I. DEFINITION. Retinopathy of prematurity (ROP) is a multifactorial vasoproliferative retinal disorder that increases in incidence with decreasing gestational age. Approximately 65% of infants with a birth weight <1,250 g and 80% of those with a birth weight <1,000 g will develop some degree of ROP.

A. Normal development. After the sclera and choroid have developed, retinal elements, including nerve fibers, ganglion cells, and photoreceptors, migrate from the optic disc at the posterior pole of the eye and move toward the periphery. The photoreceptors have progressed 80% of the distance to their resting place at the ora serrata by 28 weeks’ gestation. Before the retinal vessels develop, the avascular retina receives its oxygen supply by diffusion across the retina from the choroidal vessels. The retinal vessels, which arise from the spindle cells of the adventitia of the hyaloid vessels at the optic disc, begin to migrate outward at 16 weeks’ gestation. Migration is complete by 36 weeks on the nasal side and by 40 weeks on the temporal side.

B. Possible mechanisms of injury. Clinical observations suggest that the onset of ROP consists of two stages:

1. The first stage involves an initial insult or insults, such as hyperoxia, hypoxia, or hypotension, at a critical point in retinal vascularization that results in vasoconstriction and decreased blood flow to the developing retina, with a subsequent arrest in vascular development. The relative hyperoxia after birth is hypothesized to downregulate the production of
growth factors, such as vascular endothelial growth factor (VEGF), that are essential for the normal development of the retinal vessels.

2. During the second stage, neovascularization occurs. This aberrant retinal vessel growth is thought to be driven by excess angiogenic factors (such as VEGF) upregulated by the hypoxic avascular retina. New vessels grow within the retina and into the vitreous. These vessels are permeable; therefore, hemorrhage and edema can occur. Extensive and severe extraretinal fibrovascular proliferation can lead to retinal detachment and abnormal retinal function. In most affected infants, however, the disease process is mild and regresses spontaneously.

C. Risk factors. ROP has been consistently associated with low gestational age, low birth weight, and prolonged oxygen exposure. In addition, potential or confirmed risk factors include lability in oxygen requirement as well as markers of neonatal illness severity, such as mechanical ventilation, systemic infection, blood transfusion, intraventricular hemorrhage, and poor postnatal weight gain.

A. Screening. Because no extraocular signs or symptoms indicate developing ROP, timely and regular retinal examination is necessary. The timing of the occurrence of ROP is related to the maturity of retinal vessels and therefore to postnatal age. In the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study, for infants <1,250 g, the median postnatal ages at the onset of stage 1 ROP, prethreshold disease, and threshold disease were 34, 36, and 37 weeks, respectively. At the time of the first examination, 17% of infants had ROP, and prethreshold ROP has been reported as early as 29 weeks’ gestational age. These findings led to the current screening recommendations outlined in the following text. Because ROP that meets treatment criteria may be reached after discharge from the neonatal intensive care unit (NICU), all preterm infants who meet screening criteria and are discharged before they show resolution of the ROP or have mature retinal vasculature must continue to have ophthalmologic examinations on an outpatient basis.

B. Diagnosis. ROP is diagnosed by retinal examination with indirect ophthalmoscopy; this should be performed by an ophthalmologist with expertise in ROP screening. The current recommendation is to screen all infants with a birth weight <1,500 g or gestational age <30 weeks. Infants who are born after 30 weeks’ gestational age may be considered for screening if they have been ill (e.g., those who have had severe respiratory distress syndrome, hypotension requiring pressor support, or surgery in the first several weeks of life). Because the timing of ROP is related to postnatal age, infants who are born at <26 weeks’ gestation are examined at the postnatal age of 6 to 8 weeks, those born at 27 to 28 weeks at the postnatal age of 5 weeks, those born at 29 to 30 weeks at the postnatal age of 4 weeks, and those >30 weeks at the postnatal age of 3 weeks. Patients are examined every 2 weeks until their vessels have grown out to the ora serrata and the retina is considered mature. If ROP is diagnosed, the frequency of examination depends on the severity and rapidity of progression of the disease.

Digital imaging may be used as an alternative to indirect ophthalmoscopy, and telescreening for ROP has been shown to be a valid alternative to detect significant ROP.

A. Classification. The International Classification of Retinopathy of Prematurity (ICROP) is used to classify ROP. This classification system consists of four components (see Fig. 67.1).

1. Location refers to how far the developing retinal blood vessels have progressed. The retina is divided into three concentric circles or zones.