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Serological inflammatory factors as biomarkers for anatomic response in diabetic macular edema treated with anti-VEGF
Pedro Brito1, Jorge Costa1, Nuno Gomes1
1Ophthalmology Department, Hospital de Braga, Braga, Portugal.
Purpose:
To study the relationship between systemic pro-inflammatory factors and macular structural response to intravitreal bevacizumab for diabetic macular edema (DME).
Methods:
Prospective study including 30 cases with DME, treated with bevacizumab and a minimum follow-up of 6 months. All cases underwent baseline laboratory testing for cardiovascular risk (high sensitivity C-reactive protein (hsCRP), homocystein), dyslipidemia, renal dysfunction and glucose control. Serum levels of VEGF, soluble ICAM-1, MCP-1 and TNF-α were assessed by enzyme-linked immunosorbent assay kits. Significant associations between systemic factors and quantitative and qualitative spectral-domain optical coherence macular features were analyzed.
Results:
A mean of 4.82 ± 0.56 intravitreal injections was performed, resulting in significant improvement of central foveal thickness (CFT) (p < 0.001). A significant association with third month CFT decrease <10% was found for hsCRP (3.33 ± 2.01 vs 1.39 ± 1.15 mg/l, p = 0.007) and ICAM1 (975.54 ± 265.49 vs 727.07 ± 336.09 pg/ml, p = 0.012). ROC curve analysis indicated hsCRP and ICAM1 as significant biomarkers for 3rd month reduced anatomic response (area under the curve (AUC) = 0.807, p = 0.009 for hsCRP; AUC = 0.788, p = 0.014 for ICAM1). ROC curve analysis revealed hsCRP as a significant biomarker for 6th month CFT decrease <10% (AUC = 0.903, p < 0.001, cutoff value = 1.81 mg/l). A significant association with 6th month CFT decrease ≥25% was found for serum MCP1 (244.69 ± 49.34 pg/ml vs 319.24 ± 94.88 pg/ml, p = 0.017) and serum VEGF (90.84 ± 37.33 vs 58.28 ± 25.19 pg/ml, p = 0.027). The combined model of serum VEGF and LDL-cholesterol was found to be predictive of 6th month hard exudate severity (p = 0.001, r2 = 0.463).
Conclusions:
Increased levels of hsCRP and ICAM1 were found to be significant biomarkers for early reduced anatomic response to anti-VEGF treatment. Cases with higher serum levels of such factors had increased CFT values, despite treatment, suggesting inner blood-retinal barrier breakdown that is not adequately responsive to anti-VEGF monotherapy.
Insights
Systemic inflammation markers, high-sensitivity C-reactive protein (hsCRP) and intercellular adhesion molecule 1 (ICAM1), predict poor response to anti-VEGF therapy in diabetic macular edema. Elevated levels indicate a breakdown of the blood-retinal barrier not fully addressed by this treatment alone.
Area of Science:
- Ophthalmology
- Retinal Diseases
- Diabetic Retinopathy
- Vascular Biology
Background:
- Diabetic macular edema (DME) is a leading cause of vision loss in diabetic patients.
- Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is a standard treatment for DME.
- The variability in treatment response suggests underlying biological factors influencing efficacy.
Purpose of the Study:
- To investigate the association between systemic pro-inflammatory factors and the structural response of the macula to intravitreal bevacizumab in patients with DME.
- To identify potential biomarkers predicting treatment outcomes in DME.
Main Methods:
- Prospective study of 30 DME patients treated with intravitreal bevacizumab, with a minimum 6-month follow-up.
- Baseline laboratory tests included markers for cardiovascular risk (hsCRP, homocysteine), dyslipidemia, renal function, and glucose control.
- Serum levels of VEGF, ICAM-1, MCP-1, and TNF-α were measured. Associations with macular structural changes (central foveal thickness) were analyzed using spectral-domain optical coherence tomography (SD-OCT) and ROC curve analysis.
Main Results:
- Intravitreal bevacizumab significantly improved central foveal thickness (CFT).
- Elevated baseline hsCRP and ICAM1 levels were significantly associated with a reduced anatomic response (CFT decrease <10%) at 3 months and were identified as biomarkers for this outcome.
- Higher MCP1 and VEGF levels were associated with a greater CFT decrease (≥25%) at 6 months. Serum VEGF and LDL-cholesterol predicted hard exudate severity at 6 months.
Conclusions:
- Increased systemic hsCRP and ICAM1 levels are significant biomarkers for an early, reduced anatomic response to anti-VEGF treatment in DME.
- These findings suggest that elevated pro-inflammatory markers may indicate an inner blood-retinal barrier breakdown that is not sufficiently responsive to anti-VEGF monotherapy.
- Further investigation into combination therapies may be warranted for patients with high systemic inflammatory markers.
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