IP Library › Granted Patent US 12,295,656

Granted Patent B2

US 12,295,656 · App. 15/053,063 · Granted May 13, 2025

Composite ocular blood flow analyzer

Inventors: Robert Ogden Crane Dubois (Glen Arm, MD); Theresa Retue Kramer (Glen Arm, MD); Rhonda Richardson Grebe (Abingdon, MD); Paul Joseph Howell (Cumberland, ME)

Assignee: OCUFLOW, INC.

A61B3/0025 A61B3/0041 A61B3/10 A61B3/16 A61B5/0024 A61B5/02216 A61B5/02225 A61B5/0295 A61B5/7225 A61B5/021 A61B5/4088

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Quick Facts

Patent No.: US 12,295,656
App. No.: 15/053,063
Granted: May 13, 2025
Kind: B2

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Abstract

A composite ocular blood flow analyzer uses pneumatic tonometric techniques and structures to produce accurate, stable, and repeatable readings of intraocular pressure. A computer processes the intraocular pressure readings to produce data relating to various aspects of ocular blood flow that can be used diagnostically to identify abnormalities in the eye and other parts of the body.

Claims (178)

1. A composite ocular blood flow analyzer, comprising:

a pressure probe adapted to be placed in contact with a human eye; and

a pneumatic fluid supply adapted to supply pneumatic fluid to the pressure probe at a controlled constant fluid flow rate, in which the pneumatic fluid supply comprises:

a pump having an output adapted to provide a pressurized flow of pneumatic fluid to the pressure probe for applying force to the surface of the eye; and

a pressure compensated fluid flow rate regulator having an input and an output, the input of the pressure compensated fluid flow rate regulator connected to the output of the pump and the output of the pressure compensated fluid flow rate regulator connected to the probe, the pressure compensated fluid flow rate regulator adapted to provide a controlled constant fluid flow rate from its output to the probe regardless of pressure fluctuations.

2. The apparatus of claim 1 , in which the pressure compensated fluid flow rate regulator comprises:

a flow restrictor adapted to create a pressure drop that results in a desired fluid flow rate to the probe; and

a compensation structure responsive to changes in the pressure drop created by the flow restrictor so as to maintain a constant fluid flow rate from the pump to the probe.

3. The ocular blood flow analyzer of claim 1 , further comprising:

a pressure transducer responsive to the fluid supplied to the probe adapted to produce an electrical analog signal representing fluid pressure in the probe.

4. The ocular blood flow analyzer of claim 3 , further comprising:

an analog to digital converter connected to the pressure transducer to convert the electrical analog signal to a digital data stream representing probe pressure as a function of time.

5. The ocular blood flow analyzer of claim 4 , further comprising:

a data acquisition system responsive to the digital data stream to generate and store a representation of probe pressure as a function of time.

6. The ocular blood flow analyzer of claim 1 , further comprising:

a signal processor responsive to the probe for generating a signal representing information about blood flow in the eye.

7. The ocular blood flow analyzer of claim 6 , in which the information about blood flow in the eye is a volume per unit time blood flow rate in the eye.

8. The ocular blood flow analyzer of claim 6 , in which the information about blood flow in the eye is information about pulse rate.

9. The ocular blood flow analyzer of claim 6 , in which the information about blood flow in the eye is pulse amplitude information.

10. The ocular blood flow analyzer of claim 6 , in which the information about blood flow in the eye is pulsatile volume information.

11. The ocular blood flow analyzer of claim 6 , in which the information about blood flow in the eye is a pulsatility index.

12. The ocular blood flow analyzer of claim 6 , in which the information about blood flow in the eye is information about pulsatile composite choroidal and retinal ocular blood flow.

13. The ocular blood flow analyzer of claim 1 , in which the probe comprises:

a hollow elongated housing defining a pressure chamber having proximal and distal ends inside the housing;

an inlet in the housing adapted to admit fluid from the pump into the pressure chamber;

a port in the housing adapted to communicate with a pressure transducer to allow the pressure transducer to measure the fluid pressure in the housing;

a shaft, having proximal and distal ends, extending from inside the pressure chamber at its proximal end through the housing, the shaft being axially slideable with respect to the housing and defining a sliding bearing between the housing and the shaft;

an axially directed bore formed in the shaft, the bore having proximal and distal ends, the bore being in communication with the fluid in the pressure chamber at its proximal end inside the pressure chamber;

a tip having an open end comprising a venting chamber, secured to the distal end of the shaft, the open end also comprising a nozzle in communication with the distal end of the bore; and

a flexible membrane covering the open end of the tip, the nozzle being arranged to direct fluid from the pressure chamber and the bore in the shaft toward the flexible membrane.

14. The ocular blood flow analyzer of claim 13 , further comprising:

an exhaust vent adapted to vent fluid from the venting chamber in the tip.

15. The ocular blood flow analyzer of claim 1 , in which the pressure probe produces a pressure signal linearly related to intraocular pressure substantially over a range of intraocular pressures potentially exhibited by patients.

16. The ocular blood flow analyzer of claim 3 , further comprising: an electronic circuit that receives a probe pressure signal from the pressure transducer and converts the probe pressure signal to an intraocular pressure signal.

17. The ocular blood flow analyzer of claim 3 , further comprising: an electronic circuit responsive to a probe pressure signal from the pressure transducer, the electronic circuit configured to identify a filtered region of interest in the probe pressure signal.

18. The ocular blood flow analyzer of claim 3 , further comprising: an electronic circuit, responsive to a probe pressure signal from the pressure transducer, the electronic circuit configured to convert the probe pressure signal into an intraocular pressure signal representing intraocular pressure as function of time in an eye being examined by the ocular blood flow analyzer.

19. The ocular blood flow analyzer of claim 18 , further comprising:

an additional electronic circuit responsive to the intraocular pressure signal for generating a signal representing a change in eye volume as a function of time.

20. The ocular blood flow analyzer of claim 18 , further comprising:

a filter that removes a DC offset from a region of interest in the intraocular pressure signal.

21. The ocular blood flow analyzer of claim 1 , further comprising:

an inflow detector, responsive to the pressure probe, the inflow detector adapted to determine the amount of blood entering the eye for each heartbeat.

22. The ocular blood flow analyzer of claim 1 , further comprising:

an outflow detector, responsive to the pressure probe, the outflow detector adapted to determine the amount of blood draining from the eye after each heartbeat.

23. A method of measuring composite ocular blood flow, comprising the steps of:

applying force to an eye with a composite ocular blood flow analyzer of claim 11 ; and

detecting pressure fluctuations in the composite ocular blood flow analyzer in response to contact of the probe with an eye.

24. The method of measuring composite ocular blood flow of claim 23 , further comprising the step of:

producing data relating to blood flow in the eye in response to the pressure fluctuations in the probe.

25. Method of detecting an abnormal condition in a human being, comprising the steps of:

using the composite ocular blood flow analyzer of claim 1 to produce data relating to ocular blood flow in a patient; and

assessing an abnormal condition of a patient in response to the data relating to ocular blood flow.

26. The method of claim 25 , in which the abnormal condition is glaucoma.

27. The method of claim 25 , in which the abnormal condition is macular degeneration.

28. The method of claim 25 , in which the abnormal condition is diabetic retinopathy.

29. The method of claim 25 , in which the abnormal condition is ischemic optic neuropathy.

30. The method of claim 25 , in which the abnormal condition is retinal venous occlusive disease.

31. The method of claim 25 , in which the abnormal condition is retinopathy of prematurity.

32. The method of claim 25 , in which the abnormal condition is Alzheimer's disease.

33. The method of claim 25 , in which the abnormal condition is carotid occlusive disease.

34. The method of claim 25 , in which the abnormal condition is a systemic disease.

35. The ocular blood flow analyzer of claim 4 , wherein the analog to digital converter samples the electrical analog signal at a rate of at least 50 Hz.

36. The ocular blood flow analyzer of claim 4 , wherein the analog to digital converter samples the electrical analog signal at a rate of at least 100 Hz.

37. The ocular blood flow analyzer of claim 35 , in which the analog to digital converter is an at least 14 bit analog to digital converter.

38. The ocular blood flow analyzer of claim 36 , in which the analog to digital converter is an at least 14 bit analog to digital converter.

39. The ocular blood flow analyzer of claim 1 , further comprising:

a data acquisition system, responsive to the pressure probe, the data acquisition system adapted to collect and store probe pressure data as a function of time.

40. The ocular blood flow analyzer of claim 39 , further comprising:

a smoothing circuit responsive to at least a portion of stored probe pressure data, the smoothing circuit adapted to produce a smoothed representation of probe pressure data.

41. The ocular blood flow analyzer of claim 40 , in which the smoothing circuit comprises a boxcar filter of predetermined width.

42. The ocular blood flow analyzer of claim 40 , further comprising:

a differentiation circuit that differentiates the smoothed representation of probe pressure data; and

a first circuit responsive to the representation of differentiated and smoothed probe pressure data to identify a pulsatile region of interest in the probe pressure data.

43. The ocular blood flow analyzer of claim 42 , further comprising:

a second circuit responsive to the first circuit, the second circuit adapted to truncate the smoothed probe pressure data.

44. The ocular blood flow analyzer of claim 39 , further comprising: a conversion circuit adapted to convert the probe pressure data to intraocular pressure data in accordance with a predetermined relationship between probe pressure and intraocular pressure.

45. The ocular blood flow analyzer of claim 44 , in which the predetermined relationship is:

PP=1.96(IOP)+1.75,

where PP is the probe pressure and IOP is the intraocular pressure.

46. The ocular blood flow analyzer of claim 45 , further comprising:

a circuit, responsive to the intraocular pressure data, the circuit responsive to the intraocular pressure data adapted to produce a signal representing mean intraocular pressure.

47. The ocular blood flow analyzer of claim 46 , in which the circuit that produces a signal representing mean intraocular pressure comprises:

a circuit that fits a first order polynomial to the intraocular pressure data and computes the mean intraocular pressure in light of the intraocular pressure and the first order polynomial.

48. The ocular blood flow analyzer of claim 46 , further comprising:

a circuit responsive to the intraocular pressure data that produces flattened, zero-based intraocular pressure data.

49. The ocular blood flow analyzer of claim 48 , in which the circuit that produces flattened zero-based intraocular pressure data, comprises:

a circuit that fits a third order polynomial to the intraocular pressure data; and

a circuit that subtracts the third order polynomial from the intraocular pressure data to create a flattened zero-based region of interest in the intraocular pressure data.

50. The ocular blood flow analyzer of claim 44 , further comprising:

a peak detector responsive to the intraocular pressure data that identifies positive and negative peaks in the intraocular pressure data.

51. The ocular blood flow analyzer of claim 50 , in which the peak detector comprises:

a smoothing circuit that suppresses noise in the intraocular pressure data;

a differentiation circuit that differentiates the smoothed intraocular pressure data;

a boxcar filter that is applied to the differentiated intraocular pressure data that produces an output composed of positive and negative polarities; and

a polarity detector responsive to the boxcar filter that senses whether the boxcar filter output has a positive or negative polarity.

52. The ocular blood flow analyzer of claim 51 , in which a change in polarity in the output of the boxcar filter signifies a peak in the intraocular pressure data.

53. The ocular blood flow analyzer of claim 52 , in which a change in polarity in the output of the boxcar filter from positive to negative signifies a positive peak in the intraocular pressure data.

54. The ocular blood flow analyzer of claim 52 , in which a change in polarity in the output of the boxcar filter from negative to positive signifies a negative peak in the intraocular pressure data.

55. The ocular blood flow analyzer of claim 50 , further comprising:

a first averaging circuit that produces a signal related to the average of the positive peaks in the intraocular pressure data; and

a second averaging circuit that produces a signal related to the average of the negative peaks in the intraocular pressure data.

56. The ocular blood flow analyzer of claim 55 , further comprising:

a subtraction circuit that subtracts the signals related to the averages of the positive and negative peaks to obtain a pulse amplitude indication.

57. The ocular blood flow analyzer of claim 48 , further comprising: an adding circuit that adds the signal representing mean intraocular pressure to the flattened zero-based intraocular pressure signal to obtain a flattened intraocular pressure pulsatile region.

58. The ocular blood flow analyzer of claim 50 , further comprising:

a pulse rate determination circuit, responsive to the peaks identified by the peak detector, the pulse rate determination circuit adapted to produce a signal representing a pulse rate.

59. The ocular blood flow analyzer of claim 44 , further comprising:

a transformation circuit that converts the intraocular pressure data to change in eye volume data in accordance with a predetermined relationship between intraocular pressure and eye volume.

60. The ocular blood flow analyzer of claim 59 , in which the predetermined relationship is:

Δ V=− 49.8+30.2 ln P+ 0.242 P,

where ΔV is the change in eye volume and P is the intraocular pressure.

61. The ocular blood flow analyzer of claim 59 , in which the predetermined relationship is:

Δ V=− 52.2+31.7 ln P+ 0.254 P,

where ΔV is the change in eye volume and P is the intraocular pressure.

62. The ocular blood flow analyzer of claim 59 , in which the predetermined relationship is:

Δ V=− 47.4+28.7 ln P+ 0.230 P

where ΔV is the change in eye volume and P is the intraocular pressure.

63. The ocular blood flow analyzer of claim 59 , further comprising:

a circuit responsive to the change in volume data for generating an instantaneous rate of change of volume signal d(ΔV)/dt.

64. The ocular blood flow analyzer of claim 63 , in which the circuit that generates the instantaneous rate of change of volume signal comprises:

a smoothing circuit responsive to the change of volume data adapted to suppress noise in the change of volume data and produce a noise suppressed change in volume data.

65. The ocular blood flow analyzer of claim 64 , in which the circuit that generates the instantaneous rate of change of volume signal further comprises:

a differentiator responsive to the smoothing circuit adapted to differentiate the noise suppressed change of volume data.

66. The ocular blood flow analyzer of claim 64 , in which the smoothing circuit comprises:

a boxcar filter of predetermined width responsive to the change of volume data.

67. The ocular blood flow analyzer of claim 64 , further comprising:

a peak detector that identifies positive peaks in the instantaneous rate of change of volume signal d(ΔV)/dt; and

an averaging circuit responsive to the positive peaks to generate a signal representing a mean instantaneous peak net pulsatile flow parameter.

68. The ocular blood flow analyzer of claim 46 , further comprising a screen that displays the mean intraocular pressure.

69. The ocular blood flow analyzer of claim 58 , further comprising a screen that displays the pulse rate.

70. The ocular blood flow analyzer of claim 46 , further comprising a screen that displays the pulse amplitude.

71. The ocular blood flow analyzer of claim 67 , further comprising a screen that displays the peak net pulsatile flow.

72. The ocular blood flow analyzer of claim 44 , an acquisition circuit that receives signals representing systolic and diastolic arterial blood pressure; and a circuit that generates a mean perfusion pressure signal in response to the signals representing systolic and diastolic blood pressure.

73. The ocular blood flow analyzer of claim 72 , in which the mean perfusion pressure signal generating circuit generates the mean perfusion pressure signal in accordance with the following relationship:

mean OPP=2.0/3.0*(DBP+1.0/3.0*(SBP−DBP))−mean IOP,

where OPP is the ocular perfusion pressure, DBP is the diastolic blood pressure, SBP is the systolic blood pressure, and IOP is the intraocular pressure.

74. The ocular blood flow analyzer of claim 44 ,

an acquisition circuit that receives signals representing systolic arterial blood pressure; and

a circuit that generates a signal related to systolic ocular perfusion pressure in response to the signals representing systolic arterial blood pressure.

75. The ocular blood flow analyzer of claim 74 , in which the systolic ocular perfusion pressure signal generating circuit generates the systolic perfusion pressure in accordance with the following relationship:

systolic OPP=SBP−mean IOP,

where OPP is the ocular perfusion pressure, SBP is the systolic blood pressure, and IOP is the intraocular perfusion pressure.

76. The ocular blood flow analyzer of claim 44 ,

an acquisition circuit that receives signals representing diastolic arterial blood pressure; and

a circuit that generates a signal related to diastolic perfusion pressure in response to the signals representing diastolic blood pressure.

77. The ocular blood flow analyzer of claim 76 , in which the diastolic perfusion pressure signal generating circuit generates the diastolic perfusion pressure in accordance with the following relationship:

diastolic OPP=DBP−mean IOP,

where OPP is the ocular perfusion pressure, DBP is the diastolic blood pressure, and IOP is the intraocular pressure.

78. The ocular blood flow analyzer of claim 3 , further comprising:

a digital signal processor comprising an analog to digital converter connected to the analog signal from the pressure transducer to convert the analog signal to at least a 100 Hz 14-bit digital data stream representing raw probe pressure as a function of time; and

a data acquisition system that collects at least about 5-15 seconds of the at least 100 Hz 14-bit raw probe pressure data and stores that raw pressure data in a memory.

79. The ocular blood flow analyzer of claim 5 , further comprising:

a data processor responsive to the stored probe pressure data from the data acquisition system for generating a signal representing intraocular pressure as a function of time.

80. The ocular blood flow analyzer of claim 1 , further comprising:

a digital signal processor, responsive to the pressure probe, the digital signal processor adapted to produce probe pressure data representing raw pneumatic pressure in the probe as a function of time.

81. The ocular blood flow analyzer of claim 80 , further comprising:

an electronic circuit, responsive to the probe pressure data, the electronic circuit adapted to identify a pulsatile region of interest in the probe pressure data.

82. The ocular blood flow analyzer of claim 81 , in which the electronic circuit comprises:

a smoothing circuit responsive to the probe pressure data, the smoothing circuit adapted to create smoothed probe pressure data;

a differentiation circuit, responsive to the smoothed probe pressure data, the differentiation circuit adapted to differentiate the smoothed probe pressure data; and

a threshold circuit adapted to detect differentiation circuit output above a first predetermined value and below a second predetermined value, the pulsatile region of interest falling in a time period between the occurrence of the first predetermined value and the occurrence of the second predetermined value.

83. The ocular blood flow analyzer of claim 1 , further comprising:

a pressure transducer, responsive to the pressure probe, adapted to produce an electrical analog signal representing fluid pressure in the probe; and

an analog to digital converter, responsive to the pressure transducer, the analog to digital converter adapted to produce samples of probe pressure.

84. The ocular blood flow analyzer of claim 83 , in which the analog to digital converter samples pressure in the probe at a rate of at least 50 to 200 Hz.

85. The ocular blood flow analyzer of claim 84 , in which the probe pressure samples are at least 14-bit samples.

86. The ocular blood flow analyzer of claim 80 , in which the probe pressure data is at least 5-15 seconds of 14-bit samples taken at a rate of at least 50-200 Hz.

87. The ocular blood flow analyzer of claim 1 , further comprising:

an electronic circuit, responsive to the pressure probe, adapted to produce data representing ocular blood flow as a function of time.

88. The ocular blood flow analyzer of claim 1 , further comprising:

an electronic circuit, responsive to the pressure probe, adapted to produce data representing intraocular pressure as a function of time.

89. The method of claim 25 , in which the abnormal condition is retinal arterial occlusive disease.

90. The method of claim 25 , in which the abnormal condition is retinitis pigmentosa.

91. The method of claim 25 , in which the abnormal condition is burned skin.

92. The method of claim 25 , in which the abnormal condition is cerebral vascular flow/edema or pressure associated with traumatic brain injury.

93. The method of claim 25 , in which the abnormal condition is intracranial pressure in newborns.

94. The apparatus of claim 1 , in which the pneumatic fluid supply further comprises:

a brushless DC electric motor connected to the pump to control the pressure of the fluid from the output of the pump.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2017

From: HOWELL, PAUL JOSEPH; GREBE, RHONDA RICHARDSON; DUBOIS, ROBERT OGDEN CRANE; KRAMER, THERESA RETUE

To: OCUFLOW, LLC

Reel/Frame 041665/0958 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2017

From: OCUFLOW, LLC

To: OCUFLOW, INC.

Reel/Frame 042051/0247 →

Continuity (1)

Related Publication 20170245751A1 · Aug 31, 2017

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