Effects of Intravitreal Anti-VEGF Therapy on the Clinical Course of Bronchopulmonary Dysplasia

Objectives: To demonstrate the effects of the injection of intravitreal bevacizumab (IVB) on the clinical course of established bronchopulmonary dysplasia (BPD).
Methods: This is a multicenter retrospective case-control study performed without any randomization or masking procedure. A total of 70 patients with BPD, including 35 cases (the IVB group) and 35 controls (the control group) were studied. Patients in the IVB group received intravitreal anti-VEGF (bevacizumab) treatment for type 1 prethreshold retinopathy of prematurity (ROP). The control group consisted of infants with BPD whose gestational age, birthweight, and gender were matched with those of the IVB group. None of the infants in the control group needed to be treated for ROP using either anti-VEGF or laser photocoagulation.
Results: There was no statistically significant difference (P = 0.11) between the groups in terms of the total duration of oxygen prior to the IVB injection (65.9 ± 23.5 and 79.1 ± 33.1 days in the IVB group and control group, respectively). However, after the injection of IVB, the total duration of oxygen was significantly lower in the IVB group (mean 7 (1 - 70) days vs. 16 (1 - 98) days, P = 0.01). In 14 cases with mild BPD and their matched controls, the median time (25% - 75%) for the discontinuation of oxygen therapy was 3 (2 - 7) days and 10 (5 - 15) days, respectively (P = 0.36). In 21 cases with moderate and severe BPD and their matched controls, the median time (25 - 75%) for the discontinuation of oxygen therapy was 14 (7 - 21) days and 22 (16 - 43) days, respectively (P = 0.024).
Conclusions: Intravitreal bevacizumab injection treatment for ROP cases with BPD was found to be associated with a shorter duration of oxygen use. The results of the study not only demonstrate a pathogenic correlation between ROP and BPD through an abnormal vasculogenesis, but also raise a question regarding whether or not the systemic side effects of IVB are actually adverse.