Distinguishing spheno-orbital metastatic prostate cancer mimicking a meningioma using novel 18F-PSMA PET/CT imaging.

A 78-year-old man presented with acute-onset left temporal pain, eyelid swelling, and double vision. Computed tomography (CT) demonstrated a left sphenoid wing mass with extra-osseous intra-orbital and intracranial extension, thought to be a typical sphenoid wing meningioma by the primary team. The patient was admitted for an urgent craniotomy, which was planned for the following day. However, upon consultation with ophthalmic plastic surgery, concern was raised for an alternative diagnosis given the atypical timeline, inflammatory changes, and uncharacteristic imaging findings of mixed lytic and sclerotic bony changes without hyperostosis on CT and extensive peri-lesional dural thickening and enhancement on magnetic resonance imaging. A serum prostate-specific antigen was elevated to 206 ng/mL. Subsequent positron emission tomography (PET)/CT using 18F-fluorodeoxyglucose radiotracer was negative for metastatic disease. A prostate-specific membrane antigen (PSMA) PET/CT was then obtained and demonstrated extensive metastases. An orbital biopsy revealed poorly differentiated prostatic adenocarcinoma. The significant incongruence between the standard PET/CT and PSMA PET/CT highlights the value of this novel advanced radiographic modality in narrowing the differential diagnosis and determining the extent of disease. Findings of widespread metastasis on the PSMA PET/CT ultimately helped to avoid a large, morbid neurosurgical intervention in this patient, allowing for a minimally invasive orbital biopsy to characterize the tumor for therapeutic targeting.

Association between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis: a Taiwanese population-based study.

Purpose: Our study aimed to explore the correlation between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis. Methods: This retrospective, nationwide, population-based, matched case-control investigation involved 33,190 individuals diagnosed with optic neuritis, identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes 377.30 for optic neuritis or 377.32 for retrobulbar neuritis. Patient data were extracted from the Taiwan National Health Insurance Research Database. Demographic characteristics, the presence of Sjögren syndrome, and pre-existing comorbid conditions were analyzed using univariate logistic regression. Continuous variables were assessed with a paired t-test. Adjusted logistic regression was employed to compare the prognosis odds ratio (OR) of patients with optic neuritis to controls. Results: After adjusting for confounding variables, individuals with Sjögren syndrome exhibited a significantly higher likelihood of developing optic neuritis compared to controls (adjusted OR, 9.79; 95% confidence interval [CI], 7.28-12.98; p < 0.0001). Other conditions associated with increased odds of optic neuritis included rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, and granulomatous vasculitis (adjusted OR: 1.57, 95% CI: 1.33-1.86; adjusted OR: 2.02, 95% CI: 1.65-2.48; adjusted OR: 140.77, 95% CI: 35.02-565.85; adjusted OR: 2.38, 95% CI: 1.71-3.30; adjusted OR: 18.28, 95% CI: 2.21-151.45, respectively), as well as systemic infections such as human herpes viral infection and tuberculosis infection (adjusted OR: 1.50, 95% CI: 1.35-1.66; adjusted OR: 4.60, 95% CI: 3.81-5.56, respectively). Discussion: Our findings strongly support the existence of an association between Sjögren syndrome, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus, granulomatous vasculitis, human herpes viral infection, tuberculosis, and optic neuritis.

Evaluation of Standard Response Assessment in Neuro-Oncology, Modified Response Assessment in Neuro-Oncology, and Immunotherapy Response Assessment in Neuro-Oncology in Newly Diagnosed and Recurrent Glioblastoma.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update. MATERIALS AND METHODS: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO. CONCLUSION: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.

Risk Stratification for Oropharyngeal Squamous Cell Carcinoma Using Texture Analysis on CT - A Step Beyond HPV Status.

Background and Purpose: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasingly prevalent. Despite the overall more favorable outcome, the observed heterogeneous treatment response within this patient group highlights the need for additional means to prognosticate and guide clinical decision-making. Promising prediction models using radiomics from primary OPSCC have been derived. However, no model/s using metastatic lymphadenopathy exist to allow prognostication in those instances when the primary tumor is not seen. The aim of our study was to evaluate whether radiomics using metastatic lymphadenopathy allows for the development of a useful risk assessment model comparable to the primary tumor and whether additional knowledge of the HPV status further improves its prognostic efficacy. Materials and Methods: 80 consecutive patients diagnosed with stage III-IV OPSCC between February 2009 and October 2015, known human papillomavirus status, and pre-treatment CT images were retrospectively identified. Manual segmentation of primary tumor and metastatic lymphadenopathy was performed and the extracted texture features were used to develop multivariate assessment models to prognosticate treatment response. Results: Texture analysis of either the primary or metastatic lymphadenopathy from pre-treatment enhanced CT images can be used to develop models for the stratification of treatment outcomes in OPSCC patients. AUCs range from .78 to .85 for the various OPSCC groups tested, indicating high predictive capability of the models. Conclusions: This preliminary study can form the basis multi-centre trial that may help optimize treatment and improve quality of life in patients with OPSCC in the era of personalized medicine.

A Taiwan Nationwide Population-Based Study of Socio-Demographic Factors and Comorbid Conditions Associated with Non-Arteritic Anterior Ischaemic Optic Neuropathy.

AIMS: The aim of the study was to investigate the socio-demographic factors and systemic conditions associated with non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: This was a nationwide population-based retrospective case-controlled study that recruited 9,261 NAION patients selected from the Taiwan National Health Insurance Research Database. The control group consisted of 9,261 age-, sex-, and index date-matched non-NAION patients recruited from the Taiwan Longitudinal Health Insurance Database, 2000. NAION was designated in the database by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as "code 377.41: ischaemic optic neuropathy without ICD-9-CM code 446.5: giant cell arteritis." Associated socio-demographic factors and systemic medical conditions were analysed using the McNemar's test, and continuous variables were analysed using the paired t test. The odds ratio (OR) and adjusted OR of developing NAION were compared using univariate logistic regression and multivariable logistic regression analyses, respectively. RESULTS: Patients with systemic conditions such as diabetes mellitus, hypertension, hyperlipidaemia, chronic kidney disease, and hypotension were more likely to develop NAION than controls (adjusted OR = 1.81, 95% confidence interval [CI] = 1.67-1.97, p < 0.0001; adjusted OR = 1.46, 95% CI = 1.36-1.57, p < 0.0001; adjusted OR = 1.44, 95% CI = 1.33-1.57, p < 0.0001; adjusted OR = 3.26, 95% CI = 2.65-4.01, p < 0.0001; adjusted OR = 2.32, 95% CI = 1.31-4.10, p = 0.0039, respectively). CONCLUSIONS: NAION is strongly associated with diabetes mellitus, hypertension, hyperlipidaemia, chronic kidney disease, and hypotension.

Sociodemographic Factors and Comorbidities Including Hyperparathyroidism Are Associated With an Increased Risk of Band Keratopathy: A Population-Based Study in Taiwan.

Purpose: To investigate the association of comorbidities including hyperparathyroidism and sociodemographic factors with band keratopathy. Methods: This retrospective, population-based, matched case-control study recruited 2,545 patients suffering from band keratopathy. They were selected from the Taiwan National Health Insurance Research Database, based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 371.43. The control group included 15,270 sex-, age-, and index date-matched non-band keratopathy patients collected from the Taiwan Longitudinal Health Insurance Database 2000. To compare band keratopathy patients with controls, McNemar's test was used for nominal data and paired t- tests were used for continuous variables. Univariate conditional logistic regression analysis and multivariable conditional logistic regression were used to obtain the odds ratio (OR) and adjusted OR of developing band keratopathy. Results: Patients with hyperparathyroidism were more likely to develop band keratopathy than controls (OR, 43.5; 95% confidence interval [CI], 23.789-79.544; P < 0.001) even after conditional logistic regression (adjusted OR, 11.28; 95% CI, 5.461-23.33; P < 0.001). Other conditions that increased the odds of scleritis development included systemic diseases such as chronic kidney disease (CKD) and diabetes mellitus (DM) and ocular conditions such as iridocyclitis, phthisis bulbi, and ever silicone oil retention. Regarding sociodemographic factors, >40% of patients with band keratopathy were aged ≥65 years old. Moreover, patients living in Eastern Taiwan and fishermen had higher odds of developing band keratopathy. Conclusions: Band keratopathy is significantly associated with hyperparathyroidism, CKD, DM, iridocyclitis, phthisis bulbi, and ever silicone oil retention.

A Population-Based Study of Social Demographic Factors, Associated Diseases and Recurrent Corneal Erosion in Taiwan.

Purpose: To investigate the association of recurrent corneal erosion (RCE) with sociodemographic factors and associated ocular conditions or systemic diseases. Methods: This nationwide, population-based, retrospective, matched case-controlled study included 98,895 RCE patients, identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 371.42, were selected from the Taiwan National Health Insurance Research Database. The age-, sex-, and index date- matched control group included 98,895 non-RCE control group also selected from the Taiwan Longitudinal Health Insurance Database 2000. Sociodemographic factors and associated ocular conditions or systemic diseases were examined using univariate logistic regression analyses, and continuous variables were analyzed using paired t-test. The odds ratio (OR) of developing RCE were compared using adjusted logistic regression analysis. Results: Patients with ocular conditions including corneal abrasion, ocular allergic conditions, and corneal dystrophy were more likely to have RCE than the control group (adjusted OR = 63.56, 95% CI = 42.06-96.06, p < 0.0001; adjusted OR = 24.27, 95% CI = 20.51-28.72, p < 0.0001; adjusted OR = 17.10, 95% CI = 5.14-59.93, p < 0.0001, respectively). Patients with systemic diseases such as diabetes mellitus, hyperlipidaemia, and atopy trait have significantly higher ORs for RCE development. Patients residing in either Northern Taiwan or a metropolis city had higher odds of developing RCE; however, there were no significant differences in income or occupation on the probability to develop RCE. Conclusion: RCE is strongly associated with corneal abrasion, ocular allergic conditions, corneal dystrophy, diabetes mellitus, hyperlipidaemia, and atopy trait.

Case Report: Allogenic Simple Limbal Epithelial Transplantation From a Human Leukocyte Antigen-Matched Living Related Donor to Treat Bilateral Corneal Chemical Burns Post Laser-Assisted in situ Keratomileusis.

A 35-year-old woman who had undergone laser-assisted in situ keratomileusis in both eyes experienced bilateral total limbal stem cell deficiency (LSCD) due to chemical burns. Due to bilateral severe LSCD, allogenic simple limbal epithelial transplantation (SLET) from a human leukocyte antigen (HLA)-matched living related donor was the first choice of treatment for her left eye. We report the first case of HLA or ABO matching living related allogenic SLET for permanent restoration of the cornea for bilateral LSCD treatment. Our ABO-HLA-matched living related allogenic SLET alleviation of the systemic immunosuppressant to topical corticosteroids alone. It also came the limitations of prolonged systemic immunosuppressant usage in conjunctival-limbal allografts and keratolimbal allograft.

The Sociodemographic and Risk Factors for Fuchs' Endothelial Dystrophy: A Nationwide, Matched Case-Control Study in Taiwan.

This nationwide, population-based, retrospective, matched case-control study included 4334 newly diagnosed Fuchs' endothelial dystrophy (FED) patients who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 371.57, and selected from the Taiwan National Health Insurance Research Database. The age-, sex-, and index-date-matched control group included 4334 non-FED controls selected from the Taiwan Longitudinal Health Insurance Database 2000. Ocular allergic conditions and sociodemographic conditions were examined using univariate logistic regression analyses and paired t-test was used for continuous variables. Adjusted logistic regression was used to compare the odds ratio (OR) of the FED development. Patients with ocular allergic conditions were more likely to have FED than the controls (OR = 25.50, 95% CI = 12.58-51.68, p < 0.0001) even after conditional logistic regression was conducted (adjusted OR = 25.26, 95% CI = 11.24-56.77, p < 0.0001). Regarding the sociodemographic factors, we found that more than half of the FED patients in Taiwan were aged ≥45 years old, there was an equal female-to-male ratio (1.06:1), and patients with a lower income and living in northern Taiwan had higher odds of developing FED. The results strongly support an association between ocular allergic conditions, geographic region, residential status, income, and FED.

Associations between Sjögren Syndrome, Sociodemographic Factors, Comorbid Conditions, and Scleritis in a Taiwanese Population-Based Study.

This nationwide, population-based, retrospective, matched case-control study included 111,960 newly diagnosed patients with scleritis who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification code 379.0, selected from the Taiwan National Health Insurance Research Database. Demographic characteristics, Sjögren syndrome, and comorbid conditions within 1 year before the scleritis diagnosis were examined using univariate logistic regression analyses, and a paired t-test was used for continuous variables. Adjusted logistic regression was used to compare the prognosis odds ratio (OR) of the patients with scleritis with the controls. After adjustment for confounders, patients with Sjögren syndrome were remarkably more likely to have scleritis than the controls (OR = 33.53, 95% confidence interval (CI) = 27.43-40.97, p < 0.001). Other conditions found to have increased odds of scleritis included post ocular pterygium, glaucoma, and scleral surgery (OR = 4.01, 95% CI = 3.64-4.43; OR = 3.16, 95% CI = 2.24-4.47; OR = 6.83, 95% CI = 5.34-8.74, respectively); systemic infections, such as syphilis, tuberculosis, and a human herpes viral infection (OR = 4.01, 95% CI = 2.93-5.50; OR = 2.24, 95% CI = 1.94-2.58; OR = 8.54, 95% CI = 8.07-9.03, respectively); and systemic diseases, such as rheumatoid arthritis, granulomatous vasculitis, systemic lupus erythematosus, ankylosing spondylitis, and gout (OR = 2.93, 95% CI = 2.66-3.23; OR = 7.37, 95% CI = 3.91-13.88; OR = 3.18, 95% CI = 2.63-3.85; OR = 5.57, 95% CI = 4.99-6.22; OR = 2.84, 95% CI = 2.72-2.96, respectively). The results strongly support an association between Sjögren syndrome, post ocular surgery, systemic infection disease, systemic autoimmune disease, and scleritis.

Long-term neuroimaging follow-up of COVID-19-related leukoencephalopathy.

More than a year after the start of the COVID-19 pandemic, long-term neurological manifestations of COVID-19 are increasingly being reported. The long-term sequelae of COVID-19-related leukoencephalopathy, however, remain unclear. Here, we present long-term neuroimaging follow-up in two cases of COVID-19-related leukoencephalopathy. The two cases demonstrate the utility of brain MRI for evaluating neurologic symptoms in critically ill patients with COVID-19, for diagnosis of underlying neural injury and prognostication of future recovery. The presence of leukoencephalopathy may result in chronic neurologic manifestations and may represent a poor prognosticator of neurologic recovery. The presence of leukoencephalomalacia on follow-up neuroimaging is potentially an indicator of irreversible white matter damage, which may be associated with more severe chronic deficits.

Posterior Skull Base Anatomy and Pathology.

A posterior skull base lesion is an uncommon radiological finding that may be noted incidentally or during targeted imaging of patients with clinical symptoms attributable to the lesion. It may be inflammatory or neoplastic in etiology, or may simply be an anatomic variant or a "don't-touch" lesion that should not be misinterpreted as something more ominous. A systematic approach to the evaluation of the posterior skull base is therefore required in order to differentiate lesions requiring immediate attention from those requiring a less urgent course of action or none at all. This review will focus on the imaging features of pathologic conditions that are more commonly encountered in posterior skull base CT and MR examinations.

Association Between Atopic Keratoconjunctivitis and the Risk of Recurrent Corneal Erosion.

Purpose: To investigate the risk of recurrent corneal erosion (RCE) in patients with atopic keratoconjunctivitis (AKC). Methods: This national, retrospective, matched cohort study enrolled 184,166 newly-diagnosed AKC patients, selected from the Taiwan National Health Insurance Research Database and identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 372.05. The control group comprised 184,166 non-AKC patients matched by age, sex, and potential comorbidities and they were selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information from patients was gathered from 1 January 2004 to 31 December 2011, and both groups were traced from the index date until December 2013. The incidence and risk of RCE (ICD-9-CM code 361.42) was compared between the groups. The adjusted hazard ratio (HR) for RCE was obtained by a Cox proportional hazard regression analysis. The Kaplan-Meier analysis was performed to calculate the cumulative incidence of RCE. Results: In total, 564 AKC patients and 406 non-AKC controls developed RCE during the follow-up span. The incidence of RCE was 1.45 times higher in AKC patients than in controls (95% confidence interval [CI] = 1.27-1.64; P < 0.0001). After adjusting for potential confounders, including diabetes mellitus, keratoconjunctivitis sicca, corneal transplantation, ocular blunt trauma, corneal dystrophy, and band keratopathy, AKC patients were 1.36 times more likely to develop RCE than controls (adjusted HR, 1.36; 95% CI = 1.19-1.54; p < 0.05). Conclusions: AKC Patients had an increased risk of developing RCE and should be informed of this risk.

MicroRNA-100 Mediates Hydrogen Peroxide-Induced Apoptosis of Human Retinal Pigment Epithelium ARPE-19 Cells.

This study investigated the regulatory role of microRNA 100 (miR-100) in hydrogen peroxide (H2O2)-induced apoptosis of human retinal pigment epithelial ARPE-19 cells. H2O2 induced oxidative cell death of cultured ARPE-19 cells was measured by cytotoxicity assay. qRT-PCR was used to quantify cytosolic and extracellular contents of miR-100. Kinase and miR-100 inhibition treatments were applied to determine the regulatory signaling pathways involved in cell death regulation. H2O2 dose-dependently reduced viability of ARPE-19 cells and simultaneously upregulated miR-100 levels in both cytosolic and extracellular compartments. Western blotting detection indicated that H2O2 elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB. Further kinase inhibition experiments demonstrated that PI3K, p38 MAPK, and NF-κB activities were involved in oxidative-stress-induced miR-100 upregulation in ARPE-19 cells, while blockade of PI3K, JNK, and NF-κB signaling significantly attenuated the oxidative cell death. Intriguingly, MiR-100 antagomir treatment exerted a cytoprotective effect against the H2O2-induced oxidative cell death through attenuating the oxidation-induced AMPK hyperphosphorylation, restoring cellular mTOR and p62/SQSTM1 levels and upregulating heme oxygenase-1 expression. These findings support that miR-100 at least in part mediates H2O2-induced cell death of ARPE-19 cells and can be regarded as a preventive and therapeutic target for retinal degenerative disease.

Association between chronic kidney disease and the most common corneal ectasia disease (keratoconus): a nationwide cohort study.

BACKGROUND: Both keratoconus (KCN) and chronic kidney disease (CKD) are multifactorial conditions with multiple aetiologies and share several common pathophysiologies. However, the few studies that have described the relationship between KCN and CKD are limited to case reports and small case series. This study aimed to evaluate the association between KCN and CKD. METHODS: The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age-, sex-, and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan-Meier analysis was used to calculate the cumulative CKD incidence rate. RESULTS: The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95 % confidence interval [CI] = 0.99-1.86, p = 0.06). In total, 29 male KCN patients and 90 male controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95 % [CI] = 1.26-2.91; p = 0.002) higher in male KCN patients than in controls. After adjusting for potential confounders, including age, hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients were 1.75 times (adjusted HR = 1.75, 95 % [CI] = 1.14-2.68, p < 0.05) more likely to develop CKD. CONCLUSIONS: We found that male KCN patients have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.

Association between atopic keratoconjunctivitis and the risk of keratoconus.

PURPOSE: To investigate the risk of keratoconus (KCN) in patients with atopic keratoconjunctivitis (AKC). METHODS: This nationwide, retrospective, matched cohort study included 186 202 newly diagnosed AKC patients who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 372.05, and selected from the Taiwan National Health Insurance Research Database. The age- and sex-matched control group included 186 202 non-AKC patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Patient information was collected between 1 January 2004 and 31 December 2011, and both groups of patients were tracked from the index date until December 2013. The incidence and risk of KCN (ICD-9-CM, code 371.6) were compared between the groups. A Cox proportional hazard regression analysis was performed to obtain the adjusted hazard ratio (HR) for KCN. The cumulative KCN incidence rate was calculated with the Kaplan-Meier analysis. RESULTS: In total, 62 AKC patients and 26 controls developed KCN during the follow-up period. The incidence rate of KCN was 2.49 times (95% confidence interval [CI] = 1.57-3.93; p < 0.0001) higher in AKC patients than in controls. After adjusting for potential confounders, AKC patients were 2.25 times more likely to develop KCN than controls (adjusted HR, 2.25; 95% CI = 1.41-3.58; p < 0.05). CONCLUSION: Atopic keratoconjunctivitis (AKC) patients had an increased risk of developing KCN. Therefore, AKC patients should be advised of this risk.

Risk of retinal vein occlusion in patients with diabetes mellitus: A retrospective cohort study.

AIMS: To investigate the risk of retinal vein occlusion (RVO) in new-onset diabetes mellitus (DM) patients. METHODS: This nationwide, retrospective, matched cohort study included 240,761 DM patients registered between January 2003 and December 2005 in the Longitudinal Cohort of Diabetes Patients database. An age- and sex-matched control group comprising 240,761 non-DM patients (case: control = 1:1) was selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient from the index date until December 2013 was collected. The incidence and risk of RVO were compared between the two groups. Cox proportional hazard regression analysis was performed to calculate the adjusted hazard ratio (HR) for RVO after adjustment for potential confounders. The RVO cumulative incidence rate was obtained using Kaplan-Meier analysis. RESULTS: During the follow-up period, 1,456 DM patients developed RVO (491, central retinal vein occlusion; 965, branch retinal vein occlusion). There was a significantly elevated risk of RVO in DM patients compared with the controls (incidence rate ratio = 1.91, 95% confidence interval [CI] = 1.75-2.08). Patients with DM showed significant risk of RVO after adjustment for potential confounders (hypertension, hyperlipidemia, congestive heart failure, coronary artery disease, and chronic renal disease) in the full cohort (adjusted HR = 1.76, 95% CI = 1.61-1.93). Additionally, patients with hypertension had a significantly higher risk of RVO than patients without hypertension after adjustment for other confounders in the cohort (adjusted HR = 1.50, 95% CI = 1.36-1.65). CONCLUSIONS: We found that patients with DM have increased risks of RVO. In addition to blood pressure control, we recommend educating patients with DM about RVO, to prevent its subsequent occurrence.

Association between atopic keratoconjunctivitis and the risk of corneal ulcer.

AIMS: To investigate the risk of corneal ulcer in patients with atopic keratoconjunctivitis (AKC). METHODS: The nationwide, population-based, retrospective, matched cohort study included 171 019 newly diagnosed patients with AKC who were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code 372.05, and selected from the Taiwan National Health Insurance Research Database. The age-, sex- and potential comorbidities-matched control group included 171 019 patients with non-AKC selected from the Taiwan Longitudinal Health Insurance Database 2000. Patient information was collected between 1 January 2004 and 31 December 2011, and both groups of patients were tracked from the index date until December 2013. The incidence and risk of corneal ulcer (ICD-9-CM code 370.0 except for 370.07) was compared between the groups. A Cox proportional hazard regression analysis was performed to obtain the adjusted HR for corneal ulcer. The cumulative corneal ulcer incidence rate was calculated with the Kaplan-Meier analysis. RESULTS: In total, 2018 patients with AKC and 1481 controls developed a corneal ulcer during the follow-up period. The incidence rate of corneal ulcer was 1.42 times (95% CI1.33 to 1.52; p<0.0001) higher in patients with AKC than in controls. After adjusting for potential confounders, including diabetes mellitus, chronic renal disease, topical steroid ophthalmic agent use, lid margin disease, keratoconjunctivitis sicca, ocular blunt trauma and post-corneal transplantation, patients with AKC were 1.26 times more likely to develop a corneal ulcer than controls (adjusted HR, 1.26; 95% CI 1.14 to 1.39; p<0.05). CONCLUSIONS: Patients with AKC had an increased risk of developing a corneal ulcer and should be advised of this risk.

Temporal Association between Topical Ophthalmic Corticosteroid and the Risk of Central Serous Chorioretinopathy.

This retrospective, nationwide, matched cohort study investigated the temporal relationship of central serous chorioretinopathy (CSCR) following topical ophthalmic corticosteroid (TOC) use. Using the Longitudinal Health Insurance Database 2000 (LHID2000), we collected patients diagnosed with CSCR between January 2001 and December 2010 (n = 2921) and a control group (n = 17,526). Information for each patient was collected and tracked from the index date until December 2011. TOC users were classified based on (i) the date of the last prescription before diagnosis: current users (≤30 days) and former users (31-182 days and ≥183 days) and (ii) the prescription refill intervals: persistent users (interval ≤90 days) and non-persistent users (interval >90 days). The odds ratio (OR) was estimated from multivariate conditional logistic regression after adjusting for relevant confounders. After adjusting for age, sex, geographic region, index date, previously known comorbidities, the date of last TOC prescription before diagnosis, or prescription refilling intervals, the results revealed that patients were likely to have developed CSCR while using TOCs currently (OR = 30.42, 95% CI = 25.95-35.66, p < 0.001) and persistently (OR = 7.30, 95% CI = 6.13-8.69, p < 0.001) as compared to the controls. Our results indicate that current or persistent TOCs use increases the risk of CSCR. Thus, patients requiring TOCs should be advised of this risk, particularly in current or persistent use conditions.

Monounsaturated oleic acid modulates autophagy flux and upregulates angiogenic factor production in human retinal pigment epithelial ARPE-19 cells.

AIMS: Dyslipidemia-associated diabetic retinopathy is featured by macular edema and retinal angiogenesis. This study investigated the in vitro lipotoxicity of free fatty acids and their modulatory roles in regulation of autophagy and angiogenic factor production in cultured human retinal pigment epithelium (RPE) ARPE-19 cells. MAIN METHODS: ARPE-19 cells were exposed to monounsaturated oleic acid (OA), saturated palmitic acid (PA), or both. Cell viability, cell cycle distribution, migration, and autophagy of the treated cells were monitored. Angiogenic factor production was determined by RT-qPCR and ELISA. KEY FINDINGS: OA, but not PA, at doses higher than 500 µM significantly induced cytostasis and lipotoxicity in ARPE-19 cells. OA exposure not only markedly enhanced autophagy flux, but also enhanced cell migration, while PA suppressed motility of RPE cells. Meanwhile, OA stimulated de novo synthesis of angiogenic factors including VEGF and bFGF in ARPE-19 cells. Mechanistically, OA treatment stimulated not only AMPK/mTOR/p70S6K signaling, but also induced hyperphosphorylation of MAPK pathway mediators, including ERK, JNK and p38 MAPK, as well as NF-κB activation. Kinase inhibition assays showed that blockade of PI3K/Akt, MAPK and NF-κB pathways prevented the OA-upregulated VEGF transcription and its peptide release. Comparatively, only NF-κB inhibition significantly suppressed bFGF peptide release from ARPE-19 cells. SIGNIFICANCE: Out findings support the OA-exhibited cytostasis, autophagy modulation and angiogenic factor production in RPE cells. This study sheds light on the interrelationship between metabolic disorder and retinopathy and provides molecular strategies for preventing and treating choroidal neovascularization in diabetic retinopathy.