A. Rosentreter

Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy†

Coronin‐3 (coronin‐1C), a homotrimeric F‐actin binding protein, has been shown to be important for cell migration and brain morphogenesis. Here, we present for the first time a detailed analysis of the expression pattern of coronin‐3 in human brain tumours and demonstrate that coronin‐3 expression correlates with malignant phenotype in diffuse gliomas. In general, the expression of coronin‐3 varies in different brain tumour entities. However, in diffuse gliomas, the number of coronin‐3 expressing tumour cells correlates with the degree of malignancy. High‐grade gliomas, such as anaplastic astrocytomas, anaplastic oligodendrogliomas, anaplastic oligoastrocytomas and glioblastomas, show high numbers of tumour cells positive for coronin‐3, while diffuse low‐grade gliomas, such as diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas, exhibit low numbers of coronin‐3‐positive tumour cells. In order to explore and verify a contribution of coronin‐3 to the malignant phenotype of diffuse gliomas, we employed an efficient shRNA‐mediated coronin‐3 knockdown in U373 and A172 human glioblastoma cells. Coronin‐3 knockdown glioblastoma cells exhibited reduced levels of cell proliferation, cell motility and invasion into extracellular matrix compared to control cells. Together, our findings demonstrate evidence for a contribution of coronin‐3 expression in the malignant progression of diffuse gliomas. Copyright

Accelerated (18 mW/cm²) Corneal Collagen Cross-Linking for Progressive Keratoconus.

Purpose: The aim of this study was to determine the efficacy of accelerated riboflavin–ultraviolet A–induced corneal collagen cross-linking (CXL) (irradiance of 18 mW/cm2 for 5 minutes). Methods: In this study, we retrospectively reviewed the charts and anterior segment data of patients after accelerated CXL. Visual, topographic, pachymetry, and densitometry data were extracted and analyzed before surgery and at follow-up (minimum 12 months) after treatment. Results: A total of 28 eyes of 20 patients (mean age, 28.1 ± 8.1 years) were included in this study. The mean follow-up time was 21.7 ± 7.2 months (range, 12–34 months). No statistically significant changes were found in the mean corrected distance visual acuity, corneal astigmatism, Kmean, Kflat, Ksteep, corneal pachymetry (at the apex and at the thinnest point), and corneal densitometry at follow-up. A significant reduction of Kmax, index of surface variance, index of vertical asymmetry, and Km of the posterior corneal surface (KmB) was observed (Kmax: P = 0.018; index of surface variance: P = 0.016; index of vertical asymmetry: P = 0.038; KmB: P = 0.008). No complications were reported during the postoperative follow-up period in this study. Conclusions: Based on a mean follow-up time of 21.7 months, accelerated CXL (18 mW/cm; 5 minutes) is effective in stopping the progression of keratoconus without raising any safety concerns. Improvement in Kmax and stabilization of corrected distance visual acuity were noted after treatment. However, prospective studies with longer follow-up using different accelerated CXL settings are needed to validate these findings.

Clinical use of a new position-independent rebound tonometer.

Purpose:To compare intraocular pressure (IOP) measurements obtained by rebound tonometry (Icare PRO tonometer), applanation tonometry (Goldmann and Perkins tonometry), and dynamic contour tonometry in the upright and the supine positions, and to investigate the influence of axial length and central corneal thickness. Methods:Ninety-nine right eyes of 99 patients with glaucoma or suspect for glaucoma, admitted to our department between November 2010 and January 2011 to obtain an IOP profile including supine measurements, were included in our study. IOP measurements were obtained in an upright position using an Icare PRO rebound (RTPRO), a Goldmann applanation (GAT), and a Pascal dynamic contour tonometer (DCT). In the supine position, IOP measurements were taken using the RTPRO and a Perkins hand-held applanation tonometer (PAT). The means and SDs for all tonometers were compared. Agreement between the tonometers was calculated using the Bland-Altman method. Results:The mean IOPs obtained in the upright position were 17.7±8.0 mm Hg (RTPRO), 17.6±7.8 mm Hg (GAT), and 19.9±6.6 mm Hg (DCT). Correlation analysis of these data indicated a good correlation between IOP readings obtained using RTPRO and GAT (r=0.951; P<0.001), and RTPRO and DCT (r=0.897; P<0.001). Bland-Altman analysis revealed mean differences (bias) between RTPRO and GAT, and between RTPRO and DCT of 0.1 mm Hg and −1.8 mm Hg, with 95% limits of agreement of −3.6 to 3.8 mm Hg and −7.3 to 3.6 mm Hg, respectively. In the supine position, the mean IOPs were 19.2±6.4 mm Hg using the RTPRO and 19.6±6.2 mm Hg using the PAT. Conclusions:Measurements obtained with the RTPRO, either in the upright or in the supine position, show good correlation and agreement with those provided by applanation and dynamic contour tonometry. The study was registered with the DRKS (German Clinical Trials Register; http://www.germanctr.de; DRKS00000581).

Rebound, applanation, and dynamic contour tonometry in pathologic corneas.

Purpose: To compare the practicability of using an Icare rebound tonometer (RT) versus a Goldmann applanation tonometer (GAT) or a Pascal dynamic contour tonometer (DCT) for measuring intraocular pressure (IOP) in patients with corneal abnormalities and, furthermore, to study the influence of central corneal thickness, corneal diameter, corneal radius, and axial length. Methods: One hundred seventy-one pathologic eyes with corneal abnormalities and 26 nonpathologic control eyes of 99 patients were included. Pathologic corneas were divided into subgroups: previous keratoplasty, keratoconus, corneal scars, corneal dystrophies, and bullous keratopathy. Results: Although IOP was successfully measured using the RT in all pathologic eyes, successful measurement of IOP was only possible in 98.2% when using the GAT and in 73.1% with the DCT. Mean IOP for all enrolled eyes was 12.7 ± 4.1 mm Hg for RT, 15.5 ± 4.4 mm Hg for GAT, and 16.3 ± 4.1 mm Hg for DCT. The mean difference between RT and GAT was ⩽1 mm Hg (⩽2 mm Hg) [⩽3 mm Hg] in 23.4% (41.8%) [62.0%] of cases. Correlation analysis showed a moderate correlation between RT and GAT (r = 0.566; P < 0.001) and between RT and DCT (r = 0.364; P < 0.001). Bland–Altman analysis revealed a bias between RT and GAT and between RT and DCT of −2.8 and −3.8 mm Hg, with limits of agreement of −10.5 to 4.9 mm Hg and −12.2 to 4.6 mm Hg, respectively. Conclusion: In pathologic corneas, IOP was difficult to obtain with GAT and DCT, whereas RT was able to determine IOP in all pathologic corneas. RT significantly underestimated IOP in all groups in relation to GAT and DCT. The agreement between the methods was clinically acceptable in corneal dystrophy and keratoconus but poor in eyes after keratoplasty.

Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment.

Background Aqueous flare as determined by laser flare photometry in the anterior chamber is a strong preoperative predictor for proliferative vitreoretinopathy (PVR) in patients with primary retinal detachment (RD). We analysed various cytokines in aqueous humour samples in relation to aqueous flare and postoperative PVR incidence in patients with RD. Methods Preoperatively, the aqueous flare of patients with RD was measured quantitatively with a laser flare metre and aqueous humour samples were collected and analysed for interferon γ, tumour necrosis factor α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, platelet derived growth factor (PDGF)-aa, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, fibroblast growth factor (FGF)-aa and FGF-bb by multiplex fluorescent bead-based immunoassays. Three months after RD surgery patients were examined for PVR development. Results Of 67 consecutive patients, 10 developed at least PVR grade C. Patients with flare values >15 pc/ms (n=20) and the 10 patients with postoperative PVR all had significantly elevated levels of IL-6, IL-8, MCP-1 and TGF-β1 in aqueous humour (p≤0.05). Levels of VEGF-A, PDGF-aa and TGF-β2 were not significantly changed. Other cytokines were below the detection threshold. Eight of the 10 patients (80%) with PVR had elevated flare values of >15 pc/ms and 8 of the 20 patients (40%) with flare >15 pc/ms developed PVR. The OR for PVR with flare values >15 pc/ms was 30.7 (p=0.0001). Conclusions Laser flare photometry allows simple risk estimation for later PVR development. Elevated laser flare values correspond to an altered profibrotic intraocular cytokine milieu. These factors therefore constitute promising targets for a prophylactic intervention.

Coronin 3 and its role in murine brain morphogenesis

Coronins belong to the fundamental WD40‐repeat proteins. They are mainly found at the submembraneous area, they bind F‐actin in vitro, and most of the seven mammalian coronins have unclear roles. Coronin 3 is abundantly expressed in the adult CNS. All murine brain areas express coronin 3 during embryogenesis and the first postnatal stages. Expression in grey matter decreases postnatally, except for hippocampal pyramidal and dentate gyrus neurons, and cerebellar Purkinje cells, while levels in white matter increase in the course of myelination. Consistently, coronin 3 is abundant in differentiating neuro‐2a and PC‐12 cells and in primary oligodendrocytes. Treatment with PKC activator PMA reduced coronin 3 protein levels. To address its functions, neuro‐2a and PC‐12 cells were transfected with GFP‐tagged coronin 3 versions. Full‐length coronin 3 among other areas localized to outgrowing neurites, whereas truncated proteins efficiently suppressed neurite formation. Our results favour a role for coronin 3 in neuron morphogenesis and possibly migration.

Changes in Corneal Transparency After Cross-linking for Progressive Keratoconus: Long-term Follow-up.

PURPOSE To determine long-term changes in corneal transparency after riboflavin-ultraviolet A-induced corneal collagen cross-linking (CXL). METHODS Charts and anterior segment data of patients after CXL for progressive keratoconus were retrospectively reviewed. Patients were examined using the Scheimpflug-based Pentacam corneal densitometry module (Oculus Optikgeräte, Wetzlar, Germany) before CXL and at five postoperative follow-up visits: 1 to 3, 3 to 6, 6 to 12, 12 to 24, and 24 to 36 months. RESULTS Forty-two eyes of 28 patients (mean age: 27.9 ± 8.6 years) were included. Total corneal light backscatter was higher 1 to 3 months after CXL than before CXL (P < .001). There were significant differences, especially in the anterior (P < .001) and central (P < .001) layer at total diameter and posterior layer (P = .014) and the three central annuli at total corneal thickness (0 to 2 mm: P < .001; 2 to 6 mm: P < .001; 6 to 10 mm: P = .002). Total corneal light backscatter at total corneal thickness and total diameter faded over time following CXL. The backscatter was significantly lower 24 to 36 months after CXL than before CXL (P < .001). CONCLUSIONS Corneal densitometry peaks in the first months after CXL and returns to preoperative values approximately 1 year after CXL. Two years after CXL, corneal densitometry reaches values obtained for healthy, untreated corneas, thus achieving an improvement in corneal clarity over untreated keratoconic corneas.

Biodegradable implant for tissue repair after glaucoma drainage device surgery.

Aim/BackgroundTo report a novel technique using biodegradable material to cover exposed glaucoma tube shunts. MethodsA case report of a single patient who underwent drainage tube shunt surgery with the Baerveldt drainage device for intractable glaucoma. Four months post operation the tube became exposed through necrosis of the overlying scleral flap and conjunctiva. The defect was repaired by fixation of the tube to the sclera, with a slice of an ologen implant as a patch, covered by the adjacent conjunctiva. The patient was followed over a period of 1 year after the surgery. ResultsSuccessful, lasting closure of the conjunctival defect was achieved without any side effects or complications. ConclusionsErosion of the drainage tube after shunt surgery is a potentially serious problem. It can be successfully managed using a biodegradable implant as a patch before closing the conjunctiva.

Corneal Densitometry, Central Corneal Thickness, and Corneal Central-to-Peripheral Thickness Ratio in Patients With Fuchs Endothelial Dystrophy.

Purpose: The aim of the study was to quantify Scheimpflug corneal densitometry in patients with Fuchs endothelial dystrophy (FED). Methods: In this study, we retrospectively reviewed the charts and anterior segment data of 49 patients with FED before posterior lamellar keratoplasty and 51 healthy controls. The patients were examined using the Scheimpflug-based Oculus Pentacam. Central corneal thickness (CCT), ring-averaged (on a circle of 2, 2.4–10 mm diameter) noncentral corneal thickness, and densitometry data in different corneal layers and in different annuli were extracted and analyzed. Results: The total corneal light backscatter at total corneal thickness (CT) and at total diameter was significantly higher in the FED group when compared with the control group (FED group: 28.8 ± 6.7; control group: 24.3 ± 4.1; P < 0.001). When the corneal surface was divided into concentric annular zones at total CT, the differences were significant only in the 2 central annuli (P < 0.001). The total corneal light backscatter at total CT in the central 0–2 mm annulus correlated moderately with the central corneal thickness (Pearsons correlation = 0.55, P < 0.001). Conclusions: Corneal light backscatter in the central cornea was greater in patients with FED than in normal subjects. Corneal densitometry enables us to evaluate the optical quality of the cornea in different corneal layers and in different annuli. It is a useful, objective method that, in combination with central corneal thickness and corneal central-to-peripheral thickness ratio, can help to quantify FED severity.

Canthaxanthin retinopathy: long-term observations.

Purpose: To describe the long-term outcome of canthaxanthin retinopathy. Methods: We identified 13 patients with small golden particles near the macular region among a group of 35 patients with known consumption of canthaxanthin somewhen between 1983 and 1988. One long-term follow-up examination was possible in 5 of 13 cases after 16–24 years. The examinations included determination of visual acuity, the Amsler grid, slit lamp examination, perimetry, electro-oculography, electroretinography, optical coherence tomography and fluorescein angiography. Results: Complete disappearance of the golden particles took approximately 20 years. The patients in our study were asymptomatic and no functional defect related to canthaxanthin could be detected. Conclusions: Ingestion of canthaxanthin causes no long-term adverse effects.