The ophthalmic branch of the Gutenberg Health Study: study design, cohort profile and self-reported diseases

This paper describes the study design, methodology, cohort profile and self-reported diseases in the ophthalmological branch of the Gutenberg Health Study (GHS).The GHS is an ongoing, prospective, interdisciplinary, single-center, population-based cohort study in Germany. The main goals of the ophthalmological section are to assess the prevalence and incidence of ocular diseases and to explore risk factors, genetic determinants and associations with systemic diseases and conditions. The eye examination at baseline included a medical history, self-reported eye diseases, visual acuity, refractive errors, intraocular pressure, visual field, pachymetry, keratometry, fundus photography and tear sampling. The 5-year follow-up visit additionally encompassed optical coherence tomography, anterior segment imaging and optical biometry. The general examination included anthropometry; blood pressure measurement; carotid artery ultrasound; electrocardiogram; echocardiography; spirometry; cognitive tests; questionnaires; assessment of mental conditions; and DNA, RNA, blood and urine sampling.Of 15,010 participants (aged 35-74 years at the time of inclusion), ocular data are available for 14,700 subjects (97.9%). The mean visual acuity (standard deviation), mean spherical equivalent, median decimal visual acuity, and mean intraocular pressure were 0.08 (0.17) logMar, -0.42 (2.43) diopters, 0.9 and 14.24 (2.79) mm Hg, respectively. The frequencies of self-reported strabismus, glaucoma, surgery for retinal detachment and retinal vascular occlusions were 2.7%, 2.3%, 0.2% and 0.4%, respectively.The GHS is the most extensive dataset of ophthalmic diseases and conditions and their risk factors in Germany and one of the largest cohorts worldwide. This dataset will provide new insight in the epidemiology of ophthalmic diseases and related medical specialties

Retrograde Maculopathy in Patients With Glaucoma.

PURPOSE Macular optical coherence tomography (OCT) analysis can be used for quantitative measures of optic nerve atrophy at a location far from the optic nerve head. This recently led to the finding of microcystic macular edema (MME), that is vacuolar inclusions in the macular inner nuclear layer, in some glaucoma patients. The involvement of individual retinal layers is yet unclear in glaucoma. In this study we systematically investigated glaucoma-induced changes in macular layers to evaluate whether glaucoma-associated damage extends beyond the macular ganglion cell layer. PATIENTS AND METHODS We included 218 consecutive patients and 282 eyes with confirmed primary open-angle glaucoma or pseudoexfoliation glaucoma, and macular OCT in a cross-sectional observational study. Eyes were screened for presence of MME. Thickness of individual retinal layers was determined using a semiautomatic segmentation algorithm. Peripapillary nerve fiber layer thickness and mean defect in visual field testing were extracted from OCT and medical records, respectively. Results were compared with a small group of eyes with no apparent glaucoma. RESULTS We found MME in 5 eyes from 5 primary open-angle glaucoma patients and 3 eyes of 3 pseudoexfoliation glaucoma patients (2.8%). MME was confined to the inner nuclear layer in a perifoveal ring and was associated with thinning of the ganglion cell layer and thickening of the macular inner nuclear layer. Glaucoma eyes without MME showed a significant inverse correlation of inner nuclear layer thickness with glaucoma severity. CONCLUSIONS Glaucomatous damage leads to a gradual thickening of the inner nuclear layer, which leads to MME in more severe glaucoma cases. These changes, along with nerve fiber loss and ganglion cell loss, may be summarized as glaucoma-associated retrograde maculopathy

The impact of pseudophakia on vision-related quality of life in the general population - The Gutenberg Health Study.

Cataract surgery is the most frequently performed surgical procedure worldwide. We aim to determine the prevalence of having implanted an artificial lens (pseudophakia) and of no lens (aphakia) and to compare visual function.As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in Germany. An ophthalmological examination including slit-lamp examination was conducted. Prevalence including 95% confidential intervals were calculated and analyses were conducted for systemic and ocular associated factors with pseudophakia using multivariable logistic regression models. Vision-related quality of life was assessed using a standardized questionnaire and Rasch transformation.14,696 people were included. Of these, 1.55% [1.36%-1.77%] had unilateral pseudophakia and 3.08% [2.81%-3.37%] had bilateral pseudophakia. Unilateral aphakia was present in 21 people and bilateral aphakia in 2 people. Pseudophakia was independently associated with age, higher body weight and lower body height, diabetes and smoking. Vision-related quality of life values were similar for those with bilateral phakia and pseudophakia but were lower for those with unilateral pseudophakia.The pseudophakia status is related to several cardiovascular risk factors, indicating a relationship to an aging effect that causes premature lens opacification. Bilateral pseudophakia can almost imitate the physiological condition of phakia except for the need to use glasses

The impact of pseudophakia on vision-related quality of life in the general population -The Gutenberg Health Study

ABSTRACT Cataract surgery is the most frequently performed surgical procedure worldwide. We aim to determine the prevalence of having implanted an artificial lens (pseudophakia) and of no lens (aphakia) and to compare visual function. As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in Germany. An ophthalmological examination including slit-lamp examination was conducted. Prevalence including 95% confidential intervals were calculated and analyses were conducted for systemic and ocular associated factors with pseudophakia using multivariable logistic regression models. Vision-related quality of life was assessed using a standardized questionnaire and Rasch transformation. 14,696 people were included. Of these, 1.55% [1.36%-1.77%] had unilateral pseudophakia and 3.08% [2.81%-3.37%] had bilateral pseudophakia. Unilateral aphakia was present in 21 people and bilateral aphakia in 2 people. Pseudophakia was independently associated with age, higher body weight and lower body height, diabetes and smoking. Vision-related quality of life values were similar for those with bilateral phakia and pseudophakia but were lower for those with unilateral pseudophakia. The pseudophakia status is related to several cardiovascular risk factors, indicating a relationship to an aging effect that causes premature lens opacification. Bilateral pseudophakia can almost imitate the physiological condition of phakia except for the need to use glasses

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Haplotype reference consortium panel: Practical implications of imputations with large reference panels

Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10-61), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium.

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17 mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.Medical Research Council (G1000143), Cancer Research UK (C864/A14136), Research into Ageing (262), Wellcome Trust, Richard Desmond Charitable Trust (via Fight for Sight), National Institute for Health Research, Stichting Lijf en Leven, Krimpen aan de Lek, MD Fonds, Utrecht, Rotterdamse Vereniging Blindenbelangen, Rotterdam, Stichting Oogfonds Nederland, Utrecht, Blindenpenning, Amsterdam, Blindenhulp, The Hague, Algemene Nederlandse Vereniging ter Voorkoming van Blindheid (ANVVB), Doorn, Landelijke Stichting voor Blinden en Slechtzienden, Utrecht, Swart van Essen, Rotterdam, Stichting Winckel-Sweep, Utrecht, Henkes Stichting, Rotterdam, Lameris Ootech BV, Nieuwegein, Medical Workshop, de Meern, NWO (Graduate Programme 2010 BOO (022.002.023)), Laboratoires Thea (Clermont-Ferrand, France), inter regional grant (PHRC) and the regional Council of Burgundy, European Community’s Seventh Framework Programme (FP7/2007-2013), Rheinland-Pfalz AZ 961-386261/733), Johannes Gutenberg-University of Mainz, Boehringer Ingelheim, PHILIPS Medical Systems, Novartis Pharma, Novartis European Union (European Social Fund—ESF), Greek National Strategic Reference Framework (NSRF) (Research Funding Program: THALES), European Social FundThis is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10654-016-0191-

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (−0.17 mmHg per 10 cm; 95 % CI –0.25, −0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans

Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E3) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe

Increasing Prevalence of Myopia in Europe and the Impact of Education

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E3) Consortium. Participants The E3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively - whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). Conclusions Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia