Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation.

BACKGROUND: Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions. RESULTS: TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes. CONCLUSIONS: Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

Novel Protective Effects of Cistanche Tubulosa Extract Against Low-Luminance Blue Light-Induced Degenerative Retinopathy.

BACKGROUND/AIMS: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. METHODS: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. RESULTS: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. CONCLUSION: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Increased incidence of peptic ulcer disease in central serous chorioretinopathy patients: a population-based retrospective cohort study.

PURPOSE: To investigate peptic ulcer disease and other possible risk factors in patients with central serous chorioretinopathy (CSR) using a population-based database. METHODS: In this population-based retrospective cohort study, longitudinal data from the Taiwan National Health Insurance Research Database were analyzed. The study cohort comprised 835 patients with CSR and the control cohort comprised 4175 patients without CSR from January 2000 to December 2009. Conditional logistic regression was applied to examine the association of peptic ulcer disease and other possible risk factors for CSR, and stratified Cox regression models were applied to examine whether patients with CSR have an increased chance of peptic ulcer disease and hypertension development. RESULTS: The identifiable risk factors for CSR included peptic ulcer disease (adjusted odd ratio: 1.39, P = 0.001) and higher monthly income (adjusted odd ratio: 1.30, P = 0.006). Patients with CSR also had a significantly higher chance of developing peptic ulcer disease after the diagnosis of CSR (adjusted odd ratio: 1.43, P = 0.009). CONCLUSION: Peptic ulcer disease and higher monthly income are independent risk factors for CSR. Whereas, patients with CSR also had increased risk for peptic ulcer development.

Obstructive sleep apnea and increased risk of glaucoma: a population-based matched-cohort study.

PURPOSE: Previous studies had reported an increased prevalence of glaucoma in patients with obstructive sleep apnea (OSA). However, the risk of open-angle glaucoma (OAG) among patients with OSA remains unclear. Using a nationwide, population-based dataset in Taiwan, this study aimed to examine the prevalence and risk of OAG among patients with OSA during a 5-year follow-up period after a diagnosis of OSA. DESIGN: A retrospective, matched-cohort study. PARTICIPANTS AND CONTROLS: This study used data sourced from the Longitudinal Health Insurance Database 2000. We included 1012 subjects with OSA in the study cohort and randomly selected 6072 subjects in the comparison group. METHODS: Each subject in this study was individually traced for a 5-year period to identify those subjects who subsequently received a diagnosis of OAG. Cox proportional hazards regression was performed to calculate the 5-year risk of OAG between the study and comparison cohorts. MAIN OUTCOME MEASURES: The incidence and risk of OAG between the study and comparison groups. RESULTS: During the 5-year follow-up period, the incidence rate per 1000 person-years was 11.26 (95% confidence interval [CI], 8.61-14.49) and 6.76 (95% CI, 5.80-7.83) for subjects with and without OSA, respectively. After adjusting for monthly income, geographic region, diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, renal disease, hypothyroidism, and the number of outpatient visits for ophthalmologic care during the follow-up period, stratified Cox proportional hazards regression revealed that the hazard ratio for OAG within the 5-year period for subjects with OSA was 1.67 (95% CI, 1.30-2.17; P<0.001) that of comparison subjects. CONCLUSIONS: Our results suggest that OSA is associated with an increased risk of subsequent OAG diagnosis during a 5-year follow-up period. FINANCIAL DISCLOSURES(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Effect of myopia on the progression of normal tension glaucoma.

PURPOSE: Identify risk factors of progression in treated normal-tension glaucoma (NTG) in highly myopic and non-highly myopic eyes. METHODS: This retrospective, observational case series study included 42 highly myopic glaucoma (HMG, <-6D) eyes and 39 non-highly myopic glaucoma (NHG,≧-6D) eyes. Glaucoma progression was determined by serial visual field data. Univariate and multivariate logistic regression method were used to detect associations between potential risk factors and glaucoma progression. RESULTS: Among 81 eyes from 81 normal-tension glaucoma patients (mean follow-up, 3.10 years), 20 of 42 eye (45.24%) in the HMG and 14 of 39 eyes (35.90%) in the NHG showed progression. The HMG group had larger optic disc tilt ratio (p = 0.007) and thinner inferior macular thickness (P = 0.03) than the NHG group. Changes in the linear regression values for MD for each group were as follows: -0.652 dB/year for the HMG and -0.717 dB/year for the NHG (P = 0.298). Basal pattern standard deviation (PSD) (OR: 1.55, p = 0.016) and post treatment IOP (OR = 1.54, p = 0.043) were risk factors for visual field progression in normal tension glaucoma patients. In subgroup analysis of HMG patients, PSD (OR: 2.77, p = 0.017) was a risk factor for visual field progression. CONCLUSION: Reduction IOP was postulated to be contributing in the prevention of visual field progression, especially in highly myopic NTG patients with large basal pattern standard deviation.

Retinal protection by fungal product theissenolactone B in a sodium iodate-induced AMD model through targeting retinal pigment epithelial matrix metalloproteinase-9 and microglia activity.

Age-related macular degeneration (AMD) is the leading cause of low vision and blindness for which there is currently no cure. Increased matrix metalloproteinase-9 (MMP-9) was found in AMD and potently contributes to its pathogenesis. Resident microglia also promote the processes of chronic neuroinflammation, accelerating the progression of AMD. The present study investigates the effects and mechanisms of the natural compound theissenolactone B (LB53), isolated from Theissenia cinerea, on the effects of RPE dysregulation and microglia hyperactivation and its retinal protective ability in a sodium iodate (NaIO3)-induced retinal degeneration model of AMD. The fungal component LB53 significantly reduces MMP-9 gelatinolysis in TNF-α-stimulated human RPE cells (ARPE-19). Similarly, LB53 abolishes MMP-9 protein and mRNA expression in ARPE-19 cells. Moreover, LB53 efficiently suppresses nitric oxide (NO) production, iNOS expression, and intracellular ROS levels in LPS-stimulated TLR 4-activated microglial BV-2 cells. According to signaling studies, LB53 specifically targets canonical NF-κB signaling in both ARPE-19 and BV-2 microglia. In an RPE-BV-2 interaction assay, LB53 ameliorates LPS-activated BV-2 conditioned medium-induced MMP-9 activation and expression in the RPE. In NaIO3-induced AMD mouse model, LB53 restores photoreceptor and bipolar cell dysfunction as assessed by electroretinography (ERG). Additionally, LB53 prevents retinal thinning, primarily the photoreceptor, and reduces retinal blood flow from NaIO3 damage evaluated by optic coherence tomography (OCT) and laser speckle flowgraphy (LSFG), respectively. Our results demonstrate that LB53 exerts neuroprotection in a mouse model of AMD, which can be attributed to its anti-retinal inflammatory effects by impeding RPE-mediated MMP-9 activation and anti-microglia.

A one-year follow-up study on the incidence and risk of endophthalmitis after pyogenic liver abscess.

PURPOSE: Although endophthalmitis secondary to pyogenic liver abscess (PLA) is becoming a globally emerging infectious disease, population-based investigations evaluating the relationship between PLA and endogenous endophthalmitis remain scarce. This study aimed to investigate the incidence and risk of endogenous endophthalmitis in patients with PLA compared with unaffected individuals by using a nationwide, population-based dataset. DESIGN: Retrospective, cohort study. PARTICIPANTS AND CONTROLS: This study used data sourced from Taiwan's National Health Insurance Research Database. In total, 12 727 patients with PLA were included in the study group and 63 635 matched subjects were randomly extracted as a comparison group. METHODS: Stratified Cox proportional hazards regressions were performed to assess the effect of PLA on the hazard of developing endogenous endophthalmitis. MAIN OUTCOME MEASURES: The incidence and risk of endogenous endophthalmitis between the study group and comparison group. RESULTS: Of the total sample, 148 subjects (0.10%) were diagnosed with endophthalmitis during the 1-year follow-up period. Endophthalmitis was found in 106 patients (0.84%) with PLA and 42 comparison patients (0.07%). After adjusting for patient monthly income, geographic location, and urbanization level, those suffering from PLA were found to have a greater likelihood of developing endophthalmitis during the 1-year follow-up period than comparison patients (hazard ratio [HR], 12.83; 95% confidence interval, 8.94-18.41). Stratification did not reveal any large differences in the adjusted HRs for endophthalmitis between PLA patients suffering from diabetes and those in whom diabetes was absent. We further analyzed the etiology of cases with endogenous endophthalmitis in this investigation and found Klebsiella pneumonia to be the causative organism among 75.5% of the cases but only 33.4% of the comparison group. CONCLUSIONS: We found that the incidence and risk of developing endophthalmitis was significantly higher among patients with PLA compared with matched controls irrespective of diabetes status.

Open-angle glaucoma and the risk of erectile dysfunction: a population-based case-control study.

PURPOSE: Open-angle glaucoma (OAG) is associated with systemic metabolic and cardiovascular disorders, and both share common risk factors with erectile dysfunction (ED). However, few studies have investigated the association of ED with OAG. This study aimed to estimate the association of ED with prior OAG by using a nationwide, population-based data with a retrospective case-control cohort design in Taiwan. DESIGN: Age-matched case-control study. PARTICIPANTS AND CONTROLS: We identified 4605 patients with ED as the cases and randomly selected 23 025 subjects as the controls (5 controls to 1 case). METHODS: We used conditional logistic regression analysis to estimate the odds ratio and 95% confidence interval of having previously been diagnosed with OAG according to the presence/absence of ED after adjusting for patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse. MAIN OUTCOME MEASURES: We identified OAG cases not only based on an International Classification of Diseases, Ninth Revision, Clinical Modification code, but also by the prescription of topical antiglaucoma medication. RESULTS: In total, prior OAG was found among 137 subjects (0.5 %); 53 individuals (1.1% of the ED patients) from the cases and 84 individuals (0.4% of patients without ED) from the controls. Conditional logistic regression analysis demonstrated that, after adjusting for potential confounders, patients with ED were more likely to have prior OAG than controls (odds ratio, 2.85; 95% confidence interval, 2.10-4.07). CONCLUSIONS: This study identifies a novel association between ED and prior OAG.

Association of neovascular age-related macular degeneration with migraine.

Patients with early onset vascular pathology have been reported to manifest neovascular age-related macular degeneration (AMD). While the blood vessels involved in pathogenesis of migraine remains controversial, it is generally accepted that a major contributor is blood vessel pathology. This study aimed to examine the association between migraine and AMD using a nationwide population-based dataset. Retrospective claims data were collected from the Taiwan National Health Insurance Research Database. We identified 20,333 patients diagnosed with neovascular AMD (cases), and we selected 81,332 propensity score-matched controls from the remaining beneficiaries in Taiwan's National Health Insurance system. We used Chi-square tests to explore differences in the prevalence of migraine prior to the index date between cases and controls. We performed multiple logistic regressions to estimate the odds of prior migraine among neovascular AMD patients vs. controls after adjusting for age, sex, monthly income, geographic location, residential urbanization level, hyperlipidemia, diabetes, coronary heart disease, hypertension, and previous cataract surgery. A total of 5184 of sample patients (5.1%) had a migraine claim before the index date; 1215 (6.1%) among cases and 3969 (4.9%) among controls (p < 0.001), with an unadjusted OR of 1.239 (95% CI 1.160~1.324, p < 0.001) for prior migraine among cases relative to controls. Furthermore, the adjusted OR was 1.201 (95% CI 1.123~1.284; p < 0.001) for AMD cases relative to controls. The study offers population-based evidence that persons with migraine have 20% higher risk of subsequently being diagnosed with neovascular AMD.

Increased risk of a cancer diagnosis after herpes zoster ophthalmicus: a nationwide population-based study.

PURPOSE: Herpes zoster has been associated with immune suppression, as has an increased risk of cancer. This population-based follow-up study aimed to investigate the risk of a subsequent cancer diagnosis after herpes zoster ophthalmicus (HZO). DESIGN: A retrospective cohort study. PARTICIPANTS AND CONTROLS: Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. The study cohort comprised all patients with a diagnosis of HZO (International Classification of Diseases, 9th Revision, Clinical Modification code 053.2) in 2003 and 2004 (n=658). The comparison cohort consisted of randomly selected ambulatory care patients, 8 for every patient with HZO (n=5264) matched with the study group on age, gender, monthly income, and urbanization level of the patient's residence. METHODS: The Kaplan-Meier method was used to compute 1-year cancer-free survival rate. Stratified Cox proportional hazard regressions were carried out to compute the adjusted 1-year cancer-free survival rate after adjusting for potential confounding factors. MAIN OUTCOME MEASURES: Subsequent claims for all study and comparison patients were captured over a 1-year follow-up period from their index ambulatory care visit to identify whether the patient received a cancer diagnosis during the follow-up period. RESULTS: During 1-year follow-up, cancer was diagnosed in 4.86% of patients with HZO and 0.53% of patients in the comparison cohort. Patients with HZO had significantly lower 1-year cancer-free survival rates than the comparison cohort. After adjusting for patient age, gender, monthly income, and urbanization level, patients with HZO were found to have a 9.25-fold (95% confidence interval, 5.51-15.55) risk of a subsequent cancer diagnosis than the matched comparison cohort. No significant differences in cancer type were observed between the 2 cohorts. CONCLUSIONS: Herpes zoster ophthalmicus may be a marker of increased risk of being diagnosed with cancer in the following year. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Role of taurine on acid secretion in the rat stomach.

BACKGROUND: Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. METHODS: The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. RESULTS: We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphate) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p < 0.001) of taurine concentrations with cAMP was observed. CONCLUSIONS: Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

Neovascular age-related macular degeneration and the risk of stroke: a 5-year population-based follow-up study.

BACKGROUND AND PURPOSE: Using a nationwide population-based data set from Taiwan, this study investigated the relationship between neovascular age-related macular degeneration (AMD) and the risk of stroke over a 5-year period. METHOD: The study cohort comprised 209 patients who received treatment for AMD between 1999 and 2001. We randomly selected 1045 subjects matched with the study cohort in terms of age and gender for comparison. Cox proportional hazard regressions were performed to compare the 5-year stroke-free survival rate. RESULTS: Among the sampled patients, 142 patients (11.3%) had strokes during the 5-year follow-up period, 38 (18.2% of the patients with AMD) from the study cohort and 104 (9.9% of patients in the comparison cohort) from the comparison cohort. After adjusting for the patient's age, gender, monthly income, level of urbanization, and the geographic region of the community in which the patient resided and comorbidities, the hazard ratio for stroke during the follow-up period was 2.01 (P=0.001) times greater for patients with AMD than for patients without AMD. The adjusted hazard ratio for stroke during the follow-up period was 2.21 (P=0.001) times higher for patients with AMD > or = 65 years old compared with the same age group in the comparison cohort. However, no significant difference was observed in the risk of stroke between patients with AMD <65 years of age and comparison patients in the same age group. CONCLUSION: We conclude that neovascular AMD is associated with a higher risk of stroke for patients with AMD > or = 65 years old.

Comparison of comorbid conditions between open-angle glaucoma patients and a control cohort: a case-control study.

OBJECTIVE: To determine the prevalence of selected comorbidities in patients with open-angle glaucoma (OAG) and whether these comorbidities are more prevalent among individuals with OAG than those without OAG. DESIGN: A retrospective, nationwide, case-control study using an administrative database. PARTICIPANTS: The study group comprised 76,673 OAG patients. The comparison group comprised 230,019 subjects matched to the study cohort. METHODS: Data were collected retrospectively from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients with a diagnosis of OAG (International Classification of Diseases, 9th Revision, Clinical Modification codes 365.1-365.11) in 2005 (n = 76,673). The comparison cohort comprised randomly selected patients (3 for every 1 OAG patient; n = 230,019) matched with the study group in terms of age, gender, urbanization level, and monthly income. In total, 31 medical comorbidities were selected based mainly on the Elixhauser Comorbidity Index. Separate conditional logistic regression analyses were used to estimate the adjusted odds ratio for each of the medical comorbidities between patients with and without OAG. MAIN OUTCOME MEASURES: The prevalences of selected comorbidities. RESULTS: More than half (50.5%) of the OAG patients had hypertension, and more than 30% had hyperlipidemia or diabetes (30.5% and 30.2%, respectively). The prevalences of 28 of 31 comorbidities were significantly higher for OAG patients than subjects without glaucoma after adjusting for age, gender, urbanization level, and monthly income. The adjusted odds ratio was more than 1.50 for hypertension, hyperlipidemia, systemic lupus erythematosus, diabetes, hypothyroidism, fluid and electrolyte disorders, depression, and psychosis. Among the studied comorbidities, the prevalence difference of the OAG group minus the control group was 3% or higher for hypertension, hyperlipidemia, stroke, diabetes, liver disease, and peptic ulcer. CONCLUSIONS: Open-angle glaucoma patients are significantly more likely to have comorbidities, many of which can be life threatening or can affect the quality of life appreciably. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussedin this article

Hypothyroidism and the risk of developing open-angle glaucoma: a five-year population-based follow-up study.

OBJECTIVE: To investigate the risk of open-angle glaucoma (OAG) after a diagnosis of hypothyroidism. DESIGN: A retrospective, population-based follow-up study using an administrative database. PARTICIPANTS: The study group comprised 257 hypothyroidism patients. The comparison group included 2056 subjects. METHODS: Data were retrospectively collected from the Taiwan Longitudinal Health Insurance Database. The study cohort comprised patients aged ≥ 60 who received a first diagnosis of hypothyroidism (International Classification of Diseases, Ninth Revision, Clinical Modification code 244.9) from 1997 to 2001 (n = 257). The comparison cohort consisted of randomly selected patients without hypothyroidism who were aged ≥ 60 and had no diagnosis of glaucoma before 2001 (8 for every OAG patient; n = 2056). Each sampled patient was tracked for 5 years from their index visit. Cox proportional hazard regressions were used to compute the 5-year OAG-free survival rate, after adjusting for possible confounding factors. MAIN OUTCOME MEASURES: The risk of developing OAG during the 5-year follow-up period. RESULTS: Open-angle glaucoma developed in 7.4% of patients with hypothyroidism and 3.8% of patients in the comparison cohort during the follow-up period. Hypothyroid patients had a significantly lower 5-year OAG-free survival rate than patients in the comparison cohort. After adjusting for patients' age, gender, monthly income, urbanization level, and comorbid medical disorders, hypothyroidism patients were found to have a 1.78-fold (95% confidence interval [CI], 1.04-3.06) greater risk of developing OAG than the comparison cohort. This association remained significant in untreated hypothyroidism patients (adjusted hazard ratio [HR], 2.37; 95% CI, 1.10-5.09) and became statistically nonsignificant in patients treated with levothyroxine (adjusted HR, 1.73; 95% CI, 0.89-3.38). CONCLUSIONS: Hypothyroid patients had a significantly increased risk of OAG development during the 5-year follow-up period. Levothyroxine seemed to be protective.

Associations between Attention-Deficit/Hyperactivity Disorder and Ocular Abnormalities in Children: A Population-based Study.

Purpose: Attention-deficit/hyperactivity disorder (ADHD) was reported to be associated with disturbances in the prefrontal circuitry and seems to be associated with dysfunctions of eye motility. This study aimed to explore associations between ADHD and ocular abnormalities, including amblyopia, hypermetropia, astigmatism, and heterotropia, using a large, nationwide population-based dataset in Taiwan.Methods: We retrieved our sample for this cross-sectional study from the Taiwan National Health Insurance Research Database. In total, 116,308 children with ADHD were selected as the study group and 116,308 randomly selected children without ADHD as the comparison group. We used conditional logistic regression analyses to examine the odds ratios (ORs) of amblyopia, hypermetropia, astigmatism, and heterotropia between children with and those without ADHD.Results: We found that children with ADHD had significantly higher prevalences of amblyopia (1.6% vs. 0.9%, p< .001), hypermetropia (2.4% vs. 1.3%, p < .001), astigmatism (0.2% vs. 0.1%, p < .001), and heterotropia (1.1% vs. 0.5%, p < .001) than children without ADHD. The ORs of amblyopia, hypermetropia, astigmatism and heterotropia for children with ADHD were 1.89 (95% confidence interval (CI) = 1.76 ~ 2.05), 1.82 (95% CI = 1.68 ~ 1.92), 1.73 (95% CI = 1.34 ~ 2.16), and 2.01 (95% CI = 1.82 ~ 2.21) compared to children without ADHD.Conclusions: The findings suggest that ADHD is associated with ocular abnormalities, including amblyopia, hypermetropia, astigmatism, and heterotropia.

Open-angle glaucoma and the risk of stroke development: a 5-year population-based follow-up study.

BACKGROUND AND PURPOSE: Although open-angle glaucoma (OAG) is associated with some of the risk factors of stroke development, there is still no published study addressing whether OAG increases the risk of stroke development. We investigated the risk of stroke development after a diagnosis of OAG. METHODS: Data were retrospectively collected from the Taiwan National Health Insurance Research Database, which is comprised of 1 073 891 random subjects from among Taiwan's 23 million residents. The study cohort comprised all patients with a diagnosis of OAG (International Classification of Diseases, 9th Revision, Clinical Modification code 365.1 to 365.11) in 2001 (n=4032). The comparison cohort was comprised of randomly selected patients (5 for every patient with OAG, n=20 160) matched with the study group in terms of age, gender, geographic location, and comorbid medical disorders. Patients were tracked from their index visits for 5 years. Cox proportional hazard regression was used to compute the 5-year stroke-free survival rate after adjusting for possible confounding factors. RESULTS: Stroke developed in 14.9% of patients with OAG and 9.5% of patients in the comparison cohort during the 5-year follow-up period. Patients with OAG had significantly lower 5-year stroke-free survival rates than patients in the comparison cohort. After adjusting for patients' demographic characteristics and selected comorbidities, patients with OAG were found to have a 1.52-fold (95% CI, 1.40 to 1.72) higher risk of having a stroke than the matched comparison cohort. CONCLUSIONS: Patients with OAG demonstrated a significantly increased risk of stroke development during the 5-year follow-up period.

Increased risk of stroke after a herpes zoster attack: a population-based follow-up study.

BACKGROUND AND PURPOSE: Varicella zoster virus-induced vasculopathy and postherpes zoster attack stroke syndromes have been reported previously; nevertheless, data regarding the exact prevalence and risk of stroke occurring postherpes zoster attack are still lacking. This study aims to investigate the frequency and risk of stroke after a herpes zoster attack using a nationwide, population-based study of a retrospective cohort design. Method- A total of 7760 patients who had received treatment for herpes zoster between 1997 and 2001 were included and matched with 23 280 randomly selected subjects. A 1-year stroke-free survival rate was then estimated using the Kaplan-Meier method. After adjusting for potential confounders, Cox proportional hazard regressions were carried out to compute the adjusted 1-year survival rate. RESULTS: Of the sampled patients, 439 patients (1.41%) developed strokes within the 1-year follow-up period, that is, 133 individuals (1.71% of the patients with herpes zoster) from the study cohort and 306 individuals (1.31% of patients in the comparison cohort) from the comparison cohort. The log rank test indicated that patients with herpes zoster had significantly lower 1-year stroke-free survival rates than the control (P<0.001). The adjusted hazard ratios of stroke after herpes zoster and herpes zoster ophthalmicus during the 1-year follow-up period were 1.31 and 4.28, respectively. CONCLUSIONS: The risk for stroke increased after a zoster attack. Although varicella zoster virus vasculopathy is a well-documented complication that may induce a stroke postherpes zoster attack, it does not fully account for the unexpectedly high risk of stroke in these patients.

The fungus-derived retinoprotectant theissenolactone C improves glaucoma-like injury mediated by MMP-9 inhibition.

BACKGROUND: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that has been found to induce matrix metalloproteinase-9 (MMP-9) activation and result in eventual retinal dysfunction. Proinflammatory cytokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-1ß (IL-1ß) were also found to be involved in disease progression by mediating MMP-9 production. We previously reported that fungal derivative theissenolactone C (LC53) could exert ocular protective effects by suppressing neuroinflammation in experimental uveitis. PURPOSE: The aim of this study was to investigate the retinoprotective effects of natural compound LC53 on the high IOP-induced ischemia/reperfusion (I/R)-injury model of glaucoma and its cellular mechanisms. METHODS: A high IOP-induced I/R-injury model was manipulated by normal saline injection into the anterior chamber of the rat eye. MCP-1-stimulated monocytes and IL-1ß-activated primary astrocytes were used to investigate the cellular mechanisms of LC53. Retinal function was evaluated with the scotopic threshold response (STR) and combined rod-cone response by electroretinography (ERG). As a positive control, rats were treated with memantine. MMP-9 gelatinolysis, mRNA expression and protein expression were analyzed by gelatin zymography, RT-PCR, and Western Blot, respectively. The phosphorylation levels of MAPKs and NF-κB p65 were tested by Western Blot. Additionally, the levels of inflammatory MCP-1 and IL-1ß were determined by ELISA. RESULTS: The present study revealed that LC53 preserved the retina functional deficiency assessed by scotopic threshold response (STR) and combined rod-cone response of ERG after high IOP-induced I/R injury. These retinal protective effects of LC53 were positively correlated with inhibitory activities in I/R injury-elicited ocular MMP-9 activation and expression. The increased level of MCP-1 was not affected, and the enhanced IL-1ß production was partially reduced by LC53 in the retina after I/R injury. According to cellular studies, LC53 significantly and concentration-dependently abrogated MMP-9 activation and expression in MCP-1-stimulated THP-1 monocytes. We found the inhibitory activities of LC53 were through the ERK- and NF-κB-dependent pathways. In addition, LC53 dramatically suppressed IL-1ß-induced MMP-9 activation and expression in primary astrocytes. The phosphorylation of 65-kD protein (p65) of NF-κB was substantially blocked by LC53 in IL-1ß-stimulated primary astrocytes. CONCLUSION: LC53 exerted a retinal protective effect through NF-κB inhibition and was highly potent against MMP-9 activities after high IOP-induced I/R injury, suggesting that LC53 would be a promising drug lead for glaucoma or related medical conditions attributed to retinal ischemia.

Seasonal variations in the occurrence of retinal vein occlusion: a five-year nationwide population-based study from Taiwan.

PURPOSE: To determine whether seasonal variation exists in the incidence of retinal vein occlusion. DESIGN: Retrospective, nationwide population-based administrative database study. METHODS: We collected data on outpatient and emergency visits for the period from January 1999 through December 2003 from the Taiwan National Health Insurance Research Database, a source that covers more than 96% of Taiwan's 23 million citizens. In total, 20,792 patients with a first-time diagnosis of either central retinal vein occlusion or branch retinal vein occlusion (The International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] code 362.35 or 362.36, respectively) were identified. Monthly incidence of retinal vein occlusion was obtained for each age group, each gender group, and for the entire sample. The autoregressive integrated moving average method of analysis was adopted to examine seasonality in the monthly incidence of retinal vein occlusion. RESULTS: The monthly incidence rates of retinal vein occlusion revealed significant seasonality, with a clear peak in January for each age group and each gender group, as well as for the total sample. CONCLUSIONS: Our study demonstrates significant seasonal variations in the retinal vein occlusion incidence, with the peak occurrence in the winter month of January.