01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Retinopathy of prematurity is abnormal retinal vascular development following preterm birth. An immature retina has a substantial peripheral area that has not yet acquired its normal blood supply. Early disruption of vascular growth is followed by an ischaemic drive to form new vessels, mediated in part by vascular endothelial growth factor. Mild ROP often regresses, but severe fibrovascular proliferation can contract and detach the retina. Screening is therefore designed to detect the dangerous phase before visible external symptoms or established visual loss appear.
Current UK eligibility comes from the RCPCH guideline revised in October 2024. All infants born before 31+0 weeks, or with birthweight less than 1501 g, should be screened; meeting either criterion is sufficient. The revision additionally advises considering screening for those born at 31+0 to 31+6 weeks. This distinction matters: a relatively heavier baby in that gestational group should not simply be dismissed using the earlier 2022 threshold. The neonatal team records the eligibility decision and the first appointment from the actual gestation and date of birth.
For infants born before 31+0 weeks, the first examination is at 31+0 to 31+6 weeks postmenstrual age or four completed weeks after birth, whichever is later. Four completed postnatal weeks corresponds to the 28–34-day window. For eligible infants born from 31+0 weeks, use 36+0 to 36+6 weeks postmenstrual age or four completed postnatal weeks, whichever is sooner. Postmenstrual age is gestational age at birth plus elapsed age. Recording only a phrase such as four weeks can confuse these two clocks and delay screening in the most vulnerable infants.
The retinal assessment describes both location and severity. Zone I is the posterior area centred on the optic disc; zone II surrounds it and zone III is the remaining temporal crescent. A stage 1 line can become a stage 2 ridge, followed by stage 3 extraretinal fibrovascular growth. Partial and total detachment are stages 4 and 5. Plus disease describes pathological vascular dilation and tortuosity in the posterior retina; pre-plus is abnormality insufficient to reach that category. The stage alone does not determine urgency, and aggressive ROP may progress without following a neat sequence of stages.
Treatment is indicated for zone I ROP with plus disease, zone I stage 3 without plus, zone II stage 3 with plus, and aggressive ROP. Zone II stage 2 with plus is included in type 1 criteria but is treated as a borderline group in UK guidance: treatment or expert review within one week or less may be appropriate. This is a specialist decision requiring close observation. Aggressive ROP and zone I stage 3 with plus need treatment as soon as possible within 48 hours. The other specified treatment-requiring patterns are generally treated within 48–72 hours after the decision.
Laser treats peripheral avascular retina and reduces the angiogenic stimulus. Anti-VEGF treatment can be especially useful for posterior disease and may allow further peripheral vascular growth, but it changes the pattern and duration of recurrence risk. Consent covers ocular complications, the possibility of repeat treatment and uncertainty about systemic effects in a developing infant. Current UK SmPCs include neonatal ROP indications for selected ranibizumab and aflibercept products; the older 2022 statement that only ranibizumab is licensed is no longer current. Bevacizumab use for ROP remains off-label.
Screening and treatment are shared clinical responsibilities across neonatal and ophthalmic teams. The baby needs appropriate comfort measures, cardiorespiratory observation and staff able to respond to instability during an examination or procedure. Oxygen treatment remains controlled by the neonatal team according to the infant's respiratory needs; abruptly withholding necessary oxygen is not a treatment for ROP. Transfer letters must carry the latest findings and the next examination date, and discharge requires an actual booked appointment when surveillance is incomplete.
Key points
- Screen all infants born before 31 weeks or with birthweight below 1501 g.
- The October 2024 revision also says to consider screening infants born at 31+0 to 31+6 weeks.
- Screening timing depends on both gestational and postnatal age.
- Describe each eye by zone, stage, extent and pre-plus or plus disease.
- Stage 3 is extraretinal fibrovascular proliferation; stages 4 and 5 involve detachment.
- Laser and intravitreal anti-VEGF treatment have different follow-up requirements.
- Neonatal anti-VEGF doses and delivery devices differ from adult regimens.
- A quiet examination soon after anti-VEGF treatment does not end surveillance.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Immature retinal circulation
Preterm delivery interrupts normal retinal vascular development before the peripheral retina is fully supplied. The most immature and smallest infants have the greatest baseline vulnerability to severe disease.
Postnatal physiological disruption
Changes in oxygen exposure, growth and systemic illness influence the immature retinal circulation. ROP reflects several interacting developmental and clinical factors rather than a single episode of oxygen treatment.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Arrested vascular growth
An early phase of relatively excessive oxygen exposure suppresses normal vascular growth in the immature retina. A peripheral area remains avascular while the retina continues to develop and its metabolic demand increases.
- 2Ischaemic neovascular drive
Insufficiently vascularised retina generates proangiogenic signals, including VEGF. Abnormal new vessels and fibrovascular tissue may extend from the vascular border towards the vitreous.
- 3Traction and detachment
Fibrovascular tissue can contract and distort the retina. Progressive traction produces partial or total retinal detachment, with severe consequences when the central retina is involved.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Confirm gestational age in weeks and days, birthweight and date of birth. Current weight and apparent clinical improvement do not replace the original screening criteria.
Interpret zone, stage, extent and vascular changes together for each eye. A stage number without its zone or plus status is insufficient for deciding the next step.
Discuss any pre-plus or plus in at least two quadrants, any zone I or posterior zone II disease, or any stage 3 ROP with the treating ophthalmologist under the UK screening guidance.
Infants with worsening retinal disease may feed and behave as before. Screening is required because routine external observation does not reliably identify treatment thresholds.
A missing next date, an unacknowledged transfer or uncertainty about who will examine the baby is a clinical risk. Resolve it while the infant is still under the team's care.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Scheduled dilated retinal examinationFirst step - Why
- Detect and classify ROP at the appropriate developmental time.
- Interpretation and limitations
- A competent examiner uses binocular indirect ophthalmoscopy or an established wide-field imaging pathway. Both eyes require documented findings and a definite next review or screening-completion decision.
- 02
Serial retinal comparison - Why
- Identify progression, regression and changes in vascular activity.
- Interpretation and limitations
- At least weekly review is indicated for posterior vascularisation, any pre-plus or plus, or stage 3 in zones II or III when immediate treatment is not required.
- 03
Wide-field retinal imaging - Why
- Document disease and support competent local or remote assessment.
- Interpretation and limitations
- Images can assist comparison but may incompletely show the far periphery. The final examination may require indirect ophthalmoscopy or longer imaging surveillance until stopping criteria are satisfied.
- 04
Selective fluorescein angiography or examination under anaesthesia - Why
- Clarify uncertain activity or persistent peripheral avascular retina after treatment.
- Interpretation and limitations
- The specialist may use these when an adequate peripheral view is difficult or vascular abnormalities persist. Incomplete vascularisation alone does not automatically justify another anti-VEGF injection.
- 05
Later visual and refractive assessment - Why
- Detect consequences beyond the active neonatal retinal disease.
- Interpretation and limitations
- Children may develop myopia, strabismus or amblyopia despite successful treatment. Visual function, refraction and retinal status remain part of planned childhood follow-up.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Familial exudative vitreoretinopathy
Inherited abnormal peripheral retinal vascularisation can resemble ROP, including in a term child. Family history, gestation and specialist peripheral retinal findings help distinguish the disorders.
Persistent fetal vasculature
Residual fetal vessels may produce a stalk, cataract or tractional retinal change, often in one smaller eye. Its developmental configuration differs from the typical bilateral vascular-border pattern of ROP.
Other retinal vascular disorders
Conditions such as Coats disease or syndromic retinal vascular abnormalities can produce exudation and detachment. The age, neonatal history, vascular pattern and associated findings guide the specialist differential.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01First examinationCalculate and secure the screening dateFirst stepA preterm or low-birthweight infant meets screening criteria or needs consideration under the 2024 extension.+
- 1Record birth gestation and weight, applying the less-than-31-week or less-than-1501-g criteria and considering the 31-week group.
- 2Use the appropriate earlier-versus-later rule for the two gestational groups to calculate the first examination window.
- 3Explain the purpose of screening and the examination to the parents before it occurs.
- 4Assign responsibility for scheduling and carry the confirmed date across any hospital transfer.
02Progressive ROPEscalate findings within the treatment windowEscalationScreening detects severe or referral-warranted ROP or concerning progression between examinations.+
- 1Contact the treating ophthalmologist with each eye's zone, stage, extent and plus status.
- 2Arrange treatment within the specified urgency, including as soon as possible within 48 hours for aggressive ROP or zone I stage 3 plus.
- 3Coordinate neonatal stabilisation, anaesthesia or analgesia and transport when treatment is delivered elsewhere.
- 4Obtain informed parental consent and provide a written plan for post-treatment surveillance.
03Transfer and follow-upKeep surveillance connected to the childThe baby moves between services, leaves hospital or has received retinal treatment.+
- 1Send the complete screening and treatment record and name the clinician responsible for the next assessment.
- 2Confirm the receiving appointment and communicate its date and location to the family before discharge.
- 3Arrange prompt contact and clinical review of any missed appointment rather than waiting for symptoms.
- 4Continue the treatment-specific surveillance until the ophthalmologist records an appropriate endpoint.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Ranibizumab — Lucentis 10 mg/mL vial for neonatal ROP
Specialist neonatal dose: 0.2 mg in 0.02 mL intravitreally per treated eye. Up to three injections per eye may be given within six months if disease remains active, at least four weeks apart.Use the specified low-volume high-accuracy VISISURE equipment and a trained ophthalmologist; the full vial is not the dose. Contraindicated with hypersensitivity, active or suspected ocular or periocular infection, or severe active intraocular inflammation. Use aseptic technique, monitor for pressure rise and endophthalmitis and retain prolonged retinal follow-up. Use outside the stated licensed patterns requires an explicit specialist off-label decision.
Aflibercept — Eylea 40 mg/mL pre-filled syringe
Specialist neonatal dose: 0.4 mg in 0.01 mL intravitreally per treated eye. Up to two injections per eye may be given within six months for disease activity, at least four weeks apart.The pre-filled syringe must be used with the PICLEO paediatric dosing device; neither the full syringe nor an adult dose is appropriate. Contraindicated with hypersensitivity, active or suspected ocular or periocular infection, or severe active intraocular inflammation. Monitor pressure, optic nerve perfusion and infection; do not inject at IOP of 30 mmHg or higher. Other Eylea concentrations and presentations must not be substituted without checking their specific paediatric authorisation and delivery instructions.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Retinal detachment
Stage 4 disease involves partial detachment and stage 5 involves total detachment. Structural disruption can lead to permanent severe visual loss despite subsequent attempts at repair.
Later refractive and binocular problems
Myopia, strabismus and amblyopia can follow prematurity and ROP. They may remain relevant after active vascular disease has regressed and require continuing assessment during childhood.
Post-treatment reactivation
Vascular activity can return after initial anti-VEGF response, sometimes after a prolonged quiet interval. Persistent peripheral avascular retina provides a substrate for continuing surveillance concerns.
Treatment-related ocular injury
Intravitreal therapy can be complicated by infection, pressure elevation or injury to intraocular structures. Laser treatment can also produce ocular complications, and both procedures require neonatal physiological support.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Without treatment, examine at least every two weeks only when vessels reach mid or anterior zone II or zone III, no pre-plus or plus is present, and there is no ROP or only stage 1–2; otherwise follow the more frequent or treatment pathway.
- For untreated infants without ROP, screening usually continues until vessels extend into zone III. With ROP, the ophthalmologist requires appropriate regression on at least two consecutive examinations before stopping routine screening.
- After anti-VEGF treatment, RCOphth recommends early review at one to two days and one week, continuing at weeks 2, 3, 4, 6, 8, 10, 12, 14, 16, 20 and 24 after treatment, with extra visits when findings warrant.
- Persistent avascular retina or reactivation can require longer observation; follow-up to 65 weeks postmenstrual age has been advised after bevacizumab. Do not substitute untreated screening-stop rules for the post-treatment plan.
- Following laser, follow the specialist's early and serial review schedule for regression, incomplete treatment and complications, and maintain later childhood visual and refractive surveillance.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
The 1500 g boundary
A birthweight of exactly 1500 g meets the less-than-1501-g screening criterion. Writing the rule loosely as below 1500 g can inadvertently exclude an eligible baby.
Two clocks guide the first examination
A baby born at 25 weeks reaches four postnatal weeks before 31 weeks postmenstrual age, so the later rule determines screening. A baby born at 30 weeks reaches four postnatal weeks later than the 31-week window.
Rapid regression is not a cure certificate
Anti-VEGF can make vascular activity improve quickly while peripheral retina remains incompletely vascularised. Recurrence can occur much later, which is why continuing appointments remain essential.
Treatment licensing evolves
A guideline's therapeutic principles may remain useful while its product-licensing statements age. Check the current neonatal indication, concentration, injection volume and device for the specific medicine being supplied.
11Common pitfallsFrequent interpretation and management errors.
- 01
Requiring both low gestational age and low birthweight instead of either screening criterion.
- 02
Applying four postnatal weeks without checking the postmenstrual-age rule.
- 03
Treating all stage 2 disease alike without considering zone, plus disease and progression.
- 04
Using an adult intravitreal dose or failing to use the required paediatric dosing device.
- 05
Ending follow-up after early anti-VEGF regression or losing the next appointment during transfer.