Refractive Index Engineering for Human Corneal Tissue by Femtosecond Laser Two-Photon Cross-Linking

Clinical refractive surgeries for myopia correction generally entail stromal tissue removal with risks of postoperative complications. NIR femtosecond laser-induced corneal two-photon collagen cross-linking (two-photon CXL) through photochemical effects can lead to localized refractive index (RI) changes in the cornea, promising for non-ablative and non-incisional visual correction. However, previous studies mainly focused on hydrogels and animal corneal tissues, adopting a diffraction grating method that is difficult for biological tissue. Here we systematically investigate femtosecond laser-induced RI changes in human corneal tissue, demonstrate two-photon excitation of riboflavin leading to cross-linking, and employ direct interferometry to quantify RI changes. The maximum RI change is 3.80 ± 0.45 × 10^-3 in collagen hydrogel and 5.14 ± 0.75 × 10^-3 in corneal tissue. These findings illustrate that RI engineering by femtosecond laser two-photon CXL is promising for noninvasive refractive surgery.