Aflibercept and Brolucizumab in Diabetic Macular Edema: A Focused Review of Efficacy, Safety, and Clinical Considerations

<b>Background/Objectives:</b> Diabetic macular edema (DME) are major causes of visual impairment worldwide, with vascular endothelial growth factor (VEGF) playing a central role in disease pathogenesis. Intravitreal anti-VEGF therapy is the current standard of care for center-involving DME. <b>Methods:</b> This narrative review summarizes and compares the pharmacological properties, clinical efficacy, safety, and real-world performance of aflibercept and brolucizumab in the treatment of DME, based on randomized controlled trials and observational studies published between 2014 and 2025. <b>Results:</b> Both agents demonstrate significant improvements in visual acuity and retinal anatomy. Brolucizumab has shown non-inferior visual outcomes and, in several studies, greater reductions in central retinal thickness with the potential for extended dosing intervals, suggesting reduced treatment burden. However, post-marketing data have identified an increased risk of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, associated with brolucizumab, which has influenced its clinical use. <b>Conclusions:</b> Both aflibercept and brolucizumab are effective anti-VEGF therapies for diabetic macular edema, but they differ in durability and safety considerations. Aflibercept remains a reliable first-line option for many patients, while brolucizumab may be considered in carefully selected cases where treatment burden is a priority. Individualized treatment selection based on clinical characteristics, patient preferences, and safety considerations is essential for optimizing long-term outcomes.