Collagen is the most abundant protein in mammalian and forms various types of tissues. On ocular surface, sclera, limbus and cornea are composed with fibril form collagen. However, unlike other connective tissues with high opacity, cornea has extraordinary high transparency which originates from the regular arrangement of collagen fibers within cornea. Cornea is responsible for 80% of focusing power of our vision and any corneal damage can cause severe vision loss. The high transparency of cornea makes it difficult to probe it without invasive processes, especially stromal structure alternations. Collagen, however, is an effective second harmonic generator due to its non-centrosymmetric molecule structure and can be visualized with nonlinear optical process without labeling. In addition, the deeper penetration and point like effective volume of SHG can also provide 3-dimensional information with minimum invasion. Backward SHG imaging has been approved effectively demonstrating structure alternation in infective keratitis, thermal damage in cornea, corneal scar, post refractive surgery wound healing and keratoconus which is also a main complication after refractive surgery. In practical, backward SHG has the potentiality to be developed as clinical examination modality.
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