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Purpose: To investigate functional and anatomical results up to 12 months after Descemet’s membrane endothelial keratoplasty (DMEK) for Fuchs’ endothelial dystrophy (FED) versus bullous keratopathy (BK) in consideration of morphologic characteristics on host’s endothelium-Descemet’s membranes (EDM). Methods: In a prospective consecutive case series, 119 eyes underwent a primary DMEK for FED or BK. Intraoperatively obtained EDM were investigated immunohistologically. Clinical and morphological parameters were compared between FED and BK. Results: Overall, the 12-months best-corrected visual acuity (BCVA) was 0.14 logMAR, and 0.10 logMAR in eyes without vision-limiting comorbidities; thereby no differences were revealed between eyes with FED and BK up to 12 months postoperative (p = 0.186 and p = 0.095, respectively). Correspondingly, the mean central corneal thickness (CCT) measured 520 vs. 529 µm and the mean endothelial cell density (ECD) was 1743 vs. 1457 cells/mm2 for FED and BK, 12 months postoperative. Regarding CCT and ECD, no differences were observed between the groups (p = 0.181 and p = 0.112, respectively). The overall detachment rate was 40% (48/119). Comparing FED and BK the detachment rates did not differ, which were 41% vs. 39% and 43% vs. 35%, in pseudophakic eyes (p = 0.554 and p = 0.601, respectively). Yet, the distribution of recurring graft detachments differed between FED and BK; secondary re-detachments were more frequent in the FED group (7 cases). Regarding histologic investigations, a lower ECD was found in specimens with BK, no differences were revealed for EDM and anterior banded layer thicknesses. Immunohistologically, differences in the distribution of fibronectin and cytokeratin were observed. A rarification of matrix proteins was found in EDM complexes with FED. Conclusions: DMEK produces similar results for FED and BK. However, the postoperative course may differ with regard to the recurrence of secondary graft detachments that may be associated by histopathologic particularities. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of complement component C5a inhibition on laser-induced choroidal neovascularization (CNV) in mice using a C5a specific l-aptamer. Methods: In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor (NOX-D20) was intravitreally injected in three concentrations: 0.3, 3.0, and 30 mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 mg/ml; the vehicle (5 % glucose) was injected in controls. Vascular leakage was evaluated using fluorescence angiography, CNV area was examined immunohistochemically. Activated immune cells surrounding the CNV lesion and potential cytotoxicity were analyzed. Results: Compared to controls, CNV areas were significantly reduced after NOX-D20 injection at a concentration of 0.3 and 3.0 mg/ml ( p = 0.042; p = 0.016). NOX-D20001 significantly decreased CNV leakage but not the area ( p = 0.007; p = 0.276). At a concentration of 30 mg/ml, NOX-D20 did not reveal significant effects on vascular leakage or CNV area ( p = 0.624; p = 0.121). The amount of CD11b positive cells was significantly reduced after treatment with 0.3 and 3.0 mg/ml NOX-D20 ( p = 0.027; p = 0.002). No adverse glial cell proliferation or increased apoptosis were observed at effective dosages. Conclusions: Our findings demonstrate that the targeted inhibition of complement component C5a reduces vascular leakage and neovascular area in laser-induced CNV in mice. NOX-D20 was proven to be an effective and safe agent that might be considered as a therapeutic candidate for CNV treatment. The deficiency of activated immune cells highlights promising new aspects in the pathology of choroidal neovascularization, and warrants further investigations. [ABSTRACT FROM AUTHOR]

Purpose To investigate pathomechanisms involved in graft detachment after Descemet's membrane endothelial keratoplasty ( DMEK) and its clinical implications. Methods In a prospective case series, 30 eyes with Fuchs' endothelial dystrophy underwent DMEK. Intraoperatively obtained recipients' endothelium-Descemet's membranes ( EDMs) were investigated histologically and immunohistochemically. The postoperative donor graft status was categorized as attached or detached. Clinical and morphological parameters were analysed between the study groups. Results The detachment rate was 40% (12/30). There was no significant difference in postoperative visual acuity between the groups, but visual recovery was delayed in eyes with initially detached grafts. Gender, age, preoperative central corneal thickness or best corrected visual acuity did not influence the detachment rate. However, separation and disruption of the anterior banded layer ( ABL) were frequently observed in patients with graft detachment, and ABL thickness was identified as a significant predictor for graft detachment. The ABL thickness was 2.5 ± 0.9 μm and 3.5 ± 1.6 μm in patients with attached and detached grafts, respectively. Immunohistologically, a deficiency of fibronectin and cytokeratin was observed within the ABL of patients with detached grafts. In contrast, a complete removal of the EDM with residual stromal collagen fragments was observed in patients with adherent grafts. Conclusions Incomplete removal of the EDM, with residual ABL fragments on the recipients' corneal stroma, may be a risk factor for graft detachment after DMEK. The separation and disruption of the ABL might be promoted by a deficiency of matrix proteins, stronger biomechanical properties and a firm adherence to the posterior corneal stroma. [ABSTRACT FROM AUTHOR]

Aims: For the purpose of visual rehabilitation of subjects with photoreceptor degeneration, an implantable microelectronic device for epiretinal stimulation was developed. Our study aimed to show whether implantation and explantation could be conducted safely and to investigate tissue compatibility. Methods: The device was implanted in 5 Göttinger minipigs. Four weeks later, the implant was surgical- ly removed. Histopathological examination that followed aimed at detecting inflammatory or proliferative changes. Stains used were hematoxylin and eosin, leukocyte common antigen, CD68 and glial fibrillary acidic protein. A grinding technique was used to visualize the retinal tissue in conjunction with the retinal tacks. Results: The implantation of the devices was successful in all cases. The explantation was complicated by intraoperative hemorrhages. Complete explantation could only be achieved after modifying the implantation strategy. Histopathology revealed a mild degree of cystic disaggregation of the retina. Immunohistochemically, an increased glial fibrillary acidic protein expression of Müller cells was found, which shows a moderate glial cell activation. Inflammatory cells were absent. Using the grinding technique, tissue adjacent to the retinal tacks showed a mild gliosis. Discussion: The viability of implantation and explantation of the implant in minipigs has been shown. The absence of immunoreactive cells or a considerable glial reaction suggest that the device may be considered safe and suitable for further implantation in humans. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Anti-VEGF-directed therapies have been a milestone for treating retinal vascular diseases. Depletion of monocyte lineage cells suppresses pathological neovascularization in the oxygen-induced retinopathy mouse model. However, the question whether myeloid-derived VEGF-A expression is responsible for the pathogenesis in oxygen-induced retinopathy remained unknown. We analyzed LysMCre-driven myeloid cell-specific VEGF-A knockout mice as well as mice with complete depletion of circulating macrophages through clodronate-liposome treatment in the oxygen-induced retinopathy model by immunohistochemistry, qPCR, and flow cytometry. Furthermore, we analyzed VEGF-A mRNA expression in MIO-M1 cells alone and in co-culture with BV-2 cells in vitro . The myeloid cell-specific VEGF-A knockout did not change relative retinal VEGF-A mRNA levels, the relative avascular area or macrophage/granulocyte numbers in oxygen-induced retinopathy and under normoxic conditions. We observed an insignificantly attenuated pathology in systemically clodronate-liposome treated knockouts but evident VEGF-A expression in activated Müller cells on immunohistochemically stained sections. MIO-M1 cells had significantly higher expression levels of VEGF-A in co-culture with BV-2 cells compared to cultivating MIO-M1 cells alone. Our data show that myeloid-derived cells contribute to pathological neovascularization in oxygen-induced retinopathy through activation of VEGF-A expression in Müller cells. [ABSTRACT FROM AUTHOR]