Intraocular cytokines in neovascular age-related macular degeneration non-responder to ranibizumab treatment

Abstract

Purpose : To evaluate cytokines level in aqueous humor of ranibizumab (RN) non-responders with neovascular AMD (nAMD) who were treated with either combination of ranibizumab (RN), and photodynamic therapy (PDT) or aflibercept (AF) and explore the prediction cytokines for RN non-responders

Methods : This prospective study collected aqueous specimen prospectively from RN non-responder receiving either AF or combination PDT (Study gr.) and RN responders patients (Control gr.) for cytokine analysis at baseline, month 1, 2 and 3 visit of treatment. Cytokines level and changes in 3 treatment groups were compared by using GLMM. Weighted propensity score was used to adjusted for covariate. VEGF, PDGF,PLGF and others angiogenesis/inflammatory cytokines were analyzed by Bio-Plex® Multiplex Immunoassays.

Results : Eleven, 8 and 13 eyes received AF treatment, combined PDT, and control respectively. Mean change of visual acuity from baseline is improved [WC1] in the control gr. (P<0.05) while study gr. didn’t show significant changes. In PDT group, 75% of patients showed stabilization or improvement in AMD clinical activity while PLGF, PDGF and leptin level are significant increase at first month: At 2 months visit, VEGF-A level is increase while Endoglin and HB-EGF decline when compare to baseline. At 3 months visit, VEGF-C and HGF concentration are higher in AF group than control group (p=0.02 and 0.02). There are no different in PLGF,PDGF,VEGF-A levels between each treatment group in all visit. PLGF level was higher in study gr. while IL-7 was lower in study gr. (P=0.02 and 0.04 respectively). The combination level of Angiopoetin 2, IL-6, ICAM, Follistatin and IL-3 can predict the response of RN treatment with 83% sensitivity and 72% specificity.

Conclusions : Switching to AF may not reduce major cytokines level but resulted in improvement of visual acuity. Combination of PDT and RN resulted increase angiogenesis cytokines. The lack of IL-7 was found in non-responder patient. Apart from cytokine levels, other factors such as cytokine receptors and immune system activity may play a role in non-response patient.