Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood.

Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present.

Baseline characteristics and progression of neovascular age-related macular degeneration in patients receiving over 60 intravitreal injections of anti-vascular endothelial growth factor.

Age-related macular degeneration (AMD) is the leading cause of vision loss in older populations of industrialized countries. Antibody-based therapy inhibiting the vascular endothelial growth factor (VEGF) has been very successful in the treatment of the neovascular form of AMD. This retrospective clinical study investigates the baseline characteristics and progression of neovascular age-related macular degeneration (nAMD) in patients who received over 60 anti-VEGF intravitreal injections.

[Awareness for glaucoma in the general population].

Background: Glaucoma is not a rare entity but because very few symptoms occur and visual field defects are frequently first recognized at a late stage, a large proportion of glaucoma diseases remain undetected. The aim of this study was to identify the proportion of undiagnosed glaucoma in German population-based cohort studies and to contextualize them in the context of the literature.

Material And Methods: The prevalence of glaucoma in the Gutenberg Health Study (GHS) and the age-related investigations on health of the University of Regensburg (AugUR) was evaluated based on visual field examinations and optic disc color photography according to the ISGEO criteria.

Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration.

Purpose: The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD.

Methods: In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage.

Age-Related Macular Degeneration in an Ageing Society - Current Epidemiological Research.

Epidemiological studies on age-related macular degeneration (AMD) provide crucial data on the frequency of early and late forms as well as associated risk factors. The increasing number of population-based cross-sectional and longitudinal cohort studies in Germany and Europe with published data is making prevalence and incidence estimators for AMD more robust, although they show mostly method-related fluctuations. This review article brings together the latest published epidemiological measures for AMD from Germany and Central as well as Western Europe.

Polygenic scores for estimated glomerular filtration rate in a population of general adults and elderly - comparative results from the KORA and AugUR study.

Background: Polygenic scores (PGSs) combining genetic variants found to be associated with creatinine-based estimated glomerular filtration rate (eGFR) have been applied in various study populations with different age ranges. This has shown that PGS explain less eGFR variance in the elderly. Our aim was to understand how differences in eGFR variance and the percentage explained by PGS varies between population of general adults and elderly.

Cardiovascular Risk Factor Control in 70- to 95-Year-Old Individuals: Cross-Sectional Results from the Population-Based AugUR Study.

Cardiovascular risk factors such as high glucose, LDL-cholesterol, blood pressure, and impaired kidney function are particularly frequent in old-aged individuals. However, population-based data on the extent of cardiovascular risk factor control in the old-aged population is limited. AugUR is a cohort of the mobile "70+"-year-old population of/near Regensburg, recruited via population registries.

Photostress Recovery Time as a Potential Predictive Biomarker for Age-Related Macular Degeneration.

Purpose: The purpose of this study was to assess recovery time following photostress and its association with age-related macular degeneration (AMD) cross-sectionally and longitudinally in an elderly population-based cohort.

Methods: We analyzed photostress recovery time (PRT) and AMD in >1800 AugUR study participants aged 70+ years. On color fundus images from baseline and 3-year follow-up, presence of AMD was graded manually (Three Continent AMD Consortium Severity Scale).

Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans.

Background/aims: To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population.

Methods: We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis.

Self-report of chronic diseases in old-aged individuals: extent of agreement with general practitioner medical records in the German AugUR study.

Background: To estimate prevalence and incidence of diseases through self-reports in observational studies, it is important to understand the accuracy of participant reports. We aimed to quantify the agreement of self-reported and general practitioner-reported diseases in an old-aged population and to identify socio-demographic determinants of agreement.

Methods: This analysis was conducted as part of the AugUR study (n=2449), a prospective population-based cohort study in individuals aged 70-95 years, including 2321 participants with consent to contact physicians.

Relative Telomere Length Is Associated With Age-Related Macular Degeneration in Women.

Purpose: Relative telomere length (RTL) is a biomarker for physiological aging. Premature shortening of telomeres is associated with oxidative stress, which is one possible pathway that might contribute to age-related macular degeneration (AMD). We therefore aimed to investigate the association between RTL and AMD in a well-characterized group of elderly individuals.

Incidence, progression and risk factors of age-related macular degeneration in 35-95-year-old individuals from three jointly designed German cohort studies.

Objective: To estimate age-related macular degeneration (AMD) incidence/progression across a wide age range.

Methods And Analysis: AMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification, CC) was assessed for 1513 individuals aged 35-95 years at baseline from three jointly designed population-based cohorts in Germany: Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Fit, KORA-FF4) and Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg (AugUR) with 18-year, 14-year or 3-year follow-up, respectively. Baseline assessment included lifestyle, metabolic and genetic markers.

Changes in healthcare seeking and lifestyle in old aged individuals during COVID-19 lockdown in Germany: the population-based AugUR study.

Background: Containment measures in the COVID-19 pandemic protected individuals at high risk, particularly individuals at old age, but little is known about how these measures affected health-related behavior of old aged individuals. We aimed to investigate the impact of the spring 2020 lockdown in Germany on healthcare-seeking and health-related lifestyle in the old aged and to identify susceptible subgroups.

Methods: We conducted a follow-up survey among the pre-pandemically well-characterized participants of our AugUR cohort study, residents in/around Regensburg aged 70+ years and relatively mobile.

Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study.

Objective: European guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.

Design: A cross-sectional analysis was performed in the German AugUR study (ltersbezogene ntersuchungen zur esundheit der niversity of egensburg).

Physical Activity, Incidence, and Progression of Age-Related Macular Degeneration: A Multicohort Study.

Purpose: To investigate the impact of physical activity (PA) on the incidence or progression of age-related macular degeneration (AMD) in the general population.

Design: Meta-analysis of longitudinal cohort studies.

Methods: We included 14,630 adults with no or early AMD at baseline from 7 population-based studies and examined associations of PA with AMD incidence and progression using multistate models (MSM) per study and subsequent random effects meta-analysis.

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease.

Background: Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD.

Methods: To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB).

Chances and challenges of machine learning-based disease classification in genetic association studies illustrated on age-related macular degeneration.

Imaging technology and machine learning algorithms for disease classification set the stage for high-throughput phenotyping and promising new avenues for genome-wide association studies (GWAS). Despite emerging algorithms, there has been no successful application in GWAS so far. We establish machine learning-based phenotyping in genetic association analysis as misclassification problem.

[Mutation-Dependent Mechanisms and Their Impact on Targeted Therapeutic Strategies with Reference to Bestrophin 1 and the Bestrophinopathies].

Bestrophin 1 () encodes an integral membrane protein localized in the basolateral aspect of the retinal pigment epithelium. Mutations in BEST1 are associated with distinct retinal dystrophies, the so-called "bestrophinopathies", often causing visual impairment, even in early childhood. The clinical entities of the bestrophinopathies can be distinguished by phenotypic characteristics and mode of inheritance of the respective gene defect.

Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies.

Best vitelliform macular dystrophy (BD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and the autosomal recessive bestrophinopathy (ARB), together known as the bestrophinopathies, are caused by mutations in the bestrophin-1 () gene affecting anion transport through the plasma membrane of the retinal pigment epithelium (RPE). To date, while no treatment exists a better understanding of BEST1-related pathogenesis may help to define therapeutic targets. Here, we systematically characterize functional consequences of mutant BEST1 in thirteen RPE patient cell lines differentiated from human induced pluripotent stem cells (hiPSCs).

Assessment of Novel Genome-Wide Significant Gene Loci and Lesion Growth in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Importance: Age-related macular degeneration (AMD) is a common threat to vision loss in individuals older than 50 years. While neovascular complications in AMD are treatable, there is currently no therapy for geographic atrophy secondary to AMD. Geographic atrophy lesion progression over time shows considerable interindividual variability, but little is known about prognostic factors.

Response misclassification in studies on bilateral diseases.

Misclassification in binary outcomes can severely bias effect estimates of regression models when the models are naively applied to error-prone data. Here, we discuss response misclassification in studies on the special class of bilateral diseases. Such diseases can affect neither, one, or both entities of a paired organ, for example, the eyes or ears.

Retinal Layer Thicknesses in Early Age-Related Macular Degeneration: Results From the German AugUR Study.

Purpose: To systematically analyze thicknesses of retinal layers in an older population and their link to early age-related macular degeneration (AMD).

Methods: In the AugUR baseline survey from a population aged ≥70 years, we conducted multimodal retinal imaging, including spectral-domain optical coherence tomography. Autosegmentation of eight distinct retinal layers was followed by manual correction of segmentation errors.

Views of ophthalmologists on the genetics of age-related macular degeneration: Results of a qualitative study.

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries. It is a multifactorial disease of the retina modified by environmental/individual (e.g.

Generation of Functional Retinal Pigment Epithelium from Human Induced Pluripotent Stem Cells.

The availability of otherwise not readily accessible intraocular cells via induced pluripotent stem cell (iPSC) technology offers great potential for disease modelling, drug screening, and cell-based transplantation therapy in degenerative ocular disorders. Direct differentiation of iPSCs into retinal pigment epithelium (RPE) is particularly straightforward, and iPSC-derived RPE cell cultures have been demonstrated to yield pure populations of functional cells that display many features of native RPE. Here, I describe a protocol for the generation of iPSC-derived RPE monolayer, their propagation, and cryostorage.

On the impact of different approaches to classify age-related macular degeneration: Results from the German AugUR study.

While age-related macular degeneration (AMD) poses an important personal and public health burden, comparing epidemiological studies on AMD is hampered by differing approaches to classify AMD. In our AugUR study survey, recruiting residents from in/around Regensburg, Germany, aged 70+, we analyzed the AMD status derived from color fundus images applying two different classification systems. Based on 1,040 participants with gradable fundus images for at least one eye, we show that including individuals with only one gradable eye (n = 155) underestimates AMD prevalence and we provide a correction procedure.