Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the concerned 11 exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. Summary-level data for glaucoma were obtained from the UK Biobank, the GERA study, and the FinnGen consortium. Univariable and multivariable MR analyses were conducted separately in two populations. Our results showed that higher genetic liability to type 2 diabetes (T2D) was causally and independently associated with an increased risk of glaucoma (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06–1.16; p = 4.4 × 10⁻⁶). The association for T2D persisted after multivariable adjustment. In addition, higher genetically predicted systolic blood pressure (SBP), fasting glucose (FG), and HbA1c, were also suggestively associated with glaucoma risk. The OR was 1.08 (95% CI, 1.01–1.16; p = 0.035) for SBP, 1.24 (95% CI, 1.05–1.47; p = 0.011) for FG, and 1.28 (95% CI, 1.01–1.61; p = 0.039) for HbA1c. No evidence was observed to support the causal effects of body mass index and blood lipids for glaucoma. This study suggests a causal role for diabetes, as well as possible roles for higher SBP, FG, and HbA1c in the development of glaucoma. Further validation is needed to assess the potential of these risk factors as pharmacological targets for glaucoma prevention.

Purpose: To evaluate the corneal cross-linking (CXL) efficacy of riboflavin (RF) at 5 different concentrations (0.1%, 0.25%, 0.5%, 0.75%, 1.0%) and determine the optimal concentration for maximizing the cornea's biomechanical performance. Setting: Department of Ophthalmology, Zhongshan Hospital, Fudan University Design: Experimental study. Methods: The corneal epithelium was removed from all eyes. In the first part, 0.1% to 1.0% RF solutions were applied to rabbit eyes for 30 minutes, with 20% dextran used as the vehicle for the RF solutions. After application, RF concentration in the cornea and aqueous humor were evaluated. In the second part, after applying different RF solutions, the corneas underwent CXL with 9 mW/cm² ultraviolet-A light for 10 minutes. Stress-strain curves, Young's modulus, and resistance to enzymatic digestion were measured. Results: 107 eyes were used in total. RF concentrations in the cornea were 447.57 ± 28.72 μg/g, 536.51 ± 19.59 μg/g, 885.89 ± 111.77 μg/g, 1280.46 ± 103.86 μg/g, and 1668.68 ± 89.02 μg/g from 0.1% to 1.0% RF solutions, respectively. Following CXL, the corneal stress of the other four groups was 123%, 147%, 116%, and 69% relative to the 0.1% RF group at 10% strain. Similarly, after CXL with RF solutions at five concentrations, the residual corneal dry weights were 0.45 ± 0.08 mg, 0.53 ± 0.03 mg, 0.62 ± 0.07 mg, 0.50 ± 0.04 mg, and 0.35 ± 0.05 mg, respectively. Conclusions: The 0.5% RF group achieved the optimal corneal biomechanical performance under controlled experimental conditions, with decreased efficiency as the RF concentration further increased.