Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety.

Purpose: Glaucoma, a leading cause of blindness worldwide, is suspected to exhibit a notable association with psychological disturbances. This study aimed to investigate epidemiological associations and explore shared genetic architecture between glaucoma and mental traits, including depression and anxiety. Methods: Multivariable logistic regression and Cox proportional hazards regression models were employed to investigate longitudinal associations based on UK Biobank. A stepwise approach was used to explore the shared genetic architecture. First, linkage disequilibrium score regression inferred global genetic correlations. Second, MiXeR analysis quantified the number of shared causal variants. Third, specific shared loci were detected through conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis and characterized for biological insights. Finally, two-sample Mendelian randomization (MR) was conducted to investigate bidirectional causal associations. Results: Glaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) and anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls. Despite the absence of global genetic correlations, MiXeR analysis revealed 300 variants shared between glaucoma and depression, and 500 variants shared between glaucoma and anxiety. Subsequent condFDR/conjFDR analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression and two associated with glaucoma and anxiety. The MR analysis did not support robust causal associations but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression. Conclusions: Our study enhances the existing epidemiological evidence and underscores the polygenic overlap between glaucoma and mental traits. This observation suggests a correlation shaped by pleiotropic genetic variants rather than being indicative of direct causal relationships.

Effect of mydriasis on macular and peripapillary metrics in swept-source optical coherence tomography angiography.

Introduction: The study aimed to evaluate the effect of mydriasis on macular and peripapillary metrics with swept-source optical coherence tomography angiography (SS-OCTA) in healthy subjects. Methods: Thirty-five healthy subjects were included. The macular region was scanned by the 3×3mm mode and 6×6mm mode, and the peripapillary region was scanned by the 4.5×4.5mm mode on both eyes with SS-OCTA before and after mydriasis. Macular and peripapillary metrics, including retinal vessel density (VD) and fundus thickness were measured by the built-in program. Data of the right eye were analyzed. Results: The signal strength of the scans was comparable before and after mydriasis (all P>0.05). There were no significant differences in foveal avascular zone (FAZ) parameters and retinal VD of most sectors in both macular and peripapillary areas (all P>0.05). Choroidal thickness was decreased, outer and whole retinal thickness was increased in most of the macular sectors after mydriasis (all P<0.05). Choroidal thickness was decreased in all the peripapillary sectors, but whole retinal thickness and GCC thickness were increased in some peripapillary sectors after mydriasis (all P<0.05). Conclusions: FAZ parameters and retinal VD in the most macular and peripapillary regions are not affected by mydriasis. The thickness of the choroid is decreased after mydriasis, while the thickness of retinal layers in some sectors may be increased after mydriasis.

Shared genetic architecture between the two neurodegenerative diseases: Alzheimer's disease and glaucoma.

Background: Considered as the representatives of neurodegenerative diseases, Alzheimer's disease (AD) and glaucoma are complex progressive neuropathies affected by both genetic and environmental risk factors and cause irreversible damages. Current research indicates that there are common features between AD and glaucoma in terms of epidemiology and pathophysiology. However, the understandings and explanations of their comorbidity and potential genetic overlaps are still limited and insufficient. Method: Genetic pleiotropy analysis was performed using large genome-wide association studies summary statistics of AD and glaucoma, with an independent cohort of glaucoma for replication. Conditional and conjunctional false discovery rate methods were applied to identify the shared loci. Biological function and network analysis, as well as the expression level analysis were performed to investigate the significance of the shared genes. Results: A significant positive genetic correlation between AD and glaucoma was identified, indicating that there were significant polygenetic overlaps. Forty-nine shared loci were identified and mapped to 11 shared protein-coding genes. Functional genomic analyses of the shared genes indicate their modulation of critical physiological processes in human cells, including those occurring in the mitochondria, nucleus, and cellular membranes. Most of the shared genes indicated a potential modulation of metabolic processes in human cells and tissues. Furthermore, human protein-protein interaction network analyses revealed that some of the shared genes, especially MTCH2, NDUFS3, and PTPMT1, as well as SPI1 and MYBPC3, may function concordantly. The modulation of their expressions may be related to metabolic dysfunction and pathogenic processes. Conclusion: Our study identified a shared genetic architecture between AD and glaucoma, which may explain their shared features in epidemiology and pathophysiology. The potential involvement of these shared genes in molecular and cellular processes reflects the "inter-organ crosstalk" between AD and glaucoma. These results may serve as a genetic basis for the development of innovative and effective therapeutics for AD, glaucoma, and other neurodegenerative diseases.

The Distribution Pattern of Ocular Residual Astigmatism in Chinese Myopic Patients.

Purpose: We aimed to investigate the distribution of ocular residual astigmatism (ORA) and its associations with age, gender, manifest refraction, and other ocular indicators in Chinese patients with myopia. Design: This is a multi-center retrospective cross-sectional study. Method: The study included 7,893 patients with myopia (7,893 eyes) aged 18-40 years from five ophthalmic centers. Anterior segment biometrics of the eyes were collected from the Pentacam. ORA and its summated vector mean were calculated using Alpins vector analysis. Compensation factor (CF) was used to evaluate the relation between ORA and corneal astigmatism. ORA in different age, gender, and refraction groups was compared. The Spearman correlation was adopted to reveal multiple ocular indicators associated with ORA, which were integrated into a multiple linear regression model to predict ORA. Results: Distribution of ORA was slightly positively skewed (Skewness= 2.111, Kurtosis = 19.660, KS P < 0.0001). Mean ORA was 0.74 ± 0.39 D (95% normal range: 0.14-1.54 D). Among all the subjects, 22.4% of the eyes had an ORA magnitude of 1.0 D or more. Undercompensation or full-compensation of anterior corneal astigmatism (ACA) by ORA prevailed in both J0 (76.99%) and J45 (58.48%). Women had higher ORA power than men (0.77 ± 0.36 D vs. 0.73 ± 0.41 D, P < 0.0001). Participants with less negative spherical equivalent (SE) or higher manifest astigmatism (MA) also had higher ORA (all P < 0.0001). ORA was significantly correlated with ACA (r = 0.405) and posterior corneal astigmatism (PCA, r = 0.356). The multivariate logistic regression analysis showed strong predictability of ORA magnitude >1.0 D using anterior segment parameters (area under the receiver operating characteristic curve: 0.739). Conclusion: ORA is present in Chinese adults with myopia and is affected by multiple ocular factors. Our findings may provide valuable information about ORA distribution in candidates for refractive surgery, helping optimize the outcome of astigmatism correction.

Effect of High Myopia and Cataract Surgery on the Correlation Between Diabetic Retinopathy and Chronic Kidney Disease.

Purpose: To investigate the effect of high myopia and cataract surgery on the grading of diabetic retinopathy (DR) and their roles in the correlation between DR and chronic kidney disease (CKD). Methods: A total of 1,063 eyes of 1,063 diabetic patients were enrolled. We conducted binary and multiple multivariate regressions to analyze the ocular and systemic risk factors of DR. Based on the presence of myopia and history of cataract surgery, we divided the cases into four subgroups, namely those with high myopia, with the history of cataract surgery, with both conditions, and with neither, then determined the correlation between the stages of DR and CKD in each subgroup. Results: In the binary analysis, high myopia was identified as the protective factor for DR odds ratio (OR): 0.312 [95% confidence interval (CI): 0.195-0.500, p < 0.001], whereas cataract surgery was one of the independent risk factors for DR [OR: 2.818 (95% CI: 1.507-5.273), p = 0.001]. With increased stages of DR, high myopia played an increasingly protective role [mild non-proliferative DR (NPDR), OR = 0.461, p = 0.004; moderate NPDR OR = 0.217, p = 0.003; severe NPDR, OR = 0.221, p = 0.008; proliferative DR (PDR), OR = 0.125, p = 0.001], whereas cataract surgery became a stronger risk factor, especially in PDR (mild NPDR, OR = 1.595, p = 0.259; moderate NPDR, OR = 3.955, p = 0.005; severe NPDR, OR = 6.836, p < 0.001; PDR, OR = 9.756, p < 0.001). The correlation between the stages of DR and CKD in the group with neither high myopia nor cataract surgery history was the highest among all subgroups. Conclusion: High myopia was a protective factor, whereas cataract surgery is a risk factor for DR, and both factors showed stronger effects throughout the (natural disease) grading of DR. The stages of DR and CKD showed a higher correlation after adjustment of the ocular confounding factors.

An autophagy-related lncRNA prognostic risk model for thyroid cancer.

PURPOSE: Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long non-coding RNA (lncRNA) in thyroid cancer and explored its prognostic value. METHODS: The data used in this study were all obtained from The Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb). We construct a co-expression network by autophagy-related genes and lncRNA to obtain autophagy-related lncRNAs. After univariate Cox regression analysis and multivariate Cox regression analysis, autophagy-related lncRNAs significantly associated with prognosis were identified. Based on the risk score of lncRNA, thyroid cancer patients are divided into high-risk group and low-risk group. RESULTS: A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the TCGA database and the HADb, respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1,166 autophagy-associated lncRNAs. Subsequently, we conducted univariate Cox regression analysis and multivariate Cox regression analysis, nine autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471 and AL162231.2) significantly associated with prognosis were identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer. CONCLUSION: In this study, nine autophagy-related lncRNAs in thyroid cancer were established to predict the prognosis of thyroid cancer patients.

High HDL-C and high LDL-C are risk factors of pterygium in a population-based cross-sectional study in Southern China: the Dongguan Eye Study.

OBJECTIVES: To investigate the relationship between serum lipids and pterygium in a large-scale rural population aged 40 years or older from Southern China. STUDY DESIGN: The Dongguan Eye Study was a cross-sectional population-based study from September 2011 to February 2012. SETTING: The area was set in the rural area of Dongguan, Southern China. PARTICIPANTS: Adult rural population aged 40 or older. METHODS: Participants underwent physical, haematological and ophthalmic examinations. PRIMARY AND SECONDARY OUTCOME MEASURES: The frequency and risk factors of pterygium. RESULTS: A total of 11 357 participants were eligible for inclusion and 8952 (78.8%) participants were enrolled for the systemic and ophthalmic examinations. The prevalence of pterygium was 17.3% after adjusting the sex and age distribution, 22.0% in participants with hypercholesterolaemia (total cholesterol ≥6.22 mmol/L (240 mg/dL)) and 21.8% in those with low-density lipoprotein-cholesterol (LDL-C) ≥4.14 mmol/L (160 mg/dL), respectively. After adjusting for multiple confounding factors, higher level of high-density lipoprotein-cholesterol (HDL-C) (OR: 1.23, 95% CI: 1.06 to 1.41) and LDL-C (OR: 1.13, 95% CI: 1.06 to 1.20) were positively associated with the risk of pterygium. The ORs for HDL-C or LDL-C with pterygium were significantly greater in participants aged 40-49 years than those aged 50 years or above (P for interaction <0.001). Furthermore, increased HDL-C showed greater association with pterygium in normal body mass index (BMI) group compared with overweight group (P for interaction=0.002). CONCLUSION: Increased HDL-C and LDL-C are risk factors of pterygium, especially in people <50 years or those with normal BMI level. Strict control of HDL-C and LDL-C may be a new prevention method in reducing the risk of pterygium.

Herpes simplex virus type 1 related acute retinal necrosis following an encephalitis illness: a case report.

BACKGROUND: Virus encephalitis is found to be a risk factor for acute retinal necrosis (ARN). CASE PRESENTATION: We herein presented a case of a 20-year-old teenage boy who suffered from encephalitis of unknown etiology with early negative pathologic results, and was primarily treated with systemic administration of high-dose steroids without antiviral therapy. He later had sudden vision loss in his right eye. Intravitreal and intravenous antiviral treatments were immediately started due to suspected ARN. Herpes simplex virus (HSV)-1 was identified later in the vitreous humor of the patient. After the surgery of retinal detachment (RD), obvious improvements in vision were observed. However, the patient had recurrent RD and vision declination 5 weeks later. CONCLUSIONS: The case with suspected viral encephalitis should be treated with antiviral therapy regardless of early virologic results in order to avoid complications of a missed viral encephalitis diagnosis, especially if systemic steroid treatment is being considered.

Factors Associated With the Presence of Foveal Bulge in Eyes With Resolved Diabetic Macular Edema.

Purpose: To evaluate factors associated with the presence of foveal bulge (FB) in resolved diabetic macular edema (DME) eyes. Methods: A total of 165 eyes with complete integrity of ellipsoid zone (EZ) at the fovea and resolved DME were divided into two groups according to the presence of FB at 6 months after intravitreal injection of ranibizumab treatment. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), outer nuclear layer (ONL) thickness, height of serous retinal detachment (SRD) and non-SRD, and inner segment (IS) and outer segment (OS) lengths of the two groups were measured and compared at baseline and each follow-up. The correlations between the presence of FB and pre- and post-treatment factors were determined by logistic regression analysis. Results: At baseline, BCVA was significantly better, and CFT and incidence and height of SRD were significantly lower in the FB (+) group (all P < 0.05). At 6 months, FB was present in 65 (39.39%) eyes. Post-treatment BCVA was significantly better and OS length was significantly longer in the FB (+) group at 6 months (all P < 0.05). Multivariate analysis identified younger age, better BCVA, and lower CFT before treatment as significant predictors of the existence of FB at 6 months (all P < 0.05). At 6 months, better BCVA and longer OS length were significantly correlated with the existence of FB (all P < 0.05). Conclusions: Factors associated with the presence of FB after the resolution of DME include younger age, better baseline BCVA and lower baseline CFT, and better post-treatment BCVA and longer post-treatment OS length.

Investigation of Correlations Between Optical Coherence Tomography Biomarkers and Visual Acuity in X-Linked Retinoschisis.

PURPOSE: To investigate the imaging biomarkers of spectral-domain optical coherence tomography (SD-OCT) and their correlations with age and best-corrected visual acuity (BCVA) in patients with X-linked retinoschisis (XLRS). METHODS: OCT images of 72 eyes of 39 patients with confirmed XLRS were obtained to assess imaging biomarkers, including but not limited to the automatic evaluation of foveal thickness, central subfield thickness (CST), macular volume, and the manual measurement of area of macular schisis cavity (AMS). Correlations between age/BCVA and all OCT parameters were computed as well. RESULTS: In this study, median age was 10.5 (8-12) years old and median BCVA was 0.90 (0.70-1.00) logarithm of the minimum angle of resolution. Macular retinoschisis was found in all affected eyes, with peripheral retinoschisis (PRS) in 34 (47.2%) eyes. Cystic cavities most frequently affected inner nuclear layer (100%) in the macula. Ellipsoid zone (EZ) defects occurred in 53 (73.6%) eyes. As for correlation, BCVA was significantly correlated with several OCT parameters, including CST, AMS, EZ defect, PRS and vitreomacular adhesion, whereas no correlation was found between age and any OCT parameter. CONCLUSION: Explicable OCT imaging biomarkers such as CST, AMS, and photoreceptor defects were identified and may serve as reference parameters or potential regions of interest for future observational and interventional research design and result interpretation.

Celecoxib Exerts a Therapeutic Effect Against Demyelination by Improving the Immune and Inflammatory Microenvironments.

BACKGROUND: The myelin sheath can be damaged by genetic and/or environmental factors, leading to demyelinating diseases, for which effective treatments are lacking. Recently, cyclooxygenase-2 (COX-2) overexpression was detected in demyelinating lesions both in patients and animal models, opening an avenue for promoting endogenous remyelination. The aim of this study was to investigate the therapeutic effect of celecoxib, a selective COX-2 inhibitor, against demyelination in a zebrafish model. METHODS: The biotoxicity of celecoxib was evaluated on zebrafish embryos. Metronidazole was used to deplete the oligodendrocytes in Tg (mbp:nfsB-egfp) transgenic fish. Celecoxib was then administered both in larvae and adults. The regeneration of the myelin sheath and the underlying mechanisms were explored by immunohistochemistry, flow cytometry, Western blot analysis, quantitative real-time polymerase chain reaction, and behavioral test. RESULTS: Celecoxib had low in vivo toxicity. A stable and practical demyelination model was established by metronidazole induction. Following celecoxib treatment, the number of oligodendrocytes was increased significantly and the concentric structure of the myelin sheath reappeared. The locomotor ability was notably improved and was close to its physiological levels. The expression of arg1, mrc1, il-10, and il-4 was upregulated, while that of il-1ß, il-12, tnf-α, il-6, caspase-3 and caspase-7 was downregulated. CONCLUSION: Inhibition of COX-2 contributed to the transformation of microglia/macrophages from the M1 to the M2 phenotype, improved the inflammatory microenvironment, and suppressed caspase-dependent apoptosis, thus exerting a therapeutic effect against demyelination.

Meibomian gland dropout in Sjögren's syndrome and non-Sjögren's dry eye patients.

PURPOSE: The purpose of this study is to explore the differences in ocular symptoms and signs between Sjögren's syndrome (SS) and non-SS aqueous-deficient dry eye (ADDE) patients. METHODS: Twenty-two eyes of 22 SS patients (Group 1) and 22 eyes of 22 non-SS ADDE patients (Group 2) were enrolled. The evaluated variables included the Standard Patient Evaluation of Eye Dryness (SPEED), the Ocular Surface Disease Index (OSDI), tear meniscus height, first and average non-invasive keratographic breakup time (fNIKBUT and avNIKBUT), Schirmer I test, lipid layer thickness (LLT), meibomian gland expressibility, Marx line, corneal staining, conjunctival congestion, incomplete blinking, and meibomian gland dropout using two novel, non-invasive instruments, the Keratograph and LipiView II. RESULTS: Ocular signs of the NIKBUT (fNIKBUT: 3.8 (2.7, 5.2)s and 6.3 (3.7, 8.9)s, P = 0.024; avNIKBUT: 5.4 (4.5, 8.9)s and 7.6 (5.8, 13.7)s, P = 0.041), meibomian gland dropout of the upper eyelid (35.5% (29.1%, 54.8%) and 21.9% (16.7%, 24.9%), P = 0.000), and corneal staining (P = 0.050) were more severe but were associated with less severe symptoms, i.e., a lower SPEED score (P = 0.001), in SS subjects than in non-SS subjects. CONCLUSION: SS patients exhibit more severe meibomian gland destruction of the upper eyelid than non-SS patients. Meibomian gland dysfunction is another key cause of SS-associated dry eye.

Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion.

AIM: To investigate the predictive factors for short-term effects of intravitreal bevacizumab injections on central subfield foveal thickness (CSFT) in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO. Follow-up was three months. The Early Treatment Diabetic Retinopathy Study (ETDRS) score and CSFT measured by spectral-domain optical coherence tomography (SD-OCT) were used to observe the changes in best-corrected visual acuity (BCVA). Baseline BCVA, CSFT, age, CRVO duration and the presence of cystoid macular edema (CME) or subretinal fluid (SRF) were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections. RESULTS: BCVA improved from 0.9 logMAR at baseline to 0.6 logMAR at 3mo, which was associated with a significant reduction in CSFT from 721 µm to 392 µm 3mo after injection. About 50% of CME cases and more than 90% of SRF cases responded to treatment with a complete resolution at 3mo. Age (P=0.036) and low baseline CSFT (P=0.037) were associated with a good 3-month prognosis. Patients >60 years old achieved better CME resolution (P=0.031) and lower CSFT at 3mo (305 µm vs 474 µm, P=0.003). CONCLUSION: Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo. Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes. The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF.