Retinopathy of Prematurity: What It Is, How the NICU Screens for It, and What Treatments Are Available

Research-informed explainer — last updated April 12, 2026

Retinopathy of prematurity (ROP) is an abnormal blood vessel growth disorder affecting the developing retinas of premature infants, and it is the leading cause of childhood blindness that can be almost entirely prevented when detected and treated in time. Every infant born before 30 weeks of gestation or weighing less than 1,500 grams requires systematic screening exams by a pediatric ophthalmologist, because the window between treatable and untreatable disease can close within days.

This article draws on research from five specialist physicians. Antonio Capone, MD, Director of the Vitreoretinal Fellowship Training Program and now with Associated Retinal Consultants, co-authored the International Classification of Retinopathy of Prematurity Revisited (1,389 citations) and its 2021 third-edition update (718 citations) — the staging framework used by ophthalmologists and neonatologists worldwide. Lois Smith, MD, PhD, Professor of Ophthalmology at Harvard Medical School and Boston Children's Hospital, published the definitive Lancet review of ROP (1,293 citations), foundational research on VEGF suppression in retinal neovascularization (1,264 citations), and a review on ROP pathogenesis through the lens of angiogenesis biology (595 citations). Scott Lambert, MD, Professor of Ophthalmology at Stanford, published outcomes data comparing intravitreal bevacizumab to laser photocoagulation for ROP (229 citations). Andrew Moshfeghi, MD, Vice Chair for Clinical Affairs and Associate Professor at USC's Keck School of Medicine, published the U.S. epidemiology of ROP in a nationwide cohort (153 citations). Theodore Leng, MD, Professor of Ophthalmology at Stanford's Byers Eye Institute, published six years of SUNDROP telemedicine ROP screening outcomes (175 citations) — demonstrating that remote retinal imaging can safely replace on-site examinations in NICUs without ophthalmologist coverage.

What is ROP and why does it develop?

Retinal blood vessels begin growing at about 16 weeks of gestation and reach the edges of the retina at full term (approximately 40 weeks). Infants born prematurely have incompletely vascularized retinas. In phase 1 of ROP, the high-oxygen environment of the NICU suppresses normal vascular development, causing the existing vessels to partially regress. In phase 2, as the now highly metabolically active but under-vascularized retina becomes hypoxic, it releases large amounts of VEGF — triggering rapid, disorganized neovascularization that can scar, contract, and ultimately detach the retina.

Dr. Smith's foundational PNAS research demonstrated that this VEGF-driven process is the direct cause of retinal neovascularization, and that blocking VEGF with soluble receptor chimeric proteins suppresses neovascularization in experimental models — the scientific basis for bevacizumab as an ROP treatment.

How common is ROP?

Dr. Moshfeghi's nationwide U.S. cohort analysis found that ROP incidence has actually increased between 2000 and 2012 — likely because improved neonatal intensive care is saving increasingly premature infants who would previously not have survived. Among infants born between 22 and 27 weeks of gestation, more than 80% develop some degree of ROP; approximately 10–15% of those will progress to a stage requiring treatment.

By birthweight, infants under 1,000 grams have the highest risk. Among infants born at 23 weeks, the incidence of severe ROP approaches 40%. The overall U.S. burden is estimated at 14,000–16,000 cases of ROP annually, with approximately 1,100 progressing to severe disease.

The staging system

The International Classification of ROP, developed and updated by Dr. Capone's committee, uses three parameters: zone (I, II, or III — describing how far from the optic nerve the disease extends), stage (1–5, describing severity), and the presence of "plus disease" (dilation and tortuosity of retinal vessels indicating high VEGF activity).

• Stage 1: A demarcation line between vascularized and avascular retina. Often regresses spontaneously.
• Stage 2: A ridge of tissue at the demarcation line. Still may regress.
• Stage 3: Extraretinal fibrovascular proliferation — new vessels growing out of the plane of the retina into the vitreous. Treatment-threshold disease is typically reached here.
• Stage 4A/4B: Partial retinal detachment, extrafoveal (4A) or fovea-involving (4B). Vision loss begins.
• Stage 5: Complete retinal detachment. Visual prognosis is very poor even with surgery.

"Plus disease" at any stage substantially worsens prognosis and lowers the treatment threshold. The third-edition update by Dr. Capone's committee added "aggressive posterior ROP" (AP-ROP) as a distinct category — a rapidly progressing form in zone I that can reach stage 5 within days without treatment.

Who gets screened, and how?

Current American Academy of Ophthalmology and American Academy of Pediatrics guidelines recommend screening for all infants born at 30 weeks gestational age or less, or weighing 1,500 grams or less, or with an unstable clinical course felt by the neonatologist to place them at risk.

The first exam is timed to occur at 31 weeks postmenstrual age (gestational age + weeks of life) or four weeks after birth, whichever comes first. Subsequent exams are scheduled based on findings, typically every one to three weeks until the retina is fully vascularized or disease has resolved or been treated.

The exam itself involves dilating the infant's pupils and performing indirect ophthalmoscopy — often with a depressor to rotate the eye — to view the peripheral retina. It is uncomfortable and requires a skilled examiner, typically a pediatric retina specialist or vitreoretinal surgeon.

Telemedicine screening

In NICUs without on-site ophthalmologist coverage — particularly in rural regions — telemedicine screening using wide-field digital retinal cameras is increasingly used as an alternative. Dr. Leng's SUNDROP program at Stanford demonstrated, over six years of screening more than 1,300 infants, that telemedicine ROP screening achieved sensitivity and specificity for referral-warranted ROP comparable to in-person examination. This has significant implications for equity of access: premature infants in underserved regions should not be at higher risk of blindness simply because a specialist cannot travel to their NICU.

Treatment: laser vs. anti-VEGF injections

Laser photocoagulation (panretinal photocoagulation, PRP): Traditional treatment involves applying laser burns to the avascular peripheral retina — destroying the tissue that is producing VEGF and driving neovascularization. Laser is highly effective at preventing progression to retinal detachment and has decades of outcome data. The main drawback is permanent destruction of peripheral retinal tissue, which may cause myopia and loss of peripheral visual field.

Intravitreal bevacizumab: Anti-VEGF injection is now widely used, particularly for zone I or posterior zone II disease where laser delivery is technically difficult and retinal destruction would involve functionally important areas. Dr. Smith's mechanistic work and the subsequent BEAT-ROP randomized trial established bevacizumab's efficacy.

Dr. Lambert's retrospective outcomes comparison found that bevacizumab-treated infants had significantly lower rates of high myopia compared with laser-treated infants — an important quality-of-life consideration because myopia rates of -10 diopters or more are common after panretinal laser in very premature infants. However, bevacizumab does not eliminate the avascular retina — it suppresses VEGF temporarily, and vascularization needs to complete naturally. Relapse has been reported weeks to months after injection, requiring continued surveillance.

The choice between laser and bevacizumab involves zone of disease, severity, institutional experience, and follow-up reliability. Many centers use bevacizumab as first-line for zone I aggressive ROP and laser for zone II disease.

Stage 4 and 5: surgery

When ROP has progressed to tractional retinal detachment despite treatment, or was caught at stage 4 or 5, vitrectomy surgery is required. Dr. Capone published outcomes of lens-sparing vitreoretinal surgery for stage 4A ROP, demonstrating retinal reattachment in 90% of eyes with favorable anatomic results — though functional vision depends on how much central retina was involved before surgery.

Stage 5 outcomes are substantially worse; the retina is often funnel-shaped and severely scarred, and even with successful surgical reattachment, functional vision is limited.

Questions to ask your doctor

• What zone and stage is my baby's ROP, and is plus disease present?
• What is the treatment threshold for our NICU — at what findings would you recommend treating now?
• Is laser photocoagulation or intravitreal bevacizumab more appropriate for my baby's specific disease pattern, and why?
• If bevacizumab is used, how long and how closely will you monitor for recurrence?
• What is the expected long-term visual outcome, and when will we know whether vision is developing normally?
• Are there follow-up eye exams we need to schedule after discharge from the NICU?

The bottom line

Retinopathy of prematurity is a predictable, screenable, and — in the vast majority of cases — treatable condition when caught before retinal detachment occurs. The International Classification system developed by Dr. Capone and colleagues gives every NICU team a common language for describing disease severity and treatment decisions. Both laser photocoagulation and intravitreal bevacizumab are effective treatments, with anti-VEGF injections showing advantages in reducing myopia while requiring more vigilant post-treatment surveillance. For parents of a premature infant, understanding the ROP screening schedule and ensuring that exams happen on time is one of the most important things they can do to protect their child's long-term vision.