Chapter 118: Retinopathy of Prematurity

I. DEFINITIONS

1. Retinopathy of prematurity is a disorder resulting from the disruption of the normal development of retinal vasculature. Vasoconstriction and obliteration of the advancing capillary bed are followed in succession by neovascularization extending into the vitreous, retinal edema, retinal hemorrhages, fibrosis, and traction on, and eventual detachment of, the retina. In most cases, the process is reversed before fibrosis occurs. Because it is found chiefly in premature infants, it is called retinopathy of prematurity (ROP). Advanced stages may lead to blindness.

2. Retrolental fibroplasia. ROP was previously termed retrolental fibroplasia (RLF). The condition was first described in its most advanced form, after extensive fibrosis had already occurred behind the lens.

3. Cicatricial retinopathy of prematurity. The term cicatricial ROP refers to fibrotic disease.

II. INCIDENCE

Overall, approximately 65% of infants weighing <1251 g develop some form of ROP. Approximately 2% of infants weighing 1000 to 1250 g develop threshold stage 3+ disease eligible for treatment, and approximately 16% of infants weighing <750 g do so. Three large National Institutes of Health–sponsored studies have supported these numbers: the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study in 1986 to 1987, the Early Treatment for Retinopathy of Prematurity study (ETROP) in 2000 to 2002, and the Telemedicine Approaches for the Evaluation of Acute-Phase Retinopathy of Prematurity (e-ROP) from 2011 to 2013. These numbers have stayed consistent over almost 3 decades of study, although the incidence and survival of low birthweight infants have increased. This suggests that the overall care of these infants has improved. Threshold disease occurred at a median postconceptional age of 36 to 37 weeks, regardless of gestational age at birth or chronologic age. Of note, the International NO-ROP Group in 2005 suggested that severe ROP in larger infants is an emerging worldwide issue. Care and survival of these premature infants are improving, whereas specialized treatment for ROP is not yet as prevalent, making ROP a significant long-term morbidity in these patients.

III. PATHOPHYSIOLOGY

1. Historical perspective. RLF was first described by Terry in the 1940s and was associated with the use of oxygen in newborn infants by Patz in 1984. The first epidemic, estimated to be responsible for 30% of cases of blindness in preschool children by the end of the 1940s, occurred during a period of relatively liberal oxygen administration. After this association was recognized, oxygen use in nurseries was curtailed. Although the incidence of RLF fell, mortality rates in newborn infants increased. In the 1960s, improved oxygen monitoring techniques made possible the cautious reintroduction of oxygen into the nursery. Despite improved oxygen monitoring, however, a second epidemic of RLF (ROP) appeared in the late 1970s and was associated with the increased survival of very low birthweight infants.

2. Normal embryology of the eye. In the normally developing retina, there are no retinal vessels until approximately 16 weeks’ gestation. Until then, oxygen diffuses from the underlying choroidal ...