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BACKGROUND OF THE INVENTION
1. Field of Invention
This invention relates to a method and apparatus for assessing the
thickness and topography of the retinal nerve fiber layer by measuring the
polarization effect of the retina on an impinging light beam while
simultaneously eliminating the polarization effects of the anterior
segment of the eye on the same beam.
2. Description of the Prior Art
The retinal nerve fiber layer is the innermost layer of the human retina
and consists of the ganglion cell axons which transmit the visual signal
generated by the photoreceptors. The ganglion cell axons (nerve fibers)
converge to the optic papilla where the optic nerve is formed that
transmits the bundled visual information from the eye to the brain. In
glaucoma and certain other diseases, there is damage to these nerve fibers
which results in a loss of vision or even blindness. In order to detect
glaucoma and to prevent further loss of vision, it is important to assess
the exact condition of the retinal nerve fiber layer. One method for
making this assessment that is in widespread use is that of employing a
fundus camera with red-free illumination to photograph the retinal nerve
fiber layer. Blue light (red-free) enhances the visibility of the
transparent nerve fibers, and retinal locations with a nerve fiber layer
defect appear darker than normal. However, no quantitative measurements
can be obtained.
More recently, several methods have been developed that attempt to quantify
the three-dimensional size and shape of the optic papilla which can be
considered a bulk representation of the retinal nerve fibers. By analyzing
the topography of the optic papilla and the surrounding retina, an
indirect measure of the condition of the retinal nerve fiber layer can be
obtained.
One of the current methods is stereoscopic fundus photography where two
photographs of the fundus are obtained under different angles, and the
depth or topography information is extracted by triangulation (see, for
example U.S. Pat. No. 4,715,703).
Another method consists of projecting a stripe or grid pattern onto the
fundus, which is observed under a certain angle. An algorithm calculates
the apparent deformation of the projected stripes into the topography of
the illuminated fundus region (see, for example, U.S. Pat. No. 4,423,931).
More recent methods utilize the technique of confocal scanning laser
ophthalmoscopy where a laser beam is scanned across the eye fundus in two
dimensions in order to obtain real time video images on a TV monitor. By
focusing the scanning laser beam on different layers of the retina and
confocally detecting the light reflected from the fundus, optical section
images of the retina can be obtained. These tomographic section images are
analyzed to obtain the topography of the fundus. One apparatus (U.S. Pat.
No. 4,900,144) employs a detection system consisting of two confocal
detectors to obtain real-time topographic data from the scanning laser
beam.
All of these techniques depend on the intensity of light reflected from the
retinal surface as the sole probing tool for ascertaining the fundus
topography. They are based on the assumption that the point of brightest
reflection is at the internal limiting membrane, the interface between the
vitreous and the retina. The point of maximum reflection is, therefore,
assumed to represent the anterior surface of the nerve fiber layer. In
reality, the light detected from the fundus is a mixture of light
reflected from the internal limiting membrane and of light scattered from
many points within the retina. Therefore, the maximum of the total
intensity distribution of all light detected from the retina does not
coincide with the most anterior surface of the retina, and a false
topographic reading is presented by the conventional methods. Another
major limitation of the conventional methods is the inability to measure
thickness of the retinal nerve fiber layer. Whereas the topography of the
fundus is a reasonable indicator of the thickness of the layer, it is
indirect and suggestive only. A method of directly measuring the actual
thickness of the retinal nerve fiber layer would represent a clearly
valuable addition to the diagnostic tools available to the medical
diagnostician.
It has been known [see for example, Journal of the Optical Society of
America A 2, 72-75 (1985)] that the human retina has certain polarization
properties. The instant inventors, in a paper delivered in 1991,
[Technical Digest on Noninvasive Assessment of the Visual System, 1991
(Optical Society of America, Washington, D.C., 1991), Vol. 1, pp.
154-157], showed that the retinal nerve fiber layer was responsible for
the polarization effect of the retina. The retinal nerve fiber layer
consists of parallel axons which are form birefringent and change the
state of polarization of light double-passing through it. The thicker the
nerve fiber layer, the greater the alteration of the state of polarization
of impinging light and thus the polarization of reflected light, yielding
an opportunity to measure the thickness of the nerve fiber layer by gaging
the relative shifting in polarization between the incident and reflected
light at various points along the retinal nerve fiber layer.
The use of polarization measurements for mapping the retinal nerve fiber
layer thickness, however, suffered from another potential limitation,
which is, that the cornea and the crystalline lens of the eye also have
birefringent qualities and therefore will alter the state of polarization
of light double-passing it as well as the retinal nerve fiber layer, so
that the total polarization shift of double-passing light is the sum of
the shift caused by both the nerve fiber layer and the anterior segment of
the eye. Without compensating for the polarization effects of the anterior
segment, the measurement of the retinal polarization effect as a
diagnostic technique would be of limited value.
SUMMARY OF THE INVENTION
The object of the present invention is therefore to provide a method and
apparatus for measuring polarization effects of the retina while
compensating for the polarization effects of the anterior segment of the
eye in an automatic fashion. By compensating for the polarization effect
of the anterior segment of the eye, all nerve fiber layer testing would
yield meaningful results as a result of having the anterior segment
polarization effects substantially neutralized. Furthermore, by
neutralizing the polarization effects of the anterior segment of the eye
and by the use of polarization-sensitive detection means, the light that
has been reflected specularly from the internal limiting membrane at the
anterior surface of the nerve fiber layer can be distinguished from the
light originating from deeper retinal layers, therefore improving
conventional topographic methods.
To attain this object, systems are provided for utilizing polarization
probes for diagnosing the ocular fundus using a corneal polarization
compensator for neutralizing the polarization effects of the anterior
segment of the eye. The corneal polarization compensator comprises of a
variable retarder through which monochromatic polarized laser light is
passed and focused through the cornea onto either the posterior or
anterior surface of the lens of the eye. The reflected light double-passes
the anterior segment of the eye, travels back through the variable
retarder and is confocally detected. The light is photoelectrically
converted, and the signal is processed to control the retardation of the
variable retarder in a closed feedback mode. The optical path in the
compensation scheme is such that when the variable retarder is adjusted to
the point where it neutralizes the polarization distortion of the cornea
and lens, the signal at the photodetector is at its maximum and the
variable retarder is fixed at this setting.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagrammatic section taken through line 1--1 of FIG. 1a;
FIG. 1a is a diagrammatic view of the eye identifying parts of the anterior
segment;
FIG. 2 illustrates diagrammatically the main parts of a embodiment of the
corneal polarization compensator using an ellipsometer;
FIG. 3 illustrates diagrammatically one manner in which the nerve fiber
layer thickness is mapped with the use of a sequence of polarizers of
different states of polarization; and,
FIG. 4 illustrates a topographical mapping system;
FIG. 5 illustrates the appearance of the retinal nerve layer under
illumination with linearly polarized light and detection with a crossed
polarizer, corneal birefringence being eliminated;
FIG. 6 is identical to FIG. 5, but illustrating measurement taking place
with the orientation of the polarization axis of the illuminating beam and
the detection filter both being rotated about 45 degrees; and,
FIG. 7 is a diagrammatic illustration of a photodetector incorporating a
focusing lens and a pinhole diaphragm for use in confocal detection
techniques.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIGS. 1a and 1 illustrates the eye 11, in which the cornea 10 serves as the
foremost, transparent portion of the eye, behind which is the iris 12 and
the lens 14. The interior of the eye 11 is of course filled with vitreous
and at the rear of the eye is what is generally termed the retina composed
of the layers illustrated, in FIG. 1, including the internal limiting
membrane 16, the nerve fiber layer 18, the receptor system 20, the retinal
pigment epithelium 22, and the choroid 23. All eye structure forward of
the membrane 16 is considered the anterior segment of the eye for purposes
of this disclosure and claim definitions.
This invention concerns itself primarily with the cornea, the lens, and the
nerve fiber layer 18. It is this nerve fiber layer's topographical and
thickness measurements which are crucial to the diagnosis of certain
diseases, principal among which is glaucoma.
As indicated above, the nerve fiber layer 18 has birefringent properties,
which means, in general, that a polarized light ray incident on the
surface of the birefringent medium with its optic axis parallel to the
surface will split into two rays of different polarization propagating in
the same direction but with different velocities. The difference in
travelling velocity results in a phase shift between the two rays, called
retardation, and has the effect of altering the polarization of the light.
The thicker the birefringent medium, the larger is the retardation of
light passing through the medium. A so-called "quarter wave" retarder
incorporates a birefringent medium that retards one of the rays that is
split out of incident light 90 degrees relative to the other, and thus
will convert linear polarization to circular polarization, and vice-versa.
The nerve fiber layer 18 has the property of birefringence. The cornea and
the lens also have birefringent properties, although the birefringence of
the lens is small compared to the cornea. There are no other known
birefringent layers in the eye. The eye polarization characteristics will
be used to measure the thickness and the topography of the nerve fiber
layer.
Turning now to FIG. 2, a complete system for diagnosing the thickness of
the nerve fiber layer is diagrammatically shown. All of the structure in
FIG. 2 except for the ellipsometer 24 are for the purpose of compensating
for the polarization shifting caused by the cornea and lens. (In this
disclosure, polarization "shifting" is the term used generically to cover
all types of polarization changes, including rotation of the optical axis
of polarized light, the change of linear to elliptical or circularly
polarized light or vice-versa, and any combination of these). The term
"corneal polarization compensator" is used for describing the device for
compensating for the polarization effect of the anterior segment of the
eye.
The ellipsometer 24 is for the purpose of accurately measuring the
polarization shift of a beam of light which double-passes the nerve fiber
layer. This shift correlates to the thickness of the nerve fiber layer
once the corneal polarization compensation has been effected.
The corneal polarization compensator 25 utilizes a laser diode 26 which
provides a beam of light that is focused by a lens 27 onto the pinhole 28
and expands as a cone until it impinges upon the polarizing beamsplitter
30. This beamsplitter has two purposes, the first of which is to polarize
the incident compensation beam 32, which it does as is indicated by the
legend indicated at 32a, illustrating the linear transverse polarization
that the beam has at this point. The beam subsequently passes through a
collimating lens 34 and a quarter wave retarder 36, which converts the
beam 32 from linear polarization illustrated in the legend 32a to the
clockwise circular polarization indicated in the legend 32b.
At this point, the incident compensation beam 32 passes through a
reticulated or rectangular diffraction grating 38, which has the effect of
corpuscularizing the light into a plurality of beams, so that a plurality
of focus points as indicated at 32(e) are used by the compensator rather
than a single spot. The beam is reflected on the beamsplitter 40,
converged by the converging lens 42, and passed through the variable
retarder 44, which in the preferred embodiment is a liquid crystal
retarder. This retarder changes the polarization of the incident beams
from circular polarization to elliptical as illustrated at 32c, still
being clockwise in sense.
At this point, the plurality of converging sub-beams of the whole beam 32
from the variable retarder 44 converge, passing through the cornea 10 and
lens 14, becoming circularly polarized as indicated at 32d and reflecting
as return compensation beam 45 from the posterior surface of the eye lens
14, as illustrated. This reflected or return compensation beam is
polarization shifted by the double-passage through the cornea and lens not
only to circular polarization as indicated at 32d, but is shifted to
reverse the direction of the circular polarization as a result of the
reflection, as indicated at 45a. (For purposes of the claims, the incident
and return beams are each treated singularly, but each includes all of the
composite beams split out by the diffraction grating and then
re-converged.)
The return compensation beam 45 has polarization transversely illustrated
in the legends 45a-45d, above and to the right of the configuration.
Immediately upon reflecting from the lens surface, the right-hand circular
polarization is changed to left-hand circular polarization 45a, and shifts
to elliptical polarization as indicated at 45b upon passage through the
cornea 10 and lens 14. The return compensation beam 45 passes through the
variable retarder 44 where its polarization is restored to circular
polarization as indicated in 45c, and travels back through the elements
that the impinging beam went through, passing through a polarization shift
at 45d until the beam arrives at the polarizing beamsplitter 30.
It will be remembered that when the beam initially passed up through this
beamsplitter, it was transversely polarized as indicated at 32a. It is a
property of a polarizing beamsplitter to transmit light that is polarized
perpendicularly to its reflecting surface, and to reflect light that is
polarized parallel to its reflecting surface. As the return compensation
beam is now completely linearly polarized, parallel to the reflecting
surface of the beamsplitter 30, the return compensation beam 45 is
reflected to the right, towards the photodetector 46. The return
compensation beam is focused by the lens 34 onto the pinhole 47 in front
of the photodetector 46. The pinholes 47 and 28 are located in optically
conjugate planes to the focal points formed at the posterior surface of
the lens. This confocal arrangement assures that stray light reflected
from other areas than the focal points is blocked by the pinhole 47 and
cannot reach the photodetector 46.
In other words, when all light of the return beam 45 impinging downward
upon the polarizing beamsplitter 30 is linearly polarized orthogonally to
the direction of the upwardly travelling beam 32, all of the light
reflected from the surface of the lens 14 would travel through to the
photodetector 46. Thus, with no polarization shift at all caused by the
anterior segment of the eye, incident and return compensation beams 32 and
45 would have the polarization states shown at 32a and 45d, respectively.
The variable retarder is adjusted to maximize the intensity of light in
the polarized state shown at 45d as closely as possible.
The photodetector 46 transforms the intensity of impinging light into an
electrical signal that is fed into the electronic feedback circuit 49.
Because the cornea and lens shift the polarization, the variable retarder
is varied by the electronic circuit 49 until the electric signal coming
from the photodetector 46 is maximized. FIG. 2 illustrates states of
polarization of incident and return beams after the compensator has
already been adjusted to compensate for anterior segment polarization
shift.
After the variable retarder 44 has been adjusted for the optimal
compensation of corneal and lenticular polarization distortion, the
ellipsometer 24 is free to pass its incident diagnostic beam 48 through
the beamsplitter, having its beam polarization-compensated by the variable
retarder (compensator) 44, and receive a return beam 50 that actually
reflects not the polarization distortion caused by the cornea and lens,
but only that of the nerve fiber layer in question. This polarization
information is then captured and can be analyzed according to ellipsometry
techniques that are known in the prior art or as set forth in this
disclosure.
This process has been disclosed having the incident and return compensation
and diagnostic beams double-passing the variable retarder 44. However,
with a different geometrical arrangement, only one of the compensation
beams and one of the diagnostic beams would have to pass through the
variable retarder, and it could be either the incident beams or the return
beams, or one of each. The simplest geometry and probably the most
accurate results involve double-passing both beams through the variable
retarder as shown, however.
The corneal polarization compensator 44 is used in all of the techniques
that are discussed in this disclosure. It has already been stated that the
ellipsometer can be used basically by itself, as shown in FIG. 2, along
with scanning and analysis equipment, not shown in FIG. 2, to provide a
reasonably accurate map of the thickness of the retinal nerve fiber layer.
A computer frame 51 shown in FIGS. 3 and 4 illustrates the appearance of a
typical nerve fiber layer thickness or topography map.
One way of measuring and mapping the thickness of the nerve fiber layer is
shown in FIG. 3, with a system that uses an ellipsometer not described in
the prior art. It has an incident diagnostic beam 48 produced by the laser
52, linearly polarized by linear polarizer 54, converted to circular
polarization by quarter-wave retarder 56 and scanned across the ocular
fundus by the scanning unit 58. At each point of the scan, the return
diagnostic beam 50 is then again scanned by an oscillating mirror 60
sequentially across a plurality of polarizers 62 forming an array. Six
polarizers are shown in the array of FIG. 3, and as the return beam
reaches the detector 64 in sequence from each of the polarizers the beam
intensity is photoelectrically converted by the detector 64 into an
electrical signal that is digitized by an Analog-to-Digital Converter 65
and stored in the memory of the computer 66. From the data stored in the
computer, the four elements of the Stokes vector of the incident
diagnostic beam 48 are compared to the calculated Stokes vector of the
return diagnostic beam, and the change in polarization at the current
measuring location is displayed on the CRT display 63. Subsequently, the
incident diagnostic beam is guided by the scanning unit 58 to the next
measuring site.
The scanned polarizer system of FIG. 3 is very diagrammatic, and the
polarizers could be either reflective or transparent and would ordinarily
have a mirror system converging the respectively produced beams onto the
detector. For every point scanned on the ocular fundus, all of the
polarizers 62 would be scanned by the oscillating mirror 60.
It would be clear to a person skilled in the art that the principle
described can also be performed by changing the time sequence of the
polarization data measurement process. For example, instead of scanning a
single point at 58 while mirror 60 undergoes a complete scanning cycle,
the incident diagnostic beam 48 could first be scanned by the scanning
unit 58 over the whole examination area, while the return diagnostic beam
50 passes only one of the polarizers. In the next step, the procedure is
repeated, but the return diagnostic beam 50 is passed through the second
polarizer, and so on, scanning a complete frame for each of the polarizers
62 before moving on to the subsequent polarizer..
Furthermore, the process of imaging the examination area by a scanning
laser beam could be replaced with illuminating the fundus with an extended
light source and replacing the detector 64 with a camera.
Thus far, the specification has been discussing not topography but rather
the gaging of the thickness of the nerve fiber layer and the creation of,
in essence, a thickness map display. It is also possible using a very
similar technique to create a topographical map which is considerably more
accurate than the usual confocal-produced topographical maps that
currently are made using light intensity only, not polarization shifting.
FIG. 4 is a diagrammatic illustration of a system similar to FIG. 3 which
will produce a topographical map of the retinal nerve fiber layer. The
scanning unit 58 is replaced by a three-dimensional scanning unit 59, and
the detector 64 is replaced by a confocal detection unit 67. It is similar
to the typical confocal system that is now used, except that the optical
data that is received back from the nerve fiber layer is sorted by
discarding any data, that is any light rays, that are returning from the
eye having altered polarization. The polarization of the incident beam is
known and can be compared with the analyzer 68 to the polarization of the
return beam.
Any of the detectors, indicated at 64, 67 or 69, could be configured for
confocal detection to eliminate light not returning from the selected
focal plane in the eye by incorporating a lens 71 and a pinhole diaphragm
73 before the actual detector structure itself 75 as indicated in FIG. 7.
Because the corneal polarization compensator eliminates polarization
shifting caused by the anterior segment of the eye, and the polarization
of the incident light beam is known, any return light which is changed in
its state of polarization is known to have been reflected from a surface
deeper than the nerve fiber layer surface 16 inasmuch as there would not
be a polarization shift were the reflection to take place only from the
surface. Thus, the typical confocal topographical mapping technique can be
enhanced by discarding all light information in which the light rays have
been altered in their polarization state.
The amount of information that can be gleaned from the interior of the eye
utilizing these techniques incorporating the cornea polarization
compensator could be quite great. For example, topographical maps of
deeper layers of the eye than the surface of the nerve fiber layer can be
made by rejecting the light in the polarization state of the initial beam,
rather than vice-versa. This could possibly produce a topographical map of
a surface posterior to the nerve fiber layer. That is, light reflected
from a surface more posterior than the nerve fiber layer would have a
different polarization than the incident light, and thus it would be
recorded and mapped rather than the non-adulterated incident ray that
would be used to produce topographical map of the anterior surface of the
nerve fiber layer.
The last method of measuring nerve fiber layer thickness to be discussed
herein uses the same basic equipment shown in FIG. 4 for topography
mapping, except that a polarization rotator 70 is interposed in the light
path of the incident or return diagnostic beam, or both the incident and
the return diagnostic beams, and a second detector 69 measures the
absolute intensity of the return diagnostic beam, independent of the
polarization state of that beam. Understanding this technique depends on
understanding basic retinal anatomy illustrated in FIGS. 5 and 6. The
retinal nerve fiber layer 14 comprises an array of radially arranged nerve
fibers 72 which converge to form the optic papilla 74. The radially
arranged nerve fibers are about half the diameter of the wavelength of
visible light and at any one point simulate parallel fibers having
directional birefringent properties.
This radial array of nerve fibers acts as a linear birefringent medium due
to the local parallelism and wavelength order-of-magnitude spacing of the
fibers. It is illuminated with linearly polarized light, and the reflected
from the ocular fundus is passed through an analyzer with an orthogonally
polarized filter 68 to a photodetector or collector. The transverse
polarizations of the incident beam and the filter are indicated
respectively at 76 and 78. A "cross" pattern of brightness, indicated at
80, will appear at the detector. There will be darkness along the
polarization axes of both the incident light beam and the analyzer filter.
The bright arms correspond to areas of the nerve fiber layer having fiber
orientation rotated 45 degrees to either side of the polarization axis of
the incident beam (and the analyzer filter). The bright portions of the
cross give an accurate indication of the thickness of the nerve fiber
layer at these points, as substantial change in polarization caused by
substantial nerve fiber layer thickness will shift the polarization of the
light adequately to pass through the analyzer polarization filter.
In order to obtain a thickness analogue at every point of the nerve fiber
layer, the polarization axes of the incident beam and analyzer filter are
synchronously rotated through 90 degrees, with a brightness reading taken
every 2 degrees or so, for every point on the fundus that will appear on
the map. The brightest return beam the detector picks up for every scanned
point on the fundus is cumulated with every other brightest point and
formed into an intensity map that corresponds to the relative thickness of
the nerve fiber layer point by point.
The second photodetector 69 is used to measure the total amount of
reflected intensity of the return diagnostic beam at the corresponding
points on the fundus. By normalizing the intensity values obtained with
the first photodetector 67 with the corresponding intensity values
obtained with detector 69, absolute changes in the state of polarization
of the return diagnostic beam are calculated.
This technique produces a nerve fiber layer thickness map similar to that
produced by the first two techniques using ellipsometers. It is an
alternative technique.
All of the diagnostic techniques and equipment disclosed herein depend on
the polarization characteristics of the ocular fundus in order to be
feasible, and depend on the compensating capability of the corneal
polarization compensator in order to produce useable results. The
polarization diagnostic techniques disclosed herein make a substantial
contribution to the ability to diagnose diseases of the interior of the
eye, especially early diagnosis of glaucoma.
DEFINITIONS OF TERMS USED IN THE DESCRIPTION AND CLAIMS
ABSOLUTE INTENSITY refers to the sum of the intensities of all of the
component parts of a light beam, including polarized and unpolarized
segments.
ANALYZER, or POLARIZATION ANALYZER: a device whose output is a function of
the polarization state of analyzed light in some way, and it may be no
more than a polarization filter which attenuates light which is not
linearly polarized with a specific orientation of the POLARIZATION AXIS or
it may correlate the polarization state or shift with another quantity. An
ANALYZER may or may not produce results which are directly readable by the
operator.
ANTERIOR SEGMENT OF THE EYE refers to all parts of the eye forward of the
OCULAR FUNDUS, in this instance those parts which pass light incoming
through the cornea. It includes the vitreous, lens, aqueous, and cornea
and any membranes.
BIREFRINGENCE is a POLARIZATION PROPERTY of certain materials which retards
the propagation velocity of only part of a transmitted beam, causing it to
have a phase lag with the rest of the beam, shifting the polarization
phase; birefringence is not the only possible polarization property.
FUNDUS=ocular fundus
KNOWN STATE OF POLARIZATION refers to the POLARIZATION STATE that is
controlled so interaction with equipment such as polarization filters
produces meaningful and possibly measurable results. The phrase does not
mean that the operators necessarily know exactly what the polarization
state is at a given time.
MODULATION of the polarization state of light is the alteration of the
polarization state over time analogous to frequency or amplitude
modulation; the retardation can be modulated, which if executed through a
complete 360.degree. cycle causes the polarization to cycle through
linear, elliptical, circular, elliptical, linear, reverse-direction
elliptical, circular, elliptical and back to linear. Or, the polarization
axis can be modulated by being rotated about the optical axis. Any
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