Retinopathy of Prematurity (ROP)

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting preterm, low-birth-weight infants, caused by disruption of the normal sequence of retinal vascularization that would otherwise continue in utero until term. Risk is inversely related to gestational age and birth weight, with the most immature and lowest birth weight infants at greatest risk of severe disease; prolonged supplemental oxygen exposure, bronchopulmonary dysplasia, and other markers of a complicated neonatal course are all associated with increased risk and severity.²

Normal retinal vascularization proceeds from the optic disc toward the periphery over gestation, reaching the far periphery only near term. Premature birth interrupts this process, leaving the peripheral retina avascular. The relatively hyperoxic extrauterine environment, compounded by supplemental oxygen, suppresses VEGF-driven vessel growth; a later compensatory VEGF surge drives abnormal, disorganized fibrovascular proliferation at the vascular-avascular junction, which can progress to tractional retinal detachment in severe disease.

ROP is asymptomatic and detected only through structured screening with serial dilated fundus examinations in at-risk infants. Disease is staged by zone, extent (clock hours), stage, and the presence of plus disease (vascular dilation and tortuosity indicating aggressive activity).

Key differentials: familial exudative vitreoretinopathy (FEVR, occurring in term infants, often hereditary), Norrie disease and other genetic vitreoretinopathies, and persistent fetal vasculature (typically unilateral, with a small eye and other structural anomalies).

Type 1 ROP requiring treatment includes zone I any stage with plus disease, zone I stage 3 without plus disease, or zone II stage 2 or 3 with plus disease. Aggressive posterior ROP is a rapidly progressive, severe variant in the most posterior zone I retina requiring prompt recognition. Emerging tear and serum inflammatory biomarkers (CHI3L1, pentraxin-3) rise stepwise with worsening severity and may eventually supplement conventional risk factors, though this remains investigational.²

Type 1 ROP is managed with intravitreal anti-VEGF injection, laser photocoagulation, or occasionally vitrectomy in advanced disease with detachment. Anti-VEGF is associated with the most favorable long-term refractive outcomes among these modalities: pooled analysis found anti-VEGF-treated eyes had the least myopic mean spherical equivalent and lowest prevalence of high myopia compared to laser, and substantially better outcomes than cryotherapy or vitrectomy, which showed the highest myopic burden.¹ Anti-VEGF requires prolonged, structured follow-up given the risk of late disease reactivation as retinal vascularization continues after treatment.

• ROP is asymptomatic; gestational age and birth weight-based screening criteria, not symptoms, determine which infants require serial exams
• Plus disease is a key marker of disease activity and treatment urgency, distinct from zone and stage alone
• Anti-VEGF carries the most favorable long-term refractive profile among current treatments but requires prolonged follow-up for late reactivation¹
• Cryotherapy and vitrectomy carry the highest risk of significant myopic outcomes among ROP treatments¹
• Common pitfall: discharging an anti-VEGF-treated infant from follow-up too early, missing late reactivation
• Common pitfall: overlooking strabismus and amblyopia screening in children with a history of ROP