**1. Introduction**

Keratoconus is a bilateral, asymmetric, progressive ectatic disease of the cornea characterized by progressive corneal thinning which can lead to visual impairment and blindness as corneal protrusion progresses, irregular astigmatism increases and corneal scar occurs [1]. Keratoconus is often under the radar because of decreased awareness, underdiagnosis and undertreatment. The exact pathological mechanism remains unknown, but both genetic and environmental factors may contribute to development and progression of this disease [2]. The reported evidences of pathogenesis of keratoconus include histochemistry, biomechanics, enzymology, proteomics, and molecular genetics [2]. The disease process starts with fragmentation of the epithelial basement membrane, fibrillation of Bowman's membrane and anterior stroma [3]. Bowman's membrane breakage occurs later together with epithelial abnormality resulting in proteolytic enzymes release that weakens corneal stromal collagen and stromal thinning [3]. The reported prevalence of keratoconus varies between countries and ethnicities, in which Asian is higher than Caucasian about 4.4 to 7.5 times [4, 5]. The prevalence is ranged from 0.3 in 100, 000 to 2300 in 100,000 in Russia and India respectively [6]. However, the prevalence may be higher in tertiary eye care center or refractive

surgery center [7]. Keratoconus is more common in men than women, although both gender are affected [5]. The onset of symptoms usually presents during adolescent and may progress until the 30s. Keratoconus is associated with eye rubbing such as in allergic conjunctivitis, floppy eyelid syndrome, obstructive sleep apnea, Down's syndrome and Leber congenital amaurosis [1, 8–10]. Genetic predisposition accounts for an increased risk of keratoconus in patient that has a positive family history about 15 to 67 times [11].
