Method for non-invasive identification of individuals at risk for diabetes

• US 6,721,583 B1
• Filed: 03/20/2002
• Issued: 04/13/2004
• Est. Priority Date: 11/19/1998
• Status: Expired due to Term

• Current Assignee: Health and Human Services United States of America As Represented By The SEC
• Original Assignee: Government of the United States of America
• Inventors: Durkin, Anthony J., Chenault, Vivian M., Ediger, Marwood N.
• Primary Examiner(s): Hindenburg, Max F.
• Assistant Examiner(s): KREMER, MATTHEW J
• Application Number:
  US09/856,186
• Time in Patent Office: 755 Days
• Field of Search: 600/309-310, 600/322-326, 600/316, 600/317, 600/318-320, 600/407, 600/476, 600/473, 600/321
• US Class Current: 600/318
• CPC Class Codes: A61B 3/10 Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters

Abstract

The invention provides methods for the use of Raman spectroscopy to non-invasively detect molecular characteristics of the constituents of the aqueous humor, vitreous humor, lens or retina. The method can be employed for the detection of molecular changes underlying ocular pathologies. In one embodiment of the invention, the method involves the steps of introducing light into the eye of the subject using a laser; collecting Raman spectra emitted from the eye; dispersing the collected Raman spectra onto a detector; and analyzing detected Raman spectral data to identify a molecular change related to an ocular pathology. The non-invasive method provided by the invention makes use of techniques and equipment that enable detection of Raman spectra with light intensities that fall within acceptable safety standards.

Claims

1. A method for non-invasive detection of an ocular pathology in a subject comprising:

(a) introducing light into the eye of the subject using a laser;

(b) collecting Raman spectra emitted from the eye;

(c) dispersing the collected Raman spectra onto a detector;

(d) analyzing detected Raman spectral data to identify a molecular change associated with the ocular pathology,

wherein the ocular pathology comprises a pre-cataract marker or a pre-retinopathy marker.

2. The method of claim 1, wherein the laser is a HeNe, diode, Ti:

Sapphire, Cr;

Forsterite or Nd;

YAG.

3. The method of claim 2, wherein the molecular change is:

—

OH stretching/—

CH stretching ratio or—

SH/S—

S ratio of lens proteins.

4. The method of claim 1, wherein the laser emits light of a visible red wavelength.

5. The method of claim 4, wherein the molecular change is C═

C stretching or C—

H stretching vibrations of vitreous proteins.

6. The method of claim 1, wherein the laser emits light of an infrared wavelength.

7. The method of claim 6, wherein the molecular change comprises alterations in concentrations of metabolic molecules.

8. The method of claim 1, wherein the laser emits light of a wavelength of about 600-700 nm.

9. The method of claim 8, wherein the molecular change is the increase of products from non-enzymatic glycation of retinal proteins.

10. The method of claim 1, wherein the laser emits light of a wavelength of about 1200-1300 nm.

11. The method of claim 1, wherein the light introduced into the eye is focused into the lens.

12. The method of claim 1, wherein the light introduced into the eye is focused into the vitreous humor.

13. The method of claim 1, wherein the light introduced into the eye is focused into the aqueous humor.

14. The method of claim 1, wherein the light introduced into the eye is focused into the retina.

15. The method of claim 1, wherein the ocular pathology is a pre-cataract marker.

16. The method of claim 1, wherein the ocular pathology is a pre-retinopathy marker.

17. The method of claim 1, wherein the Raman spectra collected are in about the 4000-200 cm⁻

1 region.

18. The method of claim 1, wherein the Raman spectra collected are in the region about 3000-500 cm⁻

1.

19. The method of claim 1, further comprising the step of correlating the Raman spectra with non-Raman based markers associated with ocular pathologies.

20. The method of claim 1, wherein the light is introduced and collected in an imaging mode.

21. The method of claim 1, wherein the light is introduced and collected in a non-imaging mode.

22. The method of claim 1, wherein the light is introduced and collected through a graded index lens.

23. The method of claim 1, wherein the collected light is dispersed onto a detector using a ruled grating.

24. The method of claim 1, wherein the collected light is dispersed onto a detector using a holographic grating.

25. The method of claim 1, wherein the detector is a red/blue enhanced CCD camera.

26. The method of claim 1, wherein the spectral data are analyzed using partial least squares.

27. The method of claim 1, wherein the spectral data are analyzed using principle component analysis.

28. The method of claim 1, wherein the laser emits light of a wavelength of about 700-1300 nm or 1550-1850 nm.

29. A method for non-invasive detection of an ocular pathology in a subject comprising:

(a) introducing light into the eye of the subject using a laser;

(b) collecting Raman spectra emitted from the eye;

(c) dispersing the collected Raman spectra onto a detector;

(d) analyzing detected Raman spectral data to identify a molecular change associated with the ocular pathology;

the molecular change comprising;

—

OH stretching/—

CH stretching ratio;

—

SH/—

S—

S ratio of lens proteins;

C═

C stretching vibrations of vitreous proteins;

or

C—

H stretching vibrations of vitreous proteins.

30. The method of claim 29, wherein the molecular change is —

OH stretching/—

CH stretching ratio.

31. The method of claim 29, wherein the molecular change is —

SH/—

S—

S ratio of lens proteins.

32. The method of claim 29, wherein the molecular change is C═

C stretching vibrations of vitreous proteins.

33. The method of claim 29, wherein the molecular change is C—

H stretching vibrations of vitreous proteins.

34. The method of claim 29, wherein the laser emits light of a visible red wavelength.

35. The method of claim 29, wherein the laser emits light of an infrared wavelength.

36. The method of claim 29, wherein the laser emits light of a wavelength of about 600-700 nm.

37. The method of claim 29, wherein the laser emits light of a wavelength of about 700-1300 nm or 1550-1850 nm.

38. The method of claim 29, wherein the laser emits light of a wavelength of about 1200-1300 nm.

39. The method of claim 29, wherein the light introduced into the eye is focused into the lens.

40. The method of claim 29, wherein the light introduced into the eye is focused into the vitreous humor.

41. The method of claim 29, wherein the light introduced into the eye is focused into the aqueous humor.

42. The method of claim 29, wherein the light introduced into the eye is focused into the retina.

43. The method of claim 29, wherein the Raman spectra collected are in about the 4000-200 cm⁻

1 region.

44. The method of claim 29, wherein the Raman spectra collected are in the region about 3000-500 cm⁻

1.

45. The method of claim 29, further comprising the step of correlating the Raman spectra with non-Raman based markers associated with ocular pathologies.

46. The method of claim 29, wherein the light is introduced and collected in an imaging mode.

47. The method of claim 29, wherein the light is introduced and collected in a non-imaging mode.

48. The method of claim 29, wherein the light is introduced and collected through a graded index lens.

49. The method of claim 29, wherein the collected light is dispersed onto a detector using a ruled grating.

50. The method of claim 29, wherein the collected light is dispersed onto a detector using a holographic grating.

51. The method of claim 29, wherein the detector is a red/blue enhanced CCD camera.

52. The method of claim 29, wherein the spectral data are analyzed using partial least squares.

53. The method of claim 29, wherein the spectral data are analyzed using principle component analysis.