesos per day (approximately 13.6 US dollars), as set by the National Minimum Wage Commission (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This wage serves as a proxy for the opportunity cost of time, representing the baseline income forgone by the mother while engaged in the intervention.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eTravel expenses\u003c/b\u003e: Travel costs were estimated using the methodology proposed by the Mexican Institute of Transport (IMT) for calculating the Generalized Travel Cost (GTC), which represents both monetary and non-monetary costs of a trip (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The IMT calculates the GTC using two variables: Vehicle Operating Costs (VOC) and the Value of Time for Road Users for work-related trips (VT).\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eVOC: Calculated based on the expenses incurred by the user of driving a specific vehicle on a given road. It considers factors such as geometric alignment, pavement surface conditions, and their impact on vehicle operating costs, such as fuel, lubricants, maintenance costs, and tire wear (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eVT: Estimated using the average general minimum wage, the weighted income factor of the population and the weekly average of hours worked by the population (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe GTC is then calculated using the following formula:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Equ1\" class=\"Equation\"\u003e \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e\n$$\\:GTC=\\:\\left(distance\\:\\times\\:\\:VOC\\right)+(travel\\:time\\times\\:\\:VT)$$\u003c/div\u003e \u003cdiv class=\"EquationNumber\"\u003e1\u003c/div\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eWhere distance and travel time are both determined based on the patients\u0026rsquo; places of residence. The GTC is then multiplied by the number of visits required for the full two-eye intervention.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eFood expenses\u003c/b\u003e: These are calculated based on the cost of one meal per visit for the mother and one baby formula for the infant at IMO facilities.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFor IMO, costs include travel expenses, medical resources, depreciation of specialized equipment, human resources, and professional staff. Table\u0026nbsp;2 presents the summary statistics of these inputs.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;2 here\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Outcomes\u003c/h2\u003e \u003cp\u003eTo estimate the intervention\u0026rsquo;s impact on infants\u0026rsquo; well-being, outcomes are quantified using utility valuations based on visual acuity. Treated infants with good visual function were assigned a utility value of 0.88, while untreated infants with severe ROP were assigned a value of 0.40, based on Knauer C. and Pfeiffer N. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The difference in visual acuity between untreated and treated patients is then weighted by the Value per Statistical Life (VSL) for newborns in Quer\u0026eacute;taro, reflecting the economic value of life years gained due to treatment.\u003c/p\u003e \u003cp\u003eVSL reflects people\u0026rsquo;s willingness to trade or sacrifice other resources for reductions in mortality risk. It is calculated as the marginal rate of substitution between money and mortality risk within a specific timeframe.\u003c/p\u003e \u003cp\u003eIn this study, we use the VSL estimates provided by Becerra-P\u0026eacute;rez et al. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), who calculated the VSL for Quer\u0026eacute;taro at \u003cspan\u003e$\u003c/span\u003e1.3\u0026nbsp;million US dollars, which we converted to Mexican pesos using the average exchange rate for 2021 (20.3 Mexican pesos per U.S. dollar) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Their study followed the OECD\u0026rsquo;s guidelines outlined in the \u003cem\u003eMortality Risk Valuation in Environment, Health, and Transport Policies\u003c/em\u003e manual (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). It is important to note that the authors used GDP data from the National Institute of Geography and Statistics (INEGI) for 2021, a year in which the country's economic growth was significantly impacted by the COVID pandemic. As a result, this VSL may be somewhat underestimated.\u003c/p\u003e \u003cp\u003eThe VSL was used to derive the Value per Statistical Life Year (VSLY), which accounts for the annual value of outcomes from timely treatment. The present value of these outcomes was then computed as a decreasing annuity (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Thus, for each infant \u003cem\u003ei\u003c/em\u003e, the total benefits derived from the treatment are calculated as:\u003cdiv id=\"Equ2\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ2\" name=\"EquationSource\"\u003e\n$$\\:{Benefit}_{i}={Outcomes}_{i}^{0}[\\frac{1}{r-g}-\\:\\frac{1}{r-g}\\:\\times\\:{\\left(\\frac{1+g}{1+r}\\right)}^{T}]$$\u003c/div\u003e\u003cdiv class=\"EquationNumber\"\u003e2\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eHere, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{Outcomes}_{i}^{0}\\)\u003c/span\u003e\u003c/span\u003e is the VSLY for Quer\u0026eacute;taro, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:g\\)\u003c/span\u003e\u003c/span\u003e is the negative drop-off rate, assumed to be equal to the mortality rate per 1 000 inhabitants obtained from World Development Indicators (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:T\\)\u003c/span\u003e\u003c/span\u003e is the life expectancy at birth in Quer\u0026eacute;taro (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e is the discount rate, which in our baseline scenario is equal to the social discount rate of 10% fixed by the Mexican Ministry of Finance and Public Credit for evaluation of investment programs and projects (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe analysis also considers the benefits for primary caregivers, the infants\u0026rsquo; mothers, by estimating the reduction in opportunity costs. Without treatment, mothers were assumed to remain out of the labor market until the child reached adulthood (18 years). With treatment, this period was reduced to five years. This opportunity cost was monetized using the net present value of the mother's estimated average annual income (approximately 96 000 Mexican pesos per year, equivalent to 5 400 US dollars), multiplied by the probability of returning to work, which was assessed using Mexico\u0026rsquo;s female labor force participation rate. Both data points were sourced from the International Labour Organization (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 SROI ratio\u003c/h2\u003e \u003cp\u003eThe benefits and costs incurred by the patient, primary caregiver, and IMO, as described earlier, were used to calculate the SROI ratio. This metric provides a comprehensive assessment of the program\u0026rsquo;s social and economic impact for each patient\u0026ndash;caregiver pair \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:i\\)\u003c/span\u003e\u003c/span\u003e:\u003cdiv id=\"Equ3\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ3\" name=\"EquationSource\"\u003e\n$$\\:{SROI\\:ratio}_{i}=\\:\\frac{\\sum\\:{Benefit}_{i}}{\\sum\\:{Cost}_{i}}$$\u003c/div\u003e\u003cdiv class=\"EquationNumber\"\u003e3\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eAmong the total sample of 342 screened premature infants, only 9.6% required and received ranibizumab treatment for ROP. For this subset of infants diagnosed with ROP, on average, treatment was effectively managed with a single injection, complemented by 8 follow-up consultations. When considering all costs associated with the ROP screening program, including those related to cases that did not require treatment, and accounting solely for the benefits of treated cases, findings reveal that, on average, for every peso invested, treated patients and their caregivers gain 48 Mexican pesos in well-being, a 48:1 ratio (95% CI: 30\u0026ndash;65), with a range of 46:1 to 997:1. If the analysis focuses exclusively on the costs and benefits for program beneficiaries, the average SROI ratio increases significantly to 493:1 (95% CI: 576\u0026thinsp;\u0026minus;\u0026thinsp;410).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Sensitivity analysis\u003c/h2\u003e \u003cp\u003eTo assess the robustness of these results and explore how changes in key assumptions might affect the estimated benefits and costs, we conduct the following sensitivity analysis, as shown in Table\u0026nbsp;3. This approach provides a more nuanced understanding of the intervention\u0026rsquo;s impact and supports more informed decision-making in the future.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eYears that mothers remain out of the labor market\u003c/b\u003e: In our baseline scenario, we assume that if the patient receives timely treatment, the mother remains out of the workforce for only five years. We now adjust this value to 0, 10, and 18 years, reporting the corresponding results in case (a) of Table\u0026nbsp;3. The SROI ratios change on average by +\u0026thinsp;5.1%, -3.0% and \u0026minus;\u0026thinsp;5.6%, respectively.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eMother's opportunity cost\u003c/b\u003e: As previously mentioned, the opportunity cost of the infant\u0026rsquo;s mother was monetized using the estimated average annual income for women in 2023. To determine the sensitivity of our estimates to this parameter, we first double this amount. In a second scenario, we replace it with the 2024 minimum annual wage of 59,743 Mexican pesos (approximately 3,258 USD). The results are shown in case (b) of Table\u0026nbsp;3. Modifying the opportunity cost of time induces average changes in SROI ratios of 5.6% and \u0026minus;\u0026thinsp;2.1%, respectively, compared to the baseline scenario.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eVisual acuity utility valuations\u003c/b\u003e: As described in the Outcomes section, the baseline scenario relies on utility valuations based on visual acuity reported by Knauer and Pfeiffer (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In case (c) of the sensitivity analysis, we first vary the utility value assigned to untreated infants with ROP to 0.61, corresponding to visual acuity ranging from 20/200 to no light perception, and to 0.72, corresponding to visual acuity between 20/60 and 20/100, as reported in the same study. These changes result in average SROI variations of -41.3% and \u0026minus;\u0026thinsp;63.0%, respectively; however, the SROI remains positive under both scenarios. We then modify the utility valuation for treated infants with good visual acuity to 0.81, based on the estimates associated with visual acuity of 20/30\u0026ndash;20/50. Under this assumption, the SROI ratio changes by -13.8%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eIMO\u0026rsquo;s total costs\u003c/b\u003e: To assess the sensitivity of the results to the total costs incurred by IMO for diagnosis and treatment, we increase these costs by 50% and 75%, and then double and triple them. These adjustments reduce the average SROI ratio by -23.4%, -31.3%, -37.7%, and \u0026minus;\u0026thinsp;54.3%, respectively; however, the SROI remains positive across all scenarios. The corresponding results are presented in case (d) of Table\u0026nbsp;3.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eDiscount rate\u003c/b\u003e: Finally, we also evaluate the effect of changing the discount rate. Under the baseline scenario it is set at 10 percent, in line with the rate for socioeconomic evaluation of investment programs and projects established by SHCP. We now change it to 0, 5, and 15 percent, reporting the results in case (e). The average changes in SROI ratios are 437.6%, 79.9% and \u0026ndash; 31.6%, respectively.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTable\u0026nbsp;3 here\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eROP treatment is a quick and effective procedure with minimal complications, offering significant improvements in visual function, quality of life, and psychosocial well-being. However, timely diagnosis is imperative to ensure the treatment's effectiveness. This study conducted a comprehensive analysis of the Social Return on Investment (SROI) of the ROP screening program implemented by IMO, a Mexican nonprofit organization. The aim was to evaluate the potential social value generated by this intervention and provide valuable insights for practitioners and policymakers in the nonprofit sector.\u003c/p\u003e \u003cp\u003eInvesting in ROP treatment generates significant social and economic benefits, as it not only improves the quality of life for affected children and their families but also reduces long-term societal costs associated with untreated visual impairments. The findings underscore the pivotal role that nonprofit organizations play in addressing gaps in healthcare delivery, particularly in underserved and resource-limited regions where public health systems may fall short. By providing timely interventions and specialized care, these organizations help mitigate the far-reaching consequences of ROP, including developmental delays, educational challenges, and financial burdens on families and the healthcare system.\u003c/p\u003e \u003cp\u003eTo maximize the impact of such efforts, scaling up neonatal ocular health programs is imperative. This requires not only increased funding and resource allocation but also the development of robust frameworks for early diagnosis, treatment, and follow-up care. Promoting cross-sector collaboration among governments, nonprofits, private entities, and international organizations is equally essential.\u003c/p\u003e \u003cp\u003eNonetheless the limitations of the study must be addressed, such as sample representativeness. This study focused on the ROP screening program implemented by IMO, a specific intervention within a defined context, and while it provides valuable insights, generalizing these results to broader nonprofit initiatives necessitates caution. Future research should consider larger samples and diverse contexts to further enhance the robustness and applicability of results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eInstitutional Review Board Statement\u003c/h2\u003e \u003cp\u003eThe study was conducted in accordance with the Declara-tion of Helsinki, ensuring compliance with ethical principles for medical research involving human subjects and approved by the Ethics Committee of \u003cem\u003eInstituto Mexicano de Oftalmolog\u0026iacute;a I.A.P (IMO)\u003c/em\u003e. It is classified as a no-risk study, as the research methods did not involve any interventions that could affect the physiology, psychology, or social variables of the participants.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflicts of Interest:\u003c/h2\u003e \u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eData Availability Statement:\u003c/h2\u003e \u003cp\u003eThe data are not publicly available due to ethical, legal, or other concerns.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGyllensten H, Humayun J, Sj\u0026ouml;bom U, Hellstr\u0026ouml;m A, L\u0026ouml;fqvist C. Costs associated with retinopathy of prematurity: a systematic review and meta-analysis. 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ILOSTAT. 2023.\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"ROP, cost-benefit analysis, SROI, nonprofit organizations, Mexico","lastPublishedDoi":"10.21203/rs.3.rs-8634905/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8634905/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRetinopathy of Prematurity (ROP) is the leading cause of childhood blindness worldwide. Although effective treatments exist, their success depends on early diagnosis. In Mexico, limited public healthcare resources restrict adequate ROP screening, leaving many at-risk infants vulnerable to preventable blindness. Nonprofit organizations, such as the Mexican Institute of Ophthalmology (IMO), help bridge these gaps by providing accessible early detection and treatment. This study aims to evaluate the social and economic impact of treating ROP in Queretaro, Mexico, using a Social Return on Investment (SROI) framework.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eUsing the SROI methodology, the analysis draws on data from 342 infants to assess the costs and benefits of IMO\u0026rsquo;s screening program. Infant benefits are estimated through utility valuations based on visual acuity and weighted by the Value per Statistical Life (VSL). Caregiver benefits reflect reduced opportunity costs, as timely treatment enables earlier workforce reentry. Costs include medical resources, equipment depreciation, human resources, and caregivers\u0026rsquo; time, food, and travel expenses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong all screened infants, 9.6% required and received treatment for ROP. When accounting for all program costs, including those for infants not requiring treatment, and considering only the benefits of treated cases, findings show an average return of 48 Mexican pesos in well-being for every peso invested (a 48:1 ratio). When focusing exclusively on the beneficiaries, the average SROI rises to 493:1.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThese findings offer valuable insights for policymakers, healthcare providers, and nonprofits to support early screening and treatment programs that prevent childhood blindness and improve long-term quality of life.\u003c/p\u003e","manuscriptTitle":"From darkness to autonomy: The social and economic return of treating Retinopathy of Prematurity (ROP)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 10:33:46","doi":"10.21203/rs.3.rs-8634905/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-05-07T07:01:28+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-02-11T07:52:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-05T08:41:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-19T13:52:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2026-01-19T04:16:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"595c6184-a3f1-4806-a406-7d26f40d4764","owner":[],"postedDate":"February 16th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-05-07T07:01:28+00:00","index":1,"fulltext":"This content is not available."}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":62714374,"name":"Health sciences/Health care/Quality of life"},{"id":62714375,"name":"Health sciences/Diseases/Eye diseases/Retinal diseases"},{"id":62714376,"name":"Health sciences/Health care/Health care economics"},{"id":62714377,"name":"Health sciences/Health care/Public health"},{"id":62714378,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-02-16T10:33:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-16 10:33:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8634905","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8634905","identity":"rs-8634905","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}