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PurposeTo evaluate the corneal higher-order aberrations (HOAs) in granular, lattice and macular corneal dystrophies.MethodsThis retrospective study includes consecutive patients who were diagnosed as granular corneal dystrophy type2 (GCD2; 121 eyes), lattice corneal dystrophies type 1, type 3A (LCDI; 20 eyes, LCDIIIA; 32 eyes) and macular corneal dystrophies (MCD; 13 eyes), and 18 healthy control eyes. Corneal HOAs were calculated using anterior segment optical coherence tomography, and the correlations between HOAs and visual acuity were analyzed.ResultsHOAs of the total cornea within 4 mm diameter were significantly larger in GCD2 (0.17 ± 0.35 μm), in LCDI (0.33 ± 0.27), LCDIIIA (0.61 ± 1.56) and in MCD (0.23 ± 0.18), compared with healthy controls (0.09 ± 0.02μm, all P < 0.01). HOAs of the total cornea within 6 mm diameter were significantly larger in GCD2 (0.32 ± 0.48), in LCDI (0.60 ± 0.46), LCDIIIA (0.83 ± 2.29) and in MCD (0.44 ± 0.24), compared with healthy controls (0.19 ± 0.06, all P < 0.001). In GCD2, there was no significant correlation between logMAR and HOAs (r = 0.113, P = 0.227). In MCD, LCDI and LCDIIIA, logMAR was positively significantly correlated with HOAs (r = 0.620 and P = 0.028, r = 0.587 and P = 0.007, r = 0.614 and P < 0.001, respectively).ConclusionsIncreased HOAs occur in eyes with corneal dystrophies, especially in eye with LCD and MCD. Larger amount corneal HOAs are associated with poorer visual acuity in patients with LCD and MCD.

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.

Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated with CEnC loss. However, the full spectrum of driver proteins and molecular processes remains to be determined. Here, we defined the somatic microenvironmental landscape and cellular response across human aqueous humor in samples with poor corneal transplantation clinical outcomes using multiomics analyses and clarified specific driver alterations, including complement activation and disturbed energy homeostasis. These driver alterations were also confirmed in aqueous humor from a novel murine model that spontaneously develops iris atrophy, leading to CEnC loss. The application of the integrative multiomics performed in human samples to the novel murine model will help the development of therapeutic modalities for patients with CEnC loss after corneal transplantation.

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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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