Pathophysiology of ROP
Typically, retinal vascularization begins at approximately week 16 of gestation, proceeds from the optic nerve head to the periphery, and is completed nasally by approximately 36 weeks’ gestation and temporally by 40 weeks’ gestation. When this pattern of vascularization is disrupted, ROP may develop. Although the current understanding of the pathophysiology of ROP is incomplete, it is thought of as a 2-phase process. In the first phase, which occurs before approximately 31 weeks’ gestational age, typical vascular development ceases. This cessation occurs largely as the result of a decrease in the levels of hormones and growth factors that govern normal vascular development in the eye, such as vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1). The drop in the expression and levels of these growth factors is thought to be caused by an increase in the infant’s systemic oxygen tension that occurs following birth and the commencement of breathing by the infant.
The second phase of ROP begins at approximately 31–34 weeks’ gestational age. It is characterized by an abundance of growth factors secreted by the ischemic retina— particularly VEGF and IGF-1, among others—as well as by oxidative damage to endothelial cells, which leads to disorganized vascular growth. Initially, this process causes the formation of a visible tissue ridge (ROP stages 1, 2). As the disease progresses, vascular growth proliferates into the vitreous cavity (ROP stage 3). Eventually, growth factor and hormone shifts cause involution of the blood vessels with cicatricial contraction, which can lead to tractional retinal detachment (ROP stages 4, 5).
The more peripheral the neovascularization and the smaller its size and extent on the retina, the better the outlook is for spontaneous regression with minimal scarring. Active neovascularization with shunting of blood flow is associated with dilation and increased tortuosity of the retinal vessels posteriorly. A notable finding in active disease is the increased and abnormal terminal arborization of retinal vessels as they approach the shunt or ridge. In addition, microvascular abnormalities (eg, microaneurysms, areas of capillary nonperfusion, and dilated vessels) may be visible posterior to the ridge.
In the vasoproliferative phase, new vessels varying widely in size and extent arise from retinal vessels just posterior to the shunt. These new vessels can induce contracture of the firmly attached vitreous gel, which results in progressive tractional retinal detachment. Vitreous hemorrhage can occur in stages 3–5, as can exudative retinal detachment.
Although the systemic and/or local tissue factors that influence progression and regression of ROP are not known, the time course is predictable. ROP is a transient disease in the majority of infants, and spontaneous regression occurs in 85% of eyes. The initial clinical sign of regression is the development of a clear zone of retina beyond the shunt, followed by the development of straight vessels crossing the shunt and an arteriovenous feeder extending into the avascular retina.
Threshold ROP eventually develops in approximately 7%–10% of infants with a birth weight of 1250 g or less. Eyes that demonstrate progression undergo a gradual transition from the active to the cicatricial stage of ROP, which is associated with variable degrees of fibrosis, contracture of the proliferative tissue, vitreous and retinal traction, macular distortion, vitreous and retinal hemorrhages, and/or retinal detachment.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.