Ambient Air Pollution and the Risk of Central Retinal Artery Occlusion.

PURPOSE: To investigate whether daily changes in ambient air pollution were associated with an increased risk of central retinal artery occlusion (CRAO). DESIGN: Retrospective population-based cohort study. PARTICIPANTS: We identified patients newly diagnosed with CRAO between 2001 and 2013 in a representative database of 1 000 000 patients that were randomly selected from all registered beneficiaries of the National Health Insurance program in Taiwan. We identified air pollutant monitoring stations located near these patients' residences in different administrative areas in Taiwan to determine the recorded concentrations of particulate matter ≤2.5 µm (PM2.5), particulate matter ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3). Patients without corresponding monitoring stations were excluded. METHODS: We used a time-stratified case-crossover study design and conditional logistic regression analysis to assess associations between the risk of CRAO and the air pollutant levels in the days preceding each event. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We enrolled 96 patients with CRAO in this study. The mean age was 65.6 years (standard deviation, 12.7 years) and 67.7% of patients were male. The risk of CRAO onset was significantly increased (OR, 1.09; 95% CI, 1.01-1.17; P = 0.03) during a 5-day period following a 1 part per billion increase in NO2 levels. After multipollutant adjustment, the increase in risk was most prominent after 4 days (OR, 1.40; 95% CI, 1.05-1.87; P = 0.02) to 5 days (OR, 2.16; 95% CI, 1.10-4.23; P = 0.03) of elevated NO2 levels in diabetic patients. The risk of CRAO onset also significantly increased in patients with hypertension and in patients ≥65 years old, after 1 day of elevated SO2 levels (OR, 1.88; 95% CI, 1.07-3.29; P = 0.03 and OR, 1.90; 95% CI, 1.13-3.21; P = 0.02, respectively). The transient concentration of the other air pollutants, including PM2.5, PM10, and O3, did not significantly affect the occurrence of CRAO in this study. CONCLUSIONS: These results demonstrated a positive association between air pollution and CRAO onset, particularly in patients with diabetes or hypertension and those older than 65 years.

Amiodarone-Associated Optic Neuropathy: A Nationwide Study.

PURPOSE: To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. DESIGN: Retrospective population-based cohort study. PARTICIPANTS: Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. METHODS: Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). CONCLUSIONS: These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment.

Tanshinone IIA isolated from Salvia miltiorrhiza elicits the cell death of human endothelial cells.

Tanshinone IIA, a major component extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, is known to exhibit potent cytotoxicity against various human carcinoma cells in vitro. However, the mechanism by which tanshinone IIA produces this anti-tumor effect remains unknown. Since anti-neovascularization has generally been regarded as an effective strategy for anti-cancer therapy, we decided to investigate the mechanism underlying tanshinone IIA-mediated death of human endothelial cells. In this study, we demonstrate that tanshinone IIA elicits human endothelial cell death independent of oxidative stress. These events are partially calcium-dependent and actually dependent upon NAD(P)H: quinone oxidoreductase (NQO1) activity. Tanshinone IIA induces an increase in intracellular calcium, which triggers the release of cytochrome c, thus causing loss of the mitochondrial membrane potential (MMP), resulting in the subsequent activation of caspases. Blocking the induction of Ca2+ perturbation with BAPTA-AM partially rescued cells from tanshinone IIA-induced cytotoxicity. Additionally, blocking NQO1 activity with dicoumoral or inhibiting caspase activities with the general caspase inhibitor, z-VAD-fmk, prevented cell death induced by tanshinone IIA. Therefore, our results imply that tanshinone IIA-mediated cytotoxicity against human endothelial cells may occur through activation of NQO1, which induces a calcium imbalance and mitochondrial dysfunction, thus stimulating caspase activity.