The association of depression and all-cause mortality: Explanatory factors and the influence of gender.

BACKGROUND: The association of depression with mortality and the significance of explanatory factors, in particularly gender, have remained an issue of debate. We therefore aimed to estimate the effect of depression on all-cause mortality, to examine potential explanatory factors and to assess effect modification by gender. METHODS: We used Cox regression models to estimate the effect of depression on mortality based on data from the Gutenberg Health Study, which is a prospective cohort study of the adult population in the districts of Mainz and Mainz-Bingen, Germany. Baseline assessment was between 2007 and 2012. Effect modification by gender was measured on both additive and multiplicative scales. RESULTS: Out of 14,653 participants, 7.7% were depressed according to Patient Health Questionnaire 9 (PHQ-9), and 1,059 (7.2%) died during a median follow-up of 10.7 years. Depression elevated the risk of mortality in men and women in age-adjusted models (HR: 1.41, 95%-CI: 1.03-1.92; resp. HR: 1.96, 95%-CI: 1.43-2.69). Adjustment for social status, physical health and lifestyle covariates attenuated the effect and in the fully-adjusted model the hazard ratio was 0.96 (95%-CI: 0.69-1.33) in men and 1.53 (95%-CI: 1.10-2.12) in women. For effect modification by gender, the measure on multiplicative interaction was 0.68 (95%-CI 0.44-1.07) and on additive interaction was RERI=-0.47 (95%-CI -1.24-0.30). LIMITATIONS: The PHQ-9 is a single self-report measure of depression reflecting symptoms of the past two weeks, limiting a more detailed assessment of depression and course of symptoms, which likely affects the association with mortality. CONCLUSIONS: Depression elevates mortality by multifactorial pathways, which should be taken into account in the biopsychosocially informed treatment of depression. Effect modification by gender was not statistically significant.

Frequency of cataract surgery and its impact on visual function-results from the German Gutenberg Health Study.

PURPOSE: To determine the frequency of cataract surgery in Germany and to evaluate its impact on visual function in an adult population. METHODS: The population-based Gutenberg Health Study was conducted in Germany with its baseline examination between 2007 and 2012 and a 5-year follow-up examiantion. An ophthalmological examination including slit-lamp examination, ocular biometry, and Scheimpflug imaging was carried out. Overall and age-specific frequencies of unilateral and bilateral cataract surgery within 5 years were computed including the 95% confidential intervals [95%-CI]. Association analyses were conducted to determine social and ocular associated factors using multivariable logistic regression analysis. Vision-related quality of life was assessed using NEI VFQ-25. RESULTS: A total of 10,544 people aged 35 to 74 years were bilateral phakic at baseline and had information on lens status at the 5-year examination. Of these, 168 had unilateral cataract surgery (1.6% [1.4-1.9%]), and 448 had bilateral cataract surgery (4.2% [3.9-4.7%]) in the following 5 years. The frequency of cataract surgery increased with age: 45-54-year-old subjects had twice as often cataract surgery (in at least on eye: OR = 2.32) than at age 35-44 years. The frequency further strongly increases with age (55-64 years: OR = 10.5; 65-74 years: OR = 43.8, p < 0.001). Subjects with glaucoma were more likely to have cataract surgery (OR = 2.52, p < 0.001). Visual function increased when undergoing bilateral cataract surgery. CONCLUSIONS: The frequency of cataract surgery is low at younger ages and increases up to 26% at age 70-74 years. Persons with glaucoma are more likely to undergo cataract surgery at population-based level in Germany.

[Paraproteinemic Keratopathy as a Clinical Sign of Monoclonal Gammopathy]. / Paraproteinämische Keratopathie als klinisches Zeichen einer monoklonalen Gammopathie.

Patients with monoclonal gammopathy can show paraproteinemic keratopathy (PPK) with an indication to treatment. PPK has to be differentiated from corneal dystrophies, systemic metabolic disorders with corneal involvement, as well as from immunologic and inflammatory corneal diseases.

[Chemical burns caused by crust anemone]. / Verätzung durch Krustenanemone.

We present a case of a toxic reaction in both eyes caused by secretions from an encrusting anemone of the genus Protopalythoa. The patient presented with chemosis and follicular reaction of the conjunctiva and whitish spots on the limbus. Under local treatment with steroids and antibiotic eyedrops, remission was achieved within a few days. Palytoxin, a poisonous component of Protopalythoa secretions, leads to inhibition of the sodium-potassium-ATPase, to destabilization of the membrane potential and to cell death. Ocular exposure can lead to severe anatomical and functional impairments with systemic symptoms.

Recurrence of paraproteinemic keratopathy after penetrating keratoplasty and its assessment with confocal microscopy.

PURPOSE: To report on a case of recurrence of paraproteinemic keratopathy (PPK) associated with monoclonal gammopathy after bilateral penetrating keratoplasty. OBSERVATIONS: Penetrating keratoplasty was performed on both eyes of a 45-year-old man due to bilateral progressive corneal stromal clouding. Recurrence of the corneal stromal opacities accompanied by a decrease in visual acuity was observed on slit-lamp examination already two years after penetrating keratoplasty. Confocal laser scanning microscopy (CLSM) of the corneal grafts performed three years after penetrating keratoplasty showed bilateral morphological changes identical to that found in the patient's corneas prior to penetrating keratoplasty. A hematological work-up revealed monoclonal gammopathy of type IgG kappa. The histochemical examination of the explanted corneas confirmed the diagnosis of PPK. CONCLUSIONS AND IMPORTANCE: Paraproteinemic keratopathy is an underdiagnosed ophthalmological condition, which may be associated with potentially life-threatening hematologic disorders. A hematological workup should be performed in patients with corneal opacities of uncertain etiology. Penetrating keratoplasty should be performed with caution in patients with monoclonal gammopathy due to the possibility of a very fast recurrence of PPK in the corneal graft. This is the first presentation of the recurrence of flake-like PPK after penetrating keratoplasty assessed with CLSM.

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

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 (two months old, n of eyes = 20) and old (eight months old, n of eyes = 10) rats. Repeatability experiments showed highly corresponding data for all segments in both spectral channel, with higher repeatability in the short spectral channel. FLT decreased significantly in all areas in the short (young: 991 ±â€¯29 ps; old: 547 ±â€¯42 ps) and long (young: 382 ±â€¯28 ps; old: 261 ±â€¯16 ps) spectral channels, indicating an overall metabolic change of the fundus in old animals. FLT of veins increased in the short spectral channel (young: 385 ±â€¯43 ps; old: 424 ±â€¯25 ps) and no change was observed in the long spectral channel (young: 274 ±â€¯9 ps; old: 269 ±â€¯24 ps). FLIO represents a highly repeatable and sensitive method to detect changes of the FLT in aged eyes for monitoring the degeneration of the rodent retinae.

Prevalence of depression and anxiety among participants with glaucoma in a population-based cohort study: The Gutenberg Health Study.

BACKGROUND: To investigate the prevalence of depression and anxiety among subjects with self-reported glaucoma and the association between self-reported glaucoma and depression respectively anxiety in a European cohort. METHODS: A study sample of 14,657 participants aged 35 to 74 years was investigated in a population-based cohort study. All participants reported presence or absence of glaucoma. Ophthalmological examinations were carried out in all participants and demographic and disease related information were obtained by interview. Depression was assessed with the Patient Health Questionnaire (PHQ-9), and generalized anxiety with the two screening items (GAD-2) of the short form of the GAD-7 (Generalized Anxiety Disorder-7 Scale). Prevalence of depression and generalized anxiety were investigated for subjects with and without self-reported glaucoma. Logistic regression analyses with depression, respectively anxiety as dependent variable and self-reported glaucoma as independent variable were conducted and adjusted for socio-demographic factors, systemic comorbidities (arterial hypertension, myocardial infarction, stroke, diabetes mellitus, chronic obstructive pulmonary disease, cancer), ocular diseases (cataract, macular degeneration, corneal diseases, diabetic retinopathy), visual acuity, intraocular pressure, antiglaucoma eye drops (sympathomimetics, parasympathomimetics, carbonic anhydrase inhibitors, beta-blockers, prostaglandins) and general health status. RESULTS: 293 participants (49.5% female) reported having glaucoma. Prevalence of depression among participants with and without self-reported glaucoma was 6.6% (95%-CI 4.1-10.3) respectively 7.7% (95%-CI 7.3-8.2), and for anxiety 5.3% (95%-CI 3.1-8.7) respectively 6.6% (95%-CI 6.2-7.1). Glaucoma was not associated with depression (Odds ratio 1.10, 95%-CI 0.50-2.38, p = 0.80) or anxiety (1.48, 95%-CI 0.63-3.30, p = 0.35) after adjustment for socio-demographic factors, ocular/systemic diseases, ocular parameters, antiglaucoma drugs and general health status. A restriction to self-reported glaucoma cases either taking topical antiglaucoma medications or having a history of glaucoma surgery did not alter the result. CONCLUSIONS: This is the first study analyzing both depression and anxiety among glaucoma patients in a European cohort. Subjects with and without self-reported glaucoma had a similar prevalence of depression and anxiety in our population-based sample. Self-reported glaucoma was not associated with depression or anxiety. A lack of a burden of depressive symptoms may result from recruitment from a population-based sample as compared to previous study groups predominantly recruited from tertiary care hospitals.

[Trabeculectomy with mitomycin C : Video article]. / Trabekulektomie mit Mitomycin C : Videobeitrag.

Trabeculectomy is the most proven method for the treatment of open angle glaucoma. The long-term results of this method show an 80% success rate in lowering intraocular pressure over 20 years. The surgical technique is demonstrated in detail with the help of a video of the operation and which is available online. For more than 15 years trabeculectomy has been performed with the use of antifibrotic substances, such as mitomycin C. Long-term treatment with antiglaucoma eyedrops leads to a proven inflammation of the conjunctiva and the ocular surface with an increase in lymphocytes, mast cells, and fibroblasts. Discontinuation of antiglaucoma therapy in turn allows regeneration of the ocular surface. From the knowledge gained from these histopathological studies it has been recommended to stop glaucoma treatment prior to glaucoma surgery and to pretreat the conjunctiva with eyedrops containing cortisone. Administration of nonsteroidal antiphlogistic substances or local steroids to the conjunctiva 4 weeks prior to surgery increases long-term success of the filtering bleb function.

[Eyeball trauma caused by confetti particles]. / Bulbustrauma durch Konfettipartikel.

The two presented case examples demonstrate that scleral perforation through highly accelerated, seemingly harmless confetti particles is possible. In addition to penetrating injuries that should be treated directly, contusions with serious consequential complications can also occur. A careful assessment and examination are essential to promptly provide the patient with the right treatment and to minimize complications.

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 survivors. Objectives To investigate traditional cardiovascular risk factors (CVRFs), inflammation and the coagulation profile in long-term cancer survivors (cancer diagnosis ≥ 5 years) from a large adult population-based study sample. Methods The presence of cardiovascular risk factors (CVRFs) and laboratory markers were compared in individuals with (n = 723) and without (n = 13626) a long-term history of cancer from the Gutenberg Health Study. Data on coagulation factors, D-dimer and von Willebrand factor (VWF) activity were available for 4974 individuals (n = 244 cancer survivors). Results In multivariable regression models, a history of cancer was, independently of CVRFs and CVD, associated with higher fibrinogen levels (ß 6.99, 95% confidence interval [CI] 1.16-12.8), VWF activity (ß 5.08, 95% CI 0.02-10.1), and antithrombin activity (ß 1.85, 95% CI 0.44-3.27). Cancer survivors with CVD showed notably higher VWF activity than individuals with CVD without a history of cancer, with a difference in the means of 23.0 (7.9-38.1). Multivariate Cox regression analysis, adjusted for CVRFs, confirmed that a long-term history of cancer is associated with a 72% higher mortality. Increased mortality in cancer survivors was dependent on fibrinogen level and VWF activity level. Conclusion Cancer survivors showed a worse inflammation and coagulation profile than individuals without a history of cancer. Overall mortality in long-term cancer survivors was increased independently of traditional CVRFs. These results underline the need to further investigate plasma biomarkers as complementary cardiovascular risk predictors in cancer survivors.

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

BACKGROUND: Major 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. METHODS: Planning 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. RESULTS: Higher anxiety ratings were associated with lower planning performance (ß = -0.20; p < 0.0001) independent of age (ß = 0.03; p = 0.47). When directly comparing the predictive value of depression and anxiety on cognition, only anxiety attained significance (ß = -0.19; p = 0.0047), whereas depression did not (ß = -0.01; p = 0.71). CONCLUSIONS: Subclinical levels of anxiety but not of depression showed negative associations with cognitive functioning independent of age. Our results demonstrate that associations observed in clinical groups might differ from those in population-based samples, also with regard to the trajectory across the life span. Further studies are needed to uncover causal interrelations of anxiety and cognition, which have been proposed in the literature, in order to develop interventions aimed at reducing this negative affective state and to improve executive functioning.

[Who visits an ophthalmologist and how often? Results of the German nationwide adult health survey (DEGS1)]. / Wer geht wie oft zum Augenarzt in Deutschland? Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1).

BACKGROUND: The prevalence of eye diseases increases in the second half of life, especially cataract, glaucoma and age-related macular degeneration. In this study we examined the influencing factors for visiting an ophthalmologist in the last 12 months. METHODS: Visits to an ophthalmologist's practice in the last 12 months and the frequency were surveyed in the German nationwide adult health survey wave 1 (DEGS1) study (baseline examination from 2008 to 2011, N = 7987, 52.6% women, age 18-79 years). Data on utilization were processed by taking the complex study design into consideration. Multivariable logistic regression analysis was used to determine associated factors including age, sex, socioeconomic status, place of residence, type of health insurance (e.g. statutory or private) and diabetes. RESULTS: Between the ages of 18 and 79 years, 29.3% of survey participants in Germany visited an ophthalmologist in the last year, while after the age of 60 years this was only 50.4%. Multivariable logistic regression analysis showed an association with female sex (odds ratio OR = 1.51, p < 0.001), older age, type of health insurance (private vs. statutory: OR = 0.77, p = 0.006) and diabetes (OR = 3.84, p < 0.001), but no association with socioeconomic status (p = 0.29) or place of residence (p = 0.06). CONCLUSION: Approximately one third of the German population visit an ophthalmologist at least once a year. Especially diabetics showed a high utilization of ophthalmological consultations, which could be based on the interdisciplinary guidelines for early detection of diabetic eye complications.

[Hematological diagnosis in the corneal consultation]. / Hämatologische Diagnose in der Hornhautsprechstunde.

This case report describes a diagnostic chain in a patient with atypical bilateral corneal opacity, which led to the diagnosis of a hematological disorder. The patient's medical history, clinical appearance and findings in confocal microscopy gave rise to the suspicion of a paraproteinemic keratopathy. The hematological laboratory diagnostics revealed a monoclonal gammopathy of the IgG kappa type. The bone marrow puncture led to the diagnosis of a lymphoplasmacytic lymphoma, which belongs to the group of B­cell non-Hodgkin's lymphomas. This case demonstrates that paraproteinemic keratopathy can be associated with potentially life-threatening hematological diseases.

Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model.

Although elevated intraocular pressure (IOP) remains the major risk factor in glaucoma, neurodegenerative processes continue despite effective IOP lowering. Altered α-synuclein antibody (Abs) levels have been reported to play a crucial role. This study aimed at identifying whether α-synuclein Abs are capable to decelerate neuronal decay while providing insights into proteomic changes. Four groups of Sprague Dawley rats received episcleral vein occlusion: (1) CTRL, no intravitreal injection, n = 6, (2) CTRL IgG, intravitreal injection of unspecific IgG, n = 5, (3) Buffer, intravitreal injection of buffer, n = 6, (4), α-synuclein Ab, intravitreal injection of α-synuclein Ab, n = 5. IOP and retinal nerve fiber layer thickness (RNFLT) were monitored and immunohistochemistry, microarray and proteomic analysis were performed. RNFLT was reduced in CTRL, CTRL IgG and Buffer group (all p < 0.01) and α-synuclein Ab group (p = 0.17). Axon and RGC density showed an increased neurodegeneration in CTRL, CTRL IgG and Buffer group (all p < 0.01) and increased neuronal survival in α-synuclein Ab group (p = 0.38 and 0.06, respectively) compared with fellow eyes. Proteomic analysis revealed alterations of cofilin 1 and superoxide dismutase 1 expression. This data indicate that α-synuclein Ab might indirectly modulate the actin cytoskeleton organization and negatively regulate apoptotic processes via cofilin 1 and superoxide dismutase 1.

Revision of encapsulated blebs after trabeculectomy: Long-term comparison of standard bleb needling and modified needling procedure combined with transconjunctival scleral flap sutures.

PURPOSE: To compare two surgical approaches for treating encapsulated blebs after trabeculectomy with mitomycin C, in terms of the development of intraocular pressure and progression of glaucoma in a long-term follow up: 1. bleb needling alone vs. 2. a combined approach of needling with additional transconjunctival scleral flap sutures, to prevent early ocular hypotony. METHODS: Forty-six patients with failing blebs after trabeculectomy with mitomycin C were enrolled in this study. Patients received either needling revision alone (group 1; n = 23) or a combined needling with additional transconjuctival flap sutures, if intraoperatively the intraocular pressure was estimated to be low (group 2; n = 23). Intraocular pressure (IOP), visual acuity, visual fields, and optic nerve head configuration by means of Heidelberg Retina Tomograph (HRT®) were analysed over time. Results from both groups were compared using Mann-Whitney U-test for single timepoints. RESULTS: IOP did not differ significantly between the two groups during follow-up at three months (P = 0.13), six months (P = 0.12), one year (P = 0.92) and two years (P = 0.57) after surgery. Furthermore, there was no significant difference in the course of glaucoma concerning the optic nerve anatomy between the two groups (Rim Area Change in the Moorfields Regression Analysis of HRT®) till two years after surgery (P = 0.289). No functional impairment in visual acuity and visual fields was found in the groups of the study. CONCLUSIONS: Single needling procedure is a standard successful method for restoring the function of encapsulated blebs. Postoperative hypotony represents a possible hazard, which can be minimized by additional transconjunctival flap sutures. Long-term results suggest that this modification is equally effective in lowering the IOP and preventing the progression of glaucoma as the standard needling procedure. To our knowledge this is the first study to investigate the long-term effect of tranconjunctival sutures for the prevention of hypotony.

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-independent loss of retinal ganglion cells (RGC), which is accompanied by antibody depositions and increased levels of microglia. In a different animal model we showed that intermittent IOP elevations provoke neurodegeneration in the optic nerve and the retina and elicit changes of IgG autoantibody reactivities. The correlation between neuronal damage and changes in autoantibody reactivity suggests that autoantibody profiling could be a useful biomarker for glaucoma. In vivo studies on neuroretinal cells and porcine retinal explants demonstrated a protective effect of antibodies (eg, anti-GFAP) on RGC, which seems to be the result of reduced stress levels in the retina. We conclude that the absence of some autoantibodies in glaucoma patients reflects a loss of the protective potential of natural autoimmunity and may thus encourage neurodegenerative processes. Concluding, autoantibody profiles resemble useful biomarkers for diagnosis, progression and severity of glaucoma. Future longitudinal studies will help to improve early detection and enable better monitoring of disease progression.