JUL 29, 2011
A recent study in the New England Journal of Medicine found that intravitreal bevacizumab was more effective for treating zone I posterior stage 3+ ROP compared with conventional laser therapy. While this study opens the exciting possibility of using a biochemical treatment for severe ROP rather than conventional retinal ablation, the research committee of the American Association for Pediatric Ophthalmology and Strabismus has concerns about the study's methodology and data interpretation.
The AAPOS committee says that even though injections are less stressful for infants and may result in better outcomes, it is clearly premature to conclude that for zone I disease bevacizumab injection is superior to ablation, a treatment that has been examined in large randomized trials with 5- to 15-year outcomes.
In the study, researchers at the University of Texas Health Science Center randomized 150 infants with zone I or zone II posterior stage 3+ ROP to bilateral intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy. All infants weighed 1500 g or less at birth and had a gestational age of 30 weeks or less.
Of the 143 infants who survived to 54 weeks' postmenstrual age, retreatment was undertaken in 4 percent of the bevacizumab group and 22 percent of the laser group. This treatment effect was significant in patients with zone I disease (P = 0.003) but not those with zone II disease (P = 0.27). Five of 75 infants treated with bevacizumab died before reaching 54 weeks' postmenstrual age, as did 2 of 75 infants treated with laser therapy. This difference was not statistically significant, but the study was not powered to compare mortality rates between treatment groups. The authors found that conventional laser therapy resulted in permanent destruction of vessels in the peripheral retina, while intravitreal bevacizumab appears to allow for continued vessel growth into the peripheral retina.
While the authors observed no definite systemic or local toxic effects attributable to bevacizumab, they note that the study was too small to address safety and call for additional research.
The AAPOS research committee point out a few more flaws. They say the authors changed the primary outcome "before the date on which the data were first analyzed," but the study was unmasked and the authors do not provide results using the original endpoint. The new outcome, recurrence of neovascularization "requiring retreatment by 54 weeks' postmenstrual age," depended upon treatment decisions made by unmasked investigators and is not supported by the references provided.
The AAPOS committee also believes that the authors' assertion that visual field extent is less affected by bevacizumab than peripheral ablation is speculative. Since the trial was underpowered to determine safety, the higher number of deaths in the bevacizumab group and the potential for significant systemic effects over the long term in this vulnerable population must be systematically investigated.