In the evolving landscape of neonatal care, retinopathy of prematurity (ROP) stands as a formidable challenge that continues to perplex clinicians and researchers alike. Despite significant advances in neonatal intensive care units (NICUs) worldwide, ROP remains a leading cause of childhood blindness, particularly affecting the most vulnerable population—premature infants. The comprehensive review published by Filippi, Gulden, Cammalleri, and colleagues in World Journal of Pediatrics (2025) delves deep into how precision neonatology is revolutionizing the prevention, diagnosis, and treatment paradigms of this multifaceted retinal disease. Their work unpacks the transition from broad risk stratifications toward targeted, individualized therapies, heralding a new era of precision medicine in neonatology.
Retinopathy of prematurity is a vaso-proliferative disorder of the retina characterized by aberrant vascular development in the immature eye. The pathophysiology is complex, intertwined with premature birth, oxygen toxicity, and the immature retinal vasculature’s sensitivity to fluctuating oxygen levels and growth factors. These factors create a fragile microenvironment where initial hypoxia triggers pathological neovascularization, leading to retinal detachment and irreversible vision loss if untreated. Historically, efforts to tame ROP focused on monitoring high-risk infants based on gestational age and birth weight, but such risk stratification methods faced limitations in predictive precision and sensitivity.
The advent and maturation of precision neonatology have shifted this paradigm dramatically. Precision neonatology leverages genomic insights, biomarker identification, advanced imaging modalities, and individualized clinical data to characterize each infant’s unique risk profile. This tailored approach transcends simplistic criteria, incorporating multilayered data streams that include genetic predispositions, environmental exposures, and real-time physiological monitoring. The review outlines how next-generation sequencing and molecular profiling have uncovered specific genetic variants linked with ROP susceptibility and progression, offering novel avenues for early detection.
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One of the transformative elements discussed is the role of cutting-edge imaging technologies in ROP management. Traditional indirect ophthalmoscopy, while effective, is limited by interobserver variability and accessibility constraints. Innovations such as wide-field digital retinal imaging and optical coherence tomography (OCT) provide high-resolution, quantitative assessments of retinal microarchitecture at bedside, enabling earlier detection of subtle neovascular changes. These imaging modalities, when combined with machine learning algorithms, can predict disease trajectory with unprecedented accuracy, facilitating timely intervention before irreversible damage ensues.
The therapeutic landscape for ROP has also evolved concomitantly. Laser photocoagulation has been the gold standard for treating proliferative disease phases, ablating the avascular retina to reduce hypoxia-driven neovascular stimuli. However, this approach is destructive and can compromise peripheral vision. The review details the emergence of targeted therapies that specifically modulate pathological angiogenesis. Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents have gained prominence, demonstrating efficacy in halting abnormal vessel growth while preserving retinal tissue integrity. Importantly, the safety profiles and systemic effects of these agents are an area of active investigation, with precision medicine providing frameworks for dosing individualization.
Beyond anti-VEGF, the review emphasizes research into novel molecular targets within the angiogenic cascade. Factors such as insulin-like growth factor 1 (IGF-1), erythropoietin (EPO), and others play nuanced roles in retinal vascular development and present opportunities for pharmacological modulation. Advances in drug delivery systems, including biodegradable implants and nanoparticle carriers, are also highlighted for their potential to increase therapeutic precision and reduce systemic exposure. These innovations promise to convert ROP treatment from a reactive strategy into a proactive, finely-tuned intervention.
The review prominently discusses the integration of big data analytics and artificial intelligence (AI) in refining ROP risk models. Combining electronic health record (EHR) data with imaging and molecular biomarkers, AI algorithms can identify patterns and predictors of disease progression that elude conventional statistical approaches. These predictive models not only streamline screening processes but also potentially reduce unnecessary examinations, minimizing stress and risk to fragile neonates. The ethical dimensions and the need for robust validation of AI tools in diverse populations are thoughtfully addressed, underscoring the nuanced path to clinical adoption.
Environmental and systemic factors influencing ROP risk are also meticulously reviewed, with an emphasis on oxygen supplementation strategies. Oxygen remains both a life-saving therapy and a double-edged sword; improper administration can exacerbate retinal injury. Precision oxygen management, guided by closed-loop systems and real-time monitoring, is increasingly recognized as pivotal in preventing ROP initiation. The review presents data supporting personalized oxygen targeting protocols that consider each infant’s developmental stage and hemodynamic status.
A particularly compelling aspect of the review is the discussion about prenatal and perinatal interventions. Maternal health, intrauterine growth restriction, and inflammation contribute significantly to ROP pathogenesis, yet remain under-addressed in current strategies. The article explores how emerging biomarkers detectable at birth could stratify infants even before retinal changes manifest, opening windows for early preventive measures and close surveillance. This preventive focus aligns with the broader goals of precision neonatology, shifting the narrative from treatment to prevention.
Long-term outcomes and neurodevelopmental implications of ROP and its treatments also receive detailed exploration. Beyond visual acuity, ROP and associated prematurity complications impact cognitive development and quality of life. The authors advocate for holistic management frameworks that integrate ophthalmologic care with multidisciplinary support services. The potential of pharmacogenomics to predict therapeutic responsiveness and adverse reactions is another frontier identified for future research.
The synthesis presented by Filippi and colleagues is not purely academic; it has tangible implications for clinical practice, research, and policy. Implementation of precision neonatology in ROP requires collaboration across specialties, incorporation of new technologies, and equitable access to care. The authors caution about disparities in outcomes driven by resource limitations, emphasizing the need for scalable and cost-effective precision tools, especially in low- and middle-income settings where ROP burden remains highest.
In summation, the era of precision neonatology ushers in unprecedented opportunities to transform retinopathy of prematurity from a condition marked by reactive treatments and imperfect prognostic tools to one characterized by predictive accuracy, individualized therapy, and improved outcomes. By harnessing genomics, advanced imaging, AI, and molecular therapeutics, neonatologists and ophthalmologists can now envision a future wherein ROP-related blindness becomes a rarity rather than a common consequence of prematurity. The insights shared in this seminal review underscore the importance of continued multidisciplinary research and innovation to bring this vision to fruition for the most fragile patients.
The paradigm shift from classic risk stratification to targeted therapeutic strategies represents a microcosm of the broader transformation in neonatal medicine, where data-driven and patient-centric approaches redefine standards of care. As these advances are integrated into everyday clinical workflows, the potential for reducing lifelong disability and enhancing quality of life for preterm infants grows exponentially. The field stands on the brink of a new epoch where precision neonatology not only saves sight but also illuminates a path toward holistic, personalized health from the earliest moments of life.
Subject of Research: Retinopathy of Prematurity (ROP) in the context of precision neonatology, focusing on advancements in risk stratification and targeted therapies.
Article Title: Retinopathy of prematurity in the era of precision neonatology: from risk stratification to targeted therapies
Article References:
Filippi, L., Gulden, S., Cammalleri, M. et al. Retinopathy of prematurity in the era of precision neonatology: from risk stratification to targeted therapies. World J Pediatr 21, 430–435 (2025). https://doi.org/10.1007/s12519-025-00919-1
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