Ophthalmic solution for protecting internal structures of the eyeball against UV-A rays or for the treatment of keratoconus with a trans-epithelial cross-linking technique

1. A method for treating keratoconus in an eyeball of a subject in need thereof, the method comprising:

applying an ophthalmic solution to the corneal epithelium of the eyeball of the subject, wherein the ophthalmic solution comprises riboflavin and D-alfa-tocopheryl polyethylene-glycol 1000 succinate (TPGS), wherein the riboflavin concentration of the ophthalmic solution is at least about 0.1% and the TPGS concentration of the ophthalmic solution is at least about 10 mg % ml, and

administering UV-A rays to the eyeball of the subject, that has been treated with the ophthalmic solution, to induce collagen cross-linking in the cornea of the eyeball; and

wherein the eyeball of the subject has an intact corneal epithelium.

2. The method of claim 1 , wherein the ophthalmic solution further comprises a compound selected from the group consisting of L-proline, glycine, lysine hydrochloride, L-leucine and L-arginine.

3. The method of claim 1 , wherein the ophthalmic solution comprises a riboflavin-dextran solution, and the TPGS ranges in concentration from 10 mg % to 2000 mg % ml, and the ophthalmic solution further comprises at least one of the following compounds:

(a) L-proline at a concentration in the range from 0.0001 mg % ml to 2000 mg % ml;

(b) glycine at a concentration in the range from 0.0001 mg % ml to 2000 mg % ml;

(c) lysine hydrochloride at a concentration in the range from 0.0001 mg % ml to 2000 mg % ml;

(d) L-leucine at a concentration in the range from 0.0001 mg % ml to 2000 mg % ml; and

(e) L-arginine in the range from 0.00001% to 0.5%; and

wherein the riboflavin-dextran solution comprises 0.5% riboflavin.

4. The method of claim 1 , wherein the ophthalmic solution comprises a standard riboflavin-dextran solution, and the TPGS concentration is about 500 mg % ml; and the ophthalmic solution optionally further comprises at least one of the following compounds:

(a) L-proline at a concentration of about 0.1 mg % ml;

(b) glycine at a concentration of about 0.1 mg % ml;

(c) lysine hydrochloride at a concentration of about 0.05 mg % ml;

(d) L-leucine at a concentration of about 0.08 mg % ml;

(e) L-arginine at a concentration of about 0.1%; and

wherein the standard riboflavin-dextran solution comprises 0.1% riboflavin.

5. The method of claim 1 , wherein the ophthalmic solution is in the form of eye drops, ophthalmic gel, or in a form adapted to be applied on therapeutic contact lenses.

6. The method of claim 1 , wherein the ophthalmic solution further comprises a permeation enhancer.

7. The method of claim 1 , wherein the ophthalmic solution is administered to the cornea for an amount of time sufficient to allow permeation of the corneal stroma.

8. The method of claim 1 , which further comprises re-administering the ophthalmic solution to the treated eyeball of the subject and re-administering UV-A rays to the treated eyeball of the subject.

9. The method of claim 1 , wherein the TPGS content of the ophthalmic solution ranges in concentration from 10 mg % ml to 1000 mg % ml.

10. The method of claim 1 , wherein the ophthalmic solution further comprises dextran.

11. The method of claim 10 , wherein the riboflavin content of the ophthalmic solution is 0.1%.

12. The method of claim 1 , wherein the TPGS concentration of the ophthalmic solution is 500 mg % ml.

13. The method of claim 1 , wherein the ophthalmic solution is administered to the cornea for an amount of time sufficient to allow permeation of the cornea.