Domains of Physical Activity in Relation to Stiffness Index in the General Population.

Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex‐specific relations between domains of physical activity (PA; commuting, domestic, and leisure‐time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self‐reported PA was evaluated by the “Short Questionnaire to Assess Health‐Enhancing Physical Activity” and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrat…

A Randomized Trial of a Schlemm's Canal Microstent with Phacoemulsification for Reducing Intraocular Pressure in Open-Angle Glaucoma

Purpose To assess the safety and effectiveness of the Hydrus Microstent (Ivantis, Inc, Irvine, CA) with concurrent cataract surgery (CS) for reducing intraocular pressure (IOP) in open-angle glaucoma (OAG). Design Prospective, multicenter, randomized, single-masked, controlled clinical trial. Participants One hundred eyes from 100 patients 21 to 80 years of age with OAG and cataract with IOP of 24 mmHg or less with 4 or fewer hypotensive medications and a washed-out diurnal IOP (DIOP) of 21 to 36 mmHg. Methods On the day of surgery, patients were randomized 1:1 to undergo CS with the microstent or CS alone. Postoperative follow-up was at 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months. Wa…

Analysis of complex autoantibody repertoires by surface-enhanced laser desorption/ionization-time of flight mass spectrometry

Normal sera contain a large number of naturally occurring autoantibodies which can mask important disease-associated ones. Western blotting has evolved as the most important tool to demonstrate autoantibodies in autoimmune diseases, because of its ability to simultaneous screening for a wide spectrum of different antigens. In previous studies we have shown the diagnostic potential of the analysis of autoantibodies in autoimmune diseases by means of multivariate statistics and artificial neural networks. However, the Western blotting procedure remains very time-consuming and is also limited in sensitivity. Therefore, we used an on-chip approach for the analysis of autoantibodies. This Protei…

Suprachoroidal Bleeding After XEN Gel Implantation

Purpose To report for the first time a clinical case of suprachoroidal bleeding after XEN45 gel implantation. Observations A 84-year old female patient with pseudoexfoliation glaucoma with intraocular pressure (IOP) (20 mm Hg) above target despite maximal IOP-lowering therapy was scheduled for XEN45 gel implantation. The XEN45 gel implantation went without complications and was properly placed in the anterior chamber and beneath the conjunctiva. On the first postoperative day, the patient presented with an IOP of 4 mm Hg, a functioning bleb and a deep anterior chamber. On the second day she developed suprachoroidal bleeding. A wait and see strategy was followed and the patient monitored ste…

Reproducibility and Daytime-Dependent Changes of Corneal Epithelial Thickness and Whole Corneal Thickness Measured With Fourier Domain Optical Coherence Tomography.

To evaluate the reproducibility of Fourier domain anterior segment optical coherence tomography (RTVue) based on repeated measurements of corneal thickness (CT) and epithelial thickness (ET) and to test daytime-dependent changes of these parameters.Twenty-three eyes from 23 healthy volunteers were included in this prospective study. Three clinical observers performed 3 consecutive measurements each of CT and ET in 3 sessions using RTVue, resulting in 9 measurements per session. Session 1 was performed at 9 AM ± 1 hour, session 2 at 4 PM ± 1 hour on the same day, and session 3 at 9 AM ± 1 hour 2 days later. CT and ET were assessed in 9 areas: corneal vertex, 4 paracentral zones, and 4 periph…

Quality of Life in a German Graves Orbitopathy Population

To evaluate the validity and responsiveness of a German-language version of the disease-specific Graves orbitopathy quality-of-life questionnaire (GO-QOL).Prospective cross-sectional study.At a multidisciplinary university orbital center, 310 consecutive unselected Graves orbitopathy outpatients answered the GO-QOL before undergoing complete ophthalmic and endocrine assessment. The main outcome measures were the GO-QOL and its 2 subscales, Visual Functioning and Appearance.The QOL scores for the subscales Visual Functioning and Appearance were (mean ± SE) 72.5 ± 1.4 and 71.3 ± 1.5, respectively. Visual Functioning and Appearance were higher in mild (82.2 ± 2.2 and 86.0 ± 17.6) than in moder…

New insights into autoantibody profiles from immune privileged sites in the eye: a glaucoma study.

Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Autoantibody based immune processes are assumed to be involved in its pathogenesis. However, it is still unclear to what extent autoantibody patterns found in the eye (aqueous humor) are congruent to systemic autoantibodies (blood). Consistency would underline the specificity of known serum antibody markers for glaucoma. In this study we used antigen microarrays to analyze autoantibody reactivities in sera and corresponding aqueous humor samples of primary open-angle glaucoma patients (N=37) and non-glaucomatous controls (N=31). Compared to control subjects several divergent immunoreactivities were i…

Alterations in the tear proteome of dry eye patients--a matter of the clinical phenotype.

PURPOSE. Previous studies demonstrated alterations in the tear proteome of dry eye patients. The aim of the present study was to analyze tear protein patterns of dry eye patients considering different clinical phenotypes in order to examine their influence on tear film protein composition. METHODS. We applied a surface-enhanced laser desorption/ ionization-time-of-flight (SELDI-TOF)/matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF)/TOF mass spectrometry (MS)‐based strategy to detect/identify candidate biomarkers. Tear samples of 169 patients, enrolled in two independent studies, were analyzed. Patients were subdivided into healthy controls (CTRL: N ¼ 39), aqueous-defici…

Coagulation and inflammation in long‐term cancer survivors: results from the adult population

Essentials The increase of cancer survival remains curtailed by cardiovascular mortality. We studied a large range of inflammatory and coagulation biomarkers in long-term cancer survivors. Cancer history has an important impact on mortality independent of cardiovascular risk factors. Fibrinogen and von Willebrand factor are potential biomarkers in survivors of increased mortality. Summary Background The advances in cancer treatment and detection of early cancer have resulted in a steady increase in the number of of cancer survivors over the years. However, because of the long-term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular disease (CVD) is increasing in …

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

The author manuscript of this article is open access and is freely available online at PubMed Central

Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693…

Effect of head position on refraction in aphakic and phakic silicone-filled eyes.

BACKGROUND The refraction of the eye is altered significantly after the instillation of silicone oil into the vitreous cavity because of the silicone oil's high refractive index. The degree of the refractive change shows diurnal variation and depends on the patient's head position. PATIENTS AND METHODS To analyze the degree and time course of refractive changes with respect to head position, the authors performed objective refraction in five aphakic and five phakic silicone oil-instilled eyes with attached maculae using an automatic hand-held refractometer. In each patient, 25 measurements were taken at short intervals using a hand-held autorefractometer with the patient in different positi…

Keratopathie als Zeichen einer multifokalen kongenitalen sensiblen Polyneuropathie

Patient. Bei einer 63-jahrigen Patientin bestanden seit 10 Jahren beidseits rezidivierende korneale Ulzera mit Trubungen, Vaskularisation und aufgehobener Sensibilitat. Daneben fanden sich asymmetrisch angeordnete hypasthetische Areale. Sensible Nervenaktionspotenziale der betroffenen Regionen waren nicht ableitbar, sensorisch evozierte Potenziale fielen pathologisch aus, Muskeleigenreflexe waren ausgefallen. In der Suralisbiopsie zeigte sich ein hochgradiger Mangel an markhaltigen Axonen. Erworbene Polyneuropathieformen konnten ausgeschlossen werden. Therapie. Nach konservativen Therapieversuchen erfolgte wegen der vaskularisierten Hornhautnarbe eine perforierende Keratoplastik am linken A…

Polyphosphate, the physiological metabolic fuel for corneal cells: a potential biomaterial for ocular surface repair

The regeneration of the epithelium, covering the avascular cornea, involves the processes of differentiation, proliferation and migration of cells originating from the corneal epithelial stem cells. We ask the question if these energy-consuming processes can be fueled by the physiological, inorganic polyphosphate (polyP), the main energy storage/donor molecule in the extracellular space. The ex vivo results reveal that addition of polyP, in the form of soluble Na-polyP, to the culture medium elicits a strong stimulatory effect on cell viability/growth and migration of corneal epithelial cells. Microscopic analyses of partially denuded cornea specimens show that in the presence of polyP, but…

Changes in quality of life in visually impaired patients after low-vision rehabilitation.

The objective of the study was to assess the impact of low-vision aids on quality of life. Interviews included a modified version of the National Eye Institute Visual Functioning Questionnaire (Modified German NEI VFQ-25), the Hospital Anxiety and Depression Scale, the Mini-Mental State Examination Blind, and Indicators of the Rehabilitation Status. These were conducted before and 5 months after low-vision rehabilitation that involved recommendation of devices and instructing patients on how to use them. Of a total of 88 patients interviewed before low-vision rehabilitation, 50 patients could be reached for the follow-up interview. A huge proportion of the sample reported clinically signifi…

Analysis of Autoantibodies Against Human Retinal Antigens in Sera of Patients with Glaucoma and Ocular Hypertension

The aim of this study was to show that complex antibody patterns against retinal antigens in sera of patients with glaucoma, found in previous studies, are autoantibodies against human antigens.Sera of 179 patients were collected at the Department of Ophthalmology (University of Mainz, Germany): non-glaucomatous control patients (n=45), primary open-angle glaucoma (n=45), ocular hypertension (n=44), and normal tension glaucoma patients (n=45). The sera were tested against Western blots of human retinal antigens. IgG antibody patterns were analyzed by multivariate statistical techniques, and some significant antigens were identified by mass spectrometry.All subjects, even healthy ones, showe…

Prevalence of Strabismus and Its Impact on Vision-Related Quality of Life

Purpose This study investigates the prevalence of manifest strabismus and its subtypes in adulthood and analyzes the risk factors and its impact on vision-related quality of life (VRQoL). Design The Gutenberg Health Study (GHS) is a population-based, observational cohort study. A cross-sectional analysis of the baseline examination was conducted. Participants Participants aged 35 to 74 years were included (n = 15  010). Methods All participants were examined with a comprehensive ophthalmologic and general examination including the Hirschberg corneal reflex test to detect manifest strabismus. The following risk factors were analyzed: age, sex, socioeconomic status, birth weight, maternal age…

Correlation of Crystallin Expression and RGC Susceptibility in Experimental Glaucoma Rats of Different Ages.

Glaucoma is one of the leading causes of blindness worldwide with age being an important risk factor. However, the pathogenesis remains poorly understood. Aim of this study was to focus on age-dependent molecular changes in an experimental animal model of glaucoma.Intraocular pressure was elevated in Sprague-Dawley rats aged 3, 14, and 47 weeks for a period of 7 weeks by episcleral vein cauterization. Ganglion cell loss was monitored by an immunohistochemical staining of the Brain-specific homeobox/POU (Pit-1, Oct-2, Unc-86) domain protein 3A positive cells in retinal flat-mounts and spectral-domain optical coherence tomography measuring the retinal nerve fiber layer thickness. Molecular pr…

Autoimmune biomarkers in glaucoma patients.

There is growing evidence showing an autoimmune involvement in the pathogenesis of glaucoma, and that alterations in natural occurring autoantibody levels play a key role. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also protective characteristics and influence the protein expression of neuroretinal cells. A disbalance of natural occurring autoantibodies may shift the physiological equilibrium of protective immunity leading to a predisposition for developing glaucoma. This article highlights recent advances in understanding of autoimmune mechanisms in the pathogenesis of glaucoma.

Topical Voriconazole as Supplemental Treatment for Acanthamoeba Keratitis

Purpose Voriconazole was shown to inhibit ergosterol synthesis in various acanthamoeba species. The purpose of this study was to evaluate the clinical outcome of treatment with supplemental topical voriconazole in patients with acanthamoeba keratitis (AK). Methods All patients who had been treated for AK with voriconazole 1% drops in conjunction with topical first-line antiacanthamoeba therapy composed of polyhexamethylene biguanide (PHMB) 0.02% and propamidine isethionate 0.1% (Brolene) between November 2014 and August 2017 at the Department of Ophthalmology, University Medical Center Mainz, were included. The main outcomes were treatment failure and recurrence rate. Secondary outcomes wer…

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Item does not contain fulltext Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic ne…

Real-time control for transscleral cyclophotocoagulation.

• Background: In transscleral cyclophotocoagulation, the surgeon cannot directly observe the applied laser effects. Overdosage, possibly resulting in unwanted pop effects, or underdosage with no therapeutic effect therefore often occur. • Method and materials: Laser radiation passing through the sclera and ciliary body is partly reflected from the fundus and can be monitored from outside the eye by a detector system. Since all other parameters influencing the intensity of the recorded radiation are constant in time during one laser exposure, the time dependence of this radiation directly reflects the change of transmission of the treated tissue. The laser exposure therefore can be stopped b…

Public Health Relevance of Graves' Orbitopathy

Disfiguring proptosis and functional impairment in patients with Graves' orbitopathy (GO) may lead to impaired earning capacity and to considerable indirect/direct costs.The aim of the study was to investigate the public health relevance of GO.This cross-sectional study was performed between 2005 and 2009 at a multidisciplinary university orbital center.A total of 310 unselected patients with GO of various degrees of severity and activity participated in the study.We conducted an observational study.We measured work disability and sick leave as well as the resulting indirect/direct costs of GO-specific therapies.Of 215 employed patients, 47 (21.9%) were temporarily work disabled, and 12 (5.…

Birthweight and its association with retinal vessel equivalents – Results from the population‐based German Gutenberg Health Study

Refined atrial fibrillation screening and cost-effectiveness in the German population

ObjectiveLittle is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.MethodsWe performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables.ResultsOf 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of indivi…

Reaktion der Endothelzellen auf kurzzeitig physiologisch erhöhte hydrostatische Drücke und oxidativen Stress in vitro

Zusammenfassung Hintergrund Im Rahmen der Pathogenese des Glaukoms wird die endotheliale Dysfunktion zunehmend diskutiert. Peripapilläre Blutungen sind diagnostisch wegweisend. Die Korrelation von Glaukomerkrankungen mit vaskulärem Dysregulationssyndrom ist eindeutig. Ziel dieser Studie ist es, die genaue Reaktion der Endothelzellen auf erhöhten hydrostatischen und oxidativen Stress zu untersuchen. Material und Methoden In vitro wurden primär dissoziierte BMECs (brain microvascular endothelial cells) für 3 Tage normalem und leicht erhöhtem hydrostatischem Druck von 60 und 120 mmHg in einer Druckkammer ausgesetzt. Zusätzlich wurden sowohl druckbelastete als auch nicht druckbelastete Zellen o…

KCND3 is a novel susceptibility locus for early repolarization

AbstractThe presence of an early repolarization pattern (ERP) on the surface electrocardiogram (ECG) is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait but molecular genetic determinants are unknown. We assessed the ERP in 12-lead ECGs of 39,456 individuals and conducted a two-stage meta-analysis of genome-wide association studies (GWAS). In the discovery phase, we included 2,181 cases and 23,641 controls from eight European ancestry studies and identified 19 genome-wide significant (p<5E-8) variants in the KCND3 (potassium voltage gated channel subfamily D member 3) gene with a p-value of 4.6E-10. …

Meta-Analysis of Articles Evaluating Routine Intraocular Pressure Control in Monotherapy in the United States and Germany

Pur P ose . To evaluate routine intraocular pressure (IOP) control in monotherapy patients in the United States and Germany. Methods . Meta-analysis of published articles. We included articles that were prospective studies of ocular hypotensive therapies that measured an unaltered (visit 1) IOP on monotherapy before enrolling into a clinical trial. results . This meta-analysis included 5 studies with 7913 patients, of whom 3245 were from the United States (n=1) and 4668 were from Germany (n=4). In the United States, 2939 patients (91%), and in Germany, 4059 patients (87%), had glaucoma (p<0.0001). Of these, all the US patients (100%) and 2694 (58%) of those from Germany were treated with mo…

Algorithms for the Automated Analysis of Age-Related Macular Degeneration Biomarkers on Optical Coherence Tomography: A Systematic Review

PURPOSE To assess the quality of optical coherence tomography (OCT) grading algorithms for retinal biomarkers of age-related macular degeneration (AMD). METHODS Following a systematic review of the literature data on detection and quantification of AMD retinal biomarkers by available algorithms were extracted and descriptively synthesized. Algorithm quality was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies 2 checklist with a focus on accuracy against established reference standards and risk of bias. RESULTS Thirty five studies reporting computer-aided diagnosis (CAD) tools for qualitative analysis or algorithms for quantitative analysis were iden…

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

International audience; Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year fol…

The Prevalence of Amblyopia in Germany

Amblyopia is a condition in which reduced visual acuity is not directly caused by an organic defect (1). Amblyopia can develop when an infant or small child suffers from strabismus. Although both eyes are healthy, different images are formed on each fovea centralis (where vision is sharpest) and on other corresponding locations on the retina; this is in contrast to individuals without strabismus. To prevent double vision the child’s brain suppresses the image produced by one eye. Complete visual ability cannot develop in this eye during the sensitive phase of visual development (2). Approximately half of amblyopia cases (3) are caused by uncorrected higher refractive errors, which are frequ…

Elevated Regulatory T Cell Levels in Glaucoma Patients in Comparison to Healthy Controls.

Many studies analyzing neurodegenerative diseases demonstrate altered frequencies of regulatory T cells (Tregs). Till date, there is hardly any information concerning Tregs in glaucoma. To gather first results concerning Treg levels in glaucoma patients, we aimed to investigate whether the number of CD4(+)CD25(+)T cells vary in the patients suffering from primary open-angle glaucoma (POAG) and healthy controls.Heparinized blood samples were collected from 16 healthy individuals and 16 POAG patients. The groups were age and gender matched. A density gradient centrifugation over Ficoll-Paque was performed to isolate the peripheral blood mononuclear cells. The resulting cells were stained with…

Allopurinol has Immunomodulating Activity following Topical and Systemic Application in Experimental Autoimmune Uveitis

PurposeAllopurinol has beneficial effects in the systemic treatment of lens-induced uveitis and experimental autoimmune uveitis (EAU). This is believed to be due to a reduction of oxidative tissue damage through its dose-dependent free radical scavenging ability, and to an immunomodulating effect. The purpose of this study was to demonstrate the immunological effects on the IgG-antibody repertoire in EAU after topical and systemic allopurinol and steroids.MethodsWe assigned 43 male Lewis rats to 6 different groups: healthy rats (BASE, n=3), EAU without therapy (CTRL, n=9); systemic treatment with allopurinol (ALSYS, n=9, 50 mg/kg body wt.i.v., given every three days for two weeks), topical …

Prevalence of refractive errors in the European adult population: the Gutenberg Health Study (GHS).

Objective To study the distribution of refractive errors among adults of European descent. Design Population-based eye study in Germany with15 010 participants aged 35–74 years. Methods The study participants underwent a detailed ophthalmic examination according to a standardised protocol. Refractive error was determined by an automatic refraction device (Humphrey HARK 599) without cycloplegia. Definitions for the analysis were myopia +0.5 D, astigmatism >0.5 cylinder D and anisometropia >1.0 D difference in the spherical equivalent between the eyes. Exclusion criterion was previous cataract or refractive surgery. Results 13 959 subjects were eligible. Refractive errors ranged from −21.5 to…

Proteomics Differentiate Between Thyroid-Associated Orbitopathy and Dry Eye Syndrome.

PURPOSE: In patients with thyroid-associated orbitopathy (TAO), the dry eye syndrome occurs frequently, and symptoms and signs of both disorders overlap making early and accurate differential diagnosis difficult. A differentiation via specific markers is warranted. METHODS: Tear fluid samples of 120 subjects with TAO, TAO + dry eye, dry eye, and controls were collected. The samples were measured using matrix-assisted laser desorption ionization mass spectrometry. The identified proteins were tested with antibody microarrays. RESULTS: Proteomics identified deregulated proteins in TAO and dry eye. Compared with dry eye, proline-rich protein 1 (PROL1, P = 0.002); uridine diphosphate (UDP)-gluc…

Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach

Noninvasive biomarkers are urgently needed for early detection of breast cancer since the risk of recurrence, morbidity and mortality are closely related to disease stage at the time of primary surgery. In the past decade, many proteomics-based approaches were developed that utilize the protein profiling of human body fluids or identification of putative biomarkers to obtain more knowledge on the effects of cancer emergence and progression. Herein, we report on an analysis of proteins in the tear fluid from breast carcinoma patients and healthy women using a de novo proteomic approach and 25 mixed samples from each group. This study included 25 patients with primary invasive breast carcinom…

Comparison of Dynamic Contour Tonometry and Goldmann Applanation Tonometry in Glaucoma Patients and Healthy Subjects

To investigate the agreement in the measurement of intraocular pressure (IOP) obtained by dynamic contour tonometry PASCAL (DCT-PASCAL) and Goldmann applanation tonometry (GAT) in glaucoma eyes and healthy eyes with different central corneal thickness (CCT).Prospective cross-sectional study.In a randomized order, three consecutive IOP measurements were performed on 197 eyes of 107 subjects by one examiner using both DCT-PASCAL and GAT on all eyes. Furthermore, ultrasonic pachymetry was performed. The Spearman correlation coefficient (r) was determined to compare IOP readings between DCT-PASCAL and GAT. Regression-based Bland and Altman analysis was used to evaluate agreement between the ins…

Einsatz von Mitomycin C bei Trabekulektomien mit reduzierter Prognose

Der Antimetabolit Mitomycin C wird bei Trabekulektomien mit erhohtem Vernarbungsrisiko intraoperativ appliziert. Als Risikofaktoren fur eine Sickerkissenvernarbung durfen ein Patientenalter unter 40 Jahren, vorangegangene Entzundungen, eine durch Voroperationen oder durch langjahrige antiglaukomatose Therapie beeintrachtigte Bindehaut und eine starke Pigmentierung angesehen werden.

Long-term Results After Transconjunctival Resuturing of the Scleral Flap in Hypotony Following Trabeculectomy

Purpose To present the 4-year follow-up results in the surgical treatment of hypotony following trabeculectomy with mitomycin C in glaucoma patients with additional flap sutures. Design Retrospective interventional case series. Methods Since 2006, 53 patients with hypotony maculopathy attributable to overfiltration following glaucoma surgery (trabeculectomy with mitomycin C) were included in this institutional study. We were able to follow up intraocular pressure (IOP) and distance-corrected visual acuity in 33 (62%) over 4 years, whereas all were followed over 2 years. To elevate IOP, we placed tangential transconjunctival sutures through the scleral flap and connected them to the adjacent…

Endophthalmitis in cataract surgery

Abstract Objective To document perioperative prophylactic treatment and to evaluate the risk factors for endophthalmitis after cataract surgery. Design Cross-sectional study via anonymous survey. Participants Four hundred sixty-nine centers in Germany were queried. Results A total of 311 (67%) questionnaires were received, with each center reporting an average of 900 cataract surgeries per year (total, 340,633 surgeries in 1996). Respondents reported a total of 267 cases of endophthalmitis, which resulted in a mean responder-specific endophthalmitis rate of 0.148% versus a median rate of 0%. Statistical analysis via Poisson regression suggested that sclerocorneal incisions were associated w…

Association of Low Birth Weight With Altered Corneal Geometry and Axial Length in Adulthood in the German Gutenberg Health Study

IMPORTANCE: Low birth weight is associated with altered ocular organ development in childhood, including the morphology of the eye. However, no population-based data exist about this association in adulthood. OBJECTIVE: To evaluate whether low birth weight has a long-term association with anterior segment anatomy and axial length in adulthood. DESIGN, SETTING, AND PARTICIPANTS: The Gutenberg Health Study is a population-based, observational cohort study in Germany. All participants underwent ocular biometry. Among the participants with follow-up and self-reported birth weight available, associations were assessed between low birth weight and anterior segment anatomy and axial length using m…

Efficacy and safety of tafluprost 0.0015% and timolol maleate 0.5% fixed combination in patients with ocular hypertension or open-angle glaucoma.

Lowering intraocular pressure (IOP) is at present the only therapeutic approach to the treatment of glaucoma proven to be successful. The choice of therapy must take into account efficacy, tolerability, safety, quality of life, adherence and cost. Monotherapy fails to achieve a satisfactory IOP reduction in 40 - 75% of glaucoma patients after2 years of therapy. So far, three prostaglandin/timolol maleate 0.5% fixed combinations (FCs) are available.This review provides a background on the tafluprost-timolol FC (TTFC, Santen Oy) and its individual compounds. It summarizes the data on efficacy and safety, including comparative data with prostaglandin/timolol FCs already available.Tafluprost is…

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Author version made available in accordance with the publisher's policy.

Association of commonly used systemic medications with glaucoma prevalence and intraocular pressure across Europe: the E3 Consortium

Purpose : To investigate the association of common systemic medication use with intraocular pressure and glaucoma prevalence in the European population.Methods : We examined associations of systemic medication use with intraocular pressure and glaucoma prevalence in a meta-analysis of multiple cohort studies of the European Eye Epidemiology (E3) consortium. IOP measurement method and glaucoma ascertainment were according to individual study protocols. Multivariable regression (linear for IOP and logistic for glaucoma prevalence) was carried out in each study and results pooled using random effects meta-analysis. Age, sex, body-mass index and diabetes were included as co-variables. Associati…

Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty.

PURPOSE Posterior lamellar keratoplasty is increasingly applied in patients with endothelial decompensation after penetrating keratoplasty (PK). The aim of this study was to compare the results of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) after PK. METHODS In this retrospective study, clinical data of 30 patients who received DMEK (n = 19) or DSAEK (n = 11) for endothelial decompensation after PK were evaluated. All lamellar keratoplasties were performed at the Department of Ophthalmology at University Hospital Mainz, Germany. Primary end point included best-corrected visual acuity, and secondary end points included e…

Association of ocular, cardiovascular, morphometric and lifestyle parameters with retinal nerve fibre layer thickness.

BACKGROUND Glaucoma is a neurodegenerative disease, leading to thinning of the retinal nerve fibre layer (RNFL). The exact influence of ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFL thickness (RNFLT) is unknown and was analysed in a subgroup of the Gutenberg Health Study (GHS). METHODS Global peripapillary RNFLT was measured in 3224 eyes of 1973 subjects (49% female) using spectral-domain optical coherence tomography (SD-OCT). The association of age, sex, ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFLT was analysed using Pearson correlation coefficient and fitting a linear mixed model. RESULTS In the univariable analysis highest…

Patient and ophthalmologist attitudes concerning compliance and dosing in glaucoma treatment.

The aim of this study was to identify research avenues that might improve patient compliance with glaucoma therapy.500 patients and physicians were interviewed by telephone in 5 European countries, and the results were compiled and evaluated by 2 independent physicians.Most physicians believed that pressure reduction is useful (UK (96%), France (94%), Spain (80%), Italy (72%), and Germany (70%), p0.0001). The majority of physicians believed that noncompliance exists in 0%-25% of patients, whereas 34% of patients admitted to noncompliance. Physicians believed patients would prefer once-daily dosing (92%) and that it would help compliance, whereas 60% of patients preferred once-daily dosing, …

Assessing Planning Ability Across the Adult Life Span in a Large Population-Representative Sample: Reliability Estimates and Normative Data for the Tower of London (TOL-F) Task

AbstractObjectives:The Tower of London (TOL) test has probably become the most often used task to assess planning ability in clinical and experimental settings. Since its implementation, efforts were made to provide a task version with adequate psychometric properties, but extensive normative data are not publicly available until now. The computerized TOL-Freiburg Version (TOL-F) was developed based on theory-grounded task analyses, and its psychometric adequacy has been repeatedly demonstrated in several studies but often with small and selective samples.Method:In the present study, we now report reliability estimates and normative data for the TOL-F stratified for age, sex, and education …

Preparation Steps for Measurement of Reactivity in Mouse Retinal Arterioles &lt;em&gt;Ex Vivo&lt;/em&gt;

Vascular insufficiency and alterations in normal retinal perfusion are among the major factors for the pathogenesis of various sight-threatening ocular diseases, such as diabetic retinopathy, hypertensive retinopathy, and possibly glaucoma. Therefore, retinal microvascular preparations are pivotal tools for physiological and pharmacological studies to delineate the underlying pathophysiological mechanisms and to design therapies for the diseases. Despite the wide use of mouse models in ophthalmic research, studies on retinal vascular reactivity are scarce in this species. A major reason for this discrepancy is the challenging isolation procedures owing to the small size of these retinal blo…

A New Method for Direct Detection of Heparin on Surface-Modified Intraocular Lenses

Background: Examination of surface-bound heparin on synthetic polymers can only be performed by few staining methods. These methods are limited by an only approximate detection of heparin visible at high magnification. Other methods only measure heparin quantitatively (per square dimension) and are rather sensitive to artifacts. Due to its homogeneous staining pattern, the modified toluidine blue staining technique, using a non-protein-based substance, allows examination and analysis of the homogeneity of the monomolecular heparin layer even under critical conditions like scanning electron microscopy. Materials and Methods: For critical examination of the heparin layer, this method was used…

Monocular versus binocular pupillometry.

Purpose To quantify differences between monocular and binocular pupil size measurement under scotopic and mesopic conditions. Setting Department of Ophthalmology, Johannes Gutenberg-University, and Department of Medical Biometry, Epidemiology and Informatics, University of Mainz, Mainz, Germany. Methods Computerized dynamic pupillometry (P2000 SA, Procyon Instruments Ltd.) was used at 3 illumination levels: scotopic at 0.03 lux, mesopic low at 0.82 lux, and mesopic high at 6.4 lux. One hundred forty eyes of 70 healthy volunteers without ocular pathology were examined. The subjects were divided into 2 groups. In the first group, the pupil diameter was measured binocularly first. In the secon…

Brimonidine versus dapiprazole: Influence on pupil size at various illumination levels.

To evaluate the influence of dapiprazole versus brimonidine on pupil size at various illumination levels.Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany.In randomized prospective study, 19 healthy volunteers received 2 ophthalmic solutions, dapiprazole and brimonidine, 1 in each eye, for intraindividual comparison. Before and after application, pupil diameter was measured using an infrared binocular pupillometer at 3 illumination levels (0.03, 0.82, and 6.4 lux).Only slight pupil dilation was observed under scotopic conditions after application of both agents. After 20 minutes, the median reduction in pupil width was 1.4 mm for brimonidine and 0.9 mm for dapiprazo…

Prevalence and associations of diabetic retinopathy in a large cohort of prediabetic subjects: The Gutenberg Health Study

Abstract Aims To evaluate the prevalence of diabetic retinopathy/maculopathy (DR/DMac) and its associations with cardiovascular risk factors (CRF) in participants with prediabetes (PwPD) in a large European cohort within the population-based Gutenberg Health Study (GHS). Methods The study was based on a sub-cohort of the GHS (n=5,000, age: 35–74 y). Prediabetes was diagnosed according to HbA 1c levels (5.7–6.4%). DR/DMac was graded from fundus photographs. Blood samples and comprehensive questionnaires served for evaluation of laboratory results and CRF. Results The prevalence of prediabetes was 22.4%, and of DR/DMac 8.1%/0.2%, respectively. The majority of participants had mild DR (7.2%). …

Comparison of subconjunctival microinvasive glaucoma surgery and trabeculectomy

Purpose To assess surgical success and the post-operative development of intraocular pressure between XEN45® gelstent, Preserflo® MicroShunt and trabeculectomy with mitomycin C. Methods Data from 105 eyes from 105 patients of matched cases with refractory open-angle glaucoma, who underwent surgery between January 2019, and August 2020, were evaluated. Patients underwent either stand-alone XEN gelstent insertion with Mitomycin C, stand-alone Preserflo with Mitomycin C or trabeculectomy with Mitomycin C. The primary outcome was the proportion of complete surgical success at 6 months post-operatively (i.e. intraocular pressure between 5mmHg and 18mmHg, no revision surgery, no loss of light per…

Effect of large positioning holes on capsule fixation of plate-haptic intraocular lenses

Abstract Purpose To compare the centration and fixation of silicone plate-haptic intraocular lenses (IOLs) with different-sized positioning holes. Setting Eye Clinic of the Johannes Gutenberg-University Mainz, Mainz, Germany. Methods In a prospective randomized study, 51 Chiroflex C10 and 56 Chiroflex C11 IOLs were implanted under standardized conditions by the same surgeon. The IOL position was documented at the end of surgery and by retroillumination on the first day and 5 months postoperatively. The positioning-hole area was evaluated by ultrasound biomicroscopy (50 MHz) 5 months postoperatively. Results One day postoperatively, no IOL in either group was decentered more than 1.0 mm. Aft…

Retrobulbäre Bestrahlung bei endokriner Orbitopathie - Erfahrungen im Langzeitverlauf

Background Significance of retrobulbar irradiation in patients suffering form Graves' ophthalmopathy, though established since almost one century, is subject of scientific debate. The present study investigated the effect of retrobulbar irradiation using a standardized protocol focussing on long term results. Patients and methods Between 1981 and 1997, 104 patients treated by retrobulbar irradiation (10 to 20 Gray) due to Graves' disease. Twenty-nine of these underwent irradiation as sole treatment (mean follow-up 57 months), while in the remaining 75, it was combined with a systemic steroid treatment (mean follow-up 40 months). Patients were evaluated regarding proptosis, intraocular press…

Bioenergetic shift and actin cytoskeleton remodelling as acute vascular adaptive mechanisms to angiotensin II in murine retina and ophthalmic artery

Ocular vascular dysfunction is a major contributing factor to the pathogenesis of glaucoma. In recent years, there has been a renewed interest in the role of angiotensin II (Ang II) in mediating the disease progression. Despite its (patho)physiological importance, the molecular mechanisms underlying Ang II-mediated oxidative stress remain largely unexplored in the ocular vasculature. Here, we provide the first direct evidence of the alterations of proteome and signalling pathways underlying Ang II-elicited oxidative insult independent of arterial pressure changes in the ophthalmic artery (OA) and retina (R) employing an in vitro experimental model. Both R and OA were isolated from male C57B…

Mean Platelet Volume and Arterial Stiffness - Clinical Relationship and Common Genetic Variability

AbstractVessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific me…

Cardiovascular medication and intraocular pressure: results from the Gutenberg Health Study

BACKGROUND Intraocular pressure (IOP) is well known to be associated with blood pressure and other cardiovascular risk factors. The influence of systemic cardiovascular, in particular antihypertensive, medication on IOP is still controversial. This study analyses the association between the use of cardiovascular medications and IOP in a large European cohort. METHODS The Gutenberg Health Study is a population-based, prospective,observational cohort study in mid-western Germany. IOP was measured using a non-contact tonometer. The medication classes examined were peripheral vasodilators, diuretics, β-blockers (overall, selective and non-selective), calcium channel blockers, renin-angiotensin …

Disturbed glucose metabolism and left ventricular geometry in the general population – results from the Gutenberg health study

Abstract Background Prediabetes and type 2 diabetes mellitus (T2DM) have been demonstrated to alter left ventricular geometry and promote left ventricular (LV) hypertrophy (LVH). However, the impact of impaired glucose metabolism on cardiac structure is still not completely understood and controversially discussed. Purpose To investigate the impact of prediabetes and T2DM on left ventricular geometry and their potential interaction with LVH in the prediction of survival. Methods Data from the Gutenberg Health Study (N=15,010) – a population-based study with highly standardized phenotyping – were analysed. Information was obtained from computer-assisted personal interviews, medical-technical…

Immunological Effects of Allopurinol in the Treatment of Experimental Autoimmune Uveitis (EAU) after Onset of the Disease

Purpose Allopurinol reduces oxidative tissue damage and exerts immunomodulating effects in the treatment of experimental autoimmune uveitis (EAU). However, the mechanism of the immunologic pathway remains unclear. In previous studies, treatment was started at the time of immunization. Therefore, whether allopurinol prevents the onset of the disease (i.e., acts in a protective manner) is not known. Methods Sixteen male Lewis rats were used: 6 EAU without therapy [control]; 4 EAU with allopurinol treatment starting 7 days after immunization [AL7]; and 6 EAU with allopurinol treatment starting 11 days after immunization [AL11]. Their sera were tested against Western blots of sodium dodecyl sul…

The relationship of ocular geometry with refractive error in normal and low birth weight adults

Purpose Low birth weight (BW) individuals have an increased risk for myopic refractive error. However, it is unclear which ocular geometric alterations lead to an increase in myopic refractive error. This study aims to evaluate the impact of ocular biometry in interaction with BW on refractive error. Methods Participants of the prospective, observational, population-based Gutenberg Health Study (GHS) with self-reported BW aged 40–80 years and objective refraction and optical biometry were included. Linear regression analyses were conducted to evaluate associations between spherical equivalent with corneal power, anterior chamber depth, lens thickness and axial length and its interaction wit…

Healon5 versus Viscoat during cataract surgery: intraocular pressure, laser flare and corneal changes

Background: The use of a viscoelastic substance facilitates cataract surgery. Healon 5 is a new viscoelastic product with special rheological properties. We evaluated the postoperative effect of Viscoat and Healon5 on intraocular pressure (IOP), central corneal thickness (CCT), endothelial cell counts and laser flare. Methods: Forty-eight eyes of 48 patients undergoing routine phacoemulsification followed by foldable IOL implantation were enrolled. Either Healon5 or Viscoat was used according to a block- randomization scheme. The aspiration technique was standardized. IOP, CCT, endothelial cell counts and laser flare were compared pre- and postoperatively. Statistical analysis was performed…

Identification of the Muscarinic Acetylcholine Receptor Subtype Mediating Cholinergic Vasodilation in Murine Retinal Arterioles

To identify the muscarinic acetylcholine receptor subtype that mediates cholinergic vasodilation in murine retinal arterioles.Muscarinic receptor gene expression was determined in murine retinal arterioles using real-time PCR. To assess the functional relevance of muscarinic receptors for mediating vascular responses, retinal vascular preparations from muscarinic receptor-deficient mice were studied in vitro. Changes in luminal arteriole diameter in response to muscarinic and nonmuscarinic vasoactive substances were measured by video microscopy.Only mRNA for the M(3) receptor was detected in retinal arterioles. Thus, M(3) receptor-deficient mice (M3R(-/-)) and respective wild-type controls …

Peripapillary Choroidal Thickness and Choroidal Area in Glaucoma, Ocular Hypertension and Healthy Subjects by SD-OCT.

Background: The exact pathogenesis of open angle glaucoma and ocular hypertension remains unclear. Hemodynamic influences are discussed as potential risk factors and the choroid may play an important role in the pathogenesis of open angle glaucoma or ocular hypertension. The current study investigates peripapillary choroidal thickness and choroidal area in patients with open angle glaucoma, subjects with ocular hypertension and healthy subjects using spectral-domain OCT. It furthermore assesses the association between peripapillary choroidal thickness and age, central corneal thickness, refractive error and intraocular pressure. Patients and Methods: Prospectively recorded data of 213 eyes …

Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse …

Healon5 viscoadaptive formulation: Comparison to Healon and Healon GV

Abstract Purpose To compare the rheological characteristics of a viscoadaptive viscoelastic formulation with those of 2 standard ophthalmic viscosurgical devices (OVDs). Setting Department of Ophthalmology, Johannes Gutenberg-University, and Max Planck-Institute for Polymer Research, Mainz, Germany. Methods An independent comparative study of 3 OVDs of sodium hyaluronate (Healon®, Healon GV®, and Healon®5) was performed using the Advanced Rheometric Expansion System to analyze rheologic behavior (eg, dynamic frequency dependence of the complex viscosity) as well as rheological parameters (eg, viscosity at zero shear rate, pseudoplasticity, relaxation time, elastic and viscous modulus). Resu…

Chronisches Lidödem assoziiert mit Rosazea (Morbus Morbihan): Differenzialdiagnostische Schwierigkeiten und Therapieoptionen

Background Morbus Morbihan is a rare complication of rosacea, consisting of a persistent lymphoedema of the upper part of the face. It has typically a chronic course, unspecific histopathological findings and an extreme refractoriness to therapy. Patients and methods Between February 2008 and January 2010, 5 patients with Morbus Morbihan were observed at the Department of Ophthalmology of the University Medical Centre Mainz. In the present cohort study, we describe the clinical, laboratory and histological findings that led to the diagnosis. The course of the affection and the results of different therapeutic options are also reported. Results Each patient underwent a complete ophthalmologi…

Analysis of Autoantibody Repertoires in Sera of Patients with Glaucoma

PURPOSE Glaucoma is the second cause of blindness worldwide. It is usually considered a neurodegenerative disease. There is evidence that an autoimmune mechanism is involved in the development of glaucoma in some patients. The aim of this study was to analyze the IgG autoantibody repertoires in sera of glaucoma patients and healthy subjects. METHODS A total of 82 patients were divided into four groups: healthy volunteers without any ocular disorders (CO, n = 30), patients with primary open-angle glaucoma (POAG, n = 19), ocular hypertension (OHT, n = 16), and normal tension glaucoma (NTG, n = 17). All groups were matched for age and gender. The sera of these patients were tested against West…

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

Purpose We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. Methods The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corn…

Endothelin Antagonism: Effects of FP Receptor Agonists Prostaglandin F2αand Fluprostenol on Trabecular Meshwork Contractility

Purpose This study analyzes additional mechanisms behind the ocular hypotensive effect of prostaglandin F (PGF) receptor (FP receptor) agonists PGF2alpha and fluprostenol (fluprostenol-isopropyl ester [travoprost]), which reduce intraocular pressure (IOP) in patients with glaucoma probably by enhancing uveoscleral flow. The trabecular meshwork (TM) is actively involved in IOP regulation through contractile mechanisms. Contractility of TM is induced by endothelin (ET)-1, a possible pathogenic factor in glaucoma. The involvement of FP receptor agonists in the ET-1 effects on TM function was studied. Methods The effects of FP receptor agonists on contractility of bovine TM (BTM) were investiga…

Efficacy and tolerability of preservative-free eye drops containing a fixed combination of dorzolamide and timolol in glaucoma patients.

To evaluate the efficacy and tolerability of preservative-free eye drops (dorzolamide/timolol) in routine management of preservative-sensitive glaucoma patients.Data from 2,298 glaucoma patients requiring intraocular pressure (IOP) reduction and suffering from intolerance to benzalkonium chloride or active agents of previously used eye drops were valid for baseline and safety analysis in this prospective, open, noncomparative, multicenter, noninterventional study. Patients were treated with preservative-free dorzolamide/timolol eye drops for 12 weeks. Main efficacy endpoint was IOP reduction after 12 weeks of treatment. Two thousand forty-nine patients were considered for efficacy analysis.…

Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG…

Three-Year Results of Hydrus Microstent with Phacoemulsification

Abstract We report the 3-year IOP efficacy of the implantation of the Schlemm’s canal Hydrus® Microstent (Ivantis®) combined with phacoemulsification versus phacoemulsification alone

Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina

Visual impairment and blindness are often caused by retinal ischemia-reperfusion (I/R) injury. We aimed to characterize a new model of I/R in pigs, in which the intraocular pathways were not manipulated by invasive methods on the ocular system. After 12 min of ischemia followed by 20 h of reperfusion, reactivity of retinal arterioles was measured in vitro by video microscopy. Dihydroethidium (DHE) staining, qPCR, immunohistochemistry, quantification of neurons in the retinal ganglion cell layer, and histological examination was performed. Retinal arterioles of I/R-treated pigs displayed marked attenuation in response to the endothelium-dependent vasodilator, bradykinin, compared to sham-tre…

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects …

Association of low birth weight with myopic refractive error and lower visual acuity in adulthood: results from the population-based Gutenberg Health Study (GHS).

PurposeLow birth weight (BW) is linked to impaired organ development in childhood, including altered ocular morphological and functional development. The aim of this study was to evaluate whether low BW has long-term effects on visual acuity and refraction in adulthood.MethodsThe Gutenberg Health Study is a population-based, observational cohort study in Germany, including 15 010 participants aged between 35 and 74 years. These participants were divided into three different BW groups (low: &lt;2500 g; normal: between 2500 and 4000 g; and high: &gt;4000 g). Best-corrected visual acuity and objective refraction were examined. We used multivariable linear regression models with adjustment for …

Switching to intravitreal fluocinolone acetonide implant for refractory diabetic macular edema: 12- and 24-month results

Purpose: To report visual and anatomical outcomes of chronic/refractory diabetic macular edema (DME) treated with intravitreal fluocinolone acetonide implant. Setting: Retrospective, one arm, multicentric study. Method: Between 2013 and 2018, 27 consecutive eyes of 25 patients with chronic/refractory DME were treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed at 12 and 24 months. The need for IOP lowering treatment as well as top-up therapy during the follow-up were also assessed. Results: The duration of DME prior to treatment in our study was 54 ±…

Regulation of the HTRA2 Protease Activity by an Inhibitory Antibody-Derived Peptide Ligand and the Influence on HTRA2-Specific Protein Interaction Networks in Retinal Tissues.

The mitochondrial serine protease HTRA2 has many versatile biological functions ranging from being an important regulator of apoptosis to being an essential component for neuronal cell survival and mitochondrial homeostasis. Loss of HTRA2 protease function is known to cause neurodegeneration, whereas overactivation of its proteolytic function is associated with cell death and inflammation. In accordance with this, our group verified in a recent study that the synthetic peptide ASGYTFTNYGLSWVR, encoding the hypervariable sequence part of an antibody, showed a high affinity for the target protein HTRA2 and triggered neuroprotection in an in vitro organ culture model for glaucoma. To unravel t…

Physicochemical Surface Properties of Various Intraocular Lenses

&lt;i&gt;Purpose:&lt;/i&gt; It is of major interest to understand how intraocular lens (IOL) surfaces interact with aqueous humor or tissues after implantation. Important parameters to describe the physicochemical surface properties are the contact angle and critical surface tension. Therefore, we performed measurements of the contact angle and critical surface tension of several commercially available IOLs. &lt;i&gt;Setting:&lt;/i&gt; Department of Ophthalmology, Johannes Gutenberg University, Mainz, University Eye Hospital, Tübingen, and Max Planck Institute for Polymer Research, Mainz, Germany. &lt;i&gt;Methods:&lt;/i&gt; A total of 17 commercially available standard quality IOL types (6…

Patient-Reported Nonadherence with Glaucoma Therapy

Abstract Purpose: Effective glaucoma therapy relies to a great extent on the patients' ability to regularly self-administer eye drops. This study aimed to assess self-reported nonadherence and to identify potential barriers to adherence in glaucoma patients. Methods: Participants completed a 16-item questionnaire, designed to examine nonadherence rate and assess the therapy experience. Inclusion criteria stipulated treatment duration of at least 1 year. Nonadherence was defined as missing ≥5% of the prescribed pressure-lowering eye drops doses. Results: In total, 201 glaucoma patients aged 24–88 years were included. Mean treatment duration was 9.4 years. Nonadherence was reported by 30.3% o…

Endotoxins in ophthalmic viscosurgical devices.

Purpose To measure the endotoxin concentration (EC) of 25 commercially available, hyaluronic acid- and hydroxypropylmethylcellulose-based (HPMC) ophthalmic viscosurgical devices (OVDs). Methods The in vitro Limulus amebocyte lysate (LAL) assay, which indicates the presence of endotoxins originating from gram-negative bacteria, was used to determine the EC. The procedure was performed according to the European Pharmacopoeia/USP. EC including duplicate determinations, negative controls, dilution series with control standard endotoxin, dilution series with sample extract and positive sample control. Results 16 OVDs (Amvisc®, Amvisc® Plus, Biolon®, Coatel®, Healon®, Healon® GV, Healon®5, HPMC O…

Does autoimmunity play a part in the pathogenesis of glaucoma?

Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Several risk factors have been described, e.g. an elevated intraocular pressure (IOP), oxidative stress or mitochondrial dysfunction. Additionally, alterations in serum antibody profiles of glaucoma patients, upregulation (e.g. anti-HSP60, anti-MBP) and downregulation (e.g. anti-14-3-3), have been described, but it still remains elusive if the autoantibodies seen in glaucoma are an epiphenomenon or causative. However, it is known that elicited autoimmunity causes retinal ganglion cell loss resulting in glaucomatous-like damage and according to the autoaggressive nature of some autoantibodies we found…

Autoimmunity and Glaucoma

Elevated intraocular pressure does not explain glaucoma in all patients, but there is information that autoimmune mechanisms may be involved in this disorder. This review attempts to reveal the findings about specific changes in autoantibody profiles in glaucoma patients and their possible role in glaucoma. Considering that these changes in natural autoimmunity can be found consistently among different study populations, it might be a promising new tool for glaucoma detection.

Myopia and Cognitive Performance: Results From the Gutenberg Health Study.

Purpose To analyze the association between myopia and cognitive performance. Methods A cohort of the population-based Gutenberg Health Study included 3819 eligible enrollees between 40 and 79 years. We used the Tower of London (TOL) test to assess cognitive performance. Myopia was defined as a spherical equivalent (SE) ≤ -0.5 diopters (D) via noncycloplegic autorefractometry. We conducted linear mixed models with the SE as the dependent variable and the age, sex, duration of education, and TOL score as covariates. Results Complete data were available for 3452 participants (90.4%). The mean TOL score was 14.0 ± 3.9 in the myopes versus 12.9 ± 4.0 in the nonmyopes (P < 0.001). The mean TOL sc…

Intraocular pressure measurements during flap preparation using 2 femtosecond lasers and 1 microkeratome in human donor eyes

Purpose To evaluate and compare intraocular pressures (IOPs) during flap preparations performed using 2 femtosecond lasers and a mechanical microkeratome in human donor globes. Setting University Medical Center Mainz, Mainz, and Euroeyes Clinic Stuttgart, Stuttgart, Germany. Design Experimental study. Methods A cannula was inserted through the optic nerve in human globes. The IOP was obtained continuously during flap preparation using the 60 kHz Intralase femtosecond laser, the 200 kHz Visumax femtosecond laser, or the Amadeus II microkeratome. For each experiment, a normal lamellar flap preparation (regular procedure) and a worst-case procedure (femtosecond laser interface was pressed agai…

Fine Structural Evaluation of the Iris After Unilateral Treatment With Latanoprost in Patients Undergoing Bilateral Trabeculectomy (The Mainz II Study)

Objective To investigate by masked electron microscopy whether 6 months of topical latanoprost caused pathological changes in the peripheral iris of patients with glaucoma. Methods Seventeen patients with bilateral primary open-angle glaucoma requiring trabeculectomy were recruited for this study. The iridectomy taken during surgery on the first eye served as a control. The second test eye was treated topically with latanoprost for 6 months before its trabeculectomy. Fourteen patients completed the treatment arm of the study, and 1 of these underwent marked color change. As a result, 31 iridectomy specimens were fixed, coded, and evaluated. Results The specimens were evaluated for evidence …

Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina

Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in…

Effects of multipurpose contact lens solutions on the protein composition of the tear film

Abstract Objectives: To analyze the influence of multipurpose contact lens cleaning solutions on tear proteins. Changes in tear film protein profiles of contact lens wearers who used several marketed brands of multipurpose contact lens care solutions, were assessed by ProteinChip analysis. Methods: Three studies were conducted. Study I was a comparison of Complete and OptiFree multipurpose solutions. Study II was a study with Complete Moisture Plus solution, Study II was a comparison of Renu and Solocare contact lens solutions. Wearers of soft contact lenses were assigned to use the contact lens care solutions for 4 weeks. Non-contact lens wearing patients were used as controls. Tear sample…

Epidemiologic Analysis of Asteroid Hyalosis and Associations: The Gutenberg Health Study

Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted…

Abstract 13257: FEV1 and FVC predict Mortality in Individuals Without Manifest Lung Disease Independent of Cardiac Performance - Results From the Population-based Gutenberg Health Study

Background: Pulmonary disease has consistently been related to increased mortality. We investigated central spirometry variables in relation to total mortality in individuals from the general population without diagnosed lung disease also accounting for cardiac function. Methods: In 15,010 individuals from the general population (mean age 55±11 years, age range 35-74 years, 50.5% men) in the Gutenberg Health Study we performed spirometry and multimodal transthoracic echocardiography. The biomarkers N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (TnI) were measured in the first 5000 individuals using commercially available assays. Multivariable Cox regre…

Visual Impairment Is Associated With Depressive Symptoms—Results From the Nationwide German DEGS1 Study

Introduction: Visual impairment is associated with a variety of co-morbidities including physical and mental health in industrial countries. Our aim is to examine associations between self-reported impairment and depressive symptoms in the German population. Methods: The point prevalence of self-reported visual impairment in Germany was computed using data from the German Health Interview and Examination Survey for adults from 2008 to 2011 (N=7.783, 50.5% female, age range 18-79 years). Visual impairment was surveyed by two questions, one for seeing faces at a distance of 4 meters and one for reading newspapers. Depressive symptoms were evaluated with the PHQ-9 questionnaire and two-week pr…

Distribution of Anterior Chamber Angle Width and Correlation With Age, Refraction, and Anterior Chamber Depth—The Gutenberg Health Study

PURPOSE Scheimpflug imaging allows quantitative analysis of the width of the anterior chamber angle. We report the population-based distribution of the anterior chamber angle width using this noncontact imaging technique and investigate associated factors. METHODS A population-based cross-sectional study was carried out in Germany. A comprehensive ophthalmologic examination including refraction, biometry, and Scheimpflug imaging was performed. Automated measurement of the anterior chamber angle was performed in each anterior chamber quadrant. Exclusion criteria were previous ocular surgery or inadequate image quality. Association analyses were carried out to determine independently associat…

Expression and subcellular localization of USH1C/harmonin in the human retina provide insights into pathomechanisms and therapy

AbstractUsher syndrome (USH) is the most common form of hereditary deafness-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course, and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinas uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq…

Serum autoantibodies to alpha-fodrin are present in glaucoma patients from Germany and the United States.

PURPOSE Glaucoma is characterized by a progressive loss of retinal ganglion cells that results in a characteristic optic neuropathy associated with visual field loss. In previous studies, changes in the antibody profiles have been shown in the sera of patients with glaucoma, and these findings suggest a role for autoimmune involvement in the pathogenesis of glaucoma in some patients. The purpose of this study was to compare the antibody profiles against optic nerve antigens in patients with glaucoma in two different study populations from Germany and the United States. METHODS One hundred twenty patients were included in the study, 60 from Germany and 60 from the United States: a control gr…

Birth weight and its association with optic nerve head morphology - results from the population-based German Gutenberg Health Study.

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with i…

The Size of Subconjunctival Preparation Does Not Influence the Outcome of Trabeculectomy With Mitomycin C

PURPOSE To compare the outcome of fornix-based trabeculectomy with mitomycin C (MMC) using 2 different sizes of subconjunctival preparation (36 mm² compared with 72 mm²). METHODS Prospective, randomized interventional case series. STUDY POPULATION Patients 18 to 85 years of age with open-angle glaucoma and progressive visual field defects under maximum tolerated medical therapy were randomized to undergo initial fornix-based trabeculectomy with MMC (0.2 mg/mL for 5 min) with subconjunctival preparation of 6×6 mm (group A) or 8×9 mm (group B). Main outcome parameters were: intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of 5-fluorouracil (5-FU) injections, and laser s…

Knowledge about glaucoma in the unselected population: a German survey.

Purpose To determine the general population's knowledge about glaucoma. Materials and methods A representative survey of the German population was conducted in which 2,742 men and women were interviewed face to face. The sample was matched with the German population for age, sex, education, income, and other factors. Questions were asked concerning the nature, occurrence, possible risk factors, and course of glaucoma. Results Fifty-one percent of the population had an active knowledge of the term "glaucoma" and 75% had a passive knowledge of the term. Of those interviewees with a passive knowledge, glaucoma was thought to be associated with raised intraocular pressure (IOP) by 28% and loss …

Übereinstimmung von klinischer Beurteilung, Heidelberg-Retina-Tomograph (HRT) und Nerve Fiber Analyzer (GDx) in der Glaukomdiagnostik

BACKGROUND We have made a comparison of clinical evaluation, Heidelberg-Retina-Tomograph (HRT) and Nerve Fiber Analyzer (GDx) in diagnosing glaucoma. MATERIALS AND METHODS One eye of 38 glaucoma patients and 26 non-glaucoma patients was examined with HRT and GDx. Assignment of the patients into the two groups by clinical evaluation was performed on the basis of visual field and optic disc results. As classification criterion for glaucoma/non-glaucoma by means of the instruments we employed the statistical classification of the HRT and "the number" of the GDx. Statistical analysis was performed with Cohen's kappa and McNemar tests. Additionally, ROC curves for evaluation of the sensitivity a…

Erhöhte Schwellen für die Detektion von Phasenunterschieden in musterinduzierten Flimmerfarben bei Patienten mit Glaukom

BACKGROUND: Pattern-induced flicker-colors are subjective colors produced by rotating disks with black-and-white arcs. Changing the direction of rotation results in a different color. Small variations in the temporal sequence (phase differences) of the black-and-white pattern cause the colors to vary and can be perceived as color differences. PATIENTS AND METHODS: We investigated the thresholds for such phase differences in healthy (n = 11) and in glaucomatous (n = 19) eyes. Acuity and color vision were tested and in patients static visual field perimetry (Octopus G1) was carried out. The disks used for producing the pattern-induced flicker-colors were viewed from a distance of 2 m and had …

Autoantigens in the trabecular meshwork and glaucoma‐specific alterations in the natural autoantibody repertoire

Abstract Objectives Primary open‐angle glaucoma (POAG) is a neurodegenerative disorder leading to a gradual vision loss caused by progressive damage to the optic nerve. Immunological processes are proposed to be involved in POAG pathogenesis. Altered serological autoantibody levels have been frequently reported, but complete analyses of the natural autoantibodies with respect to disease‐related alterations are scarce. Here, we provide an explorative analysis of pathways and biological processes that may involve naturally immunogenic proteins and highlight POAG‐specific alterations. Methods Mass spectrometry‐based antibody‐mediated identification of autoantigens (MS‐AMIDA) was carried out in…

Corneal tattooing: an alternative treatment for disfiguring corneal scars.

Background: The performance and results of corneal tattooing are described in a case series of 11 patients suffering from a disfiguring corneal scar using a technique similar to conventional dermatography. Methods: Drawing ink in different shades was applied into the anterior corneal stroma by punctures performed with a conventional spatula needle. Results: Up to 4 years after surgery all patients still had satisfactory staining of the formerly cosmetically disfiguring corneal scar. Conclusion: Tattooing of unsightly corneal scars proved to be an efficient and easy to perform technique, yielding acceptable results during follow up.

Proteomics of Orbital Tissue in Thyroid-Associated Orbitopathy.

A potentially altered protein expression profile in orbital tissue from patients with thyroid-associated orbitopathy (TAO) is suspected.To detect for the first time changes in proteomic patterns of orbital connective tissue in TAO and compare these with control tissue using mass spectrometry.Proteomics cross-sectional, comparative study.Two academic endocrine institutions.A total of 64 orbital and peripheral adipose tissue samples were collected from 39 patients with TAO and 25 control subjects.Samples were analyzed and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology.Mean intensity values of all identified peptides per protein.Thirty-…

Surface Topographies of Glaucoma Drainage Devices and Their Influence on Human Tenon Fibroblast Adhesion

PURPOSE. This study was performed to investigate the surface topography of different glaucoma drainage devices and to determine the effects of surface roughness on cell adhesion of cultured human tenon fibroblasts.METHODS. The surface topography of four widely used devices (Ahmed FP7 and Ahmed S-2; New World Medical, Inc., Rancho Cucamonga, CA; Baerveldt BG101-350; Advanced Medical Optics, Irvine, CA; and Molteno S1; Molteno Ophthalmic Ltd., Dunedin, New Zealand) was investigated by scanning electron microscopy, and roughness was quantified by white-light confocal microscopy. Cells were grown for 72 hours on the surfaces of implants affixed to standard culture dishes. The cells were labeled…

Birth Weight and Diabetic Retinopathy: Results From the Population-Based Gutenberg Health Study (GHS).

Purpose: This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population. Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.5% at study entry, a doctor-diagnosis of diabetes, or diabetes medication. The presence of DR was determined by evaluating fundus photographs. BW was assessed by self-reports. GHS participants were divided into three different BW groups (low: &lt;2500 g; normal: 2500–4000 g; high:&gt;4000 g). Logistic regression analysis was conducted as uni- and multiv…

Effect of a closed foldable equator ring on capsular bag shrinkage in cataract surgery.

To evaluate the effect of a closed foldable equator ring (CFER) versus a conventional capsular tension ring (CTR) on capsular bag shrinkage.Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany.In this prospective study, 70 eyes of 70 patients were randomized to 2 groups using a 1:1 block scheme. After uneventful cataract surgery, a capsular measuring ring was implanted in all eyes to measure the capsular bag diameter in vivo. In Group 1, a CTR was implanted in the capsular bag. In Group 2, a CFER was inserted. Biometric characteristics such as axial length and the horizontal and vertical corneal radii were measured preoperatively. The capsular bag diameter and capsulor…

Retinal Imaging through Phakic Iris-Claw IOL.

AbstractBackground: Phakic anterior chamber iris-fixated IOL (PIOL) are established for the correction of high myopia. These patients require attention to macular pathologies. This study was to evaluate the quality of imaging through the PIOLs. Methods: 54 eyes of 31 myopic and hyperopic patients with Verisyse®, Verisyse toric®, and Veriflex® phakic iris-fixated IOL were included. Mean preoperative refraction was −11.0 D and +5.7 D, respectively; mean follow-up time was 7.4 years (5–11 years). A matched control group was formed without PIOL implantation. OCT scans were performed and evaluated qualitatively and quantitatively. Results: In 52 eyes of 31 patients (96%), a 3D-OCT image and fund…

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern

BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS: We identified a genome-wide significant (P < 5 × 10(–8)) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discov…

The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model

Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced b…

Longitudinal analysis of taurine induced effects on the tear proteome of contact lens wearers and dry eye patients using a RP-RP-Capillary-HPLC-MALDI TOF/TOF MS approach.

Tear proteomic studies revealed distinct similarities between contact lens wearers and dry eye patients. AMO Complete® multipurpose contact lens cleaning solutions containing taurine seem to have a beneficial effect regarding contact lens induced dry eye. To illuminate the effect of taurine on the tear proteome of contact lens wearers and sicca patients we developed a gel-based RP-RP capillary HPLC-MALDI TOF/TOF MS strategy. Two contact lens wearer groups, one using eye drops containing 0.05% taurine; the other for control physiological NaCl solution were monitored. Also, a third group of sicca patients using taurine solution was studied (N=4 individuals/group). Tear pools of each group at …

Subclinical impairment of lung function is related to mild cardiac dysfunction and manifest heart failure in the general population.

Lung function impairment has previously been related to heart failure, although no overt cardiovascular or structural heart disease is present. The extent to which pulmonary function is related to subclinical left ventricular impairment in the general population remains to be investigated.15010 individuals from the general population (mean age 55±11years, 50.5% men) in the Gutenberg Health Study underwent spirometry, transthoracic echocardiography and biomarker measurement. Forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) in percent of the predicted value and FEV1/FVC ratio were associated with echocardiographic measures of cardiac structure, systolic and diastolic func…

Subclinical levels of anxiety but not depression are associated with planning performance in a large population-based sample

BackgroundMajor depression and anxiety disorders are known to negatively influence cognitive performance. Moreover, there is evidence for greater cognitive decline in older adults with generalized anxiety disorder. Except for clinical studies, complex executive planning functions and subclinical levels of anxiety have not been examined in a population-based sample with a broad age range.MethodsPlanning performance was assessed using the Tower of London task in a population-based sample of 4240 participants aged 40–80 years from the Gutenberg Health Study (GHS) and related to self-reported anxiety and depression by means of multiple linear regression analysis.ResultsHigher anxiety ratings we…

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on …

Myopia and Level of Education

Purpose To analyze the association between myopia and educational level in an adult European cohort. Design Population-based cross-sectional study. Participants A cohort of the Gutenberg Health Study, including 4658 eligible enrollees between 35 and 74 years of age. Methods We applied a standardized protocol entailing a comprehensive questionnaire; thorough ophthalmic, general, cardiovascular, and psychological examinations; and laboratory tests, including genetic analyses. We documented achievement levels in school education and post-school professional education. The spherical equivalent (SE) was determined by noncycloplegic autorefractometry. We fitted mixed linear models including age, …

Autoreactive Antibodies and Loss of Retinal Ganglion Cells in Rats Induced by Immunization with Ocular Antigens

PURPOSE In an experimental autoimmune animal model, retinal ganglion cell (RGC) loss was induced through immunization with glaucoma-related antigens. The target of this study was to investigate the pathomechanism behind this decline and the serum antibody reactivity against ocular and neuronal tissues after immunization with glaucoma- and non-glaucoma-associated antigens. METHODS Rats immunized with optic nerve antigen homogenate (ONA) or keratin (KER) were compared to control rats (CO). Intraocular pressure (IOP) was measured, and the fundi were examined regularly. Four weeks afterward, cells were counted in retinal flat mounts. Retina, optic nerve, and brain sections from healthy animals …

Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study.

SummaryObjective To determine the age- and sex-specific prevalence and determinants of retinal vein occlusions (RVOs) in a large population-based German cohort. Methods The investigation included 15 010 participants (aged 35–74 years) from the Gutenberg Health Study. We determined the prevalence of RVO (central retinal vein occlusion [CRVO] and branch retinal vein occlusion [BRVO]) for the local population by assessing fundus photographs of 12 954 (86.3%; 49.8% women and 50.2% men) participants. Further, we analyzed the associations of RVO with cardiovascular, anthropometric, and ophthalmic parameters. Results The weighted prevalences of RVO, CRVO, and BRVO were 0.40%, 0.08%, and 0.32%, res…

Role of α1-adrenoceptor subtypes on corneal epithelial thickness and cell proliferation in mice

Adrenergic stimuli are important for corneal epithelial structure and healing. The purpose of the present study was to examine the hypothesis that the lack of a single α1-adrenoceptor (α1-AR) subtype affects corneal epithelial thickness and cell proliferation. Expression levels of α1-AR mRNA were determined in mouse cornea using real-time PCR. In mice devoid of one of the three α1-AR subtypes (α1A-AR−/−, α1B-AR−/−, α1D-AR−/−) and in wild-type controls, thickness of individual corneal layers, the number of epithelial cell layers, and average epithelial cell size were determined in cryosections. Endothelial cell density and morphology were calculated in corneal explants, and epithelial cell p…

Endothelin receptor B in trabecular meshwork

Abstract Endothelin-1 (ET-1), the most potent vasoconstrictor known to date, seems to be involved in the pathogenesis of primary open angle glaucoma. ET-1 was found in different tissues of the eye and in high concentrations in the aqueous humour. The effects of ET-1 are mediated by two receptors, ET-A receptor (ET-AR) and ET-B receptor (ET-BR), which are both expressed in bovine trabecular meshwork (TM). ET-1 induced contraction of TM predominantly by activation of ET-AR. This study analyzes the role of ET-BR in TM function and investigates the synthesis of ET-1 by human TM (HTM) cells. The effect of IRL-1620, a specific ET-BR agonist, on contractility of bovine TM (BTM) was investigated wi…

SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye.

Protein and peptides in tears play an important role in ocular surface diseases. In previous studies, changes have been demonstrated in the electrophoretic protein profiles of patients with dry eye. The purpose of this work was to determine the usefulness of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip Array (Ciphergen Biosystems, Inc., Fremont, CA) technology for the automated analysis of proteins and peptides in tear fluid.Patients with dry eye (DRY, n = 88) and healthy subjects (CTRL, n = 71) were examined. Their tear proteins were analyzed using SELDI-TOF-MS ProteinChip Arrays with three different chromatographic surfaces (CM10…

Characterization of human reflex tear proteome reveals high expression of lacrimal proline-rich protein 4 (PRR4).

In-depth studies on the proteome of reflex tears are still inadequate. Hence, further studies on this subject will unravel the key proteins which are conjectured to possess vital functions in the protection of the ocular surface. Therefore, this study investigated the differences in the expression levels in proteome of reflex compared to basal tears. Basal (n = 10) and reflex (n = 10) tear samples from healthy subjects were collected employing the capillary method, subsequently pooled and the proteomes were characterized employing 1DE combined with LC-ESI-MS/MS strategy for label-free quantitative (LFQ) analysis. The differentially expressed proteins were validated by 2DE combined with LC-E…

Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population

AIMS Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased e…

Comparison of Two Solid-Phase Extraction (SPE) Methods for the Identification and Quantification of Porcine Retinal Protein Markers by LC-MS/MS

Proper sample preparation protocols represent a critical step for liquid chromatography-mass spectrometry (LC-MS)-based proteomic study designs and influence the speed, performance and automation of high-throughput data acquisition. The main objective of this study was to compare two commercial solid-phase extraction (SPE)-based sample preparation protocols (comprising SOLA&micro

The Prevalence of Glaucoma in Young People.

BACKGROUND Earlier information on the prevalence of glaucoma among children in Germany was based solely on estimates. Reported values for congenital glaucoma range from 1 in 10 000 to 1 in 68 000 depending on ethnic origin. The estimate for juvenile glaucoma is 1 in 44 000. METHODS The Gutenberg Health Study is a populationbased, prospective, monocentric cohort study with 15 010 participants aged 35 to 74. To determine the history-based prevalence of childhood glaucoma, participants were asked about the diagnosis of glaucoma, any operations for glaucoma that were performed, regular use of drugs for glaucoma, and the age of onset of glaucoma. The affected individuals were classified in four …

Role of the M3 Muscarinic Acetylcholine Receptor Subtype in Murine Ophthalmic Arteries After Endothelial Removal

We tested the hypothesis that the M3 muscarinic acetylcholine receptor subtype mediates cholinergic responses in murine ophthalmic arteries after endothelial removal.Muscarinic receptor gene expression was determined in ophthalmic arteries with intact and with removed endothelium using real-time PCR. To examine the role of the M3 receptor in mediating vascular responses, ophthalmic arteries from M3 receptor-deficient mice (M3R(-/-)) and respective wild-type controls were studied in vitro. Functional studies were performed in nonpreconstricted arteries with either intact or removed endothelium using video microscopy.In endothelium-intact ophthalmic arteries, mRNA for all five muscarinic rece…

No evidence for an association of plasma homocysteine levels and refractive error – Results from the population-based Gutenberg Health Study (GHS)

Purpose There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007–2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. …

Noise annoyance predicts symptoms of depression, anxiety and sleep disturbance 5 years later. Findings from the Gutenberg Health Study

Abstract Background Cross-sectional studies have shown that noise annoyance is strongly associated with mental distress, however, its long-term effects on mental health is unknown. We therefore investigated whether noise annoyance predicts depression, anxiety and sleep disturbance in a large, representative sample 5 years later. Methods We investigated longitudinal data of N = 11 905 participants of the Gutenberg Health Study, a population-based, prospective, single-centre cohort study in mid-Germany (age at baseline 35–74 years). Noise annoyance was assessed at baseline and 5-year follow-up (sources: road traffic, aircraft, railways, industrial, neighbourhood indoor and outdoor noise; and …

Osmolality of various viscoelastic substances: comparative study.

Abstract Purpose To determine the osmolality of various viscoelastic substances. Setting Department of Ophthalmology, Johannes Gutenberg-University, Mainz, and Institute for Medical Device Testing, Memmingen, Germany. Methods The analysis was carried out according to the European Pharmacopoeia by means of a calibrated osmometer using the freezing-point depression method. Each syringe was analyzed as a duplicate analysis. Results Mean osmolalities (mOsmol/kg) of the sodium hyaluronate viscoelastic substances were Allervisc® 299; Allervisc® Plus 307; Amvisc® Plus 335; AMO Vitrax® 284; Biolon® 279; Dispasan® 311; Dispasan® Plus 314; Healon® 295; Healon GV® 312; Healon®5 322; HYA-Ophtal® 376; M…

Intraocular pressure after small incision cataract surgery: temporal sclerocorneal versus clear corneal incision.

To compare intraocular pressure (IOP) after phacoemulsification and foldable intraocular lens (IOL) implantation using a temporal sclerocorneal or clear corneal incision.Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany.One hundred patients (100 eyes) with cataract having phacoemulsification with posterior chamber IOL implantation were randomly assigned to receive a temporal sclerocorneal or clear corneal tunnel incision. Intraocular pressure was measured preoperatively and 6 hours, 1, 2, and 3 days, and 5 months postoperatively. Statistical significance was determined by nonparametric group comparisons using 2-sample random Wilcoxon tests.Six hours postoperatively,…

Irregularity of the posterior corneal surface after curved interface femtosecond laser-assisted versus microkeratome-assisted descemet stripping automated endothelial keratoplasty.

During donor tissue preparation for Descemet stripping automated endothelial keratoplasty (DSAEK), either microkeratome or femtosecond laser can be used for intrastromal cutting. We compared morphological and functional outcomes after DSAEK using both cutting techniques.In this retrospective study, 22 uneventful DSAEK surgeries were reviewed. Eight donor corneas were prepared for DSAEK using the VisuMax femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany). Fourteen corneas were processed using an Amadeus II microkeratome (Ziemer Ophthalmic Systems AG, Port, Switzerland). The postoperative best spectacle-corrected visual acuity was measured. Furthermore, corneal optical coherence tomogra…

Functional Role of α1-Adrenoceptor Subtypes in Murine Ophthalmic Arteries

PURPOSE To identify the α(1)-adrenoceptor (α(1)-AR) subtypes mediating vascular adrenergic responses in murine ophthalmic arteries. METHODS Expression of mRNA was quantified for individual α(1)-AR subtypes in murine ophthalmic arteries using real-time PCR. To assess the functional relevance of α(1)-ARs for mediating vascular responses, ophthalmic arteries from mice deficient in one of the three α(1)-AR subtypes (α(1A)-AR(-/-), α(1B)-AR(-/-), and α(1D)-AR(-/-), respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal artery diameter in response to the α(1)-AR agonist phenylephrine, the sympathetic transmitter noradrenaline, and to…

Results of an Adaptive Surgical Approach for Managing Late Onset Hypotony After Trabeculectomy With Mitomycin C.

OBJECTIVES The objective of this study is to investigate the results of an adaptive approach of bleb revision surgery for late onset hypotony after trabeculectomy with mitomycin C because of bleb leakage and/or scleral melting. METHODS A total of 29 eyes of 27 patients, aged 63.8±11.7 years with hypotony maculopathy [intraocular pressure (IOP), ≤6 mm Hg] because of late onset bleb leakage and/or scleral melting after trabeculectomy with mitomycin C in which minimally invasive transconjunctival suturing of the scleral flap was impossible were enrolled in this retrospective interventional case series. External bleb leakage was seen in 16 eyes, 11 eyes suffered from scleral melting. Because of…

Synthetic Polyclonal-Derived CDR Peptides as an Innovative Strategy in Glaucoma Therapy

The pathogenesis of glaucoma is strongly associated with the occurrence of autoimmune-mediated loss of retinal ganglion cells (RGCs) and additionally, recent evidence shows that specific antibody-derived signature peptides are significantly differentially expressed in sera of primary-open angle glaucoma patients (POAG) compared to healthy controls. Synthetically antibody-derived peptides can modulate various effector functions of the immune system and act as antimicrobial or antiviral molecules. In an ex vivo adolescent glaucoma model, this study, for the first time, demonstrates that polyclonal-derived complementarity-determining regions (CDRs) can significantly increase the survival rate …

Preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% in patients with open-angle glaucoma and ocular hypertension: results of an open-label observational study

Lutz E Pillunat,1 Carl Erb,2 Auli Ropo,3 Friedemann Kimmich,4 Norbert Pfeiffer5 1Department of Ophthalmology, University Hospital Carl Gustav Carus, Dresden, 2Augenklinik am Wittenbergplatz, Berlin, Germany; 3Santen Europe, Helsinki, Finland; 4eyecons, Pfinztal, 5Department of Ophthalmology, Mainz University Medical Center, Mainz, Germany Background: Efficacy, tolerability and safety of the novel preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% (Taptiqom&amp;reg;) were investigated in an observational study in Germany.Objective: To assess efficacy, tolerability and safety of the preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% in a real-life setti…

Response to Letter to the Editor: Outcome of Bleb Revision With Autologous Conjunctival Graft Alone or Combined With Donor Scleral Graft for Late-onset Bleb Leakage With Hypotony After Standard Trabeculectomy With Mitomycin C.

Optical Coherence Tomography Angiography of Optic Disc in Eyes With Primary Open-angle Glaucoma and Normal-tension Glaucoma.

PURPOSE To examine vessel density (VD) properties of the optic nerve head in eyes with ocular hypertension (OHT), high-tension glaucoma (HTG), and normal-tension glaucoma (NTG) and to evaluate associations on structural parameters of retinal nerve fiber layer (RNFL). METHODS Three groups of patients with OHT (n=15), HTG (n=36), and NTG (n=22), and a healthy control group (n=23) were included in this study. Peripapillary VD and optic disc flow area were measured using optical coherence tomography angiography, and peripapillary RNFL (pRNFL) thickness was determined. Global and sectoral analysis of optic nerve head vasculature and pRNFL thickness were measured. RESULTS Glaucomatous eyes had lo…

Clinical Relevance of Thyroid-Stimulating Immunoglobulins in Graves' Ophthalmopathy

Purpose Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. Design Cross-sectional trial. Participants A total of 108 untreated patients with GO. Methods Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compa…

Psychosomatische Medizin in der Gutenberg- Gesundheitsstudie (GHS) – Fragestellungen, Messverfahren, ausgewählte Ergebnisse

Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results Goal: Main questions from the Gutenberg Health Study (GHS) related to psychosomatic medicine are presented: (1) Prevalence and incidence of mental illnesses, (2) Sex-specific risk- and protective factors for mental health, (3) Interplay between psychological and somatic diseases and (4) methodical-psychometric developments. Methods: The GHS is an ongoing, prospective and interdisciplinary cohort study in Mainz. The comprehensive examinations include psychological characteristics and clinical and laboratory tests. 15010 respondents were selected in the baseline study fro…

Autoimmune aspects in glaucoma

The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in glaucoma patients. Furthermore we found antibody deposits in human glaucomatous retinae in a pro-inflammatory environment. Clinical studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies belong to the natural autoimmunity. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also neuroprotective characteristics and influence the protein expression …

Dynamics, alterations, and consequences of minimally invasive intraocular pressure elevation in rats.

PURPOSE: An important, yet not exclusive, aspect of primary open angle glaucoma is elevated intraocular pressure (IOP) profiles within fluctuations and pressure peaks. The study aimed at establishing minimally invasive methods for recurrent IOP elevation in rats to investigate the impact of IOP dynamics and pathomorphologic retinal alterations during and after IOP elevation. METHODS: Intraocular pressure was elevated unilaterally in Long Evans rats to a level of ≈35 mm Hg for 1 hour in a total of 30 manipulations within 6 weeks, by using two methods: (1) suction-cup oculopression and (2) loop-adjusted oculopression. Retinal thickness (RT) was measured via optical coherence tomography (OCT),…

Proteomics in ocular fluids

The focus of this article is to review recent techniques in proteomic analysis of ocular fluids. These fluids include tears, aqueous humor, and vitreous, they will also be compared to serum analysis. Furthermore, we attempt to summarize some disease correlated biomarkers in ocular fluids that were discovered through different proteomic techniques in eye diseases like dry eye, glaucoma, age-related macular degeneration, uveitis, or diabetic retinopathy. This review is trying to point out the importance of these biomarkers for clinical applications.

Biomarkers for glaucoma: from the lab to the clinic

Glaucoma, a leading cause of irreversible blindness worldwide, is often not diagnosed until many years after disease onset. Early and objective diagnostic measures are yet missing. Besides the main risk factor, an elevated intraocular pressure (IOP), age, sex, and ethnicity are known to affect disease progression and severity. Furthermore, oxidative stress, elevated glutamate concentrations, and an autoimmune component are considered possible risk factors. We could identify several potential proteomic biomarkers in glaucoma and examine distinct changes in the glaucomatous human retina proteome. Using an experimental autoimmune glaucoma animal (EAG) model we could demonstrate an IOP-independ…

2861Role of glycemic state for the relationship between abdominal obesity and markers of inflammation and hemostasis in the population

Enhanced characterization of serum autoantibody reactivity following HSP 60 immunization in a rat model of experimental autoimmune glaucoma.

Antibodies against heat shock proteins have been identified in sera of human glaucoma patients in several studies and immunization with heat shock protein 60 (HSP 60) causes retinal ganglion cell (RGC) loss in an animal model of experimental autoimmune glaucoma. The aim of this study was to observe the time course of increased anti-retina antibody appearance in the serum and characterize the identification of prominent autoantibodies that accompany HSP 60 immunization in a rat model of experimental autoimmune glaucoma.Eight weeks after immunization with HSP 60 retinal flatmounts were prepared and RGCs were counted in eight predefined areas and compared to controls. Serum collected before, a…

Refraktion, Vorderkammertiefe, Dezentrierung und Tilt nach Implantation monofokaler und multifokaler Silikonlinsen

Hintergrund. Ziel der prospektiven Studie war die Analyse von Refraktion, Vorderkammertiefe, Dezentrierung und Verkippung (Tilt) nach Implantation monofokaler (MONO) und multifokaler (MIOL) Intraokularlinsen (IOL). Patienten und Methode. Bei 103 Augen von 103 Patienten wurde entweder eine dreistuckige monofokale oder multifokale Silikon-IOL implantiert. Vorderkammertiefe (ACD), IOL-Dezentrierung und -Tilt wurden mittels Retroilluminationsfotografie und Scheimpflug-Aufnahmen objektiv quantifiziert. Die Untersuchungen einschlieslich Ermittlung der sujektiven Refraktion wurden praoperativ sowie postoperativ nach 1 Woche und nach 6 Monaten vorgenommen. Ergebnisse. Im Bereich von ±1 dpt um die Z…

Outcome of Bleb Revision With Autologous Conjunctival Graft Alone or Combined With Donor Scleral Graft for Late-onset Bleb Leakage With Hypotony After Standard Trabeculectomy With Mitomycin C

Prcis Treatment of leakage with ocular hypotony after trabeculectomy with mitomycin C (MMC) can be safely achieved through conjunctival patch alone or combined with donor scleral graft in cases of melted underlying sclera. Purpose To report outcomes of 2 surgical approaches for treating ocular hypotony in eyes with blebs with late-onset leakage after standard trabeculectomy with MMC. Methods Thirty consecutive cases with bleb leakage and hypotony underwent bleb revision surgery between 2009 and 2014 by the same surgeon (J.W.) at the Department of Ophthalmology of the Mainz University Medical Center, Germany. In 18 patients, an autologous conjunctival patch graft was applied. In 12 patients,…

Effects of Cyclooxygenase Inhibitors on Apoptotic Neuroretinal Cells

Glaucoma is characterized by a loss of retinal ganglion cells (RGC) which is associated with a decrease of visual function. Neuroprotective agents as a new therapeutic strategy could prevent the remaining neurons from apoptotic cell death. Previous studies have shown the involvement of the Cyclooxygenase (COX)-2 signalling in the apoptotic death of neurons. Herein we investigated the neuroprotective effect of COX-1/COX-2- and selective COX-2- inhibitors on apoptotic. R28, a neuroretinal cell line and determined the PGE2 levels by ELISA. Furthermore we investigated differences in protein expression in the cells after exposure to elevated pressure compared to untreated cells by ProteinChip a…

Distribution of HOMA-IR in a population-based cohort and proposal for reference intervals

Abstract Objectives Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35–74 years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteri…

Trabeculotomy in congenital glaucoma.

Background: Congenital glaucoma is a potentially blinding disease that requires surgical therapy. This paper describes the outcome of trabeculotomy in primary congenital glaucoma. Methods: Thirty-nine eyes of 22 children with congenital glaucoma who underwent trabeculotomy with or without a simultaneous trabeculectomy between 1992 and 1997 were retrospectively analyzed. Results: Mean follow-up was 24.7±17.9 months. A mean of 1.3 operations per eye were performed. The mean IOP at the end of follow-up (n=39) was 17.7±6.0 mmHg; in 8 eyes (20.5%) the IOP was >21 mmHg, in 31 eyes (79.5%) it was ≤21 mmHg. The mean difference between pretreatment IOP and IOP at the end of follow-up (n=39) was –10.…

Serum and antibodies of glaucoma patients lead to changes in the proteome, especially cell regulatory proteins, in retinal cells.

PURPOSE: Previous studies show significantly specifically changed autoantibody reactions against retinal antigens in the serum of glaucoma and ocular hypertension (OHT) patients in comparison to healthy people. As pathogenesis of glaucoma still is unknown the aim of this study was to analyze if the serum and antibodies of glaucoma patients interact with neuroretinal cells. METHODS: R28 cells were incubated with serum of patients suffering from primary open angle glaucoma (POAG), normal tension glaucoma (NTG) or OHT, POAG serum after antibody removal and serum from healthy people for 48 h under a normal or an elevated pressure of 15000 Pa (112 mmHg). RGC5 cells were additionally incubated wi…

Cross-Sectional Associations between Homoarginine, Intermediate Phenotypes, and Atrial Fibrillation in the Community—The Gutenberg Health Study

Homoarginine has come into the focus of interest as a biomarker for cardiovascular disease. Atrial fibrillation (AF) causes a substantial increase in morbidity and mortality. Whether circulating homoarginine is associated with occurrence or persistence of AF and may serve as a new predictive biomarker remains unknown. We measured plasma levels of homoarginine in the population-based Gutenberg health study (3761 patients included, of them 51.7% males), mean age 55.6 &plusmn

Latanoprost-induced iris darkening: a morphometric study of human peripheral iridectomies.

Abstract Purpose. This microscopic study was undertaken to compare the melanocytes of peripheral iridectomy specimens from two eyes that had latanoprost-induced iris darkening (LIID) with iridectomies taken from the fellow untreated eyes. Methods. The two patients in this study were the ones who underwent LIID in the latanoprost treated eye from a series of 17 patients requiring bilateral trabeculectomy. The first trabeculectomy procedure provided a control peripheral iridectomy for each patient, whereas the second eye was treated with once daily 50 μg ml−1 latanoprost drops for 6 months. The four peripheral iridectomy specimens from the two LIID patients were subjected to quantitative morp…

Serological Levels of Anti-clathrin Antibodies Are Decreased in Patients With Pseudoexfoliation Glaucoma

Evidence for immunologic contribution to glaucoma pathophysiology is steadily increasing in ophthalmic research. Particularly, an altered abundance of circulating autoantibodies to ocular antigens is frequently observed. Here, we report an analysis of autoantibody abundancies to selected antigens in sera of open-angle glaucoma patients, subdivided into normal-tension glaucoma (N = 31), primary open-angle glaucoma (N = 43) and pseudoexfoliation glaucoma (N = 45), vs. a non-glaucomatous control group (N = 46). Serum samples were analyzed by protein microarray, including 38 antigens. Differences in antibody levels were assessed by ANOVA. Five serological antibodies showed significantly altered…

Structure-function relationship between FDF, FDT, SAP, and scanning laser ophthalmoscopy in glaucoma patients.

Purpose Flicker defined form perimetry (FDF) and frequency doubling technology perimetry (FDT) are alleged to detect glaucoma at an earlier stage than standard automated perimetry (SAP). It is the purpose of this study to investigate the structure-function relationship between FDF, FDT, SAP, and confocal scanning laser ophthalmoscopy (cSLO) in patients with glaucoma. Methods Seventy-six patients with glaucoma were included in the study. Patients were tested with SAP, Matrix-FDT, FDF perimetry, and cSLO. Structure-function relationships between global and sectoral cSLO parameters and global and sectoral mean sensitivity (MS) of SAP, Matrix-FDT, and FDF were calculated using Spearman's rank c…

Proinflammatory Cytokine Profiling of Tears from Dry Eye Patients by Means of Antibody Microarrays

In the pathogenesis of keratoconjunctivitis sicca, immune processes are thought to play an important role. However, the exact details of the pathomechanisms are still unknown. In this study, the expression patterns of proinflammatory cytokines in the tears of patients with different subtypes of dry eye were analyzed.One hundred forty-three subjects subdivided into healthy controls (CTRL, n = 38), patients with aqueous-deficient dry eye (DRYaq, n = 35), patients with changes of the lipid layer (DRYlip, n = 36), and patients with a combination of both (DRYaplip, n = 34) were examined. Expression patterns of proteins (e.g., IL-1β, IL-6, ITNF-α, and IFN-γ) were examined using an advanced antibo…

Survival After Transplantation of Corneas From a Rabies-Infected Donor

To examine the tissue samples of 2 corneal recipients from a rabies-infected donor for the presence of rabies to explain their survival.Interventional case series with a review of the literature. The explanted corneal donor buttons were examined via nested reverse transcriptase polymerase chain reaction. The patients were followed up ophthalmologically and neurologically. Antirabies antibodies were measured in blood samples, and skin biopsies were examined by direct fluorescent antibody staining.Two patients received corneas from the same multiorgan donor. Six weeks after transplantation, 3 of the donor's organ recipients became symptomatic and rabies virus was confirmed in tissue from the …

Spontaneous Resolution of Delayed Suprachoroidal Hemorrhage in the Single Eye Following Needling in Congenital Glaucoma

Suprachoroidal hemorrhage (SCH) is a rare, but potentially vision-threatening event with poor long-term visual prognosis. At present, there is disagreement whether surgical intervention or conservative treatment is superior in the management. We report on a case of spontaneous resolution of severe SCH after needling procedure in the only eye of a young patient with congenital glaucoma.A 43-year-old woman with congenital glaucoma was scheduled for bleb needling in her only eye. Preoperative best-corrected visual acuity was 20/40 and intraocular pressure 20 mm Hg. On the third postoperative day, she developed a massive delayed SCH with appositional (kissing) choroidal bullae and visual acuity…

Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe

International audience; Background: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. Methods: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the…

Influence of Corneal Opacity on Intraocular Pressure Assessment in Patients with Lysosomal Storage Diseases

Aims To investigate an influence of mucopolysaccharidosis (MPS)- and Morbus Fabry-associated corneal opacities on intraocular pressure (IOP) measurements and to evaluate the concordance of the different tonometry methods. Methods 25 MPS patients with or without corneal clouding, 25 Fabry patients with cornea verticillata ≥ grade 2 and 25 healthy age matched controls were prospectively included into this study. Outcome measures: Goldmann applanation tonometry (GAT); palpatory assessment of IOP; Goldmann-correlated intraocular pressure (IOPg), corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH) assessed by Ocular Response Analyzer (ORA…

A European Study of the Performance and Safety of MINIject in Patients With Medically Uncontrolled Open-angle Glaucoma (STAR-II)

Precis In this European study (STAR-II), MINIject, a novel, ab-interno, supraciliary MIGS device, effectively lowered intraocular pressure (IOP) and the need for IOP-lowering medications in patients with primary open-angle glaucoma. Purpose To evaluate the safety and performance of a minimally invasive supraciliary glaucoma drainage device (MINIject DO627, iSTAR Medical SA, Wavre, Belgium) for surgical treatment of primary open angle glaucoma in patients refractory to topical hypotensive medications. Methods In a prospective, interventional, single-arm, multi-center, European study (STAR-II), MINIject was successfully implanted in a standalone procedure in 29 of 31 patients in 8 sites in 3 …

Characteristics and pathologies of the vitreo‐macular interface—results from the Gutenberg Health Study

Purpose We aimed to determine the prevalence of characteristics and pathologies of the vitreo-macular interface within the general population. Methods The Gutenberg Health Study is a population-based study in Germany, including an ophthalmological examination with refraction, biometry and optical coherence tomography (OCT) imaging. Characteristics of the vitreo-macular interface were graded on volume scans including visibility of an epiretinal membrane, full-thickness macular hole, lamellar hole and pseudohole. Overall and age-specific prevalences including 95% confidence intervals [95%-CI] were calculated. Association analyses were conducted to determine systemic and ocular factors that ar…

Fallzahlplanung bei ophthalmologischen Studien*

An essential aspect in the cooperation of clinic and biometry consists in designing of studies, e.g. during the preparation of grant applications or for review by official drug surveillance institutions. A central aspect in study planning is the design-adequate and well-documented prediction of sample size, which should be recommended for any intended study. Based on several examples for sample size planning in study designs, which are of common relevance for ophthalmology, guidelines are derived to enable clinical researchers to perform sample size planning on their own. The latter can be based on the various available software packages for sample size prediction.

Implantation of the modified endocapsular bending ring in pediatric cataract surgery using a viscoadaptive viscoelastic agent.

Cataract surgery and intraocular lens (IOL) implantation in pediatric eyes remain controversial. Using a viscoadaptive viscoelastic agent, we implanted a modified capsular bending ring (CBR) as well as an acrylic IOL with a sharp-optic-edge design in the capsular bag. All operated eyes demonstrated a low postoperative inflammatory reaction and a clinically well-centered IOL. The band-shaped, sharp-edged CBR facilitates the creation of a sharp, discontinuous bend in the equatorial capsule, which prevents anterior and posterior capsule opacification. Combining the viscoadaptive viscoelastic agent and the CBR enhances the safety of primary and secondary posterior chamber IOL implantation in pe…

Irregularity of the posterior corneal surface during applanation using a curved femtosecond laser interface and microkeratome cutting head.

PURPOSE: To evaluate the irregularity of the posterior corneal surface and intrastromal dissection during the preparation of donor tissue for Descemet stripping automated endothelial keratoplasty (DSAEK) using a curved interface femtosecond laser and microkeratome. METHODS: Sixteen human donor corneas unsuitable for transplantation were divided into two groups: a femtosecond (FS) laser group (n=7) using the VisuMax femtosecond laser (Carl Zeiss Meditec) and a microkeratome group (n=9) using the Amadeus II microkeratome (Ziemer Ophthalmic Group). The corneas were fixed on artificial anterior chambers. Horizontal cross-sections were obtained using spectral-domain optical coherence tomography…

The Prevalence of Visual Impairment in the Adult Population

Background The distribution of visual impairment is an indicator of the health status of the population and for the frequency of diseases of the eye. Methods The Gutenberg Health Study (GHS) is a population-based cohort study in Germany concerning adults aged 35 to 74. 15 010 subjects from the Mainz-Bingen region underwent general medical and ophthalmological examination, with measurement of the distance-corrected visual acuity in each eye separately. As per the World Health Organization criteria, visual impairment was defined as an acuity below 0.3 in the better eye, and blindness as an acuity below 0.05. All patients who were found to be visually impaired or blind underwent further indivi…

Utilization of metabolic energy in treatment of ocular surface disorders: polyphosphate as an energy source for corneal epithelial cell proliferation.

Impaired regeneration of the corneal epithelium, as found in many ocular surface diseases, is a major clinical problem in ophthalmology. We hypothesized that corneal epithelial regeneration can be promoted by the physiological, energy-delivering as well as “morphogenetically active” polymer, inorganic polyphosphate (polyP). Corneal limbal explants (diameter, 4 mm) were cultivated on collagen-coated well plates in the absence or presence of polyP (chain length, ∼40 Pi units; 50 μg ml−1) or human platelet lysate (hp-lysate; 5% v/v). Cell outgrowth and differentiation were analyzed after staining with DRAQ5 (nuclei) and rhodamine phalloidin (cytoskeleton), as well as by environmental scanning …

Series of fibrinous inflammation after implantation of capsular tension rings

Purpose To analyze the cause of fibrinous inflammation in eyes with capsular tension rings (CTRs) after cataract surgery. Setting Department of Ophthalmology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany. Design Retrospective case series. Methods High-performance liquid chromatography was implemented to eliminate impurities. One CTR was explanted for microbiologic examination. The pH values of the CTR and the storage solution were analyzed, Seldi and Maldi tests were performed, as well as toxicity tests with immortal cell lines. Material batches were analyzed. The organic carbon content of CTRs, detergents, and storage solutions was checked. The presence of…

Responses of retinal arterioles and ciliary arteries in pigs with acute respiratory distress syndrome (ARDS)

Abstract Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute lung failure in critically sick patients, which severely compromises the function of multiple organs, including the brain. Although, the optic nerve and the retina are a part of the central nervous system, the effects of ARDS on these ocular structures are completely unknown. Thus, the major goal of this study was to test the hypothesis that ARDS affects vascular function in the eye. ARDS was induced in anesthetized pigs by intratracheal injection of lipopolysaccharide (LPS). Sham-treated animals served as controls. Pigs were monitored for 8 h and then sacrificed. Subsequently, retinal arterioles and short p…

Addition of a fixed combination of brinzolamide 1%/timolol 0.5% to prostaglandin monotherapy in patients with glaucoma or ocular hypertension

Katrin Lorenz1, Klaus Rosbach2, Andreas Matt3, Norbert Pfeiffer11University Medical Center, Johannes Gutenberg-Universit&amp;auml;t Mainz, Mainz, Germany; 2Private practice, Mainz, Germany; 3Private practice, K&amp;ouml;ln-Hohenhaus, GermanyBackground: This study was conducted to evaluate the safety and efficacy of adding a fixed combination of brinzolamide 1%/timolol 0.5% to prostaglandin analog (PGA) monotherapy in patients with primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension who require additional intraocular pressure (IOP) reduction.Methods: This was a prospective, multicenter (n = 5), open-label, single-arm, Phase IV clinical trial in which patients cur…

Atrial Fibrillation Manifestations Risk Factors and Sex Differences in a Population-Based Cohort (From the Gutenberg Health Study)

Sex differences in cardiovascular risk factors, cardiac structure and function, and disease and symptom burden in the common arrhythmia atrial fibrillation (AF) have not been investigated systematically at the population level. Cross-sectional data of 14,796 subjects (age range 35 to 74 years, 50.5% men) from the population-based Gutenberg Health Study were examined to show the distribution of cardiovascular risk factors by AF status and sex, and to determine sex-specific predictors for AF. The prevalence of AF was higher in men (4.3%) than in women (1.9%). Men had a worse cardiovascular risk factor profile, a higher prevalence of cardiovascular disease, but fewer symptoms than women. Age-a…

Update on topical carbonic anhydrase inhibitors

Topical carbonic anhydrase inhibitors are a novel addition to the armamentarium of medical glaucoma treatment; dorzolamide has been available since 1995 and brinzolamide since 1998. They lower intraocular pressure by inhibiting carbonic anhydrase, a key enzyme for aqueous humor formation. Intraocular pressure-lowering activity of the substances appears to be the same and is similar to that of most other agents, but it does not reach the activity of the unselective beta-blocker timolol or the prostaglandin latanoprost. On concomitant treatment, additivity is reached with all other topical agents. A possible improvement of blood flow may offer an additional benefit, but its significance for t…

Visualization of corneal vascularization in peripheral hypertrophic subepithelial corneal opacification with OCT angiography.

Purpose The major goal of this study was to test the hypothesis that in patients with peripheral hypertrophic subepithelial corneal opacification (PHSCO), visualization of corneal vessels is better with optical coherence tomography angiography (OCTA) than with conventional slit lamp microphotography. Methods Patients with PHSCO were included in this prospective study. The corneal findings were photographed using a slit lamp camera (Haag Streit BM 900® ) and visualized with anterior-segment OCT (Optovue XR Avanti, Fremont, California, USA). Additionally, OCTA with the Angiovue Imaging™ System was performed in the area of PHSCO. Results Thirty-four eyes of 19 patients (26% male and 74% female…

Is there a relationship between the degree of preoperative motility impairment or the muscle thickness and the outcome of strabismus surgery in patients with graves' orbitopathy after decompression surgery?

There is considerable controversy regarding the performance of strabismus surgery in patients with Graves' orbitopathy (GO). The spectrum of recommendations extends from variable dose-effect correlations for these procedures (Esser, 1994; Mourits et al., 1990; Nguyen et al., 2002) to individualized approaches such as passive intraoperative motility testing and postoperative adjustment of sutures (Lueder et al., 1992; Nguyen et al., 2002), and to local anesthesia for intraoperative assessment of active motility (Kalpadakis et al., 2004). Furthermore, prior decompression surgery is known to contribute to an unpredictable outcome (Eckstein and Esser, 2003; Esser, 1994). We retrospectively anal…

Association of Type D personality with cognitive functioning in individuals with and without cardiovascular disease: The Gutenberg health study

ObjectiveDistressed (‘Type D’) personality is associated with adverse health outcomes in patients with cardiovascular disease (CVD). While personality traits from the Five-Factor Model are related to cognitive functioning, neither Type D personality nor its underlying traits negative affectivity (NA) and social inhibition (SI) have been investigated regarding cognition. We therefore compared the predictive value of Type D classification and its subcomponents NA and SI on planning performance in individuals with and without CVD.MethodsType D personality traits (DS14) were determined in a population-based sample of 4026 participants (including 549 with CVD) aged 40–80 years from the Gutenberg…

Linking cancer and mental health in men and women in a representative community sample

Abstract Objective In aging populations, a growing number of individuals are affected by cancer. However, the relevance of the disease for mental health is still controversial, especially after treatment. We drew from a representative community sample to explore the link of cancer with mental health assessing different dimensions and different periods of time. Methods A cohort of 14,375 men and women (35–74 years) underwent medical assessments and was queried about cancer history, previous diagnoses of mental disorders, current mental distress symptoms, and current subjective health appraisal. Results 1066 participants (7.4%) reported a diagnosis of cancer (survival time M = 9.79 (SD = 9.07…

Refractive lens exchange with an array multifocal intraocular lens.

ABSTRACT PURPOSE: To prospectively evaluate safety, efficacy, predictability, stability, complications, and patient satisfaction after refractive lens exchange (clear lens extraction) followed by posterior chamber implantation of a multifocal intraocular lens (IOL). METHODS: Fifty eyes of 25 patients (mean age 51 years, range 44 to 62 years) with preoperative spherical equivalent refraction between -15.50 and +5.75 D and cylinder between 0 and 1.50 D underwent bilateral implantation of a zonal progressive multifocal IOL (Array, AMO). RESULTS: Eyes were divided into group A (n=24; myopia, average preoperative spherical equivalent refraction -7.11 ± 3.25 D (-1.75 to -15.50 D), and group B (n=…

Predictive value of heidelberg retina tomograph parameters for the development of glaucoma in the European glaucoma prevention study

Purpose To determine whether baseline Heidelberg Retina Tomograph (HRT) measurements of the optic disc are associated with the development of open-angle glaucoma (OAG) in individuals with ocular hypertension in the European Glaucoma Prevention Study (EGPS). Design Retrospective analysis of a prospective, randomized, multicenter, double-masked, controlled clinical trial. Methods There were 489 participants in the HRT Ancillary Study to the EGPS. Each baseline HRT parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of OAG. Proportional hazards models were used to identify HRT variables that predicted which partici…

PREVALENCE AND ASSOCIATIONS OF MYELINATED RETINAL NERVE FIBERS

PURPOSE To determine the prevalence, ocular, and systemic associations of myelinated retinal nerve fibers (MRNF) in a Caucasian cohort. METHODS The Gutenberg Health Study (GHS) is a population-based, prospective cohort study encompassing 15,010 subjects in Germany. Gutenberg Health Study participants, aged 35 to 74 years, stratified for gender, decades of age, and residence were examined for ophthalmologic and systemic conditions. Optic disc centered and macular photographs were reviewed for the presence of MRNF. RESULTS In 25,728 eyes of 12,906 participants (86.0% of the cohort), the prevalence of MRNF was 0.4%. In a binary logistic regression analysis, MRNF was positively associated with …

Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study.

Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (β, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (β, 0.178; 95% CI, 0.128 to 0.229), hypertension (β, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (β, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV i…

Efficacy and safety of preoperative IOP reduction using a preservative-free fixed combination of dorzolamide/timolol eye drops versus oral acetazolamide and dexamethasone eye drops and assessment of the clinical outcome of trabeculectomy in glaucoma

Introduction To demonstrate that preoperative treatment for 28 days with topical dorzolamide/timolol is non-inferior (Δ = 4 mm Hg) to oral acetazolamide and topical dexamethasone (standard therapy) in terms of intraocular pressure (IOP) reduction 3 and 6 months after trabeculectomy in glaucoma patients. Materials and methods Sixty-two eyes undergoing trabeculectomy with mitomycin C were included in this monocentric prospective randomized controlled study. IOP change between baseline and 3 months post-op was defined as the primary efficacy variable. Secondary efficacy variables included the number of 5-fluorouracil (5-FU) injections, needlings, suture lyses, preoperative IOP change, hyperten…

The efficacy and safety of unfixed and fixed combinations of latanoprost and other antiglaucoma medications.

Adjunctive therapy for the management of glaucoma is commonly used. Unfixed combinations of the prostaglandin analog latanoprost and other glaucoma medications have been demonstrated to effectively lower intraocular pressure (IOP). The range of reported additional reductions in IOP compared to a monotherapy baseline are as follows: latanoprost-timolol (13-37%), latanoprost-pilocarpine 2% (7-14%), latanoprost and carbonic anhydrase inhibitors (15-24.1%), and latanoprost and dipivefrin (15-28%). There is a fixed combination of latanoprost (0.005%) and timolol (0.5%) that has been investigated in Phase III trials in Europe and the United States. In these trials, it was noted that the efficacy …

A New Method for Revision of Encapsulated Blebs after Trabeculectomy: Combination of Standard Bleb Needling with Transconjunctival Scleral Flap Sutures Prevents Early Postoperative Hypotony

Purpose A simple needling procedure is the standard method for restoring the function of an encapsulated bleb after trabeculectomy. However, postoperative hypotony represents a possible hazard. This study describes a new surgical approach for treating encapsulated blebs with reduced risk of early postoperative hypotony: bleb needling combined with transconjunctival sutures tightening the scleral flap directly. Methods The study included two groups of 23 patients with failing bleb following trabeculectomy: “Group 1” underwent simple needling revision of the filtering bleb and served as a control group, while “Group 2” received needling revision with additional transconjunctival scleral flap …

Schirmer test results: are they associated with topical or systemic medication?

To test whether Schirmer test (ST) results are associated with topical or systemic medication and to evaluate the distribution of tear fluid quantity in a 3-min and 5-min ST.The Gutenberg Health Study is a population-based, prospective, observational cohort study in Germany. ST was assessed in a sub-cohort of 1,999 participants. ST was performed under topical anesthesia for 5 min (ST-5) or of 3 min (ST-3). Anthropometric factors, systemic diseases, use of systemic and eye medications were recorded. We used multivariable quantile regression analysis to assess the influence on ST measurements.The length of wetting of the Schirmer strips for ST-5 was 23.2 ± 9.31 mm for right and 22.9 ± 9.0 mm …

Innovative Glaukomtherapie

Lokale Karboanhydrasehemmer wurden mit Dorzolamid 1995 in die medikamentose Glaukomtherapie eingefuhrt. Im Jahr 2000 wurde nun ein zweiter topischer Karboanhydrasehemmer auf dem deutschen Markt eingefuhrt: Brinzolamid. Die augeninnendrucksenkende Wirkung beider Medikamente ist vergleichbar bei einem etwas unterschiedlichen Nebenwirkungsprofil. Die Breitenanwendung von Dorzolamid zeigt ein positives Nutzen/Risiko-Verhaltnis. Eine Kombinationstherapie mit lokalen Karboanhydrasehemmern bewirkt zusatzlich zu allen anderen topischen Glaukommedikamenten eine weitere Drucksenkung. Zudem liegen im Tierversuch erste Hinweise vor, dass Dorzolamid druckunabhangig die Durchblutungssituation am hinteren…

Effects of Early Postfiltration Ocular Hypotony on Visual Acuity, Long-term Intraocular Pressure Control, and Posterior Segment Morphology

Purpose To determine whether hypotony after filtration surgery has any influence on visual acuity and intraocular pressure (IOP) lowering. Patients and methods We prospectively investigated 43 eyes of 43 patients undergoing trabeculectomy without the use of antimetabolites for 12 months. Results The lowest postoperative IOP valued 4.9 +/- 3.6 mm Hg (range, 0-14 mm Hg). It correlated statistically significant with the IOP 6 weeks (P = 0.016), 6 months (P = 0.009), and 1 year after surgery (P = 0.027). Eyes with a deterioration of visual acuity 6 weeks after surgery had undergone a stronger postoperative hypotony (correlation with lowest postoperative IOP, P = 0.035). The mean period with an …

Lipid-Mediated Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample

Abstract Background: Tissue factor pathway inhibitor (TFPI), a Kunitz-type serine protease, is a potent anticoagulant protein in the extrinsic coagulation pathway and acts by inhibiting both the FXa and the Tissue Factor-FVIIa complex. In contrast to total and free TFPI antigen levels, the reference values and clinical determinants of total TFPI activity have not yet been studied in detail in the general population. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and investigate its association with cardiovascular disease (CVD) and total mortality, in a population at large. Methods: For this study, the first 4779 subjects of the population-ba…

Changes in ocular signs and symptoms when switching from preserved latanoprost 0.005% to preservative-free tafluprost 0.0015%: phase IIIb study in patients with open-angle glaucoma or ocular hypertension

Purpose This open-label, multinational, phase IIIb study investigated the changes in ocular signs and symptoms when patients were switched from preserved latanoprost 0.005% to preservative-free tafluprost 0.0015% (q.d. at 20:00) for 12 weeks. Methods Patients with open-angle glaucoma or ocular hypertension who had received latanoprost for at least 6 months and had at least 2 ocular symptoms or one symptom and one sign were enrolled (n=158). Change from screening in ocular symptoms and signs were the main endpoints. Data from the 6-week analysis are reported here. Results After switching to preservative-free tafluprost, the proportion of patients with at least mild symptoms decreased: irrita…

Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample.

Abstract Objective Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant protein in the extrinsic coagulation pathway. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and its association with cardiovascular disease (CVD) and total mortality. Methods Total TFPI activity was assessed in a selection of the population-based Gutenberg Health Study (n = 5,000). Statistical analysis was performed to identify the determinants for total TFPI activity as well as the associations with CVD and mortality. Results Multivariable linear regression analysis identified smoking (β 0.095 [0.054–0.136]) as a positive determinant for total TFPI activity…

Cholinergic Responses of Ophthalmic Arteries in M3and M5Muscarinic Acetylcholine Receptor Knockout Mice

PURPOSE. To determine the functional role of M 3 and M 5 muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice. METHODS. Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M 3 and M 5 receptors, ophthalmic arteries from mice deficient in either subtype (M3R -/- , M5R -/- , respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal vessel diameter in response to muscarinic and nonmuscarinic receptor agonists were measured by video microscopy. RESULTS. With the use of real-time PCR, all five muscarinic receptor …

Vacuoles in the Acrysof&lt;sup&gt;TM&lt;/sup&gt; Intraocular Lens as Factor of the Presence of Serum in Aqueous Humor

&lt;i&gt;Objective:&lt;/i&gt; Acrysof™ (Alcon) foldable lenses (IOLs) have been shown to be highly biocompatible and exhibit a low incidence of posterior capsular opacification. However, minute vacuoles or ‘glistenings’ have been observed in some Acrysof IOLs. The clinical relevance of vacuole formation is presently unclear. To help clarify the influence of factors present under in vivo conditions on vacuole formation, the present experimental study examines the influence of aqueous humor components on the occurrence of vacuoles in Acrysof IOLs. &lt;i&gt;Methods:&lt;/i&gt; A total of 12 sterile Acrysof IOLs (Alcon, MA60BM) were incubated at body temperature (37°C) for 3 or 6 months in anter…

Hornhaut-Tätowierung

The Evonik-Mainz Eye Care-Study (EMECS): Development of an Expert System for Glaucoma Risk Detection in a Working Population

Purpose To develop an expert system for glaucoma screening in a working population based on a human expert procedure using images of optic nerve head (ONH), visual field (frequency doubling technology, FDT) and intraocular pressure (IOP). Methods 4167 of 13037 (32%) employees between 40 and 65 years of Evonik Industries were screened. An experienced glaucoma expert (JW) assessed papilla parameters and evaluated all individual screening results. His classification into “no glaucoma”, “possible glaucoma” and “probable glaucoma” was defined as “gold standard”. A screening model was developed which was tested versus the gold-standard. This model took into account the assessment of the ONH. Valu…

Ocular pulse amplitude in patients with open angle glaucoma, normal tension glaucoma, and ocular hypertension.

Intraocular pressure (IOP) is not a fixed constant value but rather has pulsatile components associated with cardiac action. The SmartLens dynamic observing tonometer (odc, Ophthalmic Development Company AG, Zurich, Switzerland) can measure and record simultaneously IOP and ocular pulse amplitude (OPA). It was the aim of this study to evaluate OPA in patients with primary open angle glaucoma (POAG) and high IOP, normal tension glaucoma (NTG), and ocular hypertension (OHT). Furthermore, the authors examined whether there were any correlations with blood pressure.80 subjects were divided into four groups (n=20): 20 patients each with POAG, NTG, and OHT and 20 volunteers without any ocular pat…

Analysis of the Corneal Anterior and Posterior Surface in Patients With Peripheral Hypertrophic Subepithelial Corneal Opacification

PURPOSE To characterize the corneal changes in peripheral hypertrophic subepithelial corneal opacification (PHSCO) considering elevation of the anterior and posterior corneal surface, corneal astigmatism, tear secretion, and endothelial cell density. METHODS Thirty-eight eyes of 22 patients with PHSCO on at least 1 eye and 38 eyes of 22 age- and sex-matched healthy subjects were included in this retrospective cross-sectional study. Using the Pentacam system (Oculus, Wetzlar, Germany), measurement of the anterior and posterior corneal surface was performed. In addition, the Schirmer test was conducted, and endothelial cells were counted in the central cornea with a specular microscope (SP-30…

Objective and subjective evaluation of photic phenomena after monofocal and multifocal intraocular lens implantation11The authors have no commercial or financial interest in any aspect of this study.

Abstract Objective To objectively measure and compare halo, flicker, and glare disability in pseudophakic eyes with monofocal (MONO) and multifocal (MULTI) intraocular lenses (IOLs) with respect to the influence of corneal surface quality, astigmatism, and age. Design Prospective case series. Participants This clinical trial involved 28 eyes of 28 patients after small-incision cataract surgery with a MONO silicone IOL and 28 eyes of 28 patients with zonal-progressive silicone IOL. Intervention A computer program objectively determined halo, glare, and flicker. Corneal surface quality and astigmatism were measured using computerized videokeratography. Ray-tracing analysis was performed based…

Akute Retinanekrose

Einfuhrung: Da Studien zur Behandlung der akuten Retinanekrose (ARN) inzidenzbedingt kleine Fallzahlen haben und alle verfugbaren Daten zusammengetragen werden mussen, berichten wir uber unsere operativen Ergebnisse bei Netzhautablosungen durch ARN. Patienten und Methode: Nachuntersucht wurden 13 Augen von 13 Patienten mit Netzhautablosung bei ARN, die konsekutiv in unserer Klinik zwischen Januar 1988 und Juni 1995 operiert wurden. Das Patientenalter betrug 25 – 56 Jahre. Vier Patienten waren HIV-positiv, 9 Patienten immunkompetent. Bei 5 Patienten, die primar mit segmentalen Plomben versorgt worden waren, wurde eine Vitrektomie mit Membrane peeling, Silikonolendotamponade und Endolaserbeha…

Quality of Life and Occupational Disability in Endocrine Orbitopathy

SUMMARY Background: In endocrine orbitopathy (EO), disfiguring proptosis and diplopia impair patients' quality of life both at home and at work. Methods: From late 2006 to the beginning of 2008, 250 outpatients in an interdisciplinary thyroid and eye clinic filled out a questionnaire about their quality of life, occupational disability, and use of psychotherapy. 400 physicians who referred their EO patients to the clinic also participated in a survey on these issues. Results: 45% of the patients complained of restrictions in their daily activities, and 38% reported impaired selfperception. 36% were on sick leave because of EO. 28% were disabled, 5% had retired early, and 3% had lost their j…

Peripapillary fluorescence lifetime reveals age-dependent changes using fluorescence lifetime imaging ophthalmoscopy in rats

Abstract Many fundus diseases accompany fundus autofluorescence change. Fluorescence lifetime imaging ophthalmoscope (FLIO) is a latest technique in imaging fundus autofluorescence. With FLIO, the fundus fluorescence lifetime (FLT) is recorded topographically, assisting to diagnose and monitor multiple fundus diseases. The purpose of this study was to evaluate the repeatability of FLT using FLIO on adult rats and to analyze the age-dependency of the peripapillary FLT of the fundus in a short spectral channel (498–560 nm) and a long spectral channel (560–720 nm). Sprague Dawley rats (n of eyes = 10) were used for repeatability experiments. Age-dependent changes were investigated in young (tw…

P5361The diabetic continuum and its relation with cardiovascular disease: results from the population-based Gutenberg health study

Suture Removal After Trabeculectomy With Fornix-based Conjunctival Flap Leads to Faster Visual Recovery but Not Reduced Astigmatism

PReCIS:: The closing limbal suture after trabeculectomy with a fornix-based conjunctival flap plays no critical role in the development of corneal astigmatism and intraocular pressure (IOP). A standard removal is not recommended. Purpose To investigate the effect of removal of the conjunctival suture after trabeculectomy with fornix-based conjunctival flap on corneal astigmatism, visual acuity, and IOP. Methods Eighty-seven cases of trabeculectomy with mitomycin C with a fornix-based conjunctival flap performed in the eyes of 82 patients (5 patients underwent bilateral trabeculectomy) were enrolled in a prospective randomized study. All surgeries were conducted by the same surgeon (J.W.) in…

Optical Coherence Tomography in Glaucoma

Retinal nerve fiber layer (RNFL) thinning and optic nerve head cupping are key diagnostic features of glaucomatous optic neuropathy. The higher resolution of the recently introduced SD-OCT offers enhanced visualization and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.

Learning Curve and Fatigue Effect of Flicker Defined Form Perimetry

To evaluate the learning curve and fatigue effect of flicker defined form (FDF) perimetry.Prospective cross-sectional study.One hundred forty-one eyes of 75 healthy subjects were included in the study. Every subject was measured 3 times on 3 different days within 3 months. Differences among the tests were analyzed for mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), reliability indices, test duration, and test points5% and0.5% in 75 right eyes on the basis of linear mixed models for repeated measurements. To assess the effect of fatigue, differences of MS, MD, and PSD values between 66 left and right eyes were evaluated regarding alterations between these 3 exam…

Correlations between central corneal thickness and general anthropometric characteristics and cardiovascular parameters in a large European cohort from the Gutenberg Health Study.

PURPOSE The aim of this study was to evaluate the correlations between general anthropometric features and cardiovascular parameters and central corneal thickness (CCT) in an adult European cohort. METHODS Analysis was based on a Gutenberg Health Study cohort that included 5000 subjects (2540 male, 2460 female), aged 35 to 74 years at enrollment. The participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination (slit-lamp biomicroscopy; autorefractometry; noncontact tonometry; fundus photography; CCT measurements (optical pachymetry); visual field testing; and a thorough general examination focused on cardiovascular parameters, psychosomatic evalu…

XEN-augmented Baerveldt Implantation for Refractory Childhood Glaucoma: A Retrospective Case Series

Background Tube implants can lead to long-term decompensation of the cornea after decades, in particular in complicated childhood glaucoma, because of a variety of causes including contact between the tube tip and the corneal endothelium. The augmentation of a XEN implant with a Baerveldt (250) tube implant, introduced 2016 by Mermoud et al for refractory glaucoma in adult patients, may reduce this risk in children. In our retrospective study, we report on the XEN-augmented Baerveldt (250) tube implant in children. Patients and methods Ten consecutive patients with refractory childhood glaucoma who underwent XEN-augmented Baerveldt implantation by a single surgeon (F.G.) between January 201…

Sample Preparation for Mass-spectrometry-based Proteomics Analysis of Ocular Microvessels

The use of isolated ocular blood vessels in vitro to decipher the pathophysiological state of the eye using advanced technological approaches has greatly expanded our understanding of certain diseases. Mass spectrometry (MS)-based proteomics has emerged as a powerful tool to unravel alterations in the molecular mechanisms and protein signaling pathways in the vascular beds in health and disease. However, sample preparation steps prior to MS analyses are crucial to obtain reproducible results and in-depth elucidation of the complex proteome. This is particularly important for preparation of ocular microvessels, where the amount of sample available for analyses is often limited and thus, pose…

Chronic venous insufficiency, cardiovascular disease, and mortality: a population study

Abstract Aims  Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. Methods and results  Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was…

Cigarette Smoking Is Related to Endothelial Dysfunction of Resistance, but Not Conduit Arteries in the General Population—Results From the Gutenberg Health Study

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit an…

Peptides of the variable IgG domain as potential biomarker candidates in primary open-angle glaucoma (POAG)

Autoantibody profiling has gained increasing interest in the research field of glaucoma promising the detection of highly specific and sensitive marker candidates for future diagnostic purposes. Recent studies demonstrated that immune responses are characterized by the expression of congruent or similar complementarity determining regions (CDR) in different individuals and could be used as molecular targets in biomarker discovery. Main objective of this study was to characterize glaucoma-specific peptides from the variable region of sera-derived immunoglobulins using liquid chromatography--mass spectrometry (LC-MS)-based quantitative proteomics. IgG was purified from sera of 13 primary open…

FEV1 and FVC predict all-cause mortality independent of cardiac function - Results from the population-based Gutenberg Health Study.

Abstract Background Lung function has previously been related to increased mortality. Whether pulmonary impairment is associated with an increased mortality independent of cardiac dysfunction remains unclear. Methods In 15010 individuals from the general population (age range 35–74years, 51% men) in the Gutenberg Health Study we performed spirometry and transthoracic echocardiography. N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (hsTnI) were measured in all individuals. 1819 individuals with pulmonary diseases were excluded from further analysis. Results The median for forced expiratory volume in 1s (FEV1) was 94.2% and for forced vital capacity (FVC) …

Is assessment of depression equivalent for migrants of different cultural backgrounds? Results from the German population-based Gutenberg Health Study (GHS)

BACKGROUND Bearing in mind the multicultural background of a national population, little is known about the measurement invariance across different cultures or ethnicities of frequently used screeners for depression. For this reason, the main objective of the current study is to assess the measurement invariance of the Patient Health Questionnaire (PHQ-9) across groups with different migration backgrounds. METHODS We provided psychometric analyses (descriptive statistics at item and scale level, reliability analysis, exploratory [EFA] and confirmatory factor analyses [CFA]) comparing a native population with first- and second-generation migrants of the German population-based Gutenberg Heal…

Course of serum autoantibodies in patients after acute angle-closure glaucoma attack

Background The aim of our current investigation was to analyze the autoantibody -reactivities of patients after acute angle closure glaucoma (AACG) by means of a protein microarray approach to identify intraocular pressure (IOP)-dependent antibodies. Methods Collected sera from different study time points (AACG n = 6, 0, 2, 4 and 12 weeks) and control group (CTRL n = 11, 0 and 12 weeks) were analyzed. Protein-microarrays were incubated with sera and occurring immunoreactivities were visualized with fluorescence labeled anti-human-IgG antibodies. To detect changes, spot intensities were digitized and compared with statistical techniques. Results Three autoantibodies with significant level-al…

Five-year change in refractive error and its risk factors: results from the Gutenberg Health Study.

Background/AimsTo examine the 5-year change in refractive error in phakic eyes and its risk factors in the general population.MethodsThe Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants from Germany aged 35–74 years at baseline examination (2007–2012). After 5 years, a follow-up examination was carried out (83% participation). 5-year change of spherical equivalent (SE) was computed as difference between follow-up and baseline objective refraction. Linear and logistic regression analysis were conducted analysing potential risk factors. Only phakic eyes at follow-up examination were included.ResultsRight eyes of 10 175 subjects were included. An ag…

The Evonik-Mainz-Eye-Care-Study (EMECS): Design and Execution of the Screening Investigation

Purpose To determine if screening for major ophthalmological diseases is feasible within the frame of routine occupational medicine examinations in a large working population. Methods 13037 employees of Evonik Industries aged 40 to 65 years were invited to be screened for major ophthalmological diseases (glaucoma, age related macular degeneration and diabetic retinopathy between June 2007 and March 2008 within an extended setting of occupational medicine. Ophthalmological examinations consisted of visual acuity, objective refraction, pachymetry, tonometry, perimetry (frequency doubling technology), confocal scanning laser ophthalmoscopy and digital fundus photography. Participants responded…

Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopi…

Annoyance to different noise sources is associated with atrial fibrillation in the Gutenberg Health Study

Abstract Background Annoyance is a common reaction in populations exposed to environmental noise and is associated with cardiovascular diseases. We investigated for the first time the existence of an association between noise annoyance and atrial fibrillation (AF). Methods and results Cross-sectional data from 14,639 participants of the Gutenberg Health Study were collected between 2007 and 2012. Annoyance from road traffic, aircraft, railways, industrial/construction and neighbourhood noise during daytime and sleep were collected from all participants through questionnaires using a 5-point scale. AF was assessed via self-reported medical history and/or documentation of AF on the study elec…

The distribution of whole blood viscosity, its determinants and relationship with arterial blood pressure in the community: cross-sectional analysis from the Gutenberg Health Study.

Background: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study. Methods and results: Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, mi…

Analysis of the antibody repertoire in tears of dry-eye patients.

&lt;i&gt;Purpose:&lt;/i&gt; It has recently been suggested that dry-eye disease has an underlying autoimmune mechanism. This hypothesis is further supported by the successful treatment of the disease with immunomodulatory drugs such as cyclosporin A. Although it is known that tears contain antibodies, very little is known about the antibody repertoires in tears. It was the aim of this study to analyze the IgA antibody repertoire against ocular antigens in the tears of patients suffering from dry-eye disease and compare it to those of healthy volunteers. &lt;i&gt;Methods:&lt;/i&gt; Two groups were examined: 20 healthy volunteers (controls) and 28 patients suffering from dry-eye disease. The …

Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, …

Tonographic Effect of Ocular Response Analyzer in Comparison to Goldmann Applanation Tonometry.

AIMS The tonographic effect is a phenomenon of intraocular pressure (IOP) reduction following repeated tonometry. This study examines whether the tonographic effect occurs following IOP measurement performed with Ocular Response Analyzer (ORA). METHODS Both eyes of 31 glaucoma patients and 35 healthy controls underwent nine IOP-measurements performed with GAT and ORA. The number of GAT and ORA measurements performed on each eye differed depending on the randomly allocated investigation scheme. Central corneal thickness (CCT), anterior chamber volume (ACV) and anterior chamber depth (ACD) were assessed with Pentacam before and after the repeated GAT/ORA measurements. RESULTS There was no sta…

Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.

BackgroundAntibodies against retinal and optic nerve antigens are detectable in glaucoma patients. Recent studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immun-mediated retinal ganglion cell loss in rats.Methodology/principal findingsRats immunized with a retinal ganglion cell layer homogenate (RGA) had a reduced retinal ganglion cell density on retinal flatmounts (p = 0.007) and a lower number of Brn3(+) retinal ganglion cells (p = 0.0001) after six weeks. The autoreactive antibody development against retina and optic nerve was examined throughout the study. The levels of autoreactive antibodies continuously in…

The Heidelberg retina tomograph ancillary study to the European glaucoma prevention study: study design and baseline factors.

Purpose: To describe the study design and baseline factors of the Heidelberg Retina Tomograph ancillary study within the EGPS. Furthermore, to examine the relationship between HRT optic disc topographic measurements and baseline demographic and ocular factors. Methods: Four hundred and eighty-nine ocular hypertensive participants were included. Each participant completed HRT imaging at least annually. The associations between HRT measurements and IOP, central corneal thickness (CCT), baseline photographic estimates of vertical CDR ratio (CDR), asymmetry between the two eyes in CDR ratio and baseline visual field indices were assessed using regression analysis. Results: Associations between …

Distribution of Intraocular Pressure and Its Association with Ocular Features and Cardiovascular Risk Factors

Purpose To describe the distribution of intraocular pressure (IOP) and its association with ocular features and cardiovascular risk factors in an adult European cohort. Design Population-based, cross-sectional study. Participants This analysis was based on a Gutenberg Health Study (GHS) cohort that included 4335 eligible enrollees from among 5000 subjects who participated in the survey from 2007 through 2008. The age range was 35 to 74 years at enrollment. Methods Participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination including slit-lamp biomicroscopy, noncontact tonometry, fundus photography, central corneal thickness measurement, and visu…

Capsular bag shrinkage after implantation of a capsular bending or capsular tension ring.

To evaluate the influence of a capsular bending ring (CBR) or tension ring (CTR) on capsular bag shrinkage.Department of Ophthalmology, Johannes Gutenberg-University, and Department of Medical Biometry, Epidemiology and Informatics, University of Mainz, Mainz, Germany.In 92 eyes of 92 patients, a capsular measuring ring (CMR) was implanted after phacoemulsification to measure capsular bag size in vivo. Patients were randomized into 3 groups: The first received a CMR and CBR, the second received a CMR and CTR, and the third received a CMR alone. Measurements were performed preoperatively, intraoperatively, during the first 3 postoperative days, and after 1 and 3 months. Preoperative biometri…

Is Homelessness a Risk Factor for Eye Disease?

&lt;i&gt;Background:&lt;/i&gt; There is general agreement on the presence of a correlation between poverty and impaired health. However, only scarce data are available on whether this also applies to the incidence of eye disease. The present study was carried out to evaluate the prevalence of ocular disease in homeless people in Germany. &lt;i&gt;Methods:&lt;/i&gt; 107 homeless people (97 male, 10 female; mean age 49 years, range 18–81 years) treated in specialised social service institutions were investigated prospectively according to a standardised ophthalmological screening protocol. This comprised visual acuity, assessment of pupillary light reaction, intra-ocular pressure, slit lamp e…

Modulation of central corneal thickness by various riboflavin eyedrop compositions in porcine corneas

Purpose To evaluate the modulatory effect of various riboflavin 0.1% and 0.2% compositions on the central corneal thickness (CCT) in fresh porcine corneas. Setting Department of Ophthalmology, Johannes Gutenberg University of Mainz, Mainz, Germany. Design Experimental study. Methods The CCT in freshly enucleated porcine globes was measured by ultrasound pachymetry before and after (if applicable) deepithelialization and every 10 minutes thereafter during 120 minutes of eyedrop application. In Groups 1 and 2 (controls), no eyedrops were applied. In Groups 3 and 4, isotonic riboflavin eyedrops were used. In Groups 5 to 9, hypotonic riboflavin eyedrops were given. In Groups 10 and 11, preparat…

Incidence of Retinal Detachment in Germany: Results from the Gutenberg Health Study

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; To investigate the incidence of retinal detachment in the German population and to assess potential risk factors. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The Gutenberg Health Study is a population-based cohort study in Mainz, Germany, including subjects (&lt;i&gt;n&lt;/i&gt; = 15,010) with an age range from 35 to 74 years at baseline examination. Study participants underwent a comprehensive ophthalmological examination including distant-corrected visual acuity, refraction and slit-lamp examination at baseline examination. A computer-assisted telephone interview was conducted after 2.5 and 5 years, and health events were recorded. The 5-y…

How to Predict the Suitability for Corneal Donorship?

Background: In Germany, more than one-third of donor corneas harvested are not suitable for transplantation. We evaluated the factors associated with the usability of donor corneas. Method: Data from 2032 consecutive donor corneas harvested at the Rhineland-Palatinate Eye Bank in Mainz, Germany, were retrospectively analyzed. Factors of interest were age, sex, lens status, cause of death, cardiopulmonary resuscitation (CPR), death-to-explantation-interval (DEI), and the influence of these factors on the proportion of discarded donor corneas. Factors associated with endothelial cell density (ECD) were analyzed in a linear regression mixed model. Results: Higher donor age, male gender, pseudo…

No Benefit of a Pediatric Screening in Discovering Reduced Visual Acuity in Children: Experiences from a Cross-Sectional Study in Germany

Background: The newly introduced German pediatric screening examination at the end of the third year of life (U7a) incorporates visual function testing in particular

Safety and efficacy of changing to the travoprost/timolol maleate fixed combination (DuoTrav) from prior mono- or adjunctive therapy.

Norbert Pfeiffer1, Maria-Luise Scherzer2, Hubert Maier3, Sonja Schoelzel4, Mark C Jasek5, Jeanette A Stewart6, William C Stewart6 On behalf of the DuoTravMED study group1Johannes Gutenberg-Universit&amp;auml;t Mainz, Mainz, Germany; 2Regenstauf, Germany; 3Gerolzhofen, Germany; 4Institutes of Molecular Medicine, University of Freiburg, Department of Surgery, Freiburg, Germany; 5Alcon Laboratories, Inc., Fort Worth, TX, USA; 6PRN Pharmaceutical Research Network, LLC, Charleston, SC, USAPurpose: To assess the safety and efficacy of changing to the travoprost/timolol fixed combination (TTFC) from other mono- or adjunctive therapies.Patients and methods: A prospective, open-label, observational …

Type I Diabetes is the Main Cost Driver in Autoimmune Polyendocrinopathy

Abstract Context Autoimmune polyendocrinopathy (AP), a chronic complex orphan disease, encompasses at least two autoimmune-induced endocrine diseases. Objective To estimate for the first time total, indirect and direct costs for patients with AP, as well as cost drivers. Design Cross-sectional cost of illness study. Setting Academic tertiary referral center for AP. Patients 146 consecutive, unselected AP patients. Intervention Interviews pertaining to patients’ socioeconomic situation covered a recall period of 12 months. Both the human capital (HCA) and the friction cost approaches (FCAs) were applied as estimation methods. Main outcome measures Direct and indirect annual costs, and sick l…

Symptoms of depersonalization/derealization are independent risk factors for the development or persistence of psychological distress in the general population: Results from the Gutenberg health study

Abstract Background Symptoms of depersonalization (DP) and derealization (DR) have a high prevalence in patient and community samples. Previous studies suggested that DP/DR symptoms might represent a marker of disease severity and poor prognosis. However, population-based studies investigating the impact of DP/DR symptoms on the course of depression and anxiety are sparse. Therefore, we aimed to analyze whether symptoms of DP/DR are longitudinally associated with the persistence or incidence of elevated symptoms of depression/anxiety. Methods We analyzed observational data from a sample of 13.182 participants of the Gutenberg Health Study. The outcomes were elevated symptoms of depression/a…

Urrets-Zavalia Syndrome After Combined Trabeculotomy-Trabeculectomy Surgery

We report a case of a rare complication after trabeculotomy combined with a small trabeculectomy with mitomycin C in a young patient with juvenile glaucoma. The patient underwent uneventful surgery. However, postoperatively, he experienced a long-lasting hypotony with the need of 2 revision surgeries and 2 short episodes of high-intraocular pressure. He developed a fixed dilated pupil over time.

Allogenic simple limbal epithelial transplantation (alloSLET) from cadaveric donor eyes in patients with persistent corneal epithelial defects

Background/aimTo describe the clinical outcome of allogenic simple limbal epithelial transplantation (alloSLET) utilising tissue from cadaveric donor eyes after failed re-epithelialisation of the corneal surface.MethodsMedical records of 14 eyes from 14 patients treated for persistent corneal epithelial defects with alloSLET were reviewed. The primary outcome measure was complete epithelialisation of the corneal surface. Secondary outcome measures were best corrected visual acuity (BCVA) and postoperative side effects due to surgery or medical therapy.ResultsOf the 14 eyes, 7 received alloSLET only and 7 alloSLET together with penetrating keratoplasty (PK). Thirteen (92.9%) of 14 eyes had a…

Relative Telomere Length and Cardiovascular Risk Factors

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status…

Histology and Fine Structure of the Iris and Outflow System Following Latanoprost Therapy

Latanoprost therapy can lead to iris darkening in susceptible individuals, particularly those with hazel eyes. Concerns have been raised about whether latanoprost, and for that matter other prostanoids, may have a harmful effect on the iris. In addition, it is unknown whether latanoprost causes increased pigmentation of the outflow pathways that might eventually lead to blockage and a type of pigmentary glaucoma. The present study summarizes findings from the authors' own laboratories on the effects of latanoprost as seen by light and electron microscopy of the iris and outflow tissues and reviews the as yet limited, relevant literature. The findings support the proposal that latanoprost-in…

Prevalence, Phenotype, and Psychosocial Well-Being in Euthyroid/Hypothyroid Thyroid-Associated Orbitopathy.

At the onset of thyroid-associated orbitopathy (TAO), most patients are hyperthyroid, while scarce data are available on euthyroid/hypothyroid TAO. The aim of this study was to assess the prevalence, phenotype, and psychosocial burden of patients with initially euthyroid/hypothyroid TAO.The medical records of 461 consecutive and unselected patients with TAO followed at a specialized joint thyroid-eye clinic were analyzed within this retrospective cross-sectional study. Main outcome measures were the prevalence of initially eu- or hypothyroid TAO as well as ophthalmic signs and symptoms, disease-specific quality of life (QoL), work impairment, and rate of psychotherapy in initially eu-/hypot…

The α1B-adrenoceptor subtype mediates adrenergic vasoconstriction in mouse retinal arterioles with damaged endothelium

Background and Purpose The α1-adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to determine the contribution of individual α1-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes (α1A-AR−/−, α1B-AR−/− and α1D-AR−/− respectively). Experimental Approach Using real-time PCR, mRNA expression for individual α1-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three α1-adrenoceptor subtypes for mediating vascular responses, retinal vascular…

Abstract 147: The Role of Thrombin Generation in Cardiovascular Disease and Mortality - Results from the Population-based Gutenberg Health Study

Background: Thrombin formation is one of the key enzymatic processes that direct the activity of the hemostatic system. Thrombin generation (TG), a method addressing the overall potential of a given plasma sample to form thrombin, may be a potential tool to improve risk stratification for cardiovascular diseases (CVD). This study aims to explore the relation between TG and cardiovascular risk factors (CVRFs), CVD, and total mortality. Methods: For this study, N=5000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. TG was measured by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor (TF) trigger in platelet poor …

Novel DNA Methylation Sites Influence GPR15 Expression in Relation to Smoking

Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated i…

New onset of depression in aging women and men: contributions of social, psychological, behavioral, and somatic predictors in the community.

AbstractBackgroundBased on the vulnerability–stress model, we aimed to (1) determine new onset of depression in individuals who had not shown evidence of depression at baseline (5 years earlier) and (2) identify social, psychological, behavioral, and somatic predictors.MethodsLongitudinal data ofN= 10 036 participants (40–79 years) were evaluated who had no evidence of depression at baseline based on Patient Health Questionnaire (PHQ-9), no history of depression, or intake of antidepressants. Multivariate logistic regression models were used to predict the onset of depression.ResultsPrevalence of new cases of depression was 4.4%. Higher rates of women (5.1%) than men (3.8%) were due to thei…

Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus

BACKGROUND: This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. METHODS: Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. RESULTS: Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated approximately 20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic d…

Prevalence and Time Trends in Myopia Among Children and Adolescents.

Background Myopia (near-sightedness) is increasing worldwide, especially in Asia. The aim of this study was to describe trends in the prevalence of myopia in Germany. Methods We analyzed data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS; baseline survey 2003-2006, N = 17 640; wave 2, 2014-2017, N = 15 023). The presence of myopia was determined from a parent questionnaire and validated by the use of a visual aid. The population prevalence of myopia was calculated. Based on the KiGGS wave 2 data, potential risk factors for myopia were identified by means of logistic regression. Results The prevalence of myopia at the age of 0-17 years in Germany…

Retinal vascular occlusion and deficiencies in the protein C pathway.

Abstract PURPOSE: To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS: In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also scre…

Upregulation of antibody response to heat shock proteins and tissue antigens in an ocular ischemia model.

PURPOSE. The aim of this study was to characterize the serum antibody reactivities occurring after ocular ischemia reperfusion. The time course of serum antibody responses was examined. METHODS. Wistar rats were exposed to transient ocular ischemia by elevating intraocular pressure to 130 mm Hg for 60 minutes. Axonal damage was evaluated on optic-nerve sections 2 and 4 weeks later. Blood samples collected before and several times after ischemia were used for antibody detection via customized protein microarrays. Different tissue antigens, including heat shock proteins (HSPs) and crystallins, were selected based on previous identification of antibody reactivities in studies on ischemic event…

Contribution of nitric oxide synthase isoforms to cholinergic vasodilation in murine retinal arterioles.

Abstract Nitric oxide synthases (NOSs) are critically involved in regulation of ocular perfusion. However, the contribution of the individual NOS isoforms to vascular responses is unknown in the retina. Because some previous findings suggested an involvement of inducible nitric oxide synthase (iNOS) in the regulation of retinal vascular tone, a major goal of the present study was to examine the hypothesis that iNOS is involved in mediating cholinergic vasodilation responses of murine retinal arterioles. Another subject of this study was to test the contribution of the other two NOS isoforms, neuronal (nNOS) and endothelial NOS (eNOS), to cholinergic retinal arteriole responses. Expression o…

Comparative Quantitative Analysis of Porcine Optic Nerve Head and Retina Subproteomes

Optic nerve head (ONH) and retina (RET) are the main sites of damage in neurodegenerative optic neuropathies including glaucoma. Up to date, little is known about the molecular interplay between these two adjoining ocular components in terms of proteomics. To close this gap, we investigated ONH and RET protein extracts derived from porcine eyes (n = 12) (Sus scrofa domestica Linnaeus 1758) using semi-quantitative mass spectrometry (MS)-based proteomics comprising bottom-up LC&ndash

Role of  1-Adrenoceptor Subtypes in Pupil Dilation Studied With Gene-Targeted Mice

PURPOSE The α₁A-adrenoceptor (α₁A-AR) subtype was suggested to mediate contraction and trophic effects in the iris dilator muscle, and thus its pharmacological blockade may be involved in intraoperative floppy iris syndrome. We tested the hypothesis that the α₁A-AR mediates pupil dilation and trophic effects in the mouse iris. METHODS The α₁-AR subtype mRNA expression was quantified in iris tissue by real-time PCR. To assess the role of individual α₁-ARs for mediating pupil dilation, the α₁-AR agonist phenylephrine was topically applied to the ocular surface of mice deficient in one of the three α₁-AR subtypes (α₁A-AR(-/-), α₁B-AR(-/-), α₁D-AR(-/-), respectively) and wild-type controls. Cha…

Prevalence of Age-Related Macular Degeneration in Europe

Manuscript no. 2016-1147 Supplemental material is available at www.aaojournal.org/; International audience; [u]Purpose:[/u] Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. [u]Design:[/u] Meta-analysis of prevalence data. [u]Participants:[/u] A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohor…

Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity

Summary Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid–eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) …

Inflammation after sclerocorneal versus clear corneal tunnel phacoemulsification.

Abstract Objective To compare the postoperative inflammation after phacoemulsification followed by intraocular lens (IOL) implantation by means of sclerocorneal versus clear corneal tunnel incision. Design Randomized controlled clinical trial. Participants One hundred eyes of 100 patients were examined at a German University eye hospital. Intervention One hundred eyes with cataract necessitating phacoemulsification with posterior chamber IOL implantation were randomly assigned to receive a temporal sclerocorneal or clear corneal tunnel incision by a single surgeon. Main outcome measures Preoperative and postoperative inflammation was evaluated by measurement of flare using laser flare photo…

Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication.

. Purpose:  The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan®) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan®) treatment. Methods:  A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear brea…

Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood-Results from the Population-Based German Gutenberg Health Study.

Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40–80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and…

Prevalence of myopic maculopathy in the German population: results from the Gutenberg health study.

AimsTo determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors.DesignThe Gutenberg Health Study is a population-based study, including 15 010 participants aged 35–74 years.MethodsMyopic maculopathy was graded in phakic eyes with spherical equivalent ≤−6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM). 801 eyes of 519 participants (mean age 51.0±0.77 years) met the conditions and had gradable fundus photographs. Age-specific prevalence estimates were computed. Multivariable logistic regression analysis was used to assess associa…

Biaxial Microincision versus Coaxial Small-Incision Clear Cornea Cataract Surgery

Objective To compare clinical outcomes of biaxial microincision (1.5 mm) and coaxial small-incision (2.75 mm) clear cornea cataract surgery. Design Randomized controlled clinical trial. Participants Seventy eyes of 70 patients were examined at a German university eye hospital. Intervention The 70 patients (70 eyes) were assigned randomly (1:1) to a biaxial or conventional coaxial incision group. Both groups underwent phacoemulsification using pulsed ultrasound energy with variable duty cycles, followed by microincision intraocular lens implantation. Main Outcome Measures Best-corrected visual acuity (BCVA), astigmatism, laser flare photometry value, effective phacoemulsification time (EPT),…

Antibodies to alpha B-crystallin, vimentin, and heat shock protein 70 in aqueous humor of patients with normal tension glaucoma and IgG antibody patterns against retinal antigen in aqueous humor.

To show the existence of IgG antibodies against retinal antigens in aqueous humor of normal tension glaucoma patients.Forty-two patients were included in this study. Aqueous humor was collected from control subjects (CO; n = 21) and patients with normal tension glaucoma (NTG; n = 21). Western blot methods against bovine retinal antigens were used to detect the IgG antibody patterns. The complex antibody repertoires were analyzed by multivariate statistical techniques. Mass spectrometry was used to identify the most important antigens.Very complex IgG antibody patterns against retinal antigens were found in all analyzed aqueous humor samples. Our multivariate approach could quantify differen…

Erhöhter Augeninnendruck für 7 Wochen induziert lokale Gefäßveränderungen im experimentellen Glaukommodell in vivo

Zusammenfassung Hintergrund Peripapilläre Blutungen sind diagnostisch wegweisend für das Vorliegen des Glaukoms. Dennoch ist die Rolle der Gefäße der Retina und des Sehnervs in der Pathogenese des Glaukoms weitestgehend ungeklärt. Ziel dieser Studie war es, im experimentellen Glaukommodell die lokalen Veränderungen dieser Gefäße auf erhöhten Druck in vivo zu untersuchen. Material und Methoden Das Glaukom wurde durch Veröden dreier episkleraler Venen des linken Auges von weiblichen Sprague-Dawley-Ratten induziert (n = 6). In vivo erfolgte eine Messung der Gefäßkaliber mittels peripapillärem Scan des SD-OCT (Heidelberg Engineering) als Baseline sowie 7 Wochen nach Augeninnendruckerhöhung. Die…

Role of nitric oxide synthase isoforms for ophthalmic artery reactivity in mice.

Abstract Nitric oxide synthases (NOS) are involved in regulation of ocular vascular tone and blood flow. While endothelial NOS (eNOS) has recently been shown to mediate endothelium-dependent vasodilation in mouse retinal arterioles, the contribution of individual NOS isoforms to vascular responses is unknown in the retrobulbar vasculature. Moreover, it is unknown whether the lack of a single NOS isoform affects neuron survival in the retina. Thus, the goal of the present study was to examine the hypothesis that the lack of individual nitric oxide synthase (NOS) isoforms affects the reactivity of mouse ophthalmic arteries and neuron density in the retinal ganglion cell (RGC) layer. Mice defi…

Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets-Results from the Gutenberg Health Study.

AbstractThe tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants (n = 15) have been excluded resulting in 392 subjects for further analysis. Lag time, endogenous thrombin potential (ETP) and peak height…

Association of Birth Weight With Foveolar Thickness in Adulthood: Results From a Population-Based Study

Purpose Low birth weight (BW) is associated with alterations of foveal shape development in childhood—leading to an increased retinal thickness of the fovea. The aim of the present study was to assess whether BW has a long-term effect on foveal retinal thickness (RT) and is still present in adulthood. Methods In the German population-based Gutenberg Health Study (GHS), participants were examined with spectral-domain optical coherence tomography. The association between self-reported BW and RT in the foveolar and perifoveal locations was assessed. Multivariable linear regression analyses with adjustment for potential confounders and grading of foveal hypoplasia were performed. Results Overal…

Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options.

In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia…

Problems and perspectives of ophthalmic research in Germany: results from a national survey.

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; To identify and describe the most relevant obstacles to carrying out ophthalmic research in Germany. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Two research methods were used to assess current problems in ophthalmic research. First, 55 expert interviews were conducted with major stakeholders in ophthalmic research, and key problems were identified. An online questionnaire was then sent to 3,080 German ophthalmologists, of whom 927 responded by evaluating the current research situation within ophthalmology in Germany. We devised a score to rank areas of concern by multiplying the responders' rate, ranging between -3 (‘I disagree completely')…

Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study

Background: Elevated levels of FVIII:c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma FVIII: c and its cardiovascular determinants is available. Methods: FVIII:c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for FVIII:c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease. Results and conclusions: Females (126.6% (95% CI: 125.2/128)) showed higher FVIII:c levels than males (121.2% (119.8/122.7)). FVIII:c le…

Paraproteinämische Keratopathie als klinisches Zeichen einer monoklonalen Gammopathie

ZusammenfassungPatienten mit monoklonaler Gammopathie können eine behandlungsbedürftige paraproteinämische Keratopathie (PPK) aufweisen. Die PPK muss gegenüber verschiedenen Formen von Hornhautdystrophie, einzelnen systemischen Stoffwechselstörungen mit Hornhautbeteiligung sowie gegenüber immunologischen und inflammatorischen Hornhauterkrankungen abgegrenzt werden.

Repeated intraocular pressure measurement in awake Lewis rats does not bias retinal ganglion cell survival.

The TonoPen applanation tonometry is an established method for intraocular pressure (IOP) measurement. The IOP is one of the main variables affecting retinal ganglion cell (RGC) loss in experimental animal models in ophthalmology and the main risk factor for human glaucoma. In this study, we examined if IOP measurements with the TonoPen itself lead to retinal ganglion cell loss or any other possible retina damages, such as intraocular bleedings or ablation, in Lewis rats.Three groups of rats (n = 5 each) were formed. IOP monitoring, using a TonoPen XL, was performed on groups 1 and 3. Animals in groups 1 and 2 received funduscopies before and after one and two weeks of the study, in order t…

Effects of intraocular cefotaxime on the human corneal endothelium

Abstract Purpose To ascertain whether 0.4 mL of cefotaxime 0.25% applied intracamerally causes toxic alteration of the human corneal endothelium. Methods In this prospective randomized masked study, 66 patients had cataract extraction using phacoemulsification, a frown incision, and implantation of a poly(methyl methacrylate) intraocular lens. This was followed by intraocular injection of 0.4 mL of cefotaxime 0.25% or balanced salt solution (BSS®). Contact specular microscopy and photography were performed preoperatively and 1 to 4 days and 3 months postoperatively. Results In the cefotaxime group, the mean endothelial cell count was 2729 cells/mm 2 ± 474 (SD) preoperatively, 2520 ± 462 cel…

Maggot therapy following orbital exenteration

Orbital exenteration is a radical surgery reserved for the treatment of locally invasive or potentially life-threatening orbital tumours.1 Complications occur after 20–25% of exenterations and include tissue necrosis (6%) and infection (3–4%).2–4 In the present report, we describe the management of a post-exenteration orbital infection by the use of maggots. An 82-year-old multimorbid man presented with a fist-sized painless tumour of the left orbit (fig 1A). Computed tomography demonstrated an orbital mass clearly demarcated from the surrounding tissue (fig 1B). After biopsy, the neoplasm was classified as a borderline-malignant extrapleural solitary fibrous tumour. Therefore, a total orbi…

Codierung der Tätigkeitsangaben im Basiskollektiv der Gutenberg-Gesundheitsstudie unter Anwendung der Klassifikation der Berufe KldB 2010 — Darstellung des Vorgehens und der Datenqualität

In der Basiserhebung der Gutenberg- Gesundheitsstudie Mainz wurden die Berufsbiografien von 15.010 Probanden erfasst. Um die Textangaben aus 67.389 einzelnen Tatigkeitsphasen fur epidemiologische Auswertungen nutzen zu konnen, wurde eine Codierung nach der deutschen Klassifikation der Berufe KldB 2010 durchgefuhrt. Ziel des Artikels ist, das methodische Vorgehen und die Qualitat der angewandten Berufscodierung darzustellen.

Retinal arteriole reactivity in mice lacking the endothelial nitric oxide synthase (eNOS) gene

Dysfunctional vascular endothelial nitric oxide synthase (eNOS) has been proposed to play a main pathophysiological role in various ocular diseases. The aim of the present study was to test the hypothesis that the chronic lack of eNOS impairs endothelium-dependent vasodilation in retinal arterioles. The relevance of eNOS for mediating vascular responses was studied in retinal vascular preparations from eNOS-deficient mice (eNOS-/-) and wild-type controls in vitro. Changes in luminal diameter in response to vasoactive agents were measured by videomicroscopy. The thromboxane mimetic, U46619, induced similar concentration-dependent constriction of retinal arterioles in eNOS-/- and wild-type mi…

Tolerability of 24-hour intraocular pressure monitoring of a pressure-sensitive contact lens.

Purpose To investigate tolerability and safety of a new diagnostic device for 24-hour intraocular pressure monitoring in healthy subjects and age-matched glaucoma patients. Patients and methods Twenty healthy subjects (group 1) and 20 age-matched glaucoma patients (group 2) were included in this prospective, single-center, open, observational parallel group study. The SENSIMED Triggerfish Sensor is a soft disposable contact lens embedding a telemetry chip and strain gauge sensor for continuous intraocular pressure monitoring. The Sensor was placed in 1 eye for 24 hours. Tolerability was evaluated using a visual analog scale (range, 0 to 100; 0=no discomfort; 100=very severe discomfort). Saf…

Neuroprotective effects of antibodies on retinal ganglion cells in an adolescent retina organ culture

Glaucoma, a neurodegenerative disease, is characterized by a progressive loss of retinal ganglion cells (rgc). Up- and down-regulated autoantibody immunoreactivities in glaucoma patients have been demonstrated. Previous studies showed protective effects of down-regulated antibodies [gamma (γ)-synuclein and glial fibrillary acidic protein [GFAP]) on neuroretinal cells. The aim of this study was to test these protective antibody effects on rgc in an organ culture model and to get a better understanding of cell-cell interactions of the retina in the context of the protective effect. We used an adolescent retinal organ culture (pig) with an incubation time of up to 4 days. Retinal explants were…

Characterization of lacrimal proline-rich protein 4 (PRR4) in human tear proteome

This study was initiated considering the lack of comprehensive characteristics profile of PRR4 in tears of healthy subjects. Therefore, detailed characterizations of PRR4 from basal tears employing in-gel and in-solution digestions for MS systems are presented herein. First, pooled tear samples (n = 10) were utilized to identify PRR4-rich region/spots in 1DE/2DE gels employing LC-MALDI-MS and 1DE-LC-ESI-LTQ-Orbitrap-MS systems. PRR4-rich region and ten spots with vast polymorphisms (Mr : 17-30 kDa, pI: 3.0-6.6) were identified in 1DE and 2DE gels, respectively. In addition, combinations of four types of PTMs, which are methylation, acetylation, oxidation, and pyroglutamate formation, were i…

Peripheral corneal thickness and associated factors - results from the population-based German Gutenberg Health Study.

PURPOSE Changes in peripheral corneal thickness are described in various corneal diseases such as corneal ectasia. However, few data exist describing the increase in corneal thickness from central to peripheral and reporting the normal distribution of corneal thickness in rings around the corneal centre. The aim of this study was to report these cornea characteristics and investigate associated factors in a population-based setting. METHODS The Gutenberg Health Study is a prospective, population-based study examining participants in a 5-year follow-up (age range 40-80 years) using Scheimpflug imaging. Corneal thickness was assessed in each participant at the apex, as well as in the corneal …

Recalled parental rearing behavior in adult women and men with depressive and anxiety symptoms: Findings from a community study.

Objectives: Addressing the lack of population-based data, the purpose of this representative study was to assess sex- and age-specific associations of maternal and paternal rearing behavior with depressiveness and anxiety controlling for sociodemographic and somatic variables. Methods: 8,175 subjects participating in a population-based study completed standardized questionnaires measuring Recalled Parental Rearing Behavior and distress. Results: Women recalled their fathers as more controlling and warmer, and their mothers as more rejecting than men. Comparisons between age groups (≤ 60 vs. > 60 years) revealed that younger participants recalled more parental control and emotional warmth. I…

Intravitreal ranibizumab treatment of retinal angiomatous proliferation

. Purpose:  To determine the efficacy of intravitreal injections of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) in neovascular age-related macular degeneration. Methods:  Retrospective, consecutive case series of 26 eyes (26 patients) treated with intravitreal injections of 0.5 mg ranibizumab for RAP. Patients received intravitreal injections at monthly intervals during upload phase for a 3-month period. Results:  Mean visual acuity before treatment was 0.75 ± 0.38logMAR (mean ± SD, n = 26). In the upload phase, mean visual acuity improved 4 weeks after the initial injection to 0.6 ± 0.37logMAR (n = 26) and to 0.53 ± 0.34logMAR (n = 26) 4 weeks after the third mo…

Prevalence of pterygium and identification of associated factors in a German population - results from the Gutenberg Health Study.

Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R−/−). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmenta…

Role of M1, M3, and M5 muscarinic acetylcholine receptors in cholinergic dilation of small arteries studied with gene-targeted mice

Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M1, M3, and M5 muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (M1R−/−, M3R−/−, or M5R−/− mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R−/−, M3R−/−, M5R−/−, and wild-type mice were isolated, cannulated with mic…

Longitudinal Analysis of Serum Autoantibody-Reactivities in Patients with Primary Open Angle Glaucoma and Optic Disc Hemorrhage.

Background The aim of our current investigation was to analyze the autoantibody-reactivities of primary open angle glaucoma patients with optic disc hemorrhage as possibly correlated to disease progression by means of a protein microarray approach. Methods Sera of patients with primary open angle glaucoma and optic disc hemorrhage (n = 16) were collected directly after study inclusion (0 weeks) and after 2 weeks, 4 weeks and 12 weeks. As a control group patients with primary open angle glaucoma (n = 18) were used (0 weeks and 12 weeks). Microarrays were incubated and occurring antibody-antigen-reactions were visualized with fluorescence labeled anti-human-IgG secondary antibodies. To detect…