Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study

PurposeThis study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors.DesignTwo-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method.MethodOur study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included.ResultIn the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30–1.54; P < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05–1.28; P = 0.003) were genetically predicted to be causally associated with an increased risk of DR, while patients with higher hip circumference (HC) had a lower risk of DR (OR, 95% CI = 0.85, 0.76–0.95; P = 0.004). In the analysis of subtypes of DR, the results of BMI and HC were similar to those of DR, whereas cigarettes per day were only related to proliferative DR (PDR) (OR, 95% CI = 1.18, 1.04–1.33; P = 0.009). In the MR-PRESSO analysis, a higher waist-to-hip ratio (WHR) was a risk factor for DR and PDR (OR, 95% CI = 1.24, 1.02–1.50, P = 0.041; OR, 95% CI = 1.32, 1.01–1.73, P = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures.ConclusionOur findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR

In vivo confocal microscopy assessment of meibomian glands microstructure in patients with Graves’ orbitopathy

Abstract Background To evaluate microstructural changes in the meibomian glands (MGs) in patients with active and inactive Graves’ orbitopathy (GO), using in vivo confocal microscopy (IVCM), and to investigate the correlations between clinical and confocal findings. Methods Forty patients (80 eyes) with GO (34 eyes with active GO, 46 eyes with inactive GO), and 31 age- and sex-matched control participants (62 eyes) were enrolled consecutively. A researcher recorded the clinical activity score (CAS) for each patient. A complete ophthalmic examination was then performed, including external eye, ocular surface and MGs. IVCM of the MGs was performed to determine the MG acinar density (MAD), MG longest and shortest diameters (MALD and MASD), MG orifice area (MOA), MG acinar irregularity (MAI), meibum secretion reflectivity (MSR), acinar wall inhomogeneity (AWI), acinar periglandular interstices inhomogeneity (API), and severity of MG fibrosis (MF). Results All confocal microscopy assessments of MGs significantly differed among groups (all P = 0.000). Compared to controls, GO groups showed lower MOA (1985.82 ± 1325.30 μm2 in active GO and 2021.59 ± 1367.45 μm2 in inactive GO vs. 3896.63 ± 891.90 μm2 in controls, all P = 0.000) and MAD (87.21 ± 32.69 /mm2 in active GO and 80.72 ± 35.54 /mm2 in inactive GO vs. 114.69 ± 34.90 /mm2 in controls, P = 0.001 and 0.000, respectively); greater MALD (118.11 ± 30.23 μm in active GO and 120.58 ± 27.64 μm in inactive GO vs. 58.68 ± 20.28 μm in controls, all P = 0.000) and MASD (44.77 ± 19.16 μm in active GO and 46.02 ± 20.70 μm in inactive GO vs. 27.80 ± 9.90 μm in controls, all P = 0.000); and higher degrees of MAI, MSR, and MF (all P<0.05). Eyes with active GO had higher degrees of MAI (P = 0.015), AWI (P = 0.000), and API (P = 0.000), while eyes with inactive GO had higher degrees of MSR (P = 0.000) and MF (P = 0.017). In GO groups, AWI and API were positively correlated with CAS (r = 0.640, P = 0.000; r = 0.683, P = 0.000, respectively), and MF was negatively correlated with CAS (r = − 0.228, P = 0.042). Conclusions IVCM effectively revealed microstructural changes of MGs in eyes with GO and provided strong in vivo evidence for the roles of obstruction and inflammation in the ocular surface disease process. Furthermore, it revealed discernible patterns of MG abnormalities in eyes with active GO and inactive GO, which are not easily distinguishable by typical clinical examinations

Toll-Like Receptor 4 in Bone Marrow-Derived Cells Contributes to the Progression of Diabetic Retinopathy

Diabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM) induction by streptozotocin (STZ) treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α). Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1β, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR

Effects of various extraocular muscle enlargement patterns on muscle diameter index in graves ophthalmopathy patients: a retrospective cohort study

Abstract Graves ophthalmopathy (GO) patients often undergo retrobulbar injection of glucocorticoids (GCs) as a common therapeutic approach. This study aimed to explore the impact of various patterns of extraocular muscle (EOM) enlargement on EOM changes following retrobulbar GCs injection in patients with GO. A retrospective analysis was conducted on GO patients who underwent retrobulbar GCs injections. Data pertaining to EOM diameter (EMD) and muscle diameter index (MDI) were collected from orbital computed tomography (CT) scans. The MDI change (ΔMDI) was calculated by comparing pre- and post-injection MDI values. The relationship between each pre EMD/MDI and ΔMDI was assessed using univariate and multivariate logistic regression analysis. A total of 68 patients with GO were included in this study, accounting for 118 eyes. After retrobulbar injections of GCs, 84 eyes showed a decrease in the MDI, while 34 eyes exhibited an increase in MDI. A threshold effect was observed in the relationship between medial pre EMD/MDI and ΔMDI. When the medial pre EMD/MDI was less than 0.28, a higher medial pre EMD/MDI was associated with a smaller ΔMDI (β = − 25.21, p = 0.0175). However, when the medial pre EMD/MDI was greater than 0.28, no significant association was found between pre EMD/MDI and ΔMDI. There was a negative correlation between medial + lateral pre EMD/MDI and ΔMDI (β = − 11.76, p < 0.0189). A higher medial + lateral pre EMD/MDI was associated with a greater decrease in MDI. Additionally, there was a positive correlation between superior rectus muscle-levator complex (SRLC) pre EMD/MDI and ΔMDI (β = 11.92, p = 0.040). The higher the value of SRLC pre EMD/MDI, the greater the ΔMDI. There was an association between pre EMD/MDI and changes in EOMs after retrobulbar injection of GCs in GO patients. In patients with predominantly enlarged medial rectus muscles and severe degrees of enlargement, retrobulbar injection of GCs should be assessed for its benefit; a combination of medial and lateral rectus muscle enlargement is beneficial for the shrinkage of EOMs following retrobulbar injections; the involvement of the SRLC rectus muscle may be a disadvantageous pattern of shrinkage of EOMs following retrobulbar injections. Trial registration This study is retrospectively registered. We have registered this study with the Chinese Clinical Trials Registry ( www.chictr.org.cn , registration number: ChiCTR2200063429)

Table_1_Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study.pdf

PurposeThis study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors.DesignTwo-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method.MethodOur study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included.ResultIn the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30–1.54; P ConclusionOur findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.</p