Maya Keiralla

Introduction

Retinopathy of prematurity (ROP) is a disorder of abnormal retinal vascular development unique to preterm infants, and one of the leading causes of preventable childhood blindness worldwide (1,2). Foundation doctors rotating through neonatal units, paediatrics or ophthalmology will often encounter it, and an adequate understanding supports safe handover, informed conversations with parents, and recognition of when urgent ophthalmic referral is needed. This article gives a brief, practical overview of ROP’s pathophysiology, screening and treatment for a foundation doctor audience.

Pathophysiology

Retinal vessels normally grow outward from the optic disc, reaching the periphery only by around 40 weeks’ gestation. Preterm birth interrupts this, leaving the peripheral retina avascular at birth (1). In the postnatal hyperoxic phase, relative hyperoxia, worsened by supplemental oxygen, suppresses VEGF and halts vessel growth. As the avascular retina then matures, relative hypoxia drives a surge in VEGF and IGF-1 (1,2), producing erratic neovascularisation at the vascular-avascular junction that risks traction, haemorrhage and retinal detachment.

Epidemiology

Improved survival at lower gestational ages has expanded the at-risk population. UK surveillance data show around 4% of screened infants require treatment, with a median gestational age of ~25 weeks and median birthweight of ~706 g among those treated (3). Most disease is mild and regresses spontaneously; a minority progresses to sight-threatening disease, which is largely preventable with organised screening and timely treatment.

Risk Factors

Low gestational age and low birthweight dominate, with most other factors playing a secondary or contributory role. Risk rises sharply below 28 weeks’ gestation and below 1500g birthweight (further below 1000 g) (1-3). Some other risk factors include, but are not limited to, prolonged or poorly titrated oxygen therapy, mechanical ventilation/respiratory distress syndrome, sepsis and necrotising enterocolitis, multiple gestation, poor postnatal weight gain, intraventricular haemorrhage, blood transfusions, and erythropoietin.

Classification: ICROP3

ROP is classified by zone, stage and plus disease under the International Classification of Retinopathy of Prematurity (ICROP3) (4). Zone I posterior, highest risk) to zone III (peripheral, lowest risk) describes location. Severity at the vascular-avascular junction is described by stage: stage 1, a flat demarcation line; stage 2, a ridge with height and width; stage 3, a ridge with extraretinal fibrovascular proliferation; stage 4, partial retinal detachment; and stage 5, total retinal detachment. ‘Plus disease’, posterior vessel dilation and tortuosity, marks active, aggressive disease. ICROP3 also introduced ‘Aggressive ROP’ (A-ROP), a distinct category characterised by the progression of the disease (tempo and appearance of vascular change) rather than the location of the disease. This can rapidly progress to retinal detachment if untreated (4).

UK Screening Guidelines

The joint RCPCH/RCOphth/BAPM guideline (2022, revised October 2024) recommends screening for infants born under 31 weeks’ gestation or with a birthweight under 1501 g, with screening also considered for unwell or complex infants born slightly later after discussion with ophthalmology (5). The first examination is timed to postmenstrual and postnatal age, with follow-up continuing weekly or two-weekly until the retina is fully vascularised or the risk of disease has passed.

Diagnosis and Examination

ROP is asymptomatic, so diagnosis relies entirely on structured screening. Binocular indirect ophthalmoscopy remains the gold-standard bedside examination; digital wide-field imaging (e.g. RetCam) is increasingly used alongside or instead of it, enabling storage, remote grading and comparison over time (1). Essential prerequisites are adequate pupil dilation, topical anaesthesia and comfort measures, and monitoring for the oculocardiac reflex and apnoea, with findings recorded using standardised ICROP terminology.

When to Treat: Type 1 ROP

Treatment is reserved for disease crossing a defined threshold (‘Type 1’ ROP): zone I any stage with plus disease, zone I stage 3 without plus disease, or zone II stage 2/3 with plus disease (2,6). The most urgent presentations (zone I stage 3 with plus disease or A-ROP) should be treated within 48 hours. Other Type 1 patterns should be treated within 48-72 hours to minimise progression to retinal detachment (3,6).

Laser Photocoagulation

Indirect diode laser ablates the peripheral avascular retina, removing the VEGF drive. It remains first-line, used in ~90% of treated UK infants (3), with durable outcomes and no systemic drug exposure, but requires sedation, causes permanent peripheral field loss, and can be technically difficult in very posterior zone I disease.

Anti-VEGF Therapy

Intravitreal anti-VEGF is a relatively more recent therapeutic measure that neutralises VEGF without destroying peripheral retina, used in ~8% of treated UK infants and particularly effective for posterior zone I disease where laser is difficult. Key trial evidence comes from BEAT-ROP (bevacizumab) (7) and RAINBOW (ranibizumab) (8). Limitations include a risk of late reactivation requiring prolonged follow-up, a theoretical neurodevelopmental concern from systemic VEGF suppression (9), and less mature long-term data than laser.

The Role of Tele-Ophthalmology

Digital fundus imaging allows trained non-physician staff to capture wide-field retinal images at the cotside, which are then remotely graded by an ophthalmologist: a telemedicine approach shown to extend ROP screening into areas without on-site specialists (10).

Conclusion

ROP is a preventable cause of childhood blindness driven by disrupted retinal vascularisation in preterm infants, with gestational age and birthweight as the dominant risk factors. UK screening targets infants under 31 weeks’ gestation or under 1501 g birthweight, and treatment, required once ‘Type 1’ ROP develops, should be delivered within 48–72 hours. Laser remains first-line, with anti-VEGF increasingly used for posterior disease, and tele-ophthalmology allows specialists to screen more infants on time, even in units without an ophthalmologist physically present. A working grasp of these principles helps foundation doctors recognise at-risk infants and communicate confidently about this preventable condition.

References

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2. Hellström A, Smith LEH, Dammann O. Retinopathy of prematurity. Lancet. 2013;382(9902):1445–57.
3. Royal College of Ophthalmologists. Treating Retinopathy of Prematurity in the UK [guideline]. London: RCOphth; 2022.
4. Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Chan RVP, Berrocal A, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021;128(10):e51–e68.
5. Royal College of Paediatrics and Child Health. Screening of Retinopathy of Prematurity (ROP): Clinical Guideline. London: RCPCH; 2022 (revised October 2024).
6. Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the Early Treatment for Retinopathy of Prematurity randomized trial. Arch Ophthalmol. 2003;121(12):1684–94.
7. Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603–15.
8. Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD, Chiang MF, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet. 2019;394(10208):1551-9.
9. Tan H, Blasco P, Lewis T, Ostmo S, Chiang MF, Campbell JP. Neurodevelopmental outcomes in preterm infants with retinopathy of prematurity. Surv Ophthalmol. 2021;66(5):877–91.
10. Vinekar A, Gilbert C, Dogra M, Kurian M, Shainesh G, Shetty B, et al. The KIDROP model of combining strategies for providing retinopathy of prematurity screening in underserved areas in India using wide-field imaging, tele-medicine, non-physician graders and smart phone reporting. Indian J Ophthalmol. 2014;62(1):41–9.