Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks.

BACKGROUND: Glaucoma is a leading cause of worldwide irreversible blindness. Considerable uncertainty remains regarding the association between a variety of phenotypes and the genetic risk of glaucoma, as well as the impact they exert on the glaucoma development. METHODS: We investigated the associations of genetic liability for primary open angle glaucoma (POAG) with a wide range of potential risk factors and to assess its impact on the risk of incident glaucoma. The phenome-wide association study (PheWAS) approach was applied to determine the association of POAG polygenic risk score (PRS) with a wide range of phenotypes in 377, 852 participants from the UK Biobank study and 43,623 participants from the Penn Medicine Biobank study, all of European ancestry. Participants were stratified into four risk tiers: low, intermediate, high, and very high-risk. Cox proportional hazard models assessed the relationship of POAG PRS and ocular factors with new glaucoma events. RESULTS: In both discovery and replication set in the PheWAS, a higher genetic predisposition to POAG was specifically correlated with ocular disease phenotypes. The POAG PRS exhibited correlations with low corneal hysteresis, refractive error, and ocular hypertension, demonstrating a strong association with the onset of glaucoma. Individuals carrying a high genetic burden exhibited a 9.20-fold, 11.88-fold, and 28.85-fold increase in glaucoma incidence when associated with low corneal hysteresis, high myopia, and elevated intraocular pressure, respectively. CONCLUSION: Genetic susceptibility to POAG primarily influences ocular conditions, with limited systemic associations. Notably, the baseline polygenic risk for POAG robustly associates with new glaucoma events, revealing a large combined effect of genetic and ocular risk factors on glaucoma incidents.

Role of vasorin, an anti-apoptotic, anti-TGF-ß and hypoxia-induced glycoprotein in the trabecular meshwork cells and glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH outflow, however, are poorly understood. Here, we identified the secreted form of vasorin, a transmembrane glycoprotein, as a common constituent of human AH by mass spectrometry and immunoblotting analysis. ELISA assay revealed a significant but marginal decrease in vasorin levels in the AH of primary open-angle glaucoma patients compared to non-glaucoma cataract patients. Human trabecular meshwork (HTM) cells were confirmed to express vasorin, which has been shown to possess anti-apoptotic and anti-TGF-ß activities. Treatment of HTM cells with vasorin induced actin stress fibres and focal adhesions and suppressed TGF-ß2-induced SMAD2/3 activation in HTM cells. Additionally, cobalt chloride-induced hypoxia stimulated a robust elevation in vasorin expression, and vasorin suppressed TNF-α-induced cell death in HTM cells. Taken together, these findings reveal the importance of vasorin in maintenance of cell survival, inhibition of TGF-ß induced biological responses in TM cells, and the decreasing trend in vasorin levels in the AH of glaucoma patients suggests a plausible role for vasorin in the pathobiology of ocular hypertension and glaucoma.

Cytokine profile and cytoskeletal changes after herpes simplex virus type 1 infection in human trabecular meshwork cells.

Uveitis caused by herpes simplex virus (HSV)-1 is characterized by increased intraocular pressure (IOP) in the presence of anterior chamber inflammation. Despite their clinical significance, the pathogenic changes associated with HSV-1 infection in trabecular meshwork (TM) cells, the key cell type regulating IOP, have not been completely elucidated. In this study, cytokine array analyses showed a significant stepwise increase in monocyte chemoattractant protein (MCP)-1 expression upon HSV-1 infection in TM cells (p < 0.05). HSV-1 infection led to downregulation of fibrogenic molecules (fibronectin, α-smooth muscle actin, connective tissue growth factor and TGF-ß1). Notably, HSV-1 infection caused a significant increase in actin stress fibres, with a twofold increase in active RhoA, which was enhanced by treatment with TGF-ß1 and inhibited by treatment with the Rho-kinase inhibitor, Y-27632. TM cells treated with MCP-1 exhibited a dose-dependent increase in actin stress fibres compared to untreated TM cells. Our study suggests that HSV-1 infection in TM cells increases cell contractile activity rather than fibrotic changes in the extracellular matrix (ECM) components. Taken together, these observations demonstrate the enhanced expression of MCP-1 and TM cell contractile activity upon HSV-1 infection and events with potential implications for the pathobiology of abrupt IOP elevation in HSV-1 anterior uveitis.

Long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome.

BACKGROUND: The aim of this study is to investigate the long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome (PSS). METHODS: In this retrospective case series study, a total of 98 patients with PSS from January 2014 to February 2019 were included in this study. Initial presentations and follow-up data were obtained from medical records. Vision-related quality of life (VR-QoL) was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire. RESULTS: Of the 98 patients included in the study, 66 (67%) presented with glaucoma, and among them, 21 (32%) required glaucoma surgery. The mean follow-up time was 50.1 months (range 1-263 months). Iris involvement was noted in 46 (46.9%) eyes; 26 (26.5%) had sectoral iris changes and 20 (20.4%) showed diffuse iris changes. Eyes with iris involvement had a significantly higher number of acute attacks of uveitis than those without (p = 0.010). The 5-year glaucoma surgery-free interval was 77.8% according to Kaplan-Meier analysis. Significant predictors of glaucoma surgery included iris involvement (hazard ratio [HR] = 5.215; confidence interval [CI] = 1.387-19.610), highest number of anti-glaucoma agents (HR = 5.069; CI = 1.848-13.905), baseline average retinal nerve fiber layer thickness (RNFLT) thickness (HR = 0.949; CI = 0.917-0.982), and disease duration (HR = 0.977; CI = 0.957-0.996). Overall complete surgical success and qualified success at 2 years was 35.3% and 75.5%, respectively. Patients with iris involvement, glaucoma surgery, and thinner average RNFLT had significantly poorer VR-QoL (all, p < 0.05). CONCLUSIONS: Patients with PSS and glaucoma required glaucoma surgery in a high rate. Iris involvement increased the probability of surgical treatment and lowered the VR-QoL of PSS patients.

Enhancing Personalized Ads Using Interest Category Classification of SNS Users Based on Deep Neural Networks.

The classification and recommendation system for identifying social networking site (SNS) users' interests plays a critical role in various industries, particularly advertising. Personalized advertisements help brands stand out from the clutter of online advertisements while enhancing relevance to consumers to generate favorable responses. Although most user interest classification studies have focused on textual data, the combined analysis of images and texts on user-generated posts can more precisely predict a consumer's interests. Therefore, this research classifies SNS users' interests by utilizing both texts and images. Consumers' interests were defined using the Curlie directory, and various convolutional neural network (CNN)-based models and recurrent neural network (RNN)-based models were tested for our user interest classification system. In our hybrid neural network (NN) model, CNN-based classification models were used to classify images from users' SNS postings while RNN-based classification models were used to classify textual data. The results of our extensive experiments show that the classification of users' interests performed best when using texts and images together, at 96.55%, versus texts only, 41.38%, or images only, 93.1%. Our proposed system provides insights into personalized SNS advertising research and informs marketers on making (1) interest-based recommendations, (2) ranked-order recommendations, and (3) real-time recommendations.

Imaging Guidelines for Enhancing Justifications for Radiologic Studies.

Justification in the field of radiology refers to the appropriate use of radiologic imaging modalities, and may be achieved by establishing clinical imaging guidelines (CIGs). Recently, CIGs have been shown to be useful in selecting the proper medical imaging modality, resulting in the reduction of inappropriate radiologic examinations, thereby enhancing justifications. However, the development of CIGs is both time-consuming and difficult as the methodology of evidence-based medicine should be adhered to. Thus, although the radiologic societies in developed countries such as the United Kingdom and USA are already developing and implementing CIGs in their clinical practices, CIGs are not yet readily available in many other countries owing to differences in medical circumstances and resources. In this review, we assess the role and limitations of CIGs by examining the current status of CIGs in developed countries, and also describe the specific efforts made to establish CIGs in Korea.

Retinal nerve fiber layer loss is associated with urinary albumin excretion in patients with type 2 diabetes.

OBJECTIVES: To identify the factors associated with retinal nerve fiber layer (RNFL) loss in patients with type 2 diabetes. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-six nonglaucomatous patients with type 2 diabetes without renal impairment (estimated glomerular filtration rate, ≥60 ml/minute per 1.73 m(2)). METHODS: Eyes were divided into 2 groups based on the presence or absence of RNFL defects detected by red-free retinal fundus photography. All participants underwent an eye fundus examination, and the urinary albumin-to-creatinine ratio (ACR) was determined. A cardiovascular autonomic function test was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to the Valsalva maneuver, and standing. Multiple logistic regression analyses were performed to determine potential risk factors related to the presence of RNFL defects in these patients. MAIN OUTCOMES AND MEASURES: The association between RNFL defects and diabetic complications. RESULTS: Among the patients, 43 (44.8%) had localized RNFL defects (group 1), whereas the others (55.2%) did not (group 2). The RNFL defects occurred more frequently on the superior side (75.6% and 71.0% in right and left eyes, respectively) compared with the inferior side (13.8% and 0.0% in right and left eyes, respectively). Patients with RNFL defects (group 1) had significantly higher rates of diabetic retinopathy (60.5%) compared with those without RNFL defects (group 2; 32.1%; P = 0.007). The urinary ACR was significantly higher in patients with RNFL defects than in those without defects (45.3±72.1 µg/mg vs. 15.4±17.3 µg/mg creatinine, respectively; P = 0.015), whereas autonomic function test grading was similar between the groups. The urinary ACR was the only factor related to visual field defect location in both univariate (P = 0.021) and multivariate (P = 0.036) logistic regression analyses after adjusting for age; gender; presence of diabetic retinopathy; diabetes duration; smoking; statin use; and antiplatelet, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment. CONCLUSIONS: Urinary albumin excretion was associated with nerve fiber layer loss in patients with type 2 diabetes. Careful examination of the optic nerve head may be necessary, particularly in patients with type 2 diabetes exhibiting albuminuria.

Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss.

OBJECTIVE: To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. DESIGN: Retrospective, observational study. PARTICIPANTS: Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. METHODS: All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using AUCs. RESULTS: The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). CONCLUSIONS: The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss.

Glaucoma diagnostic accuracy of optical coherence tomography parameters in early glaucoma with different types of optic disc damage.

PURPOSE: To compare the initial visual field (VF) defect pattern and the spectral-domain optical coherence tomography (OCT) parameters and investigate the effects of distinct types of optic disc damage on the diagnostic performance of these OCT parameters in early glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 138 control eyes and 160 eyes with early glaucoma were enrolled. The glaucomatous eyes were subdivided into 4 groups according to the type of optic disc damage: focal ischemic (FI) group, myopic (MY) group, senile sclerotic (SS) group, and generalized enlargement (GE) group. METHODS: The values of total deviation (TD) maps were analyzed, and superior-inferior (S-I) differences of TD were calculated. The optic nerve head (ONH) parameters, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using area under the receiver operating characteristic curves (AUCs). RESULTS: The S-I and central S-I difference of the FI group were larger than those of the GE group. The rim area of the SS group was larger than those of the 3 other groups, and the vertical cup-to-disc ratio (CDR) of the GE group was larger than that of the MY group. In addition, the minimum and inferotemporal GCIPL thicknesses of the FI group were smaller than those of the GE group. The AUC of the rim area (0.89) was lower than that of the minimum GCIPL (0.99) in the SS group, and the AUC of the vertical CDR (0.90) was lower than that of the minimum GCIPL (0.99) in the MY group. Furthermore, the AUCs of the minimum GCIPL thicknesses of the FI and MY group were greater than those of the average pRNFL thickness for detecting glaucoma, as opposed to the SS and GE. CONCLUSIONS: The OCT parameters differed among the 4 groups on the basis of the distinct optic disc appearance and initial glaucomatous damage pattern. Clinicians should be aware that the diagnostic capability of OCT parameters could differ according to the type of optic disc damage in early glaucoma.

Macular ganglion cell-inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian.

The aim of this work is to compare the thinning patterns of the ganglion cell inner-plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Twenty eyes of 11 patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5 and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5 and 1% probability level within the area corresponding to the affected VF. The 5 and 1% TAI were compared between the GCIPL and pRNFL measurements. The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5 and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all p < 0.01). Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers.

Risk Factors for Disease Progression in Glaucoma Patients with Disc Hemorrhage.

PRCIS: Glaucoma eyes with recurrent disc hemorrhage were associated with increased systolic blood pressure and diastolic blood pressure, and increased visit-to-visit diastolic blood pressure variability was associated with glaucoma progression. PURPOSE: In this study, we investigated the effects of the clinical characteristics of disc hemorrhage (DH) and hemodynamic factors on glaucoma progression. METHODS: This retrospective cohort study included 81 eyes with open angle glaucoma and non-recurrent or recurrent DH. Recurrent DH was further classified according to the DH location. Visual field (VF) progression was determined using event-based analysis and Guided Progression Analysis software. The coefficient of variation (CV) of systolic and diastolic blood pressure (SBP and DBP, respectively) was used to measure visit-to-visit variability. Kaplan-Meier survival analysis was used to compare the cumulative risk ratio of progression between groups. RESULTS: The recurrent DH group had significantly higher SBP and DBP (P=0.014 and=0.021, respectively) and a higher proportion of VF progression (P=0.019) than the non-recurrent DH group. In particular, females with recurrent DH had the highest cumulative probability of VF progression (P=0.047, log-rank test). Recurrent DH in a different quadrant was associated with the highest cumulative probability of VF progression than non-recurrent DH (P=0.038, log-rank test). In Cox regression analysis, higher visit-to-visit DBP variability, female sex, and recurrent DH in a different quadrant were significantly associated with glaucoma progression. CONCLUSION: In glaucomatous eyes with DH, increased visit-to-visit DBP variability was associated with glaucoma progression. Our results suggest that hemodynamic factors are involved in the recurrence of DH and progression of glaucoma.

Association Between High Blood Folate Levels and Glaucoma in a Representative Korean Population.

Purpose: This study aimed to investigate the association between folate levels and the prevalence of glaucoma. Methods: This nationwide population-based cross-sectional study included 1790 participants aged ≥40 years. We analyzed data regarding the participants obtained in the 2016-2018 Korean National Health and Nutrition Examination Survey. The diagnosis of glaucoma was defined according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Logistic regression analyses were used to investigate the relationship between blood folate levels and glaucoma. Results: There was a significantly lower prevalence of glaucoma in the highest quartile of blood folate levels than in the lowest quartile, after adjusting for confounding factors such as age, sex, systemic hypertension, diabetes, hypercholesterolemia, and smoking (odds ratio [OR] = 0.470; 95% confidence interval [CI], 0.291-0.759; P for trend = 0.017). There was a significantly lower risk of glaucoma in the highest quartile of blood folate levels than in the lowest quartile among women (OR = 0.188; 95% CI, 0.099-0.357; P for trend <0.001) and younger participants (OR =0.443; 95% CI, 0.229-0.856; P for trend = 0.045). Conclusions: Our findings indicate a strong inverse correlation between blood folate levels and glaucoma.

The Impact of Lifestyle on Cardiovascular Risk in Patients with Gout: a Population-based Cohort Study.

AIMS: Gout is associated with a significant burden of cardiovascular disease. The aim of this study was to evaluate the impact of a favorable lifestyle on incident cardiovascular events in patients with gout. METHODS: We identified 9 110 patients with gout from the UK Biobank cohort based on self-report and/or hospital diagnostic codes. Lifestyle behaviors, including smoking status, physical activity, obesity, and diet, were categorized into three patterns: favorable (3-4 healthy factors), intermediate (2 healthy factors), and unfavorable (0-1 healthy factor). The cardiovascular risk of participants with and without gout was estimated based on their serum uric acid levels and lifestyle patterns. RESULTS: Among 9 110 patients with gout and 457 596 participants without gout, the median follow-up duration was 8.9 years. The incidence rate of cardiovascular disease was significantly higher in the gout population than in the non-gout population (11.38 vs 5.49 per 1000 person-years). The gout population consistently exhibited a high cardiovascular risk, irrespective of uric acid levels, whereas a positive correlation was observed between uric acid levels and cardiovascular risk in the non-gout population. Adopting a favorable lifestyle pattern was associated with a lower risk of cardiovascular disease in both gout and non-gout populations. Across all categories of uric acid, a favorable lifestyle was found to reduce cardiovascular risk in patients with gout. CONCLUSION: Patients with gout remain at high risk of developing cardiovascular disease despite having normal uric acid levels. Lifestyle modifications may represent an effective and cost-efficient therapeutic approach for preventing cardiovascular events in this population.

Association of glaucoma and lifestyle with incident cardiovascular disease: a longitudinal prospective study from UK Biobank.

The shared pathophysiological features of the cerebrovascular disease (CVD) and glaucoma suggest an association between the two diseases. Using the prospective UK Biobank cohort, we examined the associations between glaucoma and incident CVD and assessed the extent to which a healthy lifestyle reduced the CVD risk in subjects with glaucoma, using a scoring system consisting of four factors: current smoking, obesity, regular physical activity, and a healthy diet. During a mean follow-up time of 8.9 years, 22,649 (4.9%) incident CVD cases were documented. Multivariable Cox regression analyses revealed that subjects with glaucoma were significantly more likely to exhibit incident CVD (hazard ratio [HR]:1.19, 95% confidence interval [CI] 1.03-1.37; p = 0.016) than controls. In the further subgroup analyses, glaucoma increased incident CVD risk both in the young (40-55 years) and the old (56-70 years) and in both sexes, with higher risk in the young (HR: 1.33, CI 1.02-1.74) and female subjects (HR: 1.32, CI 1.14-1.52). When we analyze the associations between glaucoma and incident CVD by lifestyle factors, the highest absolute risks were observed in individuals with both glaucoma and an unhealthy lifestyle (HR: 2.66, CI 2.22-3.19). In conclusion, glaucoma was an independent risk factor for incident CVD. A healthy lifestyle was associated with a substantially lower risk for CVD incidence among adults with glaucoma.

Association between atrial fibrillation and the risk of glaucoma development: a 12-year Nationwide cohort study.

OBJECTIVE: To investigate the risk of glaucoma development in patients with atrial fibrillation (A-fib) using Korean National Health Insurance Service data. METHODS: The present study used a National Sample Cohort consisting of approximately one million random subjects who were tracked from 2002 to 2013 (12 years). Newly diagnosed glaucoma and A-fib were included based on the Korean Classification of Disease codes. The A-fib group consisted of patients who received an initial A-fib diagnosis between January 2003 and December 2007 as an index period (n = 8765). The control group (n = 43,352) was selected using a 1:5 propensity-score matching for social and demographic factors. Each subject was followed up until 2013. Multivariate Cox proportional hazard regression analysis was performed to compare the risk of glaucoma development between the A-fib group and the control group. RESULTS: The rate of glaucoma development was 3.54% in the A-fib group and 2.96% in the control group (P < 0.0001). A-fib increased the risk of glaucoma development [hazard ratio = 1.31; 95% confidence interval (CI): 1.15 to 1.48] after adjusting for age, sex, comorbidities, residence, household income, and year of enrollment. In multivariable Cox regression analysis, patients with comorbidity of diabetes mellitus and chronic renal failure and those aged ≥50 years showed significantly higher risk of glaucoma development (all P < 0.001). CONCLUSIONS: A-fib was significantly associated with the development of glaucoma after adjusting for potential confounding factors. Physicians may need to monitor patients with A-fib carefully for possible glaucoma development.

Curcumin suppresses ovalbumin-induced allergic conjunctivitis.

PURPOSE: Allergic conjunctivitis (AC) from an allergen-driven T helper 2 (Th2) response is characterized by conjunctival eosinophilic infiltration. Because curcumin has shown anti-allergic activity in an asthma and contact dermatitis laboratory models, we examined whether administration of curcumin could affect the severity of AC and modify the immune response to ovalbumin (OVA) allergen in an experimental AC model. METHODS: Mice were challenged with two doses of topical OVA via the conjunctival sac after systemic sensitization with OVA in aluminum hydroxide (ALUM). Curcumin was administered 1 h before OVA challenge. Several indicators for allergy such as serum immunoglubulin E (IgE) antibodies production, eosinophil infiltration into the conjunctiva and Th2 cytokine production were evaluated in mice with or without curcumin treatment. RESULTS: Mice challenged with OVA via the conjunctival sac following systemic sensitization with OVA in ALUM had severe AC. Curcumin administration markedly suppressed IgE-mediated and eosinophil-dependent conjunctival inflammation. In addition, mice administered curcumin had less interleukin-4 (IL-4) and interleukin-5 (IL-5) (Th2 type cytokine) production in conjunctiva, spleen, and cervical lymph nodes than mice in the non-curcumin-administered group. OVA challenge resulted in activation of the production of inducible nitric oxide (iNOS), and curcumin treatment inhibited iNOS production in the conjunctiva. CONCLUSIONS: We believe our findings are the first to demonstrate that curcumin treatment suppresses allergic conjunctival inflammation in an experimental AC model.

Ocular Dominance in Open-angle Glaucoma: The Shifting Trend Depending on Stage of the Disease.

PURPOSE: To investigate the characteristics and distribution of ocular dominance in primary open-angle glaucoma eyes. In addition, we tried to catch any trend of ocular dominance according to the stage of disease. METHODS: Two hundred participants with bilateral open-angle glaucoma underwent ocular dominant testing by "the hole-ina-card" test. Using optical coherence tomography, macular ganglion cell-inner plexiform layer, as well as circumpapillary retinal nerve fiber layer thickness were measured and compared according to ocular dominance. Of the two eyes of one subject, the eye with less glaucomatous damage based on mean deviation was considered to be the "better eye" in our study. RESULTS: Ocular dominance was in the right eye in 66% of the population and ocular dominance was positioned in the better eye in 70% of the population (p = 0.001 and p = 0.002, respectively). In conditional logistic regression analyses, right eye and better mean deviation were significantly associated with ocular dominance (p = 0.001 and p = 0.002, respectively). Ocular dominance tends to be present in the better eye and this trend was more apparent as the severity of glaucoma increased. Intereye comparison of visual field indices and retinal nerve fiber layer thickness between dominant versus nondominant eye become apparent in moderate and advanced glaucoma whereas it was not as apparent in early glaucoma. CONCLUSIONS: In glaucomatous eyes, laterality and severity of glaucoma determined ocular dominance. Intereye difference between nondominant and dominant eyes increased with the severity of glaucoma. Our findings suggest the existence of potential reciprocal interactions between ocular dominance and glaucoma.

Anti-inflammatory effect of glucagon-like Peptide-1 receptor agonist on the neurosensory retina in an acute optic nerve injury rat model.

PURPOSE: To explore the possibility of using glucagon-like peptide-1 receptor agonist (GLP-1RA) as a new treatment for neuroinflammation, by analyzing retinal pathological changes in an optic nerve crush rat model. METHODS: Eight-week-old male Sprague-Dawley rats were divided into lixisenatide (LIX, n = 10), traumatic control (T-CON, n = 10), and normal control (n = 5) groups. The optic nerves of left eyes in the LIX and T-CON groups were crushed in a standardized manner. The LIX group was treated with subcutaneous injections of lixisenatide (200 µg/kg/day) for 5 days. One week after initiating treatment, quantitative polymerase chain reaction, Western blot, and immunohistochemistry analyses were performed on the retinal tissues of each group to identify inflammatory markers. RESULTS: The LIX group showed significantly lower mRNA levels of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), thioredoxin interacting protein (TXNIP), and glial fibrillary acidic protein (GFAP) than the T-CON group. Also, the LIX group exhibited decreased TXNIP and GFAP expression compared with the T-CON group, and similar expression to the normal control group, according to Western blot analysis. Significantly increased immunohistochemistry staining of Brn3a and decreased TUNEL staining were seen in the LIX group compared with the T-CON group, indicating that lixisenatide contributes to retinal ganglion cell survival in cases of acute optic nerve injury. CONCLUSIONS: Neuroinflammation was significantly reduced in lixisenatide-treated retinas compared with untreated retinas in our acute optic nerve injury rat model. The neuroprotective effect of lixisenatide indicates that it can serve a new treatment option against clinically intractable traumatic optic neuropathy.

Increased Complement-Associated Inflammation in Cytomegalovirus-Positive Hypertensive Anterior Uveitis Patients Based on the Aqueous Humor Proteomics Analysis.

Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, as well as with uncontrolled intraocular pressure (IOP) and a subsequent higher requirement for future glaucoma surgery. To gain novel insights into the pathogenesis of ocular hypertension in these patients, we investigated the proteome changes of the aqueous humor (AH) derived from the CMV hypertensive anterior uveitis (CMV-HAU; n = 10) patients and non-glaucoma (cataract; n = 10) patients using liquid chromatography with tandem mass spectrometry. Among a total of 562 proteins identified, fifty and fifteen proteins were significantly elevated and decreased, respectively, in the AH of CMV-HAU patients compared to the control subjects by ≥2 fold. Gene ontology (GO) enrichment and network analyses of elevated proteins revealed that the enrichment of protein was involved in the complement activation, the humoral immune response mediated by the circulating immunoglobulins, proteolysis, and platelet degranulation. In the AH of CMV-HAU, GDF (growth/differentiation factor)-15, the inflammatory marker belonging to the TGF-ß superfamily proteins, was significantly increased, while vasorin, an anti-TGF-ß protein, levels were decreased. The trabecular meshwork cells infected with CMV exhibited a significantly increased expression of inflammatory markers. Collectively, these data indicate increased complement factor associated inflammation and humoral immunity in CMV-HAU associated ocular hypertension.

Microvasculature Dropout and Development of Normal Tension Glaucoma in Glaucoma Suspects: The Normal Tension Glaucoma Suspect Cohort Study.

PURPOSE: To investigate the contribution of vessel parameters to identify normal tension glaucoma (NTG) suspects at risk of NTG development. DESIGN: Multicenter prospective cohort study. SUBJECTS: A total of 307 eyes of 307 NTG suspects having intraocular pressure within the normal range; a suspicious optic disc, but without definite localized retinal nerve fiber layer (RNFL) defects; and a normal visual field (VF). METHODS: To measure laminar vessel density (VD), the VD was measured in the intradisc region from images of the deep vascular layers of optical coherence tomography angiography (OCT-A). Conversion to NTG was defined either by a new localized RNFL defect in the superotemporal or inferotemporal region, or the presence of a glaucomatous VF defect on 2 consecutive tests according to the pattern deviation plots. MAIN OUTCOME MEASURE: Conversion to NTG. RESULTS: In total, 73 (23.8%) of the 307 NTG suspects converted to NTG during the follow-up period of 59.84 ± 12.44 months. Detection rate of microvasculature dropout (MvD) was significantly higher in NTG suspects who progressed to NTG (50.7%) than in those who did not (6.4%; P < .001). The macular deep VD (P = .006) and laminar deep VD (P = .004) were significantly lower in NTG suspects who progressed to NTG. The presence of MvD (P < .001) and lower laminar deep VD (P = .006) were significantly associated with NTG conversion. CONCLUSIONS: NTG suspects with baseline MvD or a lower laminar deep VD on OCT-A had a higher risk of conversion.