resources are limited, there is an increasing incidence of ROP corresponding to neonatal interventions to treat premature infants who would not previously have survived. In such cases, there is a disparity between saving premature infants and successfully diagnosing and managing their ROP [1]. The use of supplemental oxygen is a known risk factor for ROP. There is evidence that maintaining oxygen saturation levels at a lower level prior to 34 weeks’ post-menstrual age can reduce the incidence of ROP. However, it is unclear whether this benefit justifies the systemic risks to preterm infants [9]. Low early levels of insulin-like growth factor-1 (IGF-1) are associated with slower weight gain and more severe ROP. The weight, IGF-1, neonatal ROP (WINROP) algorithm uses gestational age, serum IGF-1 levels, and infant weight gain to identify babies at high risk for development of type 1 ROP [10]. Other specific postnatal factors that increase the risk for ROP include sepsis, blood transfusion, and intraventricular hemorrhage [11]. Retinopathy of Prematurity Alice L. Bashinsky Electronically published March 31, 2017. Address correspondence to Dr. Alice L. Bashinsky, Asheville Eye Associates, 8 Medical Park Dr, Asheville, NC 28803 (alicebashinsky @yahoo.com). N C Med J. 2017;78(2):124-128. ©2017 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved. 0029-2559/2017/78213 NCMJ vol. 78, no. 2 125 ncmedicaljournal.com Terminology and Classification The International Classification of Retinopathy of Prematurity was developed for the purpose of consistently describing, staging, and studying ROP (see Table 1). The classification describes the disease by location or retinal zone of involvement, disease severity or stage, extent of disease in clock hours, and whether or not plus disease is present. Plus disease refers to marked arteriolar tortuosity and venous engorgement of the posterior retinal vasculature (see Figure 1). Pre-plus disease refers to dilation and tortuosity that is abnormal but less than that seen in plus disease (see Figure 2). Aggressive posterior ROP is a severe form of ROP where vascularization ends in zone I or posterior zone II and is accompanied by plus disease. Threshold disease refers to more than 5 contiguous or 8 cumulative clock hours of extraretinal neovascularization (stage 3) in zone I or II with plus disease (see Figure 1). Prethreshold disease is terminology from the Early Treatment for Retinopathy of Prematurity (ETROP) study, further divided into type 1 (high risk prethreshold ROP) and type 2 (lower risk prethreshold ROP). Type 1 ROP refers to zone I, any stage ROP with plus disease; zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 ROP with plus disease. Type 2 ROP refers to zone I, stage 1 or 2 ROP without plus disease; or zone II, stage 3 ROP without plus disease [12]. An eye is classified according to the most advanced stage of disease noted. Careful documentation of all observed stages, zones, and extent of ROP is required. The higher the stage of ROP, the more severe the disease is. The more posterior the zone of ROP, the more non-perfused retina there is anteriorly and the worse the prognosis. Management and treatment decisions are made based on ROP stage and severity [7, 12]. Pathophysiology of ROP While not entirely understood, the pathophysiology of ROP is thought to be a two-phase process. The first phase occurs between 22 to 30 weeks’ postconceptional age when a preterm infant is born and begins to breathe. The developing retina becomes hyperoxic relative to intrauterine oxygen levels. Increased oxygen tension in the retina leads to decreased production of vascular endothelial growth factor (VEGF) and IGF-1. Low levels of VEGF and IGF-1 lead to cessation of retinal blood vessel growth. The second phase begins between 31 to 34 weeks’ postconceptional age and is characterized by disorganized retinal vascular growth. This process is due to abundant growth factors secreted by the ischemic retina (particularly VEGF and IGF-1) as well as oxidative damage to endothelial cells. Initially, a visible line between vascular and avascular retina forms (stage 1), followed by a ridge of tissue (stage 2). As the disease progresses, abnormal vessels proliferate along the ridge and into the vitreous cavity (stage 3). Progressive cicatricial contraction of the abnormal blood figure 1. Zone II stage 3 ROP with Plus Disease Source. Courtesy of Sharon Freedman, MD. figure 2. Zone II stage 2 ROP with Pre-Plus Disease Source. Courtesy of Sharon Freedman, MD. table 1. International Classification for Acute Retinopathy of Prematurity Location Zone I: Posterior retina within a 60° circle centered on the optic nerve Zone II: Extends from the edge of zone I centrifugally to the nasal ora serrata Zone III: Residual crescent of retina anterior to zone II Extent: Number of clock-hours involved Severity Stage 0: immature retinal vasculature with no ROP Stage 1: Demarcation line between vascularized and avascular retina Stage 2: Ridge (demarcation line with height, width, and volume) +/- small tufts of neovascular tissue Stage 3: Ridge with extraretinal fibrovascular proliferation Stage 4: Partial retinal detachment 4A: extrafoveal detachment 4B: retinal detachment includes fovea Stage 5: Total retinal detachment Plus disease: Vascular dilatation (venous) and tortuosity (arteriolar) of posterior retinal vessels in at least 2 quadrants of the retina NCMJ vol. 78, no. 2 ncmedicaljournal.com 126 vessels and vitreous gel produces tractional retinal detachment (stages 4 and 5) [2, 13]. Associated Conditions and Late Sequelae of ROP Myopia (nearsightedness) is a common sequela of regressed or treated ROP. High myopia may cause amblyopia as well as strabismus. Macular scarring can occur, which leads to reduced central visual acuity. It is also common to see temporal dragging of the macula, which results in the appearance of exotropia (pseudostrabismus). Conventional treatment of ROP involves ablation of the peripheral avascular retina, which leads to variable peripheral visual field defects. Less common complications of severe ROP include cataract and