In conclusion, this study discovered three novel variants in three ECM-related genes respectively in the Chinese Han population (c.95 G > A in LOX, c.1372 C > T in COL5A1, and c.476 C > T in TIMP3), and the results of QPCR indicated that the abnormally low expression of LOX and TIMP3 might contribute to the development of KC, all these highlighting the importance of ECM in the pathogenesis of KC. Here, TIMP3 is linked to keratoconus.