A method for controlling activation of Riboflavin applied to an eye includes applying the Riboflavin to a selected region of a cornea of the eye and initiating cross-linking activity in the selected region by activating the Riboflavin with pulsed light illumination. The pulsed light illumination has an irradiance, dose, and an on/off duty cycle. The irradiance, the dose, and the on/off duty cycle are adjusted in response to a determination of photochemical kinetic pathways for Riboflavin cross-linking activity and to control photochemical efficiency.