Understanding and Managing Retinopathy of Prematurity (ROP)

Every year, approximately 1.4 million premature infants worldwide are at risk of developing retinopathy of prematurity (ROP) – a disorder of the developing blood vessels in the retina that can, in its most severe form, lead to permanent blindness. What makes ROP particularly significant is that it is largely preventable. With structured screening, careful neonatal oxygen management, and timely treatment, the vast majority of at-risk infants can retain functional vision. Yet, in many parts of the world, gaps in awareness, equipment, and trained personnel continue to cost infants their sight. Understanding how ROP develops, how it is detected, and how it is treated is essential for every health and education professional working with premature or visually impaired children.

What is retinopathy of prematurity?
The role of oxygen in ROP development
Screening and monitoring premature infants
Who should be screened?
When and how is screening done?
Treatment options for ROP
Laser photocoagulation
Anti-VEGF injections
Surgical intervention for advanced disease
Prevention through optimal neonatal care
The global picture and what still needs to change

What is retinopathy of prematurity?

ROP develops in infants born prematurely with incomplete retinal development at birth. In a full-term pregnancy, retinal blood vessels begin growing at around 16 weeks of gestation and finish their development by about 40 weeks. When a baby is born early, this vascular growth is interrupted. Outside the womb, changes in oxygen levels and growth factors – particularly vascular endothelial growth factor (VEGF) – can cause the immature retinal vessels to grow abnormally. These abnormal vessels may bleed, form scar tissue, and ultimately pull on the retina, leading to detachment and blindness.

The disease progresses through five stages, classified under the International Classification of Retinopathy of Prematurity (ICROP). Stage 1 describes a line of tissue at the junction of vascular and avascular retina; stage 2 shows an elevated ridge; stage 3 involves fibrovascular proliferation; stage 4 indicates partial retinal detachment; and stage 5 represents total retinal detachment, where visual prognosis is very poor. A key clinical marker called plus disease – characterised by dilation and tortuosity of retinal blood vessels – signals that the disease is active and likely to worsen without intervention.

About half of the estimated 28,000 premature babies born each year in the United States have some degree of ROP. Globally, approximately 32,300 infants become blind or visually impaired from ROP annually, with the burden falling disproportionately on middle- and low-income countries where neonatal care systems are still developing.

The role of oxygen in ROP development

Oxygen therapy is life-saving for premature infants – but it is also the most significant environmental risk factor for ROP. ROP blindness was first observed in the 1940s and early 1950s, directly linked to unrestricted oxygen administration with no means of monitoring its use. Once the relationship between excessive oxygen and ROP was recognised, and oxygen use was brought under control, blindness rates fell dramatically. However, as neonatal technology advanced and more extremely premature infants survived, a second wave of ROP emerged – this time among very small babies whose immature lungs genuinely required oxygen support.

Today, a “third epidemic” of ROP is underway in countries like India, driven by a combination of uncontrolled supplemental oxygen and rapidly expanding – but unevenly resourced – neonatal intensive care. A recent survey from Indian neonatal units found that only one out of 18 neonates receiving oxygen had an accurately set upper oxygen saturation alarm, and none were monitored continuously.

The pathophysiology follows two phases. In the first phase, the relatively high-oxygen environment outside the womb suppresses retinal vascular growth. In the second phase, as the retina matures and metabolic demands rise, the oxygen-starved areas release excess VEGF, triggering chaotic, abnormal blood vessel growth. For every 12 hours with a high transcutaneous oxygen level, the risk of ROP doubles. This is why the duration and concentration of oxygen therapy matter enormously.

The WHO recommends maintaining a target oxygen saturation range of 90-95% for preterm newborns born before 32 weeks who require respiratory support, using neonatal pulse oximeters and appropriate oxygen delivery equipment to achieve this safely.

Screening and monitoring premature infants

Because early-stage ROP produces no outwardly visible signs, only an ophthalmologist – a doctor who specialises in eye care – can detect ROP, using special instruments to examine the retina or by reviewing images taken with specialised cameras. The entire purpose of ROP screening is to identify those infants whose disease is progressing before it becomes irreversible.

Who should be screened?

Babies considered most at risk for ROP – and who therefore undergo screening – are those with a gestational age of 30 weeks or less, or a birth weight of 1,500 grams (3.3 pounds) or less. In general, the smaller and more premature the infant, the more likely they are to develop ROP and to need treatment. Additional risk factors include prolonged need for supplemental oxygen, poor postnatal weight gain, sepsis, and intraventricular haemorrhage.

In India, national guidelines are somewhat broader: preterm infants born at fewer than 34 weeks of gestation or with birth weights under 2,000 grams should be screened for ROP, with the first screening occurring within four weeks of life. Infants born before 28 weeks or weighing under 1,200 grams should be screened even earlier – within two to three weeks of birth.

When and how is screening done?

Initial screening should be performed at 31 weeks’ postmenstrual age in infants with gestational ages of 26 weeks or less at birth, and at four weeks’ chronological age in infants with gestational ages of 27 weeks or more at birth, by an ophthalmologist skilled in the detection of ROP. The examination involves dilating the infant’s pupils with eye drops and examining the retina with an indirect ophthalmoscope. A nurse should be present during all dilated fundus examinations in the neonatal intensive care unit, as infants can experience apnea and bradycardia during the examination.

Follow-up examinations are scheduled based on the findings of each exam – more frequently if ROP is progressing, and at longer intervals if the retina appears stable. The Royal College of Paediatrics and Child Health (RCPCH) updated its screening guideline in 2022 and revised it in 2024, emphasising the importance of attending follow-up examinations and the role of a dedicated ROP service coordinator to ensure continuity of care.

In resource-limited settings, telemedicine-based screening using wide-field digital retinal cameras has opened new possibilities. Programmes such as KIDROP (Karnataka Internet-Assisted Diagnosis of Retinopathy of Prematurity) in India have improved access to timely screening in rural regions where trained ophthalmologists may not be readily available on-site.

Treatment options for ROP

Not all cases of ROP require treatment. Many extremely preterm babies will develop some degree of ROP, with the majority of cases never progressing beyond mild disease and resolving spontaneously without treatment. However, when the disease reaches a level where progression is likely – specifically Type 1 ROP, involving zone I or posterior zone II with plus disease – treatment must be initiated promptly to prevent retinal detachment and blindness.

Laser photocoagulation

For decades, the current standard for Type 1 ROP has been laser photocoagulation of the peripheral avascular retina, based on the Early Treatment for Retinopathy of Prematurity (ETROP) study. The procedure works by burning the peripheral retina – the oxygen-starved area responsible for triggering VEGF release – thereby stopping abnormal vessel growth. When laser is applied at an appropriate time, the success rate at leading institutions is well over 90% with regard to avoiding retinal detachment.

Laser can be delivered in the neonatal intensive care unit under sedation or in an operating room under general anaesthesia. However, it does carry limitations: laser therapy for ROP involving zone I and posterior disease can inevitably cause permanent peripheral visual field loss and has been associated with an increased risk of significant myopia.

Anti-VEGF injections

A more recent and increasingly used alternative is intravitreal injection of anti-VEGF agents – medications that directly block the growth factor responsible for abnormal vessel proliferation. Benefits of anti-VEGF therapy include acute regression of ROP, growth of retinal vasculature beyond the demarcation line, a lesser degree of myopia and peripheral visual field loss, and avoidance of the sedation and intubation required for laser.

Currently approved and widely studied agents include bevacizumab, ranibizumab, and aflibercept. Aflibercept was approved by the FDA for ROP treatment in 2023, making it the first and only anti-VEGF therapy formally approved in the United States for this indication. Anti-VEGF injections are typically performed at the bedside in the NICU, take less than five minutes, and do not require intubation – a significant advantage for fragile premature infants.

However, anti-VEGF therapy requires close long-term follow-up. Current guidelines recommend continued dilated retinal examinations for reactivation and additional treatment through at least 65 weeks postgestational age, as ROP recurrence can occur months after a single injection. More longitudinal randomised clinical trials are still needed to evaluate the preferred agent, appropriate dose, best follow-up protocol, and long-term outcomes following anti-VEGF treatment.

Surgical intervention for advanced disease

When ROP progresses to stages 4 or 5 – involving partial or total retinal detachment – surgical vitreoretinal intervention becomes necessary. Outcomes at these advanced stages are significantly worse, reinforcing why early detection and timely treatment at Type 1 stage is so critical. Stages 4 and 5 ROP generally require surgical intervention using vitreoretinal techniques but are fortunately rare compared with treatment-warranted ROP amenable to laser or anti-VEGF.

Prevention through optimal neonatal care

The most effective strategy against ROP is prevention – starting in the NICU. Prevention of ROP hinges on optimal neonatal care practices, including judicious use of oxygen therapy, effective infection control, proper nutrition, and early screening. A multidisciplinary approach involving neonatologists, ophthalmologists, nurses, and nutritionists is essential.

Oxygen management is at the core of prevention. Research has explored biphasic oxygen protocols – using lower oxygen saturation targets in early preterm weeks and progressively higher targets as the retina matures. One study found that a biphasic protocol resulted in a Type 1 ROP incidence of just 2%, compared with 6% under a static oxygen protocol. Careful monitoring of oxygen saturation – avoiding both excessive highs and wide fluctuations – is consistently associated with lower rates of severe ROP and reduced need for laser treatment.

Nutrition also plays a role. Research suggests that dietary omega-3 polyunsaturated fatty acids protect against pathologic neovascularisation in ROP, and since premature infants miss the key third-trimester transfer of omega-3 PUFAs from the mother, supplementation may offer preventive benefit, though further clinical trials are needed to confirm this.

Beyond individual neonatal units, systemic change is needed. Increased surveillance and further attention to equipment, personnel, and training in ophthalmology, neonatology, and nursing will not eliminate blindness due to ROP entirely, but will decrease its incidence. In countries where neonatal care is rapidly expanding, building this infrastructure in parallel – rather than after the fact – is the difference between a preventable epidemic and an avoidable one.

The global picture and what still needs to change

ROP is not simply a medical problem – it is a health systems challenge. In high-income countries with well-resourced NICUs, blindness from ROP has been largely controlled through improved neonatal care, regulated oxygen delivery, and timely laser treatment. But in middle- and low-income countries, where neonatal survival is improving faster than the systems needed to protect vision, the burden of ROP blindness is growing.

In countries such as India, China, Latin America, and sub-Saharan Africa, the ROP incidence may exceed 35% to 40%, with a higher proportion of severe and untreated cases resulting in permanent vision loss. A child blinded by ROP may live with over 70 disability-adjusted life years of visual impairment, making it one of the most impactful preventable paediatric conditions globally. The solution lies in a coordinated response: universal screening protocols, trained ophthalmologists with access to appropriate equipment, structured oxygen management programmes, and parent education so that follow-up appointments are not missed.

What do you think? Given that ROP is described as largely preventable, what systemic changes in neonatal care settings – especially in lower-resource contexts – do you think would have the greatest impact on reducing ROP-related blindness? And how can education and health professionals collaborate to ensure that families of premature infants are better informed about the importance of screening follow-ups?

References

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Table of Contents

What is retinopathy of prematurity? 🔗

The role of oxygen in ROP development 🔗

Screening and monitoring premature infants 🔗

Who should be screened? 🔗

When and how is screening done? 🔗

Treatment options for ROP 🔗

Laser photocoagulation 🔗

Anti-VEGF injections 🔗

Surgical intervention for advanced disease 🔗

Prevention through optimal neonatal care 🔗

The global picture and what still needs to change 🔗