Risk of prostate cancer with increasing years of night shift work: A two-stage dose-response meta-analysis with duration of night shift work as exposure dose.

Introduction: Night shift work could be a modifiable risk factor for prostate cancer. However, the epidemiological evidence is inconsistent. To summarize the existing evidence on this topic, we conducted a two-stage dose-response meta-analysis. Methods: Medical librarians searched PubMed, EMBASE, and the Cochrane Library on December 30, 2022. Seven criteria were used to determine the inclusion of each study in the present analysis. Results: Eleven cohort studies (12 cohort reports; total cases: 9366; and total person-years: 88,238,009) and seven case-control studies (seven case-control reports; total cases: 5593; and total controls: 6876) were included. This study estimated that the risk of prostate cancer increased by 1, 12, 24, and 39% after 1, 10, 20, and 30 years of night shift work exposure, respectively, according to four cohort and five case-control studies. Discussion: Seven inclusion criteria were used to determine which studies were eligible for this analysis. Risk ratios from cohort studies and odds ratios from case-control studies were analyzed separately. However, all odds ratios from the case-control studies were excluded because of a high likelihood of publication bias. Moreover, exposure, measured in years of night shift work, was defined based on the information provided by individual studies. Finally, we utilized a recently reported two-stage dose-response meta-analysis method. This study provides evidence that night shift work contributes to the risk of prostate cancer in a dose-dependent manner.

The association between per- and polyfluoroalkyl substances (PFASs) and brain, esophageal, melanomatous skin, prostate, and lung cancer using the 2003-2018 US National Health and Nutrition Examination Survey (NHANES) datasets.

Introduction: The purpose of this study was to use the US National Health and Nutrition Examination Survey (NHANES) datasets to examine potential relationships between four per- and polyfluoroalkyl substance (PFAS) exposures and each type of cancer, specifically perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Methods: A logistic regression analysis was performed. A directed acyclic graph was plotted to adjust for the potential confounders. Results: The odds ratio (OR) of brain cancer for a one-unit increase in ln (PFHxS) was 8.16 (95 % confidence interval [CI] 2.98-68.89). The OR of esophageal cancer for one unit increase of ln (PFOA) and ln (PFOS) was 5.10 (95 % CI 1.18-17.34) and 3.97 (95 % CI 1.24-11.42), respectively. The OR of melanoma for one unit increase of ln (PFOA) and ln (PFHxS) was 1.65 (95 % CI 1.07-2.58) and 1.55 (95 % CI 1.07-2.25), respectively. The OR of prostate cancer for one unit increase of ln (PFOS) and ln (PFNA) was 1.21 (95 % CI 1.00-1.48) and 1.27 (95 % CI 1.00-1.62), respectively. The OR of lung cancer for one unit increase of ln (PFOS) and ln (PFNA) was 2.62 (95 % CI 1.24-5.83) and 2.38 (95 % CI 1.00-5.52), respectively. Discussion: Considering that brain, esophageal, and melanomatous skin cancers have not been targets of epidemiologic studies regarding PFAS exposure, future studies could target these cancers as outcomes of interest.

Patient-Centered Economic Burden of Exudative Age-Related Macular Degeneration: Retrospective Cohort Study.

BACKGROUND: Exudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti-vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs. OBJECTIVE: This study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: This retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model. RESULTS: We identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P<.001 in all cases). CONCLUSIONS: Exudative AMD had a significantly greater economic impact (P<.001) for 2 years on reimbursement, nonreimbursement, and out-of-pocket costs than nonexudative AMD after adjusting for baseline demographic and clinical characteristics using the OMOP CDM. Although economic policies could relieve the economic burden of patients with exudative AMD over time, the out-of-pocket cost of exudative AMD was still higher than that of nonexudative AMD for 2 years. Our findings support the need for expanding reimbursement strategies for patients with exudative AMD given the significant economic burden faced by patients with incurable and fatal diseases both in South Korea and worldwide.

Comparison of treatment methods for submacular hemorrhage in neovascular age-related macular degeneration: conservative versus active surgical strategy.

The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P < 0.001). Only baseline BCVA was associated with VA gain at 12 months (Odds ratio = 3.53, P < 0.001). This study demonstrated that there was no difference in 12 month visual outcomes among treatments and a better early visual outcome can be expected with anti-VEGF monotherapy.

Real-world treatment intensities and pathways of macular edema following retinal vein occlusion in Korea from Common Data Model in ophthalmology.

Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

Visual Field Characteristics in East Asian Patients With Occult Macular Dystrophy (Miyake Disease): EAOMD Report No. 3.

Purpose: The purpose of this study was to investigate the perimetric features and their associations with structural and functional features in patients with RP1L1-associated occult macular dystrophy (OMD; i.e. Miyake disease). Methods: In this international, multicenter, retrospective cohort study, 76 eyes of 38 patients from an East Asian cohort of patients with RP1L1-associated OMD were recruited. Visual field tests were performed using standard automated perimetry, and the patients were classified into three perimetric groups based on the visual field findings: central scotoma, other scotoma (e.g. paracentral scotoma), and no scotoma. The association of the structural and functional findings with the perimetric findings was evaluated. Results: Fifty-four eyes (71.1%) showed central scotoma, 14 (18.4%) had other scotomata, and 8 (10.5%) had no scotoma. Central scotoma was mostly noted in both eyes (96.3%) and within the central 10 degrees (90.7%). Among the three perimetric groups, there were significant differences in visual symptoms, best-corrected visual acuity (BCVA), and structural phenotypes (i.e. severity of photoreceptor changes). The central scotoma group showed worse BCVA often with severe structural abnormalities (96.3%) and a pathogenic variant of p.R45W (72.2%). The multifocal electroretinogram (mfERG) groups largely corresponded with the perimetric groups; however, 8 (10.5%) of 76 eyes showed mfERG abnormalities preceding typical central scotoma. Conclusions: The patterns of scotoma with different clinical severity were first identified in occult macular dystrophy, and central scotoma, a severe pattern, was most frequently observed. These perimetric patterns were associated with the severity of BCVA, structural phenotypes, genotype, and objective functional characteristics which may precede in some cases.

Real-world incidence of endopthalmitis after intravitreal anti-VEGF injections in Korea: findings from the Common Data Model in ophthalmology.

OBJECTIVES: The aim of this study was to evaluate the real-world incidence of endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injections using data from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: Patients with endophthalmitis that developed within 6 weeks after intravitreal anti-VEGF injections were identified in 3 large OMOP CDM databases. RESULTS: We identified 23,490 patients who received 128,123 intravitreal anti-VEGF injections. The incidence rates of endophthalmitis were 15.75 per 10,000 patients and 2.97 per 10,000 injections. The incidence rates of endophthalmitis for bevacizumab, ranibizumab, and aflibercept (per 10,000 injections) were 3.64, 1.39, and 0.76, respectively. The annual incidence has remained below 5.00 per 10,000 injections since 2011 despite the increasing number of intravitreal anti-VEGF injections. Bevacizumab presented a higher incidence rate for endophthalmitis than ranibizumab and aflibercept (incidence rate ratio, 3.17; p=0.021). CONCLUSIONS: The incidence of endophthalmitis after intravitreal anti-VEGF injections has stabilized since 2011 despite the explosive increase in anti-VEGF injections. The off-label use of bevacizumab accounted for its disproportionately high incidence of endophthalmitis. The OMOP CDM, which includes off-label uses, laboratory data, and a scalable standardized database, could provide a novel strategy to reveal real-world evidence, especially in ophthalmology.

Role of Neutrophils on the Ocular Surface.

The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.

Efficacy of anti-vascular endothelial growth factor agents for treating neovascular age-related macular degeneration in vitrectomized eyes.

PURPOSE: To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for treatment of neovascular age-related macular degeneration (nAMD) in vitrectomized eyes. METHODS: The medical records were reviewed of nAMD patients treated with anti-VEGF agents who previously underwent pars plana vitrectomy (PPV). PPV was performed with complete posterior vitreous detachment induction. RESULTS: A total of 44 eyes from 44 patients were included. The mean central foveal thickness (CFT) was 478.50 ± 156.93 µm at baseline, 414.25 ± 143.55 µm (86.6% of baseline) at 1 month after first injection (P < 0.001), and 386.75 ± 141.45 µm (80.8% of baseline) after monthly multiple injections (2.30 ± 1.07; range, 1-5) (P < 0.001). The mean logarithm of the minimum angle of resolution best-corrected visual acuity visual acuity (BCVA) was 0.85 ± 0.57 at baseline, 0.86 ± 0.63 after the first injection, and 0.84 ± 0.64 after monthly multiple injections. BCVA improved in 39.5% at 1 month after first injection and 45.2% at 1 month after monthly multiple injections. In the subgroup analysis, CFT of eyes with the posterior capsule decreased significantly to 85.8% and 79.8% of baseline values at 1 month after the first injection and after monthly multiple injections, respectively. CFT of eyes without the posterior capsule decreased to 91.6% and 87.4% of baseline values at 1 month after the first injection and after monthly multiple injections, respectively, without statistical significance. CONCLUSION: Monthly injections of Intravitreal anti-VEGF agents induced favorable anatomical improvement and vision maintenance in vitrectomized eyes with nAMD.

An innovative strategy for standardized, structured, and interoperable results in ophthalmic examinations.

BACKGROUND: Although ophthalmic devices have made remarkable progress and are widely used, most lack standardization of both image review and results reporting systems, making interoperability unachievable. We developed and validated new software for extracting, transforming, and storing information from report images produced by ophthalmic examination devices to generate standardized, structured, and interoperable information to assist ophthalmologists in eye clinics. RESULTS: We selected report images derived from optical coherence tomography (OCT). The new software consists of three parts: (1) The Area Explorer, which determines whether the designated area in the configuration file contains numeric values or tomographic images; (2) The Value Reader, which converts images to text according to ophthalmic measurements; and (3) The Finding Classifier, which classifies pathologic findings from tomographic images included in the report. After assessment of Value Reader accuracy by human experts, all report images were converted and stored in a database. We applied the Value Reader, which achieved 99.67% accuracy, to a total of 433,175 OCT report images acquired in a single tertiary hospital from 07/04/2006 to 08/31/2019. The Finding Classifier provided pathologic findings (e.g., macular edema and subretinal fluid) and disease activity. Patient longitudinal data could be easily reviewed to document changes in measurements over time. The final results were loaded into a common data model (CDM), and the cropped tomographic images were loaded into the Picture Archive Communication System. CONCLUSIONS: The newly developed software extracts valuable information from OCT images and may be extended to other types of report image files produced by medical devices. Furthermore, powerful databases such as the CDM may be implemented or augmented by adding the information captured through our program.

Ten-year analysis of microbiological profile and antibiotic sensitivity for bacterial keratitis in Korea.

PURPOSE: To investigate the risk factors, microbiological profiles, antibiotic susceptibility patterns, and treatment outcome in patients with bacterial keratitis at a Korean tertiary hospital. METHODS: A retrospective chart review was performed of patients who were diagnosed with infectious keratitis and underwent corneal scrapings for cultures at Seoul National University Hospital between 2007 and 2016. Demographics, clinical characteristics, microbiological data, antibiotic resistance and sensitivity, and treatment outcome were collected. RESULTS: Out of 129 scrapings, bacteria were isolated in 101 samples (78.3%). The most frequent isolates were coagulase-negative Staphylococci (CNS) (15.9%), Staphylococcus aureus (12.1%) and Pseudomonas aeruginosa (10.3%). All gram-positive isolates were sensitive to vancomycin, but methicillin resistance was found in 29.4% of CNS and 15.4% of Staphylococcus aureus. All gram-negative isolates were susceptible to ceftazidime and carbapenem while 11.5%, 3.3% and 2.8% of gram-negative isolates were resistant to gentamicin, tobramycin and amikacin, respectively. Ciprofloxacin resistance was observed in 10.3% of gram-positive isolates and 8.8% of gram-negative isolates. No significant changes were observed in profiles of microbial isolates and antibiotic sensitivity over time. Eight eyes of 101 eyes (7.9%) eventually underwent evisceration for infection control. The use of topical glaucoma medication (p = 0.006) and history of ocular surgery (p = 0.019) were significant risk factors related to evisceration. CONCLUSIONS: CNS, Staphylococcus aureus and Pseudomonas aeruginosa were the most common microorganisms responsible for bacterial keratitis. The duo-therapy using vancomycin and ceftazidime should be considered for empirical treatment until the culture and sensitivity results become available.

Therapeutic effects of 3% diquafosol ophthalmic solution in patients with short tear film break-up time-type dry eye disease.

BACKGROUND: To investigate therapeutic effects of topical diquafosol tetrasodium 3% ophthalmic solution in patients with short tear film break-up time (TFBUT)-type dry eye (DE). METHODS: The prospective study was performed in 70 eyes of 70 patients with short TFBUT-type DE. Diagnosis of short TFBUT-type DE was made based on the presence of DE symptoms, TFBUT value ≤5 s, corneoconjunctival staining score ≤ 2 (on a scale of 0 to 4), and Schirmer I value > 5 mm. Patients with systemic immunologic disorders or ocular graft-versus-host disease were excluded. Before and after instillation of 3% diquafosol ophthalmic solution six times per day for 4 weeks, subjective DE symptoms, TFBUT, corneoconjunctival staining score, and Schirmer I value were examined and compared. Also, demographic factors were compared between patients who showed improvement in each DE parameter by treatment and those who did not. RESULTS: Four-week treatment with 3% diquafosol ophthalmic solution significantly improved DE symptoms (p < 0.0001), increased TFBUT (p < 0.0001), and reduced corneoconjunctival staining scores (p < 0.0001). Schirmer I values were not changed by treatment. The age of patients who showed improvement in subjective DE symptoms after treatment was significantly lower than that of patients who did not (53.4 ± 27.5 vs. 63.3 ± 13.9 years, p = 0.012). Ocular side effects developed in 3 patients (4.3%), including conjunctival chemosis (n = 1) and persistent stinging sensation (n = 2). CONCLUSIONS: Diquafosol tetrasodium 3% ophthalmic solution is effective in improving subjective symptoms and tear film stability in short TFBUT-type DE patients. TRIAL REGISTRATION: The study was retrospectively registered on Clinical Research Information Service (CRiS), Republic of Korea. TRIAL REGISTRATION NUMBER: KCT0003134 . Date of registration: 2018-08-15.