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Author: Claude (AI), from PubMed abstracts · Reviewed by: Dr Mina Abdelmseih · Reviewed: 2026-11-15 · Review due: 2027-11-15

Educational content only. Not personalised medical advice. Clinical decisions remain the responsibility of the treating clinician.

Retinopathy of prematurity

Retinopathy of prematurity (ROP) is a vision-threatening vasoproliferative disease of preterm infants [S3] [S2] and a leading cause of potentially avertable childhood blindness [S4]. Its rising prevalence in low- and middle-income countries, the "third epidemic", has increased the need to screen at-risk infants [S7]. Timely screening and treatment with laser or intravitreal anti-VEGF drugs are the core of care [S12].

Key points - Risk rises steeply with prematurity: each week less of gestational age carried a median 1.4 times the odds of ROP, and each 100 g less of birth weight 1.8 times [S9]. - Laser photocoagulation and intravitreal anti-VEGF injection are the standard treatments [S12]; anti-VEGF was not inferior to laser for retreatment in a network meta-analysis and gave a better refractive profile [S12]. - Anti-VEGF monotherapy does not reduce retinal detachment overall and may increase recurrence needing retreatment in zone II disease (Cochrane, low-quality evidence) [S2]. - Telemedicine, weight-gain algorithms and artificial intelligence can support screening in settings with few specialists, but AI is not yet sufficient as a sole diagnostic tool [S7] [S8] [S11].

Evidence last checked: 2026-10-17 (PubMed abstracts).

Red flags

Recognise it: who is at risk

Confirm it

Two circular retinal maps marked with concentric zone boundaries around the optic disc and macula, clock hours around the edge, and labels for the ora serrata.
Diagram of the right and left retina showing zones I, II and III and the clock-hour sectors used to describe where vessel growth and retinopathy occur. Image: Michael F Chiang, Graham E Quinn, Alastair R Fielder, Susan R Ostmo, RV Paul Chan, Audina Berrocal, Gil Binenbaum, Michael Blair, J Peter Campbell, Antonio Capone Jr, Yi Chen, Shuan Dai, Anna Ells, Brian Fleck, William V Good, M Elizabeth Hartnett, Gerd Holmstrom, Shunji Kusaka, Andrés Kychenthal, Domenico Lepore, Birgit Lorenz, Maria Ana Martinez-Castellanos, Şengül Özdek, Dupe Ademola-Popoola, James D Reynolds, Parag K Shah, Michael Shapiro, Andreas Stahl, Cynthia Toth, Anand Vinekar, Linda Visser, David K Wallace, Wei-Chi Wu, Peiquan Zhao, Andrea Zin, CC BY 4.0, via Wikimedia Commons, resized to 800 px wide and re-encoded as JPEG.

Manage it

Before acting on this section, check the national and local guidelines, product information and regulatory approvals that apply where you practise. See the medical disclaimer.

Tier A (primary care / no specialist)

Tier B (general eye clinic or screening service)

Tier C (specialist centre)

  1. Laser vs ranibizumab. In RAINBOW (225 infants under 1500 g, 26 countries), treatment success was 80% with ranibizumab 0.2 mg, 75% with 0.1 mg and 66% with laser (doses as reported in [S5]); superiority of 0.2 mg narrowly missed significance (p=0.051), with fewer unfavourable structural outcomes and similar adverse events at 24 weeks [S5].
  2. Laser vs aflibercept. In FIREFLEYE (118 infants), aflibercept 0.4 mg (as reported in [S10]) gave 85.5% vs 82.1% success but did not meet noninferiority criteria; rescue treatment was needed in 4.8% vs 11.1% of eyes [S10].
  3. Cochrane review. Bevacizumab or ranibizumab monotherapy did not reduce retinal detachment or overall recurrence, reduced recurrence in zone I but increased it in zone II, and lowered very high myopia at 30 months; evidence was very low to low quality and long-term systemic effects are unknown [S2].
  4. Choice of agent and dose. A network meta-analysis of 68 studies (6445 infants) found no agent inferior to laser for retreatment; half doses retained efficacy but were associated with shorter times to retreatment [S12]. Exact bevacizumab doses are not stated in these abstracts: follow local protocols.
  5. Neurodevelopment. A meta-analysis of 8 studies did not find increased severe neurodevelopmental impairment after bevacizumab (OR 1.39, 95% CI 0.98-1.97), with a minor difference in motor scores; evidence quality was low [S6].
  6. Propranolol prophylaxis might reduce progression to stage 3 and the need for laser or anti-VEGF, but adverse events at 2 mg/kg/day (as reported in [S3]) raise concerns, and there is insufficient evidence for routine use [S3].

Refer when

Situation Urgency
Type 1 ROP or aggressive posterior ROP found at screening Urgent, at the latest, to a treating centre; timing per your local service or specialist advice [S2] [S10]
Preterm infant meeting screening criteria and not yet examined, or due for transfer or discharge Urgent, arrange screening; timing per your local service or specialist advice
Infant treated with anti-VEGF who misses follow-up Urgent; timing per your local service or specialist advice [S2] [S12]
Child treated for ROP, for refraction Routine, periodic cycloplegic refraction [S4]

Pitfalls

Evidence notes

Source Date Design
[S1] 2015 Systematic review and meta-analysis of 5 RCTs
[S2] 2018 Cochrane systematic review, 6 trials, 383 infants
[S3] 2018 Cochrane systematic review, 3 RCTs, 366 infants
[S4] 2019 Meta-analysis of 8 case-control studies
[S5] 2019 Open-label multicentre RCT, 225 infants
[S6] 2021 Meta-analysis of 8 comparative studies
[S7] 2021 Systematic review
[S8] 2021 Diagnostic accuracy meta-analysis, 61 studies
[S9] 2022 Systematic review of 18 population-based studies
[S10] 2022 Phase 3 RCT, 118 infants
[S11] 2023 Systematic review, 27 studies
[S12] 2024 Network meta-analysis, 15 RCTs and 53 non-randomised studies

Related articles

References

See the numbered source list below. Each marker [S#] links to its PubMed and DOI record.

Sources

  1. [S1] Manja V, Lakshminrusimha S, Cook DJ Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis. JAMA pediatrics. (2015). PubMed 25664703 · doi:10.1001/jamapediatrics.2014.3307
  2. [S2] Sankar MJ, Sankar J, Chandra P Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. The Cochrane database of systematic reviews. (2018). PubMed 29308602 · doi:10.1002/14651858.cd009734.pub3
  3. [S3] Kaempfen S, Neumann RP, Jost K, Schulzke SM Beta-blockers for prevention and treatment of retinopathy of prematurity in preterm infants. The Cochrane database of systematic reviews. (2018). PubMed 29499081 · doi:10.1002/14651858.cd011893.pub2
  4. [S4] Liang J Systematic review and meta-analysis of the negative outcomes of retinopathy of prematurity treated with laser photocoagulation. European journal of ophthalmology. (2019). PubMed 30022693 · doi:10.1177/1120672118770557
  5. [S5] 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 (London, England). (2019). PubMed 31522845 · doi:10.1016/s0140-6736(19)31344-3
  6. [S6] Tsai CY, Yeh PT, Tsao PN, Chung YE, Chang YS, Lai TT Neurodevelopmental Outcomes after Bevacizumab Treatment for Retinopathy of Prematurity: A Meta-analysis. Ophthalmology. (2021). PubMed 33212122 · doi:10.1016/j.ophtha.2020.11.012
  7. [S7] Al-Khaled T, Valikodath NG, Patel SN, Cole E, Chervinko M, Douglas CE, et al. Addressing the Third Epidemic of Retinopathy of Prematurity Through Telemedicine and Technology: A Systematic Review. Journal of pediatric ophthalmology and strabismus. (2021). PubMed 34288773 · doi:10.3928/01913913-20210223-01
  8. [S8] Athikarisamy S, Desai S, Patole S, Rao S, Simmer K, Lam GC The Use of Postnatal Weight Gain Algorithms to Predict Severe or Type 1 Retinopathy of Prematurity: A Systematic Review and Meta-analysis. JAMA network open. (2021). PubMed 34812847 · doi:10.1001/jamanetworkopen.2021.35879
  9. [S9] Yu CW, Popovic MM, Dhoot AS, Arjmand P, Muni RH, Tehrani NN, et al. Demographic Risk Factors of Retinopathy of Prematurity: A Systematic Review of Population-Based Studies. Neonatology. (2022). PubMed 35124682 · doi:10.1159/000519635
  10. [S10] Stahl A, Sukgen EA, Wu WC, Lepore D, Nakanishi H, Mazela J, et al. Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial. JAMA. (2022). PubMed 35881122 · doi:10.1001/jama.2022.10564
  11. [S11] Ramanathan A, Athikarisamy SE, Lam GC Artificial intelligence for the diagnosis of retinopathy of prematurity: A systematic review of current algorithms. Eye (London, England). (2023). PubMed 36577806 · doi:10.1038/s41433-022-02366-y
  12. [S12] Ortiz-Seller A, Martorell P, Barranco H, Pascual-Camps I, Morcillo E, Ortiz JL Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis. Survey of ophthalmology. (2024). PubMed 38432359 · doi:10.1016/j.survophthal.2024.02.005