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Retinopathy of Prematurity (ROP)

Proliferative vascular disorder of developing retina in preterm infants, caused by disrupted vascular maturation with hypoxia-driven neovascularization; leading cause of preventable childhood blindness when severe

Written by: Saygı Hospital Health Guide Editorial Board
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What is Retinopathy of Prematurity (ROP)?

Retinal vasculogenesis: begins at 16 weeks GA from optic disc, advances to nasal periphery at 32 weeks, temporal periphery at 40 weeks; vessels sensitive to oxygen — lower oxygen in utero stimulates VEGF-mediated vascular growth; preterm birth disrupts this orderly vascularization.

Pathophysiology — two phases: Phase 1 (hyperoxic, ~birth to 32 weeks PMA) — relative hyperoxia (compared to in utero 30-35 mmHg PaO2) causes VEGF downregulation, vasoconstriction, and attenuation of incomplete retinal vessels, with arrested vascular development and avascular retina; Phase 2 (hypoxic, typically 32-34+ weeks PMA) — avascular retina becomes metabolically demanding, causes relative hypoxia, upregulated VEGF drives abnormal neovascularization at vascular-avascular junction, with potential for retinal detachment.

Classification (ICROP 2021): by location (Zone I innermost, II middle, III peripheral temporal), by severity/stage (1 — line of demarcation; 2 — raised ridge; 3 — ridge + extraretinal fibrovascular proliferation; 4 — partial retinal detachment, A = extrafoveal, B = foveal; 5 — total retinal detachment), and plus disease (≥2 quadrants venous dilation/arterial tortuosity at posterior pole — indicates aggressive active disease); A-ROP (aggressive posterior ROP, formerly AP-ROP) — ill-defined rapid-progression form with posterior plus disease.

Epidemiology: affects ~50-70 percent of infants <28 weeks, decreasing with higher GA; severity requiring treatment in 10-20 percent of extremely preterm; ROP prevention and management significant NICU/ophthalmologic priority.

Symptoms

ROP is asymptomatic during acute phase — no behavioral signs visible to parents; dilated fundus exam by ophthalmologist is the only way to detect ROP in real time
Late signs (after retinal detachment) — leukocoria (white pupil reflex), strabismus, poor visual behavior, nystagmus — represent severe disease often with poor outcomes
Post-treatment infants may have mild eye redness or discomfort for 1-2 days
Long-term sequelae: high myopia (detected as squinting at distance, poor visual tracking), strabismus, amblyopia, glaucoma (rare), retinal detachment years later
Associated neurodevelopmental issues — preterm infants with severe ROP often have other complications (IVH, BPD, CP) influencing visual behavior
Family observation: unusual eye movements, poor visual fixation, squinting, or white reflex in photos should prompt evaluation

Risk Factors

Gestational age (strongest — inversely proportional; <32 weeks at risk, <28 weeks highest)
Birth weight (≤1500 g main threshold, with lower BW higher risk)
Supplemental oxygen exposure and saturation fluctuations (unstable oxygenation)
Severe illness: sepsis, NEC, IVH, severe RDS
Slow postnatal weight gain
Multiple blood transfusions, hyperglycemia, chronic inflammation
Hispanic/white ethnicity higher risk than black (pigmentation hypothesis)
Male sex (slightly higher risk)

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Screening is mandatory — not symptom-driven. AAP/AAO/AAPOS guidelines: screen all infants ≤30 weeks GA or ≤1500 g BW, plus selected infants 31-34 weeks with unstable clinical course (sepsis, severe RDS, cardiac surgery, etc.); first exam 4 weeks chronological age OR 31 weeks postmenstrual age, whichever later; dilated indirect ophthalmoscopy by trained pediatric ophthalmologist; frequency of follow-up based on findings (every 1-3 weeks).
  • Continue screening until one of: retinal vascularization complete to Zone III (typically 42-44 weeks PMA), ROP regression with absence of any Zone I ROP, postmenstrual age 45 weeks without Type 1 ROP, or Type 1 ROP reached requiring treatment.
  • Treatment criteria (Early Treatment for ROP, ETROP): treat Type 1 ROP within 48-72 hours of diagnosis — any Zone I stage with plus disease; Zone I stage 3 with or without plus; Zone II stage 2 or 3 with plus disease; A-ROP; AP-ROP; careful follow-up after treatment for response/recurrence. Long-term ophthalmology follow-up for all preterm infants including those with resolved ROP for refractive errors, amblyopia, strabismus.

Treatment Methods

01
Prevention (primary strategy): targeted oxygen saturation 90-95 percent (not <85-87 percent due to mortality/ROP risk, not >95 percent due to ROP); minimize saturation fluctuations (stable oxygen delivery systems, alarm limit adherence); avoid hyperoxia; treat infections promptly; optimize nutrition with mother's own milk; minimize blood transfusions; close adherence to NICU oxygen management protocols.
02
Screening as described: timely first exam (4 weeks chronological age or 31 weeks PMA, whichever later), serial exams every 1-3 weeks by experienced pediatric ophthalmologist, follow ICROP classification, timely treatment when Type 1 criteria met.
03
Laser photocoagulation: historical gold standard, peripheral retinal ablation of avascular retina (destroys tissue releasing VEGF, stopping drive for neovascularization); performed under sedation or general anesthesia; 95 percent effective for standard disease but less effective for Zone I / A-ROP; causes peripheral visual field constriction and may exacerbate myopia.
04
Anti-VEGF injections: intravitreal bevacizumab (off-label, 0.625 mg) or ranibizumab (FDA-approved, 0.2 mg) — very effective particularly for posterior disease (Zone I, A-ROP) where laser challenging; concerns — systemic VEGF suppression (transient serum reduction — implications for developing organs unknown but suggested possible neurodevelopmental effects), late recurrence requires prolonged follow-up; emerging preferred for certain indications; combination laser + anti-VEGF in some centers.
05
Retinal surgery for advanced disease: scleral buckle for Stage 4A without central retinal detachment; vitrectomy for Stage 4B/5; salvage procedures with guarded visual prognosis; lens-sparing techniques in pediatric retinal surgery centers.
06
Long-term management: all preterm infants — regular ophthalmologic follow-up (first year every 3-6 months, then annually at minimum) for refractive errors (high myopia common), strabismus, amblyopia, glaucoma; amblyopia therapy (patching, glasses) as needed; low vision services for severe visual impairment; parental education about importance of lifelong ophthalmologic follow-up even after ROP resolution; vision-related neurodevelopmental support.

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