From Monotherapy to Combination Strategies: Redefining Treatment Approaches for Multiple-Cause Macular Edema

Qianwei Zhu,1 Xuchong Pan,1 Zhenni Du,1 Jianing Ying,2 Yiran Hu,1 Quanyong Yi,2 Xiangxiang Fu1 1Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China; 2Department of Ophthalmology, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, People’s Republic of ChinaCorrespondence: Quanyong Yi, Department of Ophthalmology, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China, Tel +8613586543802, Email [email protected] Xiangxiang Fu, Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China, Tel +8617855825160, Email [email protected]: Macular edema (ME) is a leading cause of visual impairment in various retinal disorders. Current treatment modalities, including anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids, often require repeated applications, increasing both medical and economic burdens. ME is driven by chronic inflammation and VEGF overexpression, causing fluid accumulation in the macula. Recent studies have highlighted the role of various cytokines in ME pathogenesis, necessitating a comprehensive approach to treatment. While monotherapies have shown efficacy, they are associated with limitations such as the need for frequent injections and potential side effects. Combination therapies, including anti-VEGF drugs with macular laser photocoagulation, triamcinolone acetonide, or dexamethasone intravitreal implant (Ozurdex), have emerged as promising strategies. This review analyzes the outcomes of various combination approaches in different types of ME, including diabetic macular edema (DME), retinal vein occlusion-associated ME (RVO-ME), and uveitic macular edema (UME). The potential benefits of combining anti-VEGF and anti-inflammatory treatments are discussed, along with the need for personalized treatment regimens. Future research directions are outlined, emphasizing the importance of large-scale, long-term studies to evaluate the sustained efficacy and safety of combination therapies. The integration of advanced imaging techniques, biomarker analysis, and innovative therapeutic approaches is expected to shape the future landscape of ME management, moving towards more targeted and effective combination therapies.Plain Language Summary: Why was the study done?Macular edema (ME) is a leading cause of visual impairment, particularly in patients with conditions like diabetic retinopathy, retinal vein occlusion, and uveitis. Current treatments, such as anti-VEGF injections and corticosteroids, often need to be repeated frequently, placing a significant burden on patients and healthcare systems. This study was conducted to explore whether combining therapies could improve outcomes, reduce treatment frequency, and overcome the limitations of single treatments.What did the researchers do and find?We reviewed studies on combination therapies, such as anti-VEGF drugs paired with corticosteroids or laser treatments, to see how effective they are in treating different types of macular edema. Existing evidence suggests that combination treatments often provide better visual improvements and reduce treatment frequency compared to using a single therapy. For instance:Combining anti-VEGF agents with corticosteroids improved outcomes for patients with persistent or severe ME.Using laser therapy alongside medications enhanced recovery for certain types of macular edema.However, these approaches must be carefully monitored, as corticosteroids can cause side effects like increased eye pressure and cataract formation.What do these results mean?The findings suggest that combination therapies could be a more effective and efficient way to manage macular edema, especially for patients who do not respond well to single treatments. Further research, including long-term studies, is needed to optimize these treatment strategies and make them safer and more personalized. By combining treatments, we may reduce the burden on patients while improving their vision and quality of life.Keywords: combination therapy, macular edema, ozurdex, anti-vascular endothelial growth factor, cytokines