This study reports the recurrences of retinopathy of prematurity (ROP), follow-up treatments and retinal structure outcomes of patients after low-dose intravitreal bevacizumab.
Study design
This masked, multicenter, dose de-escalation study enrolled 61 infants with type 1 ROP; 55 had bilateral disease. Patients received de-escalating doses of 0.25 mg (n=11), 0.125 mg (n=16), 0.063 mg (n=24) or 0.031 mg (n=10) of intravitreal bevacizumab in 1 eye; 57 fellow eyes received a dose that was 1 level higher than the study eye. At 4 weeks, additional treatments were administered according to the investigator’s discretion.
Researchers defined “early failure” as no improvement 3 to 5 days after injection, type 1 ROP recurrence or severe neovascularization requiring another 4 weeks of treatment. “Late recurrence” were cases of recurrent plus disease or neovascularization prompting additional treatment after 4 weeks. Several weeks or months after bevacizumab, some investigators performed laser treatment for “persistent avascular retina” as prophylaxis.
Outcomes
Twenty-five patients required additional treatment: 3 were retreated for early failure, 11 had late recurrence and 11 were retreated for persistent avascular retina. Eighteen eyes received laser as their first or only additional treatment and 7 eyes received repeated intravitreal bevacizumab. Most eyes were only retreated once (n=19). There was no relationship between lower dose levels and need for additional treatment. However, the sample size was too small for a definitive conclusion.
Retinal structural outcomes were very good. By 6 months, a majority of study eyes (n=56 eyes) had regression of ROP with normal posterior poles, 1 eye developed stage 5 retinal detachment and 4 infants died from preexisting medical conditions.
Limitations
The sample size was too small to conclusively state the results. Treatment response in study eyes and the incidence of recurrence were also likely influenced by a crossover effect from the higher dose therapy in the fellow eye.
Clinical significance
Anti-VEGF drugs are particularly useful for zone I disease by minimizing the extent of the laser, reducing the risk of myopia and better preserving macular architecture. However, the lowest dose required to control ROP and, at the same time, minimize systemic complications is still not known. This study showed that the lowest dose did not require retreatment, but larger randomized studies are required for validation.