Treatment of age-related macular degeneration

• US 7,351,193 B2
• Filed: 09/22/2005
• Issued: 04/01/2008
• Est. Priority Date: 08/06/2003
• Status: Expired due to Term

• Current Assignee: Nucletron Operations BV
• Original Assignee: Xoft Incorporated (Elekta AB)
• Inventors: Lovoi, Paul A., Smith, Peter C., Forman, Michael
• Primary Examiner(s): Lacyk; John P
• Application Number:
  US11/234,824
• Publication Number:
  US 20060078087A1
• Time in Patent Office: 922 Days
• Field of Search: 600 1- 8, 600/452, 600/459, 128897-899, 378/65, 378/119
• US Class Current: 600/3
• CPC Class Codes: A61B 2090/306 using optical fibres
• CPC Class Codes: A61F 9/0079 using non-laser electromagnetic radiation, e.g. non-coherent light or microwaves
• CPC Class Codes: A61N 2005/0651 Diodes
• CPC Class Codes: A61N 2005/0659 infrared
• CPC Class Codes: A61N 2005/1022 Generators, e.g. X-ray tubes
• CPC Class Codes: A61N 2005/1098 Enhancing the effect of the particle by an injected agent or implanted device
• CPC Class Codes: A61N 5/0601 Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61N 5/1001 using radiation sources introduced into or applied onto the body; brachytherapy
• CPC Class Codes: A61N 5/1017 Treatment of the eye, e.g. for "macular degeneration"

Abstract

Age-related macular degeneration is treated by radiation delivered from a miniature x-ray tube inserted via a catheter around the globe of the eye, to a position behind the macula. The process can employ an applicator with several parallel guides, inserted around the eye to receive the catheter with x-ray tube (or an isotope) at a matrix of different positions. Methods are described for properly locating the catheter and x-ray tube, using illumination on the catheter and viewing through the front of the eye, or sensors on the catheter and a scanned beam shone from the front of the eye. Fluorescent material excited by x-rays can also be used. Also described are methods and devices for immobilizing the probe once properly located in the eye, for standoff of the x-ray tube from the target tissue, and for achieving prescription radiation dose in the choroid while eliminating dose to adjacent tissues. The x-ray treatment can be enhanced using a radiosensitizing drug, and can be combined with PDT.

Claims

1. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina,

properly locating the catheter behind the macular region by activating one or more light sources on the catheter, and viewing the light sources using an optical instrument from the front of the eye, the light sources being visible through the sclera, choroid and retina, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

2. The method of claim 1, wherein the light sources at the catheter comprise optical fibers receiving light from a source of illumination at a console to which the fibers are connected.

3. The method of claim 2, wherein the optical fibers have angularly cleaved ends as said light sources at the catheter.

4. The method of claim 2, wherein the optical fibers are polished and wherein the light sources at the catheter include micro prism reflectors directing light from the optical fibers toward the front of the eye.

5. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina,

properly locating the distal end of the catheter behind the macular region by directing a preselected pattern of light toward the retina from the front of the eye, and detecting the pattern of light using detectors located near the distal end of the catheter, in such a way as to indicate a direction of movement for correction of the catheter'"'"'s position, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

6. The method of claim 5, wherein the pattern of light comprises repeated expanding rings of light.

7. The method of claim 5, wherein the pattern of light comprises a grid of light lines illuminated sequentially.

8. The method of claim 5, wherein the pattern of light comprises a color gradation pattern, with color indicating location.

9. The method of claim 5, wherein the pattern of light comprises a moving pattern of light and the method includes temporally sensing the position of the catheter by reference to the moving pattern.

10. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina, the switchable x-ray source comprising a miniature x-ray tube emitting a side-looking directional radiation,

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane, and including filtering the radiation emitted from the x-ray source to harden the x-ray beam, using one or more filters coated onto the tube or a sleeve over the tube, thus reducing unwanted dose in the sclera.

11. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane, and including filtering the radiation emitted from the x-ray source to harden the x-ray beam, using one or more filters coated onto the tube or a sleeve over the tube, thus reducing unwanted dose in the sclera.

12. The method of claim 11, wherein the distal end of the probe includes an adjustable standoff device for standing the x-ray source off from the sclera after insertion of the catheter, the x-ray source comprising a miniature x-ray tube, and including the step of selecting and balancing parameters of standoff distance of the source from the sclera and voltage applied to the miniature x-ray tube, to optimize the parameters to achieve a prescription radiation dose in the choroid and to limit dose in the sclera and minimize dose in the retina.

13. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina,

properly locating the distal end of the catheter by a protrusion in the surface of the catheter, near its distal end, and the method including viewing the retina from the front of the eye as the catheter is inserted, thus observing a protrusion in the retina caused by the protrusion on the catheter, until the catheter is properly positioned, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

14. The method of claim 13, wherein the protrusion in the surface of the catheter comprises an inflatable balloon, and the method including inflating the balloon of the protrusion to a selected extent after properly locating the distal end of the catheter to stand the distal end off from the sclera to a desired extent to improve the surface to depth dose ratio.

15. The method of claim 14, further including at least one additional inflatable balloon on the catheter, the additional inflatable balloon, along with said protrusion, serving to help immobilize the catheter after proper location of the distal end of the catheter.

16. The method of claim 14, wherein the x-ray source comprises a miniature x-ray tube, and including the step of selecting the extent of standoff of the x-ray source from the sclera, and selecting a voltage for the x-ray source and optimizing the standoff and the voltage to achieve a prescription dose to target tissue of the choroid and minimize dose to non-target ocular tissue.

17. The method of claim 16, further including filtering the radiation emitted from the x-ray source to harden the x-ray beam, using one or more filters coated onto the tube, thus reducing unwanted dose in the sclera.

18. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina,

the catheter including a guide having a non-round elongated internal cavity, the x-ray source having a complementary shape fitted to the non-round cavity so as to orient the x-ray tube rotationally within the guide, and the non-round cross sectional shape in the guide comprising generally a keyhole shape or an elliptical shape, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

19. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina,

administering to the patient vascularly a radiosensitizing drug, in an effective amount to sensitize the cells in the choroidal layer such that a lower dose or x-ray radiation can be delivered, and then

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

20. A method for treating AMD in combination with photodynamic therapy administered to the eye, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane,

and the method including administering a photo-activated substance vascularly to the patient and then photo-activating the substance by directing light through the front of the eye to thereby disrupt CNV vasculature in the choroid layer at the macula, the x-ray radiation serving to disable rapidly dividing cells of the CNV vasculature and to assist in the effects of the photodynamic therapy by preventing a repair response which naturally follows photodynamic treatment.

21. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina, including properly locating the catheter behind the macular region by exciting a fluorescent substance on the catheter with x-ray radiation from the source, and viewing the fluorescent substance using an optical instrument from the front of the eye, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

22. The method of claim 21, wherein the x-ray source is a miniature x-ray tube, and the fluorescent substance being on the tube.

23. A method for treating AMD, comprising:

inserting an applicator around the globe of the eye of a living patient, the applicator having at least one guide channel, and sliding a catheter into the guide channel of the applicator to slide the catheter around the globe of the eye, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the macular region of the retina, and

switching on the x-ray source to emit directed radiation through the sclera into the choroid membrane.

24. The method of claim 23, wherein the applicator has a plurality of parallel guide channels, and including inserting the catheter into each of the parallel guide channels successively to deliver radiation in a desired distribution, avoiding concentration of radiation in the sclera.

25. The method of claim 23, further including properly locating the applicator behind the macular region by activating one or more light sources on the applicator, and viewing the light sources using an optical instrument from the front of the eye, the light sources being visible through the sclera, choroid and retina.

26. The method of claim 23, wherein the guide channel and the catheter have keyed non-round cross sectional shapes so as to key a desired rotational orientation for directed radiation from the x-ray source when the catheter is positioned in the guide channel.

27. A method for treating AMD, comprising:

sliding an applicator around the globe of the eye of a living patient, the applicator having a plurality of parallel guide channels, to a position behind the macular region of the retina,

verifying accurate positioning of the applicator, and

sliding a catheter containing an x-ray source capable of directional emission through the plural guide channels in succession, to deliver a prescription dose of radiation through the sclera into targeted tissue of the choroid membrane.

28. The method of claim 27, wherein the x-ray source comprises a switchable miniature x-ray tube, and the method including switching the x-ray source on to emit radiation only when the source is in proper position behind the targeted tissue.

29. The method of claim 28, wherein the radiation is emitted in stepwise fashion in a grid of positions by pulling back the catheter to a plurality of dwell positions within each guide channel.

30. The method of claim 28, wherein the switchable miniature x-ray tube is switched on continuously through a continuous pullback routine for a prescribed distance within each of the guide channels.

31. The method of claim 27, wherein the x-ray source comprises an isotope.

32. A method for inserting and correctly locating an applicator having parallel guides by insertion peripherally around the globe of the eye, for therapeutic treatment of the eye, comprising locating the applicator behind the macular region by activating light sources on the applicator, and viewing the light sources using an optical instrument from the front of the eye, the light sources being visible through the sclera, choroid and retina.

33. The method of claim 32, wherein the light sources at the applicator comprise optical fibers receiving light from a source of illumination at a console to which the fibers are connected.

34. The method of claim 33, wherein the optical fibers have angularly cleaved ends as said light sources of the probe or applicator.

35. A method for inserting and correctly locating a therapeutic probe or applicator by insertion around the globe of the eye, for therapeutic treatment of the eye, comprising locating the distal end of the probe or applicator behind the macular region by directing a preselected pattern of light toward the retina from the front of the eye, and detecting the pattern of light using detectors located near the distal end of the probe or applicator, in such a way as to indicate a direction of movement for correction of the position of the probe or applicator.

36. The method of claim 35, wherein the pattern of light comprises repeated expanding rings of light.

37. The method of claim 35, wherein the pattern of light comprises a grid of light lines illuminated sequentially.

38. The method of claim 35, wherein the pattern of light comprises a color gradation pattern, with color indicating location.

39. The method of claim 35, wherein the pattern of light comprises a moving pattern of light and the method includes temporally sensing the position of the probe or applicator by reference to the moving pattern.

40. A method for inserting and correctly locating a therapeutic probe or applicator by insertion peripherally around the globe of the eye, for therapeutic treatment of the eye, comprising locating the distal end of the probe or applicator by a protrusion in the surface of the probe or applicator, near its distal end, and the method including viewing the retina from the front of the eye as the probe or applicator is inserted, thus observing a protrusion in the retina caused by the protrusion on the probe or applicator, until the probe or applicator is properly positioned.

41. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the sclera and not directly behind the macular region of the retina, and including properly locating the catheter behind the sclera in proper position aimed at the choroidal layer by activating light sources on the catheter and viewing the light sources using an optical instrument from the front of the eye, the light sources being visible through the sclera, choroid and retina, and

switching on the x-ray source to emit directed radiation through the sclera into the choroidal layer, in a direction essentially tangential or chordal relative to the globe of the eye, essentially not passing radiation through the retina.

42. The method of claim 41, wherein the light sources at the catheter comprise optical fibers receiving light from a source of illumination at a console to which the fibers are connected.

43. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the sclera and not directly behind the macular region of the retina, the x-ray tube being shielded to provide a desired, limited directional radiation in a tangential or chordal direction relative to the globe of the eye, and including filtering the radiation to be emitted from the x-ray source to harden the x-ray beam, using one or more filters coated onto the tube or onto a sleeve surrounding the tube, thus reducing unwanted dose in the sclera, and

switching on the x-ray source to emit directed radiation through the sclera into the choroidal layer, in a direction essentially tangential or chordal relative to the globe of the eye, essentially not passing radiation through the retina.

44. A method for treating AMD, comprising:

sliding a catheter around the globe of the eye of a living patient, the catheter containing a switchable x-ray source capable of directional emission in a distal end of the catheter, to a position behind the sclera and not directly behind the macular region of the retina, and including properly locating the distal end of the catheter by a protrusion in the surface of the catheter, near its distal end, and the method including viewing the retina from the front of the eye as the catheter is inserted, thus observing a protrusion in the retina caused by the protrusion on the catheter, until the catheter is properly positioned, and

switching on the x-ray source to emit directed radiation through the sclera into the choroidal layer, in a direction essentially tangential or chordal relative to the globe of the eye, essentially not passing radiation through the retina.

45. A method for treating a tumor in or adjacent to the eye of a patient, comprising:

inserting an applicator around the globe of the eye, the applicator having at least one guide channel, and sliding a catheter into the guide channel of the applicator to thereby slide the catheter around the globe of the eye, the catheter containing a switchable x-ray source in a distal end of the catheter, to a position adjacent to the tumor, and

switching on the x-ray source to emit radiation to deliver a prescription dose to the tumor.

46. The method of claim 45, wherein the applicator has a plurality of parallel guides, and including inserting the catheter into each of the parallel guides successively to deliver radiation in a desired distribution, avoiding concentration of radiation in ocular structure or adjacent tissue.