Systemic and inflammatory biomarkers as prognostic factors for clinical response to bevacizumab in diabetic macular edema

Session Details

Session Title: Free Paper Session 7: Vascular Diseases & Diabetic Retinopathy II

Session Date/Time: Thursday 07/09/2017 | 14:30-16:00

Paper Time: 15:24

Venue: Room 117

First Author: : P.Brito PORTUGAL

Co Author(s): :    J. Costa   N. Gomes   S. Costa   J. Correia-Pinto   R. Silva                 

Abstract Details


Current treatment for diabetic macular edema (DME) relies on intravitreal injections of vascular endothelial growth factor neutralizing agents and/or corticosteroid formulations. Despite the improved outcomes, not all patients will respond to treatment and among those that do, there is a wide variability in the number of injections and in the disease free interval. Considering that DME is local manifestation of a systemic disease, it would be important to identify systemic factors capable of interfering with clinical response in a real-world treatment setting. Therefore we intend to evaluate the role of several systemic biomarkers as prognostic factors for DME treatment.


Ophthalmology Department, Hospital de Braga, Braga, Portugal


Cross-sectional study including 32 cases with type 2 diabetes mellitus (DM) and nonproliferative diabetic retinopathy with clinically significant macular edema (CSME) and a minimum follow-up of 6 months. Treatment consisted of intravitreal bevacizumab injections in a 3 monthly + pro re nata regimen. All cases underwent baseline laboratory testing for the following systemic markers: cardiovascular risk (high sensitivity C-reactive protein, serum homocysteine), renal dysfunction (blood urea nitrogen (BUN), serum creatinine), hypercholesterolemia (low-density lipoprotein, high-density lipopretin and total cholesterol) and diabetic profile (glycated haemoglobin, blood glucose level, duration of disease). Additionally, serum levels of VEGF, soluble ICAM-1, MCP-1 and TNF-α were assessed using enzyme-linked immunosorbent assay (ELISA) kits. Laboratory results were correlated with 6th month LogMAR visual acuity (VA) and spectral-domain optical coherence tomography macular outcomes.


During the considered follow-up period, a mean of 4.76±0.71 intravitreal injections were performed, resulting in significant improvements in central foveal thickness (427.30 to 316.14 µm, p=0.001), macular volume (10.89 to 10.11 mm3, p=0.002) and mean LogMAR visual acuity (0.54 to 0.39 logMAR, p<0.001). Significant correlations with 6th month CFT were found for hsPCR (p=0.001) and duration of DM (p=0.006), but hsPCR was the only variable that was predictive of 6th month CFT (p<0.001, R2 =0.336). Mean 6th month CFT change was -83.43±121.71 µm and both duration of DM and hsPCR value were found to be predictive of such value (combined model p< 0.001, R2 =0.426). Bivariate logistic regression showed that hsPCR value was predictive of obtaining at least a 20% reduction in CFT (R2 =0.313, p=0.03) as well as 6th month CFT < 330 µm (R2 = 0.360, p=0.017). Cases with higher levels of soluble ICAM-1 tended to have higher 6th month CFT values (p=0.048). Age and baseline logMAR VA were both predictive of 6th month LogMAR VA (combined model p=0.002, R2 =0.381).


The fact that hsPCR was an important predictor of 6th month foveal outcomes suggests that clinical response to treatment for DME may be influenced by the systemic pro-inflammatory status. This acute phase protein is released by the liver in response to inflammatory conditions associated with cellular apoptosis. It is known that leukostasis is a prominent feature in the pathogenesis of DR. Therefore, increased levels of hsPCR and soluble ICAM1 may indicate a propensity to advanced inflammatory activity on the inner blood-retina barrier, leading to less favorable outcomes. A prospective study of the role of pro-inflammatory biomarkers in DME will be fundamental to developing future treatment strategies.

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