Long-term systemic outcomes following anti-VEGF therapy for ROP

A study conducted to determine the long-term effects of anti-vascular endothelial growth factor (VEGF) therapy in children with retinopathy of prematurity (ROP) found that when compared to laser treatment, anti-VEGF treatment was not associated with most systemic and neurodevelopmental outcomes. Darius D Bordbar, MD, a vitreoretinal fellow and Nimesh Patel, MD, an attending in the Retina Service at Massachusetts Eye and Ear, Harvard Medical School, Boston, presented the team’s findings at the 2026 annual meeting of the American Academy of Ophthalmology 2026 in New Orleans.
Previous research has found positive results, ie, that anti-VEGF therapies are efficacious in selected ROP populations¹ and that bevacizumab (Avastin, Genentech) enters the systemic circulation and suppresses VEGF.² However, inconsistent results have been reported among different studies.^3,4

To advance that body of knowledge, Bordbar and colleagues conducted a retrospective cohort study to evaluate if anti-VEGF for ROP is associated with long-term systemic or neurodevelopmental outcomes. They compared the mortality and systemic, developmental, and ophthalmic outcomes after anti-VEGF therapy or laser treatment administered to patients with ROP. Patient data were obtained from an electronic health record database. The matched comparison included 773 infants treated with anti-VEGF therapy and 773 with laser.

What did the analysis show?

The investigators reported that anti-VEGF treatment was associated with greater mortality (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.11-2.75) and lower rates of asthma (HR, 0.80; 95% CI, 0.64-0.98). The results also revealed that there were no differences in neurodevelopmental disorders, cerebral palsy, epilepsy, or other outcomes.

A comparison of patients who underwent two or more treatments compared with one treatment showed a mortality HR of 1.17 (95% CI, 0.59-2.32). However, while subanalyses showed greater delayed milestones and renal morbidity, the mortality signal was not replicated. A post hoc sensitivity analysis conducted in June 2026 showed a mortality HR of 2.16 (95% CI, 1.41-3.33).

Bordbar and colleagues concluded that use of anti-VEGF therapy to treat ROP was not associated with most systemic and neurodevelopmental outcomes when compared with laser treatment. However, a limited mortality signal may warrant further study.

“When we treat ROP, we are thinking about both a child’s vision and their long-term health. Our study adds real-world evidence on outcomes beyond the eye, but the mortality association does not establish that anti-VEGF treatment caused harm. Underlying illness and treatment selection may still influence these results. Prospective studies with careful long-term follow-up are needed to better inform treatment decisions and counseling for families,” Bordbar stated.

References

1. 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;364:603-15. doi:10.1056/NEJMoa1007374
2. Sato T, Wada K, Arahori H, et al. Serum concentrations of bevacizumab (Avastin) and vascular endothelial growth factor in infants with retinopathy of prematurity. Am J Ophthalmol. 2012;153:327-33.e1. doi:10.1016/j.ajo.2011.07.005
3. Morin J, Luu TM, Superstein R, et al; Canadian Neonatal Network and the Canadian Neonatal Follow-Up Network Investigators. Neurodevelopmental outcomes following bevacizumab injections for retinopathy of prematurity. Pediatrics. 2016;137:e20153218. doi:10.1542/peds.2015-321
4. Marlow N, Reynolds JD, Lepore D, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial. EClinicalMedicine. 2024;71:102567. doi:10.1016/j.eclinm.2024.102567