Method of treating ophthalmic disorders using TGF -.beta.

• US 5,767,079 A
• Filed: 08/27/1996
• Issued: 06/16/1998
• Est. Priority Date: 07/08/1992
• Status: Expired due to Term

• Current Assignee: Celtrix Pharmaceuticals, Inc. (Insmed Incorporated)
• Original Assignee: Celtrix Pharmaceuticals, Inc. (Insmed Incorporated)
• Inventors: Glaser, Bert M., Hanham, Ann F., Pharriss, deceased, Bruce B., Ksander, George A.
• Primary Examiner(s): Sayala, Chhaya D.
• Application Number:
  US08/705,694
• Time in Patent Office: 658 Days
• Field of Search: 514/12, 514/21, 530/399
• US Class Current: 424/427
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]

Abstract

This invention is a method for the treatment of ophthalmic disorders. The method is suitable for treatment of a variety of disorders including macular holes, macular degeneration, and retinal detachment and tears, cataracts, and corneal and scleral injuries. The method entails application of an effective amount of Transforming Growth Factor-β (TGF-β) to the affected region.

Claims

1. A method of improving the ocular vision in retinal disorders of the mammalian eye, said disorders characterized by an insufficiency, loss, or impending loss of fibrous tissue, said method comprising administering to the mammal is eye about 1.1 to 10 μ

g of transforming growth factor beta (TGF-β

).

2. The method of claim 1 wherein the TGF-β

is TGF-β

2.

3. The method of claim 1 wherein TGF-β

is administered by a mode of administration selected from the group consisting of intraocular injection, subretinal injection, subscleral injection, intrachoroidal injection, subconjunctival injection, topical administration, oral administration and parenteral administration.

4. The method of claim 3 wherein the intraocular administration comprises placing TGF-β

solution on, under, over, or in the retinal disorder, or any combination thereof.

5. The method of claim 1 further comprising the following steps:

removing the vitreous humor from the eye;

removing the epiretinal membrane, if present; and

administering a concentrated solution of TGF-β

by cannula to place the solution immediately over the retinal disorder.

6. The method of claim 1 wherein TGF-β

is administered once.

7. The method of claim 1 wherein TGF-β

is administered repeatedly until the retinal disorder has ameliorated.

8. The method of claim 1 wherein the dosage of TGF-β

is greater than about 100 ng.

9. The method of claim 1 wherein the dosage of TGF-β

is greater than 1500 ng.

10. The method of claim 1 wherein the retinal disorder is a macular hole.

11. The method of claim 1 wherein the retinal disorder is macular degeneration.

12. The method of claim 1 wherein the retinal disorder is a retinal tear.

13. The method of claim 1 wherein the retinal disorder is subretinal neovascularization.

14. A method of maintaining or improving the ocular vision in macular degeneration of the mammalian eye, said method comprising administering to said mammal at least 1.1 μ

g of TGF-β

effective to stabilize or improve vision.

15. A method of maintaining or improving the ocular vision in cystoid macular edema, said method comprising administering to said mammal at least 1.1 μ

g of TGF-β

effective to stabilize or improve vision.

16. A method of treating retinal disorders to improve vision, the retinal disorders being characterized by decreased connective or fibrous tissue, said method comprising the following steps:

removing the vitreous humor of the eye;

peeling off the epiretinal membrane, if present; and

administering a dose of a concentrated solution of TGF-β

2 by cannula to place the TGF-β

2 solution immediately over the portion of the retina requiring treatment, said dose comprising at least 1.1 μ

g of TGF-β

2.

17. A method for treating a mammal with an ophthalmic disorder associated with impaired healing, said method comprising administering orally, locally or systemically, to said mammal a pharmaceutical composition of TGF-β

, said composition being administered in an amount sufficient to improve healing in the eye in a dosage range comprising at least 1.1 μ

g to 10 μ

g of TGF-β

.

18. The method of claim 17 wherein the ophthalmic disorder is selected from the group consisting of retinal edema, retinal wounds, macular degeneration, secondary cataracts, corneal epithelial wounds and Sjogren'"'"'s syndrome.

19. The method of claim 17 wherein the TGF-β

is TGF-β

2.

20. The method of claim 19 wherein the TGF-β

2 is recombinant human TGF-β

2.

21. The method of claim 17 wherein the administration is performed by intraocular, subretinal, subscleral, intrascleral, intrachoroidal injection, or any combination thereof.

22. The method of claim 17 wherein the administration is performed by application to the cornea or sclera.

23. The method of claim 22 wherein the application to the cornea or sclera is placement of a timed release dosage form in the cul de sac.

24. The method of claim 17 wherein the dosage of the pharmaceutical composition is that amount which enhances healing without excessive fibroproliferation.

25. The method of claim 17 wherein the dosage of the pharmaceutical composition is that amount which enhances healing of the ocular condition and improves the mammal'"'"'s symptoms.

26. The method of claim 17 wherein the dosage of the pharmaceutical composition administered is about 1100 to 5000 nanograms of TGF-β

to the eye.

27. A method for treating a mammal that has undergone or is about to undergo or is undergoing ophthalmic surgery to promote healing without excessive scarring, said method comprising administering to said mammal TGF-β

, said TGF-β

being administered in an amount sufficient to promote healing without excessive scarring in a dosage range of at least 1.1 μ

g to 10 μ

g of TGF-β

2.

28. The method of claim 27, wherein the TGF-β

is administered by direct application in the surgical wound.

29. The method of claim 27, wherein the TGF-β

is administered by intraocular, subretinal, subscleral, intrascleral, intrachoroidal injection, or any combination thereof.

30. The method of claim 29, wherein the TGF-β

is administered in a solution.

31. The method of claim 29, wherein the TGF-β

is administered in a controlled release formulation.

32. The method of claim 27, wherein the TGF-β

is TGF-β

2.

33. The method of claim 27, wherein the TGF-β

2 is recombinant human TGF-β

2.

34. The method of claim 27, wherein the ophthalmic surgery is cataract extraction.

35. The method of claim 27, wherein the ophthalmic surgery is corneal transplantation.

36. The method of claim 27, wherein the ophthalmic surgery is glaucoma filtration surgery.

37. The method of claim 27, wherein the ophthalmic surgery is surgery to correct refraction.

38. The method of claim 37, wherein the surgery to correct refraction is radial keratotomy.

39. The method of claim 27 wherein the dosage of the pharmaceutical composition administered is at least about 1100 nanograms of TGF-β

per eye.

40. A method of treating a mammal for ocular neovascularization, said method comprising administering to a mammal an effective amount of TGF-β

2 in a dosage range of from 1.1 μ

g to μ

g of TGF-μ

2.

41. The method of claim 40 wherein the TGF-β

2 is administered intravenously, topically, intraocularly, intramuscularly, locally or in an ocular device.

42. The method of claim 40 wherein the ocular neovascularization is selected from the group consisting of neovascularization of the cornea, iris, retina, vitreous and choroid.

43. The method of claim 42 wherein the corneal neovascularization is caused by trauma, chemical burns or corneal transplantation.

44. The method of claim 42 wherein the neovascularization of the iris is caused by diabetic retinopathy, vein occlusion, ocular tumor or retinal detachment.

45. The method of claim 42 wherein the retinal neovascularization is caused by diabetic retinopathy, vein occlusion, sickle cell retinopathy, retinopathy of prematurity, retinal detachment, ocular ischemia or trauma.

46. The method of claim 42 wherein the intravitreal neovascularization occurs in diabetic retinopathy, vein occlusion, sickle cell retinopathy, retinopathy of prematurity, retinal detachment, ocular ischemia or trauma.

47. The method of claim 42, wherein the choroidal neovascularization occurs in retinal or subretinal disorders of age-related macular degeneration, presumed ocular histoplasmosis syndrome, myopic degeneration, angioid streaks or ocular trauma.

48. A method of treating uveitis in a mammal, said method comprising injecting intraocularly in said mammal an effective amount of TGF-β

2 in a dosage range of at least 1.1 μ

g to 10 μ

g of TGF-β

2.