Computer readable medium for regulating ocular blood flow

Abstract

To provide a device for treating, suppressing, or preventing an eye disease of a patient.SOLUTION: The apparatus can include a cover sized and shaped to fit over the patient's eye to define a cavity between the cover and the anterior surface of the eye when the cover is placed over the patient's eye. The apparatus can include a pressure source in communication with the cavity and capable of applying a non-atmospheric pressure within the cavity. The apparatus can include a control circuit in communication with the pressure source and configured to vary the non-atmospheric pressure applied to the cavity to affect a target pressure relationship between an indication of a first physiological pressure level and a second physiological pressure level associated with the eye of the patient.SELECTED DRAWING: Figure 1

Description

[Background technology]

[0001] Intraocular pressure (IOP) is an important physiological parameter in the field of ophthalmology. Controlled fluctuations in IOP can be used to assess and treat eye diseases.

[0002] US Patent No. 5,999,949 to Morris describes an apparatus for controlling IOP during closed-wound intraocular surgery that includes a gas pump, a liquid injectate reservoir, and an ophthalmic surgical infusion device.

[0003] US Patent No. 5,929,999 to Denninghoff describes a method for determining the autoregulatory state of the eye, which includes obtaining a first measurement of the retinal blood vessels, administering a preselected stimulus, obtaining a second measurement of the blood vessels in response to the stimulus, and determining a ratio.

[0004] U.S. Patent No. 5,999,999 to Kuenen describes a method for measuring intracranial pressure (ICP) that includes detecting SVP, identifying the head orientation at which SVP begins or ceases to occur, and using the identified head orientation to determine the subject's ICP. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] U.S. Patent No. 5,032,111 [Patent Document 2] U.S. Patent No. 6,701,169 [Patent Document 3] US Patent Application Publication No. 2016 / 0128587 Summary of the Invention

[0006] Glaucoma is the leading cause of blindness in the world today. Mechanical causes, such as elevated intraocular pressure (IOP), are widely recognized as important risk factors for glaucoma. However, the condition can progress even in the absence of excessive IOP, as seen in normal-tension glaucoma. Vascular disorders, such as insufficient blood flow to ocular tissues, are fundamentally different causes of glaucoma and may be important factors in the etiology and pathogenesis of the disease, as well as other ocular disorders.

[0007] The inventors have recognized, inter alia, that there is a need in the art for devices and methods for regulating blood flow, such as blood flow, in a patient's eye. The devices and methods described herein can regulate ocular blood flow to increase ocular perfusion, thereby treating, inhibiting, and preventing ocular diseases, including glaucoma. Furthermore, the devices and methods can be further used for patient assessment purposes, such as assessing ocular autoregulation capability and noninvasively estimating cerebrospinal fluid pressure.

[0008] The device can include a cover sized and shaped to fit over the patient's eye to define a cavity between the cover and the anterior surface of the eye. The device can include a pressure source in communication with the cavity and configured to adjust fluid pressure within the cavity. The device can include a control circuit in communication with the pressure source configured to receive an indication of a vascular parameter from a blood vessel of the eye, process the received indication, and adjust the fluid pressure within the cavity based on the received indication.

[0009] A summary of some non-limiting aspects of the present subject matter follows. Aspect 1 may include or employ subject matter (e.g., an apparatus, system, device, method, means for performing a plurality of operations, or a device-readable medium containing instructions that, when executed by a device, cause the device to perform a plurality of operations, or an article of manufacture) that may include or employ an apparatus for regulating ocular blood flow in a patient's eye. The apparatus may include a cover having a size and shape that fits over the eye to define a cavity between the cover and the anterior surface of the eye, a pressure source in communication with the cavity and configured to adjust fluid pressure in the cavity, and a control circuit in communication with the pressure source and configured to adjust fluid pressure in the cavity to regulate ocular blood flow toward a target level.

[0010] Aspect 2 may include, use, or optionally combine the subject matter of aspect 1 with an apparatus in which the control circuitry is configured to receive an indication of a vascular parameter associated with a blood vessel of the eye and adjust the fluid pressure in the cavity based at least in part on the received indication.

[0011] Aspect 3 may optionally include or use an apparatus that includes or uses, or optionally combines, the subject matter of one or any combination of aspects 1 or 2, wherein the control circuitry is configured to process the received indicators.

[0012] Aspect 4 may include or use, or optionally combine, the subject matter of one or any combination of aspects 1 to 3, and optionally include or use a device wherein the measure of vascular parameters includes an measure of ocular blood flow in intraocular vessels.

[0013] Embodiment 5 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 4, and may optionally include or use an apparatus including a blood flow sensor configured to sense an indication of blood flow from a blood vessel of the eye.

[0014] Embodiment 6 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 5, and may optionally include or use a device where the control circuitry is configured to receive an indication of IOP and an indication of blood flow within the eye, and adjust the fluid pressure within the cavity based at least in part on the received indications.

[0015] Embodiment 7 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 6, and may optionally include or use a device including an IOP sensor configured to sense an indication of IOP in the eye.

[0016] Embodiment 8 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 7, and may optionally include or use a device where the control circuitry is configured to receive an indication of the patient's systemic blood pressure and an indication of blood flow and IOP, and adjust the fluid pressure in the cavity based at least in part on the received indications.

[0017] Aspect 9 may include or use, or optionally in combination, the subject matter of one or any combination of aspects 1 through 8, and may optionally include or use an apparatus including a blood pressure sensor configured to sense an indication of a patient's systemic blood pressure.

[0018] Embodiment 10 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 9, and may optionally include or use a device configured to adjust fluid pressure in the cavity toward a target blood flow level based on a relationship between indicators received by a control circuit.

[0019] Embodiment 11 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 10, and may optionally include or use an apparatus configured to adjust cavity pressure to adjust blood flow toward a target blood flow level in the patient's eye based on a relationship between indicators received by a control circuit.

[0020] Aspect 12 may include or use, or optionally combine, the subject matter of one or any combination of aspects 1 to 11, and optionally include or use an apparatus, wherein the relationship between the received indicators includes ocular perfusion pressure (OPP) level.

[0021] Embodiment 13 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 12, and may optionally include or use an apparatus where the control circuitry is configured to process the indicator of blood flow to provide an ocular autoregulation (OA) value.

[0022] Embodiment 14 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 13, and may optionally include or use an apparatus where the target level includes a target OPP graph point level, and the control circuitry is configured to provide the OA values ​​as an ordered pair of OAs including the target OPP graph point level and an indicator of blood flow corresponding to the target OPP graph point level.

[0023] Example 15 may include, use, or optionally combine the subject matter of one or any combination of Examples 1 to 14, and may optionally include or use an apparatus in which control circuitry is configured to process at least two ordered pairs of OAs to calculate an OA index.

[0024] Embodiment 16 can include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 15, and optionally include or use an apparatus wherein the OA index comprises the slope of a best fit line between at least two ordered pairs of OAs.

[0025] Embodiment 17 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 16, and may include or use a device where the control circuitry is configured to adjust the pressure in the cavity to affect a target SVP state based at least in part on the received indication of blood flow to estimate the patient's CSFP level.

[0026] Example 18 may include or use, or optionally in combination with, the subject matter of one or any combination of Examples 1 to 17, and may optionally include or use an apparatus including an image sensor configured to sense an indication of vascular diameter from a blood vessel of the eye.

[0027] Embodiment 19 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 18, and may optionally include or use a device including an SVP sensor configured to sense an indication of vascular diameter from a blood vessel of the eye.

[0028] Embodiment 20 may include or use, or optionally combine with, the subject matter of one or any combination of embodiments 1 to 19, and may optionally include or use an apparatus where a control circuit is configured to receive an indication of systemic blood pressure including a systolic blood pressure level and a diastolic blood pressure level, and where the control circuit is configured to capture a first image of a vascular parameter corresponding to the systolic blood pressure level and a second image of a vascular parameter corresponding to the diastolic blood pressure level.

[0029] Embodiment 21 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 20, and may optionally include or use a device where the control circuitry is configured to receive an indication of IOP related to an indication of blood flow to provide an indication of CSFP at a target SVP state.

[0030] Embodiment 22 may include or use, or optionally in combination, the subject matter of one or any combination of embodiments 1 through 21, and may optionally include or use a device including a pressure sensor configured to sense an indication of IOP related to the received indication.

[0031] Embodiment 23 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 through 22, and may optionally include or use a device in which the pressure sensor includes an IOP sensor for sensing an indication of IOP.

[0032] Embodiment 24 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 23, and may optionally include or use a device, wherein the pressure sensor includes a cavity pressure sensor for sensing an estimate of an index of IOP.

[0033] Embodiment 25 may include, use, or optionally combine with the subject matter of one or any combination of embodiments 1 to 24, and may optionally include or use a device where the indicator of the vascular parameter includes a vascular diameter, and the control circuit is configured to calculate a vascular diameter coefficient and adjust the fluid pressure in the cavity to affect an associated target SVP state to estimate the patient's CSFP level based at least in part on the vascular diameter coefficient, the vascular diameter coefficient being defined as a ratio between a first vascular diameter value corresponding to a first image at a first pressure in the patient's cardiac cycle and a second vascular diameter value corresponding to a second image at a second pressure in the patient's cardiac cycle.

[0034] Embodiment 26 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 25, and may optionally include or use an apparatus where a first pressure in the patient's cardiac cycle comprises a systolic blood pressure level and a second pressure in the patient's cardiac cycle comprises a diastolic blood pressure level.

[0035] Embodiment 27 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 26, and may optionally include or use an apparatus where the indicator of the vascular parameter includes a vascular shape characteristic for a vascular cross-section, the vascular shape characteristic indicating a relationship between a long axis of the vessel and a short axis of the vessel, and the control circuit is configured to calculate a vascular shape coefficient to estimate the patient's CSFP level based at least in part on the vascular shape coefficient and adjust the fluid pressure in the cavity to affect an associated target SVP state, the vascular shape coefficient indicating a relationship between a first vascular shape characteristic corresponding to a first image at a first pressure in the patient's cardiac cycle and a second vascular shape characteristic corresponding to a second image at a second pressure in the patient's cardiac cycle.

[0036] Embodiment 28 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 27, and may optionally include or use an apparatus where a first pressure in a patient's cardiac cycle comprises a systolic blood pressure level and a second pressure in the patient's cardiac cycle comprises a diastolic blood pressure level.

[0037] Aspect 29 may include or utilize the subject matter (e.g., an apparatus, a system, a device, a method, a means for performing a plurality of operations, or a device-readable medium including instructions that, when executed by a device, cause the device to execute, or an article of manufacture), or may optionally include or utilize a method of using the apparatus, optionally in combination with the subject matter of one or any combination of aspects 1 to 28. The apparatus may include a cover having a size and shape to fit over the eye to define a cavity between the cover and the anterior surface of the eye, a pressure source in communication with the cavity and configured to adjust fluid pressure in the cavity, and a control circuit in communication with the pressure source and configured to adjust fluid pressure in the cavity to regulate ocular blood flow toward a target level. The method may include receiving, using the control circuit, an indication of a vascular parameter of the patient's eye. The method may include adjusting, using the control circuit, the fluid pressure in the cavity defined between the cover and the anterior surface of the eye based on the received indication.

[0038] Embodiment 30 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 29, and may optionally include or use a method wherein receiving an indication of a vascular parameter includes receiving an indication of blood flow in the blood vessel.

[0039] Aspect 31 may include or use, or optionally combine, the subject matter of one or any combination of aspects 1 to 30, and may optionally include or use a method including displaying the received indicator to a user via a GUI to enable the user to adjust the fluid pressure in the cavity based on the indicator of the vascular parameter.

[0040] Embodiment 32 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 31, and may optionally include or use a method wherein processing the received indicator includes calculating a difference between the received indicator and a target vascular parameter value.

[0041] Aspect 33 may include or use, or in any combination, the subject matter of one or any combination of aspects 1 to 32, and optionally include or use a method including generating a feedback signal configured to adjust the pressure source based on the received indicators.

[0042] Embodiment 34 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 33, and may optionally include or use a method wherein generating a feedback signal includes generating a feedback signal configured to adjust a pressure source toward a target blood flow level in the patient's eye.

[0043] Aspect 35 may include or use, or optionally combine, the subject matter of one or any combination of aspects 1 to 34, and may optionally include or use a method including receiving, using a control circuit, an indication of intraocular pressure (IOP) in the eye and an indication of the patient's systemic blood pressure.

[0044] Embodiment 36 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 35, and may optionally include or use a method wherein processing the received indicators includes calculating an indicator of ocular perfusion pressure (OPP) based on the received indicator of IOP and the indicator of systemic blood pressure.

[0045] Embodiment 37 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 36, and may optionally include or use a method in which the control circuit includes a graphical user interface (GUI) configured to communicate an indication of the OPP to a user, and the processing includes displaying the indication OPP to the user via the GUI so that the user can manually adjust the fluid pressure in the cavity based on the indication of the OPP.

[0046] Embodiment 38 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 37, and may optionally include or use a method wherein processing the received indication includes generating a feedback signal configured to adjust the pressure source based on the indication of the OPP.

[0047] Embodiment 39 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 38, and may optionally include or use a method wherein processing the received indicators includes forming an autoregulatory (OA) value for the eye that includes an ordered pair of OAs.

[0048] Embodiment 40 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 39, and may optionally include or use a method wherein processing the received indicators includes calculating an ocular autoregulation (OA) index based on at least two OA values.

[0049] Embodiment 41 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 40, and may optionally include, or use, a method wherein calculating the OA index includes calculating a slope of a best-fit line between at least two OA values.

[0050] Aspect 42 may include or use, or optionally in combination with, the subject matter of one or any combination of aspects 1 to 41, and may optionally include or use a method including receiving an indication of pressure associated with a patient's eye, including at least one of an indication of fluid pressure in the cavity or IOP of the eye.

[0051] Embodiment 43 may include or use, or in any combination, the subject matter of one or any combination of embodiments 1 to 42, and may optionally include or use a method, wherein receiving an indication of a vascular parameter includes receiving an indication of a vascular diameter, and processing the received indication includes determining an indication of SVP status.

[0052] Embodiment 44 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 43, and may optionally include or use a method in which the control circuitry includes a graphical user interface (GUI) configured to communicate an indication of the SVP status to a user, and the processing includes displaying the indication of the SVP status to the user via the GUI and enabling the user to manually adjust the fluid pressure in the cavity based on the indication of the SVP status.

[0053] Embodiment 45 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 44, and may optionally include or use a method wherein processing the received indication includes generating a feedback signal configured to adjust the pressure source based on the indication of the SVP condition.

[0054] Embodiment 46 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 45, and may optionally include or use a method, wherein generating a feedback signal includes generating a feedback signal configured to adjust the pressure source toward a target SVP state.

[0055] Embodiment 47 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 through 46, and may optionally include or use a method where generating a feedback signal includes generating a feedback signal to adjust the pressure source from an SVP on state to an SVP off state.

[0056] Embodiment 48 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 through 47, and may optionally include or use a method where generating a feedback signal includes generating a feedback signal to adjust the pressure source from an SVP off state to an SVP on state.

[0057] Embodiment 49 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 48, and may optionally include or use a method in which processing the received indicator includes displaying an indicator of pressure associated with the patient's eye at the target SVP state as an estimate of the patient's CSFP level.

[0058] Embodiment 50 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 49, and may optionally include or use a method wherein receiving an indication of a vascular parameter includes visualizing vascular characteristics.

[0059] Embodiment 51 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 50, and may optionally include or use a method in which visualizing the vascular parameter includes imaging the vascular parameter using an image sensor.

[0060] Embodiment 52 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 51, and may optionally include or use a method in which visualizing the vascular parameter includes sensing an indication of SVP using an SVP sensor.

[0061] Embodiment 53 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 52, and may optionally include or use a method in which using the control circuitry includes increasing the cavity pressure above atmospheric pressure toward a target SVP state to estimate the patient's CSFP.

[0062] Embodiment 54 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 53, and may optionally include or use a method in which using the control circuitry includes reducing the cavity pressure below atmospheric pressure toward a target SVP state to estimate the patient's CSFP.

[0063] Aspect 55 may include or utilize subject matter (e.g., an apparatus, a system, a device, a method, a means for performing a plurality of operations, or a device-readable medium including instructions that, when executed by a device, cause the device to perform a plurality of operations, or an article of manufacture), or may optionally include or utilize a method of using the apparatus, optionally in combination with the subject matter of one or any combination of aspects 1 to 54. The apparatus may include a cover having a size and shape to fit over the eye to define a cavity between the cover and the anterior surface of the eye, a pressure source in communication with the cavity and configured to adjust fluid pressure in the cavity, and a control circuit in communication with the pressure source and configured to adjust fluid pressure in the cavity to regulate ocular blood flow toward a target level. The method may include forming a cavity between a patient's eye and the cover, the cover having a size and shape to fit over the eye. The method may include adjusting fluid pressure in the cavity to affect a target SVP state to estimate the patient's CSFP.

[0064] Embodiment 56 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 through 55, and may optionally include or use a method including increasing the fluid pressure in the cavity such that adjusting the fluid pressure in the cavity affects the transition from the initial SVP state to the target SVP state.

[0065] Embodiment 57 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 through 56, and may optionally include or use a method including increasing the fluid pressure in the cavity such that adjusting the fluid pressure in the cavity affects the transition from the initial SVP state to the target SVP state.

[0066] Embodiment 58 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 through 57, and may optionally include or use a method comprising reducing the fluid pressure in the cavity such that adjusting the fluid pressure in the cavity affects the transition from the initial SVP state to the target SVP state.

[0067] Embodiment 59 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 58, and may optionally include or use a method wherein adjusting the fluid pressure in the cavity includes visualizing the SVP status of the ocular blood vessels using an image sensor.

[0068] Embodiment 60 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 59, and may optionally include or use a method comprising detecting an IOP of a patient's eye where adjusting the fluid pressure in the cavity corresponds to a transition from an initial SVP to a target SVP state, to estimate the patient's CSFP.

[0069] Embodiment 61 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 through 60, and may optionally include or use a method including reducing the fluid pressure in the cavity such that adjusting the fluid pressure in the cavity affects the transition from the initial SVP state to the target SVP state.

[0070] Embodiment 62 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 61, and may optionally include or use a method in which adjusting the fluid pressure in the cavity includes visualizing the SVP status of the ocular blood vessels using an image sensor.

[0071] Embodiment 63 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 62, and may optionally include or use a method comprising detecting an IOP of a patient's eye where adjusting the fluid pressure in the cavity corresponds to a transition from an initial SVP to a target SVP state, and estimating the patient's CSFP.

[0072] Embodiment 64 may include or employ subject matter (e.g., an apparatus, system, device, method, means for performing a plurality of operations, or a device-readable medium including instructions that, when executed by the device, cause the device to perform a plurality of operations, or an article of manufacture) that may include or employ an apparatus for regulating ocular blood flow in a patient's eye. The apparatus may include a cover having a size and shape to fit over the eye to define a cavity between the cover and the anterior surface of the eye, a pressure source in communication with the cavity and configured to adjust fluid pressure within the cavity, and a control circuit in communication with the pressure source and configured to receive an indication of pressure associated with the patient's eye and an indication of systemic blood pressure (BP), and process the received indication based at least in part on at least one of the received indications to adjust the fluid pressure within the cavity.

[0073] Embodiment 65 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 64, and may optionally include or use a device wherein the indicator of pressure associated with the eye includes at least one of an indicator of pressure in a cavity of a fluid indicator or an indicator of intraocular pressure (IOP) in the eye.

[0074] Embodiment 66 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 65, and may optionally include or use a device in which an indication of fluid pressure is sensed by a pressure sensor and an indication of IOP is sensed by an IOP sensor.

[0075] Embodiment 67 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 66, and may optionally include or use a device in which an indicator of systemic BP is sensed by a BP sensor.

[0076] Embodiment 68 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 67, and may optionally include or use an apparatus including a graphical user interface (GUI) configured to communicate an indication of pressure associated with the eye to a user, and processing including displaying the indication of pressure to the user via the GUI and enabling the user to manually adjust the fluid pressure in the cavity based on the indication of pressure.

[0077] Embodiment 69 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 68, and may optionally include or use a device where the control circuitry includes a graphical user interface (GUI) configured to communicate an indication of pressure associated with the eye to a user, and the processing includes displaying the indication of IOP to the user via the GUI and enabling the user to manually adjust the fluid pressure in the cavity based on the indication of IOP.

[0078] Embodiment 70 may include, use, or optionally combine the subject matter of one or any combination of embodiments 1 to 69, and may optionally include or use a device wherein the processing includes displaying to a user via a GUI a first indicator of an IOP level at a first indicator of a systemic BP level and a second indicator of an IOP level at a second indicator of a systemic BP level, and allowing the user to manually adjust the fluid pressure in the cavity based on at least one of the first or second indicators of IOP.

[0079] Embodiment 71 may include or use, or optionally in combination with, the subject matter of one or any combination of embodiments 1 to 70, and may optionally include or use an apparatus wherein the first indicator of systemic BP level includes an indicator of systolic BP in the patient's cardiac cycle, and the second indicator of systemic BP level includes an indicator of diastolic BP in the patient's cardiac cycle.

[0080] Embodiment 72 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 71, and may optionally include or use an apparatus in which a control circuit is configured to regulate fluid pressure in the cavity toward a target level.

[0081] Embodiment 73 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 72, and may optionally include or use a device in which the control circuit is configured to adjust the fluid pressure in the cavity toward a target IOP level for the eye.

[0082] Embodiment 74 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 through 73, and may optionally include or use an apparatus configured to adjust fluid pressure in the cavity toward a target level based on a relationship between indicators received by a control circuit.

[0083] Embodiment 75 may include or use, or optionally combine, the subject matter of one or any combination of embodiments 1 to 74, and may optionally include or use a device in which a control circuit is configured to process an indication of an ocular perfusion pressure (OPP) level of a patient's eye and adjust the fluid pressure in the cavity toward a target ocular perfusion pressure (OPP) level based on the indication of OPP.

[0084] Each of these non-limiting examples can stand on its own or can be combined in various permutations or combinations with one or more of the other examples. This Summary is intended to provide an overview of the subject matter of this patent application. It is not intended to provide an exclusive or exhaustive description of the invention. The Detailed Description is included to provide further information regarding this patent application. [Brief explanation of the drawings]

[0085] In the drawings, which are not necessarily drawn to scale, like numerals may describe like components in different figures. Like numerals with different letter suffixes may represent different instances of like components. The drawings illustrate generally, by way of example, and not by way of limitation, various embodiments discussed herein. [Figure 1] 1 illustrates an example of a device for controlling the environment above a patient's eye. [Figure 1A] 1 shows an example of a device that includes a manual pressure source. [Figure 2A] FIG. 1 illustrates a side view of an example positive pressure cavity check valve in an open position. [Figure 2B] FIG. 1 illustrates a side view of an example positive pressure cavity check valve in a closed position. [Figure 3A] FIG. 1 illustrates a side view of an example negative pressure cavity check valve in a closed position. [Figure 3B] FIG. 1 illustrates a side view of an example negative pressure cavity check valve in an open position. [Figure 4] FIG. 1 illustrates a side view of an example check valve assembly. [Figure 5A] 1 shows a cross section of an example of a first dual lumen conduit. [Figure 5B] 10 shows a cross section of an example of a second dual lumen conduit. [Figure 5C] 10 shows a cross section of an example of a third dual lumen conduit. [Figure 6] 1 illustrates an example method for regulating blood flow in an ocular vessel of a patient's eye using a device. [Figure 7A]1 shows a graph illustrating a first example of the AR function of the eye. [Figure 7B] 10 shows a graph illustrating a second example of the AR function of the eye. [Figure 8] An example method for quantifying OA potential in a patient's eye using the device is shown. [Figure 9] 1 illustrates an example method for non-invasively detecting CSFP levels in a patient using a device. DETAILED DESCRIPTION OF THE INVENTION

[0086] 1 illustrates an example of an apparatus 100 for controlling the environment above a patient's eye. In at least one example, the patient's eye can include an organ of the visual system, such as the anterior surface of the patient's eye. The apparatus 100 can include a cover 110, a fluid regulator 120, a sensor 130, a control circuit 140, and a pressure source 150.

[0087] The cover 110 can be sized and shaped to surround and be spaced apart from the patient's eye, such as without contacting the eye, including the anterior surface of the eye. The cover 110 can be sized and shaped to surround and cover both of the patient's eyes, such as the patient's left and right eyes. In one example, the cover 110 can include a mask, such as a cover 110 similar in shape and function to a diving or snorkeling mask. The cover 110 can include a lens portion 182 to allow the patient to see outward through the cover 110 or to view inward through the cover 110 the eye, such as the external structures of the eye, including the cornea, or the internal structures of the eye, including the retina. The lens portion 182 can serve as a corrective lens for the patient, such as to correct astigmatism in the eye. The lens portion 182 can include a lens blank, such as an A8 lens blank, that can be shaped as a prescription lens for the patient, such as to correct refractive errors in the eye. The lens portion 182 may include an interchangeable lens portion 182, e.g., a first lens portion of the device 100 may be interchangeable with a second lens portion, such as to change the lens power presented to the patient. In one example, the lens power may be selected to enable examination of the intraocular space of the eye, including evaluation of the retina and choroid, such as for at least one of diagnostic or therapeutic purposes. The lens power may be selected to enhance the examination of the eye, such as by focusing the lens portion 182 to enhance visualization of a portion of the eye. The inner surface of the lens portion 182 may be treated, such as with an anti-fog coating, to prevent condensation from obscuring the patient's vision.

[0088] The cover 110 can define a sealed cavity 112, such as when the cover 110 is placed over the eye and against the patient. The cavity 112 can define a sealed cavity 112 over both eyes, such as when the cover 110 includes a mask positioned over the patient's left eye and the patient's right eye. In one example, the peripheral edge of the cover 110 can be positioned on the eye such that the peripheral edge can contact at least a portion of the orbit (e.g., the eye socket). The cavity 112 can include a spatial volume, such as a spatial volume defined between the inner surface 188 of the cover 110 and the front surface of the patient's eye. The cavity 112 can contain a working fluid, such as a liquid or gaseous fluid, that can form an ocular environment in contact with the patient's eye. In one example, the ocular environment can be used to characterize a physiological condition of the patient's eye, e.g., the ocular environment can include physiological components including biomarkers released from the eye. Information sensed by the device 100, such as biomarkers sensed from the working fluid in the cavity 112, can provide patient information to a medical professional, such as for diagnosing an ocular disease associated with the patient's eye. In one example, the ocular environment can be used to treat the patient's eye, e.g., the device 100 can adjust the ocular environment to change at least one of the pressure or working fluid composition in the cavity 112 to treat an ocular disease.

[0089] The ocular disease may refer to an ocular condition, such as a physiological condition of the eye, that may affect a patient's vision. The ocular disease may include at least one of an acute ocular disease, such as an ocular disease that may persist for a period measured in seconds, minutes, or days, or a chronic ocular disease, such as an ocular disease that may persist for a period measured in days, weeks, months, or years. In one example, the ocular disease may include an abnormal ocular disease, such as an eye condition. The ocular condition may include at least one of glaucoma, papilledema, such as optic disc edema, Fuchs dystrophy, diabetic retinopathy, macular degeneration, such as wet or atrophic macular degeneration, cataract, dry eye, corneal infection, meibomian gland dysfunction, Demodex mites, corneal ectasia, or periocular skin laxity.

[0090] Ocular diseases may be affected by device 100, such as by exposing a patient's eye, including the anterior portion of the eye, to an ocular environment within cavity 112. In one example, glaucoma may be treated, inhibited, or prevented by device 100, such as by exposing the eye to an ocular environment comprising a negative gauge pressure. In one example, optic nerve head edema may be treated, inhibited, or prevented by device 100, such as by exposing the eye to an ocular environment comprising a positive gauge pressure. In one example, aerobic eye infections may be treated, inhibited, or prevented by device 100, such as by exposing the eye to an aerobic environment (e.g., an environment without oxygen) to address the underlying cause of the aerobic eye infection.

[0091] By exposing the eye to the environment within cavity 112, one or more eye conditions can be affected, such as simultaneously, by device 100. In one example, if a patient is suspected of having one or more eye conditions, such as glaucoma and optic disc edema, device 100 can treat, inhibit, or prevent the multiple eye conditions, such as by exposing the patient's eye to an eye environment that includes an aerobic eye environment at a negative gauge pressure, such as a negative pressure environment for treating glaucoma and an aerobic environment for treating aerobic eye infections.

[0092] The ocular environment can be defined by environmental parameters, such as properties of the working fluid within the cavity 112. The environmental parameters can include at least one of: working fluid flow within the cavity 112, such as the volumetric flow rate of the working fluid into or out of the cavity 112; working fluid humidity within the cavity 112, such as the relative humidity of the working fluid within the cavity 112; working fluid temperature within the cavity 112; working fluid pressure within the cavity 112 (e.g., cavity pressure), such as the working fluid gauge pressure within the cavity 112 and the atmospheric pressure of the environment surrounding the cavity; or working fluid composition within the cavity 112, such as the working fluid composition as measured by at least one of constituent fluid concentrations or partial fluid pressures.

[0093] Exposure of the eye to the ocular environment can cause changes in the eye, such as absorption of the working fluid into the eye, which can cause changes in physiological parameters associated with the eye, including at least one of intraocular pressure (IOP), intracranial pressure (ICP), such as cerebrospinal fluid pressure (CSFP), or spontaneous venous pulsation (SVP) (e.g., SVP state).

[0094] The cover 110 can hold a working fluid against a patient, such as in contact with an anterior portion of the patient's eye, to create an ocular environment within the cavity 112. Exposing the patient's eye to the ocular environment can affect an ocular treatment, such as at least one of a diagnostic examination of the eye or an ocular therapeutic treatment, such as treating, inhibiting, or preventing an ocular disease associated with the eye. The ocular treatment can include exposing the eye to at least one of a working fluid pressure within the cavity 112, such as to apply a force to the anterior portion of the eye to regulate the intraocular pressure (IOP) level of the eye, or exposing the eye to a working fluid composition within the cavity 112, such as to promote absorption of the working fluid into the eye, including through the anterior portion of the eye.

[0095] The cover 110 can maintain a fluid pressure differential, such as a gauge pressure of the working fluid in the cavity 112, in contact with the patient's eye. In one example, gauge pressure can be defined as the pressure difference between the working fluid pressure in the cavity 112 and the atmospheric pressure surrounding the cover 110. A positive gauge pressure, such as when the working fluid pressure in the cavity 112 is higher than atmospheric pressure, can create a compressive working fluid force against the anterior surface of the eye, such as to increase intraocular pressure (IOP) in the eye. A negative gauge pressure, such as when the working fluid pressure in the cavity 112 is lower than atmospheric pressure, can create a negative (i.e., "vacuum") working fluid force against the anterior surface of the eye, such as to decrease IOP in the eye. In at least one example, the working fluid in the cavity 112 can include a readily compressible fluid, such as a gaseous fluid having the same composition as ambient air.

[0096] The working fluid force applied to the anterior surface of the eye can include a perturbation force, such as a force for a diagnostic test. The perturbation force can be applied to the anterior surface of the eye for a period sufficient to allow measurement of a deflection of the eye, such as a deflection from a first position to a second position. In one example, applying the perturbation force for a period measured in seconds or minutes can be sufficient for a deflection measurement. The perturbation force can be generated by a positive gauge pressure within the cavity 112 to apply a positive perturbation force to the eye, such as to decrease the curvature of the eye for a diagnostic test, including a diagnostic measurement. The perturbation force can be generated by a negative gauge pressure within the cavity 112 to apply a negative perturbation force to the eye, such as to increase the curvature of the eye for a diagnostic test, including a diagnostic measurement.

[0097] The force applied to the anterior surface of the eye can include a therapeutic force, such as a force that applies a therapy regimen to the anterior surface of the eye for a period of time sufficient to treat an ocular condition, including an acute or chronic ocular condition. In one example, applying a therapeutic force for a period of time measured in days, weeks, months, or years can be applied depending on the ocular condition being treated. The therapeutic force can be generated by a positive gauge pressure, which applies a positive therapeutic compressive force to the eye, such as to increase the intraocular pressure (i.e., IOP) of the eye to inhibit, treat, or prevent ocular conditions, including optic nerve edema. The therapeutic force can be generated by a negative gauge pressure, which can apply a negative therapeutic force to the eye, such as to lower the IOP of the eye to inhibit, treat, or prevent ocular conditions, including glaucoma.

[0098] The eye disease can include at least one of an acute eye disease, such as an eye disease that may persist for a period measured in seconds, minutes, or days, or a chronic eye disease, such as an eye disease that may persist for a period measured in days, weeks, months, or years. In at least one example, the eye disease can include at least one of glaucoma, edema, such as optic disc edema, Fuchs' dystrophy, diabetic retinopathy, macular degeneration, such as wet or atrophic macular degeneration, cataracts, dry eye, corneal infection, memobian (meibomian) gland dysfunction, Demodex mites, corneal ectasia, or periocular skin laxity.

[0099] The working fluid can be comprised of one or more constituent fluids, such as a combination of one or more liquids or gases. The working fluid can include a combination of two constituent fluids, such as a combination of gaseous nitric oxide or gaseous carbon dioxide. The constituent fluids can include therapeutic fluids, e.g., components of the constituent fluids can be absorbed through the eye to inhibit, treat, or prevent ocular diseases. For example, the working fluid can include a combination of nitrogen and nitric oxide, e.g., the nitric oxide component can be absorbed through the surface of the eye to promote vasodilation of blood vessels in the eye to treat ocular diseases, including glaucoma.

[0100] The therapeutic fluid can include gaseous therapeutic fluids such as carbon dioxide (CO), oxygen (O), nitric oxide (NO), ozone (O), nitrogen (N), helium (He), hydrocarbons including fluorocarbons and perfluorocarbons, sulfur hexafluoride, cannabinoids including tetrahydrocannabinol (THC) and cannabidiol (CBD), and combinations of two or more gaseous therapeutic fluids. In one example, the therapeutic gas can include a mixture of at least one of carbon dioxide, oxygen, or nitric oxide, such as for treating ocular disorders. In one example, the therapeutic gas can include a mixture of nitric oxide and oxygen, including a mixture of 50% nitric oxide and 50% oxygen, a mixture of helium and oxygen (also known as heliox), and medical air, including Medical Grade Air USP, such as for treating ocular disorders. In one example, the therapeutic gas combination can include a mixture of nitric oxide and oxygen, such as a mixture of 50% nitric oxide and 50% oxygen, including gases from The BOC Group plc under the trade name ENTONOX, for treating ocular diseases. In one example, the therapeutic gas combination can include a mixture of helium and oxygen, such as a mixture of 21% oxygen and 79% helium, also known as heliox, for treating ocular diseases. In one example, the therapeutic gas combination can include a mixture of at least one of fluorine or chlorine, for treating ocular diseases, including ocular infections. In one example, the therapeutic gas combination can include at least one of a mixture including a lower volume fraction of oxygen than ambient air, such as a mixture including less than about 21% volume fraction of O, for treating aerobic ocular infections, or a mixture including a higher volume fraction of oxygen than ambient air, such as a mixture including more than about 21% volume fraction of O, for treating aerobic ocular infections.

[0101] The treatment fluid can include a liquid treatment fluid, such as a treatment solution. The treatment solution can include a solvent, such as water (H2O), and a solute, such as a treatment solute. The treatment solute can include at least one of vitamin A, B vitamins, such as riboflavin (vitamin B2), vitamin C, vitamin D, vitamin E, beta-carotene, zinc, lutein, or folic acid. The treatment solution can be converted from a liquid treatment fluid to a gaseous treatment fluid, such as by a nebulizer or atomizer, that forms a treatment mist or fog for delivery to the cavity 112 and contact with the patient's eye. In one example, the patient's eye can be exposed to a gaseous treatment fluid, such as a treatment mist containing vitamin A, to achieve a first treatment result, such as treating a corneal ulcer. In one example, the patient's eye can be exposed to a gaseous treatment fluid, such as a treatment mist containing riboflavin, and then exposed to augmenting energy, such as ultraviolet light, to achieve a second treatment result, such as promoting corneal cross-linking to treat keratoconus.

[0102] The cover 110 can include a first port 114. The first port 114 can be located on a surface of the cover 110, for example, the first port 114 can extend from an outer surface 187 of the cover 110 to an inner surface 188 of the cover 110 to allow access to the ocular environment within the cavity 112. The first port 114 can include a septum, such as a flexible septum, located over the first port 114 to isolate the cavity 112 from the surrounding environment. The flexible septum can maintain a gauge pressure, such as at least one of a positive gauge pressure or a negative gauge pressure, within the cavity 112.

[0103] The flexible diaphragm can include a resealable septum, such as a septum formed from a self-sealing material, including a self-sealing polymeric material, that can allow an instrument to be inserted and withdrawn into the cavity 112 through the septum while maintaining a gauge pressure in the cavity 112. In one example, the resealable septum allows a hypodermic needle to be inserted and withdrawn through the resealable septum while maintaining a gauge pressure (e.g., a positive gauge pressure or a negative gauge pressure) in the cavity 112. For example, the resealable septum allows a hypodermic needle to be placed in proximity to the eye, such as to contact a therapeutic fluid with the eye, while maintaining a gauge pressure in the cavity 112.

[0104] The flexible diaphragm may include a measurement diaphragm, such as a diaphragm that enables a sensor, such as sensor 130, to sense an indication of the ocular environment within cavity 112 without contacting the ocular environment. In one example, a pressure sensor may be positioned in contact with the measurement diaphragm covering first port 114 of cover 110, such as to sense an indication of working fluid pressure within cavity 112 through the pressure measurement diaphragm.

[0105] The cover 110 may include a second port 116 extending from an outer surface 187 of the cover 110 to an inner surface 188 of the cover 110. In one example, the second port 116 may connect the cavity 112 to a pressure source 150, such as by a conduit 117.

[0106] The cover 110 may include a seal 119, such as to provide an interface between the cover 110 and the patient, including a cover-patient interface, to enhance patient comfort when wearing the device 100. The seal may also function as a barrier, such as to separate the ocular environment within the cavity 112 from the surrounding environment. The seal 119 may be attached to the periphery of the cover 110, such as at least a portion of the periphery of the cover 110. In one example, the seal 119 may extend continuously around the periphery of the cover, such as to form a sealing surface between the cover 110 and the patient to separate the volume of the cavity 112 from the surrounding environment.

[0107] Apparatus 100 can include a cavity check valve 189. Cavity check valve 189 can be located in apparatus 100 in communication with cavity 112, such as in at least one of cover 110, including any surface of cover 110, conduit 117, control circuit 140, or pressure source 150. In one example, cavity check valve 189 can be located proximate first port 114, such as in, on, or above first port 114.

[0108] Cavity check valve 189 can limit the actuation fluid pressure applied to cavity 112. In one example, cavity check valve 189 can be used as a safety valve, such as to ensure that the pressure within cavity 112 does not exceed a cavity pressure level that could cause eye damage. In one example, cavity check valve 189 can limit the pressure within cavity 112 to a target cavity pressure level.

[0109] The cavity check valve 189 can include a cracking pressure, such as a characteristic of the cavity check valve 189, that can control the initiation of fluid flow through the valve. In one example, the cracking pressure can indicate an inlet pressure level of the cavity check valve 189 at which fluid can begin to flow through the cavity check valve 189. The working fluid pressure in the cavity 112 can be limited to a target cavity pressure level by selecting or setting the cracking pressure of the cavity check valve 189, such as by selecting or setting the cracking pressure of the cavity check valve 189 to be equal to the target cavity pressure level. For example, if the working fluid pressure in the cavity 112 is lower than the cracking pressure of the cavity check valve 189, the cavity check valve 189 can assume a closed state, such as to prevent the flow of working fluid from the cavity to the ambient atmosphere. When the working fluid pressure in cavity 112 is equal to or greater than the cracking pressure of cavity check valve 189, cavity check valve 189 may assume an open state, such as to allow the flow of working fluid from cavity 112 to the ambient atmosphere.

[0110] The cavity check valve 189 may include a passive cavity check valve, such as a flapper valve or a poppet valve. The cracking pressure of a passive cavity check valve may be adjusted, such as by changing the dimensions of the passive cavity check valve or the components of the passive cavity check valve. In one example, the cracking pressure of a flapper cavity check valve may be adjusted, such as by changing at least one of the following: flapper check valve dimensions (e.g., length, width, thickness), flapper check valve construction materials (e.g., material type, material durometer, single or multi-layer material, valve stiffness), or flapper check valve hinge. In one example, the cracking pressure of a poppet cavity check valve may be adjusted, such as by changing at least one of the poppet valve dimensions (e.g., spring stiffness, poppet diameter).

[0111] 2A and 2B show side views of an example of a positive pressure cavity check valve, such as a flapper valve, configured to control the pressure in cavity 112 to a target positive cavity pressure level. The target positive cavity pressure level may be specified by a medical professional, such as to treat, inhibit, or prevent an eye disease. The positive pressure cavity check valve may be located on cover 110, such as on outer surface 187 of cover 110, to allow the positive pressure working fluid in cavity 112 to flow from cavity 112 to the ambient environment at a pressure greater than the cracking pressure of the check valve.

[0112] 2A, cavity check valve 189 can be in a closed position, e.g., to prevent working fluid from passing from cavity 112 through cavity check valve 189 to the ambient environment. In the closed position, device 100 can maintain a positive gauge pressure environment within cavity 112, such as a positive gauge pressure level that is less than a target positive cavity pressure level. The target positive cavity pressure level can be controlled, such as by setting the cracking pressure of the positive pressure cavity check valve to be equal to the target positive cavity pressure level.

[0113] 2B, cavity check valve 189 can be in an open position to allow working fluid to exit cavity 112 through cavity check valve 189 to the ambient environment, such as when the positive gauge pressure in cavity 112 is equal to or greater than the positive target cavity pressure level. In the open position, device 100 can limit the positive gauge pressure environment in cavity 112 to a pressure level approximately equal to the positive target cavity pressure level, such as to protect the eyes from excessive working fluid pressure.

[0114] 3A and 3B show side views of an example of a negative pressure cavity check valve, such as a flapper valve, configured to control the pressure in cavity 112 to a negative target cavity pressure level. The negative target cavity pressure level may be specified by a medical professional, such as to treat, inhibit, or prevent an eye disease. The negative pressure cavity check valve may be located on cover 110, such as on interior surface 188 of cover 110, to allow fluid from the ambient environment to flow into cavity 112.

[0115] 3A, cavity check valve 189 can be in a closed position, e.g., ambient fluid cannot pass from the ambient environment through cavity check valve 189 into cavity 112. In the closed position, apparatus 110 can maintain a negative gauge pressure environment in cavity 112, such as a negative gauge pressure level that is higher than a negative target cavity pressure level. The negative target cavity pressure level can be controlled, such as by setting the cracking pressure of the negative pressure cavity check valve to be equal to the negative target cavity pressure level.

[0116] 3B, cavity check valve 189 can be in an open position, allowing ambient fluid to enter cavity 112 from the ambient environment through cavity check valve 189, such as when the negative gauge pressure in cavity 112 is equal to or less than the negative target cavity pressure level. In the open position, device 100 can limit the negative gauge pressure environment in cavity 112 to a pressure level approximately equal to the negative target cavity pressure level, such as to prevent possible damage to the eye from excessive working fluid pressure.

[0117] As the patient's ocular condition changes, such as improving or worsening, the medical professional can adjust the prescribed treatment regimen, such as to change at least one of the positive target cavity pressure level or the negative target cavity pressure level. To adjust the target pressure levels, the assembly 100 can include an adjustable valve. In one example, the adjustable valve can include a replaceable valve, such as a replaceable check valve assembly.

[0118] 4 shows a side view of an example check valve assembly 190, such as a flapper check valve assembly, in an open position. Device 100 can include a check valve assembly 190, such as a replaceable check valve assembly 190, that adjusts the target cavity pressure level within cavity 112. In one example, device 100 with a first check valve assembly including a first cavity check valve with a first cracking pressure set to a first target pressure level can be replaced with a second check valve assembly including a second cavity check valve with a second cracking pressure set to a second target pressure level, such as to implement a change in the pressure applied to the eye specified in a prescribed patient treatment regimen that includes a change in the target cavity pressure level.

[0119] Cavity check valve assembly 190 can include a base 192 having a first surface 193, a second surface 194 parallel to first surface 193, a base perimeter 195 extending from first surface 193 to second surface 194, a base port 196 extending through base 192 from first surface 193 to second surface 194, and a cavity check valve 189 located on first surface 193 above base port 196, such as at least a portion of base port 196. Cavity check valve assembly 190 can be positioned within device 100, such as cover 110, such that base perimeter 195 can contact cover 110, such as at least a portion of a surface of port 114.

[0120] The check valve assembly 190 can be located in the device 100 in communication with the cavity 112, such as on at least one of the cover 110, the conduit 117, the control circuit 140, or the pressure source 150, including any surface of the cover 110. The cavity check valve assembly 190 can be located in contact with the cover 110, for example, the base perimeter 195 can be in contact with at least a portion of the cover 110, such as at least one of the surface of the port 114, the outer surface 187, or the inner surface 188. The cavity check valve assembly 190, such as a positive pressure check valve assembly, can be configured to control the pressure in the cavity 112 to a positive target cavity pressure level, for example, the check valve assembly 190 can be located in the port 114 such that the cavity check valve 189 can be located outside the cavity 112. A cavity check valve assembly 190, such as a negative pressure check valve assembly, can be configured to control the pressure in the cavity 112 to a negative target cavity pressure level, for example, the check valve assembly 190 can be located in the port 114 so that the cavity check valve 189 can be located inside the cavity 112.

[0121] Referring again to FIG. 1 , the fluid regulator 120 can regulate the flow of fluid between two reservoirs, such as between the cavity 112 and a fluid source 170, such as a pressurized gas cylinder. The fluid regulator 120 can include a regulator valve, such as one that regulates the flow of fluid between a first reservoir and a second reservoir. The regulator valve can include a passive valve, such as a check valve, that closes when the pressure exceeds a critical value. In one example, the fluid regulator 120 with a check valve can be located between the cover 110 and the fluid source 170. For example, if the pressure of the fluid source 170 exceeds a critical value, such as a pressure that could cause damage to the patient's eye, the check valve can close to isolate the pressure of the fluid source 170 from the patient's eye, such as to protect the patient's eye from excessive force. The regulator valve can include an active valve, such as an electrically operated valve, including a servo valve, or a proportional valve, such as a piezoelectrically actuated proportional valve. In one example, the regulator valve can receive a control signal, such as from a control circuit 140, to adjust the position of an electrically-modulated spool relative to the valve body, such as to regulate fluid flow through the electrically operated valve.

[0122] The fluid regulator 120 can be attached to the fluid source 170, such as to regulate the flow of fluid from the fluid source 170 to the cavity 112. The fluid source 170 can include a fluid container, such as a storage container of a pressurized gaseous fluid. The fluid source 170 can include a generator, such as a device that concentrates or distills a constituent fluid from another fluid. In one example, the generator can include a concentrator, such as an oxygen concentrator or a carbon dioxide concentrator. In one example, the generator can include an atomizer, such as an ultrasonic humidifier or an aerosolizer, that converts a liquid therapeutic fluid, such as a miscible solution or colloidal suspension, into a gaseous working fluid, such as a therapeutic mist or fog.

[0123] Fluid regulator 120 can be in communication with device 100, for example, fluid regulator 120 can be in communication with cavity 112. In one example, fluid regulator 120 can be connected to cover 110, such as by a conduit 117 that communicates directly with cover 110 through second port 116. In one example, fluid regulator 120 can be connected to conduit 117 that communicates with cover 110 by a tubing connector 118, such as a Y-connector. In one example, fluid regulator 120 can be connected to control circuit 140, such as to receive a control signal from control circuit 140 to adjust the position of a servo valve.

[0124] The sensor 130 may sense an indicator of the ocular environment within the cavity 112, such as an indicator of a property of the working fluid within the cavity 112, or at least one of an indicator of a physiological parameter of the patient. The sensor 130 may include sensor circuitry, such as sensor circuitry, that receives the indicator of the physical parameter sensed by the sensor 130 and processes the received indicator, such as into an indicator comprising an electrical signal suitable for reception by at least one of the control circuit 140 or the pressure source 150.

[0125] The sensor 130 can be located proximate to the device 100, such as in communication with the cavity 112 or at least partially attached to the patient. In one example, the sensor 130 can be separate from the device 100. For example, the sensor 130 can include a handheld pressure gauge, such as pressed against a measuring diaphragm located over the port 114 to sense an indication of the working fluid pressure in the cavity 112. In one example, the sensor 130 can be in fluid communication with the cavity 112, e.g., the sensor 130 can be located within the cavity 112 or on the control circuit 140 in fluid communication with the cavity 112. In one example, the sensor 130 can be at least partially attached to the patient, such as to the surface of the eye, including the anterior surface of the eye, or to patient tissue overlying the skull, including tissue over the frontal, parietal, sphenoid, temporal, zygomatic, maxilla, occipital, and mandible bones. For example, sensor 130 may include an electroretinography device, a portion of which may include electrodes attached to patient tissue to sense indices of electrical activity within the patient, including electrical activity associated with a pattern electroretinography (or PERG) test. Sensor 130 may be in electrical communication with a device, such as at least one of control circuitry 140 or pressure source 150. Sensor 130 may provide at least one of continuous or periodic (e.g., intermittent) sensing of the working fluid, such as to monitor an indication of the ocular environment by sensor 130 or an indication of a physiological parameter associated with the patient, such as IOP or CSFP.

[0126] Sensor 130 can include an intraocular pressure (IOP) sensor, such as a device for sensing an indication of an IOP level in an eye. The IOP sensor can include at least one of an invasive IOP sensor, such as an IOP sensor implantable in the intraocular space of an eye to sense IOP, including sensors sold under the trademark EYEMATE® by Implandata Oftalmic Products GmbH (Hannover, Germany), or a non-invasive IOP sensor for sensing IOP without being implanted in the body, such as a contact lens-based sensor sold under the trademark SENSIMEDTRIGGERFISH® by Sensimed AG (Lausanne, Switzerland).

[0127] The IOP sensor may include at least one of a continuous IOP sensor, such as an IOP sensor capable of continuously sensing the IOP level of a patient's eye, or a periodic IOP sensor, such as an IOP sensor capable of sensing the IOP level of a patient's eye at periodic or aperiodic intervals. In one example, the periodic IOP sensor may include a tonometer, such as a handheld tonometer designed for patient self-monitoring of IOP. Data sensed by the IOP sensor may be received by control circuitry 140, such as to facilitate use of device 100.

[0128] The sensor 130 may include a cardiac sensor, such as to detect an indicator of the patient's cardiac activity. The indicator of cardiac activity may include at least one of an indicator of systemic blood pressure, such as an indicator of systolic blood pressure and an indicator of diastolic blood pressure, or an indicator of heart rate.

[0129] The cardiac sensor can include a blood pressure (BP) sensor, such as a device for sensing an indicator of blood pressure level, including systemic blood pressure level, in a patient. The BP sensor can include at least one of an invasive BP sensor, such as a BP sensor implantable within a patient, and a non-invasive BP sensor, such as a BP sensor capable of sensing BP without being implanted within a patient.

[0130] The sensor 130 may include a working fluid flow sensor, such as a device for detecting an indication of the flow of the working fluid, including at least one of a volumetric flow rate or a mass flow rate into or out of the cavity 112. The sensor 130 may include a humidity sensor, such as a device for detecting an indication of the relative humidity of the working fluid in the cavity 112. The sensor 130 may include a thermometer, such as a device for detecting an indication of the temperature of the working fluid in the cavity 112. The sensor 130 may include a displacement sensor, such as a device for detecting an indication of displacement, including an optical coherence tomography device configured to detect displacement of a structure associated with the patient's eye.

[0131] The sensor 130 may include a pressure sensor, such as a device that senses an indication of the pressure of the working fluid within the cavity 112. The pressure sensor may be located in proximity to the cavity 112, such as in communication with the cavity 112. In one example, the pressure sensor may include a cavity pressure sensor, such as a pressure sensor located within the cavity 112.

[0132] In one example, in some cases, the working fluid pressure within cavity 112 can serve as an estimate (e.g., an approximation) of the intraocular pressure (IOP) within the eye. However, due to characteristics of the eye, such as corneal thickness and corneal stiffness, the cavity pressure may not serve as a proxy for the eye's IOP.

[0133] A static cavity pressure level within cavity 112, such as the pressure level sensed by a pressure sensor when pressure source 150 is not regulating the actuating fluid pressure within cavity 112, can be the same anywhere within cavity 112. A dynamic cavity pressure level, such as the pressure level sensed by a pressure sensor when pressure source 150 is regulating the actuating fluid pressure within cavity 112, can vary depending on the location of the pressure sensor in communication with cavity 112.

[0134] Sensor 130 may include a pressure sensor combined with another indicator, such as an indicator of the operating state of pressure source 150, to estimate a static cavity pressure level within cavity 112. In one example, a pressure sensor, such as a pressure-flow sensor including a sensor capable of measuring both working fluid pressure (static and dynamic) and working fluid flow rate at a measurement location, may be located proximate pressure source 150, such as at an inlet or outlet port of pressure source 150, to include circuitry, such as a sensor circuit, that senses an indicator of dynamic pressure at the pressure sensor location and receives an indicator of the operating state of pressure source 150, including an indicator of flow rate (e.g., pump speed may be proportional to flow rate). The pressure-flow sensor may process at least one of the indicator of dynamic pressure or the indicator of flow rate, such as to generate a control signal that pressure source 150 may receive to achieve a static cavity pressure, such as a target pressure level, within cavity 112. The control signal may be based on a relationship between the indicator of dynamic pressure and the indicator of flow rate, such as a relationship between pressure and flow rate, including a relationship described by a pQ (e.g., pressure-flow) chart, which may take into account the operating characteristics of pressure source 150.

[0135] In one example, the pressure sensor can be located proximate to the pressure source 150. The control circuit 140 can be configured to receive an indication of the dynamic pressure from the pressure sensor and an indication of the operating conditions of the pressure source 150, including an indication of the pump speed. The control circuit 140 can process at least one of the indication of the dynamic pressure or the indication of the operating conditions of the pressure source 150, such as to form a control signal that the pressure source 150 can receive to achieve a static cavity pressure level, such as a target pressure level, in the cavity 112.

[0136] The sensor 130 can include a concentration sensor or working fluid composition sensor, such as a device for detecting an indication of a chemical component in the working fluid. In one example, the concentration sensor can be configured to detect an indication of the working fluid, such as a component in the working fluid. The component in the working fluid, such as the component in the working fluid delivered to the cavity 112, can include a therapeutic fluid. In at least one example, the working fluid composition sensor can detect at least one of a therapeutic fluid, such as (CO), oxygen (O), nitric oxide (NO), ozone (O), nitrogen, helium (He), hydrocarbons, including fluorocarbons and perfluorocarbons, sulfur hexafluoride, cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD), or a combination of therapeutic gases.

[0137] The sensor 130 can include a biomarker sensor, such as a device for detecting an indication of a biomarker, including a chemical component. The chemical component in the working fluid can include a biomarker, such as a biomarker released from or detected within the patient's eye. The biomarker can indicate a physiological condition of the eye, such as a state of distress where medical intervention may be required. Biomarker sensors can include ketones, such as those detectable by volatile gas sensors including quartz crystal nanobalance (QCN) sensors; glucose, such as those detectable by optical glucose sensors including OCT imaging systems; oxygen levels, such as those detectable by noninvasive optical oxygen sensors; dissolved salts, such as those detectable by salinity sensors; and vascular endothelial growth factor (i.e., VEGF), such as those detectable by aptamer-based sensors, including the sensors and methods described in the publication by Kwon et al., "Flexible FET-Type VEGF Aptasensor Based on Nitrogen-Doped Graphene Converted from Conducting Polymer," ACS Nano, Vol. 6, No. 2, pp. 1486-1493, published February 2012, and incorporated herein by reference in its entirety. The biomarkers can include at least one of an enzyme, such as matrix metallopeptidase 9 (MPP-9), which can be detected by an enzyme sensor, or a protein, such as brain-derived neurotrophic factor (BDNF), which can be detected by a protein sensor.

[0138] The sensor 130 may include a biosensor, such as a sensor configured to sense an indicator of a physiological parameter associated with the patient. The physiological parameter may include an indicator of a physiological process associated with the patient, such as a process associated with the patient's eye or a process associated with physiological activity of the patient's eye. In one example, the physiological parameter may include at least one of an indicator of intraocular pressure (IOP) in the patient's eye (e.g., an IOP level), an indicator of cerebrospinal fluid pressure (CSFP) associated with the patient (e.g., a CSFP level), and an indicator of cardiac activity, such as at least one of systemic blood pressure or heart rate. The physiological parameter may include an indicator of retinal activity, such as measured by an electroretinogram device, including a pattern electroretinogram (i.e., PERG) device.

[0139] The sensor 130 may include an image sensor for sensing an ocular indicator, such as an intraocular portion of the eye. The image sensor may be located proximate to the eye, such as attached to the apparatus 100 including the cover 110, or may be separate from the apparatus, such as included as a stand-alone device. In one example, the image sensor may include a camera, such as a single image capture camera, or multiple image capture cameras, including a video camera, such that one or more captured images can be transferred to the apparatus 100 for image processing. In one example, the image sensor may include an optical coherence tomography (OCT) device.

[0140] The sensor 130 can include a blood flow sensor, such as an ocular blood flow sensor. The blood flow sensor can include an invasive blood flow sensor ophthalmic imaging system, such as a blood flow sensor imaging system that requires insertion of at least some components of the system into a patient. In one example, an invasive blood flow sensor ophthalmic imaging system can include a fluorescein angiography system.

[0141] The blood flow sensor can include a non-invasive ocular blood flow sensor ocular imaging system, such as an ocular blood flow sensor imaging system that does not require insertion of a sensor imaging system component into a patient. The non-invasive ocular blood flow sensor ocular imaging system can include a system for sensing an indicator of ocular blood flow from a patient or circuitry that processes information from the patient to generate an indicator of ocular blood flow. The indicator of ocular blood flow can include at least one of peak systolic blood velocity (PSV), end diastolic blood velocity (EDV), mean blood velocity (MV), a resistivity index (RI) such as RI = (PSV - EDV) / PSV, or a pulsatility index (PI) such as PI = (PSV - EDV) / MV.

[0142] An ophthalmic imaging system for a noninvasive ocular blood flow sensor can include an ophthalmic energy source for irradiating tissue, including ocular tissue, with energy to elicit a response from the tissue that can be detected by the sensor. The ocular tissue can be irradiated with electromagnetic (EM) energy generated by the ophthalmic energy source, for example, EM energy in a frequency range from about 3 hertz (Hz) to about 300 exahertz (EHz). In one example, the ophthalmic energy source can include a diffuse light source, such as generated by a light bulb, and a collimated light source, such as generated by a laser diode.

[0143] A non-invasive ocular blood flow sensor ophthalmic imaging system can include an ocular blood flow sensor for detecting energy emitted from ocular tissue, including energy induced from ocular tissue by irradiating the ocular tissue with an energy source, etc. The ocular blood flow sensor can be configured to detect EM energy, such as EM energy in a frequency range from about 3 Hertz (Hz) to about 300 Hertz (EHz).

[0144] In one example, the ocular blood flow sensor can include an ultrasonic sensor, such as an ultrasonic sensor configured to detect EM energy in a frequency range of about 3 Hz to about 300 gigahertz (GHz), including a frequency range of about 20 kilohertz (kHz) to about 400 kHz and a frequency range of about 1 megahertz (MHz) to about 18 MHz.

[0145] The ocular blood flow sensor can include a charge-coupled device (CCD) sensor, including a complementary metal-oxide semiconductor (CMOS) sensor, that can be configured to detect EM energy in the frequency ranges of about 300 GHz to about 300 EHz (infrared radiation, corresponding to wavelengths of about 1,000 micrometers to about 750 nanometers (i.e., nm)), about 400 THz to about 800 THz (visible light, corresponding to wavelengths of about 750 nm to about 375 nm), and about 800 THz to about 30 petahertz (i.e., PHZ) (ultraviolet radiation, corresponding to wavelengths of about 375 nm to about 10 nm), including the frequency ranges of about 300 GHz to about 400 tetrahertz (i.e., THz).

[0146] The ophthalmic imaging system of the non-invasive ocular blood flow sensor can include a color doppler imaging (CDI) system, such as a medical ultrasound imaging system, including at least one of an ophthalmic energy source such as an ultrasound transducer, an ophthalmic blood flow sensor such as an ultrasound receiver, or a combination of an ophthalmic energy source such as an ultrasound transceiver and an ophthalmic blood flow sensor. In one example, the CDI system can be configured with an energy source capable of generating EM energy at a frequency of about 6.5 mL / s.

[0147] The ocular imaging of the noninvasive ocular blood flow sensor system can include a laser speckle flowgraphy (LSF) system or a laser speckle contrast imaging (LSCI) system. In one example, the LSF system can be configured with an energy source capable of generating EM energy at a frequency of approximately 361 THz (corresponding to a wavelength of approximately 830 nm). In one example, the LSF system can include a system sold under the trade name LSFG-Retflow by Nidek Co., Ltd. (Aichi, Japan).

[0148] The non-invasive ocular blood flow sensor system can include a laser Doppler flowmeter (LDF), such as a confocal scanning laser Doppler flowmetry (CSLDF) system. In one example, the LDF system can be configured with an energy source capable of generating EM energy at a frequency of approximately 384 THz (corresponding to a wavelength of approximately 780 nm). In one example, the CSLDF system can include a system sold under the trade name Heidelberg Retina Flowmeter by Heidelberg Engineering GmbH (Heidelberg, Germany).

[0149] The noninvasive ocular blood flow sensor system can include an ocular coherence tomography angiography (OCTA) system. In one example, the functionality of an ocular coherence tomography (OCT) system can be enhanced, such as by placing an OCTA module in communication with the OCT system. The OCTA module can include control circuitry that executes coded instructions to cause the OCT system to repeatedly scan cross sections of ocular tissue, store each scan of the ocular tissue in a memory, and process the stored scans to identify differences between the scans, such as to generate an index of ocular blood flow. In one example, the OCTA system can include at least one of an OCT system sold under the trade name Spectralis® by Heidelberg Engineering GmbH (Heidelberg, Germany) or an OCTA module sold under the trade name Spectralis OCT Angiography Module by Heidelberg Engineering GmbH (Heidelberg, Germany).

[0150] The non-invasive ocular blood flow sensor system can include a laser doppler velocimetry (LDV) system. In one example, the LDV system can be configured with an energy source capable of generating EM energy at a frequency of about 444 THz (corresponding to a wavelength of about 675 nm).

[0151] The non-invasive ocular blood flow sensor system can include a retinal vessel analyzer (RVA) system that illuminates the blood vessels of the eye and detects at least one of an optical reflection coefficient or an optical absorption coefficient.

[0152] The non-invasive ocular blood flow sensor system can include a Doppler optical coherence tomography (DOCT) system including a collimated light source, such as a collimated light source, configured to illuminate ocular tissue and a CCD sensor configured to receive the collimated light reflected from the ocular tissue. In one example, the DOCT system can be configured with an energy source capable of generating EM energy at a frequency of approximately 356 THz (corresponding to a wavelength of approximately 841 nm). In one example, the DOCT system can include a DOCT system sold under the trade name RTVue by Optovue, Inc. (Fremont, California).

[0153] The non-invasive ocular blood flow sensor system can include at least one of a retinal functional imager (RFI) system, a pulsatile ocular blood flow (POBF) system, a fundus pulsation amplitude (FPA) system, a fluorescein and indocyanine angiography (FA, ICG) system, a color doppler imaging (CDI) system, a retinal oximetry system, a magnetic resonance imaging (MRI) system, a blue light coherence tomography system, a frequency domain optical coherence tomography (FD-OCT) system, an angiography system, or a Spectrum Amplitude Decorrelation Angiography with Optical Coherence Tomography (SSADA-OCT) system.

[0154] The non-invasive ocular imaging system can include an electroretinography (ERG) system, such as at least one of a full-field, multifocal, pattern, or visual evoked potential (VEP) electroretinography system. In one example, the ERG system can be configured with an energy source capable of generating EM energy at a frequency of about 440 THz (corresponding to a wavelength of about 680 nm or greater). In one example, the ERG system can include a system sold under the trade name DiopsysNova-ERG by Diopsys, Inc. (Pine Brook, New Jersey).

[0155] The ERG system can include recording electrodes, such as to detect an indication of electrical activity of the eye, including at least one of neuronal and non-neuronal cells in the retina, from a stimulus applied to the eye, including EM energy, such as visible light. In one example, the recording electrodes can be used with the ERG system to measure an indication of electrical activity of the eye, such as a pattern electroretinogram (PERG) test, as an indication of ocular blood flow. The recording electrodes can include at least one of an electrode that can contact the eye, such as an electrode attached to a contact lens and configured to contact the surface of the eye, or an electrode in close proximity to the eye, such as an electrode that can be placed on the lower eyelid of the eye.

[0156] The non-invasive ocular imaging system can include a retinal functional imaging (RFI) system. The RFI system can be configured with an energy source capable of generating EM energy at a frequency of approximately 547 THz (corresponding to a wavelength of approximately 548 nm). In one example, the RFI system can include a system sold by Optical Imaging, Ltd. (Rehovot, Israel) under the trade name RFI3000. The RFI system can be configured with an energy source capable of generating EM energy at a frequency of approximately 666 THz (corresponding to a wavelength of at least 450 nm). In one example, the RFI system can include a system sold by OcuScience Inc. (Ann Arbor, Michigan) under the trade name OcuMet Beacon.

[0157] The control circuitry 140 can enable and regulate the operation of the device 100. In one example, the control circuitry 140 can be coupled to, for example in communication with, at least one of the fluid regulator 120, the sensor 130, the pressure source 150, or the fluid source 170.

[0158] The control circuitry 140 may include a data interface configured to receive signals, such as at least one of indicators of the ocular environment sensed by the sensor 130. In one example, the sensed indicators may include at least one of an indicator of the ocular environment, such as a sensed indicator from the sensor 130, or an indicator of a relationship between an indicator of the left ocular environment and an indicator of the right ocular environment. The control circuitry 140 may process the received signals, such as into processed signals, and transmit the processed signals to one or more components of the device 100.

[0159] The control circuit 140 can communicate with the fluid regulator 120, such as to adjust the position of the regulator valve to control the working fluid composition. The control circuit 140 can communicate with the sensor 130, such as to receive and process indicators of the ocular environment, including sensed data from the sensor 130. The control circuit 140 can communicate with the pressure source 150, such as to generate a pressure source control signal to regulate at least one of the working fluid pressure or working fluid flow rate in the device 100.

[0160] The control circuitry 140 may provide a communications interface, such as to enable a user to operate and interact with the device 100. The communications interface may include a graphical user interface (i.e., GUI), such as to communicate information to or receive information from the user, including information about the device 100 (e.g., readings of detected indicators, fault status, etc.). The information received from the user may include at least one of information for managing basic functions of the device 100, such as cycling power to the device 100, or an indicator of user preferences, such as operating parameters including target levels defining a treatment protocol and safety parameters, such as maximum and minimum limits. In one example, the communications interface may receive a safety pressure level, such as at least one of a maximum pressure level or a minimum pressure level in the cavity 112 selected by the user to prevent damage to the patient's eye, and adjust the pressure of the working fluid delivered to the cavity 112 or set the target pressure level in the cavity 112.

[0161] The control circuitry 140 may include digital signal processing (DSP) circuitry, such as for receiving and recording indicators, including indicators of the ocular environment sensed by the sensor 130, such as at least one of an environmental parameter or a physiological parameter. The indicators of the ocular environment may be monitored and recorded by the control circuitry 140 over a period of time, such as over a period of seconds, minutes, hours, days, years, or over a period of the patient's life.

[0162] Control circuitry 140 may include a processing unit, such as a programmable central processing unit (CPU), that can execute instructions that implement a method of using device 100, such as to treat, inhibit, or prevent an eye disease in a patient. In one example, the CPU may be a component of a computer, such as computer 1500.

[0163] The CPU may be configured as a control circuit, such as a feedback control circuit, that receives information, such as at least one of an indication sensed by the sensor 130, an indication of a user preference from the communication interface, or an indication of a processed signal, including a signal processed by the CPU, and processes the sensed indication, such as to form a control signal.

[0164] The CPU may be configured as a pressure feedback control circuit, such as generating a control signal (e.g., a pressure source control signal) to the pressure source 150 to adjust the pressure level within the cavity 112 based on an indication of the cavity pressure level from a pressure sensor in communication with the cavity 112.

[0165] In one example, the pressure source control signal may be based on an indication of cavity pressure, such as the pressure within cavity 112, to achieve a target pressure level within cavity 112. The pressure feedback control circuit may receive an indication of the working fluid pressure within cavity 112, such as an indication of the cavity pressure level sensed by sensor 130, which may include a pressure sensor in communication with cavity 112. The pressure feedback control circuit may process the received indication of the pressure level to form a control signal, such as a control signal that adjusts pressure source 150 to achieve the target pressure level within cavity 112.

[0166] Processing the received pressure indicator may include calculating an indicator, such as calculating an indicator of a difference between the cavity pressure level indicator and an indicator of a user preference, including the cavity pressure setpoint level received from the communications interface to form an indicator of a cavity pressure differential value. Processing the received indicator may include generating a control signal based on the cavity pressure differential value indicator by a proportional-integral-derivative (PID) control algorithm executing on the CPU to regulate pressure source 150. Generating the control signal may include generating a control signal that minimizes the difference between the received pressure level indicator and the cavity pressure setpoint level.

[0167] In one example, the pressure source control signal can be based at least in part on an indicator of a physiological parameter associated with the patient, such as an indicator of IOP in the patient's eye, to achieve a target IOP level in the patient's eye. The pressure feedback control circuit can receive an indicator of an IOP level in the patient's eye, such as an indicator of an IOP level sensed by a sensor 130 including a biosensor configured to sense IOP. The pressure feedback control circuit can process the received indicator of the IOP level to form a control signal, such as a control signal that adjusts the pressure source 150 to achieve a target cavity pressure level in the cavity 112, such as a target cavity pressure level sufficient to achieve the target IOP level in the patient's eye.

[0168] Processing the received indication of IOP can include calculating a difference between the indication of IOP level and an indication of user preference, including an IOP setpoint level, received from the communications interface to generate an IOP difference value. Processing the received indication can include generating a control signal based on the IOP difference value by a proportional-integral-derivative (PID) control algorithm executing on the CPU to regulate pressure source 150. Generating the control signal can include generating a control signal that minimizes the difference between the received indication of pressure level and the cavity pressure setpoint level.

[0169] The CPU may be configured as a concentration feedback control circuit, such as to generate regulator control signals to adjust chemical component levels within cavity 112 . In one example, the regulator control signal can be based on an indicator of a chemical constituent associated with the working fluid, such as an indicator of nitric oxide (NO) concentration, to achieve a target NO concentration level in the working fluid. The concentration feedback control circuit can receive an indicator of an NO concentration level in the working fluid, such as an indicator of an NO level sensed by sensor 130, which includes a concentration sensor configured to sense NO. The concentration feedback control circuit can process the received indicator of the NO level to form a control signal, such as a control signal that adjusts regulator 120 to achieve the target NO concentration level in cavity 112.

[0170] Processing the received indicator of NO concentration may include calculating a difference between the indicator of NO concentration and an indicator of user preference, including an NO setpoint level, received from the communication interface to generate an NO difference value. Processing the received indicator may include generating a control signal based on the NO difference value. Processing the received indicator may include generating a control signal based on the NO difference value by a proportional-integral-derivative (PID) control algorithm executing on the CPU to adjust regulator 120. Generating the control signal may include generating a control signal that minimizes the difference between the received indicator of NO concentration and the NO setpoint level.

[0171] Control circuitry 140 may include a pressure source circuit, such as a pressure source circuit configured to adjust operation of pressure source 150 based on at least one of the indicators sensed by sensor 130. The pressure source circuit may include a pressure source logic circuit, such as a pressure source logic circuit configured to generate a system fault based on at least one of the sensed indicators received at the data interface or an indicator of a user preference received through the communications interface. In one example, the pressure source logic circuit may generate a system fault upon the occurrence of a fault event, such as when an indicator of cavity pressure in cavity 112 exceeds a pressure safety level, such as a pressure safety level set by a user through the communications interface.

[0172] The control circuit 140 may include a power source 152, such as to provide electrical energy to the device 100. In one example, the power source 152 may include a battery, such as a lithium-ion battery, and a transformer, such as to receive power from a wall outlet at a specified voltage and current for use with the device 100. The control circuit 140 may include a heating element, such as a heating element in communication with the treatment fluid, including a heating element located on or near the cover 110, including the inner surface 188 of the cover 110, or in the fluid regulator 120, to increase the temperature of the treatment fluid.

[0173] Pressure source 150 may generate a volumetric flow of working fluid within device 100, such as to move working fluid from pressure source 150 to cavity 112 or to move working fluid from cavity 112 to at least one of pressure source 150 or the ambient environment. Pressure source 150 may be configured to apply a non-atmospheric pressure to cavity 112, such as to adjust an indication of fluid pressure, including an indication of a pressure level within cavity 112, from a first pressure level to a second pressure level different from the first pressure level.

[0174] Pressure source 150 can include a pump, such as a pump capable of generating at least one of a positive gauge pressure or a negative gauge pressure. Pressure source 150 can include a powered pressure source, such as a pump, including a positive displacement pump or a centrifugal pump. For example, pressure source 150 can include a diaphragm pump, such as a diaphragm vacuum pump. Pressure source 150 can include a manual pressure source, such as a hand pump, including a bellows-style pump. In one example, pressure source 150 can be integrated into a component of device 100, such as cover 110.

[0175] 1A illustrates an example of apparatus 101, including an example manual pressure source. In one example, apparatus 101 can include all of the components of apparatus 100. Apparatus 101 can include a bellows cover 111, such as at least one of left bellows cover 111A or right bellows cover 111B, a cavity check valve 189, such as at least one of left cavity check valve 189A or right cavity check valve 189B, and a seal 119, such as at least one of left seal 119A or right seal 119B.

[0176] The bellows cover 111 can be sized and shaped to surround and be spaced from the patient's eye, such as without contacting the eye, including the anterior surface of the eye. The bellows cover 111 can be sized and shaped to surround and cover both of the patient's eyes, such as the patient's left and right eyes. In one example, the bellows cover 111 can include a mask, such as a bellows cover 111 similar in shape and function to a diving or snorkeling mask.

[0177] The bellows cover 111 can include a bellows portion, such as a portion of the bellows cover 111 between the lens 182 and the seal 119. The bellows portion can assume a first bellows position, as defined by a first bellows distance between the lens 182 and the seal 119. The bellows portion can assume a second bellows position, such as a position displaced from the first bellows position. The bellows portion can exhibit resistance to movement, e.g., require an external force to displace the bellows portion from the first bellows position to the second bellows position. The level of resistance to movement can be controlled through selection of the bellows material, bellows portion design, including the number of bellows folds, and the like. The bellows portion can exhibit resilience, e.g., the tendency of the bellows portion to recover to an equilibrium position, including a force equilibrium position, after removal of the external force.

[0178] The second bellows position can include a compression bellows position to generate a negative gauge pressure (e.g., a vacuum) on the patient's eye. In one example, the distance between the lens 182 and the seal 119 can be reduced from a first bellows position, such as a compression bellows position, when a compressive force is applied to the bellows cover 111 to the compression bellows position. When the bellows cover 111 moves from the first bellows position to the compression bellows position, the volume of the cavity 112 can be reduced, such as by increasing the pressure of the working fluid in the cavity 112, which can then expel a volume of working fluid from the cavity 112, such as through the check valve 189. When the compressive force is removed, the resilience of the bellows portion can restore the bellows portion to a third bellows position, such as a position between the first bellows position and the compression bellows position, such as to create a “suction” or negative gauge pressure on the patient's eye.

[0179] The second bellows position can include an extended bellows position that generates a positive gauge pressure (e.g., an increase in pressure compared to atmospheric pressure) on the patient's eye. In one example, the distance between the lens 182 and the seal 119 can increase from the first bellows position to the extended bellows position, etc., when an expansion force is applied to the bellows cover 111. When the bellows cover 111 moves from the first bellows position to the extended bellows position, the volume of the cavity 112 can increase, such as by decreasing the working fluid pressure in the cavity 112, and the cavity 112 can then receive a volume of ambient air from the surrounding environment, such as through the check valve 189. When the external force is removed, the resilience of the bellows portion can restore the bellows portion to a third bellows position, such as a position between the first bellows position and the extended bellows position, such as to create a "pressurized" or positive gauge pressure on the patient's eye.

[0180] Pressure source 150 can include a pressure source, such as a pressurized gas cylinder or a source of pressurized fluid separate from apparatus 100, that can be used to regulate the pressure of the actuating fluid in cavity 112. Pressure source 150 can include a pressure source used in combination with an auxiliary device to regulate the pressure in the cavity. In one example, pressure source 150 can include a venturi-type pump, such as a venturi jet pump, in combination with a pressure source to regulate the fluid pressure in cavity 112.

[0181] The pressure source 150 can be characterized by physical properties, such as the relationship between physical properties. A useful criterion for comparing the performance of several sources of flow is a volume-pressure characteristic, such as the relationship between the volume of working fluid flow from the flow source and the pressure, such as static pressure, resulting from the fluid flow. In one example, the pressure source 150 can be characterized by a volume-pressure characteristic, such as a pQ chart.

[0182] The pressure source 150 can generate pressure within the cavity 112, such as to adjust the pressure within the cavity 112 to move toward or achieve a target cavity pressure within the cavity 112. The target cavity pressure can include a cavity pressure that affects a measurement procedure, including a diagnostic procedure, on the patient's eye. In one example, the pressure within the cavity 112 can be adjusted by the pressure source 150 toward a target cavity pressure, such as a first target cavity pressure that affects a first displacement of the anterior surface of the patient's eye. An indication of the first displacement can be sensed by the sensor 130, which includes a displacement sensor. A second target cavity pressure can then affect a second displacement of the anterior surface of the patient's eye, such as an indication of a second displacement that can be sensed by the displacement sensor. A difference between the indications of displacement between the first and second target pressures can provide an estimate of a physiological parameter, such as an estimate of an index of IOP within the patient's eye.

[0183] The target cavity pressure can include a cavity pressure that affects a treatment of the patient's eye, such as a cavity pressure prescribed by a medical professional to treat, inhibit, or prevent an ocular disease. In one example, the pressure within cavity 112 can be adjusted by pressure source 150 toward a target cavity pressure that affects an indicator of a physiological parameter of the patient's eye, including an indicator of an IOP level within the patient's eye that can be detected by sensor 130, which includes a biosensor configured to detect the indicator of IOP. A treatment of the patient's eye can be affected by pressure source 150, such as by adjusting the pressure source to achieve a target cavity pressure within cavity 112 that affects a desired indicator of an IOP level within the patient's eye.

[0184] The target cavity pressure can include a target IOP cavity pressure, such as a pressure applied to the cavity 112 to achieve a target IOP level in the patient's eye. The target IOP cavity pressure can include a cavity pressure that can adjust or achieve an IOP level in the patient's eye, such as to increase or decrease the IOP level in the patient's eye. The target IOP level can include an IOP level in the range of about 5 mmHg to about 30 mmHg, an IOP level in the range of about 10 mmHg to about 21 mmHg, and an IOP level in the range of about 12 mmHg to about 18 mmHg.

[0185] Translaminar pressure describes the pressure difference across the lamina cribrosa. The translaminar pressure difference (TPD) can be defined as the difference between the intraocular pressure in a patient's eye and the cerebrospinal fluid pressure in the patient's body. The translaminar pressure gradient (TPG) is related to TPD and can be defined as the difference between IOP and CSFP per unit thickness of the lamina cribrosa. Indicators of TPD, such as TPD levels, can indicate the physiological health of a patient's eye, such as the presence or absence of ocular disease. Physiologically normal eyes, such as patient eyes without ocular disease, can be characterized by normal TPD levels, such as normal TPD levels in at least one of the ranges of about -4 mHg to about 4 mmHg or about -6 mHg to about 6 mmHg. In contrast, abnormal eyes, such as those of patients with ocular diseases including glaucoma, can be characterized by TPD levels that are outside the range of normal TPD levels; for example, such TPD levels can be less than about -4 mmHg or greater than about 4 mmHg.

[0186] The target cavity pressure can include a target equalization cavity pressure, such as a pressure applied to the cavity 112 that can equalize the TPD level in the eye. The cavity pressure that can equalize the TPD level in the eye can include any pressure applied to the cavity 112 that can reduce the TPD level in the eye, such as from a first TPD level to a second TPD level, including where the absolute value of the second TPD level can be less than the absolute value of the first TPD level.

[0187] The target cavity pressure may include a target translaminar pressure (TPD) cavity pressure, such as a pressure applied to the cavity 112 that can achieve a target TPD level in the patient's eye. The target TPD cavity pressure may include a pressure level applied to the cavity 112 sufficient to adjust the TPD level of the patient's eye to a range, such as a target TPD level range. The target TPD level range may include at least one of TPD levels ranging from about −4 mmHg to about 4 mmHg, about −6 mmHg to about 6 mmHg, about −7 mmHg to about 7 mmHg, or about −10 mmHg to about 10 mmHg. In one example, the normal TPD level range may include at least one of TPD levels ranging from about −4 mmHg to about 4 mmHg or about −6 mmHg to about 6 mmHg.

[0188] Adjusting TPD, such as adjusting TPD in a patient's eye from a first TPD level to a second TPD level lower than the first TPD level, can improve physiological processes in the patient's eye, such as to improve the health of the patient's eye. Axonal transport, such as a collection of cellular processes responsible for maintaining cell viability in the patient's optic nerve, can be adversely affected by the presence of elevated TPD, such as when an indicator of TPD in the patient's eye is not within a normal TPD level range. Indicators of axonal transport levels, such as in the optic nerve, can be detected by a sensor 130 including an axonal transport sensor. In one example, the axonal transport sensor can include at least one of an optical coherence tomography (OCT) imaging system or a confocal scanning laser ophthalmoscope (CSLO) system.

[0189] The target cavity pressure can include a target axonal transport cavity pressure, such as a cavity pressure applied to cavity 112 to achieve a target axonal transport level in the patient's eye. The target axonal transport cavity pressure can include a cavity pressure that can improve (or increase) an index of axonal transport level in the eye, such as from a first index of axonal transport level to a second index of axonal transport level, where the second index of axonal transport level can be higher than the first index of axonal transport level.

[0190] The rate of axonal transport can vary based on the physiological component being transported, etc. In one example, "slow" axonal transport can refer to the movement of cytoplasmic components along the axon, including, for example, the cytoskeleton of intermediary metabolism and soluble enzymes. Target axonal transport levels for slow axonal transport components can include axonal transport levels ranging from about 0.2 mm / day to about 2 mm / day. In one example, "fast" axonal transport can refer to the movement of mitochondrial polypeptides, such as synaptic vesicle polypeptides, and neuropeptides along the axon. Target axonal transport levels for fast axonal transport components can include axonal transport levels ranging from about 50 mm / day to about 100 mm / day for mitochondrial polypeptides, etc., and axonal transport levels ranging from about 100 mm / day to about 200 mm / day for neuropeptides, etc.

[0191] The target cavity pressure may include a target treatment cavity pressure that treats, inhibits, or prevents ocular disease in a patient's eye. A target treatment cavity pressure for treating an ocular disease can include a cavity pressure selected to modulate an indicator of a physiological parameter, such as a physiological parameter sensed by sensor 130. In one example, modulating the indicator of a physiological parameter can include alleviating subjective patient symptoms, such as alleviating patient discomfort, or improving patient function, such as patient function impaired by an ocular disease or condition.

[0192] The target treatment cavity pressure for inhibiting ocular disease can include a cavity pressure selected to maintain patient function, such as to halt or slow further deterioration of patient function due to the diagnosed ocular disease. In one example, maintaining a measure of patient function can include minimizing fluctuations in a measure of a physiological parameter of the patient's eye. For example, the target treatment cavity pressure for inhibiting ocular disease can include a cavity pressure selected to minimize fluctuations in a measure of IOP over a period of time.

[0193] The target treatment cavity pressure for preventing ocular disease can include a cavity pressure selected as a preventative measure applied to a patient's eye before the ocular disease manifests. In one example, for a patient exhibiting a predictive characteristic for ocular disease, such as an abnormal cup-to-disc ratio as a potential indicator of glaucoma, the device 100 can apply a cavity pressure to the patient's eye, such as at a pressure level appropriate for the patient's physiology, to prevent a physiological process from progressing to a clinical diagnosis of ocular disease. Thus, the target cavity pressure level can include a cavity pressure level sufficient to adjust the cup-to-disc diameter ratio in the patient's eye from a first cup-to-disc diameter ratio to a second cup-to-disc diameter ratio lower than the first cup-to-disc diameter ratio, such as to decrease the cup-to-disc diameter ratio in the patient's eye.

[0194] The conduit 117 may provide a patient fluid transmission path between one or more components of the device 100, such as a continuously open fluid transmission path between the cavity 112 and the sensor 130 or between the cavity 112 and the pressure source 150. The conduit 117 may include lumens, such as one or more lumens.

[0195] 5A illustrates a cross-section of an example conduit 117, such as a first dual lumen conduit. The first dual lumen conduit can include a first lumen 113A defined by a first lumen wall 115A and a second lumen 113B defined by a second lumen wall 115B, e.g., the first lumen 115A can be located adjacent to the second lumen 115B. In one example, the first lumen 113A can provide fluid communication between the pressure source 150 and the cavity 112, e.g., the pressure source 150 can transport a working fluid through the lumen 113A to the cavity 112 to achieve a target cavity pressure level. In one example, the second lumen 113B can provide a fluid communication path between the cavity 112 and a sensor 130, such as a hydraulic fluid pressure sensor located in the control circuit 140, so that the sensor 130 can sense an indication of the cavity pressure level within the cavity 112, such as for use as a feedback signal to control the operation of the pressure source 150.

[0196] Potential operational hazards of device 100 can include an occlusion of conduit 117, such as a condition of conduit 117 that may interrupt a patent fluid transmission path, including a kink in conduit 117. In one example, a kink can include an occlusion, such as an occlusion due to a bending force applied to conduit 117, where at least one of first lumen 113A or second lumen 113B may buckle and collapse, e.g., a first portion of the inner surface of the lumen may contact a second portion of the inner surface of the lumen, preventing fluid transmission through the lumen. A kink in conduit 117 between cavity 112 and sensor 130, such as an actuating fluid pressure sensor located in control circuit 140, can result in the pressure source 150 becoming uncontrollable; for example, control circuit 140 may command pressure source 150 to generate a cavity pressure level based on an erroneous indication of cavity pressure level from sensor 130.

[0197] In one example, a kink in first lumen 113A can interrupt fluid communication between cavity 112 and the actuating fluid pressure sensor, causing the actuating fluid pressure sensor to detect an erroneous indication of the cavity pressure level, including no cavity pressure level (e.g., an indication of a cavity pressure level of approximately 0 mmHg gauge). The erroneous indication of the cavity pressure level can cause control circuit 140 to instruct pressure source 150 to adjust, e.g., increase or decrease, fluid delivery to cavity 112, such as by operating pressure source 150 to compensate for the cavity pressure level in cavity 112, such as to achieve or maintain a target cavity pressure level. Continued detection of an erroneous indication of the cavity pressure level can cause pressure source 150 to operate in a “runaway” (i.e., uncontrolled) manner, such as by generating cavity pressure levels that could be damaging to the patient's eye. To avoid a runaway condition, the conduit 117 may include features, such as one or more features designed to improve the safety of the device 100, such as the operational safety of the device 100 due to blockages, including kinks, in the conduit 117.

[0198] FIG. 5B shows a cross section of an example of a second dual lumen conduit, such as conduit 117, in which the first lumen wall 115A can contact the second lumen wall 115B, such as to form a first lumen 113A and a second lumen 113B within the second lumen wall 115B.

[0199] FIG. 5C shows an example of a third dual lumen conduit, such as conduit 117, in which the first lumen 113A can be located entirely within the second lumen 113B, and the first lumen wall 115A can be separate from the second lumen wall 115B, for example.

[0200] The patency of the conduit 117 can be controlled, such as by the orientation of the first lumen 113A relative to the second lumen 113B. In one example, a kink in a conduit 117, such as at least one of the example conduits 117 shown in Figure 5B or 5C, can occlude the first lumen 113A, such as by preventing fluid transfer from the pressure source 150 to the cavity 112, but can leave the second lumen 113B open and prevent the second lumen 113B from collapsing, such as by preventing the outer surface of the first lumen wall 115A from contacting a first portion of the inner surface of the second lumen 113B with a second portion of the inner surface of the second lumen 113B.

[0201] The patency of the conduit 117 can be controlled, for example, by the design of the conduit 117, including the design of at least one of the first lumen 113A or the second lumen 113B. The dimensions of the conduit 117 can be selected, for example, to maintain the patency of the second lumen 113B. In one example, the thickness of the first lumen wall 115A can be different from the thickness of the second lumen wall 115B, for example, to prevent a first portion of the second lumen 113B from collapsing, for example, when the conduit 117 is subjected to a bending force. The material used to construct the conduit 117 can be selected to maintain the patency of the second lumen 113B. In one example, the type or durometer of the material used to form the first lumen wall 115A can be different from the type or durometer of the material used to form the second lumen wall 115B, for example, to prevent a first portion of the second lumen 113B from collapsing, for example, when the conduit 117 is subjected to a bending force.

[0202] Conduit 117 may include a reinforcing structure, such as to prevent blockage of at least one of first lumen 113A or second lumen 113B. The reinforcing structure may be located in first lumen wall 115A or second lumen wall 115B and may include a coil of wire, such as a wire coil, extending around at least one of first lumen wall 115A or second lumen wall 115B.

[0203] The cross-sectional shape of the conduit 117 can be any shape, such as any shape, that does not affect the function of the conduit 117. The cross-sectional shape of the conduit 117, such as the cross-sectional shape of the first lumen 113A and the cross-sectional shape of the second lumen 113B, can include at least one of a circle, an oval, a crescent, a triangle, a rectangle, or any polygonal cross-sectional shape.

[0204] The flexibility of the conduit 117, such as the overall stiffness of the conduit 117 due to the stiffness of the first lumen wall 115A and the second lumen wall 115B, can be controlled. In one example, the stiffness of the conduit 117 can be reduced by a structural configuration of the conduit 117, such as a structural configuration that minimizes a moment of inertia associated with the cross-sectional shape of the conduit 117. For example, a first dual lumen conduit having a first moment of inertia, such as where the first moment of inertia can be greater than the second moment of inertia or the third moment of inertia, can demonstrate a higher overall stiffness, such as in bending or torsion, when compared to at least one of a second dual lumen conduit having a second moment of inertia or a third dual lumen conduit having a third moment of inertia. In one example, the second dual lumen conduit or the third dual lumen conduit can minimize torsional biases, such as torsional biases that may result from at least one of bonding or extrusion, compared to the first dual lumen conduit.

[0205] The device 100 can affect intraocular structures of the eye, such as by adjusting the ocular environment in contact with the anterior surface of the patient's eye. In one example, applying a non-atmospheric pressure to the anterior surface of the eye can adjust the IOP within the eye, e.g., generate a force that can be reacted to by an intraocular structure of the eye. The intraocular structure can include at least one of the retina, choroid, or blood vessels, including one or more intraocular blood vessels that can perfuse the intraocular structure. In response to the applied force, characteristics of the intraocular blood vessels, such as vascular parameters, can be adjusted or otherwise altered in response to the applied force.

[0206] The vascular parameters represent characteristics associated with a blood vessel and may include at least one of a blood vessel diameter (e.g., blood vessel diameter), such as changes in blood vessel diameter associated with retinal vein pulsation (SVP), including dynamic blood vessel diameter changes, a blood vessel shape, such as a cross-sectional shape, a blood vessel color, or blood flow within the blood vessel, such as at least one of blood volume or blood flow velocity. By adjusting the force applied to the intraocular structure, such as by adjusting the non-atmospheric pressure applied to the anterior surface of the eye, device 100 can adjust one or more vascular parameters.

[0207] The device 100 may include a blood flow apparatus (i.e., BFA) for regulating blood flow in a patient's eye, etc. The BFA may include a cover 110, a fluid regulator 120, a sensor 130, a control circuit 140, and a pressure source 150.

[0208] The control circuit 140 can be configured to regulate blood flow in the patient's eye. For example, the control circuit 140 can be configured to communicate with the pressure source 150 to adjust the fluid pressure in the cavity to regulate ocular blood flow, such as toward a target level, including a target level of blood flow. The control circuit 140 can receive an indication of a vascular parameter from a blood vessel in the eye and process the received indication, such as to adjust the pressure of the working fluid in the cavity 112 (e.g., cavity pressure) to regulate blood flow in the patient's eye based at least in part on the received indication.

[0209] Control circuit 140 may include a central processing unit (CPU), which may be configured as a feedback control circuit, such as to generate a control signal (e.g., a pressure source control signal) for pressure source 150. The pressure source control signal may cause pressure source 150 to adjust the actuating fluid pressure level in cavity 112 based at least in part on the received indicator, which includes the vascular parameter.

[0210] The pressure source control signal can be based at least in part on an indicator of a vascular parameter, such as an indicator of blood flow in a blood vessel, which can be sensed by a blood flow sensor. The CPU can execute a pressure source adjustment cycle, such as a series of operations to adjust the cavity pressure applied to the anterior surface of the eye, as described in the following steps.

[0211] In an example pressure source adjustment cycle, the CPU may receive an indicator of sensed blood flow, such as a first indicator of blood flow. The CPU may generate a pressure source control signal to adjust the pressure source 150 based at least in part on the indicator of blood flow, e.g., to incrementally adjust the non-atmospheric pressure applied to the cavity 112, such as to adjust the blood flow. The CPU may receive a second indicator of blood flow, such as an indicator of blood flow resulting from the incremental application of non-atmospheric pressure to the cavity 112. The CPU may compare the received indicators, such as the first and second received indicators, and adjust the applied non-atmospheric pressure, such as to increase or decrease the non-atmospheric pressure, based on a difference between the first and second received indicators. The pressure source adjustment cycle may be performed multiple times until a target criteria is met.

[0212] The target criteria can include a target blood flow level, such as a blood flow level selected to treat an ocular disease, such as to restore ocular perfusion to a "normal" blood flow level. In one example, the normal blood flow level can be characterized by a total retinal blood flow rate (TRBFR), e.g., a TRBFR within a range of about 68 μl / min to about 92 μl / min (e.g., 80 μl / min + / - 12 μl / min). The CPU can compare a received indicator, such as a sensed indicator of blood flow, to the target blood flow level and adjust pressure source 150 to apply a non-atmospheric pressure to cavity 112, such as to adjust the IOP within the eye to influence blood flow within the eye toward the target blood flow level.

[0213] The target blood flow level can include a blood flow level selected to maximize blood flow in the patient's eye that is targeted for the target IOP level. In one example, the target IOP level can include an IOP level in at least one of a range of about 5 mmHg to about 30 mmHg, a range of about 10 mmHg to about 21 mmHg, and a range of about 12 mmHg to about 18 mmHg. The CPU can generate test pressure source signals, such as to incrementally apply a range of test non-atmospheric pressure levels to the cavity 112, while simultaneously monitoring the associated blood flow level for each incremental test pressure level. The CPU can then select and apply a pressure source control signal to the pressure source 150, such as to achieve a pressure level within the target IOP range associated with the maximum blood flow level.

[0214] Organ perfusion, such as providing sufficient blood flow to maintain cell viability, is necessary for tissue health and general well-being. Perfusion can depend on pressure differences across the perfused organ, such as arterial and venous pressure differences. Ocular perfusion pressure (i.e., OPP) can be characterized as the relationship between a patient's blood pressure (BP), such as their systemic blood pressure, and the intraocular pressure (IOP) of the patient's eye. In one example, the OPP level can be defined as the difference between the BP level and the IOP level, such as OPP = BP - IOP. In one example, the OPP level, including the mean OPP level, can be defined as MOPP = 2 / 3 * (MAP - IOP), e.g., MAP = mean arterial pressure = DBP + 1 / 3 * (SBP - DBP), where SBP is the systolic blood pressure and DBP is the diastolic blood pressure.

[0215] A patient's systemic blood pressure can vary greatly depending on the patient's activity level, which can affect the OPP level in the patient's eye. Insufficient OPP can result in abnormal ocular metabolic activity, such as decreased metabolic activity, or ischemic damage that can lead to retinal cell apoptosis, such as inducing or worsening chronic eye diseases, including glaucoma.

[0216] The target blood flow level can include a blood flow level selected to maximize the blood flow level in the patient's eye that is subject to the target OPP level. In one example, the target OPP level can include at least one of a range of about 30 mmHg to about 70 mmHg, a range of about 40 mmHg to about 60 mmHg, and a range of about 45 mmHg to about 55 mmHg. The CPU can generate test pressure source signals, such as to incrementally apply a range of test non-atmospheric pressure levels to the cavity 112, while simultaneously monitoring the associated blood flow level for each incremental test pressure level. The CPU can then select and apply a pressure source control signal to the pressure source 150, such as to achieve a pressure level within the target OPP range associated with the maximum blood flow level.

[0217] The target blood flow level may include a blood flow level selected to adequately perfuse ocular tissue regardless of the patient's activity level, such as a target ocular perfusion pressure (OPP) level. In implementing the target blood flow level, the control circuit 140 may receive an indicator of blood flow, an indicator of systemic BP, and an indicator of IOP, and process the received indicators, such as to adjust the fluid pressure in the cavity based on at least one of the received indicators.

[0218] In one example, a pressure source adjustment cycle based on an indication of OPP can be performed. The CPU can receive the sensed indicators of IOP and blood pressure to form an indicator of OPP, such as a first indicator of OPP. The CPU can generate a pressure source control signal to adjust the pressure source 150 to apply a non-atmospheric pressure to the cavity 112, for example, to adjust blood flow within the blood vessel, based on the indicator of blood flow. The CPU can receive a second indicator of blood flow, such as an indicator of blood flow resulting from the application of the non-atmospheric pressure to the cavity 112. The CPU can compare the received indicators, such as the first and second received indicators, to adjust the applied non-atmospheric pressure. The pressure source adjustment cycle can be performed multiple times until a target criteria is met.

[0219] 6 illustrates an exemplary method 600 for adjusting blood flow in an ocular blood vessel of a patient's eye using device 100. Control circuitry 140 can be configured to receive an indication of a vascular parameter from a blood vessel of the eye, process the received indication, and adjust the fluid pressure in cavity 112 based at least in part on the received indication. In one example, control circuitry 140 can adjust the blood flow of the eye from a first indication of blood flow to a second indication of blood flow, such as to improve perfusion of ocular tissue.

[0220] At 610, an indication of a vascular parameter may be received, such as by using control circuitry 140. Receiving the indication may include receiving an indication of blood flow, such as at least one of blood volume or blood velocity, in a blood vessel of the eye.

[0221] Receiving the indicator may include receiving an indicator of at least one of an environmental parameter or a physiological parameter associated with the eye. Receiving the indicator may include receiving an indicator of fluid pressure within the cavity 112, such as with a pressure sensor. Receiving the indicator may include receiving an indicator of intraocular pressure (IOP) of the eye, such as with an IOP sensor. Receiving the indicator may include receiving an indicator of systemic blood pressure (BP) of the patient, such as with a BP sensor.

[0222] Receiving the indicator may include receiving the indicator from a user, such as a human or machine, interacting with device 100. Receiving the indicator from a user may include receiving user input, such as via a GUI in communication with control circuitry 140. In one example, the user input may include a target level, such as at least one of target criteria including a target blood flow level and a target OPP level, or other input related to operation of device 100.

[0223] Receiving the indicator can include receiving a target OPP level, such as an OPP level specified by a medical professional, to regulate the patient's ocular tissue perfusion. The target OPP level can include a target OPP level for maintaining sufficient blood flow in the eye, such as to inhibit, treat, or prevent ocular disease.

[0224] At 620, the received indication of the vascular parameter may be processed, such as by using control circuitry 140, to adjust the fluid pressure within cavity 112 based at least in part on the received indication.

[0225] Processing the received indicators may include displaying the indicators of the received indicators, such as the indicators of the vascular parameters, to a user. The display may be via a graphical user interface (GUI), such as via a GUI in communication with control circuitry 140. In one example, a user may visualize a representation of the received indicators on the GUI and manually adjust device 100, such as by manually adjusting pressure source 150 towards a target standard based on the received indicators of the vascular parameters.

[0226] Processing the received indicators may include, for example, calculating an indicator based on at least one of the received indicators. Calculating the indicator may include, for example, calculating an indicator of ocular perfusion pressure (OPP) based at least in part on the received indicator of IOP level and the received indicator of systemic BP level. The indicator of systemic BP level may include an indicator of systolic BP level and an indicator of diastolic BP level.

[0227] Processing the received indicators may include forming a feedback signal, such as a feedback signal configured to adjust pressure source 150. In one example, the feedback signal may include a pressure source control signal. The feedback signal may be based at least in part on at least one of the received indicators or the calculated indicators. In one example, control circuit 140 may automatically adjust pressure source 150 toward a target criteria based at least in part on the received indicators of the vascular parameters, such as via a feedback loop executing on control circuit 140.

[0228] At 630, achievement of the target criteria can be identified, such as by using control circuitry 140. The target criteria can be defined by a relationship, such as a relationship between the received indicators. In one example, the relationship can include a target difference value, such as the difference between the indicator of the parameter sensed by sensor 130 and a target level specified by a user.

[0229] The target criterion can be achieved if the target criterion is within a target range. If the target criterion is within the target range, control circuit 140 can generate a null (e.g., zero) pressure source control signal, such as to stop adjusting pressure source 150. If the target criterion is not within the target range, control circuit 140 can generate a non-zero pressure source control signal, such as to adjust pressure source 150 to change the fluid pressure in cavity 112 to achieve a target level within the target range.

[0230] In one example, identifying the achievement of the target blood flow level may include calculating a target blood flow difference value. The target blood flow difference value may be defined as the difference between the target blood flow level and the blood flow indicator received from the ocular flow sensor. The target blood flow level may be achieved when the target blood flow difference value is within a target blood flow range, for example, a total retinal blood flow rate (TRBFR) within a range of about 68 μL / min to about 92 μL / min (e.g., 80 μL / min + / - 12 μL / min).

[0231] In one example, identifying achievement of the target OPP level may include calculating a target OPP value. The target OPP value may be defined as the difference between the target OPP level and the calculated OPP level indicator. The target OPP level may be achieved when the target OPP value is within a range of target OPP values, such as a range of OPP levels centered around the target OPP value. In one example, the range of target OPP values ​​may include at least one of a range of about -15 mmHg to about 15 mmHg, a range of about -10 mmHg to about 10 mmHg, and a range of about -51 mmHg to about 5 mmHg.

[0232] At 640, the level of non-atmospheric pressure applied to cavity 112 can be adjusted. Adjusting the level of non-atmospheric pressure in cavity 112 can include adjusting an environmental parameter, such as the pressure of the working fluid in cavity 112, using pressure source 150. Adjusting the level of non-atmospheric pressure can include generating a pressure source control signal using control circuit 140. The pressure source control signal can be based at least in part on an indicator associated with control circuit 140, such as a received indicator or a calculated indicator. The level of non-atmospheric pressure adjustment can be changed, such as by adjusting a patient's physiological parameter, including at least one of the patient's IOP or CSFP. The physiological parameter can be adjusted, such as by administering a drug that can increase or decrease the patient's IOP or CSFP.

[0233] At 650, maintenance of the target criterion can be identified, such as by using control circuitry 140. Maintaining the target criterion can include identifying when a target difference value is within a target range for a period of time. The duration can include a period of time during which device 100 can be used by a user. If the target criterion is within the target range, control circuitry 140 can generate a null (e.g., zero) pressure source control signal, such as to stop adjusting pressure source 150. If the target criterion is not within the target range, control circuitry 140 can generate a non-zero pressure source control signal, such as to adjust pressure source 150 to change the fluid pressure in cavity 112 to achieve a target level within the target range. Maintaining the target criterion can include calculating a target OPP value and identifying when the target OPP value is within the target OPP range.

[0234] Autoregulation can be defined as the intrinsic mechanism of an organ to maintain a constant blood flow within the organ to meet metabolic demands despite fluctuations in arterial and venous pressure. Autoregulation, such as ocular autoregulation (OA), can refer to the eye's ability to maintain a constant blood flow within the eye, even when subjected to fluctuations in pressure across the eye, including fluctuations in OPP.

[0235] FIG. 7A shows a graph illustrating a first example of OA performance in an eye, such as a physiologically normal eye. The ocular autoregulation (OA) plateau indicates that the eye can maintain a constant blood flow, such as a constant volume (i.e., "steady-state"), over a range of OPP levels, such as a range that may depend on each patient's unique physiology, to adequately perfuse the eye. In one example, the OA plateau can be considered an optimal level of blood flow to adequately perfuse ocular tissues. In contrast, for OPP levels outside the OA plateau, such as OPP levels in Region 1 or Region 2, the eye is unable to maintain a constant intraocular blood flow; for example, intraocular blood flow will depend on the OPP level experienced by the eye. A decrease in blood flow below the threshold level required to adequately perfuse ocular tissues, such as low OPP levels experienced in Region 1, can cause damage to the eye, such as ischemic damage, which may contribute to the development or progression of ocular diseases, including glaucoma.

[0236] The size of OA plateau, such as the range of OPP levels that define OA plateau, can predict predisposition to eye disease or indicate the existence of eye disease.In one example, a "small" OA plateau (compared to the OA plateau of physiologically normal eyes) or the absence of OA plateau can indicate the existence of eye disease, such as before the patient shows symptoms.Therefore, the evaluation of OA capacity of eyes can be a useful clinical tool for the diagnosis and treatment of eye disease.

[0237] 7B shows a graph illustrating a second example of OA performance in an eye, such as displaying a lack of an OA plateau, which may indicate a physiologically dysfunctional eye. In an eye experiencing ocular disease, the OA performance graph may show blood flow dependent on the ocular OPP level, e.g., linearly dependent on the OPP level over a range of OPP levels. As a result, the range of OPP levels required to maintain optimal blood flow levels for adequate perfusion of ocular tissues may be significantly reduced compared to the OA performance of a physiologically normal eye shown in FIG. 7A.

[0238] The lack of an OA plateau can be a major concern for the health of a patient's eyes. Due to natural fluctuations in physiological pressure levels, such as system blood pressure and IOP, OPP levels in a patient's eyes can fluctuate over a 24-hour cycle each day. For example, a decrease in OPP levels during the night, such as during sleep, when body position causes a decrease in the patient's systemic BP and an increase in IOP, can reduce blood flow to the patient's eyes, causing an ischemic state and potentially causing or worsening eye disease.

[0239] The ability to adjust OPP for diagnostic purposes, such as identifying abnormal OA potential in asymptomatic patients, allows medical professionals to identify ocular diseases and take preventative measures, such as prescribing treatment regimens to maintain optimal perfusion of ocular tissues. Because the range of OPP levels required to maintain threshold blood perfusion in diseased eyes can be much smaller than that in physiologically normal eyes, identifying OA potential is crucial in identifying and treating ocular diseases.

[0240] The device 100 may include an ocular autoregulation apparatus (i.e., OAA) for, e.g., identifying indicators of ocular autoregulation (OA) ability in a patient's eye. The OAA may include a cover 110, a fluid regulator 120, a sensor 130, a control circuit 140, and a pressure source 150.

[0241] The control circuitry 140 may be configured to process indices of OA performance, including an ocular autoregulation (OA) index. The control circuitry 140 may receive and process indices of vascular parameters from the ocular blood vessels, such as to form an ocular autoregulation (OA) value.

[0242] The control circuitry 140 may include a CPU configured as a data processing circuit to receive and process the indices, including one or more indices from one or more sensors 130 associated with the device 100, such as to provide an indication of a relationship between the received indices, which relationship may be characterized by an independent variable and an associated dependent variable, such as to form an OA value.

[0243] The OA value can be defined as a relationship between an independent variable and an associated dependent variable, such as to form an ordered pair of received indicators. In one example, the OA value can include an OPP level (the independent variable) and a blood flow level in the patient's eye associated with the OPP level (the dependent variable). The OA value can include a first OA value, such as a first ordered pair of a first OPP level and a first blood flow level associated with the first OPP level, and a second OA value, such as a second ordered pair of a second OPP level and a second blood flow level associated with the second OPP level.

[0244] The control circuit 140 can be configured to adjust the pressure in the cavity toward a target level, such as toward a target OA mark level. The target OA mark level can include an independent variable of the OA value, such as an independent variable specified by a user of the apparatus 100. The target OA mark level can include a target OPP graph point level, such as an OPP level selected by a user as a reference for forming an OA value for use in an OA performance graph. In one example, one or more OA performance graphs, such as OA performance graphs with the same target OA mark level, can be generated over time to allow a user to compare one or more OA performance graphs in a point-by-point examination, such as to identify changes in OA performance over time. In one example, two or more OA values ​​can form an OA performance graph, such as with uniform increments between the independent variables (e.g., uniform target OA mark levels).

[0245] The control circuit 140 can be configured to process an ocular autoaccommodation (OA) index. A collection of two or more OA values ​​can define an OA power line, such as a line that characterizes the OA power of the eye over a range of OPP levels. The OA power line can be characterized by an OA index, such as a characteristic of the OA power line. The OA index can include at least one of a slope of the OA power line or a length of the OA power line, such as the length of a portion of the OA power line having a particular slope.

[0246] In one example, the control circuitry 140 can be configured to calculate the slope of a best-fit line between at least two OA values, such as to form an OA index for the patient's eye based on the OA values. In one example, the best-fit line can include a linear regression selected to minimize error in a least mean squares (LMS) manner, such as by minimizing the sum of squares of the residuals. The OA index from the patient's eye can be compared to a composite OA index, such as a composite OA index collected from epidemiological data or a series of OA indices associated with ocular disease, to identify ocular disease, such as in asymptomatic patients.

[0247] 8 illustrates an example method 800 for quantifying OA power in a patient's eye using the device 100. In one example, the control circuit 140 can collect OA value data to form an OA power line, such as to estimate an OA index.

[0248] At 610, receiving the indicators may include receiving an indicator of a vascular parameter, such as an indicator of blood flow in a blood vessel of the eye. Receiving the indicators may include receiving an indicator of IOP in the patient's eye and an indicator of systemic blood pressure in the patient.

[0249] At 620, processing the received indicators may include forming an OA value, such as an ordered pair of indicator data, that includes the received or calculated indicator data. The OA value may include an independent variable, such as an indicator of an OPP level, and a dependent variable, such as an indicator of a blood flow level in the ocular blood vessels that is related to the indicator of the OPP.

[0250] Processing the indicators may include calculating parameters of the OA function line. The parameters of the OA function line may include a slope of the OA function line, such as a slope of a best-fit line between at least two OA values. The parameters of the OA function line may be a length of the OA function line, such as a length of an OA function line having a specified slope. The length of the OA function line may include a length of an OA plateau on the OA function line between a first independent value and a second independent value. In one example, the length of the OA function line may vary based on the slope of the OA function line, such as between a first independent value and a second independent value on an OA function graph.

[0251] Calculating the slope of the OA performance line may include, for example, calculating a spline based on two or more OA values. In one example, a first OA value and a second OA value can define a two-point spline, such as a straight line connecting the first and second OA values. The slope of the two-point spline can define an OA index for quantifying the OA performance of the eye. An additional OA value, such as a third OA value, can be combined with the first and second OA values ​​to define a three-point spline, such as a mathematical formula representing a piecewise smooth curve between the first, second, and third OA values. The slope of the three-point spline can be defined as at least one of the arithmetic mean of the slopes of the piecewise smooth curves or the slope of a best-fit line through the first, second, and third OA values ​​defined by the least mean squares (LMS) method.

[0252] At 830, control circuitry 140 may determine sufficiency of OA data collection. Determining sufficiency of OA data may include determining whether enough OA values ​​have been collected by control circuitry 140 to estimate an OA index. In one example, at least two OA values ​​may be collected, such as to define a line from which a slope can be calculated to define the OA index. In an example, a user may specify the number of OA values ​​to collect to calculate the OA index.

[0253] Determining sufficiency of OA data may include averaging two or more dependent variables associated with a specified independent variable. In one example, an arithmetic mean of two or more indices of blood flow associated with a specified indices of OPP may be determined, such as to increase the accuracy of the resulting OA value.

[0254] At 840, the control circuit 140 can adjust the non-atmospheric pressure applied to the cavity 112, such as from a first non-atmospheric pressure to a second non-atmospheric pressure. Adjusting the non-atmospheric pressure applied to the cavity can include incrementally adjusting the non-atmospheric pressure applied to the cavity based on a received indication of a pressure level related to the eye, such as an indication of a pressure level within the cavity 112 (e.g., cavity pressure) or an indication of an IOP level of the eye. The second non-atmospheric pressure level applied to the cavity 112, such as an incremental pressure level for adjusting the first non-atmospheric pressure level, can be based on the received first non-atmospheric pressure level; for example, the second non-atmospheric pressure level can be a function of the received first pressure level. For example, the second non-atmospheric pressure level applied to the cavity 112 can be a function of the difference between the first non-atmospheric pressure level and a target level, or a percentage of the first non-atmospheric pressure level.

[0255] Adjusting the non-atmospheric pressure applied to the cavity may include adjusting the non-atmospheric pressure applied to the cavity based on a percentage multiple of the received pressure level indicator. The percentage multiple may include a predetermined percentage multiple of the received pressure level indicator, such as 1%, 2%, 3%, 5%, 10%, 20%, 30%, etc. The second non-atmospheric pressure applied to the cavity 112 may be based on a percentage multiple of the received first pressure level. In one example, if the predetermined percentage multiple may be approximately 25%, the second non-atmospheric pressure may be approximately 75% to approximately 125% of the received first pressure level indicator, such as the first IOP level. In one example, if the predetermined percentage multiple may be approximately 10%, the second non-atmospheric pressure may be approximately 90% to approximately 110% of the received first pressure level indicator, such as the first IOP level.

[0256] At 850, the control circuitry 140 can compare the collected ordered pairs to target criteria, such as to determine whether the calculated OA index can meet a set of metrics to ensure data quality and consistency. For example, the received pressure level indicators may include extraneous data, such as data that does not reflect the true nature of the sensed pressure level. In one example, the sensing of pressure level data, such as IOP level data, can be confounded by events unrelated to the sensed data, such as a patient rubbing their eye while the device 100 is operating. To mitigate the effects of confounding events, the device 100 can compare the ordered pair data, such as at least one of the pressure level data and the OA index data, to quality criteria, such as by using the control circuitry 140.

[0257] Comparing the ordered pair data to a reference may include comparing a measure of the calculated OA index, such as the slope of a two-point spline, to a predetermined slope value. In one example, the slope of the two-point spline may be compared to a predetermined slope value, such as a measure of the slope from a predetermined reference point that includes the positive horizontal axis of a Cartesian coordinate system.

[0258] Knowledge of pressures within the body, such as intracranial pressure levels, including cerebrospinal fluid pressure (CSFP) levels, is of great interest in diagnosing or treating eye diseases. A patient's CSFP level can be measured by a lumbar puncture, a medical procedure in which a needle is inserted into the patient's spinal canal to perform intracranial pressure monitoring. However, a lumbar puncture is an invasive procedure that can cause complications, such as headache, nausea, and paralysis.

[0259] Retinal venous pulsation (SVP) is a subtle periodic variation in the caliber of retinal vessels that can occur in a patient's eye, such as due to a pressure gradient between the intraocular retinal veins and the retrolaminar portion of the central retinal vein. Retinal vessels may remain patent, such as when the intravenous pressure exceeds the patient's IOP and CSFP. Ocular pulse pressure (e.g., fluctuations between systolic and diastolic intraocular venous pressure) can normally be higher than the cerebrospinal fluid (CSF) pulse pressure; for example, ocular blood flow from the eye may increase during systole and decrease or reverse during diastole. When the ocular pulse pressure equilibrates with the CSF pulse pressure, such as when the patient's IOP equilibrates with the intravenous pressure, the retinal vessels may collapse, such as by disappearing SVP. The pressure level at the time of disappearance of SVP, such as the cavity pressure level or IOP level at which SVP disappears, can indicate the equilibrium between IOP, venous intraluminal pressure, and CSFP, e.g., the IOP level at equilibrium can approximate or be a surrogate for the CSFP in the patient.

[0260] SVP in the eye can be described by parameters such as SVP state parameters (or SVP states), including binary SVP states. Binary SVP states can include an SVP-on state, such as when the sensor 130 can detect an indication of a change in a vascular parameter over a period of time, such as the duration of a patient's cardiac cycle. A cardiac cycle includes the processes of myocardial relaxation (diastole) and contraction (systole) necessary to perfuse the body. The change in the vascular parameter can include at least one of a change in vessel diameter or a change in blood flow within the vessel. Binary SVP states can include an SVP-off state, such as when the sensor can detect no change in the vascular parameter over the duration of a patient's cardiac cycle. Target SVP states can include transition states, such as a transition state from a first SVP state to a second SVP state, including at least one of an SVP-on state to an SVP-off state or an SVP-off state to an SVP-on state. A transition state can include a state in which the IOP is approximately equal to (or otherwise balanced with) the patient's CSFP.

[0261] The target SVP state can be defined by the state of a vascular parameter, such as blood flow within the blood vessel. In one example, an SVP on state includes a blood vessel in which blood flow is occurring within the blood vessel, such as a blood flow within the blood vessel of greater than about 0 ml / sec, and an SVP off state includes a blood vessel in which no blood flow is occurring within the blood vessel, such as a blood flow within the blood vessel of about 0 ml / sec.

[0262] The SVP state of the patient's eye can be adjusted to a target SVP state, including a transitional SVP state, by adjusting the non-atmospheric pressure applied to the anterior surface of the patient's eye. In adjusting the non-atmospheric pressure applied to the eye, the IOP of the patient's eye can be adjusted (e.g., increased or decreased) to equilibrate the patient's IOP with the CSFP. When the target SVP state is reached, the IOP of the patient's eye acts as a proxy for the patient's CSFP.

[0263] The device 100 may include a CSFP device (i.e., a CSFPA), such as for non-invasively measuring a patient's physiological pressure level, including the patient's CSFP level. The CSFPA may include a cover 110, a fluid regulator 120, a sensor 130, a control circuit 140, and a pressure source 150.

[0264] The sensor 130 can include an SVP sensor, such as a sensor configured to detect an indicator of a vascular parameter. The vascular parameter can include a change in vascular diameter, such as an indicator of dynamic vascular diameter fluctuations in an ocular blood vessel. The dynamic vascular diameter fluctuations can be related to a physiological parameter, such as ocular pulse pressure. The SVP sensor can include a pressure-based sensor, such as a pressure sensor, disposed in fluid communication with the cavity 112 and configured to detect dynamic variations in cavity pressure, e.g., the pressure sensor configured to detect dynamic variations in cavity pressure, such as due to corneal movement in response to ocular vascular pulsations, including movements correlated with ocular pulse pressure. The SVP sensor can include a strain-based sensor, such as a strain sensor integrated into an ocular contact lens, configured to detect dynamic variations in at least one of corneal or scleral displacement, such as due to changes in intraocular volume correlated with ocular pulse pressure. In one example, a strain-based SVP sensor may include a contact lens-based sensor sold under the trademark SENSIMED TRIGGERFISH® by Sensimed AG (Lausanne, Switzerland).

[0265] The control circuitry 140 can be configured to process the estimate of CSF pressure based on vascular parameters, such as an indication of vascular diameter, including SVP. The control circuitry 140 can receive indications of vascular parameters from the ocular blood vessels and process the received indications, such as to adjust the fluid pressure within the cavity 112 based on the received indications.

[0266] The control circuit 140 may include a CPU configured as a feedback control circuit, such as to generate a control signal (e.g., a pressure source control signal) for the pressure source 150 to adjust the pressure level within the cavity 112 based on the received indication of the vascular parameter. The received indication may include at least one of an indication of blood flow within the blood vessel, as sensed by a blood flow sensor, or an indication of blood vessel diameter, as sensed by an image sensor or an SVP sensor. The image sensor may detect and capture one or more retinal images including one or more retinal blood vessels over a period of time, such as the patient's cardiac cycle. In one example, the control circuit 140 may be configured to adjust the pressure within the cavity 112 to alter the IOP level of the patient's eye to achieve a target level, such as a target IOP level for the patient's eye. In one example, the control circuit 140 may be configured to adjust the pressure within the cavity 112 to alter a target state of the eye, such as adjusting the pressure within the cavity 112 to adjust the IOP level within the eye toward a target SVP state, including a transition state.

[0267] The CPU can execute a CSFP pressure source adjustment cycle, such as a series of operations to adjust the SVP state of the eye. In one example of a CSFP pressure source adjustment cycle, the anterior surface of the eye can experience an initial pressure applied to the cavity 112, such as a non-atmospheric pressure. The control circuit 140 can receive a first indicator of a vascular parameter, such as related to a first BP, including a diastolic BP, in the patient's cardiac cycle, and a second indicator of a vascular parameter, such as related to a second BP, including an associated systolic BP, in the patient's cardiac cycle. The CPU can compare the first indicator to the second indicator, such as to determine whether a target criterion has been achieved. If the target criterion has been achieved, the CPU can display the initial pressure applied to the cavity 112, such as as an estimate of the patient's CSFP. If the target criterion has not been achieved, the control circuit 140 can incrementally adjust the initial pressure applied to the cavity 112, such as to increase or decrease the pressure applied to the cavity 112, toward achieving the target criterion. The pressure source adjustment cycle can be performed multiple times, such as to incrementally adjust the pressure within cavity 112 until the target criteria is achieved.

[0268] The target criteria can include a target CSFP blood flow level, such as an ocular blood flow level selected to indicate an equilibrium between the patient's IOP, intraluminal pressure, and CSFP. The target CSFP blood flow level in the ocular blood vessels can vary depending on the diameter of the blood vessels, etc. In one example, the target CSFP blood flow level can include a range of blood flow, such as a range of about 5 μl / min to about zero (or null) blood flow in the ocular blood vessels.

[0269] The target criteria may include a target CSFP vessel index. The target CSFP vessel index may include at least one of a vessel diameter index or a vessel property index. The vessel index may be a function of a measure of a vessel parameter, such as at least one of vessel flow, vessel diameter, or vessel shape. The vessel parameter may be sensed by a sensor 130, such as an image sensor, and subsequently captured for processing, etc., by the control circuitry 140.

[0270] The vessel diameter coefficient can quantify a change in a vascular parameter, such as a change in vessel diameter between a first image and a second image at a particular pressure applied to the anterior surface of the patient's eye. The vessel diameter coefficient can represent a state of collapse of a vessel subjected to a particular pressure applied to the anterior surface of the eye. In one example, the target vessel diameter coefficient can include a range of values, such as at least one of a range of about 0.6 to about 0.7, a range of about 0.7 to about 0.8, or a range of about 0.8 to about 0.9. A target vessel diameter coefficient of about 0.63 can indicate complete collapse of the vessel, such that at least a portion of the vascular intima may contact another portion of the vascular intima.

[0271] The vessel diameter coefficient can be defined as a ratio between a first vessel diameter value and a second vessel diameter value of a vessel, such as a vessel at the anterior surface of the eye, subjected to a particular applied pressure. In one example, the first vessel diameter value can include a major axis of the vessel diameter in a first image corresponding to a first blood pressure level at the particular applied pressure, and the second vessel diameter value can include a major axis of the vessel diameter in a second image corresponding to a second blood pressure level at the particular applied pressure. In one example, the first blood pressure level can correspond to a patient's systolic blood pressure level, and the second blood pressure level can correspond to an associated diastolic blood pressure level.

[0272] A vascular characteristic coefficient for quantifying a change in a vascular parameter, such as a change in a vascular cross-sectional shape between a first image and a second image at a specific pressure applied to the anterior surface of a patient's eye. The vascular characteristic coefficient can represent a state of circular deformation of a blood vessel subjected to the specific pressure applied to the anterior surface of the eye. In one example, the target vascular characteristic coefficient can include a range of values, such as at least one of a range of about 100 to about 1,000, a range of about 1,000 to about 10,000, or a range of about 10,000 to about 100,000.

[0273] The vascular characteristic coefficient can be defined as a ratio between a first vascular shape characteristic, such as a ratio between a long axis of a vessel and a short axis of a vessel in a first image corresponding to a first blood pressure level, and a second vascular shape characteristic, such as a ratio between a long axis of a vessel and a short axis of a vessel in the first image corresponding to the first blood pressure level. In one example, the first blood pressure level can correspond to a systolic blood pressure level of the patient, and the second blood pressure level can correspond to an associated diastolic blood pressure level.

[0274] 9 illustrates an example method 900 for non-invasively detecting a patient's CSFP level using device 100. Control circuitry 140 can be configured to receive an indication of SVP from the ocular blood vessels, process the received indication, and adjust the fluid pressure in cavity 112 based on the received indication. In one example, control circuitry 140 can adjust an SVP state, such as from a first SVP state to a second SVP state, to estimate the patient's CSFP level.

[0275] At 610, an indicator of a vascular parameter can be received by control circuitry 140. Receiving the indicator may include receiving an indicator of SVP, such as from a blood vessel of the eye, including an indicator of SVP status. In one example, receiving the indicator may include capturing retinal images, such as one or more retinal images, over a single cardiac cycle. Receiving the indicator may include receiving an indicator of IOP in the patient's eye and an indicator of systemic blood pressure in the patient.

[0276] At 620, processing the received vascular indicators can be processed by the control circuitry 140. Processing the received indicators can include determining an SVP state, such as a binary SVP state including at least one of SVP on or SVP off. The SVP state can be determined, such as by using steps associated with the pressure source adjustment cycle of the CSFP described herein. The ocular vascular parameters can include at least one of vessel diameter, vessel shape, vessel color, or vascular blood flow, such as at least one of volume or velocity. A change in the vascular parameter during the patient's cardiac cycle can characterize an SVP on state. A lack of change in the vascular parameter can characterize an SVP off state.

[0277] At 930, achievement of target criteria, including target SVP criteria, can be identified. The target SVP criteria can include transition SVP criteria, such as a transition from a first binary SVP state to a second binary SVP state, to notify the user that the IOP indicator can approximate the CSFP indicator. The transition SVP state can include at least one of a change from an SVP-on state to an SVP-off state or a change from an SVP-off state to an SVP-on state. Identifying achievement of the target SVP criteria can include comparing the first SVP state to a second SVP state, such as to determine equivalence of the SVP states. In one example, the transition SVP criteria can be met, such as when the first binary SVP state is not equivalent to the second binary SVP state.

[0278] At 940, the level of non-atmospheric pressure applied to cavity 112 can be adjusted. Adjusting the level of non-atmospheric pressure can include incrementally adjusting the level of non-atmospheric pressure. The incremental adjustment can include at least one of a fixed incremental pressure adjustment as defined by a user or a percentage of the fixed incremental pressure adjustment based on an index of a vascular parameter.

[0279] Incrementally adjusting may include calculating a difference between the first and second received vascular parameters and generating a pressure source control signal based on a percentage of the calculated difference. Illustratively, a small difference between the first and second received vascular parameters may indicate a large difference between IOP and CSFP, resulting in a relatively large adjustment increment of the non-atmospheric pressure applied to cavity 112, e.g., to more quickly achieve a transitional SVP state. In one example, if the difference between the first and second vascular parameters is in a range of about 0% to about 25% of the first vascular parameter value, the fixed incremental pressure adjustment may be modified by a multiplier in a range of about 1x to about 5x.

[0280] A large difference between the first and second received vascular parameters may mean a small difference between IOP and CSFP, allowing for a relatively small increment of non-atmospheric pressure adjustment applied to cavity 112, e.g., to more accurately estimate CSFP based on attainment of a transitional SVP state. In one example, if the difference between the first and second vascular parameters is in the range of about 25% to about 99% of the first received vascular parameter, the fixed incremental pressure adjustment may be modified by a multiplier in the range of about 0.01 to about 1.

[0281] At 950, a maintenance of a target criterion, including a target SVP criterion, can be identified. Identifying the maintenance of a target SVP criterion can include comparing a first SVP state to a second SVP state, such as to determine equivalence of the SVP states. In one example, a transition SVP criterion can be maintained, such as when a first binary SVP state is equivalent to a second binary SVP state.

[0282] Various notes The above description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, certain embodiments in which the invention may be practiced. These embodiments are also referred to herein as "examples." Such examples may include elements in addition to those shown or described. However, the inventors also contemplate examples in which only the elements shown or described are provided. Furthermore, the inventors also contemplate examples that use any combination or permutation of the elements shown or described (or one or more aspects thereof) with respect to the particular example (or one or more aspects thereof) shown or described herein, or with respect to other examples (or one or more aspects thereof).

[0283] In the event of a conflicting usage between this specification and any document incorporated herein by reference, the usage in this specification shall prevail. The terms "a" and "an" are used herein, as is common in patent documents, to include one or more, regardless of any other instance or usage of "at least one" or "one or more." The term "or" is used herein to refer to an exclusive or, such that "A or B" includes "A but not B," "B but not A," and "A and B," unless otherwise indicated. The terms "including" and "in which" are used herein as the plain English equivalents of the respective terms "comprising" and "wherein." Also, in the following claims, the terms "including" and "comprising" are open-ended, i.e., systems, devices, articles, compositions, formulations, or processes that include elements in addition to those recited after such terms in a claim are still deemed to be within the scope of that claim. Moreover, in the following claims, the terms "first," "second," "third," etc. are used merely as labels and are not intended to impose numerical requirements on their objects.

[0284] Geometric terms such as "parallel," "perpendicular," "circular," and "square" are not intended to require absolute mathematical precision unless the context dictates otherwise. Instead, such geometric terms allow for variations due to manufacturing or equivalent functions. For example, if an element is described as "round" or "approximately round," components that are not exactly circular (e.g., slightly elliptical or polygonal) are also included in this description.

[0285] The example methods described herein may be implemented, at least in part, by a machine or computer. Some examples may include a computer-readable or machine-readable medium encoded with instructions operable to configure an electronic device to perform a method such as that described in the examples. Implementations of such methods may include code, such as microcode, assembly language code, higher-level language code, or the like. Such code may include computer-readable instructions for performing various methods. The code may form part of a computer program product. Furthermore, in one example, the code may be tangibly stored, such as during execution or at other times, on one or more volatile, non-transitory, or non-volatile tangible computer-readable media. Examples of these tangible computer-readable media may include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memory (RAM), read-only memory (ROM), and the like.

[0286] The above description is intended to be illustrative, not limiting. For example, the above-described examples (or one or more aspects thereof) can be used in combination with each other. Other embodiments may be employed by those skilled in the art upon review of the above description. The Abstract is provided pursuant to 37 CFR 1.72(b) to allow the reader to quickly ascertain the nature of the technical disclosure. The Abstract is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Additionally, various features may be grouped together in the above Detailed Description to streamline the disclosure. This should not be construed as intending that any unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Accordingly, the following claims are incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it is intended that such embodiments can be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

1. 1. A non-transitory computer readable medium comprising program instructions configured to cause a control circuit to operate a pressure source to vary a fluid pressure within a cavity, the cavity being defined by a cover, the cover being sized and shaped to fit over a patient's eye to form the cavity between the cover and an anterior surface of the patient's eye, the pressure source being configured to adjust an index of ocular perfusion pressure (hereinafter OPP) within the patient's eye, the index of OPP comprising a relationship between an index of the patient's systemic blood pressure and an index of intraocular pressure (hereinafter IOP) within the patient's eye, the program instructions comprising: receiving, with the control circuitry, the measure of systemic blood pressure and the measure of IOP; calculating an index of the OPP; adjusting the pressure source to vary the fluid pressure in the cavity such that the OPP indicator moves toward a target OPP in the patient's eye.

2. 2. The non-transitory computer-readable medium of claim 1, wherein the control circuitry is configured to vary the fluid pressure in the cavity toward the target OPP based at least in part on at least one of an index of the patient's systemic blood pressure or an index of the IOP of the patient's eye.

3. 3. The non-transitory computer-readable medium of claim 2, wherein the control circuitry is configured to vary the fluid pressure in the cavity based on a difference between the index of systemic blood pressure and the index of IOP so that the index of OPP moves toward the target OPP.

4. 3. The non-transitory computer-readable medium of claim 2, wherein the control circuit is configured to vary the fluid pressure in the cavity based on a mean ocular perfusion pressure (MOPP) so that the indicator of OPP moves toward the target OPP.

5. 10. The non-transitory computer-readable medium of claim 1, wherein the control circuit is configured to adjust the fluid pressure in the cavity so that the indicator of OPP moves toward a target IOP level.

6. 6. The non-transitory computer-readable medium of claim 5, wherein the control circuit is configured to adjust the fluid pressure in the cavity based at least in part on at least one of the index of IOP and the index of OPP so that the index of OPP moves toward a target IOP level.

7. 2. The non-transitory computer-readable medium of claim 1, wherein the control circuitry is configured to receive an indicator of blood flow in the patient's eye associated with the indicator of OPP and generate an ocular autoregulation (hereinafter OA) value.

8. 8. The non-transitory computer-readable medium of claim 7, wherein the control circuit is configured to adjust the fluid pressure in the cavity so that the indicator of OPP moves toward a target level, the target level comprising a target OPP graph point level, and the control circuit is configured to generate the OA value as an ordered pair of OAs comprising the target OPP graph point level and the indicator of blood flow corresponding to the target OPP graph point level.

9. 10. The non-transitory computer-readable medium of claim 8, wherein the control circuitry is configured to process an ordered pair of at least two OAs to calculate an OA index.

10. 10. The non-transitory computer-readable medium of claim 9, wherein the OA index comprises a slope of a best fit line between at least two ordered pairs of OAs.

11. 2. The non-transitory computer-readable medium of claim 1, wherein the control circuit is configured to adjust fluid pressure in the cavity to move the indicator of OPP toward a target SVP state, including a transition SVP state, to estimate a CSFP level in the patient.

12. the control circuitry is configured to receive an indication of systemic blood pressure, the indication including at least one of a systolic blood pressure level or a diastolic blood pressure level; 12. The non-transitory computer-readable medium of claim 11, wherein the control circuitry is configured to capture at least one of a first image of a vascular parameter corresponding to the systolic blood pressure level or a second image of the vascular parameter corresponding to the diastolic blood pressure level.

13. The non-transitory computer-readable medium of claim 1 , wherein the target OPP comprises a target OPP range of about 30 mmHg to about 70 mmHg.

14. The non-transitory computer-readable medium of claim 1 , wherein the target OPP comprises a target OPP range of about 40 mmHg to about 60 mmHg.

15. The non-transitory computer-readable medium of claim 1 , wherein the target OPP comprises a target OPP range of about 45 mmHg to about 55 mmHg.

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