438 - Systemic hypertension after intravitreal bevacizumab therapy for type I ROP: is there evidence for concern?

Poster Number: 438

Elizabeth W. Freeman, Comer Children's Hospital at University of Chicago Medical Center, Chicago, IL, United States; Ema Avdagic, University of Chicago Division of the Biological Sciences The Pritzker School of Medicine, Chicago, IL, United States; Sarah H. Rodriguez, University of Chicago Division of the Biological Sciences The Pritzker School of Medicine, Chicago, IL, United States; Kristen Wroblewski, Department of Public Health Sciences, The University of Chicago, Chicago, IL, United States

Background: A recent case report published in Pediatrics describes the first known instance of a premature infant developing systemic hypertension 10 days after intravitreal bevacizumab (IVB) treatment for stage 3 retinopathy of prematurity (ROP). Brain MRI was notable for cortical vasogenic edema that improved after resolution of the hypertensive crisis, similar in both radiographic appearance and time course to posterior reversible encephalopathy syndrome (PRES), which has been described as a rare complication of systemic bevacizumab in adults. This suggests the possibility of PRES as an adverse effect of IVB for ROP, but it remains unknown whether PRES may occur in neonates after IVB.

Objective:
The treatment of ROP varies depending on disease severity and may include observation, laser, or anti-VEGF therapy such as IVB. While studies have shown notably lower rates of disease recurrence and better refractive outcomes in infants treated with IVB compared to laser therapy, more data will be helpful to assess the safety of IVB in neonates.

Design/Methods:
This is a retrospective cohort study evaluating neonates with ROP who have been treated with IVB for the development of sustained hypertension after treatment. 77 infants with type 1 ROP who were treated with IVB were compared with 78 control infants with either type 1 ROP treated with laser or type 2 ROP with spontaneous regression. Additionally, in collaboration with pediatric neuroradiology, we are re-reviewing the available neuroimaging for the presence of vasogenic edema that may be indicative of PRES.

Results:
When controlling for sex, birth weight, gestational age, umbilical arterial catheter placement, steroid use, and other medical risk factors for hypertension, no differences in diagnosis of hypertension were found between infants with type 1 ROP treated with IVB and control infants who had been treated with laser (OR: 0.747, 95% CI: 0.27 – 2.07) or experienced spontaneous regression (OR: 0.66, 95% CI: 0.27 – 1.57). Of the neonates in the IVB group, 4/77 neonates had a diagnosis of hypertension; two had had an MRI and both were without explicit vasogenic edema. In the control group 4/78 neonates had a diagnosis of hypertension and all four had an MRI without explicit vasogenic edema, although none of the studies in either group were performed during episodes of uncontrolled hypertension.
Conclusion(s):
Our data thus far is reassuring against the possibility that IVB for type I ROP increases risk of hypertension or vasogenic brain edema suggestive of PRES. This has implications for the safety profile of bevacizumab in ROP.