SYSTEMS, METHODS, AND COMPOSITIONS FOR CROSS-LINKING
Various agents and additives for cross-linking treatments are identified in disclosed studies. The characteristics of the various agents and additives may be advantageously employed in formulations applied in cross-linking treatments of the eye. In some embodiments, riboflavin is combined with Iron(II) to enhance the cross-linking activity generated by the riboflavin. In other embodiments, cross-linking treatments employ an Iron(II) solution in combination with a hydrogen peroxide pre-soak. In yet other embodiments, 2,3-butanedione is employed to increase the efficacy of corneal cross-linking with a photosensitizer, such as riboflavin. In further embodiments, folic acid is employed in combination with a photosensitizer, such as riboflavin, to enhance cross-linking activity. In yet further embodiments, 2,3-butanedione, folic acid, a quinoxaline, a quinoline, dibucaine, Methotrexate, menadione, or a derivative thereof is applied as a cross-linking agent.
1 . A composition for applying therapy to a cornea of an eye, comprising:
a cross-linking agent that generates cross-linking activity in the cornea in response to exposure to a photo-activating light; and
at least one additive different from the cross-linking agent and selected from the group consisting of iron, copper, manganese, chromium, vanadium, aluminum, cobalt, mercury, cadmium, nickel, arsenic, 2,3-butanedione, and folic acid, wherein the at least one additive enhances the cross-linking activity generated by the cross-linking agent.
2 . The composition of claim 1 , wherein the cross-linking agent is selected from the group consisting of riboflavin, 2,3-butanedione, folic acid, quinoxalines, quinolines, dibucaine, Methotrexate, menadione, and derivatives thereof.
3 . The composition of claim 1 , wherein the at least one additive is iron.
4 . The composition of claim 3 , wherein the iron is provided by FeSO 4 .
5 . The composition of claim 1 , wherein the at least one additive is 2,3-butanedione.
6 . The composition of claim 1 , wherein the at least one additive is folic acid.
7 . A method for applying therapy to a cornea of an eye, comprising:
applying a composition to the cornea, the composition including
a cross-linking agent that generates cross-linking activity in the cornea in response to exposure to a photoactivating light; and
at least one additive different from the cross-linking agent and selected from the group consisting of iron, copper, manganese, chromium, vanadium, aluminum, cobalt, mercury, cadmium, nickel, arsenic, 2,3-butanedione, and folic acid; and
applying photoactivating light to the cornea to generate cross-linking activity in the cornea,
wherein the at least one additive enhances the cross-linking activity generated by the cross-linking agent.
8 . The method of claim 7 , wherein the cross-linking agent is selected from the group consisting of riboflavin, 2,3-butanedione, folic acid, quinoxalines, quinolines, dibucaine, Methotrexate, menadione, and derivatives thereof.
9 . The method of claim 7 , wherein the at least one additive is iron.
10 . The method of claim 9 , wherein the iron is provided by FeSO 4 .
11 . The method of claim 7 , wherein the at least one additive is 2,3-butanedione.
12 . The method of claim 7 , wherein the at least one additive is folic acid.
13 . The method of claim 7 , wherein the photoactivating light is ultraviolet light.
14 . The method of claim 7 , wherein the photoactivating light is pulsed.
15 . The method of claim 7 , further comprising applying oxygen to the cornea.
16 . A method for applying therapy to a cornea of an eye, comprising:
applying a cross-linking agent to the cornea, the cross-linking agent being selected from the group consisting of 2,3-butanedione, folic acid, quinoxalines, quinolines, dibucaine, Methotrexate, menadione, and derivatives thereof; and
applying photoactivating light to the cornea to generate cross-linking activity in the cornea.
17 . The method of claim 16 , wherein the photoactivating light is ultraviolet light.
18 . The method of claim 16 , wherein the photoactivating light is pulsed.
19 . The method of claim 16 , further comprising applying oxygen to the cornea to control the cross-linking activity generated by the cross-linking agent.
20 . A method for applying therapy to a cornea of an eye, comprising:
applying a hydrogen peroxide to the cornea; and
applying an iron solution to the cornea after applying the hydrogen peroxide, the hydrogen peroxide and iron solution combining to generate cross-linking activity in the cornea.