Bevacizumab Shows Potential as First-Line Retinopathy of Prematurity Treatment

Premature Baby Retinopathy
Retinopathy In Premature Infant. Retinal Fluorescein Angiogram Showing Hypoxia Of The Retinal Periphery. Recolorized, Black And White Image. (Photo By BSIP/UIG Via Getty Images)
While researchers call study results “encouraging,” they note that very low doses may be linked with reactivation.

Type 1 retinopathy of prematurity (ROP) patients may benefit from initial treatment with low or very low doses of the anti-vascular endothelial growth factor (VEGF) drug bevacizumab, according to an investigation conducted by the Pediatric Eye Disease Investigator Group. Their research, published in Ophthalmology, shows that, at 12 months, 91% of patients who undergo the treatment have normal retinal and other structural outcomes; however, reactivation rates are high (22% in this study). 

The research included 2 sequential masked, multicenter, dose de-escalation phase 1 studies to determine the lowest dose of intravitreal bevacizumab effective for type 1 ROP. The research group reviewed records from 113 eyes of 120 infants diagnosed with type 1 ROP in at least 1 eye. Patients were given either 2 doses of low-dose (0.25, 0.125, 0.063, and 0.031 mg) or very low-dose (0.016, 0.008, 0.004, and 0.002 mg) injections to the study eye. If both eyes had ROP, the fellow eye received 1 dose level higher than the study eye.  

More than half of the eyes treated with an injection (study and fellow) required some additional treatments, with 31 (27%) of the study eyes requiring additional ROP treatment specifically (6 for initial treatment failure, 4 for reactivation ≤4 weeks, and 21 for later reactivation). Another 31 (27%) underwent prophylactic laser treatment for persistent avascular retina.

At 12 months, patients were evaluated for cycloplegic refractive error, retinal outcomes, and abnormalities of the cornea, lens, or other anterior segment locations.

The study shows that, while reactivation itself was not linked to either dosage, the eyes that received the very low dosages had a shorter time-to-reactivation than the low dose group (mean 76.4 vs 85.7 days). The follow up exam found strabismus in 29% of the participants at 12 months, and optic atrophy in 10%. Anterior segment abnormalities were seen in 5% of patients and poor retinal outcomes were seen in 3%. The median refraction was mildly myopic at -0.31 D, according to the study results.

“Ocular outcomes at 12 months are encouraging for initial doses of IVB from 0.25 mg down to as low as 0.004 mg as initial treatment for type 1 ROP,” according to the research group. They suggest that future studies focus “particular attention to timing and characteristics of reactivation, extent of vascularization, need for additional treatment, and longer-term outcomes such as visual acuity, macular structure by imaging, and neuro-development.” 

The study was limited by its focus on the short-term (4-week) response to different initial bevacizumab doses, the low numbers of participants, and a lack of photographic documentation of initial category of Type 1 ROP.


Writing Committee, Freedman SF, Hercinovic A, Wallace DK, et al, on behalf of the Pediatric Eye Disease Investigator Group. Low- and very low-dose bevacizumab for retinopathy of prematurity: reactivations, additional treatments, and 12-month outcomes. Ophthalmol. Published online May 31, 2022. doi:10.1016/j.ophtha.2022.05.019