The Effects of Anti-Vascular Endothelial Growth Factor Loading Injections on Retinal Microvasculature in Diabetic Macular Edema

Purpose: To evaluate changes in the retinal microvasculature using widefield swept-source optical coherence tomography angiography (SS-OCTA) following three anti-vascular endothelial growth factor (anti-VEGF) loading injections for diabetic macular edema (DME). Methods: Thirty-four treatment-naïve patients with DME received an initial three loading injections, followed by injections on an as-needed basis. Macular ischemia was evaluated based on the foveal avascular zone (FAZ) area, perfusion density, and vessel density on a 3 × 3-mm SS-OCTA image. Midperipheral ischemia was analyzed by dividing a 12 × 12-mm image into 16 boxes to compare changes in the nonperfusion area (NPA). Participants were categorized as aggravated, stable, or improved based on changes in the NPA after three injections. Results: Of the 34 included patients, eight (23.5%) demonstrated aggravation of the NPA, 23 (67.6%) remained stable, and three (8.8%) exhibited improvement. Although FAZ area, perfusion, and vessel density increased, the differences were not significant compared to baseline. The number of injections and glycated hemoglobin (HbA1c) levels in the NPA aggravation group were significantly higher than in the stable and improvement groups. Logistic regression analysis revealed that NPA aggravation was independently associated with the number of anti-VEGF injections. Conclusions: Changes in NPA following anti-VEGF loading injections varied among patients with DME and were significantly associated with HbA1c levels and injection frequency. Worsening mid-peripheral NPA after the anti-VEGF injections independently risked DME recurrence. Translational Relevance: We revealed that worsening mid-peripheral retinal ischemia after anti-VEGF loading injections contributes to the recurrence of DME.