U.S. patent application number 14/733015 was filed with the patent office on 2015-09-24 for devices and methods for noninvasive measurement of intracranial pressure.
The applicant listed for this patent is Third Eye Diagnostics, Inc.. Invention is credited to Anthony Bellezza, Terry A. Fuller, William Lai, Yongping Wang.
Application Number | 20150265172 14/733015 |
Document ID | / |
Family ID | 48524502 |
Filed Date | 2015-09-24 |
United States Patent
Application |
20150265172 |
Kind Code |
A1 |
Fuller; Terry A. ; et
al. |
September 24, 2015 |
Devices and Methods for Noninvasive Measurement of Intracranial
Pressure
Abstract
Provided are systems and methods for noninvasively assessing
intracranial pressure by controllably applanating at least a
portion of a subject's ocular globe so as to collapse an
intraocular blood vessel and correlating the collapse pressure to
intracranial pressure. Also provided are ophthalmic components
useful in ophthalmic imaging applications, as well as methods of
assessing intracranial pressure that are based, at least in part,
on the degree of papilledema, if any, present in the subject.
Inventors: |
Fuller; Terry A.; (Rydal,
PA) ; Wang; Yongping; (Philadelphia, PA) ;
Bellezza; Anthony; (Cherry Hill, PA) ; Lai;
William; (Philadelphia, PA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Third Eye Diagnostics, Inc. |
Bethlehem |
PA |
US |
|
|
Family ID: |
48524502 |
Appl. No.: |
14/733015 |
Filed: |
June 8, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13309920 |
Dec 2, 2011 |
9078612 |
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14733015 |
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Current U.S.
Class: |
600/405 |
Current CPC
Class: |
A61B 5/031 20130101;
A61B 5/7278 20130101; A61B 3/14 20130101; A61B 3/16 20130101; A61B
3/0066 20130101 |
International
Class: |
A61B 5/03 20060101
A61B005/03; A61B 3/14 20060101 A61B003/14; A61B 5/00 20060101
A61B005/00; A61B 3/16 20060101 A61B003/16 |
Claims
1. A system, comprising: an applanator configured to controllably
applanate at least a portion of the ocular globe of a subject, a
first image collector configured to collect light reflected from an
intraocular blood vessel of the subject; and an illumination train
configured to direct light through an ophthalmic component to the
intraocular blood vessel of the subject and to direct light
reflected from the intraocular blood vessel to the image collector.
the system being configured to, during operation, record retinal
fundus images, score features of the optic disc using image
processing algorithms, or both, the system being configured to
compare feature scores to a database of images so as to grade
papilledma, if present, according the Modified Frisen Scale.
2. The system of claim 1, wherein the illumination train is further
configured to direct illumination reflected from an interface
between the ophthalmic component and an applanated region of the
subject's ocular globe, wherein a portion of the illumination
passes through a contacted portion of the interface and a portion
of the illumination reflects off the interface.
3. A system, comprising: an applanator configured to controllably
applanate at least a portion of the ocular globe of a subject, a
first image collector configured to collect light reflected from an
intraocular blood vessel of the subject; and an illumination train
configured to direct light through an ophthalmic component to the
intraocular blood vessel of the subject and to direct light
reflected from the intraocular blood vessel to the image collector.
the system being configured to obtain one or more images of the
fundus of the subject, compare at least one of these images to a
library image of a fundus, and generate a papilledema grade for the
subject.
4. The system of claim 3, wherein the illumination train is further
configured to direct illumination reflected from an interface
between the ophthalmic component and an applanated region of the
subject's ocular globe, wherein a portion of the illumination
passes through a contacted portion of the interface and a portion
of the illumination reflects off the interface.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional of U.S. patent application
Ser. No. 13/309,920, filed Dec. 2, 2011, "Devices and Methods for
Noninvasive Measurement of Intracranial Pressure," filed Dec. 2,
2011, the entirety of which application is incorporated herein by
reference for any and all purposes.
TECHNICAL FIELD
[0002] The present disclosure relates to the field of neurological
instrumentation and more specifically to the field of measuring
intracranial pressure.
BACKGROUND
[0003] Intracranial pressure (ICP) is measured for the diagnosis
and the management of disorders such as hydrocephalus and
pseudotumor cerebri. ICP is often measured following serious head
injury, stroke edema, and intracranial hemorrhage, and is also of
value in the management of certain neurological or ophthalmic
diseases that are associated with increased cerebral pressure.
[0004] The current standard of care to measure ICP involves
surgically inserting a sensor into the cranium through an access
hole drilled through the skull. Present treatment techniques for
monitoring ICP or managing intracranial hypertension (ICH)
generally require invasive placement of subarachnoid bolts,
counter-pressure epidural devices (Ladd or Camino fiber-optic
monitors) or intra-ventricular catheters coupled to external
pressure monitors. Such surgical procedures carry the risk of
complications including infections, hemorrhage, herniation, damage
to nervous tissue, and death, and are very expensive. In addition,
cerebrospinal fluid pressure may be altered the instant the
measurement is performed as a result of leakage of cerebrospinal
fluid. Despite the risks, invasive measurements of ICP are
nonetheless commonplace, as they provide a treatment option in
addition to a diagnostic option, which non-invasive devices
cannot.
[0005] Because of these risks, ICP is only measured in patients who
are critically ill and is not a practical solution for assessing
the severity of a patient's injury or in triage. Accordingly, there
is a need for non-invasive, momentary assessment of ICP in certain
acute situations such as patients with acute shunt obstruction, in
the neuro-intensive care unit (NICU) when lumbar puncture is not
practical, in the emergency room or by emergency medical
technicians (EMT) and other civilian and military first-responders
in response to head injury or the like.
[0006] Existing attempts to accurately and non-invasively determine
ICP are not optimal, as such approaches do not provide a reliable
measure of ICP. Individual baseline variability due in part to
anatomical variances further limits the application of these
methods. Additionally, these methods have demonstrated insufficient
precision when compared to invasive ICP monitors. Accordingly,
there is an unmet need in the art for easy to use, portable and
inexpensive devices and methods capable of non-invasive
determination of intracranial pressure.
[0007] In addition to the patient conditions summarized above in
which an assessment of ICP is desirable, the field would also
benefit from devices and methods capable of providing a more
accurate diagnosis of glaucoma. Traditionally, a patient's
intraocular pressure (IOP) has been to the single most important
metric that determines a patient's susceptibility to glaucoma.
Knowledge of a patient's ICP in addition to a patient's IOP will
provide the clinician with the translaminar pressure (i.e., the
pressure difference between IOP and ICP that is applied to the
optic nerve head), which may be a more accurate indicator of
glaucoma susceptibility than IOP alone.
SUMMARY
[0008] In a first aspect, the present disclosure provides methods
of estimating intracranial pressure in a subject, comprising
imaging an intraocular blood vessel while applying a force so as to
at least partially applanate (i.e., flatten) a portion of the
ocular globe and increase intraocular pressure to a level
sufficient to collapse an intraocular blood vessel; estimating, by
one of several methods of determining intraocular pressure, the
intraocular pressure that collapses the intraocular blood vessel;
and correlating the estimated intraocular pressure that collapses
the intraocular blood vessel to an estimated intracranial pressure
of the subject. Exemplary methods of determining intraocular
pressure include, e.g., corneal applanation tonometry,
pneumotonometry, electronic indentation tonometry, transpalpebral
tonometry, and the like.
[0009] In another aspect, the present disclosure provides systems
for measuring intracranial pressure configured to controllably at
least partially applanate at least a portion of the ocular globe of
a subject's eye, measuring intraocular pressure and suitably
collecting images from retinal blood vessels. In one illustrative
embodiment, retinal blood vessel images are concurrently collected
with a means of determining intraocular pressure from the measured
force on the globe and determination of the area of flattening or
depression of the ocular globe.
[0010] The present disclosure further provides ophthalmic
components that may be referred herein as applanation caps. These
components suitably include a body having an optical surface
adapted to contact a subject's cornea, the body being adapted to
engage with an applanating instrument, and the component comprising
a lens, a prism, or both. In some embodiments, the lens or prism is
formed in the body. In others, the lens or prism is bonded to the
body. The applanation cap may contain one or more indicia to assist
the ICP measurement system to know its type or function. Further,
the indicia may alter or control system electronics to modulate
system operation and data collection. The ophthalmic component may,
in some embodiments, include a refractive surface approximating
that of an unapplanated cornea. The lens, prism, or both, may be
formed on one surface of the ophthalmic component.
[0011] The present disclosure further provides systems for imaging
the retinal fundus concurrently collected with a means of
determining intraocular pressure for the purposes of determining
intracranial pressure in the presence of papilledema or grading
papilledema.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The summary, as well as the following detailed description,
is further understood when read in conjunction with the appended
drawings. For the purpose of illustrating the invention, there are
shown in the drawings exemplary embodiments of the invention;
however, the invention is not limited to the specific methods,
compositions, and devices disclosed. In addition, the drawings are
not necessarily drawn to scale or proportion. In the drawings:
[0013] FIG. 1 depicts an exemplary intracranial pressure measuring
system according to the present disclosure;
[0014] FIG. 2 depicts an exemplary single image sensor optical
imaging system according to the present disclosure;
[0015] FIG. 3 depicts exemplary results of imaging an applanation
surface according to the present invention;
[0016] FIG. 4 depicts an image from a single retina-cornea image
sensor system according to the present disclosure;
[0017] FIG. 5 depicts a first exemplary dual image sensor system
according to the present invention;
[0018] FIG. 6 depicts an exemplary retinal imaging and illumination
system shown in FIG. 5 and according to the present invention;
[0019] FIG. 7 depicts a first exemplary cross-section view of an
illumination pattern of the applanation cap in accordance with the
present invention;
[0020] FIG. 8 depicts a second exemplary cross-section view of an
illumination pattern of the applanation cap in accordance with the
present invention.
[0021] FIG. 9A depicts a portion of a corneal imaging and
illumination system shown in FIG. 5 and according to the present
invention;
[0022] FIG. 9B depicts a corneal applanation image from the system
shown in FIG. 5 and according to the present invention.
[0023] FIG. 10 depicts exemplary applanation caps in accordance
with the present invention; and
[0024] FIG. 11 depicts a second exemplary dual image sensor system
according to the present invention; and
[0025] FIG. 12 depicts an exemplary flow diagram of the operation
of an intracranial pressure measuring system.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0026] The present invention may be understood more readily by
reference to the following detailed description taken in connection
with the accompanying figures and examples, which form a part of
this disclosure. It is to be understood that this invention is not
limited to the specific devices, methods, applications, conditions
or parameters described and/or shown herein, and that the
terminology used herein is for the purpose of describing particular
embodiments by way of example only and is not intended to be
limiting of the claimed invention. Also, as used in the
specification including the appended claims, the singular forms
"a," "an," and "the" include the plural, and reference to a
particular numerical value includes at least that particular value,
unless the context clearly dictates otherwise. The term
"plurality," as used herein, means more than one. When a range of
values is expressed, another embodiment includes from the one
particular value and/or to the other particular value. Similarly,
when values are expressed as approximations, by use of the
antecedent "approximately" or "about," it will be understood that
the particular value forms another embodiment. All ranges are
inclusive and combinable, and all publications cited herein are
incorporated by reference in their entireties for any and all
purposes.
[0027] It is to be appreciated that certain features of the
invention which are, for clarity, described herein in the context
of separate embodiments, may also be provided in combination in a
single embodiment. Conversely, various features of the invention
that are, for brevity, described in the context of a single
embodiment, may also be provided separately or in any
subcombination. Further, reference to values stated in ranges
include each and every value within that range.
[0028] To fully describe the application of the disclosed methods
and systems to ICP measurement and to describe why pressure in
retinal vessels is well-correlated to ICP, a review of the anatomy
and physiology of the eye and surrounding tissues is useful. The
optic nerve connects the retinal ganglion cell axons within the eye
to the brain and is completely surrounded by the subarachnoid
space. The subarachnoid space is filled with cerebrospinal fluid
(CSF), and the pressure of this fluid is equivalent to ICP. The
central retinal artery, vein and central retinal nerve travel
through the central region of the optic nerve, converging at the
optic nerve head in the back of the eye. As CSF pressure increases,
the pressure in the subarachnoid space increases, which exerts an
increasing pressure on the optic nerve. This increased fluid
pressure in turn applies a pressure around the central retinal
vessels that travel within the optic nerve, causing an increase in
blood pressure in the central retinal vessels proportional to the
CSF constriction pressure.
[0029] In one aspect, the present disclosure provides methods of
estimating intracranial pressure in a subject. These methods
include, inter alia, imaging an intraocular blood vessel while
applying a force to a subject's ocular globe so as to at least
partially applanate at least a portion of the ocular globe and
increase intraocular pressure so as to collapse an intraocular
blood vessel. The force may be applied directly to the subject's
cornea or sclera, but this is not a requirement, as force may be
applied to an eyelid (upper or lower) of the subject so as to
indirectly applanate a portion of the ocular globe.
[0030] The methods also include estimating, suitably by
controllably imaging the applanated portion of the subject's ocular
globe, the intraocular pressure that collapses the intraocular
blood vessel; and correlating the estimated intraocular pressure
that collapses the intraocular blood vessel to an estimated
intracranial pressure of the subject. This may be performed in an
automated fashion, and embodiments where a computer controller and
processor act to controllably apply the applanating force and
collect images of the applanated portion of the eye and of the
blood vessel are considered especially suitable. Embodiments where
a computer processor correlates the applanated area of the ocular
globe to the applied pressure that collapses the blood vessel are
considered suitable.
[0031] The at least partially applanated portion of the subject's
ocular globe suitably includes a portion of the sclera, a portion
of the cornea, or even both. This may be affected by a
manually-controlled device or by an automated or
computer-controlled device. The user may suitably applanate the
ocular globe by pressing directly on the ocular globe.
Alternatively, the user may press on an eyelid of the subject so as
to applanate the ocular globe. The applantation may be effected by
a flat-end rod or other shaped device. Ultrasound probes may be
used as applanators, as an ultrasound probe may be used to apply
force to the eye, and even to image the blood vessel of the eye, in
some cases. In some embodiments, the ultrasound probe may be
contacted to the eyelid or the cornea of the subject so as to
applanate the ocular globe, with the ultrasound probe also being
used to image the blood vessel in the eye.
[0032] In some embodiments, the methods suitably include estimating
the intraocular pressure that collapses the intraocular blood
vessel by correlating one or more images of the applanated portion
of the subject's ocular globe to the applied force corresponding to
the one or more images of the applanated portion of the subject's
ocular globe. The user may image the applanated portion of the
subject's ocular globe while applying a first, reference
applanating force. Subsequent to or continuous with application of
this first reference force, a known increasing force is
continuously applied while images of the applanated area are
simultaneously obtained.
[0033] Concurrent with obtaining images of the applanated area, the
user may obtain images of the retina in which the central retinal
vessels can be observed. These retinal images may be synchronized
with the applanation area images and force application data so that
when a collapse of one of the central retinal vessels is observed
in the retinal images, the applanation area and applied force at
that moment in time is known.
[0034] Knowledge of the applanation area and applied force at that
moment allows the user to calculate the intraocular pressure at the
time of vessel collapse, and therefore estimate the pressure within
the vessel at the time of collapse. Alternatively, applanation area
images and force application data from moments immediately before
and/or immediately after the moment of observed retinal vessel
collapse may be used to calculate intraocular pressure at the
moment of vessel collapse. Other means of measuring intraocular
pressure at the moment of collapse can also be utilized in
accordance with the invention. For example, applanating the ocular
globe and viewing the retinal vessels, synchronized with
transpalpebral or pneumatonometric estimates of intraocular
pressure may be used.
[0035] Imaging may, as described herein, be effected by one or more
image collectors. As shown in FIG. 2, for example, a user may
collect images of the ocular globe and of the collapsed or
collapsing blood vessel on a single image detector. Alternatively,
a user may employ one image detector to collect an image of the
ocular globe and another image collector to collect images of the
blood vessel or vessels of interest, as illustrated in FIG. 5.
[0036] Applanating the globe to elevate and measure intraocular
pressure and to view retinal vessels to determine the point of
retinal vessel collapse is one central element that may be
accomplished, for example, by sharing optical elements, an imaging
axis and imaging sensors as shown in FIGS. 1 and 2 or accomplished
using separate optical elements, imaging axes and imaging sensors
as shown in FIG. 5 for example. It is understood that imaging of
the retina may be accomplished in a variety of optical
configurations understood in the art. In the present invention and
using such configurations, accommodation may be made to permit
concurrent applanation of the ocular globe and determination of
intraocular pressure through applanation area and force.
[0037] Illustrative FIG. 1 shows an optically clear applanation cap
at the distal end of a device used to applanate the cornea, which
cap also provides an optical pathway through which the retinal
images can be obtained. In this embodiment, the central anterior
portion of the cap has a convex-plano shape to enhance retinal
imaging. It should be understood that an applanation cap may have a
plano, convex, concave, a prism, or any combination of surfaces
thereof. For example, a cap may be plano-plano in configuration.
Alternatively, a cap may be a prism-plano. A cap may also be
convex-concave. The convex surface or lens compensates for some or
all of the refractive power of the cornea lost when the cornea is
flattened or applanated. The cap may have a plano-plano
configuration or may contain other prismatic corrections to image
the off-axis optic disk, as convex-plano caps are not a
requirement. The retinal vessels observed in the retinal images may
be illuminated by ambient light or by a provided illumination
system. The retinal illumination system can comprise an
illumination source that is co-axial with the optical path and
converge at an apex. Alternatively, in one embodiment the
illumination source can comprise multiple off-axis illumination
paths.
[0038] Estimation of the intraocular pressure at which a central
retinal vessel will collapse may be performed by analyzing
synchronized retinal images, applanation surface images and force
application data. This estimation may be performed during or after
the ocular globe has been applanated. In such an estimation the
user may review or inspect the retinal blood vessel images, the
synchronized applanation surface images and the force applied to
the globe to determine the intraocular pressure at the moment of
collapse of the intraocular blood vessel. A function can be derived
based on using the resting IOP as an initial condition and the
calculating the amount of fluid displaced from the anterior chamber
as the cornea is applanated. For example, for an eye with a resting
IOP of 10 mmHg (millimeters mercury), a 9.8 gram-force to applanate
an area of 38 square millimeters would result in an IOP estimate of
18 mmHg. With a resting IOP of 15 mmHg, a 12 gram-force to
applanate an area of 34 square millimeters would result in an IOP
estimate of 25 mmHg. One exemplary method of estimating IOP (e.g.,
for applanated areas greater than 3.06 mm in diameter is set forth
by Eisenlohr et al., Brit J. Ophthal. (1962) 46, 536).
[0039] In some embodiments of the present invention, the methods
include automated or semi-automated determination of the pressure
that collapses the intraocular blood vessel. In such embodiments,
the user may employ an automated image processing that compares
sequential images of the intraocular blood vessels to determine the
moment in time when collapse of the central retinal blood vessel
occurs, and therefore through the synchronized data the applanating
force at that moment in time. One or more of the optical density,
color, and caliber of the vessels will change upon vessel collapse,
and these characteristics are suitable for automated or manual
determination.
[0040] Imaging the intraocular blood vessel is suitably
accomplished by collecting an image of the retinal fundus on an
image collector. Suitable image collectors include focal plane
arrays, such as CCD devices, CMOS devices, and the like. The focal
plane array may be a two-dimensional array such as those available
from Aptina (San Jose, Calif.), or Cypress Semiconductor
Corporation (San Jose, Calif.), or even be a linear array such as
those available from Goodrich Corporation (Princeton, N.J.).
[0041] The periocular arteries that supply blood to tissues and
structures of the eye pass through the cerebral spinal fluid (CSF)
and are sensitive to changes in CSF pressure. Systolic and
diastolic blood flow velocities are subject to a complex
auto-regulatory process in which the periocular arteries continue
to supply sufficient blood circulation to the eye even when a
patient has an elevated ICP. As pressure increases surrounding the
blood circulation to the eye, various blood flow parameters in the
central retinal and ophthalmic arteries are also affected.
[0042] The user may, in some embodiments, obtain Doppler ultrasound
information from a periocular blood vessel of the subject to
improve the accuracy of correlation between the present invention
and invasive measurements of ICP. Periocular blood vessels within
the cranium are located within or close to the eye. Examples
include the ophthalmic artery, the central retinal artery and vein,
superior and inferior ophthalmic veins, the middle cerebral artery,
etc. Locating a periocular blood vessel is suitably performed by
insonating the vessels that supply the globe and exit the cranium
through the optic canal or cavernous sinus. Auditory and/or visual
signals without imaging may also be used to indicate that a vessel
has been identified. An example of an auditory signal may include
changes in sound pitch in response to changes in blood flow. An
example of a non-imaging visual signal may include a linear LED
array that lights successive LED's in response to increased sensed
blood flow.
[0043] A variety of blood flow parameters may be used in estimating
ICP (see, e.g., U.S. Pat. No. 7,122,007 to Querfurth, incorporated
herein by reference in its entirety). Pulsatility index ("PI"),
resistivity index ("RI"), systolic velocity, diastolic velocity,
and the like are all suitable velocity indicia for use in the
system. PI is considered a particularly suitable velocity parameter
for use in the system. Blood velocity in vessels within the cranium
is affected by intracranial pressure. Blood velocity, particularly
in the arteries, is not constant for a given intracranial pressure,
but varies in relation to the status of the cardiac cycle. Maximum
blood velocity is termed "peak systolic blood velocity", and
corresponds to maximum heart contraction. Minimum blood velocity
occurs during the time that the heart is filling with blood
(diastole) and is termed "end diastolic blood velocity."
PI = ( Peak systolic velocity - End diastolic velocity ) Mean
velocity ##EQU00001## RI = ( Peak systolic velocity - End diastolic
velocity ) Peak systolic velocity ##EQU00001.2##
As pressure increases surrounding the blood circulation to the eye,
the resistivity and pulsatility of the blood flow in the central
retinal and ophthalmic arteries are also affected.
[0044] It has been determined that intracranial pressure can be
accurately estimated as a function of ophthalmic parameters
including central retinal venous pressure (CRVP) and arterial blood
velocity (ABV), where ABV may be assessed using PI, RI, or another
blood velocity metric:
ICP=f(CRVP,ABV)
Using sequential measurements from multiple devices one may fit
data to the form ICP=A+Bx. Following the methods and systems
described herein, one such functional relationship may be expressed
in the form ICP=A+Bx+Cy, where x is central retinal vein pressure
(CRVP) and y is the pulsatility index (PI) of the ophthalmic
artery. A, B and C are scalars used to fit clinical data and depend
on the manner of which the ophthalmic parameters are collected. For
instance, A and B can be adjusted based on the method of tonometry
(pneumotonometry, transpalpebral, or applanation) and C can be
adjusted based on the periocular vessel chosen for the measurement.
By way of example and based on clinical experience following the
methods and systems described, one may correlate the CRVP plus the
Doppler ultrasound pulsatility index of the ophthalmic artery to
ICP using the following regression equation:
ICP = 0.294 + 0.735 ( CRVP ) + 0.735 ( 1 PI ) . ##EQU00002##
[0045] ICP functions like the one above may be further improved in
accuracy by including additional independent variables. The
embodiments described herein focus on ophthalmic parameters not
previously considered in a unified expression; biomechanical
variables including but not limited to optic disc swelling or other
ocular biomechanical properties that are affected by elevated ICP.
These peripapillary ophthalmic parameters can be incorporated into
an independent ophthalmic tissue variable (OT), in units of stress.
Thus:
ICP=f(CRVP,ABV,OT).
[0046] In addition, patients in need of a determination of
intracranial pressure may, in some cases, also have papilledema, a
swelling of the optic disc that occurs secondary to elevated
intracranial pressure. Papilledema develops in a stepwise fashion,
and can be tracked by medical professionals using a widely accepted
grading scheme first proposed by Frisen (Stavern 2007 "Optic Disc
Edema" in Seminars in Neurology, vol. 27, no. 3, pages 233-243,
2007); and S. Echegaray, "Automated Analysis of Optic Nerve Images
for Detection and Staging of Papilledema" (in Investigative
Ophthalmology and Visual Science, vol. 52, no. 10, pages 7470-7478,
2011). The Modified Frisen Scale classifies papilledema into six
grades from 0 (normal) to 5 (severe). Each grade is characterized
by a set of objective, visual features observed on the optic disc
and peripapillary retina. A device that captures images of the
optic disc and surrounding peripapillary retina and classifies
papilledema using the Frisen grading method will not only provide
the ability to objectively assess papilledema severity, but will be
able to use the level of papilledema severity as an input to an
algorithm for more accurately determining ICP. Various implications
and assessment of ICP are discussed in U.S. patent application Ser.
No. 12/959,821 (filed Dec. 3, 2010), the entirety of which is
incorporated herein by reference for all purposes.
[0047] Another method of assessing papilledema severity in order to
more accurately determine ICP is to use ocular coherence tomography
(OCT) to measure peripapillary retinal nerve fiber layer (RNFL)
thickness. Swelling of the peripapillary retina due to elevation in
ICP will cause an increase in the RNFL thickness. Therefore, a
technique that can provide RNFL thickness can be used to improve an
algorithm for determining ICP.
[0048] For example, one such variable, the severity of papilledema
present in some patients with elevated ICP, may be used to modify
the above equation. Papilledema and its associated swelling of the
tissues of the optic disc and surrounding retina due to an increase
in axoplasmic fluid surrounding the axons, may cause an increase in
bulk tissue pressure (P.sub.BT). This bulk tissue pressure will
contribute (along with the cerebrospinal fluid pressure, or ICP) to
the overall pressure being applied to the central retinal vein. The
magnitude of P.sub.BT is correlated with the severity of
papilledema, and may therefore correlate with the papilledema grade
from the modified Frisen scale (MFS). In this case OT is a function
of P.sub.BT or, OT=f(P.sub.BT). One may use MFS to obtain OT or,
OT=f(MFS).
[0049] Another method of assessing papilledema (and therefore
assessing P.sub.BT) is to use OCT to measure peripapillary RNFL
thickness. OCT is a non-invasive technique that provides
cross-sectional images of the RNFL and provides absolute
measurements of the fiber layer thickness. Increases in the
thickness of this fiber layer are directly correlated to the
severity of papilledema, and so OT=f(RNFL). Incorporating the OT
component into the ICP functional equation above yields:
ICP = A + B ( CRVP ) + C ( 1 PI ) - D ( OT ) , ##EQU00003##
where A is directly proportional to the Frisen Scale papilledema
grade. As set forth above, a user may estimate intracranial
pressure by basing that estimate at least in part on an assessment
of the degree, of any, of papilledema that may be present in the
subject. The papilledema assessment is suitably based on the Frisen
or modified Frisen scale. The assessment may be performed in an
automated fashion. One such approach to an automated assessment of
papilledema presence is set forth by S. Echegarry et al.
Alternatively, the assessment of papilledema may be made by way of
optical coherent tomography (OCT), as described herein.
[0050] Accordingly, as set forth above, the present disclosure
provides methods of assessing the intracranial pressure of a
subject. These methods include, inter alia, estimating intracranial
pressure by combining an assessment of the level of papilledema, if
any, present in the subject with one or more of a blood velocity of
the subject, a blood vessel pressure of the subject, a tissue
thickness of the subject, or any combination thereof. The tissue
thickness may, for example, be the thickness of the retinal nerve
fiber layer, the thickness of the prelaminar optic nerve head
tissue, or some combination of these. The blood velocity may be a
systolic velocity, a diastolic velocity, or any combination
thereof, such as the PI and RI indices described herein. The
papilledema level comprises a Frisen scale score of the
papilledema. The assessment of the papilledema level, the tissue
thickness, or both, is based on optical coherent tomography (OCT)
or other methods to measure peripapillary RNFL thickness,
prelaminar optic nerve head tissue thickness, or other ocular
tissues.
[0051] The present disclosure also provides systems for measuring
intracranial pressure in a subject. These systems suitably include
a portion (the "applanator") to controllably at least partially
applanate (i.e., at least partially flatten) at least a portion of
the ocular globe of a subject's eye. This applanation may be
effected by contacting to the eye an applanation portion or even by
an ophthalmic component, which may also be referred to as an
applanation cap. It should be understood that the applanation may
be effected by applying a force to, e.g., the eyelid of the
subject, the cornea or sclera of the subject, or two or more of the
foregoing.
[0052] The systems suitably include at least a first image
collector configured to collect light from an intraocular blood
vessel of the subject's eye, and a retinal illumination train that
may be configured to direct light through an ophthalmic component
(which may be referred to as an applanation cap) to the intraocular
blood vessel of the subject's eye and to direct light reflected
from the intraocular blood vessel to the image collector and a
microprocessor. An image collector may be configured to view the
intraocular blood vessel in the absence of a system illumination
train. For example, a sensitive, low-light image sensor may be used
to collect images illuminated by ambient light. Alternatively, an
infrared sensitive image sensor may also be used. The applanation
cap (as one illustrative ophthalmic component) may be sterile and
removably affixed or otherwise engage with an applanator. The
applanator may be a motor-controlled optical module as describe
below, but may also be manually controlled and advanced.
[0053] The system of the present disclosure can be configured using
one or more focal plane array image sensors for imaging the retina
and the applanated portion of the globe of the subject. In one
embodiment a single image sensor is configured to collect images
from both the retina and the interface between the cornea and an
applanation cap (which may be referred to as "corneal imaging" or
"corneal image"). The images can be collected simultaneously or in
rapid and repeating succession. A single image sensor system may be
configured into a light weight, compact system. In a single sensor
system the image sensor may be required to continuously collect
high-speed images for applanation analysis and high-resolution
images of retinal vessel analysis. Alternatively, rapid sequential
image collection may be utilized that require the single sensor to
sequentially change from high-speed low-resolution to low-speed
high-resolution data collection. Presently, sensors operating in
either configuration are suitable but relatively expensive.
[0054] In another embodiment, two separate arrays may be utilized
for retinal and corneal image capture to overcome the limitations
of a single sensor system. A system has been effectively
constructed using a first sensor to collect images from the retina
and a second sensor to collect images from the applanated portion
of the globe.
[0055] The motion of the applanator may be manually-controlled.
Alternatively, the applanator may be computer-controlled. Any
suitable method of advancing the applanator can be used.
Electromagnetically driven mechanisms, e.g. a voice coil motor,
were successfully clinically tested. However, other motion control
mechanisms such as conventional and stepper motors, pneumatic
actuators and the like may also be utilized. Electromagnetically
driven mechanisms, including voice coil motors, have added
advantages. In addition to inducing controllable displacement of
the applanator, they also produce an electrical indication of the
force being exerted.
[0056] The applanation cap may be of any material compatible with
the cornea such as polycarbonate, polymethyl methacrylate (PMMA) or
even glass. Transparent materials are especially suitable for
applanation caps and ophthalmic components. The applanation cap
diameter can range from about under 4 mm to over 15 mm. One
parameter that may at least partially determine the applanation cap
size is the degree to which the globe is applanated. For an adult
cornea, a convenient size is 10 mm. The applanation cap may
suitably be transparent, although transparency is not a
requirement. The applanation cap may be translucent or opaque as
well, which may be suitable for use when the applanation portion
(e.g., ophthalmic component or applanation cap) contacts the eyelid
or sclera. In some embodiments, the applanation portion includes a
lens, prism, or both formed in a plano body.
[0057] The applanation cap may have an engagement portion
configured to engage with an optical module suitably movable for
contact with the ocular globe. The applanation cap is suitably
constructed to be sterile and removably affixed to the optical
module and able to snap on, screw onto, be magnetically held or
otherwise affixed thereto. The cap may be reusable or
disposable.
[0058] The applanation cap may bear one or more indicia. These
indicia (which may be present in the form of letters, numbers,
barcodes, or even electronic form) may be used to identify the
applanation cap in terms of clinical use, size, shape, or other
characteristic. For example, a particular index may convey that the
applanation cap bearing the index is sized for use in pediatric
patients. Since a child's globe is far smaller than an adult's, use
of an appropriate applanation cap may eliminate the need for focus
adjustments and associated mechanical and optical complexity.
Further, it can notify system electronics of the requisite
operating parameters (maximum force, etc.) that can be exerted on
the child's eye.
[0059] The disclosed methods and systems may be used for
indications other than traumatic head injury. For example, when
measuring resting intraocular pressure in patients with glaucoma or
ocular hypertension, one would not require an applanation cap
incorporating retinal imaging compensation optics. The indicia will
notify the system parameters of the device's intended use and
settings and, in this case, appropriately limit the applanation
force. In this manner, a system may include a set of one or more
applanation caps so as to accommodate subjects that are themselves
different. For example, an emergency medical team might maintain a
set or kit of multiple caps so as to accommodate patients of
various sizes. The systems and methods may also be configured
obtain a translaminar pressure (i.e., the pressure difference
between IOP and ICP that is applied to the optic nerve head), which
may be used as a more accurate indicator of glaucoma susceptibility
than IOP alone.
[0060] In some embodiments, the ophthalmic component is configured
so as to direct light reflected from the intraocular blood vessel
to the first image collector. The ophthalmic component may also be
configured to direct an image of an interface between the
ophthalmic component and an applanated region of the ocular globe
to the first image collector. The system may be configured to
direct an image of the collapsing or collapsed blood vessel and an
image of the component-ocular globe interface to a single image
collector, as illustrated in FIG. 2. In other embodiments, the
images are directed to separate image collectors, as illustrated in
FIG. 5
[0061] In some embodiments, the system is capable of
self-configuring in response to indicia on the applanation cap. For
example, the system may adjust the applanator, the image collector,
or even the illumination train in response to one or more indicia
present on the applanation cap. As one example, an auto-focus motor
could pre-adjust the location of the imaging sensor prior to the
beginning of data collection, corresponding to the patient's eye
size (as indicated by the choice of applanation cap).
[0062] The system may be configured such that during operation it
concurrently applies a force to the subject's globe and collects,
from an image collector, images from at least one of an intraocular
blood vessel of a subject's eye and an interface between the
applanating portion and the ocular globe of the subject's eye.
Applanation of the cornea and simultaneous visualization of the
retina has been found to be a particularly convenient
configuration. In this configuration, applanation does not cause
lateral movement of the ocular globe or distort the view of retinal
vessels. In addition, all measurements are made along the same
axis. In certain embodiments, the system is configured to, during
operation, concurrently applanate at least a portion of the
subject's ocular globe and collect, on the first image collector,
light reflected from the intraocular blood vessel of the subject's
eye.
[0063] An illumination train may, in some embodiments, include one
or more light sources such as a light-emitting diode (LED), an
incandescent lamp, an electroluminescent light source, and the
like. In some embodiments and as most clearly shown in FIG. 6 in
conjunction with FIGS. 7 and 8, the illumination train includes
light-emitting diodes arranged in a circular or ring configuration.
It should be understood that light emitted from the light sources
may have a wavelength in the visible light range (wavelength
approximately 400 nm to 700 nm), but may also be infrared light
(wavelength approximately 700 nm to over 1,200 nm). Thus, the term
"light" as used herein shall be understood to mean energy in the
visible and near infrared regions of the electromagnetic
spectrum.
[0064] Systems may also include a fixation illuminator configured
so as to provide a reference point for the subject to align the
ocular globe. Such illuminators may be a light source upon which
the subject focuses while the system is operating on the subject.
In this way, the subject's eye is stabilized and maintains a
consistent orientation during operation of the device.
[0065] Systems may further include a Doppler instrument configured
so as to collect ultrasound data from a periocular blood vessel of
the subject. Examples of periocular blood vessels include the
ophthalmic artery, the central retinal artery and vein, the
lacrimal artery, posterior ciliary arteries, superior and inferior
ophthalmic veins, and middle cerebral artery. Ophthalmic artery
insonation requires penetration of approximately 40 to 50 mm. For
this amount of tissue penetration, an ultrasound probe of between 7
MHz and 10 MHz is preferred. Locating a periocular blood vessel is
suitably performed by using a color Doppler ultrasound imaging
system. Examples of such devices are commercially available from
General Electric (www.ge.com) and Philips (www.philips.com).
Alternatively, a non-imaging Doppler ultrasound system with
auditory and/or visual feedback signals locate a periocular blood
vessel by scanning the anatomical volume of interest using a linear
probe can be used. One such device is an ultrasound transducer
manufactured by Multigon Industries. The Doppler sensor may be
adjustably fixed to the body of the invention as shown in FIG. 1 or
may be separately held.
[0066] The systems may, in some embodiments, be configured so as to
be capable of assessing the degree, if any, of papilledema present
in the subject. In one illustrative embodiment, the system is
configured to obtain one or more images of the fundus of the
subject and compare at least one of these images to a library image
of a fundus, and generate a papilledema grade for the subject. The
system may include a processor configured to estimate intracranial
pressure of the subject based on one or more images of the at least
partially applanated portion of the subject's eye and one or more
images of the intraocular blood vessel of the subject's eye. The
papilledema assessment method of S. Echegaray et al., is considered
especially suitable for application to the disclosed systems and
methods.
[0067] The systems in the present disclosure may include an
applanator configured to controllably contact an applanation
portion (which may also be referred to as an ophthalmic component
or an applanation cap) to the ocular globe of a subject's eye.
Suitable applanators are described elsewhere herein. The systems
may also include an image collector configured to collect light
reflected from an intraocular blood vessel of the subject's eye.
The system may also include an illumination train configured to
direct light through the applanation portion to the intraocular
blood vessel of the subject's eye and to direct light reflected
from the intraocular blood vessel to the image collector. During
operation, the system may record retinal fundus images and score
features of the optic disc using image processing algorithms known
to those of skill in the art. The system may be configured to
compare feature scores to a database of images for the purpose of
grading papilledema according the Modified Frisen scale. The system
may be configured to output a Frisen scale score of papilledema
paired with an image of the optic disc for purposes of tracking
papilledema progression. The system may thus assess a subject's
papilledema and assess the patient's condition over time. In some
configurations, the system generates a papilledema score in an
automated fashion. The systems may be configured to, during
operation, record retinal fundus images, score features of the
optic disc using image processing algorithms, or both. The systems
may also be configured to compare feature scores to a database of
images for so as to grade the purpose of grading papilledma, if
present, according the Modified Frisen Scale.
[0068] Further disclosure is now made by reference to the attached
figures.
[0069] FIG. 1 illustrates a cutaway view of an exemplary
intracranial pressure measuring system according to the present
disclosure. As shown, ICP measuring system 100 suitably includes a
movable optical module 102 that engages with applanation cap 135. A
motion control module 104 (not shown) may modulate the motion of
the applanator. Electronics module 108 contains units adapted to
control and modulate the device's actions and operations. Optical
module 102 collects retinal images simultaneously with electronic
module 108 collecting force and position data from force sensor 105
and position sensor 106, respectively. Motion of optical module 102
to applanate a portion of ocular globe 15 may be manual or
automatic. Automatic motion of the optical module is suitably
controlled by motor 111, force transducer 105 and position sensor
106. Optical module 102 suitably translates in a range of several
centimeters, e.g., by 0.5, 1, 2, 3, 4, or even 5. During operation
and upon contact with the cornea, force transducer 105 limits the
force to appropriately safe levels of intraocular pressure and the
portion of ocular globe 15 applanated. Position sensor 106 may
limit translation to under approximately 4 mm (subject to the size
of the subject's eye) so as not to harm the subject. Following data
collection, which nominally takes approximately 5 to 10 seconds,
optical module 102 automatically retracts. If desired by the user,
a scroll wheel, lever, slide or the like may be used to review the
applanation force and the images of the retina on display 112
collected during actuation so as to identify the instant of vessel
collapse. The identification of the instant of vessel collapse may
also be automatic.
[0070] The sensor used to determine force applied to the globe may
be any form of force transducer, including one or more of
electrical resistance, foil, semiconductor or thin film strain
gauges and other force measurement devices. Force transducer 105
can be located in any position in ICP measuring system 100 that
will provide a signal proportional to the force applied to the
ocular globe. As shown, force transducer 105 is positioned between
motor 111 and the movable optical module 102. The determination of
force by sensing a change in the current from a voice coil motor
drive is of particular value due to use of a single device to drive
the optical module and sensitively measure the forces exerted.
Locating a force sensor in close proximity to applanation cap 135
may be advantageous. Position sensor 106 provides information on
the absolute position and velocity of the applanation cap. Several
position sensors are readily available for this application. Hall
effect sensors have been found to be suitably small, inexpensive
and accurate. However, other sensors including but not limited to
inductive sensors, linear variable differential transformer (LVDT)
sensors, etc. may be used. ICP measurement system 100 may be
equipped with a head support (not shown) so as to stabilize the
position of the device on the subject. For the convenience of the
operator and safety of the subject, optical module 102 and
applanation cap 135 may be positioned such that applanation cap 135
will not touch the subject's globe until the system is stabilized
on the subject and determined appropriate by the operator.
Batteries 109 may be used to power the device. The device may also
run off of household or commercial electrical lines. A trigger (not
shown) may be used to actuate the device, e.g., to advance the
applanator, ro take one or more images, or to effect one or more
other action
[0071] FIG. 12 depicts an exemplary flow diagram of the operation
of an intracranial pressure measuring system. Upon powering on the
apparatus ("Start"), the system senses the presence of an
applanation cap and turns on the video monitor. System electronics
setup the system per information provided in the selected cap's
indicia. After placement of the system over the subject's eye (not
shown in flow diagram), the operator depresses a trigger 110 to
simultaneously advance the optical module and initiate recording of
data from the five sensors. A position sensor is monitored to
determine the optical modules location and velocity. A primary
force sensor senses the force required to advance the cap and
optical module as detect the increase in force resulting from
contact with the globe. A secondary force sensor is monitored to
insure that the force measured by the primary force sensor is
within safe limits; else the optical module is withdrawn. A
sequence of movements of the optical module is followed in
accordance with the cap indicia information. Once the sequence is
completed, the optical module is withdrawn from the cornea, sensor
monitoring processes cease, data is analyzed and the value of ICP
is displayed.
[0072] The embodiment shown in FIG. 1 also illustrates Doppler
ultrasound transducer 115 suitably mounted on transducer pivot arm
116 to permit contact of Doppler transducer 115 in the periocular
region and oriented towards the ophthalmic artery. A signal such as
an auditory signal varies in pitch and volume that may help the
operator aim the probe in the correct orientation. The Doppler
device may be constantly collecting Doppler ultrasound data using
either an auditory or visual feedback signal. Once transducer 115
is correctly positioned, pulsatility data may be collected and
averaged over at least three heart cycles.
[0073] FIG. 2 depicts an exemplary optical configuration of a
single image sensor system 10 according to the present disclosure.
In such an ICP measurement system, a first image may be collected
of optic disc region 32 of retina 30 and focused on a first portion
of retina/cornea image sensor 50 so as to distinguish a collapsed
blood vessel such as the central retinal vein. A second image may
be collected indicative of the degree of applanation of the globe
and focused on a second portion of retina/cornea image sensor 50.
Exemplary retinal imaging path 55 is also shown, as is corneal
imaging path 65.
[0074] A portion of ocular globe 15 is flattened by applanation cap
35. In the embodiment shown, the portion of globe 15 that is
applanated is cornea 20. The distal surface of applanation cap 35
is shown as a flat or plano surface and proximal side is shown as a
convex surface (referred to as "cap lens 36"). Light reflected from
retina 30 passes through ocular lens 26, flattened cornea 20,
applanation cap 35 and objective lens 40. Objective lens 40 may be
comprised of one or more lenses. The light reflected from retina 30
is then reflected by dichroic beam splitter 45 onto retina/cornea
image sensor 50. Light from retina 30 may be reflected from an
external source of illumination (not shown). In one exemplary
embodiment, retina 30 is illuminated using visible light source at
565 nm. Any number of dichroic beam splitter 45 could be utilized
such as, for example purposes only, a 580 nm single-edge long-pass
dichroic beam splitter that reflects >95% of wavelengths in the
range of 350 nm to 570 nm and transmits 93% of wavelengths from 591
nm to >950 nm (Semrock, Inc., Rochester, N.Y.). Alternatively,
light from retina 30 may be infrared energy emitted as a result of
heat from retina.
[0075] Applanation of cornea 20 by applanation cap 35 causes
flattening of the cornea and a resulting change in the pattern and
intensity of light reflected by the cornea onto retina/cornea
sensor 50. The force required to flatten cornea 20 increases with
increased applanation. It is well known that by measuring the force
required to applanate the cornea to a known area (typically 3.06 mm
in diameter) one may estimate the intraocular pressure. So-called
corneal applanation tonometry has been one standard means of
measuring intraocular pressure for screening and routine management
of patients with ocular hypertension and glaucoma.
[0076] In traditional applanation tonometry, corneal flattening
substantially under 3.06 mm results in loss of measurement accuracy
due to effects of corneal rigidity and tear-film complications.
Applanation of the cornea to an area substantially greater than
3.06 mm decreases the accuracy of the measurement to greater than
accepted norms of +/-0.5 mmHg. This is due to an induced increase
in the patient's intraocular pressure. As a result, applanating the
cornea beyond 3.06 mm is generally contraindicated, although the
3.06 mm applanation area is not a requirement or limit. In the
present invention, the operator suitably elevates intraocular
pressure so as to intentionally generate intraocular pressure
sufficient to collapse the retinal vasculature. Estimating IOP for
applanation areas greater than 3.06 mm requires modeling of the
biomechanics of the cornea to determine pressure as a function of
force and area. A function can be derived based on using the
resting IOP as an initial condition and the calculating the amount
of fluid displaced from the anterior chamber as the cornea is
applanated. One exemplary method of estimating IOP (e.g., for
applanated areas greater than 3.06 mm in diameter is set forth by
Eisenlohr et al., Brit J. Ophthal. (1962) 46, 536).
[0077] Flattened cornea 20 can be visualized and the area of
applanation determined by imaging cornea-cap interface 34 using an
image sensor illuminated by any wavelength sensitive to the image
sensor. However, it is preferable to select a wavelength different
from that used to illuminate retina 50. In the example above using
the described beam splitter and retina 50 illumination (not shown),
cornea illumination source (not shown) was selected to be a 850 nm
LED. It is preferable, but not a requirement, that the retina be
illuminated by 540 nm to 570 nm green light. Such wavelengths
provide excellent contrast and enhance visibility of the retinal
vasculature. Light reflected by flattened cornea 20 passes through
applanation cap 35, objective lens 40 and dichroic beam splitter
45. Bending mirrors 60 positions reflected cornea light to pass
through corneal imaging lens assembly 62 and corneal portion (left)
of aperture 67 and focus the corneal image on retina/cornea image
sensor 50. Aperture 67 serves to reduce unwanted vignetting and
backscatter of illumination from the system optics and anatomical
structures such as the lens and cornea.
[0078] FIG. 3 shows the results of illuminating applanation
cornea-cap interface 34 of a pig using near infrared light.
However, similar results are obtained using visible illumination
light. A portion of the illumination light reaching cornea-cap
interface 34 will be reflected back and be visible by retina-cornea
image sensor 50. Indicia 70 are also shown. The reflection is the
result of the differences in the index of refraction between the
applanation cap and either ambient air or aqueous from the
subject's tear film. When the applanation cap is in contact with
the cornea, the contacted portion of the illumination light is
transmitted through the applanation cap and will appear darker when
viewed by the image sensor as shown as applanation area 74. Thus,
the darker circle will grow in size as greater force is exerted on
the cornea. In this example, the pressure in the pig's eye was
initially set at 10 mmHg with a monometer. Incremental increases in
force on the ocular globe will result in incremental increases in
intraocular pressure above the initially set 10 mmHg. Maximum
applanation area 72 is shown as a circular line as a reference to
the user. In this example and upon contact of the applanator with
the pig's eye, the results are as follows:
TABLE-US-00001 Diameter/Area Force Measured pressure FIG. 3A 0.91
mm/0.007 cm.sup.2 0.50 gF -- FIG. 3B 3.54 mm/0.098 cm.sup.2 1.06 gF
10.8 mmHg FIG. 3C 6.31 mm/0.313 cm.sup.2 3.55 gF 11.3 mmHg
[0079] FIG. 4 shows an image taken by a single retina-cornea image
sensor system similar to that shown in FIG. 2. The larger retinal
fundus 76 and smaller corneal applanation area 74 were taken of a
rabbit. In the image shown, a 1.3 megapixel (1280H.times.1024V)
CMOS sensor was used. However, the selection of sensor depends upon
the design of the optical train, the illumination, the desired
field of view, the frame rate, etc. A person of skill in the art
will select appropriate optical and opto-mechanial elements to meet
the desired system specifications. A large field of view and
high-resolution image is beneficial for retinal imaging. The large
retinal field of view allows for more rapid identification of the
optic disk. Higher resolution also permits the ability to
electronically select the area of interest and maintain sufficient
resolution to observe vessel collapse. In this illustrative
example, satisfactory retinal images were obtained using
approximately 1024.times.1024 px field. In contrast, determination
of corneal applanation size was effectively obtained using a
256.times.256 px field.
[0080] FIG. 5 depicts an exemplary dual sensor system 150 according
to the present invention. This system provides retinal illumination
and imaging, corneal illumination and imaging, and a fixation point
as described below. For convenience, the retinal illumination
aspect of the system 150 is described first and is highlighted in
FIG. 6. While reference to retinal illumination is used herein, it
should be understood that reference to the `retina` or `retinal` is
to include blood vessels leading to and from the retina and more
particularly the central retinal artery and vein.
[0081] Retinal illumination light source 160 may be a ring of light
sources including for example light emitting diodes (LED's) that
emit light along path 157 (one LED illustrated for simplicity of
the explanation and shown as a dotted line). Retinal illumination
light 158 is reflected by dichroic beam splitter 154, passes
through and is focused by objective lens 153 and is incident on
applanation cap 35. As shown in FIG. 6 and in cross-section A-A' in
FIG. 7, retinal illumination light 158 is focused and forms a
circular illumination pattern 161 on applanation cap 35 peripheral
to convex shaped applanation cap lens 36. Cap lens 36 serves to
compensate for the refractive power of the cornea lost due to
applanating (flattening) cornea 20. Retinal illumination light 158
diverges and forms illumination pattern 161 as it passes through
pupil 24. The iris is shown, but not labeled. Section B-B' in FIG.
6 shown in cross section in FIG. 8, illustrates the relative size
of retinal illumination pattern 161 in the plane of iris 28. A
constricted iris may vignette a portion of the light, yet provide
sufficient illumination to image retina 30 on retina image sensor
170 through an un-dilated, 2.4 mm pupil. However, adequate
illumination through smaller diameter pupils is also possible. In
this embodiment and as shown in FIGS. 6, 7 and 8, illuminating the
retina through illumination path 157 peripheral to cap lens 36 and
central pupil 24, obviates the illumination path being coaxial with
retina imaging path 155 that is positioned along the central
optical axis of globe 15. The sclera is shown but not labeled.
However, in this configuration, both illumination and imaging paths
share objective lens 153. As a result this configuration minimizes
or eliminates illumination light reflected back to retina image
sensor 170 from objective lens 153, applanation cap 35, cornea 20
and ocular lens 26. Various image stops or apertures such as
retinal image aperture 162 may be added to further reduce stray
light from entering retina image sensor 170. One or more focusing
lenses 165 may be present to adjust retinal or other lighting.
Corenal focusing lens 210 may also be present.
[0082] There are numerous techniques known in the art to illuminate
the retina with light entering the eye through the central pupil.
For example a total reflecting mirror with an aperture positioned
along the illumination axis may be used in place of dichroic beam
splitter 154. This is shown in FIG. 11 as aperture 146 in aperture
mirror 145. In this configuration a ring of illumination light is
created thereby minimizing reflections back to the retinal image
sensor.
[0083] FIG. 5 shows a scheme for illuminating and imaging
cornea-cap interface 34 along the central axis of the globe and
sharing objective lens 153. Cornea illumination source 220 light
passes through dichroic beam splitters 205 and 235. Field lens 200
focuses illumination source light to an apex in proximity to
dichroic beam splitter 154. Illumination light is then collimated
by objective lens 153 onto applanation cap 35 as better shown in
FIG. 9A illustrating cornea illumination rays 223. The collimated
illumination light is reflected by applanation cap 35 back to
dichroic beam splitter 205 and corneal focusing lens 201, aperture
212 onto corneal image sensor 215. Retinal imagine axis 155 is
shown. Cornea illumination path 222 is shown, as well. Fixation
light source 230 is also shown.
[0084] As used in one illustrative corneal applanation imaging
system, applanation cap 35 is flat plane of PMMA with a very small,
2 mm in diameter cap lens 36. The incident illumination light will
be normal to flat plane of applanation cap 35. Therefore, the
reflectance, R, from each surface, proximal and distal, with a
refractive index n.sub.0 of air=1 and a refractive index n.sub.1 of
PMMA=1.492, is given by
R P = [ ( n 0 - n 1 ) ( n 0 + n 1 ) ] 2 . ##EQU00004##
Therefore, 3.9% of the incident light is reflected from the
proximal surface of the cap and 3.9% from the distal surface where
the cap is not applanating the cornea. When the distal surface of
applanation cap 35 is contacting cornea 20 having an index of
refraction n.sub.C=1.33, the distal surface will reflect
R D = [ ( n 1 - n C ) ( n 1 + n C ) ] 2 = 0.3 % . ##EQU00005##
As a result, the applanated area of cap 35 cornea will reflect
3.9%+0.3% or 4.2% of the incident light and the non-applanated area
will reflect 3.9%+3.9% or 7.8%. Thus cornea image sensor 215 will
show an almost 2:1 contrast ratio of applanated to non-applanated
areas on contact. FIG. 9B illustrates an applanated area using
collimated light. In this example, darker applanated area 177 has a
grey value of approximately 36 and is surrounded by lighter maximum
applanation area 176 having a grey value of approximately 64. 175
represents an applanation image.
[0085] FIG. 10 depicts various configurations of applanation cap 34
that are within the scope of the present disclosure. Alterations in
the anterior refractive surface of an applanation cap provide a
host of optical design options. For example, FIG. 9A shows the
cornea of globe 15 being applanated by plano-plano applanation cap
35A. As shown, the function of the cap is solely to applanate the
cornea. Upon applanation, the pressure in the eye will be elevated
and there will be complete loss of the refractive power by the
cornea. Conventional fundus cameras are dependent on corneal
refractive power to view the retina. As a result plano-plano
applanation cap 35A obviates use of such camera to view the retina.
Further, such cameras have no means to simultaneously view the
cornea.
[0086] The configuration of the system shown in FIG. 5 and
highlighted in FIGS. 6 and 9A overcome the limitations of a
conventional fundus camera. Such a configuration will permit
viewing the retina along the optical axis of the eye centered on
the fovea. The optic disc, from which the optic nerve and central
retinal artery and vein enter the retina, is located approximately
3 mm nasal and 1 mm superior to the fovea.
[0087] FIG. 10B illustrates applanation cap 35B, which is similar
to applanation cap 35A but has a prismatic element permitting a
shift in the image of the retina. This may permit viewing the
retina with the system aligned along the optical axis of the eye,
but centered on the optic disc. FIGS. 10 C, D and E show
applanation caps 35C, 35D and 35E with applanation cap lenses 36C,
36D and 36E respectively. The cap lenses have suitably positive
(convex) surfaces on the anterior surface to replace some or all of
the optical power of the cornea lost during applanation. The
configuration and size of the applanation cap and cap lens is
chosen in concert with the rest of optical module. Three
representative optical module configurations are illustrated herein
and are not to be viewed as limiting. Other optical module
configurations and caps can be designed within the teaching and
spirit of the invention by one of skill in the art.
[0088] As stated, the applanation cap may be of any material
compatible with the cornea such as polycarbonate, polymethyl
methacrylate (PMMA) or even glass. The applanation cap diameter can
range from about under 4 mm to over 15 mm.
[0089] The parameter that determines the applanation cap diameter
is the degree of globe applanation. For applanating an adult
cornea, a convenient size is 10 mm. This diameter does not include
the area for handling or conveniently mounting the applanation
cap.
[0090] In another embodiment of the disclosed invention, a
conventional optical configuration for viewing the retinal fundus
is used that does not share the optical path for viewing
applanation area of the globe. While corneal applanation techniques
for collapsing the retinal vessels and determination of intraocular
pressure is one preferred embodiment, it is understood that
applanation may be accomplished by applanation of the sclera as
well. However, any means of applanation can be used that can be
configured to permit a view of the blood vessels within the optic
disk and determine intraocular pressure. Suitable methods may
include but not be limited to corneal applanation tonometry,
pneumotonometry (also referred to a `air-puff tonometry"),
electronic indentation tonometry, transpalpebral (through the
eyelid) tonometry, and the like.
[0091] FIG. 11 depicts an exemplary embodiment based on use of a
retinal fundus viewing system that does not share an optical path
with the path used for measuring intraocular pressure. Several
retinal imaging and illumination configurations are well known in
the art, one of which is shown in this embodiment. Applanation cap
135 is positioned to applanate the cornea and form cornea-cap
interface 34. Cornea-cap interface 34 is preferably flat but may be
shaped to accommodate placement on the cornea and modifications in
the intraocular pressure measuring scheme. As shown in this figure,
retinal illumination source 120 emits light along retina
illumination path 126, which light is directed by lens or lenses
122 and is reflected by apertured mirror 145. Apertured mirror 145
has aperture 146 positioned along retinal imaging path 121.
Aperture 146 permits an un-obscured optical path for imaging the
retina. Further, it does not reflect retinal illumination along the
central axis of imaging path 121, and as a result it reduces or
eliminates light reflected back toward retinal imaging sensor 124.
Retinal illumination is transmitted through and focused by
applanation cap lens 136, passes through pupil 24 and suitably
reflects from one or more intraocular blood vessels of retina 30.
Cap lens 136 is a convex surface on proximal side of applanation
cap 135 designed to replace some or all of the refractive power of
the cornea during applanation.
[0092] Light reflected from retina 30 passes through pupil 24 and
applanation cap 135 and is focused by cap lens 136 to an apex at or
near aperture 146. Reflected light is then focused by retinal
focusing lens or lenses 140 onto retina image sensor 124.
[0093] An exemplary cornea applanation measurement scheme is also
shown in FIG. 11. Corneal illumination source 125 projects
illumination light by way of corneal illumination lens 127 to
cornea-cap interface 34. As described herein and as a result of
changes in the index of refraction at the cornea-cap interface, the
pattern of light at cornea-cap interface 34 changes as a function
of the force applied and resulting degree of applanation of the
cornea by applanation cap 135. The pattern of reflection and
resulting intensity of illumination light from cornea-cap interface
34 is focused by cornea imaging lens 129 onto cornea image sensor
131. Thus, ICP measuring system 118 is suitable to simultaneously
image the degree of applanation by applanation cap 135 on the
cornea and, image blood vessels in the optic disk of the retina.
Imaging axis 121 is also shown. An imaging aperture (not labeled)
may be present in communication with the image sensor 124.
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