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Chirag J. Patel, K.V. Chalam, Sandeep Grover, Ravi Keshavamurthy, Joshua C. Priluck; Aqueous Interleukin-6 (IL-6) Levels Are Superior To Vascular Endothelial Growth Factor (VEGF) Levels In Predicting Therapeutic Response To Bevacizumab In Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2012;53(14):5175.
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To prospectively evaluate the effect of intravitreal Bevacizumab on aqueous levels of IL-6 and VEGF in Wet AMD and correlate clinical outcomes to aqueous cytokine levels before and after injection.
29 eyes from 29 patients with Exudative AMD, confirmed with fluorescein angiogram and Spectral-domain optical coherence tomography were included in the study. Control group included 30 eyes from 30 patients without concurrent eye disease undergoing cataract surgery. All study subjects underwent intravitreal injection of Bevacizumab three times at four week intervals. Aqueous samples from patients with Ex-AMD were collected prior to the 1st injection and 3rd injection. The aqueous samples from the control group were acquired prior to undergoing cataract surgery. The aqueous samples were then analyzed via a Multiplex bead analysis using the Luminex 100™ IS fluoroanalyzer. In order to correlate clinical outcomes and cytokine levels, study patients were subsequently sub-grouped based upon CSMT change. Group 1 included patients (n=14) that had a CSMT reduction greater than 10% or more than the baseline. Group 2 included patients (n=15) that had a CSMT change less than 9.99% and were considered treatment resistant.
Mean aqueous VEGF concentration in the controls was 3.69 + 1.26 pcg compared to 6.02 + 2.9 pcg in the study group (p=0.0002). The mean aqueous IL-6 concentration in controls was 5.09 + 2.22 pcg compared to 17.09 + 21.3 pcg in study group (p<0.0001). The differences (P= 0.38; P=0.32) between baseline and post injection levels of VEGF and IL-6, respectively, were not significant. On sub-group analysis, Group 1 and 2 baseline aqueous VEGF concentrations were 5.66 + 2.19 pcg and 6.36 + 3.56 pcg. Following treatment, mean VEGF levels were 4.52 + 5.76 pcg (p=0.5) and 4.12 + 5.54 pcg (p=0.5). The mean baseline aqueous IL-6 concentration in Groups 1 and 2 were 24.5 + 26.5 pcg and 10.18 + 12.4 pcg, respectively. Following treatment, mean IL-6 levels were 13.12 + 7.62 pcg (p=0.62) and 14.6 + 15.5 pcg (p=0.006). The mean IL-6 levels declined with a reduction in CSMT and rose with an increase in CSMT.
In the study, a consistent increase in aqueous IL-6 levels was observed in patients who showed treatment resistance with intravitreal Bevacizumab. We found that IL-6 levels and CSMT have a direct and correlative relationship. Furthermore, the data from our study suggests that aqueous IL-6 may be an important predictor of non-responsiveness to AMD. Future therapeutic strategies may include combination of anti-VEGF and anti-IL6 treatment in patients who do not respond to anti-VEGF treatment alone.
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