PURPOSE: We combined classical association analyses with one-sample and two-sample Mendelian randomization (MR), to comprehensively assess the causal relation among central corneal thickness (CCT), corneal hysteresis, Fuchs endothelial corneal dystrophy (FECD), and open-angle glaucoma (OAG). METHODS: We analyzed data from a large population-based cohort study (the Rotterdam Study), an FECD case-control study, and genome wide association study summary statistics. We defined OAG as reproducible visual field loss, independent of IOP. Multivariable regression was performed. One-sample MR was performed using the same regression models, with the corresponding genetic risk score (GRS) as independent variable. Two-sample MR was performed using inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods. RESULTS: In total, 303 participants with OAG and 10,598 controls from the Rotterdam Study were included, with 753 FECD cases from the FECD cohort. The odds ratio (OR) 95% confidence interval (CI) of OAG was 0.67 (95% CI = 0.56-0.81) per standard deviation (SD) increase in CCT (P < 0.001). However, one-sample MR showed no significant association between a CCT-GRS and OAG (P = 0.688). Two-sample MR found an OR (95% CI) of 1.23 (95% CI = 1.06-1.42) for each SD increase in the CCT instrumental variable. We observed no association between an FECD-GRS and OAG (P = 0.946). CONCLUSIONS: We found no evidence for a causal link between CCT and OAG. Nevertheless, CCT measurements are still valuable for population-based risk stratification. We found no clear relationship between FECD and OAG.

• MeSH
• Genome-Wide Association Study MeSH
• Fuchs' Endothelial Dystrophy * genetics   MeSH
• Glaucoma, Open-Angle * genetics   physiopathology   diagnosis   epidemiology   MeSH
• Polymorphism, Single Nucleotide MeSH
• Middle Aged MeSH
• Humans MeSH
• Mendelian Randomization Analysis * methods   MeSH
• Intraocular Pressure physiology   MeSH
• Risk Factors MeSH
• Cornea * pathology   physiopathology   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Visual Fields physiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a common, age-related cause of visual impairment. This systematic review synthesizes evidence from the literature on artificial intelligence (AI) models developed for the diagnosis and management of FECD. METHODS: We conducted a systematic literature search in MEDLINE, PubMed, Web of Science, and Scopus from January 1, 2000, to June 31, 2024. Full-text studies utilizing AI for various clinical contexts of FECD management were included. Data extraction covered model development, predicted outcomes, validation, and model performance metrics. We graded the included studies using the Quality Assessment of Diagnostic Accuracies Studies 2 tool. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. RESULTS: Nineteen studies were analyzed. Primary AI algorithms applied in FECD diagnosis and management included neural network architectures specialized for computer vision, utilized on confocal or specular microscopy images, or anterior segment optical coherence tomography images. AI was employed in diverse clinical contexts, such as assessing corneal endothelium and edema and predicting post-corneal transplantation graft detachment and survival. Despite many studies reporting promising model performance, a notable limitation was that only three studies performed external validation. Bias introduced by patient selection processes and experimental designs was evident in the included studies. CONCLUSIONS: Despite the potential of AI algorithms to enhance FECD diagnosis and prognostication, further work is required to evaluate their real-world applicability and clinical utility. TRANSLATIONAL RELEVANCE: This review offers critical insights for researchers, clinicians, and policymakers, aiding their understanding of existing AI research in FECD management and guiding future health service strategies.

• MeSH
• Fuchs' Endothelial Dystrophy * diagnosis   therapy   MeSH
• Humans MeSH
• Tomography, Optical Coherence methods   MeSH
• Artificial Intelligence * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH