Aflibercept Reduces Retinal Hemorrhages and Intravitreal Microvascular Abnormalities But Not Venous Beading

Purpose Approximately 50% of patients receiving anti–vascular endothelial growth factor (VEGF) therapy show significant improvement in diabetic retinopathy severity score (DRSS), in particular at DRSS level 47 to 53 (moderately severe to severe nonproliferative diabetic retinopathy). Level 47 to 53 consists of 3 main features: deep hemorrhages (DH), venous beading (VB), and intraretinal microvascular abnormalities (IRMAs). It is unclear whether these features respond to anti-VEGF therapies differently. Design Post hoc analysis of Intravitreal Aflibercept versus Panretinal Photocoagulation in Patients with Proliferative Diabetic Retinopathy (CLARITY) study. Participants Treatment-naive participants randomized to intravitreal aflibercept. Methods We reanalyzed the fundus images at baseline, week 12, and week 52 to assess the changes of the 3 main features in DRSS level 47 to 53 in those patients who were treatment naive and had received aflibercept. Main Outcome Measures Changes in DH, VB, and IRMA after aflibercept therapy at weeks 12 and 52. Results Fifty-five treatment-naive eyes at baseline that received aflibercept were included in the study. Severe DH and severe IRMA improved in approximately 75% of eyes at week 12 and mostly remained improved at week 52; VB remained unchanged in all eyes at week 12. From 12 weeks, 32 eyes that had received injections showed improved or stable DH compared with 7 eyes that did not receive injections, and DH deteriorated in 6 eyes with no further injections compared with 4 eyes that had received more injections (P = 0.0072). Similarly, 15 eyes that continued to receive injections from week 12 showed improved or stable IRMA compared with 4 who did not receive injections (P = 0.006). Worsening of IRMA was seen in 5 eyes with no further injections compared with 4 eyes that continued to receive injections. The improvements in DH and IRMA are more likely to be maintained if less than 16 weeks have elapsed since the last anti-VEGF injection. Conclusions Aflibercept seems to improve DH and IRMA after just 3 injections. As soon as the frequency of injections were reduced, DH and IRMA can deteriorate again. It is unclear whether these results can be translated to patients without PDR.