Amelioration of vitrectomy-induced cataracts
View Patent ↗Methods to prevent, inhibit, or slow the development of vitrectomy-induced cataracts are disclosed. The methods comprise administering to the eye of a subject a composition comprising an ophthalmologically acceptable carrier or diluent and at least one hydroxylamine compound in a therapeutically sufficient amount to prevent, inhibit, or slow the development of a vitrectomy-induced cataract in the subject to which the composition is administered.
1. A method for inhibiting the development of a vitrectomy-induced cataract comprising administering to the vitreous of a subject undergoing a vitrectomy a composition comprising an ophthalmologically acceptable carrier or diluent and at least one hydroxylamine compound of the following formula:
wherein R 3 and R 4 are, independently C 1 to C 3 alkyl; and
where R 1 and R 2 , taken together, or R 3 and R 4 , taken together, or both may be cycloalkyl;
R 5 is H, OH, or C 1 to C 6 alkyl;
R 6 is C 1 to C 6 alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl;
R 7 is C 1 to C 6 alkyl, alkenyl, alkynyl, substituted alkyl, alkenyl, cycloalkyl, or heterocycle or where R 6 and R 7 , or R 5 , R 6 and R 7 , taken together, form a carbocycle or heterocycle having from 3 to 7 atoms in the ring;
in a therapeutically sufficient amount to inhibit the development of a vitrectomy-induced cataract in the subject.
2. The method of claim 1 , wherein the composition is administered before, during or after the vitrectomy is performed.
3. The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 0.1 μM to about 10 mM.
4. The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 1 μM to about 5 mM.
5. The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 10 μM to about 2.5 mM.
6. The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 50 μM to about 1 mM.
7. The method of claim 1 wherein the composition is administered to achieve in the eye tissue and fluids of the subject a concentration of about 1 μM to about 100 μM.
8. The method of claim 1 wherein the hydroxylamine compound is 1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride.
9. The method of claim 1 further comprising administering a reducing agent to the vitreous of the subject.
10. The method of claim 9 , wherein the reducing agent is coadministered with the composition.
11. The method of claim 9 , wherein the reducing agent is formulated as part of the composition.
12. The method of claim 9 , wherein the reducing agent is administered separately from the composition.
13. The method of claim 9 , wherein the reducing agent is a sulfhydryl compound.
14. The method of claim 13 , wherein the reducing agent is mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine or glutathione.
15. The method of claim 1 , wherein the composition is administered by injection.
16. The method of claim 1 , wherein the composition is coadministered with irrigation solution during vitrectomy.
17. The method of claim 1 , wherein the composition is formulated as part of the irrigation solution during vitrectomy.
18. The method of claim 1 further comprising administering to the vitreous of the subject after said vitrectomy a composition comprising an ophthalmologically acceptable carrier or diluent and at least one hydroxylamine compound of the following formula:
wherein R 3 and R 4 are, independently C 1 to C 3 alkyl; and
where R 1 and R 2 , taken together, or R 3 and R 4 , taken together, or both may be cycloalkyl;
R 5 is H, OH, or C 1 to C 6 alkyl;
R 6 is C 1 to C 6 alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl;
R 7 is C 1 to C 6 alkyl, alkenyl, alkynyl, substituted alkyl, alkenyl, cycloalkyl, or heterocycle or where R 6 and R 7 , or R 5 , R 6 and R 7 , taken together, form a carbocycle or heterocycle having from 3 to 7 atoms in the ring;
in a therapeutically sufficient amount to inhibit the development of a vitrectomy-induced cataract in the subject.
19. The method of claim 18 , wherein the composition administered after the vitrectomy is performed to achieve in the vitreous tissue and fluids of the subject a hydroxylamine concentration of about 0.1 μM to about 10 mM.
20. The method of claim 18 , wherein the composition administered after the vitrectomy is injected into the vitreous.
21. The method of claim 18 , wherein said composition administered after said vitrectomy is an eyewash, eye drop or ophthalmic ointment.
22. The method of claim 18 , wherein the composition administered after said vitrectomy is administered from a polymeric disc or wafer placed on the surface of the eye.
23. The method of claim 18 wherein the hydroxylamine compound is 1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride.