Corneal Crosslinking Using Brillouin Microscopy May Lead To Better Treatment of Nearsightedness Interview with:

Sheldon J.J. Kwok MD/PhD Candidate Harvard-MIT Health Sciences and Technology | Harvard Medical School Yun Bio-Optics Lab  Wellman Center for Photomedicine MGH

Sheldon j. .J.Kwok

Sheldon J.J. Kwok
MD/PhD Candidate
Harvard-MIT Health Sciences and Technology | Harvard Medical School
Yun Bio-Optics Lab
Wellman Center for Photomedicine
MGH What is the background for this study?
Response: Corneal collagen crosslinking (CXL) using UV light and riboflavin has become a popular and effective technique for treating corneal ectatic disorders, such as keratoconus, by mechanically strengthening the corneal stroma. We were interested in enhancing the capabilities of CXL using the principle of two-photon excitation, which uses a femtosecond laser to confine crosslinking to only where the laser is focused.  By scanning the laser, this allows us to crosslink any arbitrary three-dimensional region deep inside tissue.

With two-photon collagen crosslinking (2P-CXL), treatment of thin corneas is possible without affecting the underlying endothelium. Irradiation can also be patterned to improve keratocyte viability. Furthermore, selective crosslinking in three dimensions offers the possibility of modulating corneal curvature for refractive error correction. What are the main findings?
Response: One of the major challenges faced by researchers interested in 2P-CXL was being able to visualize and characterize the cross-linked region non-invasively. In our study, we used a novel technique developed in our lab, Brillouin microscopy, to visualize the crosslinked region. After optimizing the laser parameters needed for 2P-CXL, we demonstrated selective, subsurface crosslinking of animal corneas for the first time. We also found that the degree of stiffening obtained with 2P-CXL was similar to that with conventional CXL. What should readers take away from your report?

Response: 2P-CXL is likely to find applications in not only ophthalmology, but also tissue engineering, and regenerative medicine. Our technique combines two-photon collagen crosslinking and Brillouin microscopy to provide three-dimensional control of tissue stiffness at high spatial resolution. What recommendations do you have for future research as a result of this study?

Response: We are currently investigating how controlling local collagen crosslinking can lead to refractive changes in the cornea. We are excited about this research direction and the possibility of using 2P-CXL as a non-surgical, non-invasive technique for refractive error correction, such as in myopic patients. Is there anything else you would like to add?

Response: Since corneal crosslinking (CXL) is already commercially available in Europe, Asia, and recently the US (as of April 2016), we hope clinical translation of 2P-CXL will not be too far away. Many types of femtosecond lasers are already available in the clinic, and we hope that by optimizing 2P-CXL with those lasers, regulatory approval can be expedited. Thank you for your contribution to the community.


Sheldon J. J. Kwok, Ivan A. Kuznetsov, Moonseok Kim, Myunghwan Choi, Giuliano Scarcelli, Seok Hyun Yun.
Selective two-photon collagen crosslinking in situ measured by Brillouin microscopy. Optica, 2016; 3 (5): 469 DOI: 1364/optica.3.000469

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