A 12-year nationwide cohort study on the association between central retinal artery occlusion and cancer.

PURPOSE: This study aims to investigate the association between incident central retinal artery occlusion (CRAO) and the subsequent development of cancer. METHODS: We included incident CRAO patients from the 2002-2013 National Health Insurance Service database in South Korea. For the patient cohort, we included patients diagnosed with CRAO from the database, and excluded patients having CRAO or any cancer history during the first 2-year washout period (2002-2003). Then, we defined their 1:4 propensity-score matched non-CRAO subjects as controls, all of whom also had no history of cancer during the washout period. Time-varying covariate Cox regression models were conducted to determine the association of CRAO with cancer. Kaplan-Meier curves with log-rank test were also analyzed. RESULTS: A total of 9712 patients with CRAO and 38,848 controls were included in the study. CRAO was associated with an increased risk of subsequent cancer (hazard ratio = 1.27; 95% confidence interval, 1.19-1.35). The incidence rate of overall cancer during the study period was 29.12 per 1000 person-years in the CRAO group and 22.77 per 1000 person-years in the control group. Incidence probability of overall cancer was significantly higher among CRAO patients than controls (P < 0.001, log-rank test). CONCLUSION: The risk of cancer occurrence was increased in patients with CRAO. The results supported that CRAO could be attributed to one of the consequences of arterial thrombosis in cancer patients.

Antihypertensive Use and the Risk of Cataract in Patients with Hypertension: A Nationwide Case-control Study.

PURPOSE: This study aims to investigate the association between antihypertensive use and the risk of cataract in a matched case-control study. METHODS: We analysed the Korean National Health Insurance Service-Health Screening Cohort database from 2002 to 2013. We defined 'cases' as patients prescribed antihypertensives and underwent their first eye cataract surgery between 2010 and 2013. 'Controls' were patients prescribed antihypertensives and no history of cataract surgery or diagnosis between 2002 and 2013. Four controls were matched to each case by several variables. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated for cataract risk using a conditional logistic regression model after adjustment. RESULTS: The analyses comprised 12,166 cases and 48,664 controls. The adjusted ORs for cataracts were 1.18 (95% CI: 1.12-1.24) in thiazide diuretics, 1.12 (95% CI: 1.07-1.18) in beta-blockers, 0.94 (95% CI: 0.90-1.00) in calcium channel blockers, 1.22 (95% CI: 1.14-1.30) in angiotensin-converting enzyme (ACE) inhibitors, and 0.97 (95% CI: 0.91-1.03) in angiotensin II receptor blockers compared to 'non-use' of each antihypertensive. CONCLUSION: In a nationwide case-control study, the use of thiazide diuretics, beta-blockers, or ACE inhibitors do not represent minimal clinical important difference in the risk of cataract and the use of calcium channel blockers or angiotensin II receptor blockers is not associated with an increased risk of cataracts compared to non-use of each antihypertensive. Given the benefits of treating hypertension, such as the reduction in further complications, we suggest there is no need to change current clinical practice for antihypertensives.

Fracture risk and impact of osteoporosis in patients with Parkinson's disease: a nationwide database study.

INTRODUCTION: Patients with Parkinson's disease (PD) showed an increased risk of fractures in previous studies and a high prevalence of osteoporosis is reportedly a potential contributor. We conducted a nationwide database study on the risk of fractures and the impact of osteoporosis on patients with PD compared to controls. MATERIALS AND METHODS: Using a nationwide database in South Korea, we identified incident patients with PD in 2004-2006 and selected four age- and sex-matched controls. We checked the occurrence rates of overall and hip fractures and plotted Kaplan-Meier curves and a Cox proportional hazards model to determine risk. We also conducted stratified analyses according to the presence or absence of osteoporosis. RESULTS: We identified 9126 patients with PD and 35,601 controls. Patients with PD had a greater probability of fractures throughout the study period in Kaplan-Meier curves, and an increased risk of overall (aHR 1.35, 95% CI 1.297-1.405) and hip (aHR 1.814, 95% CI 1.66-1.983) fractures in a Cox proportional hazards model. In the stratified analysis, the increased risk of overall fracture (aHR 1.333, 95% CI 1.273-1.396 and aHR 1.412, 95% CI 1.301-1.532, respectively) and hip fracture (aHR 1.773, 95% CI 1.604-1.96 and aHR 2.008, 95% CI 1.657-2.434, respectively) due to PD was similar between patients with and without osteoporosis. DISCUSSION: Patients with PD, with or without osteoporosis, are more likely to experience fractures, especially hip fractures. There seems to be no interaction between PD and osteoporosis in regard to the occurrence of fractures, and therefore no effect modification by osteoporosis.

Risk of Stroke or Acute Myocardial Infarction in Subconjunctival Hemorrhage: A Nationwide Cohort Study.

PURPOSE: To investigate whether subconjunctival hemorrhage (SCH) raises the risk of subsequent stroke or acute myocardial infarction (AMI) in the general population. METHODS: Using the National Health Insurance Service-National Sample Cohort database records from 2002 to 2013. Of 1,025,340 individuals in the database, we included 703,090 aged ≥ 20 years old without any history of SCH, cerebrovascular diseases, and ischemic heart diseases in the analyses. Of these, we identified 46,251 cases of incident SCH and regarded it as a time-varying covariate. We performed sensitivity analyses using 1:4 propensity score (PS)-based matched controls. To adjust for potential confounders, we investigated Cox regression models using defined demographic information, comorbidities, co-medications, and the Charlson Comorbidity Index score. RESULTS: The SCH group showed higher incidence probability of stroke or AMI than the general population (3.17% versus 2.71%, respectively; p < .001); however, when compared to the PS-based matched controls, there was no difference (3.17% versus 3.03%, respectively; p = .76). Time-varying covariate Cox regression analyses without adjusting for confounders showed that SCH was associated with increased risk of subsequent stroke or AMI; however, after adjusting for confounders, SCH did not increase the risk of stroke or AMI. CONCLUSION: This population-based cohort study showed that SCH itself is not a risk factor for stroke or AMI. Clinicians could reassure patients with SCH that it would not increase the risk for stroke or AMI. We recommend attentive evaluation of underlying diseases for patients with SCH for identifying risk factors of stroke or AMI.

Statin use and pneumonia risk in Parkinson's disease.

INTRODUCTION: Previous studies reported that statin use was related to a lower risk of pneumonia in the general population. This study investigated the association between statin use and pneumonia risk in patients with Parkinson's disease (PD). METHODS: Patients that had been newly diagnosed with PD between 2004 and 2006 in the 2002-2017 National Health Insurance Service database in South Korea were identified. PD patients who had received one or more statin prescriptions, and experienced pneumonia during the observation period were included in the self-controlled case series (SCCS) analysis. Patients who had no previous statin prescription record were included in the Cox proportional hazard model with a time-varying covariate (statin use). The risk of pneumonia in PD patients with statin use was estimated after adjusting potential confounders. RESULTS: Of the 10,159 patients with PD, 337 individuals were eligible for the SCCS analysis. The median duration of statin exposure was 2.63 years (IQR, 0.83-5.83). The incidence of pneumonia was reduced in the statin-exposed period compared to the unexposed period (incidence rate ratio, 0.88; 95% CI, 0.86-0.91). A total of 8,022 patients were included in the Cox proportional hazard model. Statin use was related to a significantly reduced pneumonia risk (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.78). CONCLUSIONS: Statin use was associated with a lower risk of pneumonia in PD patients. Statins might affect pneumonia occurrence by lowering cholesterol levels or slowing the progression of PD as neuroprotective agents. Further clinical studies are needed to delineate our findings with the underlying biological mechanisms.

Risk and mortality of aspiration pneumonia in Parkinson's disease: a nationwide database study.

This retrospective cohort study investigated the risk and mortality rate due to aspiration pneumonia in patients with Parkinson's disease (PD) using a nationwide database. We identified 10,159 newly diagnosed PD patients between 2004 and 2006, and four age- and sex-matched controls for each PD patient from the National Health Insurance Service database in Korea. We analyzed the relative risk of aspiration pneumonia and mortality after the first occurrence of aspiration pneumonia until 2017. Throughout the study period, PD patients showed a higher incidence of aspiration pneumonia than their matched controls (3.01 vs. 0.59 events per 1,000 person-years), and they were at an increased risk of aspiration pneumonia (hazard ratio = 4.21; 95% confidence interval, 3.87-4.58). After the first occurrence of aspiration pneumonia, the mortality rate of PD patients was 23.9% after one month, 65.2% after 1 year, and 91.8% after 5 years, while that of controls was 30.9%, 67.4%, and 88.9%, respectively. Patients with PD are at an increased risk of aspiration pneumonia, and approximately two-thirds of the patients die within a year after experiencing aspiration pneumonia. Further studies are warranted to prevent aspiration pneumonia and implement proper treatments to prevent death after aspiration pneumonia in patients with PD.

Assessment of Trends in the Incidence Rates of Central Retinal Artery Occlusion in Korea From 2002 to 2015.

IMPORTANCE: Central retinal artery occlusion (CRAO) is associated with and shares common risk factors with cardiovascular diseases. Over the past several decades, the incidence rates of stroke and ischemic heart disease have substantially decreased in high-income industrialized countries. However, little is known regarding current trends in CRAO incidence rates. OBJECTIVE: To estimate trends in the incidence rates of CRAO in Korea. DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based cohort study was designed on September 7, 2017, and used data from the Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. Individuals with incident CRAO between 2002 and 2015 were identified using the CRAO diagnostic code (H34.1) from the International Classification of Diseases, Tenth Revision. Unadjusted CRAO incidence rates were calculated using the number of CRAO cases identified and the corresponding midyear population, which was obtained from resident registration data. Standardized incidence rates were calculated based on the 2015 census population, and weighted mean annual incidence rates with 95% CIs were computed based on the Poisson distribution. To identify trends in incidence rates, joinpoint regression analysis was performed using standardized incidence rates, and annual percentage changes (APCs) were calculated across the 12-year study period. Data were analyzed from May 1, 2019, to April 30, 2020. MAIN OUTCOMES AND MEASURES: Temporal trends in CRAO incidence rates (measured as cases per 100 000 person-years) and age-standardized APCs in CRAO incidence rates using joinpoint and birth cohort analyses. RESULTS: Among 50 million residents of Korea, 9892 individuals (5884 men [59.5%]) with incident CRAO between 2002 and 2015 were identified. The mean age of Korean individuals diagnosed with CRAO was 62.4 years (range, 0-97 years); among men and women, the mean age was 61.5 years (range, 0-96 years) and 63.6 years (range, 0-97 years), respectively. The mean standardized incidence rate of CRAO was 2.00 cases per 100 000 person-years (95% CI, 1.97-2.04 cases per 100 000 person-years) among the entire population, 2.43 cases per 100 000 person-years (95% CI, 2.37-2.49 cases per 100 000 person-years) among men, and 1.61 cases per 100 000 person-years (95% CI, 1.57-1.66 cases per 100 000 person-years) among women. The highest incidence rate (9.85 cases per 100 000 person-years; 95% CI, 9.10-10.60 cases per 100 000 person-years) was observed among those aged 80 to 84 years (13.74 cases per 100 000 person-years [95% CI, 12.16-15.32 cases per 100 000 person-years] for men and 8.04 cases per 100 000 person-years [95% CI, 7.21-8.86 cases per 100 000 person-years] for women). The incidence rate in the overall study population decreased over time (APC, -3.46%; 95% CI, -4.3% to -2.6%), and this decreasing trend was more evident in women (APC, -4.56%; 95% CI, -5.7% to -3.4%) than in men (APC, -2.90%; 95% CI, -3.9% to -1.9%). The decrease in the incidence rate was more evident among participants younger than 65 years (APC, -6.80%; 95% CI, -8.3% to -5.2%) than among those 65 years and older (APC, -0.57%; 95% CI, -1.5% to -0.4%). Among participants born after 1930, a decrease in the CRAO incidence rate over time was observed in every age group, while the same decreasing trend was not present among those born before 1930. CONCLUSIONS AND RELEVANCE: This study found that the CRAO incidence rate has been decreasing among residents of Korea, especially among women, individuals younger than 65 years, and individuals born after 1930. This observed decrease may be associated with the development of a national health care system and the general improvement in chronic disease management.

Cardiovascular risk in patients receiving ranibizumab for exudative age-related macular degeneration: a nationwide self-controlled case-series study.

AIMS: To identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD). METHODS: We identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately. RESULTS: Among 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI. CONCLUSIONS: Ranibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.

Increased risk of cancer in patients with retinal vein occlusion: a 12-year nationwide cohort study.

AIMS: To investigate the association between incident retinal vein occlusion (RVO) and the subsequent development of cancer. METHODS: In this nationwide population-based retrospective study using 2002-2013 National Health Insurance Service database which covers the entire South Korean population, 186 701 incident RVO patients and their 1:1 propensity-score matched controls were included. We defined the fixed cohort from January 1st, 2004 to December 31st, 2013; the cohort included patients who suffered incident RVO after entering the cohort and their matched controls, and excluded patients having any cancer history before entering the cohort. The association of RVO and cancer was assessed by time-varying covariate Cox regression models; Model 1 included RVO as a time-varying covariate, Model 2 included Model 1 plus demographic information and Model 3 included Model 2 and comorbidities. RESULTS: RVO was associated with an increased risk of subsequent cancer (HR=1.29; 95% CI, 1.26-1.31 in Model 1), which was consistent in Models 2 and 3. The incidence rate of overall cancer during the study period was 25.55 (95% CI, 25.19-25.91) per 1000 person-years in the RVO group and 18.62 (95% CI, 18.46-18.79) per 1000 person-years in the control group. In the subgroup analysis, haematological malignancies showed the highest association with RVO (HR=1.65; 95% CI, 1.49-1.83). CONCLUSION: Patients with RVO have an increased risk of subsequent cancer development even after adjusting for demographic factors and comorbidities. Further study is warranted to elucidate these associations to provide proper recommendations for RVO patients regarding the cancer screening.

Ten-Year Relative Survival From the Diagnosis of Parkinson's Disease: A Nationwide Database Study.

OBJECTIVES: Varying early survival rates have been reported across studies on patients with Parkinson's disease (PD). In this study, we reported the 10-year relative survival rate of patients with PD using a nationwide database. DESIGN: This was a population-based cohort study. SETTING AND PARTICIPANTS: We identified incident PD cases from 2004 to 2006 using the PD registration codes from the National Health Insurance Service database covering the entire South Korean population. METHODS: Relative survival up to 10 years was evaluated by adjusting all-cause survival for expected survival, estimated from population life tables and matched by sex, age, and year of diagnosis. RESULTS: Of the 10,159 patients with PD, 4675 (46.0%) patients survived 10 years after diagnosis. Relative survival rates decreased with time after diagnosis (0.972 after 1 year, 0.772 after 5 years, and 0.588 after 10 years). Ten-year relative survival gradually decreased with age at diagnosis. Men had a lower relative survival rate than women 2 years post diagnosis, and if they were older than 60 years. CONCLUSIONS AND IMPLICATIONS: Patients diagnosed with PD are expected to have a lower 10-year relative survival. In the real world, patients with PD might have lower survival than the general population even in the early disease stage. Our results suggest further efforts to prevent premature mortality among patients with PD.

Twelve-year incidence of retinal vein occlusion and its trend in Korea.

PURPOSE: To estimate the 12-year incidence and trends of clinically diagnosed retinal vein occlusion (RVO) in Korea. METHODS: This is a nationwide population-based retrospective study using the Korean national health claims database from 2002 to 2015. The study consisted of the entire Korean population based on the 2015 Census of Population. We identified patients with incident RVO in 2004-2015. We estimated the crude incidence rates and age- and sex-standardized incidence rates in each 12-year study period. To determine the trend, we also performed joinpoint regression analyses. RESULTS: We identified 240,495 incident RVO cases. The average incidence rate was 48.09 (95% confidence interval [CI], 47.92-48.27). Women showed a 1.24 times higher incidence rate (53.18 [95% CI, 52.92-53.44]) compared with men (42.78 [95% CI, 42.55-43.02]), while, among patients aged less than 50 years and those aged 80 years or over, men showed higher incidence rates than did women. The highest incidence of 193.56 (95% CI, 191.06-196.06) was observed in the age group of 75 to 79 years. The joinpoint analysis showed an increasing trend of RVO incidence among patients at the age of 70 years and older (annual percentage change, 2.1; 95% CI, 0.2-4.0; p < 0.01). CONCLUSION: RVO is a disease of the elderly that peaks in the late 70s and occurs more in women than in men. In Korea, RVO incidence increased from 2004 to 2015 among the population aged 70 years or older, while among those aged less than 70 years, no trend was observed in RVO incidence rates.

Pneumonia risk and its associated factors in Parkinson's disease: A National Database Study.

BACKGROUND: Despite pneumonia being an emerging burden on Parkinson's disease patients, there is essentially nothing known on whether they are at an increased risk of pneumonia occurrence and their associated factors. OBJECTIVES: To determine whether Parkinson's disease is associated with the risk of pneumonia and its associated factors. METHODS: Using nationwide database that covers the whole population in South Korea from 2002 to 2017, we identified newly diagnosed Parkinson's disease patients in 2004-2006, and selected four age- and sex-matched controls for each patient from the general population. From these patients and controls, we identified pneumonia occurrence until the end of the study period, and plotted Kaplan-Meier curves and Cox proportional hazards model to determine its risk. RESULTS: We identified 10,159 Parkinson's disease patients and matched 39,574 controls. These patients showed a higher incidence rate than controls (11.21 vs. 3.61 events/1000 person-years) throughout the study period, and were at an increased risk of pneumonia (hazard ratio = 2.26; 95% CI, 2.17-2.36) even after adjusting for confounders. Old age, male sex, region of residence, diabetes mellitus, congestive heart failure, tuberculosis, atrial fibrillation, chronic kidney disease, cerebrovascular disease, dementia, chronic obstructive pulmonary disease, seizure disorder and antidiabetic drug usage were all associated with a higher risk of pneumonia, while dyslipidemia and antihypertensive medication usage lowered the risk. CONCLUSIONS: Parkinson's disease patients may be more likely to experience pneumonia compared to the general population throughout the disease course from diagnosis. Therefore, physicians should focus on the modifiable risk factors of pneumonia in such patients.

Effects of Hypertension, Diabetes, and Smoking on Age and Sex Prediction from Retinal Fundus Images.

Retinal fundus images are used to detect organ damage from vascular diseases (e.g. diabetes mellitus and hypertension) and screen ocular diseases. We aimed to assess convolutional neural network (CNN) models that predict age and sex from retinal fundus images in normal participants and in participants with underlying systemic vascular-altered status. In addition, we also tried to investigate clues regarding differences between normal ageing and vascular pathologic changes using the CNN models. In this study, we developed CNN age and sex prediction models using 219,302 fundus images from normal participants without hypertension, diabetes mellitus (DM), and any smoking history. The trained models were assessed in four test-sets with 24,366 images from normal participants, 40,659 images from hypertension participants, 14,189 images from DM participants, and 113,510 images from smokers. The CNN model accurately predicted age in normal participants; the correlation between predicted age and chronologic age was R2 = 0.92, and the mean absolute error (MAE) was 3.06 years. MAEs in test-sets with hypertension (3.46 years), DM (3.55 years), and smoking (2.65 years) were similar to that of normal participants; however, R2 values were relatively low (hypertension, R2 = 0.74; DM, R2 = 0.75; smoking, R2 = 0.86). In subgroups with participants over 60 years, the MAEs increased to above 4.0 years and the accuracies declined for all test-sets. Fundus-predicted sex demonstrated acceptable accuracy (area under curve > 0.96) in all test-sets. Retinal fundus images from participants with underlying vascular-altered conditions (hypertension, DM, or smoking) indicated similar MAEs and low coefficients of determination (R2) between the predicted age and chronologic age, thus suggesting that the ageing process and pathologic vascular changes exhibit different features. Our models demonstrate the most improved performance yet and provided clues to the relationship and difference between ageing and pathologic changes from underlying systemic vascular conditions. In the process of fundus change, systemic vascular diseases are thought to have a different effect from ageing. Research in context. Evidence before this study. The human retina and optic disc continuously change with ageing, and they share physiologic or pathologic characteristics with brain and systemic vascular status. As retinal fundus images provide high-resolution in-vivo images of retinal vessels and parenchyma without any invasive procedure, it has been used to screen ocular diseases and has attracted significant attention as a predictive biomarker for cerebral and systemic vascular diseases. Recently, deep neural networks have revolutionised the field of medical image analysis including retinal fundus images and shown reliable results in predicting age, sex, and presence of cardiovascular diseases. Added value of this study. This is the first study demonstrating how a convolutional neural network (CNN) trained using retinal fundus images from normal participants measures the age of participants with underlying vascular conditions such as hypertension, diabetes mellitus (DM), or history of smoking using a large database, SBRIA, which contains 412,026 retinal fundus images from 155,449 participants. Our results indicated that the model accurately predicted age in normal participants, while correlations (coefficient of determination, R2) in test-sets with hypertension, DM, and smoking were relatively low. Additionally, a subgroup analysis indicated that mean absolute errors (MAEs) increased and accuracies declined significantly in subgroups with participants over 60 years of age in both normal participants and participants with vascular-altered conditions. These results suggest that pathologic retinal vascular changes occurring in systemic vascular diseases are different form the changes in spontaneous ageing process, and the ageing process observed in retinal fundus images may saturate at age about 60 years. Implications of all available evidence. Based on this study and previous reports, the CNN could accurately and reliably predict age and sex using retinal fundus images. The fact that retinal changes caused by ageing and systemic vascular diseases occur differently motivates one to understand the retina deeper. Deep learning-based fundus image reading may be a more useful and beneficial tool for screening and diagnosing systemic and ocular diseases after further development.

Association Between Acetylcholinesterase Inhibitors and Osteoporotic Fractures in Older Persons With Alzheimer's Disease.

OBJECTIVE: To identify the association between the use of acetylcholinesterase inhibitors (AChEIs) and risk of osteoporotic fractures in older persons with Alzheimer's disease (AD). DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was conducted using the Korean National Health Insurance Service-National Elderly Cohort database. Patients with AD who were newly diagnosed with osteoporotic fractures were identified as cases. Up to 3 controls were matched with cases according to age, sex, and duration of follow-up. METHODS: Participants were considered as exposed to AChEIs if they had been prescribed at least 1 AChEI during a period of 2 years before the index date. A conditional logistic regression was performed to estimate the adjusted odds ratios with 95% confidence intervals for the association between the use of AChEIs and osteoporotic fractures in patients with AD. We also examined the impact of dose, duration of treatment, and timing of exposure on the estimates of the association between the use of AChEIs and risk of osteoporotic fractures. RESULTS: The study cohort comprised 45,006 patients diagnosed with AD, of which 9470 patients, including 2385 cases and 7085 controls, were available for the study. The mean ages (standard deviations) were 78.6 (6.9) years in the cases and 80.0 (6.9) years in the controls. Adjusted odds ratios for the association between the use of AChEIs and osteoporotic fractures in patients with AD was 1.18 (95% confidence interval 1.07-1.31). CONCLUSIONS AND IMPLICATIONS: Our data indicated that the use of AChEIs was not associated with a reduced risk of osteoporotic fractures in patients with AD; in contrast, their use was associated with a mild increased risk of osteoporotic fractures. Thus, clinicians should consider the possibility of AChEIs-associated fractures among older persons with AD. Findings of this study will support shared decision making among prescribers, patients, and caregivers.

Incremental economic burden associated with exudative age-related macular degeneration: a population-based study.

BACKGROUND: The exudative age-related macular degeneration (AMD) causes considerable healthcare costs for patients and healthcare system, which are expected to grow as the population ages. The objective of this study was to assess the incremental economic burden of exudative AMD by comparing total healthcare costs between the exudative AMD group and non-AMD group to understand economic burden related to exudative AMD. METHODS: This retrospective cohort study used the National Health Insurance Service database including the entire Korean population. Exudative AMD group included individuals with at least one claim for ranibizumab and one claim using the registration code for exudative AMD (V201). Non-AMD group was defined as individuals without any claims regarding the diagnostic code of H35.3 or ranibizumab. The exudative AMD group and non-AMD group were matched using a propensity-score model. Incremental healthcare resource utilization and healthcare costs were measured during a one-year follow-up by employing econometric models: ordinary least squares (OLS) with log transformation and heteroscedastic retransformation; and generalized linear model (GLM) with a log link function and gamma distribution. RESULTS: A total of 7119 exudative AMD patients were matched to 7119 non-AMD patients. The number of outpatient visits was higher in the exudative AMD group (P-value < 0.0001), while the length of hospitalization was shorter in exudative AMD group (P-value < 0.0001). Exudative AMD patients had total costs 2.13 times (95%CI, 2.08-2.17) greater than non-AMD group using OLS, and total costs 4.06 times (95%CI, 3.82-4.31) greater than non-AMD group using GLM. Annual incremental total costs were estimated as $5519 (OLS) and $3699 (GLM). CONCLUSIONS: Exudative AMD was associated with significantly increased healthcare costs compared to the non-AMD group. Attention is needed to manage the socioeconomic burden of exudative AMD.

Nonarteritic anterior ischemic optic neuropathy is associated with cerebral small vessel disease.

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p<0.001), which was also observed after adjusting for age, sex, comorbid conditions including hypertension, diabetes, and dyslipidemia, and smoking using the standardized mortality ratio (68% vs. 37%, p<0.001). A multivariate logistic regression analysis showed that the odds of cerebral SVD were 4.86 (95% CI, 2.10 to 11.24, p<0.001) times higher in patients with NAION than in the controls. We found that there was an association between cerebral SVD and NAION even after adjusting for age, sex, and medical histories. Clinicians should consider brain MRI scans in patients with NAION to prevent neurological impairment after cerebral SVD.

Primary Open-angle Glaucoma and Increased Risk of Chronic Kidney Disease.

PRECIS: The association between primary open-angle glaucoma (POAG) and subsequent development of chronic kidney disease (CKD) was investigated using a nationwide, population-based, retrospective cohort in South Korea. POAG increases the risk of subsequent CKD development. PURPOSE: The purpose of this study was to investigate the risk of subsequent CKD development in patients with POAG. METHODS: In this nationwide, population-based longitudinal cohort, 1,025,340 beneficiaries in the 2002-2013 Korean National Health Insurance database were included. We identified patients with incident POAG and evaluated the risk of subsequent CKD development using diagnostic codes from the database after 2-year wash-out periods. We applied time-varying covariate Cox regression analyses to determine the effect of POAG on the development of CKD: Model 1 included only POAG as a time-varying covariate; Model 2 included Model 1 and demographic information; and Model 3 included Model 2, comorbidity, comedication, and the Charlson Comorbidity Index score. RESULTS: The fixed cohort included 478,303 eligible subjects, and of these subjects, 1749 suffered incident POAG, and 3157 developed CKD. POAG was associated with an increased risk of CKD development [hazard ratio (HR)=7.63; 95% confidence interval (CI), 5.89-9.87] in Model 1; HR=3.54 (95% CI, 2.73-4.58) in Model 2; and HR=2.90 (95% CI, 2.24-3.76) in Model 3]. CONCLUSION: POAG increased the risk of subsequent CKD in the general population, suggesting that POAG and CKD might share a common pathogenic mechanism.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy After Cataract Surgery.

PURPOSE: To determine whether the development of nonarteritic anterior ischemic optic neuropathy (NAION) is increased after receiving cataract surgery in a large general population. DESIGN: Nationwide, population-based, retrospective cohort study. METHODS: Setting: A 12-year nationwide, population-based, retrospective cohort study including 1,025,340 beneficiaries in the 2002-2013 Korean National Health Insurance Service database. PATIENTS: We identified 40,356 patients who had undergone cataract surgery and matched non-cataract surgery controls (1:2) using estimated propensity scores in reference to age, sex, demographics, comorbidities, and co-medications. OBSERVATIONS: Kaplan-Meier curves and Cox proportional hazard models were generated to determine the risk of developing NAION in the cataract surgery group compared to the non-cataract surgery group. MAIN OUTCOME MEASURES: Effect (hazard ratio [HR]) of cataract surgery on NAION development. RESULTS: The 10-year incidence probability of NAION was 0.70% (95% confidence interval [CI], 0.55%-0.86%) in the cataract surgery group and 0.27% (95% CI, 0.25%-0.29%) in the non-cataract surgery group (P < .0001, log-rank test). The cataract surgery group had an increased risk of developing NAION compared to the non-cataract surgery group (HR = 1.80; 95% CIs, 1.46-2.21) even after adjusting for demographics, comorbidities, Charlson comorbidity index, and co-medications. CONCLUSION: Our results suggest that patients undergoing cataract surgery have an increased risk of NAION.