Background: Homocystinuria caused by cystathionine β-synthase (CBS) deficiency is the most common congenital disorder related to sulfur amino acid metabolism, manifested by neurological, vascular, and connective tissue involvement. Methods: This study analyzed the pathogenic gene and molecular mechanism of two classic homocystinuria families through whole exome sequencing and in vitro experiments including minigene assay and expression analysis. Results: Both probands presented with ectopia lentis, high myopia, and abnormally elevated homocysteine level, but one of them had more severe clinical manifestations, including general growth retardation, mild intellectual disability, and severe pectus excavatum. Their family members were phenotypically normal but presented slightly higher levels of homocysteine in plasma. Whole exome sequencing revealed that the two probands carried c.833T>C (p.Ile278Thr) and c.1359-1G>C, and c.919G>A (p.Gly307Ser) and c.131delT (p.Tle44Thrfs*38) compound heterozygous mutations in the CBS gene, respectively. Bioinformatics and in vitro functional analysis showed that the c.1359-1G>C mutation affects the normal splicing of CBS gene, resulting in the production of two abnormal transcripts and the production of two truncated proteins. One of the c.1359-1G>C splicing events (c.1359_1467del) and c.131delT (p.Tle44Thrfs*38) both lead to a significant decrease in CBS mRNA and protein levels. Conclusions: Accurate diagnosis of patients with homocystinuria is of great importance for timely and effective treatment, as well as for the provision of appropriate genetic counseling and prenatal diagnosis guidance to the affected families.

Purpose: This study aims to explore the factors influencing refractive error following Phacoemulsification combined with intraocular lens implantation (PE + IOL) in patients with primary angle-closure glaucoma (PACG), providing a theoretical basis for preoperative consultation and IOL power selection in clinical practice.Methods: A retrospective analysis was conducted on 404 PACG patients from Shenzhen Eye Hospital between 2019 and 2024. Preoperative ocular biometric parameters and combined surgical approaches were evaluated using Spearman correlation, multinomial logistic regression, and receiver operating characteristic (ROC) curve analysis.Results: Axial length (AL), lens thickness (LT), and white-to-white distance (WTW) were key predictive factors for prediction error and postoperative refractive outcomes. AL > 22.56 mm (AUC = 0.692) and LT > 5.055 mm (AUC = 0.633) increased the risk of myopic shift (MS), while AL < 22.25 mm (AUC = 0.604) and WTW 2.986 further indicated a higher risk of MS (AUC = 0.639) postoperatively. Among patients who underwent PE + IOL combined with capsular tension ring, the proportion of HS was significantly higher (Z value = +2.95).Conclusion: The unique anatomical characteristics of PACG patients are key contributors to postoperative refractive instability. Preoperative assessment for PE + IOL surgery should comprehensively evaluate AL, LT, WTW, and AL/CR ratio. When combined with other surgical approaches to control intraocular pressure, IOL power should be adjusted according to these thresholds to ensure postoperative refractive stability.

Précis: This study developed and validated a machine learning–based risk prediction model to estimate the likelihood of postoperative hyperopic shift in patients with primary angle closure glaucoma after IOL implantation, which may help guide individualized surgical decision-making. Objective: This study aims to construct a predictive model for the risk of hyperopic shift (HS) after phacoemulsification combined with intraocular lens (PE+IOL) surgery in patients with primary angle closure glaucoma (PACG), with the goal of providing scientific evidence for personalized treatment and early warning. Materials and Methods: This is a retrospective cohort study that included PACG patients who underwent PE+IOL surgery between June 2019 and June 2024, according to predefined inclusion and exclusion criteria. We collected patients’ demographic information, preoperative ocular examination data, and refractive changes 3–6 months postsurgery. The Boruta algorithm was used for feature selection of all clinical variables, and various machine learning models, including logistic regression (LR), random forest, support vector machine (SVM), k-nearest neighbors (KNN), and XGBoost, were developed. Model performance was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC). The best-performing model was selected for visualization and interpretability analysis. Data processing and analysis were performed using R version 4.2.3. All statistical tests were 2-sided, with a P -value <0.05 considered statistically significant. Results: A total of 423 eyes were included, with n=267 in the non-HS group and n=156 in the HS group. Key predictive variables identified by the Boruta algorithm included target refraction, preoperative best-corrected visual acuity (BCVA), axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white-to-white distance (W2W), and pupil diameter (P). Both the SVM and LR models exhibited the best predictive accuracy, with AUCs of 0.704 and 0.696, respectively, demonstrating moderate classification ability. Conclusion: This study successfully developed a risk prediction model for HS after PE+IOL surgery in PACG patients based on various clinical features. The SVM and LR models show promising clinical application in predicting HS risk and can provide personalized postoperative management strategies for glaucoma surgery patients.