Response to Initial Anti-Vascular Endothelial Growth Factor for Diabetic Macular Edema Is Significantly Correlated with Response to Third Consecutive Monthly Injection.

Purpose: To determine whether the response to the initial anti-vascular endothelial growth factor (anti-VEGF) injection to treat diabetic macular edema (DME) is significantly correlated with the response to the third consecutive monthly injection of the same anti-VEGF agent. Methods: Seventy eyes with DME that were treated with an anti-VEGF agent (16 eyes with 1.25-mg bevacizumab, 35 eyes with 0.5-mg ranibizumab, and 19 eyes with 2.0-mg aflibercept) were studied. They were treated with three consecutive monthly injections of one of the three anti-VEGF agents. The best-corrected visual acuity (BCVA) in the logarithm of the minimum angle of resolution (logMAR units) and the central macular thickness (CMT) were measured at the baseline, 1 week after the initial injection, and 1 month after the third consecutive monthly injection. The changes of both values from the baseline 1 week after the initial injection (day 7) and 1 month after the third monthly injection were determined. The significance of the correlations between the BCVA and the CMT was determined. Results: The mean BCVA improved significantly for all three agents (0.38 ± 0.22 logMAR units at the baseline to 0.27 ± 0.25 logMAR units) after the three monthly injections (p < 0.05, repeated ANOVA). For all cases, a moderate but significant correlation was found between the BCVA at day 7 and 1 month after the third injection (r = 0.58, p < 0.01; Spearman's rank correlation). No significant correlation was found for bevacizumab (r = 0.09, p = 0.73), moderate correlation was found for ranibizumab (r = 0.42, p < 0.05), and a strong correlation was found for aflibercept (r = 0.83, p < 0.001) between the BCVA at day 7 and at 1 month after the third injection. The mean CMT improved significantly for all three agents (481.9 ± 96.3 µm at the baseline to 364.1 ± 116.0 µm after the three monthly injections, p < 0.05), and a moderate correlation was found for the three agents between CMT at day 7 to that at one month after the third anti-VEGF injection (r = 0.54, p < 0.01). A moderate correlation was found for all three agents between CMT at day 7 to that at one month after the third anti-VEGF injection (r = 0.68 for bevacizumab, r = 0.41 for ranibizumab and r = 0.53 for aflibercept, p < 0.05). Conclusions: The significant correlations between the results on day 7 to that one month after the third anti-VEGF treatment for DME indicates that the long-term effects of anti-VEGF therapy can be predicted by the short-term response. In addition, the results indicate that there may be differences in the effectiveness between the three anti-VEGF agents.

Expression of vascular infarction-related molecules after anti-vascular endothelium growth factor treatment for diabetic macular edema.

To determine whether an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in eyes with diabetic macular edema (DME) affects the vascular infarction-related molecules (VIRMs). Nineteen eyes with DME were treated with 0.5 mg of intravitreal ranibizumab (IVR), and 22 eyes with DME were treated with 2 mg of intravitreal aflibercept (IVA). Blood was collected before, 1 week and 1 month after the injections. Aqueous humor was collected before and 1 month after the injections. The concentration of the VIRMs (cardiac myoglobin, cardiac troponin, intercellular adhesion molecule, monocyte chemotactic protein-1, matrix metalloproteinase-8, placental growth factor [PlGF], tenascin-C, tissue inhibitor of metalloproteinase-1, thrombospondin-2, vascular cell adhesion molecule-1, and VEGF) were determined by the multiplex assay. After the single injection of both types of anti-VEGF agents, the concentration of aqueous VEGF decreased significantly (P < 0.01). The plasma VEGF was reduced significantly at 1 week after the IVA (93.7 ± 17.6 to 39.5 ± 11.6 pg/ml; P < 0.01) but no significant change was seen after IVR (120.2 ± 11.3 to 137.4 ± 17.7 pg/ml). No significant changes were detected for the other VIRMs in the plasma and aqueous. A single intravitreal injection of anti-VEGF for DME does not significantly affect the concentration of several VIRMs.

Multiple Effects of Intravitreal Aflibercept on Microvascular Regression in Eyes with Diabetic Macular Edema.

PURPOSE: To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME). DESIGN: Interventional, prospective study. PARTICIPANTS: Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections. METHODS: Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined. MAIN OUTCOME MEASURES: The mean number of microaneurysms and NPA evaluated as the ISI. RESULTS: At baseline, the mean CRT was 485.7±90.6 µm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 µm (P = 0.1 × 10-5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P = 0.3 × 10-5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P = 0.3 × 10-5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r = 0.56; P = 0.004) and after treatment (r = 0.53; P = 0.006). A significant correlation was found between CRT and ISI at baseline (r = -0.39; P = 0.03) but not after treatment (r = -0.06; P = 0.79). CONCLUSIONS: The reduction in the number of microaneurysms was correlated with reduction in CRT.