Bevacizumab (Avastin, Genentech) is a VEGF inhibitor with U.S. regulatory approval for use in certain types of cancers. It is widely used off-label by ophthalmologists for treatment of a number of retinal vascular diseases. VEGF levels have been shown to be elevated in retinopathy of prematurity (ROP),1 and there are reports of successful use of bevacizumab in treatment of ROP.2,3

It is hoped that this pharmacologic agent will provide a therapeutic alternative for ROP and possibly improve outcomes over the gold standard treatment, laser photocoagulation. However, the unknown risks and possible complications of this invasive treatment are of concern to insurers.

Risk is introduced when a new treatment is used in lieu of a treatment considered to be the standard of care. This is especially so when the risk-benefit ratio of a new therapy will not be known for many years, as in the treatment of premature infants. Proper informed consent, outlining the known risks of intravitreal injection and the off-label nature of the treatment, is therefore important.

Injections into the small eyes of premature infants raise a number of concerns, including the risks of lens damage, retinal perforation, and hemorrhage, as well as the need to prep the eye against infection. None of these risks, except the possibility of lens damage, are present with laser treatment. In the event of a claim, plaintiffs can point out that such a complication would not have occurred if the standard of care had been followed. In addition, proper dosage and timing for ROP treatment are not established, and the long-term consequences of systemic absorption of bevacizumab are not yet known.

Standard follow-up protocols for laser may not be appropriate for intravitreal injection. For example, retinal detachments may be seen later in bevacizumab-treated eyes than in laser-treated eyes. Therefore, the follow-up period may need to be extended, which may be a risk if the parents are not compliant with the follow-up schedule. An undiagnosed retinal detachment poses a risk for litigation.

VEGF is crucial for fetal growth and development in the third trimester, and the systemic effects of anti-VEGF injection in premature infants are not well understood.4 If the use of bevacizumab results in long-term systemic problems, this could result in significant liability in future years. The statute of limitations for premature infants extends a few years beyond their majority.

For high-risk eyes in which laser would cause severe field loss or result in a poor prognosis, detailed informed consent is crucial if bevacizumab therapy for ROP is elected. In general, caution is recommended if intravitreal bevacizumab is used instead of the established standard of laser photocoagulation, until the indications, dosage, timing, and complications of this new treatment modality are established.

Arthur W. Allen Jr, MD, is President of Pacific Eye Associates and Vice Chairman of the Ophthalmology Department at California Pacific Medical Center in San Francisco, CA. He previously served on the Claims Committee and as Chairman of the Board of OMIC. Dr. Allen states that he has no financial interests relevant to the material discussed in this article. He may be reached at +1 415 923 3007; or email at awmikeallen@yahoo.com.

  1. Nonobe NI, Kachi S, Kondo M, et al. Concentration of vascular endothelial growth factor in aqueous humor of eyes with advanced retinopathy of prematurity before and after intravitreal injection of bevacizumab. Retina. 2009;29(5):579-585.
  2. 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(7):603-615.
  3. Wu WC, Yeh PT, Chen SN, Yang CM, Lai CC, Kuo HK. Effects and complications of bevacizumab use in patients with retinopathy of prematurity: a multicenter study in Taiwan. Ophthalmology. 2011;118(1):176-183.
  4. Hård AL, Hellström A. On the use of antiangiogenetic medications for retinopathy of prematurity. Acta Paediatr. 2011;100(8):1063-1065.