The potential of ultraviolet-A light (UVA) to cross-link tissues in the presence of the non-toxic photosensitising agent riboflavin had been known for some time, but it was not until 1998 that a group from Dresden suggested it as a potential therapeutic treatment to strengthen the corneal stroma.  The concept was based on the observation that naturally occurring protein cross-linking, which accelerates with age, strengthens and stiffens the cornea. This suggested that artificial cross-linking may have a similar effect, particularly in conditions such as keratoconus, where the constituent collagen is prone to enzymatic degradation and fibrillar slippage.  Over recent years, cross-linking the cornea using riboflavin and ultraviolet A light has been widely adopted, refined and applied in a range of corneal surgeries and pathologies where the strength of the cornea might be compromised.

Although riboflavin/UVA cross-linking is now considered to be the standard care treatment for progressive Keratoconus and post-LASIK ectasia, the potential of other collagen cross-linking therapies such as Rose Bengal with green light, bacteriochlorophyll derivative WST11 with near infrared light and  aliphatic beta-nitro alcohols are also being investigated.