Quarter-descemet membrane endothelial keratoplasty : one- to two-year clinical outcomes

Purpose:To report clinical outcomes of the first Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) case series performed for central Fuchs endothelial corneal dystrophy.Methods:This is a prospective, interventional case series analyzing the clinical outcomes of 19 eyes of 19 patients with central Fuchs endothelial corneal dystrophy, that is, with guttae predominantly in the 6- to 7-mm optical zone, who underwent unilateral Quarter-DMEK at a tertiary referral center. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative complications. Included eyes had up to 2 years of postoperative follow-up.Results:At 6 months postoperatively, all eyes reached a BCVA of >= 20/40 (>= 0.5): 18 of 19 eyes (95%) with >= 20/25 (>= 0.8) and 9 of 19 eyes (42%) with >= 20/20 (>= 1.0). Thereafter, BCVA remained stable up to 2 years postoperatively. The mean donor ECD decreased from 2842 139 cells/mm(2) (n = 19) before implantation to 913 +/- 434 cells/mm(2) (-68%) at 6 months (n = 19), 869 +/- 313 cells/mm(2) (-70%) at 12 months (n = 18), and 758 +/- 225 cells/mm(2) (-74%) at 24 months (n = 13) after Quarter-DMEK. Visually significant graft detachment requiring rebubbling occurred in 8 of 19 eyes (42%).Conclusions:Quarter-DMEK surgery yields visual outcomes similar to those of conventional DMEK and may potentially quadruple the availability of endothelial grafts. Further modifications of the graft preparation and the surgical technique may improve clinical outcomes in terms of lower ECD decrease and fewer graft detachments.Ophthalmic researc

Systemic and Renal Dynamics of Free Sulfhydryl Groups during Living Donor Kidney Transplantation

During ischemia-reperfusion injury (IRI), reactive oxygen species are produced that can be scavenged by free sulfhydryl groups (R-SH, free thiols). In this study, we hypothesized that R-SH levels decrease as a consequence of renal IRI and that R-SH levels reflect post-transplant graft function. Systemic venous, arterial, renal venous, and urinary samples were collected in donors and recipients before, during, and after transplantation. R-SH was measured colorimetrically. Systemic arterial R-SH levels in recipients increased significantly up to 30 sec after reperfusion (p < 0.001). In contrast, renal venous R-SH levels significantly decreased at 5 and 10 min compared to 30 sec after reperfusion (both p < 0.001). This resulted in a significant decrease in delta R-SH (defined as the difference between renal venous and systemic arterial R-SH levels) till 30 sec after reperfusion (p < 0.001), indicating a net decrease in R-SH levels across the transplanted kidney. Overall, these results suggest trans-renal oxidative stress as a consequence of IRI during kidney transplantation, reflected by systemic and renal changes in R-SH levels in transplant recipients

Calmodulin/CaMKII inhibition improves intercellular communication and impulse propagation in the heart and is antiarrhythmic under conditions when fibrosis is absent

Aim In healthy hearts, ventricular gap junctions are mainly composed by connexin43 (Cx43) and localize in the intercalated disc, enabling appropriate electrical coupling. In diseased hearts, Cx43 is heterogeneously down-regulated, whereas activity of calmodulin/calcium-calmodulin protein kinase II (CaM/CaMKII) signalling increases. It is unclear if CaM/CaMKII affects Cx43 expression/localization or impulse propagation. We analysed different models to assess this. Methods and results AC3-I mice with CaMKII genetically inhibited were subjected to pressure overload (16 weeks, TAC vs. sham). Optical and epicardial mapping was performed on Langendorff-perfused rabbit and AC3-I hearts, respectively. Cx43 subcellular distribution from rabbit/mouse ventricles was evaluated by immunoblot after Triton X-100-based fractionation. In mice with constitutively reduced CaMKII activity (AC3-I), conduction velocity (CV) was augmented (n = 11, P <0.01 vs. WT); in AC3-I, CV was preserved after TAC, in contrast to a reduction seen in TAC-WT mice (-20%). Cx43 expression was preserved after TAC in AC3-I mice, though arrhythmias and fibrosis were still present. In rabbits, W7 (CaM inhibitor, 10 μM) increased CV (6-13%, n= 6, P<0.05), while susceptibility to arrhythmias decreased. Immunoconfocal microscopy revealed enlarged Cx43 cluster sizes at intercalated discs of those hearts. Total Cx43 did not change by W7 (n= 4), whereas Triton X-100 insoluble Cx43 increased (+21%, n= 4, P<0.01). Similar findings were obtained in AC3-I mouse hearts when compared with control, and in cultured dog cardiomyocytes. Functional implication was shown through increased intercellular coupling in cultured neonatal rat cardiomyocytes. Conclusion Both acute and chronic CaM/CaMKII inhibition improves conduction characteristics and enhances localization of Cx43 in the intercalated disc. In the absence of fibrosis, this reduced the susceptibility for arrhythmias