1. Cytokines previously not found to be associated with proliferative diabetic retinopathy (GM-CSF, IL-12p40, sCD40L, MCP-3, and IFNa2) were discovered to be significantly elevated in the vitreous humor of these patients independent of VEGF (p<0.05).
2. Age, hypertension, and smoking history were correlated with proliferative diabetic retinopathy, but not with the specific elevation of the aforementioned cytokines.
Evidence Rating Level: 2 (Good)
Study Rundown: Many patients with proliferative diabetic retinopathy (PDR) are often treated with anti-VEGF therapy successfully, but subsequently recur within a few months. Other patients simply do not respond to anti-VEGF therapy. This study identifies multiple cytokines that may also be involved in PDR aside from VEGF, demonstrating that they are significantly elevated in PDR eyes independent of VEGF levels. These compounds may serve as future therapeutic targets. Strengths of this study include the fact that it involved quite a large sample of patients. Limitations include that indications for vitrectomy that could affect the proteomic analyses (e.g., retinal hemorrhage) were not accounted for. In addition, control samples included patients who were diabetic but did not have any PDR, which complicates the validity of these comparisons. Nonetheless, this is limited by the few indications for vitrectomy.
In-Depth [basic science study]: In this study, the vitreous humor of 72 patients undergoing vitrectomy was analyzed for 39 different cytokines; approximately half of these patients had proliferative diabetic retinopathy (PDR), while the other half served as controls. Additional demographic data (e.g., gender, age, smoking history, cancer) were obtained in order to identify any associations between certain cytokines and specific demographics. Vitrectomy samples were analyzed using magnetic microsphere immunoassays. Approximately 19 cytokines were found to be elevated in PDR vitreous samples compared to control samples. These include GM-CSF, IL-12p40, sCD40L, MCP-3, and IFNa2, which were not previously reported to be associated with PDR (p<0.05). Sixteen of these were found to still be significantly elevated in PDR patients even after accounting for elevated VEGF levels. While PDR was negatively correlated with age and positively correlated with hypertension and smoking history, none of these characteristics were associated with elevation of these cytokines.
By Swarup Swaminathan and Andrew Bishara
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