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Background <p>Anti-angiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) is currently the first-line treatment for macular edema (ME), but the specific metabolic changes in the aqueous humor (AH) after intravitreal anti-VEGF injections remain poorly understood.</p> Methods <p>A total of 120 AH samples from 60 ME patients before and after anti-VEGF treatment were collected from the ophthalmology clinic and ward of the Eye Hospital of Wenzhou Medical University. Non-targeted metabolomics analysis of the AH samples was performed using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify metabolite differences before and after anti-VEGF treatment in patients with different ME etiologies.</p> Results <p>Distinct metabolomic profiles were observed between pre- and post-treatment samples. A total of 145 significantly altered metabolites were identified after anti-VEGF treatment, with 84 upregulated metabolites related to carbohydrate and amino acid metabolism, and 61 downregulated metabolites involved in amino acid metabolism. Both common and etiology-specific metabolic alterations were observed. In age-related macular degeneration (AMD)-ME, treatment-induced metabolic changes mainly involved amino acid metabolism, whereas in branch retinal vein occlusion (BRVO)-ME, lipid metabolism was primarily affected. Diabetic macular edema (DME) patients showed more complex metabolic alterations, involving amino acid, lipid and carbohydrate metabolism.</p> Conclusions <p>Intravitreal anti-VEGF injections significantly alter AH metabolites in ME patients. These findings provide insight into underlying metabolic processes in ME pathogenesis and treatment efficacy.</p>

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Metabolomics analysis uncovers metabolic changes and remodeling of anti-VEGF therapy on macular edema

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月14日

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  • Congcong Yan,
  • Quanyong Yi,
  • Lina Ge,
  • Ying Huang,
  • Chun Yang,
  • Bing Lin,
  • Dan Jiang,
  • Meng Zhou

摘要

Background

Anti-angiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) is currently the first-line treatment for macular edema (ME), but the specific metabolic changes in the aqueous humor (AH) after intravitreal anti-VEGF injections remain poorly understood.

Methods

A total of 120 AH samples from 60 ME patients before and after anti-VEGF treatment were collected from the ophthalmology clinic and ward of the Eye Hospital of Wenzhou Medical University. Non-targeted metabolomics analysis of the AH samples was performed using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify metabolite differences before and after anti-VEGF treatment in patients with different ME etiologies.

Results

Distinct metabolomic profiles were observed between pre- and post-treatment samples. A total of 145 significantly altered metabolites were identified after anti-VEGF treatment, with 84 upregulated metabolites related to carbohydrate and amino acid metabolism, and 61 downregulated metabolites involved in amino acid metabolism. Both common and etiology-specific metabolic alterations were observed. In age-related macular degeneration (AMD)-ME, treatment-induced metabolic changes mainly involved amino acid metabolism, whereas in branch retinal vein occlusion (BRVO)-ME, lipid metabolism was primarily affected. Diabetic macular edema (DME) patients showed more complex metabolic alterations, involving amino acid, lipid and carbohydrate metabolism.

Conclusions

Intravitreal anti-VEGF injections significantly alter AH metabolites in ME patients. These findings provide insight into underlying metabolic processes in ME pathogenesis and treatment efficacy.