Effects of oxygen on the development and severity of retinopathy of prematurity

Abstract

SUMMARY In 1942, when retinopathy of prematurity (ROP) first manifested as retrolental fibroplasia, the technology to monitor or regulate oxygen did not exist, and a fundus examination of preterm infants was not routinely performed. Supplemental, uncontrolled oxygen at birth has since been found to cause retrolental fibroplasia. At the same time, technological advances have made it possible to regulate oxygen and detect early forms of ROP. Nevertheless, despite our better understanding of ROP and ongoing investigations of supplemental therapeutic oxygen, including recent clinical trials (Surfactant, Positive Airway Pressure, Pulse Oximetry Randomized Trial [SUPPORT] and Benefits of Oxygen Saturation Targeting [BOOST]), the best oxygen profiles to reduce ROP risk while optimizing preterm infant health and development remain unknown. This article reviews major studies on oxygen use in preterm infants and the effects on the development of ROP.

Vascular Endothelial Growth Factor Antagonist Therapy for Retinopathy of Prematurity

“…26,27 More recent studies tested the hypotheses that lower than conventional oxygen saturation targets would reduce severe ROP. 28–30 In two studies, the Surfactant, Positive Airway Pressure, Pulse Oximetry Randomized Trial (SUPPORT) 31 and Benefits of Oxygen Saturation Targeting (BOOST), 31 low oxygen saturation targets were associated with lower incidence of ROP but higher mortality, whereas in the Canadian Oxygen Trial (COT), 32 there was no effect on ROP or mortality. 31 However, the studies had important differences, including regional differences in the phenotype of ROP of enrolled infants [Table 1].…”

Evaluation of Oxygen Supplementation Status as a Risk Factor Associated with the Development of Severe Retinopathy of Prematurity

“…Previous reports have documented the risk factors for severe ROP in various countries, which include low postmenstrual age, low birth weight and a male gender [2,3,4,5,6,7]. Excessive oxygen supplementation is also known as a potential risk factor for severe ROP, since delivery of a higher oxygen concentration creates a higher risk of developing severe ROP [8]. A recent randomized controlled trial demonstrated that, after postnatal stabilization, keeping preterm babies within a high saturation target range (91-95%) increases the risk of ROP as compared to keeping them in a lower saturation range (85-89%) [9].…”

Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity

“…The retinovascular growth attenuation and vascular obliteration created by hyperoxia lead to retinopathy of prematurity (ROP), a leading cause of childhood blindness worldwide, accounting for 100,000 new cases of infant blindness each year (1). Recent prospective clinical trials paradoxically have demonstrated that targeting oxygen saturations to levels commensurate with in utero saturations reduces ROP but increases mortality (2,3). The response to oxygen tension within the cell is regulated by hypoxia-inducible factors (HIFs), which are transcription factors that modulate adaptation to hypoxia and normoxia by directing the expression of gene products that increase glycolysis, hematopoiesis, angiogenesis, and vasculogenesis (4)(5)(6).…”