Abstract
Purpose :
To investigate changes of cytokine patters in the aqueous humor of neovascular age-related macular degeneration (nAMD) eyes before and after aflibercept treatment.
Methods :
Twenty-five eyes of 25 nAMD patients with no history of cataract surgery were enrolled (males / females; 19 / 6, average age ± SD; 67.9 ± 10.1 years old). The patients were given intravitreal injection of aflibercept (IVA) every 4 weeks for 2 months. Undiluted aqueous humor samples were collected before first and third IVA. The levels of IL-6, IL-7, IL-8, IL-9, IL-12, IL-13, Eotaxin, IP-10, MCP-1, MIP-1α, MIP-1β and VEGF in the samples were measured by a multiplex bead array. Visual acuity was converted to logMAR units. The retinal thicknesses of central 1 mm on the ETDRS grid were defined as central retinal thickness (CRT). Principal component analysis (PCA) and hierarchical cluster analysis were used to summarize various individual factors to simple groups with similar properties.
Results :
In PCA, first principal component (PC1) of nAMD eyes before first IVA accounted for 43.4% of all variability in the data. All inflammatory cytokines showed positive principal component loadings (PCL), and the cytokines with PCLs of 0.7 or above were IL-7, MIP-1β, VEGF, IL-8, MCP-1 and IL-6. In nAMD eyes before third IVA, PC1 accounted for 51.7% of all variability in the data. All inflammatory cytokines showed positive PCLs, and the cytokines with PCLs of 0.7 or above were IL-6, IL-7, IL-9, IL-8, MIP-1β, IL-13, MCP-1 and MIP-1α, but the PCL of VEGF was only 0.08. In hierarchical cluster analysis, the factors of nAMD eyes before first IVA were roughly classified into three principal groups as follows: 1) one high expression group consisting of CRT and IP-10, 2) the other high expression group consisting of MCP-1 and VEGF, and 3) a low cytokine expression group consisting of logMAR VA and the remaining cytokines. The factors of nAMD eyes before third IVA were roughly divided into two principal groups and one independent factor as follows: 1) a high expression group consisting of CRT and MCP-1, 2) a low cytokine expression group consisting of logMAR VA and the remaining cytokines, 3) IP-10.
Conclusions :
These findings suggest that inflammatory immune response is the principal etiologic factor of nAMD, and has influence continuingly after IVA.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.