Less may be more for intravitreal bevacizumab in retinopathy of prematurity

Lower dose performs as effectively as a higher dose when treating ROP.

Reviewed by Thomas Wayne Hejkal, MD, PhD.

A 30-mcg intravitreal dose of bevacizumab (Avastin, Genentech, Inc.) is as effective as 20 times that much for treating retinopathy of prematurity (ROP), reported Thomas Hejkal, MD, PhD, who is in private practice at Eye Consultants, P.C., Omaha, NE, and chair emeritus, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha.

A 625-mcg dose of intravitreal bevacizumab is effective for treating ROP, but with that higher dose are concerns about the possibility of development of systemic side effects. Because limited data also have indicated that 30 mcg is effective, Dr. Hejkal and colleagues retrospectively compared the post-treatment results in 22 patients treated with the low dose and compared the results to 22 who had been treated with the high dose of bevacizumab for ROP.

Dr. Hejkal based the use of the markedly lower dose of bevacizumab on a study by Wallace et al.1 In that study, none of 10 eyes in the lowest dose group (0.031 mg) had an ROP recurrence or needed additional treatment. This group had the best outcome in that study.

Dose comparisons of intravitreal bevacizumab

The investigators conducted a non-randomized, non-masked, consecutive case series study that included infants with ROP treated with the 2 doses of intravitreal bevacizumab. The same retina specialist treated both groups of infants.

In this study 22 patients (44 eyes; mean estimated gestational age ± 95% confidence interval [CI] at birth, 24.7 ± 0.44 weeks; mean birth weight, 612 ± 51.8 grams) were treated with the 30-mcg dose in 0.03 ml and compared to 22 consecutive previously treated patients (44 eyes; mean estimated gestational age ± 95% CI] at birth, 24.6 ± 0.57 weeks; mean birth weight, 672 ± 71.5 grams) treated with the 625-mcg dose in 0.025 ml.

The primary outcome measures were the percentage of eyes with initial ROP regression and the percentage of eyes that required subsequent laser treatment. A secondary outcome measure was the time between bevacizumab treatment and subsequent laser treatment.

The results indicated that all eyes in the 30-mcg and 625-mcg groups had initial regression of ROP and that 50% of all eyes in both groups were treated with laser at some point after the bevacizumab treatment. The respective mean estimated gestational ages at the time of laser treatment were 53.5 ± 4.48 weeks and 50.7± 2.40 weeks, a difference that did not reach significance (P = 0.54).

The times to the need for laser treatment were also similar and nonsignificant (P = 0.23) in both groups, 16.3 ± 4.23 weeks and 15.0 ± 2.10 weeks, respectively.

In the higher dose group, 1 eye developed a 4B retinal detachment and three babies died from causes presumably unrelated to treatment, Dr. Hejkal reported.

He concluded, “A 30-mcg dose of intravitreal bevacizumab was as effective as a 625-mcg dose for treating ROP. The subsequent laser treatment rates were identical (50%) in each group and the times to laser treatment also were similar. These data provide additional evidence from clinical practice to support the use of a 30-mcg dose of bevacizumab for treating ROP.”

Thomas Wayne Hejkal, MD, PhD
E: tom@eyeconsultantspc.com
This article is adapted from Dr. Hejkal’s presentation at the American Society of Retina Specialists 39th annual meeting, October 8-12, 2021, San Antonio, Texas. He has no financial interest in this subject matter.
Reference
1. Wallace DK, Dean TW, Hartnett ME, et al; Pediatric Eye Disease Investigator Group. A dosing study of bevacizumab for retinopathy of prematurity: late recurrences and additional treatments. Ophthalmology 2018;125:1961-6. doi: 10.1016/j.ophtha.2018.05.001. Epub 2018 Jun 7.