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 of 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 in 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.

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

Risk factors. ROP has been consistently associated with low gestational age, low birth weight, and prolonged oxygen exposure. In addition, the 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.

Screening. Because no early clinical signs or symptoms indicate developing ROP, early and regular retinal examination is necessary. The timing of the occurrence of ROP is related to the maturity of retinal vessels and, therefore, 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 of gestational age. Because ROP that meets treatment criteria may be reached at a later postnatal age, 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.

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 with a gestational age <30 weeks. Infants who are born after 30 weeks of 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 of gestation are examined at the postnatal age of 6 weeks, those who are born at 27 to 28 weeks of gestation are examined at the postnatal age of 5 weeks, those born at 29 to 30 weeks of gestation are examined at the postnatal age of 4 weeks, and those >30 weeks of gestation are examined 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 the progression of the disease.

Classification. The International Classification of Retinopathy of Prematurity (ICROP) is used to classify ROP. This classification system consists of four components (see Fig. 64.1).