Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study.

AIMS/HYPOTHESIS: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset. METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings. RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised ß=-0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; ß=-0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (ß=0.090; p<0.001 for eGDR) and MZ (ß=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis. CONCLUSIONS/INTERPRETATION: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.

Association of Systemic Medication Use with Glaucoma and Intraocular Pressure: The European Eye Epidemiology Consortium.

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. PARTICIPANTS: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. METHODS: We examined associations of 4 categories of systemic medications-antihypertensive medications (ß-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. MAIN OUTCOME MEASURES: Glaucoma prevalence and IOP. RESULTS: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic ß-blockers was associated with a lower IOP (ß coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic ß-blockers (ß coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic ß-blockers (ß coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (ß coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. CONCLUSIONS: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic ß-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Feasibility and repeatability of ocular biometry measured with IOLMaster 700 in a large population-based study.

PURPOSE: To evaluate the feasibility and repeatability of IOLMaster 700 biometry measurements in an adult population. Furthermore, to assess the value of the Quality Indicators (QIs) provided by the device. METHOD: As part of the large population-based Leipzig Research Centre for Civilization Diseases (LIFE) Adult-Study, randomly selected participants from Leipzig, Germany were evaluated with the ZEISS IOLMaster 700. Age range was 26-85 years, with 53% of participants above 70 years of age. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT) and keratometry (K) were assessed in 1767 right eyes. Measurements were repeated twice and in a subset of 1331 eyes, three times. Measurement feasibility was evaluated for three levels; successful, with warnings and failed, using the inbuilt QIs. Repeatability was assessed as within-subject standard deviation (SD) and repeatability limits were calculated. RESULTS: First measurement success rate for phakic eyes was over 99% for AL, CCT, ACD, over 98% for LT and over 97% for K. K had 16% eyes with warnings and the recommendation to repeat the measurement. Excluding the measurements with warnings resulted in a reduction of mean SD for AL from 48 to 4 µm and for mean K from 0.08 to 0.04 D. Repeatability for phakic eyes was 8 µm for AL, CCT, ACD and LT and 2.3 µm for CCT; 0.07 D and 0.12 D for mean K and delta K, respectively, for phakic cases without warnings (two measurements). CONCLUSIONS: In our population-based sample, the IOLMaster 700 collected data for AL, CCT, ACD, LT and K from the vast majority of eyes. Considering the built-in QIs improved the measurement variability substantially. Repeatability measurements indicate that clinically meaningful changes can be detected reliably with this instrument.

Monochromatic ocular high-order aberrations in children and adolescents.

PURPOSE: To investigate the prevalence and repeatability of high-order aberrations (HOAs) from non-cyclopleged eyes in 1515 children and adolescents 2.5-18 years of age. METHODS: The Leipzig Research Centre for Civilization Diseases (LIFE)-Child study is a population-based, prospective, observational single-centre study that investigates the development of children and adolescents in Germany. Wavefront measurements were repeated three times in each eye of 1515 healthy subjects. Results were described by 36 Zernike coefficients for a 5 mm reference pupil diameter. Short-term repeatability is given for each coefficient. The impact on vision is described by the root mean squared (RMS) value of the HOA Zernike coefficients. RESULTS: High-order aberrations were dominated by five contributions. For 1004 right eyes: spherical aberration (c12 = 0.06 ± 0.07 µm), coma (c7 = 0.03 ± 0.09 µm, c8 = 0.03 ± 0.06 µm) and trefoil (c6 = -0.01 ± 0.07 µm, c9 = 0.008 ± 0.06 µm). The RMS value was 0.18 ± 0.06 µm. Modes higher than fourth order do not contribute clinically to the aberrations. HOAs show no clinically significant dependency with age. Instead, HOA values agree well with previous results on aberrations in adult eyes. Spherical aberration was highly correlated between the two eyes. Repeatability was worst for coma, 0.033 µm, due to variability in the alignment of the pupil centre. The left eye showed, on average, a 0.08 mm larger pupil diameter than the right eye (p < 0.02). CONCLUSIONS: Across the age span from 2.5 to 18 years, we see the same distribution of HOA as for adults. We established that only five Zernike coefficients, spherical aberration, coma and trefoil were of clinical significance in healthy eyes. A high correlation between the two eyes for spherical aberration suggests a common blueprint for each eye in any one subject.

The relationship between myopia and near work, time outdoors and socioeconomic status in children and adolescents.

BACKGROUND: To investigate environmental and social risk factors for myopia in children and adolescents in Germany. METHODS: 1437 children aged between 3 and 18 inclusive were examined as part of the LIFE Child study based in Leipzig, Germany. Information about leisure time activities and social status was ascertained by parents and children in a questionnaire. Refractive status was attained by measuring noncycloplegic autorefraction. Myopia was defined as spherical equivalent (SE) ≤ - 0.75 D. Risk factors were identified using multiple logistic regression analysis. RESULTS: In multiple logistic regression analysis, myopia was significantly associated with less frequent outdoor activity ("once a week" vs. "twice a week or more": odds ratio (OR) 4.35, 95% confidence interval (CI) 1.89-9.98, p<0.01) and longer near work sessions (1-2 h vs. < 1 h: OR 1.83, CI 1.10-3.04, p=0.02; > 3 h vs. < 1 h: OR 3.71, CI 1.43-9.61, p<0.01) after adjustment for age, sex and socioeconomic status (SES). Duration of outdoor activity, near work frequency and SES showed no significant association with myopia (p > 0.05). Children with a lower SES were involved in longer periods of outdoor and near work activities but on fewer occasions over the course of the week, although this connection was not significant. CONCLUSION: Myopia is associated with environmental factors. The present findings suggest that daily exposure to sunlight and a restriction of long-duration near work activities might protect against pathological eye growth. Prevention strategies should be implemented for children at all ages.

Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness-the LIFE-Adult Study.

BACKGROUND: Circumpapillary retinal nerve fiber layer thickness (cpRNFLT) as assessed by spectral domain optical coherence tomography (SD-OCT) is a new technique used for the detection and evaluation of glaucoma and other optic neuropathies. Before translating cpRNFLT into clinics, it is crucially important to investigate anthropometric, biochemical, and clinical parameters potentially affecting cpRNFLT in a large population-based dataset. METHODS: The population-based LIFE-Adult Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. All participants underwent standardized systemic assessment of various cardiometabolic risk markers and ocular imaging, including cpRNFLT measurement using SD-OCT (Spectralis, Heidelberg Engineering). After employing strict SD-OCT quality criteria, 8952 individuals were analyzed. Multivariable linear regression analyses were used to evaluate the independent associations of various cardiometabolic risk markers with sector-specific cpRNFLT. For significant markers, the relative strength of the observed associations was compared to each other to identify the most relevant factors influencing cpRNFLT. In all analyses, the false discovery rate method for multiple comparisons was applied. RESULTS: In the entire cohort, female subjects had significantly thicker global and also sectoral cpRNFLT compared to male subjects (p < 0.05). Multivariable linear regression analyses revealed a significant and independent association between global and sectoral cpRNFLT with biomarkers of renal function and lipid profile. Thus, thinner cpRNFLT was associated with worse renal function as assessed by cystatin C and estimated glomerular filtration rate. Furthermore, an adverse lipid profile (i.e., low high-density lipoprotein (HDL) cholesterol, as well as high total, high non-HDL, high low-density lipoprotein cholesterol, and high apolipoprotein B) was independently and statistically significantly related to thicker cpRNFLT. In contrast, we do not observe a significant association between cpRNFLT and markers of inflammation, glucose homeostasis, liver function, blood pressure, or obesity in our sector-specific analysis and globally. CONCLUSIONS: Markers of renal function and lipid metabolism are predictors of sectoral cpRNFLT in a large and deeply phenotyped population-based study independently of previously established covariates. Future studies on cpRNFLT should include these biomarkers and need to investigate whether incorporation will improve the diagnosis of early eye diseases based on cpRNFLT.

Ocular biometry in children and adolescents from 4 to 17 years: a cross-sectional study in central Germany.

PURPOSE: To evaluate ocular biometry in a large paediatric population as a function of age and sex in children of European descent. METHODS: Children were examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Disease), a population-based study in Leipzig, Germany. Altogether, 1907 children, aged from 4 to 17 years, were examined with the Lenstar LS 900. Data from the right eye was analysed for axial length, central corneal thickness, flat and steep corneal radii, aqueous depth, lens thickness and vitreous depth. Wavefront-based autorefraction was employed for analysis. RESULTS: Axial length increased in girls from 21.6 mm (4 years) up to 23.4 mm (17 years); this increase (0.174 mm per year) was statistically significant up to age 14 (23.3 mm). Axial length increased in boys from 22.2 mm (4 years) up to 23.9 mm (17 years); this increase (0.178 mm per year) was statistically significant up to age 10 (23.3 mm). No change was observed for central corneal thickness (average: girls 550 µm; boys 554 µm). Corneal curvature in girls was somewhat flatter at age 4 (7.70 mm) compared to age 10 (7.78 mm), whereas it was constant in boys (7.89 mm). Aqueous depth at age 4 was 2.73 mm for girls and 2.86 mm for boys, with the same rate of increase per year (girls: 0.046 mm; boys: 0.047 mm) from age 4 to 10. At age 17, aqueous depth was 3.06 mm in girls and 3.20 mm in boys. Lens thickness was reduced from age 4 (3.75 mm) to age 10 (3.47 mm) in girls and from age 4 (3.73 mm) to age 10 (3.44 mm) in boys, with the same rate of decrease per year of 0.046 and 0.047 mm, respectively. At age 17, lens thickness was 3.52 mm in girls and 3.50 mm in boys. Vitreous depth at age 4 was 14.51 mm for girls and 15.08 mm for boys; with 0.156 mm (girls) or 0.140 mm (boys) increase per year until age 14 (girls: 16.08 mm; boys: 16.48 mm). At age 17, vitreous depth was 16.29 mm in girls and 16.62 mm in boys. CONCLUSIONS: Eye growth (axial length) in girls showed a lag of about four years compared to boys. Aqueous depth increase matches the lens thickness decrease from ages 4 to 10 years in girls and boys. Lens thickness minimum is reached at 11 years in girls and at 12 years in boys. All dimensions of the optical ocular components are closely correlated with axial length. These data may serve as normative values for the assessment of eye growth in central European children and will provide a basis for monitoring refractive error development.

Feasibility and repeatability of ocular biometry measured with Lenstar LS 900 in a large group of children and adolescents.

PURPOSE: To evaluate the feasibility and repeatability of Lenstar LS 900 biometry measurements in a paediatric population. METHODS: Children were examined as part of the LIFE Child Study (Leipzig Research Centre for Civilization Diseases), a population-based study in Leipzig, Germany. Altogether, 1917 children, aged from 3.5 to 17.5 years, were assessed with the Haag Streit Lenstar LS 900. Three consecutive measurements of the right eye were analysed for axial length, central corneal thickness, anterior chamber depth, aqueous depth, lens thickness and flat and steep corneal radii. The number of successful measurements and repeatability were evaluated for each parameter and three age bands (3.5 to 6.5 years, 6.5 to 10.5 years and 10.5 to 17.5 years). RESULTS: Best measurement feasibility was found for axial length and central corneal thickness (91% to 100%), followed by flat and steep corneal radii (86% to 100%), anterior chamber and aqueous depth (76% to 92%) and lens thickness (50% to 81%), with higher numbers for older children. Repeatability values (in mm) were: axial length 0.025 to 0.035; central corneal thickness 0.003 to 0.027; aqueous depth 0.024 to 0.058; anterior chamber 0.024 to 0.054; lens thickness 0.034 to 0.067. An overall trend showed better repeatability for older children, especially for central corneal thickness, aqueous depth and lens thickness. CONCLUSIONS: For ocular biometry in the paediatric population, axial length, central corneal thickness, flat and steep corneal radii can be measured very reliably even in children from 4 years old onward using the Lenstar LS 900. Lens thickness can be quantified in a limited number of younger children. Repeatability was high for all variables investigated. Repeatability improved with age, reaching adult values in the adolescent age band. Established repeatability limits can be applied in future studies as a quality parameter.

Sex-Specific Differences in Circumpapillary Retinal Nerve Fiber Layer Thickness.

PURPOSE: To investigate the role of sex on retinal nerve fiber layer (RNFL) thickness at 768 circumpapillary locations based on OCT findings. DESIGN: Population-based cross-sectional study. PARTICIPANTS: We investigated 5646 eyes of 5646 healthy participants from the Leipzig Research Centre for Civilization Diseases (LIFE)-Adult Study of a predominantly white population. METHODS: All participants underwent standardized systemic assessments and ocular imaging. Circumpapillary RNFL (cRNFL) thickness was measured at 768 points equidistant from the optic nerve head using spectral-domain OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). To control ocular magnification effects, the true scanning radius was estimated by scanning focus. Student t test was used to evaluate sex differences in cRNFL thickness globally and at each of the 768 locations. Multivariable linear regression and analysis of variance were used to evaluate individual contributions of various factors to cRNFL thickness variance. MAIN OUTCOME MEASURES: Difference in cRNFL thickness between males and females. RESULTS: Our population consisted of 54.8% females. The global cRNFL thickness was 1 µm thicker in females (P < 0.001). However, detailed analysis at each of the 768 locations revealed substantial location specificity of the sex effects, with RNFL thickness difference ranging from -9.98 to +8.00 µm. Females showed significantly thicker RNFLs in the temporal, superotemporal, nasal, inferonasal, and inferotemporal regions (43.6% of 768 locations), whereas males showed significantly thicker RNFLs in the superior region (13.2%). The results were similar after adjusting for age, body height, and scanning radius. The superotemporal and inferotemporal RNFL peaks shifted temporally in females by 2.4° and 1.9°, respectively. On regions with significant sex effects, sex explained more RNFL thickness variance than age, whereas the major peak locations and interpeak angle explained most of the RNFL thickness variance unexplained by sex. CONCLUSIONS: Substantial sex effects on cRNFL thickness were found at 56.8% of all 768 circumpapillary locations, with specific patterns for different sectors. Over large regions, sex was at least as important in explaining the cRNFL thickness variance as was age, which is well established to have a substantial impact on cRNFL thickness. Including sex in the cRNFL thickness norm could therefore improve glaucoma diagnosis and monitoring.

Pseudoexfoliation syndrome: analysis of systemic comorbidities of 325 PEX-positive patients compared with 911 PEX-negative patients.

PURPOSE: Pseudoexfoliation syndrome (PEX) is an age-related systemic elastic fibrillopathy disorder featuring an excessive production and accumulation of elastic fibre components in the extracellular matrix and is associated with impaired protective mechanisms against oxidative and cellular stress. PEX is diagnosed solely by ophthalmologists; however, PEX deposits have been detected in the connective tissues of many extraocular organ systems. This large, retrospective case-control study investigates whether patients with PEX have an increased risk of extraocular comorbidities. METHODS: Cases and controls were drawn from consecutive patients over 50 years of age undergoing in-house ophthalmological operations under general anaesthesia or in standby preparedness for general anaesthesia. The participants were grouped based solely on PEX-positive (n = 325) or PEX-negative (n = 911) status. The same teams of ophthalmologists and anaesthesiologists uniformly documented every known systemic comorbidity of each patient through two independent rounds of standard anamnestic procedure and protocols in preparation for general anaesthesia. For the purpose of this study, every systemic comorbidity was registered from these forms and subsequently categorized into 17 disease groups based on the International Classification of Diseases (ICD-10) of the World Health Organization (WHO). Odds ratios (ORs) comparing comorbidities in cases and controls were adjusted for age and gender using logistic regression. RESULTS: After adjustment for multiple testing, patients with PEX had an increased odds ratio for respiratory OR 2.1 [1.4; 3.0], cardiac OR 2.5 [1.6; 4.2], vascular OR 2.0 [1.4; 2.8], and urogenital conditions OR 2.3 [1.4; 3.7]. Renal and psychiatric comorbidities were nominally significant. While no substantially higher frequency was found for hernias, aneurysms, aortic dissection, or varicose veins among PEX-positive patients, higher rates of cardiac valve disorders and benign prostate hyperplasia were found among the PEX-positive individuals. CONCLUSION: In addition to confirming an increased risk of respiratory, cardiovascular, and urogenital comorbidities, our data found an increased risk of cardiac valve disorders and benign prostate hyperplasia among PEX-positive patients, which may be manifestations of the underlying systemic elastotic fibrillopathy and warrants further exploration, including future histological study.

Agreement and Repeatability of Noncycloplegic and Cycloplegic Wavefront-based Autorefraction in Children.

SIGNIFICANCE: Increasing prevalence of refractive error requires assessment of ametropia as a screening tool in children. If cycloplegia is not an option, knowledge about the increase in uncertainty for wavefront-based autorefraction is needed. The cycloplegic agent as the principal variant presents cross-reference and allows for extraction of the influence of accommodation. PURPOSE: The purpose of this study was to determine the repeatability, agreement, and propensity to accommodate of cycloplegic (ARc) and noncycloplegic (ARnc) wavefront-based autorefraction (ZEISS i.Profiler plus; Carl Zeiss Vision, Aalen, Germany) in children aged 2 to 15 years. METHODS: In a clinical setting, three consecutive measurements were feasible for 145 eyes (OD) under both conditions. Data are described by spherical equivalent (M), horizontal or vertical astigmatic component (J0), and oblique astigmatic component (J45). In the case of M, the most positive value of the three measurements was chosen, whereas the mean was applied for astigmatic components. RESULTS: Regarding agreement, differences for ARc minus ARnc were statistically significant: for M, 0.55 (0.55 D; mean [SD]; P < .001), that is, more hyperopic in cycloplegia; for J0, -0.03 (0.11 D; P = .002); and for J45, -0.03 D (SD, 0.09 D; P < .001). Regarding repeatability, astigmatic components showed excellent repeatability: SD < 0.11 D (ARnc) and SD < 0.09 D (ARc). The repeatability of M was SD = 0.57 D with a 95% interval of 1.49 D (ARnc). Under cycloplegia, this decreased to SD = 0.17 D (ARc) with a 95% interval of 0.50 D. The mean propensity to accommodate was 0.44 D from repeated measurements; in cycloplegia, this was reduced to 0.19 D. CONCLUSIONS: Wavefront-based refraction measurement results are highly repeatable and precise for astigmatic components. Noncycloplegic measurements of M show a systematic bias of 0.55 D. Cycloplegia reduces the propensity to accommodate by a factor of 2.4; for noncycloplegic repeated measurements, accommodation is controlled to a total interval of 1.49 D (95%). Without cycloplegia, results improve drastically when measurements are repeated.

Cortical Cataract and Refractive Error.

PURPOSE: To evaluate the relationship between the presence of cortical cataract and accommodation effort, using refractive error as a proxy. METHODS: Patients between 50 and 90 years, scheduled for cataract surgery, were selected with the help of a photographic database. Nuclear and cortical cataract were graded and patients grouped having no cataract, pure cortical, mixed or pure nuclear cataract. Refraction data at the time of the photograph was converted to estimated spherical equivalent refractive error each patient would have had at the age of 45 years. RESULTS: From the initial 239 eyes from 239 patients, cases with myopia below -6.5 dpt and hyperopia above 6.5 dpt were excluded, resulting in 199 cases for final analysis. Eyes with no cataract showed the lowest median refractive error (-3.65 dpt), followed by the pure nuclear group (-2.69 dpt). The median refractive error for pure cortical (-0.23 dpt) and mixed cataracts (-0.87 dpt) were close to emmetropia. Cortical cataracts were found in 37% of myopes, 82% of emmetropes, and 85% of hyperopes. CONCLUSION: Emmetropes and hyperopes tend to develop more cortical cataract than myopes. These cortical cataracts might be caused by shear stress inside the crystalline lens due to accommodation efforts at the time of onset of presbyopia.

Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population.

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3-82.1±4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8±21.4 µm in the Rotterdam Study I to 104.7±12.5 µm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (ß = -0.38 µm/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (ß = -0.36 µm/mmHg; 95% CI, -0.56 to -0.15), visual impairment (ß = -5.50 µm; 95% CI, -9.37 to -1.64), and history of systemic hypertension (ß = -0.54 µm; 95% CI, -1.01 to -0.07) and stroke (ß = -1.94 µm; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (ß = -3.11 µm; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (ß = 1.39 µm/diopter; 95% CI, 1.19-1.59) and smoking (ß = 1.53 µm; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities.

The LIFE Child study: a population-based perinatal and pediatric cohort in Germany.

The LIFE Child study is a large population-based longitudinal childhood cohort study conducted in the city of Leipzig, Germany. As a part of LIFE, a research project conducted at the Leipzig Research Center for Civilization Diseases, it aims to monitor healthy child development from birth to adulthood and to understand the development of lifestyle diseases such as obesity. The study consists of three interrelated cohorts; the birth cohort, the health cohort, and the obesity cohort. Depending on age and cohort, the comprehensive study program comprises different medical, psychological, and sociodemographic assessments as well as the collection of biological samples. Optimal data acquisition, process management, and data analysis are guaranteed by a professional team of physicians, certified study assistants, quality managers, scientists and statisticians. Due to the high popularity of the study, more than 3000 children have already participated until the end of 2015, and two-thirds of them participate continuously. The large quantity of acquired data allows LIFE Child to gain profound knowledge on the development of children growing up in the twenty-first century. This article reports the number of available and analyzable data and demonstrates the high relevance and potential of the study.

Hessian-LoG filtering for enhancement and detection of photoreceptor cells in adaptive optics retinal images.

Automated analysis of retinal images plays a vital role in the examination, diagnosis, and prognosis of healthy and pathological retinas. Retinal disorders and the associated visual loss can be interpreted via quantitative correlations, based on measurements of photoreceptor loss. Therefore, it is important to develop reliable tools for identification of photoreceptor cells. In this paper, an automated algorithm is proposed, based on the use of the Hessian-Laplacian of Gaussian filter, which allows enhancement and detection of photoreceptor cells. The performance of the proposed technique is evaluated on both synthetic and high-resolution retinal images, in terms of packing density. The results on the synthetic data were compared against ground truth as well as cone counts obtained by the Li and Roorda algorithm. For the synthetic datasets, our method showed an average detection accuracy of 98.8%, compared to 93.9% for the Li and Roorda approach. The packing density estimates calculated on the retinal datasets were validated against manual counts and the results obtained by a proprietary software from Imagine Eyes and the Li and Roorda algorithm. Among the tested methods, the proposed approach showed the closest agreement with manual counting.

Biometry and visual function of a healthy cohort in Leipzig, Germany.

BACKGROUND: Cross-sectional survey of ocular biometry and visual function in healthy eyes across the life span of a German population aged 20 to 69 years (n = 218). Subject number in percent per age category reflected the percentage within the respective age band of the population of Leipzig, Germany. METHODS: Measurements obtained: subjective and objective refraction, best-corrected visual acuity, accommodation, contrast sensitivity, topography and pachymetry with Scheimpflug camera, axial length with non-contact partial coherence interferometry, and spectral-domain optical coherence tomography of the retina. Pearson correlation coefficients with corresponding p-values were given to present interrelationships between stature, biometric and refractive parameters or their associations with age. Two-sample T-tests were used to calculate gender differences. The area under the logarithmic contrast sensitivity function (AULCSF) was calculated for the analysis of contrast sensitivity as a single figure across a range of spatial frequencies. RESULTS: The results of axial length (AL), anterior chamber depth (ACD) and anterior chamber volume (ACV) differed as a function of the age of the participants (rho (p value): AL -0.19 (0.006), ACD -0.56 (< 0.001), ACV-0.52 (< 0.001)). Longer eyes had deeper ACD (AL:ACD 0.62 (< 0.001), greater ACV (AL:ACV 0.65 (< 0.001) and steeper corneal radii (AL:R1ant; R2ant; R1post; R2post 0.40; 0.35; 0.36; 0.36 (all with (< 0.001)). Spherical equivalent was associated with age (towards hyperopia: 0.34 (< 0.001)), AL (-0.66 (< 0.001)), ACD (-0.52 (< 0.001)) and ACV (-0.46 (< 0.001)). Accommodation was found lower for older subjects (negative association with age, r = -0.82 (< 0.001)) and contrast sensitivity presented with smaller values for older ages (AULCSF -0.38, (< 0.001)), no change of retinal thickness with age. 58 % of the study cohort presented with a change of refractive correction above ±0.50 D in one or both eyes (64 % of these were habitual spectacle wearers), need for improvement was present in the young age-group and for older subjects with increasing age. CONCLUSION: Biometrical data of healthy German eyes, stratified by age, gender and refractive status, enabled cross-comparison of all parameters, providing an important reference database for future patient-based research and specific in-depth investigations of biometric data in epidemiological research. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01173614 July 28, 2010.

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Early peripheral laser photocoagulation of nonperfused retina improves vision in patients with central retinal vein occlusion (Results of a proof of concept study).

BACKGROUND: To evaluate the effect of combination of ranibizumab and laser photocoagulation to peripheral retinal areas of nonperfusion in patients with non-ischemic central retinal vein occlusion (CRVO) without neovascularizations. METHODS: This prospective, proof of concept study randomized 22 CRVO patients into two arms. The RL group (ranibizumab + laser; n = 10) received ranibizumab with additive laser photocoagulation; the control R group (n = 12) was treated with ranibizumab only. All patients received three initial monthly ranibizumab injections followed by PRN regimen. Changes in best corrected visual acuity (BCVA) and in central retinal thickness (CRT) were documented over 6 months. RESULTS: Median of BCVA improved in the RL group from 65 ETDRS letters (interquartile range IQR = 10 letters) at baseline to 70 (IQR = 23.2) letters at month 6. In the control group BCVA remained stable [baseline: 61 (IQR = 19.5) and month 6: 61 (IQR = 22) letters]. CRT decreased between baseline and final visit in the RL group from 547 (IQR = 513) µm to 246.5 (IQR = 346.3) µm, and in the control group from 637.5 (IQR = 344) µm to 423 (IQR = 737) µm. More pronounced improvements in BCVA were seen in the RL group (medians = 14 vs. 6.5 letters) although the observed group differences were not statistically significant due to small samples. CONCLUSIONS: The selective laser photocoagulation of peripheral areas of nonperfusion seems to lead to additional visual improvement in patients with CRVO. A larger replication trial is necessary to confirm the results of this proof of concept study.

Retinal OCT biomarkers and their association with cognitive function-clinical and AI approaches.

Retinal optical coherence tomography (OCT) biomarkers have the potential to serve as early, noninvasive, and cost-effective markers for identifying individuals at risk for cognitive impairments and neurodegenerative diseases. They may also aid in monitoring disease progression and evaluating the effectiveness of interventions targeting cognitive decline. The association between retinal OCT biomarkers and cognitive performance has been demonstrated in several studies, and their importance in cognitive assessment is increasingly being recognized. Machine learning (ML) is a branch of artificial intelligence (AI) with an exponential number of applications in the medical field, particularly its deep learning (DL) subset, which is widely used for the analysis of medical images. These techniques efficiently deal with novel biomarkers when their outcome for the applications of interest is unclear, e.g., for diagnosis, prognosis prediction, disease staging, or any other relevance to clinical practice. However, using AI-based tools for medical purposes must be approached with caution, despite the many efforts to address the black-box nature of such approaches, especially due to the general underperformance in datasets other than those used for their development. Retinal OCT biomarkers are promising as potential indicators for decline in cognitive function. The underlying mechanisms are currently being explored to gain deeper insights into this relationship linking retinal health and cognitive function. Insights from neurovascular coupling and retinal microvascular changes play an important role. Further research is needed to establish the validity and utility of retinal OCT biomarkers as early indicators of cognitive decline and neurodegenerative diseases in routine clinical practice. Retinal OCT biomarkers could then provide a new avenue for early detection, monitoring and intervention in cognitive impairment with the potential to improve patient care and outcomes.