METHODS AND APPARATUS FOR INTRAOCULAR BRACHYTHERAPY

• US 20070118010A1
• Filed: 11/15/2006
• Published: 05/24/2007
• Est. Priority Date: 02/11/2005
• Status: Active Grant

• Current Assignee: Oraya Therapeutics, Inc.
• Original Assignee: Neovista, Inc.
• Inventors: Trip, Roelof, Pintaske, Rainer, Larsen, Charles, Woodward, Benjamin, Hillstead, Richard, Fritz, Eberhard, Anderson, Cory, Hendrick, John
• Granted Patent: US 7,803,103 B2
• Time in Patent Office: Days
• US Class Current: 600/3
• CPC Class Codes: A61N 2005/1058 using ultrasound imaging
• CPC Class Codes: A61N 5/1007 Arrangements or means for the introduction of sources into the body
• CPC Class Codes: A61N 5/1017 Treatment of the eye, e.g. for "macular degeneration"
• CPC Class Codes: A61N 5/1049 for verifying the position of the patient with respect to the radiation beam

Abstract

Methods and apparatus for intraocular brachytherapy are disclosed in which a cannula is introduced into the eye for delivery of radiation to a target tissue. Techniques for properly locating the cannula with respect to the target tissue, for protecting non-target tissue, for regulating heat generated by x-ray emitters, and for combining therapies are disclosed.

Claims

1. A device for local intraocular delivery of radiation to a target tissue comprising:

a cannula sized for insertion into an eye and having a proximal end and a distal end;

a radiation-emitting source adapted to be located in the distal end of the cannula; and

an ultrasound transducer located in the distal end of the cannula.

2. The device of claim 1 wherein the ultrasound transducer is located in the distal end of the catheter proximal to the radiation-emitting source.

3. The device of claim 1 wherein the ultrasound transducer is located in the distal end of the cannula distal to the radiation-emitting source.

4. A method of positioning a device according to claim 1 for local delivery of radiation to intraocular target tissue comprising:

calibrating the ultrasound transducer in accordance with a predetermined spacing for the distal end of the cannula from the target tissue so as to generate a signal when the predetermined spacing is achieved;

introducing the cannula into an eye through an access site on the eye; and

moving the distal end of the cannula toward the target tissue until the signal generated by the ultrasound transducer is perceived by a user.

5. The method of claim 4 wherein the signal generated by the ultrasound transducer is an audible signal.

6. The method of claim 4 wherein the signal generated by the ultrasound transducer is a visual signal.

7. A method of positioning a first cannula within an eye for delivery of a therapeutic treatment to a target tissue within the eye comprising:

introducing the first cannula into the eye through an access site on the eye;

introducing a second cannula into the eye through an access site on the eye, the second cannula including an ultrasound transducer;

positioning the distal end of the first cannula between the ultrasound transducer associated with the second cannula and the target tissue; and

moving the distal portion of the first cannula toward the target tissue until a predetermined spacing between the distal end of the first cannula and the target tissue is achieved, at which time a signal is generated by the ultrasound transducer.

8. The method of claim 7 wherein the signal generated by the ultrasound transducer is an audible signal.

9. The method of claim 7 wherein the signal generated by the ultrasound transducer is a visual signal.

10. The method for positioning a cannula for the intraocular delivery of a therapeutic treatment to a target tissue within an eye comprising:

providing the cannula with a compliant inflatable balloon that obtains a predetermined size when inflated to a specified pressure, the predetermined size corresponding to a desired spacing between the cannula and the target tissue for the delivery of the therapeutic treatment;

introducing the cannula into the eye through an access site on the eye;

inflating the balloon to the specified pressure; and

advancing the cannula toward the target tissue until the target tissue is contacted by the inflated balloon.

11. The method of claim 10 wherein the balloon is inflated with a fluid having a density lower than the density of the fluid displaced by the inflation of the balloon.

12. The method of claim 10 comprising selecting the balloon to have a shape corresponding to the shape of the target tissue.

13. A method for positioning a cannula for the intraocular delivery of a therapeutic treatment to a target tissue within an eye comprising:

providing the cannula with a non-compliant inflatable balloon that obtains a predetermined sized upon inflation, the predetermined size corresponding to the desired spacing between the cannula and the target tissue for delivery of the therapeutic treatment;

introducing the cannula into the interior of the eye through an access site in the surface of the eye;

inflating the balloon; and

advancing the cannula toward the target tissue until the target tissue is contacted by the inflated balloon.

14. The method of claim 13 wherein the balloon is inflated with a fluid having a density less than the density of the fluid displaced by the inflation of the balloon.

15. The method of claim 13 comprising selecting the balloon to have a shape corresponding the shape of the target tissue.

16. A method for positioning a cannula having a distal end for the intraocular delivery of a therapeutic treatment to a target tissue within an eye filled with a first fluid comprising:

displacing the first fluid adjacent the target tissue with a known volume of a second fluid having a density different from the density of the first fluid so as to create a visual interface between the first fluid and second fluid spaced a predetermined distance from the target tissue;

introducing the cannula into the eye through an access site on the eye; and

advancing the cannula toward the interface of the first fluid and the second fluid until the distal end of the cannula contacts the interface.

17. The method of claim 16 further comprising providing the cannula with a visible mark proximal to the distal end and advancing the cannula through the interface of the first fluid and the second fluid until the visible mark on the cannula is aligned with the interface of the first fluid and the second fluid.

18. The method of the claim 16 or 17 in which the density of the second fluid is greater than the density of the first fluid.

19. The method of claim 16 or 17 in which the density of the second fluid is less than the density of the first fluid.

20. A method of positioning a first cannula having a distal end for the intraocular delivery of a therapeutic treatment to a target tissue within an eye having a lens so that the distal end of the cannula is in contact with the target tissue comprising:

introducing a second cannula into the eye through an access site on the eye, the second cannula having a light source that projects a beam of light toward the target tissue;

introducing the first cannula into the eye through a second access site on the eye so that the distal end of the first cannula is between the second cannula and the target tissue within the beam of the light projected toward the target tissue by the second cannula so that a shadow is cast by the distal end of the first cannula that falls on the target tissue, the shadow being observable through the lens of the eye; and

advancing the distal end of the first cannula toward the target tissue until the shadow cast by the distal end of the first cannula coincides with the distal end of the first cannula as viewed through the lens, thus indicating contact of the distal end of the first cannula with the target tissue.

22. The device of claim 20 or 21 wherein the source of light is a light pipe.

23. The device of claim 20 or 21 wherein the source of light is a laser.

21. A device for local intraocular delivery of a therapeutic treatment to a target tissue comprising:

a cannula sized for intraocular insertion into an eye and having a proximal end and a distal end;

a therapeutic treatment source adapted to be located in the distal end of the cannula, the source intended to be spaced a predetermined distance from the target tissue for the delivery of the therapeutic treatment; and

at least one source of light adapted to project two visible beams of light out of the distal end of the cannula, the beams of light forming an intersection such that when the intersection is coincident with the target tissue, the treatment source is spaced the predetermined distance from the target tissue.

24. A device for local intraocular delivery of a therapeutic treatment to a target tissue comprising:

a cannula sized for insertion into an eye and having a surface that is electropolished to reduce friction.

25. A device for local intraocular delivery of a therapeutic treatment to a target tissue comprising:

a cannula sized for insertion into an eye and having a surface that is dimpled to reduce friction.

26. A device for local intraocular delivery of a therapeutic treatment to a target tissue comprising:

a cannula sized for insertion into an eye and having a surface to which a liquid lubricant is applied to reduce friction.

27. The device of claim 26 wherein the liquid lubricant is glycerin.

28. A device for local intraocular delivery of therapeutic treatment to a target tissue comprising:

a cannula sized for insertion into an eye and having a surface to which a low-friction coating is applied.

29. The device of claim 28 wherein the low-friction coating is polytetrafluoroethylene.

30. A method of delivering x-ray radiation to a target tissue in an eye from the interior of the eye with an x-ray delivery device having an elongated probe with an x-ray emitter associated therewith comprising:

introducing the probe into the eye through an access site on the eye;

positioning the probe with respect to the target tissue; and

intermittently activating the x-ray emitter until a desired radiation dose is delivered to the target tissue.

31. The method of claim 30 wherein the x-ray emitter is activated at a known frequency.

32. The method of claim 30 wherein the x-ray emitter is activated and deactivated by a thermocouple located interior of the eye.

33. The method of claim 32 wherein the thermocouple is associated with the probe.

34. A device for local intraocular delivery of x-ray radiation to a target tissue comprising:

an elongated probe sized for insertion into an eye having a proximal end and a distal end;

an x-ray emitter associated with the distal end of the probe; and

a heat exchanger associated with the distal end of the probe.

35. The device of claim 34 wherein the heat exchanger comprises a flow path for receiving a cooled fluid.

36. The device of claim 35 wherein the heat exchanger comprises a sheath.

37. The device of claim 34 wherein the probe is made of an material having a relatively low coefficient of thermal conductivity.

38. A device for local intraocular delivery of radiation to a target tissue comprising:

a probe sized for insertion into an eye and having a proximal end and a distal end;

a radiation-emitting source having a predetermined length adapted to be located in the distal end of the probe, the radiation-emitting source having a proximal end and a distal end; and

a filter associated with the distal end of the probe that blocks a greater amount of radiation at the distal end of the radiation-emitting source than at the proximal end of the radiation-emitting source so that a generally-symmetrical dose profile is delivered to the target tissue by the radiation emitting source when the distal end of the probe is orientated at an angle with respect to a plane defined generally by the target tissue.

39. The device of claim 38 wherein the filter is greater in thickness adjacent the distal end of the radiation-emitting source than adjacent the proximal end of the radiation-emitting source.

40. The device of claim 38 wherein the filter has a higher density adjacent the distal end of the radiation-emitting source than adjacent the proximal end of the radiation-emitting source.

41. A device for local intraocular delivery of x-ray radiation to target tissue comprising:

a cannula sized for insertion into an eye and having a proximal end and a distal end;

a cathode within the distal end of the cannula;

an anode on the distal end of the cannula; and

a layer of high density metal associated with the distal end of the cannula in proximity to the anode for attenuating x-ray radiation, the metal layer having an area of reduced thickness therein to allow x-ray radiation to pass therethrough substantially unimpeded, the opening being located and sized to direct and confine the x-ray radiation to the target tissue.

42. A device for local intraocular delivery of x-ray radiation to a target tissue comprising:

a cannula sized for insertion into an eye and having a proximal end and a distal end;

a cathode within the distal end of the catheter;

an anode on the distal end of the cannula; and

the distal end of the cannula and the anode having a hemispherical shape.

43. A device for local intraocular delivery of x-ray radiation to a target tissue comprising:

a cannula sized for insertion into an eye and having a proximal end and a distal end;

a cathode within the distal end of the cannula;

an anode on the distal end of the cannula; and

the distal end of the cannula and the anode being generally planar and being orientated generally perpendicular to a longitudinal axis of the distal end of the cannula.

44. The device of claim 43 wherein the distal end of the cannula comprises an x-ray permeable material.

45. The device of claim 44 wherein the distal end of the cannula comprises an x-ray blocking material for attenuating the x-ray radiation received by the target tissue.

46. A method for treating a target tissue located on the interior of an eye with radiation and a further therapeutic agent comprising:

providing an intraocular probe containing an ionizing radiation source;

introducing the intraocular probe into the interior of the eye in proximity to the target tissue;

irradiating the target tissue with a prescribed dose of ionizing radiation; and

selecting the further therapeutic agent from one or more of anti-VEGF pharmaceuticals, small interfering RNA, photodynamic therapy, corticosteroids, angiostatic steroids, implants of encapsulated human ciliary neurotrophic factor, VEGF traps, dietary supplements, anti-inflammatory medicines, interferon, antimetabolite drugs, aminosterols, protein kinase beta inhibitors, fluocinolan implants, monoclonal antibodies and anti-oxidants;

treating the target tissue with a prescribed first dose of the further therapeutic agent; and

wherein the irradiation of the target tissue and the treatment of the target tissue with the further therapeutic agent occur within a period of time of 14 days or less.

47. The method of claim 46, in which the period of time is 4 hours or less.

48. The method of claim 46 in which the further therapeutic agent is administered prior to the irradiation of the target tissue.

49. The method of claim 46 in which the further therapeutic agent is administered following the irradiation of the target tissue.

50. The method of claims 46, in which the radiation source is a beta emitter.

51. The method of claims 46, in which the radiation source is an x-ray emitter.

52. The method of claims 46, in which the radiation dose is 20 to 35 Gy.

53. The method of claim 52, in which the radiation dose is delivered at a rate is 5 to 30 cGy/sec.

54. The method of claim 52, in which radiation dose is delivered at a rate of 8 to 15 cGy/sec.

55. The method of claims 46, in which a second dose of the further therapeutic agent is given after the first dose.

56. The method of claim 55, in which the second dose of the further therapeutic agent is given 2 to 8 weeks after the first dose.

57. The method of claim 55, in which the second dose of the further therapeutic agent is given 25 to 35 days after the first dose.