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. It was suggested that artificial cross-linking may have a similar effect, and be particularly useful in the management of conditions where the strength of the cornea is compromised, such as keratoconus or post-LASIK ectasia. Over recent years, riboflavin/UVA corneal cross-linking has been widely adopted, refined and applied in a range of corneal surgeries and pathologies.

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, genipin and aliphatic beta-nitro alcohols are also being investigated.