Risk of stroke associated with intravitreal ranibizumab injections in age-related macular degeneration: a nationwide case-crossover study.

OBJECTIVE: To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD). METHODS: A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model. RESULTS: A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab. CONCLUSIONS: This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.

Association between Ranibizumab Injections and Risk of Acute Myocardial Infarction in Age-related Macular Degeneration: A Case-crossover Study.

PURPOSE: This study aimed to evaluate the risk of acute myocardial infarction (AMI) associated with intravitreal ranibizumab in age-related macular degeneration (AMD). METHODS: This nationwide retrospective case-crossover study using data from the Korean National Health Insurance Service database included patients diagnosed with exudative AMD using the registration code for exudative AMD (V201) from 2009 to 2014. We identified all incident AMI cases among these exudative AMD cases from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined the case period as one to 60 days and four control periods as 121 to 180, 181 to 240, 241 to 300, and 301 to 361 days, respectively, before the index date. A prescription of ranibizumab was searched for during the case and control periods. We calculated the adjusted odds ratios and their 95% confidence intervals using a conditional logistic regression model. RESULTS: From a cohort of patients with exudative AMD (n = 41,860), a total of 181 AMI patients with exudative AMD were included. Among all the patients, 11.05% were treated during the 2 months preceding the index date as compared with 8.29% to 9.39% treated during control periods. The adjusted odds ratio of AMI associated with intravitreal ranibizumab during the preceding 2 months was 1.22 (95% confidence interval, 0.673-2.213; p = 0.5124). Analyses based on case periods of 15 days and 1 month yielded similar results. CONCLUSIONS: Intravitreal ranibizumab injection does not appear to increase the risk of hospitalization for AMI within 60 days in exudative AMD patients.

Incidence and characteristics of cataract surgery in South Korea from 2011 to 2015: A nationwide population-based study.

IMPORTANCE: Detailed incidence data for cataract surgery in the general population are limited, yet important for determining the surgical needs of the community and formulation of healthcare policies. BACKGROUND: To report incidence rates of cataract surgery in South Korea. DESIGN: Nationwide, retrospective population-based study. PARTICIPANTS: This study involved the entire population of South Korea (n = 47 990 761); 2 236 107 eyes of 1 591 176 patients confirmed as having cataract surgery from 1 January 2011 to 31 December 2015 were included. METHODS: Data for all patients who underwent primary cataract surgery in South Korea were retrieved using Korean Electronic Data Interchange and Korean Standard Classification of Diseases-7 codes. Annual incidence rates were calculated and adjusted to the national population data for the corresponding year. MAIN OUTCOME MEASURES: The average incidence of cataract surgery during the 5-year study period was estimated using population data from the 2010 Korean census. RESULTS: The incidence of cataract surgery increased from 8.54/1000 person-years in 2011 to 9.67/1000 person-years in 2015. The probability of second-eye surgery within 12 months after the first-eye surgery increased from 42.98% in 2011 to 48.01% in 2015. In total, 85.72% of surgeries were performed in non-rural areas: 43.18% in individuals with a higher household income and 76.65% in primary healthcare centres. The rate of vitrectomy for posterior capsular rupture was 0.72%. CONCLUSIONS AND RELEVANCE: The incidence of cataract surgery in South Korea is increasing over time. Our findings are expected to aid in the formulation of future healthcare policies concerning cataract surgery in South Korea.

Changes in Human Tear Proteome Following Topical Treatment of Dry Eye Disease: Cyclosporine A Versus Diquafosol Tetrasodium.

Purpose: To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. Methods: A total of 18 patients were diagnosed with non-Sjögren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change >1.5 or <0.67 (P < 0.05) were considered differentially expressed (DEP). Results: A total of 794 proteins were identified, with no significant difference observed between pretreatment and posttreatment conditions. Proteomic analysis identified 54 and 106 DEPs between treatment groups (CsA and DQS, respectively), with gene ontology analysis indicating that both treatments enhanced innate and adaptive immune responses and cellular detoxification. Protein-network analysis showed that inflammation associated with the immune response was primarily responsible for the therapeutic process in both groups. Conclusions: These results provide insight into the broad scope of changes at the ocular surface in DED and indicated that although both drugs improved the clinical parameters, the activated tear-specific biomarkers differed significantly between treatments. Our findings suggest that the DEPs identified here and those correlated with the clinical parameters might represent candidate biomarkers for DED.

Incidence and risk factors for retinal detachment after cataract surgery in Korea: a nationwide population-based study from 2011 to 2015.

PURPOSE: To evaluate the incidence and risk factors for retinal detachment (RD) after cataract surgery in the years 2011 to 2015 in Korea. METHODS: A nationwide retrospective cohort study was performed using health claim data from the Korean National Health Insurance Service (KNHIS) database. Patients over 40 years of age who underwent cataract surgery from 2011 and 2015 in Korea were retrospectively identified using Korean Electronic Data Interchange (KEDI) code and Korean Classification of Diseases (KCD)-7 code. RESULTS: A total of 2,191,510 eyes in 1,455,968 patients (58.63% female; mean age, 69.19 ± 9.82 years) underwent cataract surgery from 2011 to 2015 in Korea and 17,351 patients experienced RD (45.4% female; mean age, 60.89 ± 10.21 years). The 5-year cumulative risk of RD after cataract surgery was 1.19%, and 80.9% of RD occurred within 1 year after cataract surgery. In multivariate analysis, adjusted hazard ratio (HR) of RD was 1.335 [95% confidence interval (CI), 1.293-1.378] for male gender, 1.422 [95% CI, 1.371-1.475] for preoperative myopia, and 2.596 [95% CI, 2.367-2.849] for anterior vitrectomy during cataract surgery. Younger age was one of the factors highly associated with RD after cataract surgery, with HR [95% CI], 5.873 [5.527-6.240] in 40 to 54 years of age, 4.037 [3.811-4.277] in 55 to 64 years, and 2.026 [1.911-2.147] in 65 to 74 years. Adjusted HR of RD for surgery in secondary and primary healthcare centers were 0.495 [95% CI, 0.477-0.513] and 0.108 [95% CI, 0.104-0.113], respectively. Residence in non-metropolitan area and lower household income was associated with higher risk of RD. CONCLUSIONS: Younger age, anterior vitrectomy for posterior capsule rupture, preoperative myopia, male gender, surgery in tertiary referral centers, residence in non-metropolitan area, and lower household income were associated with an increased risk of RD after cataract surgery. The optimal timing of cataract surgery should be determined considering patient's risk factors, and appropriate pre- and postoperative evaluation is needed to prevent RD in patients with higher risks.

Prospective Memory Loss and Related White Matter Changes in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Prospective memory (PM) has a known relationship with frontal function, and PM decline has been observed in amnestic mild cognitive impairment (aMCI). Cerebral small vessel disease, as evidenced by white matter hyperintensities (WMHs), is linked to frontal dysfunction. This study was undertaken to evaluate the relationship between PM decline and WMHs in patients with aMCI. METHODS: Of 74 enrollees with aMCI, 69 completed this prospective study. We compared total scores and sub-scores of the Prospective and Retrospective Memory Questionnaire (PRMQ) administered at baseline and 3 months later, stratifying patients by degree of WMHs. RESULTS: A significant decline was seen in PRMQ total scores and PM scores at the 3-month mark in patients with moderate (vs. mild) degrees of WMHs (-2.8±7.2 vs. 0.2±7.1; p=0.032). In addition, patients with moderate (vs. mild) degrees of deep WMHs (DWMHs) showed greater PM decline, whereas PM loss in patients with mild, moderate, or severe degrees of periventricular WMHs (PVWMHs) did not differ significantly. CONCLUSIONS: Findings of this study indicate that the burden of WMHs is consistently implicated in PM deterioration experienced by patients with aMCI, and signifies greater PM decline, especially in instances of extensive DWMHs. Greater attention to the change of PM is therefore needed in aMCI patients with WMHs.

The family-wide structure and function of human dual-specificity protein phosphatases.

Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling. A family-wide structural library of human DUSPs was constructed based on experimental structure determination supplemented with homology modelling. The catalytic domain of each individual DUSP has characteristic features in the active site and in surface-charge distribution, indicating substrate-interaction specificity. The active-site loop-to-strand switch occurs in a subtype-specific manner, indicating that the switch process is necessary for characteristic substrate interactions in the corresponding DUSPs. A comprehensive analysis of the activity-inhibition profile and active-site geometry of DUSPs revealed a novel role of the active-pocket structure in the substrate specificity of DUSPs. A structure-based analysis of redox responses indicated that the additional cysteine residues are important for the protection of enzyme activity. The family-wide structures of DUSPs form a basis for the understanding of phosphorylation-mediated signal transduction and the development of therapeutics.

1alpha,25-Dihydroxyvitamin D(3) Protects Dopaminergic Neurons in Rodent Models of Parkinson's Disease through Inhibition of Microglial Activation.

BACKGROUND: Recent studies have demonstrated the molecular basis of the immunomodulatory and anti-inflammatory activities of 1,25-dihydroxyvitamin D(3)(1,25-(OH)(2)D(3)). This hormone improves behavioral deficits and normalizes the nigral dopamine levels in animal models of Parkinson's disease (PD). METHODS: We studied whether the administration of 1,25-(OH)(2)D(3) would protect against 6-hydroxydopa (6-OHDA)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, and its potential regulatory effect on microglia activation. RESULTS: We found that 1,25-(OH)(2)D(3) pretreatment significantly decreased 6-OHDA- and MPTP-induced dopaminergic neuronal loss in the substantia nigra pars compacta by preventing the activation of microglia. This observed neuroprotective effect in MPTP-treated mice that were given 1,25-(OH)(2)D(3) may be attributable to inhibition of proinflammatory cytokine expression. CONCLUSION: These results suggest that 1,25-(OH)(2)D(3) is a potentially valuable neuroprotective agent; it may therefore be considered for the treatment of pathologic conditions of the central nervous system, such as PD, where inflammation-induced neurodegeneration occurs.