Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life

Abstract

Retinopathy of prematurity (ROP) is a major complication of preterm birth. It encompasses a spectrum of pathologies that affect vision, from mild disease that resolves spontaneously to severe disease that causes retinal detachment and subsequent blindness. The pathologies are characterized by an arrest in normal retinal vascular development associated with microvascular degeneration. The resulting ischemia and retinal hypoxia lead to excessive abnormal compensatory blood vessel growth. However, this neovascularization can lead to fibrous scar formation and culminate in retinal detachment. Present therapeutic modalities to limit the adverse consequences of aberrant neovascularization are invasive and/or tissue-destructive. In this Review, we discuss current concepts on retinal microvascular degeneration, neovascularization, and available treatments, as well as present future perspectives toward more profound elucidation of the pathogenesis of ROP.Retinopathy of prematurity (ROP) is the major ocular disorder of the neonate (1, 2) and the dominant cause of severe visual impairment in childhood in North America and Europe. ROP is associated with significant sequelae, the most serious being retinal detachment, which results in blindness. However, even milder forms of ROP increase the incidence of pathologies that negatively impact visual acuity, for example, ametropias, refractive errors that reduce visual acuity; strabismus, a condition in which the eyes are not properly aligned, preventing proper binocular vision and adversely affecting depth perception; and disorders of color discrimination (3-6). ROP proceeds following an initial phase of degeneration of the retinal microvasculature (vasoobliteration) (7,8) (Figure 1) that is associated with cessation of progression of vascular growth toward the retinal periphery. In the subsequent phase of the disease, the ensuing retinal ischemia predisposes to abnormal compensatory neovascularization (9, 10). Of the various factors that have been associated with the development of ROP, low birth weight, low gestational age, supplemental oxygen therapy, and its associated relative hyperoxia dominate.The development of the human retinal vasculature commences at approximately the 16th week of gestation and concludes at term (i.e., the 40th week of gestation) (11). Hence, when an infant is born prematurely, its retinal blood supply is incomplete and highly vulnerable to decay. This immaturity in vascular development predisposes the retina to complications. Major advances have been made over the past 30 years in identifying mechanisms implicated in the genesis of ROP. Comprehension of mechanisms underlying this disorder has, in turn, enhanced understanding of the pathogenesis of ischemic retinal vasculopathies in the adult, for example, diabetic retinopathy (a complication of diabetes mellitus) and neovascular forms of age-related macular degeneration (the major cause of visual impairment in adults over 50 years of age).The oxygen-induced retinopathy (OIR) model of ischemic retinop...

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“…In particular, retinopathy of prematurity, which is a leading cause of visual impairment in low birth weight infants in developed countries, is initiated by delayed retinal vascular growth and insufficient vascularization after premature birth (3). The ensuing retinal ischemia triggers the release of angiogenic factors that promote formation of abnormal neovessels that break through the inner limiting membrane into the vitreous (4). Prevention of neovessel growth is a promising strategy of intervention to improve long term prognosis of visual outcome and quality of life for many patients.…”

Endothelial colony-forming cell therapy for heart morphological changes after neonatal high oxygen exposure in rats, a model of complications of prematurity

“…2008; Sapieha et al. 2010). In experimental neonatal models, human circulating EPCs were shown to normalize vascular growth in retinopathy of prematurity and cord blood ECFC improved long‐term neurological exam in hypoxic ischemic encephalopathy (Wang et al.…”

Retinochoroidal anastomoses in RCS rat eyes?

“…Therefore, the idea of metabolic or oxygen needs from the vasculature as a trigger event can be ruled out. Hypoxia might only count for inner retinal neovascularization [31,32].…”