To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Meta-analysis of eleven population-based cohort studies of the European Eye Epidemiology (E3) consortium. A total of 143240 participants were included in the glaucoma analyses and 47177 participants in the IOP analyses. We examined associations of four categories of systemic medications (antihypertensive medications: beta-blockers, diuretics, calcium channel blockers [CCBs], alpha-agonists, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers; lipid-lowering medications; antidepressants; antidiabetic medications) with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Multivariable regression analyses were carried out in each study and results were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in diabetic participants only. Glaucoma prevalence and IOP. In the meta-analyses of our maximally-adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR] with corresponding 95% confidence interval [95% CI]: 1.23 [1.08 to 1.39]). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR [95% CI]: 1.96 [1.23 to 3.12]). The use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications were not clearly associated with glaucoma. Use of systemic beta-blockers was associated with a lower IOP (Beta [95% CI]: -0.33 [-0.57 to -0.08] mmHg). Monotherapy of both selective (Beta [95% CI]: -0.45 [-0.74 to -0.16] mmHg) and non-selective (Beta [95% CI]: -0.54 [-0.94 to -0.15] mmHg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (Beta [95% CI]: -0.30 [-0.47; -0.14] mmHg), but not when used as monotherapy. Use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not associated with IOP. 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 beta-blocker use. Both findings are potentially important given that glaucoma patients frequently use systemic antihypertensive medications. Determining whether the CCB association is causal should be a research priority.

The 2013 World Health Organization Status Report on Road Safety estimated that approximately 1.24 million deaths occur annually due to road traffic crashes with most of the burden falling on low- and middle-income countries. The objective of this research is to study the prevalence of road traffic crashes in Mekelle, Tigray, Northern Ethiopia and to identify risk factors with the ultimate goal of informing prevention activities and policies. This study used a cross-sectional design to measure the prevalence and factors associated with road traffic crashes among 4-wheeled minibus (n = 130) and 3-wheeled Bajaj (n = 582) taxi drivers in Mekelle, Ethiopia. Bivariate and multivariate logistic regression were used to evaluate the association between risk factors and drivers’ involvement in a road traffic crash within the 3 years prior to the survey. Among the 712 taxi drivers, 26.4% (n = 188) of them reported involvement in a road traffic crash within the past 3 years. Drivers who listened to mass media had decreased likelihood of road traffic crash involvement (AOR = 0.51, 0.33–0.78), while speedy driving (AOR = 4.57, 3.05–7.44), receipt of a prior traffic punishment (AOR = 4.57, 2.67–7.85), and driving a mechanically faulty taxi (AOR = 4.91, 2.81–8.61) were strongly associated with road traffic crash involvement. Receiving mobile phone calls while driving (AOR = 1.91, 1.24–2.92) and history of alcohol use (AOR = 1.51, 1.00–2.28) were also associated with higher odds of road traffic crash involvement. The results of this study show that taxi drivers in Mekelle habitually place themselves at increased risk of road traffic crashes by violating traffic laws, especially related to speedy driving, mobile phone use, and taxi maintenance. This research can be used to support re-evaluation of the type, severity, and enforcement of traffic violation penalties.

Purpose: We investigated relationship of glaucoma with measurements related to autonomic dysfunction, including heart rate variability (HRV) and blood pressure (BP). Methods: Glaucoma was defined using a questionnaire-based algorithm for 86,841 LifeLines Cohort Study participants. Baseline HRV (root mean square of successive differences [RMSSD]) was calculated from resting electrocardiograms; systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) were oscillometric-based measurements. We used a generalized linear mixed model, adjusted for age, age square, sex, body mass index, and familial relationships to assess the relationship of baseline HRV and BP (continuous and quartiles), hypertension, and antihypertensive medication with glaucoma at follow up (median, 3.8 years). Results: The odds ratio (OR) of glaucoma was 0.95 (95% confidence interval [CI], 0.92–0.99) per unit increase in log-transformed RMSSD (in ms), indicating that autonomous dysfunction (low HRV) is associated with a higher risk of glaucoma. Per 10-mm Hg increase in BP, we found ORs of 1.03 (95% CI, 1.01–1.05; P = 0.015) for SBP, 1.01 (95% CI, 0.97–1.05; P = 0.55) for DBP, 1.03 (95% CI, 1.00–1.06; P = 0.083) for MAP, and 1.04 (95% CI, 1.01–1.07; P = 0.006) for PP. The OR for the lowest versus highest RMSSD quartile was 1.15 (95% CI, 1.05–1.27; P = 0.003). The ORs for the highest versus second quartile were 1.09 (95% CI, 0.99–1.19; P = 0.091) for SBP and 1.13 (95% CI, 1.02–1.24; P = 0.015) for PP. Glaucoma was more common among hypertensives (OR, 1.25; 95% CI, 1.16–1.35; P < 0.001); among those using angiotensin-converting enzyme (ACE) inhibitors (OR, 1.35; 95% CI, 1.18–1.55; P < 0.001); and among those using calcium-channel blockers (OR, 1.19; 95% CI, 1.01–1.40; P = 0.039). Conclusions: Low HRV, high SBP, high PP, and hypertension were associated with glaucoma. Longitudinal studies may elucidate if autonomic dysregulation and high BP also predict glaucoma incidence.

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all P <0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (−0.20/−0.16) and with diastolic BP (−0.15/−0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, −0.08 to −0.23) and diastolic BP (range, −0.20 to −0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap.

Background: Primary open-angle glaucoma (POAG) is the most prevalent glaucoma subtype, but its exact etiology is still unknown. In this study, we aimed to prioritize the most likely ‘causal’ genes and identify functional characteristics and underlying biological pathways of POAG candidate genes. Methods: We used the results of a large POAG genome-wide association analysis study from GERA and UK Biobank cohorts. First, we performed systematic gene-prioritization analyses based on: (i) nearest genes; (ii) nonsynonymous single-nucleotide polymorphisms; (iii) co-regulation analysis; (iv) transcriptome-wide association studies; and (v) epigenomic data. Next, we performed functional enrichment analyses to find overrepresented functional pathways and tissues. Results: We identified 142 prioritized genes, of which 64 were novel for POAG. BICC1, AFAP1, and ABCA1 were the most highly prioritized genes based on four or more lines of evidence. The most significant pathways were related to extracellular matrix turnover, transforming growth factor-β, blood vessel development, and retinoic acid receptor signaling. Ocular tissues such as sclera and trabecular meshwork showed enrichment in prioritized gene expression (>1.5 fold). We found pleiotropy of POAG with intraocular pressure and optic-disc parameters, as well as genetic correlation with hypertension and diabetes-related eye disease. Conclusions: Our findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and have prioritized many novel candidate genes for functional follow-up studies.