Retinopathy of Prematurity

Excerpt

Retinopathy of prematurity (ROP) is a disease of retinal vascular and capillary proliferation affecting premature infants undergoing oxygen therapy. Oxygen treatment can lead to the pathologic growth of vessels in the developing retina, potentially resulting in permanent damage to the retina, as well as retinal detachment and macular folds. Screening guidelines for this leading cause of childhood blindness are based on gestational age and birth weight, although numerous factors contribute to both the incidence and severity of disease development. Early treatment of disease with cryotherapy, laser photocoagulation, and anti-vascular endothelial growth factor therapy has improved visual outcomes for patients. However, early recognition through screening is critical. Prevention of ROP requires a multidisciplinary approach that begins before the infant is born and continues throughout the child's development.

ROP is a vasoproliferative disorder of the developing retina in preterm infants and remains a leading cause of preventable childhood blindness globally. As neonatal survival continues to improve due to advancements in perinatal and neonatal care, particularly in low- and middle-income countries, the incidence and recognition of ROP have risen significantly. ROP represents a unique interplay of systemic immaturity, disordered retinal vascular development, and exposure to environmental risk factors, primarily oxygen therapy. This condition highlights the importance of timely screening, diagnosis, and intervention to prevent lifelong visual impairment.

ROP develops due to incomplete retinal vascularization at the time of premature birth. Normally, the retina becomes fully vascularized between 36 and 40 weeks of gestation. In preterm infants, however, vascular development is interrupted, and the subsequent abnormal neovascularization can result in fibrous proliferation, retinal traction, and ultimately retinal detachment if left untreated. The pathogenesis of ROP is classically divided into 2 phases. Phase 1 involves hyperoxia-induced vaso-obliteration; phase 2 is characterized by hypoxia-driven pathological neovascularization due to increased expression of vascular endothelial growth factor.

Multiple risk factors contribute to the development of ROP. The most significant include low gestational age, low birth weight, and the need for supplemental oxygen. Additional contributors include prolonged mechanical ventilation, sepsis, intraventricular hemorrhage, blood transfusions, and poor postnatal weight gain. The advent of the STOP-ROP (Supplemental Therapeutic Oxygen for Prethreshold–Retinopathy of Prematurity), WINROP (Weight, Insulin-like Growth Factor, Neonatal Retinopathy of Prematurity), and e-ROP (Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity) models has clarified how systemic risk factors and early biomarkers can predict disease progression, aiding in individualized screening strategies.

Clinically, ROP is classified based on the International Classification of Retinopathy of Prematurity (ICROP), which considers the zone of retinal involvement, the stage of disease (ranging from stage 1 to 5tage 5), and the presence or absence of "plus disease"—a marker of severe vascular activity. Notably, Type 1 ROP, defined as threshold or pre-threshold disease with plus disease, mandates prompt treatment to prevent progression. The 2021 ICROP3 revision further refined disease classification by incorporating posterior zone location and aggressive posterior retinopathy of prematurity (AP-ROP), thereby improving diagnostic consistency and treatment planning.

ROP screening and timely intervention are crucial to avoid permanent vision loss. Screening guidelines vary slightly across countries but are generally based on birth weight (<1500 g) and gestational age (younger than 32 weeks). Dilated retinal examination using indirect ophthalmoscopy remains the gold standard; however, advances in teleophthalmology and wide-field digital imaging are increasingly being used, particularly in resource-limited settings. Programs such as KIDROP (Karnataka Internet-Assisted Diagnosis of Retinopathy of Prematurity) in India have revolutionized access to timely screening in rural regions through a hub-and-spoke model, featuring real-time image transmission and remote expert grading.

Treatment modalities for ROP have undergone significant evolution over the past 2 decades. Traditionally, laser photocoagulation of the avascular retina has been the standard of care for threshold ROP. However, intravitreal anti–vascular endothelial growth factor (anti–VEGF) agents, particularly bevacizumab and ranibizumab, have gained widespread use, especially for posterior zone I disease and AP-ROP. The Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) and the Ranibizumab Compared With Laser Therapy for the Treatment of Infants Born Prematurely With Retinopathy of Prematurity (RAINBOW) trials demonstrated the efficacy of anti–VEGF therapy in regressing neovascularization and reducing myopia compared with laser treatment. Nevertheless, concerns remain about systemic VEGF suppression, long-term neurodevelopmental safety, and disease recurrence, necessitating prolonged follow-up.

Surgical management is reserved for advanced stages (eg, 4 and 5) where tractional retinal detachment occurs. Vitreoretinal procedures, including lens-sparing vitrectomy or lensectomy with vitrectomy, have demonstrated variable success rates, depending on the extent of detachment and the timing of intervention. However, visual prognosis in these advanced cases remains guarded, emphasizing the importance of early identification and treatment.

From a public health perspective, the "third epidemic" of ROP in developing countries is marked by high survival of preterm infants without adequate ROP screening infrastructure. National programs, such as the Rashtriya Bal Swasthya Karyakram (RBSK) in India, have prioritized ROP and are working to integrate neonatal care and ophthalmic services. The interprofessional collaboration among neonatologists, nurses, ophthalmologists, and public health workers plays a pivotal role in achieving universal ROP screening and management.

Recent advances in artificial intelligence (AI), machine learning, and predictive analytics have shown promise in enhancing ROP care. AI-based image grading tools have achieved expert-level diagnostic accuracy, potentially reducing interobserver variability and optimizing resource allocation. Moreover, innovations in portable imaging, smartphone-based retinal photography, and AI-assisted screening may bridge care gaps in underserved regions.

Despite the progress, several lacunae persist in ROP care. Challenges include inconsistent adherence to screening protocols, delayed referrals and follow-ups, a lack of trained pediatric retinal specialists, and inadequate parental education. Furthermore, the long-term outcomes of anti-VEGF therapy on systemic development and ocular growth remain under investigation. Research into predictive biomarkers, individualized treatment thresholds, and integration of AI-based screening platforms could significantly impact ROP outcomes.

This activity aims to contribute to the growing literature on ROP by evaluating the real-world effectiveness of screening models and analyzing treatment trends in a tertiary care setting. By identifying gaps in implementation and variations in clinical outcomes, this research seeks to inform policy decisions and optimize neonatal ocular care. Furthermore, this activity examines the interprofessional dynamics that enhance ROP surveillance and management, underscoring the importance of cohesive teamwork in improving infant vision and quality of life.