Related Experiment Video
Updated: Sep 13, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology
Rowena Cayabyab1, Rangasamy Ramanathan
1Division of Neonatal Medicine, Department of Pediatrics, LAC+USC Medical Center and Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, Calif., USA.
Insights
Retinopathy of prematurity (ROP) is a leading cause of preventable blindness in infants. Understanding its two phases and optimizing oxygen saturation (SpO2) may prevent severe ROP and improve visual outcomes.
Area of Science:
- Ophthalmology
- Neonatology
- Perinatal Care
Background:
- Retinopathy of prematurity (ROP) is a significant cause of preventable blindness in preterm infants globally.
- Improved perinatal care increases survival but also the incidence of severe ROP, particularly in developing nations.
- ROP pathophysiology involves two distinct phases: vaso-obliteration (Phase I) and abnormal vasoproliferation (Phase II).
Purpose of the Study:
- To review the pathophysiology of ROP and current strategies for prevention and treatment.
- To evaluate the impact of oxygen saturation (SpO2) titration on ROP incidence and mortality.
- To discuss emerging therapeutic agents and long-term management of ROP.
Main Methods:
- Review of existing literature on ROP pathophysiology, treatment, and prevention.
- Analysis of clinical trial data regarding SpO2 targets and their outcomes.
- Discussion of current and investigational treatments for ROP.
Main Results:
- Two phases of ROP involve changes in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1).
- Optimal SpO2 targets remain debated, with trials showing trade-offs between ROP reduction and mortality.
- Graded SpO2 strategies targeting different ROP phases show promise.
Conclusions:
- A phased approach to SpO2 management may be optimal for preventing severe ROP.
- Further research is needed on oxygen therapy, biological agents like IGF-1, and nutritional support.
- Comprehensive screening, early intervention, and long-term follow-up are crucial for managing ROP and its complications.
Abstract:
Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally.
