A method is provided for treating a targeted area of ocular tissue in a tissue-sparing manner comprising use of two or more therapeutic modalities, including thermal radiation source (such as an CW infrared fiber laser), operative in a wavelength range that has a high absorption in water, and photochemical collagen cross-linking (CXL), together with one or more specific system improvements, such as pen-operative feedback measurements for tailoring of the therapeutic modalities, an ocular tissue surface thermal control/cooling mechanism and a source of deuterated water/riboflavin solution in a delivery system targeting ocular tissue in the presence of the ultraviolet radiation. Additional methods of rapid cross-linking (RXL), are provided that enables cross-linking (CXL) therapy to be combined with thermal therapy.