Implantable Devices and Methods for Measuring Intraocular, Subconjunctival or Subdermal Pressure and/or Analyte Concentration

Abstract

Methods, apparatus and systems for measuring pressure and/or for quantitative or qualitative measurement of analytes within the eye or elsewhere in the body. Optical pressure sensors and/or optical analyte sensors are implanted in the body and light is cast from an extracorporeal light source, though the cornea, conjunctiva or dermis, and onto a reflective element located within each pressure sensor or analyte sensor. The position or configuration of each sensor's reflective element varies with pressure or analyte concentration. Thus, the reflectance spectra of light reflected by the sensors' reflective elements will vary with changes in pressure or changes in analyte concentration. A spectrometer or other suitable instrument is used to process and analyze the reflectance spectra of the reflected light, thereby obtaining an indication of pressure or analyte concentration adjacent to the sensor(s). The wavelength of the interrogating beam of light may vary to control out potential interference or inaccuracies in the system.

Claims

1. An intraoccular pressure sensing system comprising: an inplantable optical pressure sensor sized for implantation within the eye, said optical pressure sensor comprising an optical reflecting element which varies relative to changes in intraoccular pressure and a window through which light will pass; a light source useable to pass light through the cornea of the eye and through the window of the pressure sensor such that the light will strike the optical reflecting element; a receiver/processor which receives light which has reflected from the optical reflecting element and processes such reflected light so as to obtain an indication of intraoccular pressure.

2. A system according to claim 1 wherein the implantable pressure sensor is attached to a support that holds the implantable pressure sensor in a substantially fixed position within the eye.

3. A system according to claim 2 wherein the support comprises a haptic.

4. A system according to claim 2 wherein the support comprises a haptic and and optic.

5. A system according to claim 4 wherein the sensor is mounted on the haptic.

6. A system according to claim 4 wherein the sensor is mounted on the optic.

7. A system according to claim 2 wherein the support is configured to hold the implantable pressure sensor substantially within the anterior chamber of the eye.

8. A system according to claim 2 wherein the support is configured to hold the implantable pressure sensor substantially within the posterior chamber of the eye.

9. A system according to claim 2 wherein the support comprises a shunt apparatus that may be implanted in the eye to decrease the intraocular pressure of that eye.

10. A system according to claim 2 wherein the support comprises a prosthetic lens that has been implanted in place of the patient's native ophthalmic lens.

11. A system according to claim 1 wherein the implantable pressure sensor is attached to a phakic intraocular lens.

12. A system according to claim 11 wherein the phakic intraocular lens is constructed to perform a vision correcting function as well as the function of holding the implantable pressure sensor in a substantially fixed position.

13. A system according to claim 2 wherein the support holds the implantable pressure sensor within the eye such that light may pass from the light source, through the cornea of the eye and onto the optical reflecting element.

14. A system according to claim 1 wherein the implantable optic pressure sensor comprises a Fabry-Perot interferometer pressure sensor.

15. A system according to claim 1 wherein the light source is a visible light source.

16. A system according to claim 1 wherein the light source is an LED light source.

17. A system according to claim 1 wherein the receiver/processor unit comprises a spectrometer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1 is a partial, cross-sectional view of a human eye having an implantable pressure sensor device of the present invention implanted within the anterior chamber of the eye.

[0022] FIG. 2 is a schematic diagram of a pressure sensing system of the present invention, including the implantable pressure sensor device of FIG. 1 in combination with an extracorporeallly positioned microscope/light source and an extracorporeallly positioned spectrophotometer.

[0023] FIG. 3A is a cross sectional view of the implantable pressure sensor device of FIG. 1 with its diaphragm positioned in response to a low intraocular pressure.

[0024] FIG. 3B is a cross sectional view of the implantable pressure sensor device of FIG. 1 with its diaphragm positioned in response to a high intraocular pressure.

[0025] FIGS. 4-7 are previously published graphs (excerpted from Wolthius et al.) showing the linearity and accuracy of Fabry-Perot interferometers of the type used in the present invention. Specifically; FIG. 4 shows reflecting cavity depth for light emitted at 820, 850 and 880 nm; FIG. 5 shows sensor reflectance and dichroic ratio plotted with respect to optical cavity depth; FIG. 6 shows absolute pressure vs. dicrotic ratio; FIG. 7 also shows absolute pressure vs. dicrotic ratio.

[0026] FIG. 8 is a schematic diagram of a analyte sensing system of the present invention comprising an implantable analyte sensor implanted within the anterior chamber of a human eye in combination with an extracorporeal microscope/light source and an extracorporeal spectrometer.

[0027] FIG. 9A is a cross sectional view of the implantable analyte sensor device of FIG. 8 with its diaphragm positioned in response to a high concentration of analyte in the aqueous humor of the eye.

[0028] FIG. 9B is a cross sectional view of the implantable analyte sensor device of FIG. 8 with its diaphragm positioned in response to a low concentration of analyte in the aqueous humor of the eye.

[0029] FIG. 10 shows an embodiment of the present invention wherein an optical pressure sensor and optical analyte sensor are attached to a common support.

DETAILED DESCRIPTION AND EXAMPLES

[0030] Recently intracavity pressure sensors (e.g. brain and intravascular space) based upon the Fabry-Perot interferometer, in which two parallel, minimally separated, partially reflecting surfaces form an optical reflecting cavity, have been proposed. If one of the parallel surfaces is a pressure-sensitive diaphragm, changes in external pressure cause a change in the depth of the optical reflecting cavity, which in turn alters optical cavity reflectance spectra. Because brain and intravascular elements are optically opaque, current use requires that a single wavelength light-emitting diode be physically coupled to an input and read-out fiber optic. In contrast, for the purposes of the current invention, the cornea and conjunctiva are optically clear and that the dermis poses no optical obstruction to various defined wavelengths of light (or the dermis may be treated with one of more chemical agents to minimize the light scattering properties of the dermis). Thus the input optical wavelengths and reflected output from the optical pressure sensors and optical analyte sensors of the present invention can be detected externally through intact corneal, conjunctival and dermal media and will not be restricted by the spectral bandpass of an optical fiber and because of the optical clarity of these structures. Also, in the systems of the present invention, almost any light source, including various LEDs, lasers or white light emitters (filtered and unfiltered) may be used (in the case of skin, the dermis must be transparent to the wavelengths). The advantages of direct pressure sensing and/or analyte determination systems of the present invention include; the lack of any need for electrical power to the implant, the capability of non-invasive external monitoring, and a comparatively high signal-to-noise ratio have been realized in this invention.

[0031] As described in detail herebelow, FIGS. 1-7 relate to one particular non-limiting example of an intraocular pressure sensing system of the present invention, FIGS. 8-9b relate to one particular non-limiting example of an intraocular analyte determining system of the present invention and FIG. 10 relates to one particular non-limiting example of an intraocular pressure sensing and analyte determining system of the present invention. Several of these figures depict anatomical structures of the human eye. Such anatomical structures are labeled as follows:

TABLE-US-00001 AC Anterior Chamber C Cornea I Iris P Pupil L Native Lens

EXAMPLE 1

Intraocular Pressure Sensing System

[0032] An intraocular pressure sensing system of the present invention is shown in FIGS. 1-3b. As may be seen in FIG. 1, an optical pressure sensor 10 is mounted on a support 11. This support 11 comprises a haptic 14 and an optic 12, in the nature of a typical phakic intraocular lens adapted for implantation within the anterior chamber AC of the eye. In the embodiment shown, the optical pressure sensor 10 is attached to one edge of the optic 12, but it is to be appreciated that the optical pressure sensor could also be attached to the optic 12 and/or haptic 14 at other locations or in other ways. The optic may or may not provide some refractive vision correction in addition to performing the function of a support 11 for the optical pressure sensor 10. On example of a 2-piece phakic intraocular lens that may be used to form the support 11 is the Kelman Duet Implant manufactured by TEKIA, Inc., Irvine, Calif.

[0033] The support 11 holds the optical pressure sensor 10 at a substantially fixed (e.g., substantially stationary) position within the anterior chamber AC such that the pressure sensor 10 will sense changes in the aqueous humor that fills the anterior chamber. Such pressure of the aqueous humor typically becomes abnormally high in patients who suffer from glaucoma and, thus, this embodiment of the invention is useable to monitor disease progression and/or treatment efficacy in glaucoma patients.

[0034] FIGS. 3a and 3b show details of the intraocular pressure sensor 10. As shown, this intraocular pressure sensor 10 comprises a translucent body 16 (or alternatively an opaque body having a translucent window formed therein) with an optical reflecting cavity 18 formed at one end thereof. A flexible diaphragm 20 forms the bottom wall of such cavity 18. A reflective surface 22 is formed on the upper surface of the diaphragm 20. A separate reflective surface may also be formed on the wall of the cavity 18 that is opposed to the reflective surface 22 of the diaphragm 20. The optical pressure sensor 10 is positioned in the anterior chamber AC such that the underside of the outer surface of the diaphragm 20 is in contact with the aqueous humor that fills the anterior chamber AC. When the intraocular pressure is normal, the force exerted on the diaphragm 20 by the aqueous humor will allow the diaphragm 20 to substantially remain in a first position, as shown in FIG. 3A. However, as the intraocular pressure increases, the diaphragm 20 will progressively move upwardly, as shown in FIG. 3B.

[0035] The optical pressure sensor 10 may be a miniaturized Fabry-Perot interferometer in which two parallel, minimally separated, partially reflecting surfaces form an optical reflecting cavity which is commercially available as Model 20 and Model 60, from RJC Enterprises, Woodinville, Wash. The size of the optical pressure sensor is about 300 μm×300 μm with about 200 μm depth. One of the parallel surfaces 22 is a surface of the pressure-sensitive diaphragm 20 that changes position with changes in external pressure. This results in a change in the depth of the optical reflecting cavity 18 and a resultant change in the reflectance spectra. Thus, the changes in the reflectance spectra correlate with changes in depth of the reflecting cavity 18 and, thus, also correlates to changes in the pressure of the aqueous humor in the other side of the diaphragm 20.

[0036] FIG. 2 illustrates the manner in which intraocular pressure is read from the implanted optical pressure sensor 10. A light source 30 is positioned in front of the patient's eye. A beam of light is cast from the light source 30, through the cornea C of the eye, though the translucent body (or window) of the sensor 10 and upon the reflective surface 22 of the diaphragm 20. This light is then reflected from the reflective surface 22, outwardly through the cornea C and is received by a receiver 32 such as a mirror, lens, waveguide or other light directing member. The reflected light is directed by the receiver 32 to a processor 34, such as a spectrometer, which then processes the reflected light in a manner that determines a parameter of the reflected light that is dependent upon the depth of the reflecting cavity 18 and, thus, can be used to calculate the pressure of the fluid exerted against the pressure sensitive diaphragm 20.

[0037] The processor 34 may be a reflectance spectrum analyzer that measures the difference in reflected light emanating from the optical sensor 10 at different wavelengths. The reflectance of the optical sensor 10 is not only dependent on the depth of the reflecting cavity 18 cavity and thus on the pressure, but is also dependent on the wavelength of the light that is transmitted against the reflecting surface 22 of the diaphragm 20 from the light source 30. In this regard, FIG. 4 (excerpted from Wolthius et al.) shows the relationship between the depth of the reflecting cavity 18 and reflectance determined by the processor 34 when the light source 30 emits light at wavelengths of 820, 850 and 880 nm. By determining the ratio of the reflectance of different wavelengths, the signal to noise ratio can be improved and the linearity range can be extended, as demonstrated in FIG. 5 and the following equation:

Δ=π(λc−λc′)/2ω where w is the spectral width of the light source, λA.sub.c, λ.sub.c′ are the wavelengths of the two probing light sources

K=(1−R′)2/2R′ where R′ is the mean reflectance of the surfaces

Ratio=1/2+2 /π [(1−K) sin Δ′/2K−(1−K) cos Δ′]

[0038] FIG. 5 shows the total sensor reflectance (measured photocurrent) and the output from dichroic ratio signal analysis(dichroic ratio) plotted with respect to optical cavity depth (absolute pressure), as measure over part of a reflectance cycle. (Excerpt from Wolthuis et. al).

[0039] Thus, by using this ratiometric technique the intraocular pressure measuring system of the present invention is insensitive to source intensity and coupling efficiency. In this regard, this type of optical pressure sensor 10 has been coupled to a fiber optic/LED/dicrotic mirror/photodiode system manufactured by Integra Neurosciences, San Diego, Calif. to measure pressure. FIGS. 6 and 7 (excerpted from Wolthius et al.) demonstrate the linearity and reproducibility of the measurements obtainable from this type of sensor 10.

[0040] Although FIGS. 1 and 2 show the optical sensor 10 positioned in the anterior chamber AC of the eye, it will be appreciated that this optical sensor 10 may be positioned anywhere in the eye where intraocular pressure may be measured. For example, the sensor 10 may be positioned in the posterior chamber of the eye. Such positioning of the sensor 10 within the posterior chamber of the eye may be accomplished by removing all or a portion of the vireous humor using known vitrectomy techniques and then placing the sensor 10 (with or without an appropriately configured support 11) within the posterior chamber at a location where light may pass through the cornea, through the pupil and be reflected from the reflective surface 22 of the diaphragm 20. In another example, in a patient who's native lens has been removed due to cataracts or some other pathology, a prosthetic lens may be implanted in place of the previously removed native lens and the sensor 10 may be attached that prosthetic lens implant. Also, it is to be appreciated that various other types of supports 11 may be used. In some instances, the support 11 may be a structure which functions only to support the sensor 10. In other instances, the support may perform some secondary function is addition to holding of the sensor 10. For example, in embodiments where the support 11 is a phakic intraocular lens, the phakic intraocular lens may be constructed to provide some refractive vision correction in addition to holding of the sensor 10. In other instances, in patients who suffer from glaucoma, a shunt may be surgically implanted to facilitate drainage of aqueous humor and resultant lowering of intraocular pressure. Such shunts are typically tubular and one end of the shunt typically protrudes into the anterior chamber AC of the eye. Thus, the optical sensor 10 may be attached to such a shunt (e.g., to the portion of the shunt that resides in the anterior chamber of the eye) such that the shunt will perform the dual function of draining aqueous humor and holding the sensor 10 at a desired location within the eye.

EXAMPLE 2

Intraocular Analyte Determining System

[0041] FIGS. 8, 9A and 9B show a system for quantitative or qualitative determination of an analyte within the eye of a human or veterinary patient. This system comprises an optical analyte sensor 40 that is implanted within the eye. This optical analyte sensor 40 may be configured for implantation as a stand alone device or may be attached to a support 11A. In the particular embodiment shown, the support 11A comprises an intraocular lens system that comprises an optic 12a and a haptic 14a, of the same type as described hereabove in reference to FIG. 2.

[0042] The optical analyte sensor 40 is shown in detail in FIGS. 9A and 9B. As shown, the optical analyte sensor 40 comprises a translucent body 46 (or an opaque body having a translucent window) having a hollow cavity 48 formed at one end thereof. One or more walls of the cavity 48, or at least a portion of one wall of the cavity 48, is/are formed of a semipermeable membrane 50 through which a particular analyte (e.g., glucose or some other endogenous substance, a drug, a metabolite, a toxin, etc) will pass. In the embodiment shown, a flexible diaphragm 42 having a reflective surface 44 is mounted transversely within the cavity 48. As the concentration of the analyte increases in the body fluid adjacent to the outer surface of the semipermeable membrane 50, the analyte will diffuse through the semipermeable membrane 50 and into the cavity 48. Some quantity of water may also diffuse into the cavity 48 along with the analyte. This results in an increase in pressure on the diaphragm 42 and will cause the diaphragm to move as shown in FIG. 9A. When the concentration of the analyte in the body fluid decreases, analyte (and possibly water) will diffuse out of the cavity 48, thereby decreasing the pressure on the diaphragm and causing the diaphragm 42 to move in the opposite direction, as shown in FIG. 9B. It will be appreciated that as an alternative to positioning of the diaphragm 42 within the cavity 48, the semipermeable membrane may either abut the pressure-sensitive interferometric cavity, or the membrane may itself serve as the pressure-sensitive diaphragm of the inteterferometer. The ability to measure concentrations of analytes by these optical analyte sensors 40 may be quite sensitive.

[0043] In some embodiments of this invention, chemicals that either react or interact with specific analytes may be placed in the cavity 48. Changes such as altered optical spectroscopic (direct sensing) or volumetric properties (pressure transduction) may then be detected. In this case the semipermeable membrane could be fairly non-selective. The membrane 50 may be any suitable type of membrane that will allow measurement of the analyte(s) of interest. Biomembranes permeable to specific analytes (e.g. glucose) have been developed (e.g., UPE Membrane, Millipore, Bedford, Mass.). Selectively permeable membranes may be used for different analytes, including glucose.

[0044] The concentration of the analyte is read using a light source 30, receiver 32 and processor (e.g., a spectrometer) 34 in the same manner as described hereabove with respect to the optical pressure sensor 10.

EXAMPLE 3

Combined System for Measuring Intraocular Pressure and Analyte Concentration

[0045] FIG. 10 shows another embodiment of the present invention wherein both the optical pressure sensor 10 and optical analyte sensor 40 are attached to a common support 11B that comprises an intraocular lens assembly implanted in the anterior chamber Ac of a patient's eye. The support includes an optic 12b and haptic 14c which may be the same as those described above with respect to FIG. 2.

[0046] In this embodiment wherein the optical pressure sensor 10 and the optical analyte sensor 40 are used in combination, a single light source 30 or separate light sources 30, may be used to cast light on the reflective surfaces 22 and 44 of the optical pressure sensor diaphragm 20 and the optical analyte sensor diaphragm 40, respectively. In embodiments where a single light source is used, such single light source may be adjustable to vary the direction, wavelength and/or other characteristics of the of the light beam that emanates from the light source, thereby facilitating its use for both applications. Also, a single receiver/processor 34 or separate receiver processors 34. May be used to receive and process the light reflected from the reflective surfaces 22 and 22. In embodiments where a single receiver/processor is used, such single receiver/processor may be adjustable to vary the direction from which the reflected light is received and/or the particular characteristic(s) of the reflected light that are processed by the processor,

[0047] Although the invention has been described above with respect to certain embodiments and examples, it is to be appreciated that such embodiments and examples are non-limiting and are not purported to define all embodiments and examples of the invention. Indeed, those of skill in the art will recognize that various modifications may be made to the above-described embodiments and examples without departing from the intended spirit and scope of the invention and it is intended that all such modifications be included within the scope of the following claims.