Predicting vision-threatening diabetic retinopathy in patients with type 2 diabetes mellitus: Systematic review, meta-analysis, and prospective validation study.

Background: Delayed diagnosis and treatment of vision-threatening diabetic retinopathy (VTDR) is a common cause of visual impairment in individuals with type 2 diabetes mellitus (T2DM). Identification of VTDR predictors is the key to early prevention and intervention, but the predictors from previous studies are inconsistent. This study aims to conduct a systematic review and meta-analysis of the existing evidence for VTDR predictors, then to develop a risk prediction model after quantitatively summarising the predictors across studies, and finally to validate the model with two Chinese cohorts. Methods: We systematically retrieved cohort studies that reported predictors of VTDR in T2DM patients from PubMed, Ovid, Embase, Scopus, Cochrane Library, Web of Science, and ProQuest from their inception to December 2023. We extracted predictors reported in two or more studies and combined their corresponding relative risk (RRs) using meta-analysis to obtain pooled RRs. We only selected predictors with statistically significant pooled RRs to develop the prediction model. We also prospectively collected two Chinese cohorts of T2DM patients as the validation set and assessed the discrimination and calibration performance of the prediction model by the time-dependent ROC curve and calibration curve. Results: Twenty-one cohort studies involving 622 490 patients with T2DM and 57 107 patients with VTDR were included in the meta-analysis. Age of diabetes onset, duration of diabetes, glycosylated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), hypertension, high albuminuria and diabetic treatment were used to construct the prediction model. We validated the model externally in a prospective multicentre cohort of 555 patients with a median follow-up of 52 months (interquartile range = 39-77). The area under the curve (AUC) of the prediction model was all above 0.8 for 3- to 10-year follow-up periods and different cut-off value of each year provided the optimal balance between sensitivity and specificity. The data points of the calibration curves for each year closely surround the corresponding dashed line. Conclusions: The risk prediction model of VTDR has high discrimination and calibration performance based on validation cohorts. Given its demonstrated effectiveness, there is significant potential to expand the utilisation of this model within clinical settings to enhance the detection and management of individuals at high risk of VTDR.

Plasma Proteomics to Identify Drug Targets and Potential Drugs for Retinal Artery Occlusion: An Integrated Analysis in the UK Biobank.

Retinal artery occlusion (RAO), which is positively correlated with acute ischemic stroke (IS) and results in severe visual impairment, lacks effective intervention drugs. This study aims to perform integrated analysis using UK Biobank plasma proteome data of RAO and IS to identify potential targets and preventive drugs. A total of 7191 participants (22 RAO patients, 1457 IS patients, 8 individuals with both RAO and IS, and 5704 healthy age-gender-matched controls) were included in this study. Unique 1461 protein expression profiles of RAO, IS, and the combined data set, extracted from UK Biobank Plasma proteomics projects, were analyzed using both differential expression analysis and elastic network regression (Enet) methods to identify shared key proteins. Subsequent analyses, including single cell type expression assessment, pathway enrichment, and druggability analysis, were conducted for verifying shared key proteins and discovery of new drugs. Five proteins were found to be shared among the samples, with all of them showing upregulation. Notably, adhesion G-protein coupled receptor G1 (ADGRG1) exhibited high expression in glial cells of the brain and eye tissues. Gene set enrichment analysis revealed pathways associated with lipid metabolism and vascular regulation and inflammation. Druggability analysis unveiled 15 drug candidates targeting ADGRG1, which demonstrated protective effects against RAO, especially troglitazone (-8.5 kcal/mol). Our study identified novel risk proteins and therapeutic drugs associated with the rare disease RAO, providing valuable insights into potential intervention strategies.

Accelerometer-Measured Daily Behaviors That Mediate the Association Between Refractive Status and Depressive Disorders.

Purpose: To identify the accelerometer-measured daily behaviors that mediate the association of refractive status with depressive disorders and enhance the understanding of behavioral differences in depression. Methods: Participants with baseline mean spherical equivalent (MSE) and 7-day accelerometer measurements from the UK Biobank were included in this cohort study. Refractive status was categorized as hyperopia and non-hyperopia. Four daily behaviors, including moderate to vigorous intensity physical activity (MVPA), light physical activity (LPA), sedentary, and sleep were recorded between 2013 and 2015. We also assessed 24-hour behavior patterns. Depression cases were defined through both questionnaires and hospital records over 10 years of follow-up. Results: Among 20,607 individuals, every 0.5-diopter increase in MSE was associated with a 6% higher risk of depressive disorders, with hyperopia participants at a higher risk than non-hyperopia participants (odds ratio, 1.14; 95% confidence interval, 1.05-1.23; P = 0.001). MVPA and sleep time significantly correlated with depressive disorders, with odds ratios of 0.79 and 1.14 (P < 0.05). MSE showed significant correlations with all four behaviors. The effects of MVPA and sleep duration on MSE and depressive disorders varied throughout the day. Mediation analyses showed that MVPA and sleep partially mediated the relationship between MSE and depressive disorders, with 35.2% of the association between moderate to high hyperopia and depression mediated by MVPA. Conclusions: Physical activity and sleep significantly mediate the relationship between MSE and depressive disorders. Translational Relevance: The mediation effect of MVPA highlights its therapeutic potential in reducing the risk of depression among individuals with moderate to severe hyperopia. Interventions aimed at increasing daytime MVPA and decreasing daytime sleep could enhance mental health in this vulnerable group.

The association between cataract surgery and mental health in older adults: a review.

BACKGROUND: Although cataract surgery has been proposed as a potentially modifiable protective factor for enhancing emotional well-being in cataract patients, studies examining the relationship between anxiety or depression and cataract surgery have yielded inconsistent findings. This review summarizes existing evidence to establish whether cataract surgery is associated with depression and anxiety in older adults. METHODS: A literature search was conducted across PubMed, Medline, Web of Science, and Embase databases. An initial screening by abstracts and titles was performed, followed by a review and assessment of the methodological quality of the relevant full papers, and final inclusion of 44 studies were deemed eligible for inclusion in this review. RESULTS: Among 44 included studies, 36 studies (81.8%) were observational studies concerning the association of cataract surgery or cataracts with anxiety or depression, four studies (9.1%) were interventional studies, and four studies (9.1%) were reviews. Cataract surgery notably enhances the mental health of individuals with impaired vision. However, the multifaceted nature of psychological well-being, influenced by various factors, suggests that cataract surgery may not address all aspects comprehensively. Additionally, preoperative anxiety and depression significantly impact cataract surgery outcomes. CONCLUSION: Vision impairment in older adults is closely associated with increased symptoms of depression and anxiety. While surgical intervention for cataracts improves these symptoms, it might be less effective for mental disorders with multifactorial causes. Notably, anxiety or depression poses challenges to successful preoperative and intraoperative cataract surgeries.