Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study.

Background: Diabetic retinopathy (DR) is a microvascular complication of diabetes, severely affecting patients' vision and even leading to blindness. The development of DR is influenced by metabolic disturbance and genetic factors, including gene polymorphisms. The research aimed to uncover the causal relationships between blood metabolites and DR. Methods: The two-sample mendelian randomization (MR) analysis was employed to estimate the causality of blood metabolites on DR. The genetic variables for exposure were obtained from the genome-wide association study (GWAS) dataset of 486 blood metabolites, while the genetic predictors for outcomes including all-stage DR (All DR), non-proliferative DR (NPDR) and proliferative DR (PDR) were derived from the FinnGen database. The primary analysis employed inverse variance weighted (IVW) method, and supplementary analyses were performed using MR-Egger, weighted median (WM), simple mode and weighted mode methods. Additionally, MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were also conducted to guarantee the accuracy and robustness of the results. Subsequently, we replicated the MR analysis using three additional datasets from the FinnGen database and conducted a meta-analysis to determine blood metabolites associated with DR. Finally, reverse MR analysis and metabolic pathway analysis were performed. Results: The study identified 13 blood metabolites associated with All DR, 9 blood metabolites associated with NPDR and 12 blood metabolites associated with PDR. In summary, a total of 21 blood metabolites were identified as having potential causal relationships with DR. Additionally, we identified 4 metabolic pathways that are related to DR. Conclusion: The research revealed a number of blood metabolites and metabolic pathways that are causally associated with DR, which holds significant importance for screening and prevention of DR. However, it is noteworthy that these causal relationships should be validated in larger cohorts and experiments.

Analysis of retinal microvasculature features in amblyopic eyes: A meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate retinal vessel density (VD) in amblyopic patients using optical coherence tomography angiography (OCTA). METHODS: PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for published articles comparing retinal microvasculature characteristics in patients with amblyopia and controls. Continuous variable outcomes were assessed using the mean difference (MD) with a 95% confidence interval. Review Manager Version 5.30 was used for the analysis. RESULTS: Thirteen qualified articles were pooled in this meta-analysis. Compared with controls, the foveal whole enface VD of superficial (SCP) and deep capillary plexus (DCP) of patients as measured by 3×3-mm scans were significantly lower in amblyopia eyes (MD: -1.37, P = 0.0003; MD: 1.70, P < 0.00001, respectively). Similarly, in the 6×6-mm scans, foveal whole enface VD of the SCP and DCP were remarkably lower in amblyopia eyes than in controls (MD: -2.24, P = 0.03; MD: -5.08, P = 0.04, respectively). The parafoveal VD of SCP in 3×3-mm scans (MD: -1.96, P < 0.00001) was also lower in amblyopic patients than in controls. Similarly, in 6×6-mm scans, amblyopia eyes showed a significant decrease, and a trending decrease in the parafoveal VD of the SCP (MD: -3.85, P = 0.007) and DCP (MD: -3.03, P = 0.10), respectively. For whole radial peripapillary capillary (RPC), VD was significantly reduced in amblyopic patients compared to controls (MD = -0.83, P < 0.00001). In addition, the deep foveal avascular zone (FAZ) was larger in amblyopic eyes than in the controls (MD = 0.55, P= 0.007). CONCLUSIONS: Our data suggest that whole foveal and parafoveal VD and RPC whole VD were reduced in patients with amblyopia. Moreover, our results reveal that the FAZ is larger in amblyopic patients. Consequently, OCTA may have the potential for diagnosing and monitoring patients with amblyopia.