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Retinopathy of prematurity (ROP) is a disorder that affects the developing retinal blood vessels of premature infants. It is the leading cause of both acquired and preventable childhood blindness in the United States. The disease was first recognized in the 1940s and was initially thought to be due to the normal primitive vascular system in the vitreous cavity persisting in an abnormal fibrotic state. By 1952, ROP became recognized as an acquired disease, and in 1955, the role of excessive supplementary oxygen for premature infants was proven to be a significant causative factor. Despite many improvements in neonatal care practices, ROP continues into the 21st century as a major complication of premature birth.


ROP occurs almost exclusively in premature babies, especially those born below a gestational age of 31 weeks or a birth weight below 1500 g. The development of ROP usually correlates with the overall extent of medical illnesses and complications associated with prematurity, such as intraventricular hemorrhage, necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia, patent ductus arteriosus, acidosis, anemia, and blood transfusion. Medical risk factors are dominated by the fact that the incidence and severity of ROP increase inversely with birth weight and gestational age. Full-term infants rarely, if ever, develop significant ROP.

In the data from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study, black infants demonstrated 65% lower odds of reaching severe ROP in need of treatment. The reason for this is unclear, but genetic influences are a possibility. In addition, there are relatively rare genetic disorders of the eye with similarities to ROP, including familial exudative vitreoretinopathy (FEVR), Norrie disease, and incontinentia pigmenti. The main pediatric retinal vascular diseases to distinguish from ROP are considerably rarer than ROP. Premature infants at risk for ROP typically undergo routine ophthalmologic examination, so, in general, the ability to observe the classical appearance and development of ROP allows a firm diagnosis.

In the United States, problematic ROP is limited to infants with birth weights less than 1500 g. As of the early part of this millennium, the average birth weight for US infants requiring treatment for ROP is about 700 g. ROP occurs in about 60% of infants born weighing 1500 g or less. In that same group, about 5% require treatment.


In utero, the normally developing human retinal vasculature proceeds centrifugally outward from the optic nerve head, reaching the ora serrata on the nasal side of the eye by about 36 weeks, and the temporal ora serrata at the full gestational term of about 40 weeks. Premature birth occurs at a time when there is incomplete vascularization of the retina. In ROP, extrauterine factors perturb the finalization of this vascularization process, interrupting normal vessel growth and sometimes leading to a cascade of disruptive events.

Although supplemental oxygen administration plays a role in the pathogenesis ...

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