Patent Application
20220218201
The subject matter described herein relates to systems, devices, and methods for measuring intraocular pressure (IOP) in human eyes. These systems, devices, and methods have particular, but not exclusive, utility for treating eye diseases, including but not limited to glaucoma.
Intraocular pressure (IOP) quantifies the pressure of fluid inside the eye. Many individuals suffer from disorders, such as glaucoma, that cause chronic heightened IOP. Over time, heightened IOP can cause damage to the optical nerve of the eye, leading to loss of vision. Presently, treatment of glaucoma mainly involves periodically administering pharmaceutical agents to the eye to decrease IOP. These drugs can be delivered, for example, by injection or eye drops. However, effective treatment of glaucoma requires adherence to dosage schedules and a knowledge of the patient's IOP. The more current or recent the measurement is, the more relevant it will be and hence the more effective the resulting treatment can be. The IOP for a given patient can vary significantly based on time of day, exercise, recency of medication use, and other factors. This means that any given measurement is subject to uncertainty, so it may take a plurality of measurements over time to provide confidence as to the health status of the patient. IOP measurements performed in a doctor's office typically only take place once or twice per year. These infrequent measurements are less able to account for variation in patient IOP. Annual or biannual measurements in a doctor's office may also grow stale or obsolete due to time lag since the previous measurement. Frequent measurements at home could allow for better treatment at lower cost.
IOP may be measured through tonometry, however commonly used tonometry techniques and devices have numerous drawbacks. Contact tonometry is performed in a medical setting and carries both an infection risk and a risk of injury. The procedure may also require numbing of the patient's eyes, resulting in both inconvenience and discomfort. Noncontact tonometry involves directing a puff or jet of air at the patient's eye and measuring the resulting deflection of the eye. However, this requires piston pumps with fast acceleration, which in turn requires a large solenoid, high coil force and high electrical power, and thus a relatively large device to accommodate a coil, piston, and power supply. Accordingly, such pumps can be relatively heavy and expensive. The cost, weight, size, and power consumption of non-contact tonometers make them impractical for home use. In addition, noncontact tonometry is often not as accurate as contact tonometry. Accordingly, long-felt needs exist for IOP measurement tools that address the forgoing and other concerns.
The information included in this Background section of the specification, including any references cited herein and any description or discussion thereof, is included for technical reference purposes only and is not to be regarded as subject matter by which the scope of the disclosure is to be bound.
Disclosed here are systems, devices, and methods for measuring intraocular pressure (IOP) in human eyes.
According to one embodiment, an intraocular pressure measurement system is presented. The intraocular pressure measurement system includes a pressure sensor implantable in an eye, wherein the pressure sensor defines an optical cavity with a depth that varies based on an intraocular pressure of the eye. The intraocular pressure measurement system further includes an external device. The external device includes a light source, a spectrometer, and a processor. The light source is configured to emit a plurality of beams. The spectrometer is configured to receive light reflected from at least two beams and produce an output based on the light reflected from the at least two beams, wherein the output varies based on the depth of optical cavity. The processor is configured to receive the output and, based on the output, estimate the intraocular pressure of the eye.
According to another embodiment, a method for measuring an intraocular pressure of an eye using a pressure sensor having an optical cavity and implanted in the eye is presented. The method includes emitting light into the eye from a light source configured to emit a plurality of beams configured such that at least two non-overlapping beams strike and reflect from the pressure sensor. The method further includes receiving light reflected from the at least two non-overlapping beams into a spectrometer to produce a spectrum, wherein the spectrum varies based on the optical cavity depth of the pressure sensor. The method further includes communicating an output based on the spectrum to a processor configured to receive the output and, based on the output, estimate the intraocular pressure of the eye.
According to another embodiment, a device for measuring intraocular pressure from a pressure sensor implanted in an eye having a dimension that varies according to intraocular pressure of the eye is presented. The device includes a light source, a spectrometer, and a processor. The light source is configured to emit spatially coherent light in an array of beams, wherein the beams are sized and spaced such that any two adjacent beams are separated by a distance less than a cross-sectional dimension of the implanted pressure sensor. The spectrometer is configured to receive light reflected from at least two beams and produce a spectrum output, wherein the spectrum output varies based on the dimension of the pressure sensor. And the processor is configured to receive the spectrum output and, based on the spectrum output, estimate the intraocular pressure of the eye.
This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to limit the scope of the claimed subject matter. A more extensive presentation of features, details, utilities, and advantages of the IOP measurement system, as defined in the claims, is provided in the following written description of various embodiments of the disclosure and illustrated in the accompanying drawings.
Illustrative embodiments of the present disclosure will be described with reference to the accompanying drawings, of which:
The present disclosure describes systems, devices, and methods for optical interrogation of a pressure sensor implantable within the eye. Interferometry is employed on one or more reflections from the implantable sensor of light from a broadband (e.g., a source having a full-width-half-maximum bandwidth of 50 nm or more), spatially coherent light source (e.g., a superluminescent diode or SLD). The implantable pressure sensor may comprise a cavity (e.g., a low-finesse cavity) formed between a rigid substrate and a flexible membrane, whose deflection affects the depth of the cavity (i.e., the distance between the substrate and the membrane) and is indicative of IOP.
The light source may comprise an array (e.g., a linear array) of spatially coherent beams, forming small (e.g., close to the diffraction limit) spots of broadband light that may pass through the cornea, vitreous humor, and aqueous humor of the eye. In some embodiments, the implant is in the cornea or on top of the iris. In such embodiments, the light may still go through all of the structures but may not do so all of the time and may not in their intended use.
Power output of the light source may be selected such that spots that are incident on absorbing anatomical structures of the eye (e.g., the iris or retina) are not damaged by the incident energy. In an example, the system may generate near-diffraction-limited spots (e.g., with diameters less than 150% of the diffraction limited diameter), with power output of about 1-2 microwatts per spot, although other power outputs may be found to be advantageous. Spots that are incident on the implantable pressure sensor will reflect from the sensor and may be captured by a spectrometer located outside the eye (e.g., in a handheld device that also includes the light source). Readings from the spectrometer are indicative of IOP as described below.
In general, a reflection off a cavity will yield different measured distance between the substrate and membrane based on the viewing angle. For example, a head-on measurement (incident angle of 0 degrees, measured from the normal) will yield a first distance, whereas an incident angle of 45 degrees will yield a different distance due to the geometry of the beam and cavity. Generally, a measurement taken off-normal will mimic a shorter cavity. An incident angle close to 90 degrees will generally not return a reflection to the optical interrogation system. This presents a challenge to IOP measurement systems, as small movements of the eye or measuring device may change the incident angle and thus result in inaccurate readings.
However, the systems of the present disclosure may be relatively insensitive to lateral alignment, as the spacing between emitted beams from the light source may be less than the width or diameter of the implantable pressure sensor membrane.
Alternatively, or additionally, the systems may provide fiducial markers on the implantable sensor (e.g., an annulus surrounding the central cavity that has a depth that is independent of pressure), which can be detected by the spectrometer or by another sensor (e.g., a camera), such that the measured spectrum from the fiducials can be used to calculate the incidence angle. Fiducial markers provided immunity against angular misalignment. In summary, an array of spots or beams provides immunity against lateral misalignment, and one or more fiducial markers provide immunity against angular misalignment.
The IOP measurement system may employ low coherence interferometry to obtain accurate readings of the intraocular pressure. Light with a broad spectrum may be incident on a cavity 140, such that only the primary reflections from two surfaces need to be considered: the surface of the substrate 130 that is closest to the light source, and the surface of the membrane 120 that is closest to the light source. The membrane 120 bends predictably and reversibly in proportion to increasing pressure (e.g., intraocular pressure), which in turn reduces the distance between the centers (or other corresponding points) of the two surfaces 120 and 130. For example, the distance between a point on the surface of membrane 120 and a point on a surface of the substrate 130 decreases (increases) as pressure increases (decreases). The membrane 120 and the substrate 130 differ in stiffness, such that for a range of expected IOP, the substrate exhibits little-to-no deflection, whereas the membrane exhibits measurable deflection. In various embodiments, the stiffness of the substrate 120 exceeds the stiffness of the membrane by a factor of 100 or 1000 or more. In operation, the membrane 120 exhibits flexibility with respect to IOP, whereas the substrate exhibits rigidity. The embodiment in
Optical pressure sensors are known that employ a fiber optic coupling, meaning the light source and spectrometer are both attached to the pressure sensitive diaphragm. This is not practical for measurement of intraocular pressure, since the size of the source and a spectrometer with sufficient spectral resolution would be too large for a practical surgical implant. The present disclosure describes a system to interrogate a pressure sensor, such as sensor 110, through free space. Thus, the light source and spectrometer are located outside the eye, whereas the pressure sensor is implantable and located within the eye. This significantly relaxes size and power constraints of the system.
In an embodiment, the external device 350 also includes a memory (not shown) that stores instructions for the processor 380. The memory may also store TOP measurement values. In an embodiment, the external device 350 also includes a communication device (not shown) that is capable of wireless communication using any known technique for one-way or two-way wireless communication, such as Bluetooth, Wi-Fi, or cellular communication. The communication device may be used to download software to the device 350 and/or may be used to communicate measured TOP values to another device, such as a smartphone. In an embodiment, the external device 350 also includes a display to display measured TOP values. The display may be any known display, such as light-emitting diode (including organic LED), or liquid crystal display (LCD). Thus, computed IOP values may be displayed on external device 350 and/or communicated to another device (e.g., a smartphone) for display.
One of the challenges for this type of optical sensing is to ensure that the measurement is not substantially affected by relative motion (translational or rotational) between the sensor and the light source/spectrometer. Thus, the system may need to know when it is properly interrogating the sensor as well as minimize the chances that motion would affect the result. To ensure the sensor is sufficiently interrogated, in some embodiments, the TOP measurement system projects a plurality of spots onto the eye in the plane that the sensor is believed to be located. A “spot” refers to a cross-section of a light beam. Examples of the plurality of spots include a line, a linear array of spots, a grid, or a two-dimensional (2D) array of spots. The plurality of spots may extend beyond the “active” area of the sensor so that fiducials could also be located that would have a characteristic signature on the spectrometer. In an example, the reflected light from the sensor and fiducial markers from a projected line would be dispersed across a two-dimensional sensor. These fiducials could also be used, for example, to calibrate tilt error for example. Alternately, the fact that the membrane would be flexing, bowing, or deforming in a spherical type shape allows the system to use that shape as a locating feature even in the absence of fiducials. In some embodiments, the system includes sufficient spatial resolution to discriminate the size and shape of the feature, and to discern the displacement of the membrane even at the lowest levels of IOP that are of clinical concern. For example, the displacement is measured relative to a reference displacement and associated pressure (e.g., zero pressure).
One method to bring the light source and spectrometer to the patient would be to have the system as a handheld device (e.g., a wand), although this approach may introduce motion artifacts and other inaccuracies under some circumstances. Alternatively, the light source and spectrometer may also be mounted in goggles or spectacles that retain a relatively fixed position with respect to the eye, thus significantly reducing any motion artifacts due to movement of the head.
In some embodiments, the placement and securing of a pressure sensor 110 within an eye 360 is selected according to various criteria. First, it may be desirable to ensure that the sensor 110 is securely placed and will not move within the eye 360 over time. Second, since it is desirable for the sensor to not obscure vision, the sensor may be placed in the periphery of the eyeball. If the sensor were located behind the iris 463 in a non-obscuring position, then it might be desirable for the pupils of the iris 463 to be fully dilated in order for the implantable pressure sensor 110 to be visible to the light source 352 and spectrometer 358. This may be inconvenient for patients and may be problematic for elderly patients in whom dilation response tends to be low.
Thus, in some embodiments it may be preferable to place the pressure sensor in front of the iris near the angle of the eye, oriented in such a way that light enters the sensor implant 110 at an angle well separated from any angles of total internal reflection, i.e., the angles at which light rays entering the eye or the implantable pressure sensor will be internally reflected and thus not escape back outside the eyeball where they can be read by the spectrometer.
In some embodiments, the system may scan a line across the eye 360 to find the proper location of the sensor 110. An alternate embodiment may have a point scanned across the eye to further reduce the background. In other embodiments, the implantable pressure sensor 110 may be placed within the cornea 462. Although a typical thickness of the cornea may be only ˜0.5 mm at the center of the eye, the thickness increases to nearly 0.9 mm closer to the scleral boundary. Thus, it may be reasonable to place an implantable device 110 that is up to 0.3 mm thick and 1 mm in diameter into the cornea 462. Such a surgery may be less invasive and may allow for easier optical access to the implant. Still other embodiments may integrate both optical and electrical readout of the IOP. In this case, the flexible membrane is available for optical readout, this membrane could also be used in conjunction with a strain gauge or capacitive pressure readout.
In this example, the layers are circular, and the spacer 530 includes an opening (such as a circular opening) such that a cavity 140 is formed between the substrate 130, the spacer 530, and the cover 520. The bezel 540 also has an opening (such as a circular opening), such that a portion of the cover is exposed, forming a membrane that is able to flex in response to the pressure from fluid in the eye (e.g., intraocular pressure). In an embodiment, the opening in the bezel 540 is smaller in area than the opening on the spacer 530, and the opening in the bezel 540 is sufficiently aligned with the opening in the spacer 530 that a cross-sectional area of the bezel opening 540 completely overlaps a cross-sectional area of the spacer 530 opening.
To ensure long-term stability of the device, it is desirable to ensure that any gas that is in the cavity 140 does not diffuse out to the environment. Good practices of hermetic sealing should significantly reduce leakage. In addition, instead of air (comprising mostly small nitrogen and oxygen molecules), an insert gas may be used, such as SF6 or C3F8, which comprise larger gas molecules. These larger molecules would diffuse out much more slowly. Molecular weight or size is less relevant to the lifetime of the sensor if the cavity 140 is truly hermetically sealed, and more relevant to the lifetime of the sensor if the cavity 140 is less well sealed.
One of the challenges of this approach is to obtain a good signal-to-noise ratio (SNR) of the optical signal. Background reflections within the eye could reduce the SNR in some embodiments. The present disclosure helps to mitigate this issue with several techniques. These techniques may be employed individually or in combination. First, a low coherence source is employed in some embodiments, so that reflections that are more than a few hundred microns away from each other are unlikely to produce coherent artifacts that will influence the fringe pattern in the received spectrum. Second, an array of beams may be employed that are focused very tightly, and, as a result, the beam spread may reduce fringe visibility in regions that are not within the Rayleigh range of the focus. Also, the refractive index difference between the substrate and the surrounding ocular environment may be designed to be much smaller than the index difference between the substrate and the gas in the well. Likewise, the refractive index difference between the membrane and the surrounding ocular environment may be designed to be much smaller than the index difference between the substrate and the gas in the well. This reduces the magnitude of the reflection at the undesired interfaces.
The graph shows the spacing between adjacent peaks at the interferogram measured at the spectrometer, as a function of cavity depth (identical to the spacer thickness or “spacing”) and the center wavelength of the light source. The different curves each represent different center wavelengths. This result suggests that if an inexpensive light source is desired that has a bandwidth of about 30 nm, such that two distinct spectral peaks can be captured, a cavity depth of a few microns is sufficient, particularly if longer center wavelengths (e.g., near-infrared light with a center wavelength of 900 nm) are employed. In some embodiments, only one spectral peak is needed to deduce the membrane deflection and thus the IOP. In these cases, even thinner spacers may be used than are shown in this figure.
The entire spectrum may provide information on the membrane deflection. This includes both peak separation (useful for broadband sources) or peak location (useful for more narrowband sources). In some embodiments, both could be used together. The choice could be dependent on the dynamic range of the deflection expected. If the source is narrow such that only a single peak is captured, then as the deflection increases, the adjacent peak would eventually move in to replace the peak in the non-deflected case. It could be difficult to distinguish between the two cases if you took snapshots of the two, but the two cases can be distinguished since the width of the peak is also slightly modified.
In order to effectively record reflectance spectrograms (such as shown in
Such a light source also offers the ability to pulse the illumination light, which allows illumination of the sensor only for a fraction of each spectrogram image capture time, for example for 1 microsecond during 1 millisecond spectrometer camera chip exposure. In such a manner, the system can capture a ‘snapshot’ of reflected light interference, not corrupted by motion artifacts. This also relaxes requirements for the camera chip acquisition rates (which may permit corresponding reductions in cost and complexity of the system).
There are several advantages to this proposed solution. First, the implanted surgical device is very simple. It has no electronics (passive or active). Thus, the implant can be made extremely compact with a high degree or reliability. Second, the complexity of the readout system is placed in the handheld/goggle device. This allows for repairs/upgrades to be done more easily. Furthermore, the system could have tiered readout systems where moderate accuracy readouts can be done at home (e.g., +/−2 mmHg) and high accuracy readouts (that might require more expensive electronics and/or a more time-consuming measurement) could be done in a doctor's office. Third, there is no need to communicate with the device or power the device using external wireless or RF power.
One of the challenges for optical readout is to ensure that the measurement is not impacted by relative motion (translational or rotational) between the sensor and the light source/spectrometer. This means that the system may need to detect when it is properly interrogating the sensor as well as minimize the chances that motion would affect the result. For example, when interrogating the membrane with a single focused light beam any deviation of focus position from the center (due to handheld misalignment) causes measurement error because the membrane deflection is not uniform across its area. In the context of a handheld measurement, this limitation becomes prohibitive.
To overcome the above limitation, the IOP measurement system of the present disclosure projects an array (such as a linear or 1D array) of spots onto the sensor implanted in the eye. The array of spots extends beyond the “active” area of the sensor (membrane) such that when it makes a cross-section of the membrane, a processor within the system can determine the length/position of the line and correctly convert the read-out signal into pressure reading (as shown in
To determine the length of the line that hits the active area, the system can employ fiducials having a characteristic signature on the spectrometer and located on the perimeter of the sensor. The reflected light from the sensor and fiducials from the projected line may be spectrally dispersed across a 2D sensor. This approach allows the system to estimate the positions of the spots with modulated reflectance spectrum and consequently properly estimate the intraocular pressure causing membrane deflection. The linear array of spots can be measured from almost anywhere along the diameter of the membrane in a direction perpendicular to the array of spots, thereby increasing the dimensional tolerance in that dimension. Fiducials could also be used to compensate for the implant tilt. Alternatively, the system can use the number of spots with modulated spectrum to determine their positions on the membrane without referring to fiducials and use the asymmetry in their spectral profiles as before. Overall, interrogation of an implanted sensor with an array of spots (as opposed to a single spot) allows for a much greater volume (e.g., based on an increase in lateral area) where the handheld may be positioned to take the intraocular pressure measurement.
An alternate embodiment could have the system scan the line across the eye to find the proper location of the sensor. An alternate embodiment could have a point scanned across the eye to further reduce the background.
Accordingly, it can be seen that an IOP measurement system fills a long-standing need in the art, by providing an implantable pressure sensor which can be read without contact to the eye, via a light source and spectrometer that are relatively insensitive to alignment or positioning errors and will yield consistent readings across a wide range of alignments and positions.
Generally, any creation, storage, processing, and/or exchange of user data associated with the method, apparatus, and/or system disclosed herein is configured to comply with a variety of privacy settings and security protocols and prevailing data regulations, consistent with treating confidentiality and integrity of user data as an important matter. For example, the apparatus and/or the system may include a module that implements information security controls to comply with a number of standards and/or other agreements. In some embodiments, the module receives a privacy setting selection from the user and implements controls to comply with the selected privacy setting. In other embodiments, the module identifies data that is considered sensitive, encrypts data according to any appropriate and well-known method in the art, replaces sensitive data with codes to pseudonymize the data, and otherwise ensures compliance with selected privacy settings and data security requirements and regulations.
A number of variations are possible on the examples and embodiments described above. The above specification, examples and data provide a complete description of the structure and use of exemplary embodiments of the IOP measurement system as defined in the claims. Although various embodiments of the claimed subject matter have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of the claimed subject matter. Changes in detail or structure may be made without departing from the basic elements of the subject matter as defined in the following claims.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2020/032510 | 5/12/2020 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62847127 | May 2019 | US |
