FBN1-related Marfan syndrome is associated with significant quantitative and morphological alterations of the corneal subbasal nerve plexus, suggesting that corneal nerve assessment using IVCM may provide a noninvasive marker of microstructural involvement in this systemic connective tissue disorder.
Key Findings
Results
Patients with FBN1-related Marfan syndrome showed significantly reduced corneal nerve fiber length, density, branching, area, and fractal dimension compared to healthy controls.
49 participants were included: 30 with genetically confirmed FBN1-related MFS and 19 healthy controls
Significantly reduced parameters included CNFL, CNFD, CNBD, CTBD, CNFA, and CNFraD (all P < 0.001)
Corneal nerve fiber width (CNFW) did not differ between groups (P = 0.33)
Between-group differences were assessed using the Mann-Whitney U test
Imaging was performed using in vivo confocal microscopy (IVCM) with ACCMetrics software analysis of six representative subbasal nerve plexus images per participant
Results
Corneal nerve reductions in MFS were consistent across both pediatric and adult age subgroups, with no significant group-by-age interaction.
Age-stratified analyses were performed for participants under 18 years and 18 years or older
Similar reductions in corneal nerve parameters were observed in both age subgroups
No significant group-by-age interaction was detected
Interaction models were adjusted for sex to examine consistency of group effects across age categories
Results
Qualitative morphological abnormalities of the corneal subbasal nerve plexus were identified in MFS patients beyond quantitative reductions.
Observed qualitative abnormalities included reduced corneal nerve density with simplified branching
Microneuroma-like terminal enlargements were identified in MFS patients
Hyper-reflective deposits adjacent to nerve fibers and the epithelial basement membrane were observed
These morphological findings represent novel descriptive features of MFS corneal involvement
Conclusions
IVCM-based corneal nerve assessment was proposed as a potential noninvasive marker of microstructural involvement in FBN1-related Marfan syndrome.
The study design was a cross-sectional case-control study
All MFS cases were genetically confirmed FBN1-related
IVCM allows noninvasive imaging of the subbasal nerve plexus at the microstructural level
The authors suggest corneal nerve assessment may serve as a marker of systemic connective tissue disorder involvement
What This Means
This research suggests that people with Marfan syndrome caused by FBN1 gene mutations have measurable changes in the tiny nerves found in the clear front surface of the eye (the cornea). Using a specialized microscope that can image living tissue without surgery (called in vivo confocal microscopy), the researchers found that these corneal nerves were shorter, less dense, less branched, and had a simpler overall structure compared to healthy individuals. These differences were statistically significant across multiple measurements. Notably, the width of the nerve fibers was the one measurement that did not differ between the two groups.
Beyond the numerical differences, the researchers also observed unusual physical features in the MFS patients' corneal nerves, including abnormal bulb-like enlargements at nerve endings and bright deposits near the nerves and the basement membrane of the eye's surface layer. Importantly, these nerve changes were found in both children (under 18) and adults, suggesting the abnormality is present early in the disease course and is not simply a consequence of aging.
This research suggests that examining corneal nerves with a noninvasive eye microscope could potentially serve as a window into how Marfan syndrome affects the body's connective tissue at a microscopic level. Since Marfan syndrome involves multiple body systems and is caused by defects in connective tissue proteins, finding measurable changes in corneal nerves may help researchers and clinicians better understand and monitor the disease. The study was relatively small (30 MFS patients and 19 controls), so larger studies would be needed to confirm these findings and explore their clinical utility.
Xiao B, Ma Y, Zheng K, Liu S, Chen S, Zhang X, et al.. (2026). Novel findings of corneal neural features in FBN1-related marfan syndrome.. International ophthalmology. https://doi.org/10.1007/s10792-026-04265-7