Anti-fumarase antibody as a predictor of functional efficacy of anti-VEGF therapy for diabetic macular edema

Abstract

PURPOSE. To evaluate whether baseline titers of anti-fumarase antibody are associated with visual prognosis after anti-VEGF treatment for diabetic macular edema (DME). METHODS. In this retrospective study, we investigated 52 eyes of 52 DME patients who received intravitreal injections of anti-VEGF drugs (ranibizumab or aflibercept) after blood sampling at baseline. Optical coherence tomography (OCT) images were obtained at every monthly visit. The serum titer of anti-fumarase antibody at baseline was measured using ELISA. We evaluated the relationship between the titer of anti-fumarase antibody at baseline and visual acuity (VA) improvement at 12 months. RESULTS. The serum titer of anti-fumarase IgG was related to the logMAR visual acuity (VA; R ¼ 0.329, P ¼ 0.017) and the disrupted ellipsoid zone (EZ; R ¼ 0.364, P ¼ 0.008) at baseline. The titer of this autoantibody was not associated with logMAR VA (R ¼ 0.007, P ¼ 0.980) but was associated with VA improvement (R ¼ 0.465, P < 0.001) at 12 months upon anti-VEGF treatment. The transverse length of the disrupted EZ line was shortened at 12 months (P < 0.001), and restoration of the EZ line was correlated to the autoantibody titer (R ¼ 0.396, P ¼ 0.004) compared with the decrease in central subfield (CSF) thickness. Multivariate analysis showed that pretreatment logMAR VA (b ¼ 0.296, P ¼ 0.045) and the autoantibody titer (b ¼ 0.328, P ¼ 0.017) were associated with VA improvement after anti-VEGF treatment. In contrast, the titer was not associated with logMAR VA at 12 months. CONCLUSIONS. Anti-fumarase antibody is a novel serum biomarker predicting better functional efficacy of anti-VEGF treatment for DME.