Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a disorder of the developing blood vessels of the retina in infants born preterm. Because retinal vascularization is incomplete at preterm birth, the immature retina is vulnerable to abnormal, disordered vessel growth that, in severe cases, can lead to retinal detachment and blindness. It is a leading preventable cause of childhood visual impairment worldwide and is grouped here as a developmental injury of prematurity alongside the neurological complications of the immature newborn.

Definition

Retinopathy of prematurity is a vasoproliferative retinal disorder of preterm infants in which incomplete retinal vascularization is followed by pathological neovascularization, classified by the zone, stage, and extent of involvement and by the presence of plus disease.

Scope

This entry covers the developmental basis of the disease, its two-phase pathogenesis, the internationally agreed terms for describing its location and severity, and the broad evidence behind screening and treatment. It is a reference description of the condition and does not provide screening schedules, treatment thresholds, dosing, or individualized clinical advice.

Core questions

• Why does preterm birth predispose to abnormal retinal vessel growth?
• What are the two phases of the disease's pathogenesis?
• How is ROP classified by zone, stage, and plus disease?
• What is the evidence basis for screening and for treatment?

Key concepts

• Incomplete retinal vascularization at preterm birth
• Two-phase pathogenesis (vaso-obliteration then neovascularization)
• Vascular endothelial growth factor (VEGF) and oxygen
• Zone, stage, and extent
• Plus disease
• Threshold and type 1 disease
• Screening examination and treatment

Mechanisms

Retinopathy of prematurity is generally described as a two-phase process. After preterm birth the relatively high extrauterine oxygen environment, compared with the womb, slows or halts normal retinal vessel growth and may obliterate vessels, leaving an incompletely vascularized retina (phase one). As the metabolically active but poorly perfused retina matures, it becomes hypoxic and drives the production of angiogenic factors, especially vascular endothelial growth factor, provoking disorganized neovascularization (phase two) that can lead to fibrovascular proliferation and tractional retinal detachment. The international classification provides the vocabulary of zone, stage, extent, and plus disease used to capture severity (ICROP 2005), and anti-VEGF therapy reflects the central role of vascular endothelial growth factor (Mintz-Hittner 2011).

Clinical relevance

Severe retinopathy of prematurity is an important and largely preventable cause of childhood blindness, so at-risk preterm infants undergo structured retinal examination, and treatment of severe disease can reduce unfavourable visual outcomes. This entry describes the disease, its classification, and the broad evidence base, and is not a source of screening criteria, treatment thresholds, or individualized management.

Epidemiology

Retinopathy of prematurity affects preterm and low-birth-weight infants, with risk rising as gestational age and birth weight fall; epidemiological patterns vary internationally, reflecting differences in neonatal survival and oxygen management. The condition has historically appeared in epidemics tied to oxygen practices and remains a major cause of preventable childhood visual loss, especially where care for larger preterm infants is expanding (ICROP 2005).

Evidence & guidelines

The shared descriptive framework comes from the International Classification of Retinopathy of Prematurity and its revisions (ICROP 2005). Randomized trials redefined which eyes benefit from earlier treatment of severe disease (ETROP 2003) and evaluated intravitreal anti-VEGF therapy as an alternative to ablative treatment for certain severe disease (Mintz-Hittner 2011). Professional screening recommendations are derived from this evidence and are not reproduced here.

History

Severe retinopathy of prematurity, historically termed retrolental fibroplasia, emerged as a major cause of infant blindness in the mid-twentieth century, when its association with unmonitored supplemental oxygen was recognized. Later decades brought an international classification to standardize description, randomized trials that refined treatment timing for severe disease, and the introduction of anti-vascular-endothelial-growth-factor therapy, while improving survival of very preterm infants kept the condition globally relevant.

Debates

What is the role of anti-VEGF therapy relative to ablative treatment?

Intravitreal anti-vascular-endothelial-growth-factor therapy offered an alternative to ablative treatment for certain severe disease, but questions about long-term ocular and systemic effects of suppressing a growth factor important to development continue to be debated.

Key figures

• Helen A. Mintz-Hittner
• Lois E. H. Smith
• William V. Good

Seminal works

• icrop-2005
• etrop-2003
• mintz-hittner-2011

Frequently asked questions

Why does prematurity cause retinopathy of prematurity?

Retinal blood vessels are still growing at the time of preterm birth. The change to the extrauterine environment can disrupt this growth, and the immature, incompletely vascularized retina may later drive abnormal, disordered new vessel formation.

Does retinopathy of prematurity always cause blindness?

No. Many cases are mild and resolve as the retina matures; only a minority progress to severe disease that, without treatment, can lead to retinal detachment and visual loss, which is why at-risk infants are examined and severe disease is treated.