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Shih-Chun Chao,1–3,* Chia-Yi Lee,1,* Chan-Wei Nien,1 Shih-Hao Tzeng,1 Hung-Yu Lin1,4–6 1Department of Ophthalmology, Show Chwan Memorial Hospital, Changhua, Taiwan, Republic of China; 2Department of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan, Republic of China; 3Department of Optometry, Central Taiwan University of Science and Technology, Taichung, Taiwan, Republic of China; 4Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 5Department of Optometry, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 6Department of Optometry, Yuanpei University of Medical Technology, Hsinchu, Taiwan, Republic of China *These authors contributed equally to this work Background: Postoperative endophthalmitis is a dreaded postsurgery complication which may lead to legal blindness. In addition to typical risk factors, some minor episodes may also lead to the occurrence of endophthalmitis. The purpose of the current study was to report a case of acute postoperative endophthalmitis caused by Staphylococcus hyicus in a patient with a contact history of felines.Case presentation: A 58-year-old Taiwanese female who had a history of contact with felines due to her occupation had received clear lens extraction surgery of the left eye on July 10, 2015. One day after the surgery, the best-corrected visual acuity (BCVA) of the left eye was 20/40, which rapidly deteriorated to light perception with hypopyon formation. She was admitted for acute postoperative endophthalmitis and received antibiotic therapy with topical levofloxacin instillation and intravitreal vancomycin plus amikacin injection. Trans pars plana vitrectomy (TPPV) was then performed 1 day after admission. The specimen obtained from the vitreous and anterior chambers yielded the growth of S. hyicus. The patient was discharged with BCVA measured by counting fingers. Another TPPV was arranged for the persistent vitreous opacity on October 20, 2015, and the BCVA recovered to 20/32 at the last visit.Conclusion: To our knowledge, this is the first case of acute postoperative endophthalmitis caused by S. hyicus due to feline contact. Unusual pathogens in the environment and personal hygiene status should be validated preoperatively to prevent the development of postoperative endophthalmitis. Keywords: Staphylococcal hyicus, feline, endophthalmitis, clear lens extraction

Background: Sjögren's syndrome may be a risk factor for carotid artery stenosis. Bilateral common carotid artery occlusion (BCCAO) in a patient with Sjögren's syndrome was not reported before. In this report, we describe a female with Sjögren's syndrome who had acute visual loss due to ocular ischemic syndrome (OIS) with BCCAO., Case Presentation: A 50-year-old female with Sjögren's syndrome visited our clinic with acute visual loss in the left eye. The best corrected visual acuity (BCVA) was 2/100 in the left eye, and the intraocular pressure (IOP) was normal in both eyes. Ocular ischemic change was observed during the ophthalmic examination. Aortography and computed tomography angiography (CTA) showed nearly total occlusion of the bilateral CCA. Thus, OIS with BCCAO was diagnosed. The vision in the left eye improved to 30/100 after carotid artery stenting for the left common carotid artery., Conclusions: BCCAO may be present in patients with Sjögren's syndrome. Large vessel abnormalities should be considered when acute visual loss is found in a patient with Sjögren's syndrome., (© 2021. The Author(s).)

Background: The effect of diabetic retinopathy (DR) on the development of sight-threatening cataracts was assessed using the National Health Insurance Research Database of Taiwan., Methods: Patients diagnosed with diabetes mellitus (DM) and DR were enrolled in the study group. Age- and sex-matched DM individuals without DR and patients without DM served as the DM control group and non-DM control group, respectively, both with 1:4 ratios. The outcome was set as the performance of cataract surgery. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (aHR) of DR considering multiple factors underlying cataract formation., Results: A total of 3297 DR patients, 13,188 DM control patients and 13,188 non-DM control subjects were enrolled. The study group included 919 events of sight-threatening cataracts (27.87%), the DM control group included 1108 events (8.40%), and the non-DM control group included 957 events (7.26%). A multivariable analysis indicated that the study group presented a higher aHR of cataract surgery (2.93, 95% CI: 2.60-3.30) and a higher cumulative probability of cataract surgery than both the DM control and non-DM control groups (both log rank P < 0.001). In addition, both the proliferative DR (3.90, 95% CI: 3.42-4.45) and nonproliferative DR (2.35, 95% CI: 2.08-2.65) subgroups showed a higher aHR of cataract surgery than the DM control group., Conclusion: The presence of DR increases the risk of sight-threatening cataracts that warrant surgery, and the effect is prominent among patients with both proliferative DR and nonproliferative DR., (© 2021. The Author(s).)

The aim of the present study was to survey the relationship between central serous chorioretinopathy (CSC) and several cardiovascular diseases (CVDs) with different severities using the National Health Insurance Research Database. A retrospective cohort study was conducted. Subjects with CSC were enrolled according to the relevant diagnostic codes, and an age- and gender-matched population was used as the control group with a 1:4 ratio. The main outcome being considered was the development of CVD after CSC exposure. Cox proportional hazard regression was applied to calculate the adjusted hazard ratio (aHR) of CSC and CVD of different types. A total of 2865 patients that were diagnosed with CSC were enrolled in the study group, while another 11,460 non-CSC subjects were selected as the control group. There were 171 events of CVD which occurred in the study group, while another 557 cases were found in the control group. No significant differences were observed among the CVD cases between the study and control group, whether they had an acute or chronic form, according to the aHR. In the subgroup analysis, there was a significantly higher risk of CVD development in the male population aged from 40 to 59 years (aHR: 1.351, confidence interval (CI): 1.063-1.716), which was mainly due to the higher risk of mild CVD (aHR: 1.391, CI: 1.062-1.822). On the contrary, there was no significant difference in CVD development in any of the age subgroups of the female population. In conclusion, the existence of CSC is correlated with a higher rate of chronic CVD occurrence in the middle-aged male population., Competing Interests: The authors declare no conflicts of interest.

This study investigates the development of glaucoma in subjects with surgery-indicated chronic rhinosinusitis (CRS) by the use of the National Health Insurance Research Database in Taiwan. Individuals that received the functional endoscopic sinus surgery (FESS) with a diagnostic code of CRS were regarded as surgery-indicated CRS and enrolled in the study group. Four non-CRS patients were age- and gender-matched to each patient in the study group. The exclusion criteria included legal blindness, ocular tumor, history of eyeball removal, and previous glaucoma. The outcome was regarded as the development of glaucoma, and conditional logistic regression was used for the statistical analysis, which involved multiple potential risk factors in the multivariate model. A total of 6506 patients with surgery-indicated CRS that received FESS and another 26,024 non-CRS individuals were enrolled after exclusion. The age and gender distributions were identical between the two groups due to matching. There were 108 and 294 glaucoma events in the study group and control group, respectively, during the follow-up period, and the study group had a significantly higher adjusted hazard ratio (1.291, 95% confidential interval: 1.031-1.615). The cumulative probability analysis also revealed a correlation between the occurrence of glaucoma and the CRS disease interval. In the subgroup analysis, the chance of developing open-angle glaucoma and normal-tension glaucoma was significantly higher in the study group than in the control group. In conclusion, the existence of surgery-indicated CRS is a significant risk factor for the development of glaucoma, which correlated with the disease interval.

Background: To evaluate the risk of developing optic neuropathy (ON) in patient with both non-surgery and surgery-indicated chronic rhinosinusitis (CRS) via the national health insurance research database in Taiwan., Methodology/principal Findings: 44,176 Patients with a diagnostic code of CRS was selected, which included 6,678 received functional endoscopic sinus surgery (FESS) regarded as the surgery-indicated CRS. Each individual in the study group was matched to two non-CRS patients by age and gender. The outcome was set as the occurrence of ON according to the diagnostic codes occurred after the index date. Poisson regression was used to calculate the adjusted relative risk (aRR) and conditional Cox proportional model was used to estimate the adjusted hazard ratio (aHR). There were 131 and 144 events of ON occurred in the study group and the control group respectively during the follow-up period. The whole study group, whether received FESS or not, demonstrated both significant aRR and aHR compared to the control group after adjusting demographic data, prominent ocular diseases, and systemic co-morbidities. In addition, both the aRR and aHR were higher in CRS patient received FESS than those with CRS but without FESS management., Conclusion: The existence of CRS, especially the surgery-indicated CRS is a significant risk factor for the following ON using multivariable analysis., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan., Methods: Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four non-uveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed., Results: A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR = 1.765) and panuveitis (aHR = 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group., Conclusions: The presence of uveitis significantly elevates the risk for developing keratopathy.

Aim: To study the effects of curcumin on the secretion of interleukin (IL)-6 and IL-8 by corneal limbus epithelial cells., Methods: Human corneal limbus epithelial cells were isolated and cultured from donor eyes and irradiated by UVB at different dosages with or without curcumin. MTT test was used for studying the effects of UVB and curcumin on the cell viability. The role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways on the UVB-induced secretion of IL-6 and IL-8 were tested by addition of their inhibitors to the culture with or without UVB-radiation. Levels of various signal pathways, IL-6 and IL-8 in the cells and in the conditioned culture medium were measured by ELISA analysis., Results: UVB at 20 mJ/cm 2 or less and curcumin at 20 µmol/L or less did not affect the cell viability of cultured limbus epithelial cells ( P >0.05). UVB irradiation at 10 and 20 mJ/cm 2 induced a significant increase of secretion of IL-6 and IL-8 and upregulated NF-κB and phosphorylated MAPK pathways of cultured limbus epithelial cells ( P <0.05). Various signal pathway inhibitors, including SP600125 (JNK inhibitor), SB203580 (p38 MAPK inhibitor) and BAY11-7082 (NF-κB inhibitor) significantly decreased the UVB-induced secretion of IL-6 and IL-8 secretion ( P <0.05). Curcumin at 5-20 µmol/L significantly inhibited UVB-induced secretion of IL-6 and IL-8 by limbus epithelial cells in a dose-dependent manner; while curcumin alone did not affect the secretion of IL-6 and IL-8. The upregulation of NF-κB and MAPK pathways induced by UVB treatment was significantly inhibited by curcumin, suggesting that NF-κB and MAPK pathways are involved in the inhibitory effect of curcumin on UVB-induced production of IL-6 and IL-8., Conclusion: Curcumin may be a promising agent to be explored for the prevention and treatment of pterygium.

Dry eye is a common disorder characterized by deficiency of tear. Hyperosmoticity of tear stimulates inflammation and damage of ocular surface tissues and plays an essential role in the pathogenesis of dry eye. Cultured human corneal epithelial (CE) cells were used for the study of effects of lutein and hyperosmoticity on the secretion of IL-6 by CE cells. Cell viability of CE cells was not affected by lutein at 1-10 μM as determined by MTT assay. Hyperosmoticity significantly elevated the secretion of IL-6 by CE cells as measured by ELISA analysis. The constitutive secretion of IL-6 was not affected by lutein. Lutein significantly and dose-dependently inhibited hyperosmoticity-induced secretion of IL-6. Phosphorylated- (p)- p38 MAPK, p-JNK levels in cell lysates and NF-κB levels in cell nuclear extracts were increased by being exposed to hyperosmotic medium. JNK, p38, and NF-κB inhibitors decreased hyperosmoticity-induced secretion of IL-6. Lutein significantly inhibited hyperosmoticity-induced elevation of NF-κB, p38, and p-JNK levels. We demonstrated that lutein inhibited hyperosmoticity-induced secretion of IL-6 in CE cells through the deactivation of p38, JNK, and NF-κB pathways. Lutein may be a promising agent to be explored for the treatment of dry eye.

Objective: To determine the nationwide incidence of non-traumatic subconjunctival hemorrhage (NTSCH) in Taiwan from 2000-2011 and to analyze the risk factors for NTSCH using a case-control analysis., Methods: This is a population-based cohort administrative database study. Randomly selected 1,000,000 residents from the Taiwan National Health Insurance Research Database in 2000 and followed for 12 years to determine the population incidence of NTSCH. Individuals with the first diagnosis of subconjunctival hemorrhage were identified by the corresponding International Classification of Diseases code (ICD) 372.72. Traumatic subconjunctival hemorrhages (ICD-9 codes 921, 871, 850-854 and 959.01) were excluded. The association of NTSCH with various demographic factors, comorbidities and use of medications was studied by a population based case-control analysis using data of 2008-2011., Results: A total of 67,720 patients with a first-time diagnosis of NTSCH were identified during the 12 years period. The mean annual incidence was 65 per 10,000 individuals (crude incidence) and 60 per 10,000 individuals (age- and sex-standardized incidence). The incidence rate of NTSCH was higher in women than in men, [men-women ratio: 0.80 (95% confidence interval: 0.78-0.81)]. The age-specific incidence decreased from childhood to the group of teenagers, after which it increased to a maximal value of 136.2 per 10,000 people in the age group of 60-69 years. Case-control analysis showed that comorbidities of hypertension, purpura and thrombocytopenia, and the use of aspirin were significantly associated with the risk of NTSCH., Conclusions: This study indicates that NTSCH is a common eye disease that occurs once in 167 individuals in a general East Asian population per year. It occurs more often in women than in men and the age-specific incidence peaked in the age group of 60-69 years. Hypertension, purpura and thrombocytopenia, and the use of aspirin are the major risk factors for NTSCH.

The effects of lutein and zeaxanthin on lipopolysaccharide- (LPS-) induced secretion of IL-8 by uveal melanocytes (UM) were tested in cultured human UM. MTT assay revealed that LPS (0.01-1 μg/mL) and lutein and zeaxanthin (1-10 μM) did not influence the cell viability of cultured UM. LPS caused a dose-dependent increase of secretion of IL-8 by cultured UM. Lutein and zeaxanthin did not affect the constitutive secretion of IL-8. However, lutein and zeaxanthin decreased LPS-induced secretion of IL-8 in cultured UM in a dose-dependent manner. LPS significantly increased NF-κB levels in cell nuclear extracts and p-JNK levels in the cell lysates from UM, but not p-p38 MAPK and p-ERG. Lutein or zeaxanthin significantly reduced LPS-induced increase of NF-κB and p-JNK levels, but not p38 MAPK and ERG levels. The present study demonstrated that lutein and zeaxanthin inhibited LPS-induced secretion of IL-8 in cultured UM via JNK and NF-κB signal pathways. The anti-inflammatory effects of lutein and zeaxanthin might be explored as a therapeutic approach in the management of uveitis and other inflammatory diseases of the eye.

Purpose: Effects of ultraviolet (UV) B on the pterygium and its cells have been studied previously, whereas little is known on the effects of UVA. Urokinase-type plasminogen activator (uPA) is a protease involved in tissue remodeling and cell migration, and its levels are increased in pterygium. The purpose of our study was to investigate the effects of UVA on the expression of uPA in cultured pterygium fibroblasts., Methods: Cultured fibroblasts from early-stage pterygia and normal conjunctiva were irradiated with different dosages of UVA and compared to nonirradiated cells. uPA activities in the medium and uPA mRNA in the cells were measured by casein zymography and RT-PCR, respectively. Total and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), and c-Jun N-terminal kinase (JNK) levels of cells treated with and without UVA were measured by Western blotting. Inhibitors of p38 (SB203580), ERK (UO1026), and JNK (SP600125) were added before the irradiation of UVA to test their effects., Results: UVA irradiation increased the uPA mRNA levels in pterygium fibroblasts and the uPA activities in cultured medium, which was accompanied with an increase in phosphorylated ERK and JNK. The ERK and JNK inhibitor, but not p38 MAPK inhibitors, significantly decreased the UVA-induced expression of uPA by pterygium fibroblasts. Normal conjunctival fibroblasts were less sensitive to UVA irradiation compared to the pterygium fibroblasts., Conclusions: UVA stimulated the production of uPA, a key factor in the modulation of extracellular matrixes, inflammatory processes, and angiogenesis. This may have a role in the development and progression of pterygium.