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Classification of Diabetic Retinopathy Severity with Aqueous VEGF Levels: A Prospective, Observational Study
Megan S Steinkerchner1, Lok Hin Lee2, Abhiram R Manda2
1Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
Ophthalmology Science
|November 11, 2025
Summary
Vascular Endothelial Growth Factor-A (VEGF-A) in aqueous humor correlates with diabetic retinopathy (DR) severity. Elevated VEGF-A levels can help classify DR stages and guide early treatment to prevent vision loss.
Area of Science:
- Ophthalmology
- Endocrinology
- Biomarker Discovery
Background:
- Diabetic retinopathy (DR) classification and treatment guidance require improved biomarkers.
- Vascular Endothelial Growth Factor-A (VEGF-A) is implicated in DR pathogenesis.
Purpose of the Study:
- To investigate the relationship between aqueous VEGF-A levels and DR severity.
- To determine if VEGF-A can serve as a biomarker for DR classification and intervention.
Main Methods:
- Prospective, controlled trial involving 107 non-diabetic eyes and 164 type II diabetic patients.
- Aqueous humor sampling, ETDRS visual acuity, OCT, fundus photography, and HbA1c measurements were performed.
- Aqueous VEGF-A was quantified using a multiplex assay.
Main Results:
- Aqueous VEGF-A levels significantly increased with DR severity, from no DR to proliferative DR (P < 0.001).
- Elevated VEGF-A was strongly correlated with DR severity, even after controlling for confounders (P < 0.001).
- VEGF-A levels did not correlate with diabetic macular edema (DME) presence (P = 0.39).
Conclusions:
- Aqueous VEGF-A is a promising biomarker for classifying DR severity.
- VEGF-A measurement can guide early preventative treatment and resource allocation.
- This biomarker may help reduce DR progression and vision loss.

