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NIR femtosecond laser\u2010induced corneal two\u2010photon collagen cross\u2010linking (two\u2010photon CXL) through photochemical effects can lead to localized refractive index (RI) changes in the cornea, promising for non\u2010ablative and non\u2010incisional 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\u2010induced RI changes in human corneal tissue, demonstrate two\u2010photon excitation of riboflavin leading to cross\u2010linking, and employ direct interferometry to quantify RI changes. The maximum RI change is 3.80\u2009\u00b1\u20090.45\u2009\u00d7\u200910\n                    <jats:sup>\u22123<\/jats:sup>\n                    in collagen hydrogel and 5.14\u2009\u00b1\u20090.75\u2009\u00d7\u200910\n                    <jats:sup>\u22123<\/jats:sup>\n                    in corneal tissue. These findings illustrate that RI engineering by femtosecond laser two\u2010photon CXL is promising for noninvasive refractive surgery.\n                  <\/jats:p>","DOI":"10.1002\/jbio.70336","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T12:56:12Z","timestamp":1786020972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Refractive Index Engineering for Human Corneal Tissue by Femtosecond Laser Two\u2010Photon Cross\u2010Linking"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2885-2072","authenticated-orcid":false,"given":"Pengfei","family":"Qi","sequence":"first","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"},{"name":"Academy for Advanced Interdisciplinary Studies Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshi","family":"An","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Chang","sequence":"additional","affiliation":[{"name":"Liaoning Province Key Laboratory of Corneal and Ocular Surface Diseases Research Dalian Third People's Hospital Affiliated to Dalian University of Technology  DaLian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"},{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye Hospital  Tianjin China"},{"name":"Clinical College of Ophthalmology Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-6635","authenticated-orcid":false,"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Micro\u2010Scale Optical Information Science and Technology, Institute of Modern Optics, Eye Institute Nankai University  Tianjin China"},{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye Hospital  Tianjin China"},{"name":"Clinical College of Ophthalmology Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5754-1057","authenticated-orcid":false,"given":"Olga","family":"Kosareva","sequence":"additional","affiliation":[{"name":"International Laser Center &amp; Faculty of Physics M. 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