Oral Riboflavin for Sunlight-Induced Corneal Cross-linking: Efficacy Assessment in a Rabbit Model In Vivo Using...

To evaluate whether a non-invasive approach to treat keratoconus with corneal cross-linking (CXL) using oral riboflavin and natural sunlight could represent a cost-effective alternative.

In a prospective, controlled study, 16 male New Zealand White rabbits (32 eyes) underwent a two-step protocol. Step 1 quantified stromal riboflavin in 4 rabbits (8 eyes) after 14 days of oral riboflavin (6 mg/kg/day). Step 2 randomized the remaining 12 rabbits (24 eyes) 1:1 to oral riboflavin plus natural sunlight or sunlight alone. After a 2,700 klux·h cumulative sunlight dose, corneal biomechanics were assessed by optical coherence tomography elastography and uniaxial stress-strain extensometry.

The mean stromal riboflavin concentration after oral administration was 0.000081% ± 0.000011%. Stress-strain testing showed no significant differences in stress at 0.1 strain (152 ± 11.5 kPa in controls vs 146 ± 7.0 kPa in treated eyes; P = .57) or mean elastic modulus between 0.1 and 0.2 strain (4.1 vs 4.0 MPa; P = .870). OCT elastography demonstrated significantly higher posterior corneal strain in treated eyes (0.551‰ vs 0.398‰; P = .039), consistent with reduced apparent stiffness.

Oral riboflavin combined with ambient sunlight did not induce corneal stiffening under the tested conditions. Stromal riboflavin levels were nearly 500-fold lower than those achieved with standard CXL, indicating the tested approach is unlikely to serve as an effective standalone cross-linking strategy. The observed posterior corneal stiffness reduction may reflect ultraviolet-A-induced stromal degradation or subthreshold photochemical effects rather than true cross-linking.