Keratoconus is estimated to affect 1 in 500 to 2,000 individuals worldwide.

The cause of keratoconus is unknown. Researchers have studied many different factors, both genetic and environmental, that are thought to influence the risk of developing keratoconus.

The environmental factors that may contribute to keratoconus include excessive eye rubbing and the tendency to develop allergic disorders (atopy).

Excessive and vigorous eye rubbing can cause trauma to the cornea and may lead to its thinning. However, it is unclear whether eye rubbing leads to keratoconus or if eye rubbing is a response to eye discomfort in the early stages of the condition. If eye rubbing is not involved in the development of keratoconus, it likely contributes to worsening of the condition.

Approximately one-third of individuals with keratoconus have an allergic disorder, although it is unclear how allergic disorders are related to the development of keratoconus. Allergies might trigger eye rubbing, which can aggravate eye problems.

Changes in multiple genes have been associated with developing keratoconus. Many of these variants have been found only in small populations or single families. In most individuals with keratoconus, a combination of genetic and environmental factors is needed for the condition to develop. However, some affected individuals seem to have a largely environmental cause for the condition while others seem to have a largely genetic cause. Individuals with a relative who has keratoconus have an increased risk of developing the condition compared to people without a family history.

More than a dozen genes have been associated with keratoconus. These genes have varied functions. The most frequently associated genes play roles in eye development, the formation and structure of the cornea, the intricate lattice of proteins and other molecules that forms in the space between cells (extracellular matrix), an immune system response called inflammation, and the regulation of cell growth. It is thought that a disruption in one of these processes, in combination with an environmental trigger, may lead to the development of keratoconus.

Keratoconus can be a feature of genetic syndromes, such as Leber congenital amaurosis and arterial tortuosity syndrome. When it is part of a syndrome, keratoconus is caused by the same genetic mutation that causes the syndrome. Mutations in the genes that cause syndromes with keratoconus have not been found to cause keratoconus without other features.