Retinopathy of prematurity (ROP) is one of the leading causes of childhood blindness worldwide. This intricate disease stems from the abnormal retinal vessel development in preterm infants and can have devastating consequences if left untreated. In an effort to advance our understanding and improve treatments, a groundbreaking new study delves into the risk factors enabling reactivation of ROP post-treatment with intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) agents.

Conducted between 2017 and 2022, the research recently published in ‘The Journal of Pediatrics’ sheds light on integral factors that contribute to the reemergence of ROP. The study’s compelling findings provide valuable insights imperative for healthcare professionals to enhance patient care and outcomes in those most vulnerable.

The DOI for this study is 10.1016/j.jpeds.2024.113913.


In this meticulously orchestrated study, a cohort of 114 infants who received IVI therapy was observed, adding up to a total of 223 eyes. These infants were categorized based on the response to the treatment—reactivation of ROP versus no reactivation. A thorough analysis was then carried out using multivariable logistic regression, taking into account variables related to ROP as well as patient-specific factors.


The reactivation of ROP was noted in 11.4% of infants and affected 9.9% of the treated eyes with a mean reactivation time of 84 ± 45 days. The rate of reactivation varied significantly among different anti-VEGF agents with 6% for bevacizumab, 13.9% for aflibercept, and a considerably higher 22.2% for ranibizumab. Notably, ranibizumab emerged as an independent risk factor for reactivation (OR: 11.4, p=0.008).

Additional risk factors identified included the presence of periventricular leukomalacia (OR: 13.8, p=0.003), patent ductus arteriosus ligation (OR: 10.7, p=0.032), and the requirement of invasive mechanical ventilation on the day of IVI therapy (OR: 7.0, p=0.018).


This research underscores the necessity for vigilant monitoring of ROP reactivation, particularly in infants exposed to higher risks. The disparity in reactivation rates between anti-VEGF agents places a spotlight on ranibizumab’s elevated odds, suggesting a reassessment of the preferred treatment modalities for ROP could be imperative. Furthermore, the critical analysis of additional clinical factors that may predispose infants to ROP reactivation will assist clinicians in creating individualized care plans minimizing potential risks.

Future Prospects

Given the findings, there is an unequivocal demand for further research to determine the optimal anti-VEGF agent and dosage tailored for high-risk infants. This study could spur future clinical trials and investigations catered to refining treatments and ultimately preventing ROP reactivation.


While anti-VEGF therapy remains a cornerstone in the fight against ROP, this study casts an important light on the potential for reactivation post-treatment. It calls for an increased awareness amongst practitioners in monitoring and administering the right therapeutic protocols. The collaboration among neonatologists and ophthalmologists becomes more critical than ever, as it aids in ensuring that those most susceptible to ROP receive the most efficacious care possible.


1. Lee, C.-C., Chiang, M.-C., Chu, S.-M., Wu, W.-C., Ho, M. M.-C., & Lien, R. (2024). Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Anti-Vascular Endothelial Growth Factor Injection. _The Journal of Pediatrics_, 10.1016/j.jpeds.2024.113913.
2. Mintz-Hittner, H. A., Kennedy, K. A., & Chuang, A. Z. (2011). Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. _New England Journal of Medicine_, 364(7), 603-615.
3. Hellström, A., & Smith, L. E. H. (2016). Retinopathy of prematurity: pathophysiology and mechanisms of disease. _Annual Review of Pathology: Mechanisms of Disease_, 11, 475-496.
4. Hartnett, M. E. (2015). Advances in understanding and management of retinopathy of prematurity. _Survey of Ophthalmology_, 60(5), 440-455.
5. Stahl, A., Lepore, D., Fielder, A., Fleck, B., Reynolds, J. D., Chiang, M. F., … & Morin, J. (2019). Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): a randomised controlled multicentre trial. _Lancet_, 394(10208), 1551-1559.


1. Retinopathy of Prematurity Reactivation
2. Intravitreal Anti-VEGF Treatment
3. Ranibizumab for ROP
4. Premature Infants Eye Health
5. ROP Clinical Risk Factors

Using these keywords effectively will improve search engine visibility and educate a wider audience on this critical subject matter, thereby enhancing preventative and post-treatment interventions for ROP.