Treatment of retinopathy of prematurity:when and how?

Abstract

Retinopathy of prematurity is a serious vascular disorder of the immature retina and remains one of the
leading causes of preventable childhood blindness among infants born before term. The condition results from disrupted development of the retinal vascular network and may progress to pathological neovascularisation, formation of fibrovascular membranes, tractional retinal detachment and irreversible visual loss. Although the early and milder forms frequently regress without treatment, certain stages, including aggressive posterior disease and cases with pronounced vascular activity in the posterior pole, require timely therapeutic intervention to prevent structural complications. This review analyses the principal treatment methods used in retinopathy of prematurity. Laser photocoagulation remains a widely
applied and well-studied option that effectively suppresses pathological vascular activity, although it may lead to loss of peripheral visual field and an increased risk of later myopic refractive errors. Intravitreal administration of agents targeting vascular growth factors represents a more recent therapeutic strategy that preserves peripheral retina and is particularly effective in severe posterior forms, but requires prolonged follow-up due to the possibility of late disease recurrence.

Combined therapeutic approaches and surgical treatment play an important role in advanced stages with
structural complications. This review highlights the need for individualised treatment decisions, early detection through rigorous screening of high-risk infants and long-term follow-up of all treated children.

Key words: retinopathy of prematurity, laser photocoagulation, intravitreal therapy, surgical treatment, pediatric ophthalmology

Bibliography

1. Blencowe H, Lawn JE, Vazquez T, Fielder A, Gilbert C. Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatr Res. 2013;74(Suppl 1):35–49. doi:10.1038/pr.2013.205. PMID:24366462; PMCID:PMC3873709.

2. Dimitrova-Grozeva A, Grozev G, Topalov N. Retinopathy of Prematurity – a Bulgarian Perspective of a Global Epidemic. Scripta Scientifica Salutis Publicae. 2017;3(1):41–46. Available from: https://journals.mu-varna.bg/index.php/sssp/article/view/1499

3. Kaur K, Mikes BA. Retinopathy of Prematurity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. PMID:32965990.

4. Chan-Ling T, Gole GA, Quinn GE, Adamson SJ, Darlow BA. Pathophysiology, screening and treatment of retinopathy of prematurity: a multi-disciplinary perspective. Prog Retin Eye Res. 2018;62:77–119. doi:10.1016/j.preteyeres.2017.09.002. PMID:28958885.

5. Kim SJ, Port AD, Swan R, Campbell JP, Chan RVP, Chiang MF. Retinopathy of prematurity: a review of risk factors and their clinical significance. Surv Ophthalmol. 2018;63(5):618–637. doi:10.1016/j.survophthal.2018.04.002. PMID:29679617; PMCID:PMC6089661.

6. Strube YNJ, Wright KW. Pathophysiology of retinopathy of prematurity. Saudi J Ophthalmol. 2022;36(3):239–242. doi:10.4103/sjopt.sjopt_18_22. PMID:36276256; PMCID:PMC9583358.

7. Hartnett ME. Pathophysiology of Retinopathy of Prematurity. Annu Rev Vis Sci. 2023;9:39–70. doi:10.1146/annurev-vision-093022-021420. PMID:37164029.

8. Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Chan RV, Berrocal A, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021;128(10):e51–e68. doi:10.1016/j.ophtha.2021.05.031. PMID:34247850; PMCID:PMC10979521.

9. Posterior zone I retinopathy of prematurity: spectrum of disease and outcome after laser treatment. Katoch, Deeksha et al. Canadian Journal of Ophthalmology, Volume 54, Issue 1, 87 – 93

10. Good WV; Early Treatment for Retinopathy of Prematurity Cooperative Group. Final results of the Early Treatment for Retinopathy of Prematurity randomized trial. Trans Am Ophthalmol Soc. 2004;102:233–248. PMID:15747762; PMCID:PMC1280104.

11. Ghergherehchi L, Kim SJ, Campbell JP, Ostmo S, Chan RVP, Chiang MF. Plus Disease in Retinopathy of Prematurity: More Than Meets the ICROP? Asia Pac J Ophthalmol. 2018;7(3):152–155. doi:10.22608/APO.201863. PMID:29797825; PMCID:PMC7880619.

12. Boskabadi H, Abrishami M, Shoeibi N, Kakavandi M, Moradi M, Zakerihamidi M. Incidence of retinopathy of prematurity in neonates with neonatal sepsis. Arch Iran Med. 2023;26(5):248–251. doi:10.34172/aim.2023.38. PMID:38301087; PMCID:PMC10685868.

13. Chernodrinska V, Mladenov O. Results of treatment of retinopathy of prematurity with laser therapy at the Children’s Eye Department of the University Hospital “Aleksandrovska”. Bulgarian Review of Ophthalmology. 2019;63(2):15–21.

14. Veleva N, Chernodrinska V. Refractive status in children with laser-treated retinopathy of prematurity: Our experience in Bulgaria. Open Access Maced J Med Sci. 2019;7(8):1320–1323. doi:10.3889/oamjms.2019.309. PMID:31110577; PMCID:PMC6514343.

15. Kıran Yenice E, Kara C. Development of myopia in laser-treated infants with retinopathy of prematurity: prematurity or laser photocoagulation? Int Ophthalmol. 2023;43(5):1453–1458. doi:10.1007/s10792-022-02540-x. PMID:36149616.

16. 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;328(4):348–359. doi:10.1001/jama.2022.10564. PMID:35881122; PMCID:PMC9327573.

17. Patel NA, Acaba-Berrocal LA, Hoyek S, Fan KC, Martinez-Castellanos MA, Baumal CR, et al; Retinopathy of Prematurity Injection Consortium (ROPIC). Comparison in retreatments between bevacizumab and ranibizumab intravitreal injections for retinopathy of prematurity: A multicenter study. Ophthalmology. 2023;130(4):373–378. doi:10.1016/j.ophtha.2022.11.012. PMID:36396121; PMCID:PMC10280429.

18. Modrzejewska M, Nazwalska M. Long-term observation of treatment effects of anti–vascular endothelial growth factor monotherapy or combined therapy with diode laser in retinopathy of prematurity. J Clin Med. 2023;12(17):5644. doi:10.3390/jcm12175644. PMID:37685711; PMCID:PMC10488330.

19. Gotz-Więckowska A, Chmielarz-Czarnocińska A, Pawlak M, Gadzinowski J, Mazela J. Ranibizumab after laser photocoagulation failure in treatment of retinopathy of prematurity. Sci Rep. 2017;7(1):11894. doi:10.1038/s41598-017-12264-z. PMID:28928468; PMCID:PMC5605713.

20. Chandra P, Kumawat D, Agarwal D, Chawla R. Combined vitrectomy and anti–vascular endothelial growth factor treatment for stage 4 retinopathy of prematurity with extensive neovascular proliferation. J Pediatr Ophthalmol Strabismus. 2020;57(1):61–66. doi:10.3928/01913913-20191030-01. PMID:31972043.

21. 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 factor therapy versus laser for retinopathy of prematurity: A network meta-analysis. Surv Ophthalmol. 2024;69(4):585–605. doi:10.1016/j.survophthal.2024.02.005. PMID:38432359.

22. Sen P, Jain S, Bhende P. Stage 5 retinopathy of prematurity: An update. Taiwan J Ophthalmol. 2018;8(4):205–215. doi:10.4103/tjo.tjo_61_18. PMID:30637192; PMCID:PMC6302569.

23. Hellström A, Smith LEH, Hård AL. Retinopathy of prematurity: eighty years after its detection – current status and future perspectives. Neonatology. 2024;121(5):608–615. doi:10.1159/000538907. PMID:38776885; PMCID:PMC11446300.

24. Wu AL, Wu WC. Anti–vascular endothelial growth factor therapy for retinopathy of prematurity and pediatric retinal diseases. Asia Pac J Ophthalmol. 2018;7(3):145–151. doi:10.22608/APO.201837. PMID:29633587.

25. Sen P, Agarwal AAK, Bhende P, Ganesan S. Treatment outcomes of combined anti–vascular endothelial growth factor injection and laser photocoagulation in type 1 and aggressive posterior retinopathy of prematurity. Int Ophthalmol. 2022;42(1):95–101. doi:10.1007/s10792-021-02004-8. PMID:34415476.

26. Arthur N, Byrne E, Kehinde F, Bhandari V, Quinones Cardona V. Respiratory complications in infants with retinopathy of prematurity requiring laser photocoagulation. Am J Perinatol. 2024;41(4):439–444. doi:10.1055/s-0041-1740347. PMID:34891193.

27. Albalawi HB, Hashem F, Alharbi ANJ, Alali NM, Alshehri WMS, Alharfy AAN, et al. Retinopathy of prematurity as a multidisciplinary challenge: a pediatricians’ standpoint. J Multidiscip Healthc. 2022;15:153–159. doi:10.2147/JMDH.S351878. PMID:35082499; PMCID:PMC8786345.

28. Велева-Кръстева НВ, Чернодринска ВС. Ретинопатия на недоносеното: скрининг и лечение. София: ИК „Св. Иван Рилски“; 2019. 48 с. ISBN:978-954-353-388-6.

Адрес за кореспонденция:

A. Levi

Eye Clinic, University Hospital “Alexandrovska”, Department of Ophthalmology, Ministry of
Medicine, Medical University – Sofia

Blvd. “St. Georgi Sofiyski”, 1
1431, Sofia
e-mail: alinna.levi@gmail.com