Hypotension Associated With Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity

Abstract

Bevacizumab is an antivascular endothelial growth factor (VEGF) monoclonal antibody, approved as an additional medication with other chemotherapy drugs for the treatment of metastatic cancer. 1 It has been used off-label to decrease retinal thickening in age-related macular degeneration and to diminish intraoperative complications in diabetic retinopathy patients. 2,3 In addition, randomized trials have shown improvement of the retina and reduced zone I disease progression with intravitreal bevacizumab therapy for retinopathy of prematurity (ROP) in preterm infants. 4 Systemic cardiovascular complications of intravenous bevacizumab have been reported, including hypertension, thromboembolic events, cardiac ischemia, cerebrovascular ischemia, and bleeding. 5 Although local intravitreal bevacizumab therapy might minimize the systemic side effects, cardiovascular adverse effects such as hypertension have been observed in some studies. 6 In theory, bevacizumab will elevate blood pressure by reducing nitric oxide synthase in endothelial cells, decreasing vascular permeability. 7 Thus, bevacizumabrelated hypotension needs more attention because this mechanism is unexpected, although it has been mentioned in product information, presenting an incidence rate of 7% to 15%. 8 One retrospective study in Japan also reported that 25 colorectal patients with cancer presented a temporary blood pressure drop within 90 minutes of intravenous bevacizumab. 9 Neither systemic adverse events nor hypotension effects were reported in clinical trials after treatment with bevacizumab for ROP 4,10,11 ; however, the serum level of bevacizumab has been detected after intravitreous injection in preterm infants. 12 To provide more safety information for bevacizumab in preterm infants, we report a case of twin preterm infants treated abstract Intravitreal bevacizumab therapy in preterm infants for retinopathy of prematurity (ROP) can be associated with hypotension. We report twin preterm infants who developed hypotension within 1 day after intravitreal bevacizumab therapy for ROP. Before receiving the medication, their clinical statuses were stable and similar. The dose, procedure, and premedication were the same; however, twin B presented with hypotension for 3 days. Although bevacizumab-related hypotension has been described in product information (incidence rate 7%-15%), this is the first case report of intravitreal bevacizumab for ROP inducing hypotension. Physicians should be aware of intravitreal bevacizumab therapy-related hypotension when treating ROP. We suggest conducting a postmarketing active surveillance on the systemic adverse effects of this regimen in preterm infants.

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention

“…Intravitreal pegaptanib or bevacizumab injection alone or in combination with laser photocoagulation are so far considered as therapeutic modalities for the management of ROP [14] but the systemic toxicity of intravitreal bevacizumab is of concern [15]. …”

Augenärztliche Screening-Untersuchung bei Frühgeborenen (S2k-Level, AWMF-Leitlinien-Register-Nr. 024/010, März 2020)

“…Als kurzfristige Komplikation nach Anti-VEGF-Therapie wurde eine arterielle Hypotension beschrieben [88]. Zur Frage, ob sich eine Behandlung mit Anti-VEGF-Antikörpern negativ auf die langfristige psychomotorische Entwicklung der Kinder auswirkt, gibt es bislang nur wenige und widersprüchliche Daten [38,54].…”

Aggressive Posterior Retinopathy of Prematurity (APROP): LASER as the Primary Modality of Treatment

“…[29] A study by Morin et al reported that severe neurodevelopmental disabilities (Bayley scores <70) was seen 3.1 times higher with bevacizumab compared to laser. [30] Most recently, hypotension-related reports [31] and histopathologically proven new or reactivation of bronchopulmonary dysplasia have been noted after anti-VEGF administration. [32] Few studies were designed to study specific abnormalities related to anti-VEGF treatment and detected no systemic complications.…”