Quantitative assessment of the biomechanical properties of healthy human myopic corneas using Brillouin spectroscopy

Abstract

Background: The importance of corneal biomechanics in ocular health and treatments is well-recognized, but reports on associated factors are inconsistent. We established normative data for corneal stiffness using Brillouin spectroscopy in a large cohort of healthy myopic corneas, exploring potential influences on Brillouin modulus (BM) measurements. Methods: Data from 1744 healthy corneas of 885 subjects (17–52 years; 422 females) were retrospectively collected, including intraocular pressure (IOP in mmHg), manifest refraction spherical equivalent (MRSE in dioptres [D]), and Pentacam measurements (central corneal thickness [CCT in µm]), K1 and K2 in D). Corneal scans were recorded on a Brillouin Optical Scanning System (BOSS®) using an automated 10-point pattern to measure Central, Mean, Minimum and Maximum BM values in gigapascals (GPa). Monocular data (primarily right eye) were used for correlations; binocular data for interocular comparisons. Parametric analyses included Pearson correlations, t-tests for sex differences, paired t-tests for interocular differences, and multivariate linear regression to isolate independent factors (e.g., age, sex, CCT, IOP) with interaction terms. Results: Normative BM values were Central = 2.856 ± 0.053 GPa, Mean = 2.845 ± 0.038 GPa, Min = 2.819 ± 0.046 GPa, and Max = 2.885 ± 0.042 GPa. Interocular comparisons revealed statistically significant but small increases in OS compared to OD for Mean BM (0.003 GPa [95% CI: 0.001–0.005]; OD = 2.855 ± 0.038 GPa, OS = 2.858 ± 0.038 GPa; P = 0.01) and Max BM (0.004 GPa [95% CI: 0.002–0.006]; OD = 2.886 ± 0.042 GPa, OS = 2.890 ± 0.042 GPa; P = 0.003), as well as in K1 and CCT (P < 0.0001). No significant interocular differences were found in Central or Min BM (P ≥ 0.15). Central, Mean and Min BM values correlated significantly with CCT (P ≤ 0.04) but not with IOP, K1, K2, or MRSE (P ≥ 0.20); Max BM did not correlate with any of these clinical parameters (P ≥ 0.07). Males had higher BM values than females (P ≤ 0.006), with effect sizes (d = 0.21) and r = 0.09 –0.1. Regional mapping showed small overall differences in BM values between zones (P = 0.04), with slightly higher values in the Superior region. Multivariate regression confirmed independent associations: Central BM ~ age (β = 0.0008 [95% CI: 0.0001–0.0015], P = 0.04), sex (β = 0.010 [95% CI: 0.003–0.017], P = 0.008), CCT (β = 0.00015 [95% CI: 0.00005–0.00025], P = 0.003); IOP was non-significant (β = 0.0004 [95% CI: −0.0008–0.0016], P = 0.50, R² = 0.048). Age*sex interaction was non-significant (β=−0.0002, P = 0.62). While statistical significance was observed, the correlation coefficients were not large, suggesting a weak linear relationship. Conclusions: Non-contacting Brillouin scans in a large cohort of healthy myopic eyes established robust normative BM standards, revealing associations between corneal stiffness and age, sex, and CCT. These findings provide reference values that enhance diagnostic accuracy for conditions like keratoconus and inform biomechanical assessments in refractive surgery.