Oral Riboflavin for Sunlight-Induced Corneal Cross-linking: Efficacy Assessment in a Rabbit Model In Vivo Using Extensometry and OCT Elastography
Emilio A. Torres-Netto, M. Enes Aydemir, Nan-Ji Lu, Sabine Kling, Nikki Hafezi, Mark Hillen, Michalina L. Depczynska, Farhad HafeziPurpose:
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.
Methods:
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.
Results:
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;
Conclusions:
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.