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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.
Objective:
A biomarker to classify diabetic retinopathy (DR) severity and guide preventative treatment is a major unmet need. We analyzed the relationship of aqueous VEGF-A with DR severity to determine if VEGF-A is a candidate biomarker.
Design:
A prospective, controlled trial at a tertiary academic medical center.
Subjects:
One hundred seven eyes of 107 patients without diabetes and 328 eyes of 164 adult type II diabetic patients with varying levels of DR.
Methods:
Aqueous was sampled in 107 consecutive eyes without diabetes undergoing elective vitrectomy surgery. All diabetic eyes had aqueous sampling of both eyes, ETDRS visual acuity, spectral-domain OCT, and color fundus photograph testing. Blood glucose and hemoglobin A1c (HbA1c) were measured. Aqueous VEGF-A was measured using a microparticle bead-based multiplex assay.
Main Outcome Measures:
Aqueous VEGF-A, DR severity, and diabetic macular edema (DME).
Results:
Median and interquartile range (IQR) aqueous VEGF-A levels for the 107 eyes without diabetes was 55.74 pg/ml (23.56-76.72). Median (IQR) VEGF-A levels increased with DR severity: 100.34 pg/ml (72.31-126.07) in the no DR group, 162.69 pg/ml (113.76-233.89) in the moderate nonproliferative DR (NPDR) group, and 295.48 pg/ml (193.80-409.99) in the proliferative DR (PDR) group (P < 0.001). The moderate NPDR group was further subdivided based on ETDRS severity into mild-moderate NPDR (N = 154 eyes) and moderate-severe NPDR (N = 82 eyes). Median (IQR) VEGF-A levels were 147.24 pg/ml (108.15-187.50) and 206.75 pg/ml (136.18-303.25) in the mild-moderate and moderate-severe NPDR groups, respectively. Using the no DR group as reference, odds ratios with 95% confidence intervals for VEGF-A were 2.72 (1.3-5.7) in the mild-moderate NPDR (P = 0.008), 6.79 (2.75-16.73) in the moderate-severe NPDR (P < 0.001), and 15.02 (4.86-46.44) in the PDR (P < 0.001) groups, respectively. After controlling for gender, age, and HbA1c, increasing VEGF-A was significantly correlated with increasing DR severity (P < 0.001), but not with the presence of DME (P = 0.39).
Conclusions:
Aqueous VEGF-A levels tightly correlate with DR severity and support VEGF-A as a novel biomarker to classify DR and guide early intervention. Use of VEGF-A levels may guide preventative treatment, reduce the risk of progression and vision loss, and allow optimal allocation of health care resources.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
