Selective two-photon collagen crosslinking: Why more is better

Reviewed by Seok Hyun Yun, PhD, and Sheldon J.J. Kwok, BA

Cambridge, MA—Investigators at five top research centers have developed a new light-based polymerization, two-photon crosslinking (2P-CXL) that mechanically strengthens corneal tissue in situ without damaging surrounding untreated tissue.

CXL is used extensively in Europe and Canada for treating patients with keratoconus and has recently received FDA approval in the United States.

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The currently used single-photon CXL process typically uses ultraviolet light to treat the cornea. 2P-CXL differs from standard CXL in that it uses two-photon absorption-mediated processes using near infrared light supplied by a femtosecond laser, according to Seok Hyun Yun, PhD, who explained that this technologic advance offers the benefit of “far superior spatial resolution that is confined to the focal volume.”

This technology itself, while not entirely new, has been used for a liquid-based, three-dimensional printing process, in the fabrication of micro-optic components, and hydrogel-based cellular scaffolds.

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However, its newest application is for treatment of soft biologic tissue.

To date, results have been reported with artificial cardiac tissue and collagen hydrogels, and a previous study reported using 2P-CXL in corneal tissue in which changes in collagen second harmonic generation were seen but no evidence of tissue stiffening.

Dr. Yun and colleagues have moved another step forward in a study in which they showed spatially selective 2P-CXL of intact tissue for the first time. The investigators reported their findings in the journal Optica (2016;3:469-472).

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