Fabry disease involves subclinical ocular autonomic and structural alterations, reflected by reduced maximal redilation velocity and peripheral epithelial thinning correlated with biochemical disease load, suggesting dynamic pupillometry and AS-OCT-based epithelial mapping may serve as complementary, non-invasive biomarkers for early diagnosis and monitoring.
Key Findings
Results
Maximal Redilation Velocity (MRV) was significantly reduced in patients with Fabry disease, possibly indicating sympathetic dysfunction.
Comparison between 25 eyes of genetically confirmed FD patients and 25 age- and sex-matched healthy controls
MRV reduction was statistically significant at p = 0.015
MRV reflects the speed at which the pupil redilates after constriction, and its reduction is interpreted as a marker of sympathetic nervous system dysfunction
Static pupil diameters were wider in Fabry patients under all light conditions but did not reach statistical significance (p > 0.05)
Results
Peripheral corneal epithelial thickness (5–7 mm zone) was significantly thinner in patients with Fabry disease compared to controls.
Peripheral epithelial thinning was statistically significant at p = 0.031
Corneal epithelial thickness was quantified using anterior-segment optical coherence tomography (AS-OCT)
Central and paracentral zones were also assessed but the abstract specifically highlights peripheral thinning as the significant finding
Study included 25 eyes from genetically confirmed FD patients
Results
Plasma Lyso-Gb3 concentrations showed moderate, statistically significant negative correlations with corneal epithelial thickness across all zones.
Lyso-Gb3 data were available for 14 of the 25 patients
Correlation coefficients: central r = -0.659, paracentral r = -0.638, peripheral r = -0.607; all p < 0.05
Higher Lyso-Gb3 levels (reflecting greater glycosphingolipid accumulation) were associated with thinner corneal epithelium
Spearman correlation analysis was used to assess these relationships
Results
No significant associations were found between plasma Lyso-Gb3 levels and pupillometric or ocular surface parameters.
All correlations between Lyso-Gb3 and pupillometric parameters were non-significant (p > 0.05)
Ocular surface parameters assessed included non-contact tear break-up time, Schirmer I testing, and meibography
Lyso-Gb3 data were available for only 14 of the 25 FD patients, which may have limited statistical power for these analyses
This contrasts with the significant correlations found between Lyso-Gb3 and corneal epithelial thickness
Methods
The study design was a prospective cross-sectional study comparing genetically confirmed Fabry disease patients to age- and sex-matched healthy controls using multiple non-invasive ocular imaging modalities.
Sample size: 25 eyes of FD patients and 25 eyes of healthy controls
Diagnostic modalities included dynamic pupillometry, non-contact tear break-up time, Schirmer I testing, meibography, and AS-OCT for corneal epithelial thickness mapping
Group comparisons were performed using Mann-Whitney U and t-tests
Plasma Lyso-Gb3 levels, a biomarker of glycosphingolipid accumulation and disease activity, were available for 14 of the 25 patients
What This Means
This research suggests that Fabry disease — a rare inherited condition where fatty substances accumulate throughout the body — causes subtle but measurable changes in the eyes that can be detected using non-invasive imaging tools. Specifically, patients with Fabry disease showed a slower pupil re-expansion after light exposure (reduced Maximal Redilation Velocity) and thinner outer layers of the cornea (the clear front surface of the eye) compared to healthy individuals. These findings were detected in 25 Fabry disease patients compared to 25 healthy controls of similar age and sex.
This research also suggests that the severity of these corneal changes tracks with how much of the toxic substance (Lyso-Gb3) is circulating in a patient's blood. Patients with higher blood levels of Lyso-Gb3 — indicating greater disease burden — tended to have significantly thinner corneal tissue across all measured zones (central, paracentral, and peripheral). This relationship was moderate in strength but statistically meaningful, suggesting that eye changes may reflect what is happening systemically throughout the body.
These findings matter because Fabry disease is difficult to diagnose early and monitor, and current methods often involve invasive procedures or are costly. This research suggests that routine, non-invasive eye examinations — specifically measuring how the pupil responds to light and mapping the thickness of the cornea's surface layer — could serve as accessible tools to help detect and track Fabry disease involvement, potentially even before symptoms become apparent.
Dal A, Kutluksaman B, Akikol T, Erdağ M, Canleblebici M, Turgut F. (2026). Evaluation of corneal morphology, pupillometry, and ocular surface parameters in Fabry disease patients: correlation with plasma Lyso-Gb3 levels.. International ophthalmology. https://doi.org/10.1007/s10792-026-04133-4