Pathophysiology of Retinopathy of Prematurity in Preterm Neonates

Phase I: Vaso-Obliteration

Retinal vessels normally begin growing at approximately 16 weeks gestation, but premature birth interrupts this process, leaving vessels incomplete and highly susceptible to injury, according to the American Thoracic Society 1, 2
High arterial oxygen levels slow the process of normal vascularization during this phase, as stated by the American College of Chest Physicians 1
The incomplete vessels are damaged by prolonged elevated arterial oxygen exposure and other severe physiologic stressors, leading to a marked decrease in vascular growth factors, as reported by the American Journal of Respiratory and Critical Care Medicine 1

When vessels resume growth, they do so excessively in response to large amounts of vascular growth factors produced by the now-avascular retina, which has become increasingly mature and metabolically demanding, as described by the American College of Chest Physicians 1
The resulting ischemia and retinal hypoxia lead to excessive abnormal compensatory blood vessel growth, which clinically manifests as ROP in the eye, according to the American Academy of Pediatrics 1
The abnormal vessels grow into the retina and vitreous cavity of the premature infant, as stated by the American College of Chest Physicians 1, 2

During Phase I (vaso-obliteration): High arterial oxygen levels slow normal vascularization, while during Phase II (neovascularization): Marginally low arterial oxygen aggravates the amount of neovascularization following initial injury, as reported by the American Thoracic Society 1

Most infants' vessels progress through the neovascularization phase to completion, representing the healing phase of ROP, as described by the American Academy of Pediatrics 1
This regression phase can be prolonged for weeks, requiring different management approaches, as stated by the American College of Chest Physicians 1

Vision loss from ROP is ultimately a consequence of this excessive overgrowth of new vessels, analogous to how fibrosis in chronic lung disease follows initial pulmonary injury, as reported by the American Thoracic Society 1, 2

The single most important risk factor is extreme prematurity, with both incidence and severity of disease increasing as gestational age at birth decreases, as stated by the American College of Chest Physicians 1, 2
Preterm infants are born before retinal vessels reach the edge of the retina, leaving incomplete vascularization that is vulnerable to injury, according to the American Academy of Pediatrics 1