Incidence of retinal artery occlusion following intravitreal antivascular endothelial growth factor injections.

Abstract

Numerous multicenter clinical trials have demonstrated the efficacy of antivascular endothelium growth factor (VEGF) therapy for multiple retinal and choroidal vascular diseases. Although generally well tolerated, certain complications can occur, while rare, ocular vascular events have been reported following anti-VEGF injections in several prior studies (Papadopoulou et al. 2009; Bonnin et al. 2010; von Hanno et al. 2010; Mansour et al. 2010, 2012). We aim to determine the incidence of retinal artery occlusion (RAO) and to assess associated clinical features in patients undergoing intravitreal anti-VEGF injections. All patients receiving intravitreal anti-VEGF injections from 1 January 2016 to 31 December 2017 who also developed a RAO from a large tertiary care retina practice were identified in this retrospective study. A total of 16 686 unique patients received 125 108 anti-VEGF injections during the study period. Twelve patients developed a RAO (eight cases of central RAO and four cases of branch RAO) within 90 days of injection, resulting in an incidence of 1/1389 (0.072%). There were six males and six females with an average age of 81.9 ± 10.4 years (range: 58–94 years). A prior history of systemic hypertension was documented in 91.7% of patients (11 out of 12). Four patients underwent injections for AMD, one for DME, three for central retinal vein occlusion (RVO) and four for branch RVO. Prior to RAO occurrence, bevacizumab was injected in one case, ranibizumab in seven cases and aflibercept in four cases. The average period from the closest injection to RAO diagnosis was 37.0 ± 19.3 days (range: 14–70 days). The mean logarithm of the minimal angle of resolution visual acuity decreased from 0.43 ± 0.37 (20/54 Snellen equivalent) at the visit preceding diagnosis of RAO to 1.63 ± 1.10 (20/853 Snellen equivalent) after the occurrence of RAO. Table 1 shows no statistically significant difference of RAO incidence based on gender, age or laterality. The incidence of RAO varied by underlying ocular disease. Retinal artery occlusion (RAO) occurred in four out of 8212 (0.05%) patients with AMD, one out of 3502 (0.03%) patients with DME, seven out of 2811 (0.25%) patients with RVO and 0 out of 2161 patients receiving injections for other conditions. There was a significant difference in the rate of RAO only between AMD and RVO patients (p = 0.01). Retinal artery occlusion (RAO) occurred in one of 18 125 bevacizumab injections (0.006%), seven of 54 019 ranibizumab injections (0.013%) and four in 52 964 aflibercept injections (0.008%). No significant difference was found between these three groups (p = 0.55). There was a significant difference in RAO incidence between patients with hypertension and those without (p < 0.001). However, no difference was detected between patients with diabetes and those without diabetes (p = 0.41). Of the 10 of 13 088 patients undergoing unilateral injections, no RAO was detected in the fellow eye (p = 0.001). Due to its retrospective nature, there is an absence of controls in the current study. Nevertheless, from this large database, RAO was detected in approximately 1 in 1389 patients following intravitreal anti-VEGF injection. Anti-VEGF medications have been associated with vasoconstriction, decreased blood flow velocity (Sacu et al. 2011), as well as an increase in activated platelets, all of which can increase the risk of developing a RAO. However, it is unknown whether RAO was related to the intravitreal injection procedure, injected drug or comorbidities of these patients. Larger population-based studies may help confirm these findings and elucidate other underlying risk factors.