伊野田 悟

PURPOSE: To investigate the association between aqueous humor (AH) suppressant eye drops and the concentration of aflibercept at 1 month after intravitreal injection. METHODS: This retrospective study included 17 eyes of 17 patients with neovascular age-related macular degeneration (nAMD) who used eye drops for their glaucoma and received their first intravitreal aflibercept (IVA) at two centers between July 2013 and November 2020. As controls, we enrolled 40 age-, sex-, and axial length-matched eyes of 40 patients with nAMD who were not using any medication that would affect AH circulation. AH was collected 1 month after the first IVA. Aflibercept levels were measured by enzyme-linked immunosorbent assay and were compared between controls and cases using the Kruskal-Wallis test and Dunn's test. The drugs were categorized into two groups based on their mechanism of action on the AH: outflow drugs (e.g., prostaglandin analog) and inflow drugs (e.g., carbonic anhydrase inhibitor, beta-blockers, and alpha-2 agonists). RESULTS: Mean (interquartile range) aflibercept levels in the AH in controls and in cases who used outflow and inflow drugs were 6.83 µg/mL (1.94-10.34), 9.93 µg/mL (2.58-17.44), and 15.95 µg/mL (7.20-22.57), respectively. A Kruskal-Wallis test showed a significant difference among the control, inflow, and outflow drugs (P = 0.0075). Dunn's test showed that aflibercept levels in the aqueous humor were significantly higher in cases using inflow drugs compared to both controls and cases using outflow drugs (P = 0.0085 and P = 0.044, respectively). CONCLUSIONS: Aflibercept levels in the AH 1 month after the first IVA were higher in cases using eye drops that reduce AH secretion than in controls. TRANSLATIONAL RELEVANCE: Our results, together with previous studies in animals, suggest that combined use of these eye drops might extend the half-life of intravitreally injected drugs.

PURPOSE: To investigate whether sub-Tenon injection of triamcinolone acetonide (STTA) combined with anti-vascular endothelial growth factor (VEGF) prolongs the recurrence intervals of macular edema (ME) for chronic retinal vein occlusion (RVO) and to investigate the differences in intraocular inflammatory cytokines between good responders (GRs) and non-responders (NRs). METHODS: This retrospective, observational study involved 42 eyes of 42 patients with ME due to chronic RVO who had received only anti-VEGF for ≥ 1 year and were transitioned to combination therapy. GRs were defined as patients whose recurrence intervals were prolonged by ≥ 2 weeks compared with patients receiving anti-VEGF alone. Moreover, immediately before starting the combined therapy, aqueous humor was collected and the following inflammatory cytokines were compared between GRs and NRs: CCL11, MCP-3, IP-10, CCL13, G-CSF, GM-CSF, IL-1α, IL-15, IL-4, M-CSF, MMP-9, TNF-α, MCP-1, CXCL-1, CXCL12, IL-8, galectin-1, IFN-γ, IL-12, IL-2, IL-6, MMP-1, PDGF-AA, and VEGF-A. These results were analyzed by nominal logistic regression after stepwise variable selection. RESULTS: There were 26 eyes (62%) in the GR group. Nominal logistic analyses showed that a higher concentration of IL-1α (P = 0.016) and lower concentrations of IL-5 (P = 0.015), IL-6 (P = 0.022), and galectin-1 (P = 0.015) were significantly associated with the extension of the time from injection to recurrence of ME. CONCLUSION: Combined anti-VEGF and STTA therapy for chronic RVO was effective in 62% of patients, suggesting the effectiveness of STTA. Higher IL-1α and lower IL-5, IL-6, and galectin-1 were the factors associated with combined treatment effectiveness.