Anti-VEGF treatment for ROP requires further study

April 3, 2013

Intravitreal injection of anti-VEGF agents for treatment of severe retinopathy of prematurity (ROP) requires close scrutiny and further study.

Philadelphia-While there is strong evidence supporting the use of peripheral retinal ablation for treatment of severe retinopathy of prematurity (ROP), intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents requires closer scrutiny, according to Graham E. Quinn, MD.

Results of the BEAT-ROP study showed intravitreal bevacizumab was effective in preventing retinal detachment in the large majority of eyes with severe acute phase disease, noted Dr. Quinn, professor of ophthalmology at the University of Pennsylvania, Philadelphia.

However, he pointed out several methodological limitations of the study and raised other concerns.

Dr. Quinn noted that random assignment to treatment in BEAT-ROP was by patient rather than within subjects, and outcome determination was unmasked. In addition, BEAT-ROP was underpowered to assess safety in terms of mortality and systemic morbidity. Dr. Quinn also questioned the high rates of failure and complications that occurred in the control arm that received laser treatment.

Furthermore, while recurrence of ROP requiring re-treatment before 54 weeks postmenstrual age (PMA) was the primary outcome measure, the mean time to recurrence was 19 ± 8 weeks after intervention, which was at about 33 to 34 weeks (PMA).

Cautioning about late recurrence after anti-VEGF treatment, Dr. Quinn cited a recent study of 17 eyes of 9 patients treated with bevacizumab that had a mean age at treatment-requiring recurrence of 49 weeks PMA, but a range of 37 to 69 weeks. In the latter study, mean time between initial treatment and re-treatment for recurrence was 14 weeks, and five eyes went on to develop retinal detachment.

“What do these data mean for us in determining how to follow children who have been treated with anti-VEGF agents and how to treat recurrences? Does bevacizumab treatment suppress acute-phase retinopathy but change it to a smoldering disease?” Dr. Quinn said.

He also pointed out that optimal bevacizumab dosing has not been determined. Raising concerns about systemic absorption of the anti-VEGF agent and implications for affecting organogenesis, Dr. Quinn cited a paper showing rising bevacizumab serum levels and falling systemic VEGF levels in infants followed for a 2-week period postintravitreal injection.

“We need to consider treatments other than bevacizumab. We need bevacizumab pharmacokinetics studies in infants, and an adequately sized, randomized trial that is controlled and has a masked outcome [determination],” Dr. Quinn concluded.

Dr. Quinn did not indicate any financial interest in this topic. This article is based on Dr. Quinn’s presentation at the 2012 Pediatric Subspecialty Day during the annual meeting of the American Academy of Ophthalmology.

For more articles in this issue of Ophthalmology Times eReport, click here.