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PURPOSE. To evaluate the association between iris damage and cytokine levels in the aqueous humor (AqH). METHODS.A total of 201 AqH samples from 201 consecutive patients (mean age 73.7 6 10.6) were collected at the beginning of corneal transplantation or cataract surgery. Iris damage of each case was assessed from preoperative slit-lamp findings based on its severity. The subjects were classified into three groups: eyes without iris damage (126 eyes), eyes with mild iris damage (51 eyes), and eyes with severe iris damage (24 eyes RESULTS. The levels of aqueous protein, IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-17A, MCP-1, TNF-a, E-selectin, P-selectin, and sICAM-1 in eyes with mild and severe iris damage were higher than in those without iris damage (P < 0.033). Multivariate analyses of clinical factors revealed that iris damage was associated with the history of complicated glaucoma, and the number of previous intraocular surgeries. The levels of AqH IL-6, IL-8, IL-13, MIP1a, TNF-a, and sICAM-1 were significantly elevated in eyes with mild and severe iris damage in phakic eyes, and the levels of AqH IL-8 and sICAM-1 were significantly elevated in eyes with severe iris damage in pseudophakic eyes, compared with the eyes without iris damage (P < 0.045). CONCLUSIONS.Iris damage was associated with the elevation in the levels of aqueous protein and cytokines.

Citation: Yazu H, Yamaguchi T, Aketa N, et al. Preoperative aqueous cytokine levels are associated with endothelial cell loss after Descemet's stripping automated endothelial keratoplasty. Invest Ophthalmol Vis Sci. 2018;59:612-620. https://doi.org/ 10.1167/iovs.17-23049 PURPOSE. To evaluate the association between endothelial cell density (ECD) after Descemet's stripping automated endothelial keratoplasty (DSAEK) and preoperative cytokine levels in the aqueous humor (AqH).METHODS. This prospective consecutive case series included 97 consecutive patients who underwent DSAEK (64 eyes) or cataract surgery (33 eyes). AqH samples were collected at the beginning of each surgery. The levels of cytokines (IL-1a, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-a, IFN-c, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured by multiplex beads immunoassay. The correlations between preoperative aqueous cytokine levels and the ECD at 12 months after DSAEK were analyzed.RESULTS. The ECD decreased from 2747 6 259 cells/mm 2 in the donor graft to 1235 6 607 cells/mm 2 at 12 months after DSAEK. In all subjects undergoing DSAEK, the postoperative ECD at 12 months was significantly correlated with the preoperative levels of MCP-1 (r ¼ À0.467, 95% confidence interval [CI]: À0.650 to À0.222, P ¼ 0.0003). In an analysis excluding Fuchs endothelial corneal dystrophy (11 eyes), the ECD at 12 months after DSAEK was significantly correlated with preoperative levels of IL-17A (r ¼ À0.635, 95% CI: À0.819 to À0.319, P ¼ 0.0004), MCP-1 (r ¼ À0.605, 95% CI: À0.779 to À0.345, P < 0.0001), IFN-c (r ¼ À0.633, 95% CI: À0.796 to À0.385, P < 0.0001), E-selectin (r ¼ À0.516, 95% CI: À0.756 to À0.276, P ¼ 0.0004), and sICAM-1 (r ¼ À0.537, 95% CI: À0.735 to À0.253, P ¼ 0.0005).CONCLUSIONS. Higher preoperative levels of IL-17A, MCP-1, IFN-c, E-selectin, and sICAM-1 in the AqH were associated with lower ECD after DSAEK for bullous keratopathy.

Annual reduction rate of corneal endothelial cell density (ECD) varies among etiologies, however, the cause of chronic endothelial cell loss is still unknown. We recently reported the elevation of inflammatory cytokines in the aqueous humor (AqH) in eyes with bullous keratopathy and low ECD. To evaluate the association between ECD and aqueous cytokine levels, we collected a total of 157 AqH samples prospectively. The AqH levels of cytokines were measured and multivariate analyses were conducted to find the correlation between ECD, aqueous cytokine levels and clinical factors, such as number of previous intraocular surgeries and protein concentration in AqH. As a result, ECD was negatively correlated with specific cytokine levels, including IL-1α, IL-4, IL-13, MIP-1β, TNF-α and E-selectin (all P < 0.05). The aqueous cytokine levels showed different correlations with these clinical factors; the number of previous intraocular surgeries was associated with all cytokines except MIP-1α. The AqH protein concentration and the status of intraocular lens showed similar patterns of elevation of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, MIP-1β, MCP-1, E-selectin, P-selectin and sICAM-1. In conclusion, elevation of AqH cytokine levels was associated with reduced ECDs. AqH cytokine levels showed significant correlations with clinical factors associated with low ECDs.

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