Aqueous humor cytokine levels in patients with diabetic macular edema refractory to anti-VEGF treatment

Abstract

PurposeTo determine aqueous cytokines association with response to intravitreal bevacizumab (IVB) injection in diabetic macular edema (DME).MethodWe compared the concentrations of IL (interleukin)-1β, IL-2, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor of 64 naïve DME patients with those of 13 cataract patients. Factors associated with central subfield thickness (CST) in DME patients were identified. DME patients were then subgrouped in terms of responsiveness to three IVB injections; cytokine concentrations were compared, and factors associated with responsiveness were identified.ResultsLevels of IL-2, IL-8, PlGF, and VEGF were significantly elevated in DME patients (p = 0.007, p < 0.001, p < 0.001, and p = 0.004 respectively). Regression analysis showed that the preoperative CST was associated with the preoperative best-corrected visual acuity and the aqueous IL-10 level (p < 0.001, p = 0.006, respectively). Of the 64 DME patients, 28 (43.75%) exhibited either CST < 300 μm or reduction in CST ≥ 50 μm after three consecutive IVB injections. On sub-group analysis, the mean IL-8 concentration was higher in the refractory group than in the responsive group, and multivariate logistic regression analysis showed that the IL-8 was the only factor associated with responsiveness (OR = 0.95, p = 0.017).ConclusionsThe IL-8 concentration in the aqueous humor was associated with responsiveness to IVB in DME patients.

Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema

“…Previous studies show, that the concentrations of various cytokines were significantly different between healthy patients and patients with DME (Jonas et al. ; Kwon & Jee ). As we focused on the changes in cytokine levels during two different treatments regimens in DME, no control group was used.…”

“…). A recent study associated higher level of IL‐8 with therapy responsiveness, with higher levels of IL‐8 in the therapy refractory group under anti‐VEGF treatment (Kwon & Jee ). Furthermore, the CXC chemokine family is known for its role in angiogenesis (Romagnani et al.…”

Cytokines and Growth Factors as Predictors of Response to Medical Treatment in Diabetic Macular Edema

“…Another previous study reported that only ICAM-1 levels were associated with CMT JPET # 262956 (Jonas et al, 2012). Nevertheless, other study suggested that IL-10 also could be associated not only with CMT but also with BCVA (Kwon and Jee, 2018).…”

“…As previously mentioned, the efficacy of DME treatment may be related to aqueous humor concentration of some cytokines. Therefore, it is possible that the baseline levels of these molecules could be used to predict response to therapy (Shimura et al, 2017;Hillier et al, 2018;Kwon and Jee, 2018).…”

“…Although the great majority of patients improved DME after anti-VEGF treatment, some patients fail to respond to this therapy. In order to identify which patients will not respond to anti-VEGF injections and that will benefit of treatment with corticosteroids, recent studies start to evaluate the hypothesis of cytokine and growth factors as predictors of response to anti-VEGF or corticosteroids intravitreal injections (Shimura et al, 2017;Hillier et al, 2018;Kwon and Jee, 2018).…”