To examine the quality of evidence and the variability in the off-label use of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in the treatment of retinopathy of prematurity (ROP) and to discuss the implications for the design of future randomized controlled trials.

Systematic literature review.

A systematic review of the literature indexed by Ovid MEDLINE, EMBASE, and the Cochrane database was performed with a broad and inclusive search strategy. All case reports and retrospective and prospective trials in peer-reviewed journals reporting the use of bevacizumab in ROP were included.

Nine articles, including 6 case reports, 2 retrospective studies, and 1 prospective case series representing 77 eyes of 48 infants, were selected for the review. The doses used ranged from 0.4 to 1.25 mg, with 0.75 mg being the most common, used in 3 of the 9 studies. A total of 8 of the 11 eyes in the case received bevacizumab as a first-line therapy and two articles noted worsening of an already present retinal detachment. One retrospective study and the prospective case series used bevacizumab alone, whereas the other retrospective study used bevacizumab before and with retinal surgery.

Considerable variability exists in how bevacizumab is used for the treatment of ROP in the literature to date. Further randomized control trials are warranted and should aim to assess statistically the optimal timing, frequency, and dose of the drug. Careful attention should be given to the potential for systemic complications and long-term effects of intravitreal bevacizumab in infants.