Abstract
BACKGROUND: We investigated the corneal biomechanical properties and their genotype-phenotype correlation correlations in patients with Marfan syndrome (MFS) and ectopia lentis (EL). METHODS: Patients with MFS with EL underwent panel-based next-generation sequencing in this retrospective cohort study. The FBN1 genotypes were categorized into the dominant-negative (DN) group and the haploinsufficiency (HI) group. The DN variants were further subclassified based on the affected residues and their locations. Corneal biomechanical parameters were measured using dynamic Scheimpflug-based biomechanical analysis (CorVis ST). The correlations between corneal biomechanical properties and FBN1 genotype or nongenetic factors were analyzed. The differences between patients with MFS and normal control were also evaluated after matching confounding factors. RESULTS: One hundred one consecutive MFS probands participated in this study, with a median age of 6 years. Patients with HI and DN variants affecting critical residues, namely the DN (-Cys + CaB) variants, exhibited significantly higher deformation amplitude ratios (P = 0.029) and lower stress-strain index values (P = 0.007) compared with those in the DN (others) group, indicating lower corneal stiffness in the former group. DN variants in the FUN-EGF3 region were associated with lower deformation amplitude ratios (P = 0.011) and higher stress-strain index values (P = 0.002), whereas those in the DN-CD region exhibited the opposite pattern. Compromised corneal stiffness was significantly associated with HI and DN (-Cys + CaB) variants (b = -0.184; P = 0.01) and variants located outside the FUN-EGF3 region (b = 0.256; P = 0.001), after adjusting for confounding factors. Compared with matched controls, patients with MFS demonstrated significantly higher deformation amplitude ratios (P = 0.023), further confirming decreased corneal stiffness in this population. CONCLUSIONS: The FBN1 genotype impacts the corneal biomechanical properties of patients with MFS and EL. Corneal biomechanics provide a novel platform to study the genotype-phenotype correlation of MFS.