Abstract:
The magnitude and axial orientation of birefringence of the anterior and the posterior segments of the human eye are determined. The anterior segment includes essentially the combined birefringence of the cornea and the crystalline lens, and the posterior segment includes regions at the fundus. The optical axis and the magnitude of the birefringence of the anterior segment is first determined, then the birefringence of the posterior segment is nulled by a variable retarder. The birefringence of the posterior segment is then determined without interference of the birefringence of the anterior segment. The apparatus and method are applicable to the measurement of the birefringence of the retinal nerve fiber layer at the peripapillary region and the birefringence of the Henle fiber layer at the macular region of the retina.

Description:
FIELD OF THE INVENTION 
     The present invention relates generally to diagnosing maladies of the eye using polarized light sources. 
     BACKGROUND 
     Knowing the thickness of a patient&#39;s retinal nerve fiber layer can be crucial in diagnosing glaucoma and other optic nerve diseases. It happens that the nerve fiber layer is “form birefringent”, which means that, if the polarization axis of a polarized beam of light passing through the layer is neither parallel nor perpendicular to the nerve fiber bundles, retardation is introduced into the beam. More specifically, birefringence is an optical property that arises from the anisotropy of a medium through which polarized light propagates, and it is manifested by the varying of the velocity of the light, with the velocity depending on the direction of propagation and polarization axis of the light. When light propagates perpendicular to the optic axis of an anisotropic material, two orthogonally polarized components of the light, one with polarization parallel to the optic axis and the other with polarization perpendicular to the optic axis, will travel at different velocities, resulting in a phase shift between the two components. This phase shift is referred to as “retardation”. The polarization state of the emerging backscattered light changes based on the amount of retardation between the two components. A retardation map can be generated based on the backscattered light that represents the thickness of the nerve fiber layer and, hence, that is useful for diagnosing maladies of the eye. 
     Accordingly, the present assignee has disclosed laser diagnostic devices in U.S. Pat. Nos. 5,303,709, 5,787,890, 6,112,114, and 6,137,585 that measure the thickness of the nerve fiber layer by measuring the amount of retardation of laser light in the fiber layer, with the amount of retardation then being correlated to layer thickness in accordance with principles known in the art. Likewise, as understood by the present invention the so-called Henle fiber layer, which includes photoreceptor axons and which has radially distributed slow axes centered about the fovea in the macula of the eye, is also form birefringent and consequently, its thickness also can be measured for diagnostic purposes using laser light. 
     As further recognized herein, however, portions of the eye (hereinafter collectively “anterior segments”) that are anterior to the nerve fiber layer and Henle fiber layer are also birefringent. For instance, both the cornea and lens are birefringent. Moreover, the axial orientation and magnitude of birefringence of the anterior segments can vary significantly from person to person. Since the diagnostic beam must pass through these anterior segments, the present invention understands that the laser beam retardation caused by these portions must be accounted for, to more accurately map posterior segments such as the nerve fiber layer and Henle fiber layer. 
     In the above-mentioned U.S. Pat. No. 5,303,709, a corneal compensator was disclosed for neutralizing the effects of the birefringence of anterior segments of the eye on a diagnostic beam meant to measure the thickness of the nerve fiber layer. The compensating structure in the &#39;709 patent includes a polarization sensitive confocal system attached to a scanning laser retinal polarimeter. The detector of this apparatus includes a pinhole aperture set to be conjugate with the laser source and the posterior surface of the crystalline lens so that only reflected light from the posterior surfaces of the crystalline lens is captured and analyzed. A variable retarder is then set to null any retardation in the returned light beam. 
     While effective for its intended purposes, the compensating features of the &#39;709 patent, as recognized herein, require that several optical components be added to the already complex optical system of a scanning laser polarimeter. Moreover, the &#39;709 invention uses the patient&#39;s lens as a reference surface for determining anterior segment birefringence. As recognized herein, a patient&#39;s lens reflection intensity which is captured by the confocal imaging can fluctuate due to eye movement, and consequently it can be difficult to accurately compensate for anterior segment birefringence when using the lens as a reference surface. 
     As also recognized herein, apart from the present invention&#39;s understanding that no method has yet been disclosed for compensating for the birefringence of anterior segments of the eye by post-measurement calculations, such post-measurement compensation can be complicated. This is because the particular contribution of the Henle fiber layer to overall retardation is not necessarily known, and instead is mixed in with the overall anterior segment birefringence. 
     The present invention accordingly recognizes that it would be desirable to provide a method and apparatus for measuring the birefringence of segments of the eye that are anterior to the retina, despite eye movement. 
     SUMMARY OF THE INVENTION 
     The apparatus and methods disclosed herein overcome the shortcomings of the above-mentioned corneal measurement apparatus. Instead of detecting the polarization state of the reflection from the back surface of the crystalline lens, polarimetry is performed on reflections from the fundus to determine the anterior segment retardation magnitude and axial orientation. The anterior segment birefringence is determined by analyzing the polarization state of the back-scattered light from one of the following fundus regions: the macula, the major retinal vessels, and locations where the retinal birefringence is inconsequential compared to the birefringence of the anterior segment. 
     To do this, the present invention uses a polarized light beam of known polarization state. One of the two simple polarization states are preferred: a rotating linearly polarized light, and a circularly polarized light. A variable retarder is provided to cancel out the anterior segment birefringence so that the incident beam remains a linearly polarized light beam or circularly polarized light beam when impinging on the fundus. 
     With this invention, a simplified scanning laser polarimeter can use the same beam path to measure the corneal and lens birefringence as is used to measure the retinal nerve fiber layer birefringence. Also, the anterior segment birefringence can be determined without eye movement interfering with the determination. Moreover, by measuring the anterior segment birefringence along substantially identical beam paths as are used for the measuring beams of retinal nerve fiber layer, a more accurate measurement of the anterior segment birefringence can be made, since corneal birefringence varies with the incidence angle of the beam and with the location of the cornea. 
     As disclosed in greater detail below, the reference target used for the backscattering of the probe beam to detect birefringence of the anterior segment is not on the lens, but rather is associated with the retina. For example, the target can be the Henle fiber layer in the macula. Alternatively, major retinal blood vessels can be used as the target. This is because, as recognized herein, retinal blood vessels are close to the retinal surface and the specular reflection from the top surface of the major retinal vessels maintains the polarization state of the incident beam. As a consequence, retardation measured at major blood vessels is a measurement of the birefringence from the anterior segment. Fundus regions where the retinal birefringence is at a minimum can also be used as a reference target, because the back-scattered light from these regions preserves the polarization state of the incident light. 
     The output of the invention is a retardation map of the nerve fiber layer or of the Henle fiber layer (photoreceptor axon layer), which can be used as a tool to diagnose and monitor glaucoma, macular degeneration, optic neuropathy, optic neuritis, aging, and other eye diseases, such as those that cause ganglion cell or photoreceptor axon atrophy. 
     In one aspect, a method is disclosed for determining a birefringence of a posterior segment of an eye having an anterior segment and a retina. The method includes directing a first beam against a portion of the retina to render a first reflected beam, and based on polarization properties of the first reflected beam, determining a birefringence of the anterior segment. The method further includes configuring a polarization compensating device to null the birefringence of the anterior segment. A second beam is directed through the polarization compensating device and against a portion of the retina to render a second reflected beam. Then, based on polarization properties of the second reflected beam, the method determines a birefringence of the posterior segment. 
     In a preferred embodiment, the birefringence of the anterior segment is determined by configuring the polarization compensating device to have a null setting, and then directing the first beam through the device to render the first reflected beam. Next, the polarization compensating device is configured to have a non-null setting. The method once again directs the first beam through the device to render the first reflected beam. 
     As set forth in greater detail below, in one presently preferred embodiment, the birefringence of the anterior segment is determined by determining a maximum magnitude derived from the first reflected beam, determining a Henle fiber layer value based on a difference between the maximum magnitude and a minimum magnitude derived from the first reflected beam, and then determining a retardation value of the anterior segment by subtracting from the maximum magnitude the Henle value and a setting value of the polarization compensating device. An algorithm is also disclosed for determining the birefringence of the anterior segment. The algorithm includes determining a retardation value δ as follows: δ=[λ/360°]sin −1 [I max /I total ] ½ , wherein I max  is a maximum output intensity of a first detector detecting the reflected beam, I total  is the sum of the intensities output by two detectors detecting the reflected beam, and λ is the wavelength of the first reflected beam. 
     The birefringence of the anterior segment alternatively can be estimated as followed. In this embodiment, a slow polarization axis of the anterior segment is observed. The method then determines a magnitude of a retardation of the anterior segment based on an average retardation value taken from a ring area centered on the fovea of the eye within a cone of 6° as measured from the pupil of the eye, where the fiber layer is relatively thin. 
     Circularly polarized light can be used in another embodiment. In this method, the circularly polarized light beam is directed onto the macula. A quarter wave retarder is set to zero, and then the axis of retardation is determined from the below-described “bow tie”. The quarter wave retarder axis is aligned with the observed axis and its value increased from zero until the “bow tie” disappears from the image. At this point, the axis and value of the retarder represent the axis and value of the anterior segment retardation. 
     The details of the present invention, both as to its structure and operation, can best be understood in reference to the accompanying drawings, in which like reference numerals refer to like parts, and in which: 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic view of the eye identifying various parts of the anterior segment; 
     FIG. 2 is a schematic cross-sectional view of the retina as seen along the line  1 — 1  of FIG. 1; 
     FIG. 3 is a schematic diagram showing the scan beam paths in the eye; 
     FIG. 4 is a block diagram of an optical system in accordance with the present invention; 
     FIG. 5 is a flow chart of the overall method of the present invention; 
     FIG. 6 is a flow chart of the method for determining the anterior segment birefringence in a first embodiment using retinal blood vessels or predetermined areas of the fundus; 
     FIG. 7 is a graph illustrating the relationship between detector outputs and the polarization axis; 
     FIG. 8 is a schematic view illustrating the relationship between the polarization axis and retarder axes; 
     FIG. 9 is a flow chart of the method for determining the anterior segment birefringence in a second embodiment using the Henle fiber layer; 
     FIG. 10 is a schematic illustration of the appearance of the retardation distribution of the Henle fiber layer; 
     FIG. 11 is a flow chart of the method for determining the anterior segment birefringence in a third embodiment using a single measurement; and 
     FIG. 12 is a flow chart of the method for determining the anterior segment birefringence in a fourth embodiment using circularly polarized light. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     As used herein, the term polarization “shifting” generically covers all types of polarization changes, including the rotation of the optical axis of polarized light, the change of linear to elliptically or circularly polarized light or vice-versa, and any combination of these. The term “polarimetry” refers to techniques for determining the polarization “shift” of a light beam. The term “polarimeter” refers to devices for performing polarimetry. The terms “spatially resolved retinal polarimetry” and “spatially resolved retinal polarimeter”, refer to the technique and device for performing polarimetry, point by point, on the retina. The term “retardation map” refers to a two-dimensional display of retardation distribution measured with a spatially resolved polarimeter. The term “corneal birefringence” means anterior segment birefringence, including contributions of the lens in addition to the cornea; and the term “corneal compensator” is used to describe a device for neutralizing the birefringence of the anterior segment of the eye, such as a variable retarder. 
     Referring initially to FIGS. 1 and 2, an eye  11  has a cornea  10  that serves as the foremost, transparent portion of the eye. Behind the cornea  10  is the iris  12  and the lens  14 . The interior of the eye  11  is filled with vitreous, and at the rear of the eye is the retina  15  which is composed of the layers as illustrated in FIG.  2 . The locations of the fovea  17  and the optic nerve head  13  are also shown in FIG.  1 . 
     As shown in FIG. 2, the retina  15  includes an inner limiting membrane  16 , followed by the nerve fiber layer  18 , the receptor system  21 , the Henle fiber layer  20 , the retinal pigment epithelium  22 , and the choroid  23 . All eye structure anterior to the inner limiting membrane  16  is referred to herein as the “anterior segment” of the eye. 
     As set forth further below, the thickness of the Henle fiber layer  20  and nerve fiber layer  18  can be measured. FIG. 3 illustrates the different beam paths that can be used to undertake these measurements. Specifically, the scan beam path in the eye is shown at  46  to be centered on the fovea  17  for macula measurement, whereas the scan beam path shown at  47  is centered on the optic nerve head  13  for peripapillary nerve fiber layer measurement. These measurement zones are adjacent to each other and are substantially overlapping. As recognized by the present invention, substantially the same region of the cornea and that of the lens are used in both measurements. Consequently, the effect of the anterior segment is substantially same in both measurements. 
     FIG. 4 shows one optical system that can be used to undertake the present invention. A monochromatic light source  30 , such as a laser, generates a monochromatic light beam indicated by the line labelled “beam”. The beam passes through a polarizer  31  to polarize the light, the polarization axis of which is set either parallel or perpendicular to the incidence plane of a non-polarizing beam splitter  32 . The light beam is then collimated by a lens  33 . The collimated beam passes through a polarization rotator  34 , which rotates the polarization axis of the beam by an angle θ while the light beam remains linearly polarized. 
     From the rotator  34 , the polarized light propagates through a scanning unit  35 . In one preferred embodiment, the scanning unit  35  includes a two dimensional scanning device. An appropriate conventional two dimensional scanning unit can be used. In one embodiment, a first line scanner performs a line scan and a second scanner performs step scan at the completion of each line scan. The two-dimensional scan field generated thereby is then projected through an imaging optics unit  36 , which can include an objective lens and a focusing unit to compensate for the refraction error of the eye. 
     The beam next passes through a variable retarder  37 . As set forth further below, the variable retarder  37  is an example of a corneal compensator that is used to measure the birefringence of the anterior segment of the eye. Also, the variable retarder  37  serves as a compensator to neutralize the anterior segment birefringence of the eye. The variable retarder  37  can be a liquid crystal variable retarder with controlled axes or it can be configured with two zero order fixed retarders. 
     Backscattered light, i.e., reflections from the fundus, propagates back through the same optical components until it is redirected by the beam splitter  32  towards a polarizing beam splitter  38 . The polarizing beam splitter  38  separates the light into two components. One component with a polarization axis perpendicular to the incidence plane of the beam splitter  38  is reflected to a first detector  39 , and the other component with polarization axis parallel to the incidence plane is transmitted to a second detector  40 . 
     Now referring to FIG. 5, the overall method steps for measuring the birefringence (as manifested in the light beam retardation it causes) of the anterior segment can be seen. Commencing at block  42 , the polarized light beam is directed onto a predetermined area of the fundus. More generally, the beam is directed onto the retina. 
     Moving to block  44 , the backscattered beam is used to determine the birefringence of the anterior segment, in accordance with disclosure below. Then, at block  46 A the variable retarder  37  is set to a value and axis that nulls the anterior birefringence. Next, at block  48  polarized light is directed on the fiber layer sought to be mapped, e.g., on the nerve fiber layer  18  or Henle fiber layer  20 . This causes backscattered light to be collected, with the backscattered light representing only the retardation caused by posterior segments, since the anterior segment birefringence is nulled by the variable retarder  37 . At block  50 , a layer thickness map is output by converting the birefringence values to layer thickness values in accordance with principles known in the art. 
     FIG. 6 shows a first method for determining the birefringence of the anterior segment, using retinal blood vessels or non-birefringent portions of the fundus. Commencing at block  52 , the variable retarder is set to a value of zero. Moving to block  54 , polarimetry is undertaken by directing the light beam against retinal blood vessels or non-birefringent portions of the fundus. 
     It is useful to note here that if the polarizer  31  is set with its axis parallel to the incidence plane of the beam splitter  32 , then the first detector  39  receives the cross-polarized light and the second detector  40  receives the light of the original polarization state. The output of detector  39  and detector  40  both depend on the retardation and the axis of polarization. FIG. 7 shows the relationship between the output of the two detectors and the linear polarization axis. In FIG. 7, “θ” is the orientation of the linear polarization after the rotator  34 . The retardation value δ is calculated at block  54  using the following formula: 
     δ=[λ/360°]sin −1 [I max /I total ] ½ , wherein I max  is the maximum output intensity of the first detector  39 , I total  is the total intensity of output by the detectors  39 ,  40 , and λ is the wavelength of the beam. 
     Note that, in the event of eye movement or lens accommodation, the light beam intensity would fluctuate. However, I max  and I total  would fluctuate proportionately, hence, the value of δ is not affected by eye movement accommodation. 
     It is to be understood that the angle θ max  is the polarization axis corresponding to I max  and is 45° from either the slow or fast axis of the retardation of the beam. The relationship between the various axes can be appreciated in reference to FIG. 8, wherein F and S stand for the fast and slow axis of the retardation, respectively, P represents the axis of the linear polarized light, θ is the angle of rotation of the linear polarization, and θ max  is the polarization axis corresponding to I max  of the first detector  39  as defined in FIG.  8 . Retardation axes are determined at block  56  in FIG. 6 by shifting the polarization by θ max  as shown in FIG.  8  and then adding and subtracting 45° therefrom. 
     It must then be determined which retardation axis is the fast axis and which is the slow. Accordingly, continuing the process of determining the fast and slow axes of the anterior segment birefringence in FIG. 6, at block  58  the value of the variable retarder is set to a predetermined bias value. At block  60 , the axes of the variable retarder  37  are aligned with the axes of the original retarder. At block  62 , if the maximum of the detector  39  output is higher than it was before the addition of the bias, it is thereby determined that the slow axis of the bias retarder is aligned with the slow axis before the bias. On the other hand, if the maximum of the detector  39  output is lower, the slow axis of the bias retarder is aligned with the fast axis. 
     Now referring to FIG. 9, the method for measuring anterior segment birefringence using the Henle fiber layer  20  can be seen. Commencing at block  64 , the value for the variable retarder  37  is set to zero, and the value of the retardation of the macula (i.e., retardation caused by the Henle fiber layer in the macula) is measured in accordance with the following disclosure. 
     As recognized herein, the slow axis of the birefringence of the Henle fiber layer  20  is parallel to the axons and is therefore radially distributed. Accordingly, at block  66  in FIG.  9  and as shown best at reference numeral  68  in FIG. 10, a bow-tie pattern is usually observed. The bow-tie pattern is a result of the combined retardation of the anterior segment of the eye  11  and the variable retarder  37  superimposed onto the uniformly distributed retardation of the Henle fiber layer. The orientation where the bow-tie pattern is brightest, indicated at  70  in FIG. 10, corresponds to the slow axis of the combined retardation. In contrast, the orientation of where the bow-tie pattern is darkest corresponds to the fast axis. When the combined retardation of the anterior segment and the variable retarder is zero, the bow-tie pattern disappears and the macula consequently exhibits a uniform retardation map. Thus, the fast and slow axes of the combined retardation can be determined immediately from observing the bow-tie pattern at block  66 . 
     However, the magnitude of the combined retardation cannot be determined from a single Henle fiber layer measurement because the retardation of the Henle fiber layer is unknown. Therefore, the logic moves to block  72  in FIG. 9, wherein the variable retarder  37  set to a known value and the slow axis of the variable retarder  37  is aligned with the slow axis of the anterior segment birefringence observed at block  66 . Proceeding to block  74 , the light beam is directed against the Henle fiber layer  20  of the macula, and the retardation of the anterior segment is then sampled from a ring area centered on the fovea  17  where the bow-tie pattern has maximum modulation (i.e. where the Henle fiber layer is thickest). The difference between the maximum and minimum of the measured values is two times the retardation of the Henle fiber layer, and this is determined at block  76 . At block  78 , the anterior segment retardation is determined by subtracting from the maximum value both the retardation of the Henle fiber layer and the set retardation value of the variable retarder  37 . 
     Now referring to FIG. 11, a method for estimating the anterior segment birefringence using a single measurement is illustrated. Commencing at block  80 , the variable retarder  37  is set to zero. Then, at block  82  the light beam is directed against the Henle fiber layer and the slow axis of the anterior segment is observed per the above discussion. The magnitude of the retardation of the anterior segment is estimated as being the average retardation value taken from an area centered at the fovea  17  where the Henle fiber layer is relatively thin anywhere in 6° as measured from the center of the pupil. 
     FIG. 12 shows yet another embodiment for using circularly polarized light as the probing beam. It is to be understood that when circularly polarized is used, the system shown in FIG. 4 is modified as follows. The variable retarder  37  is replaced with a quarter-wave retarder to generate a circularly polarized light beam. The axes of the quarter-wave retarder are offset 45° from the axis of the linearly polarized light. In this embodiment, the second detector  40  receives the cross-polarized light and the first detector  39  receives the light of the original polarization state. The macular intensity image generated by the second detector  40  is used to determine the anterior segment birefringence. 
     The method for using circularly polarized light begins at block  84 , wherein a circularly polarized light beam is directed onto the macula. The variable retarder is set to zero at block  86 , and then the axis of retardation is determined at block  88  from the resulting “bow tie” image, with the intensity map being used in lieu of the birefringence map. Moving to block  90 , the variable retarder axis is aligned with the observed axis and its value increased from zero while maintaining its axis alignment until, at block  92 , the “bow tie” disappears from the image. At this point, the axis and value of the variable retarder represent the axis (exactly crossed) and a value that is equal to that of the anterior segment retardation. Accordingly, these values are output at block  94  as representing the axis and value of the anterior segment retardation. 
     Once the anterior segment retardation and axis are determined, the retarder is set to neutralize the corneal birefringence as discussed above. The retardation map of the nerve fiber layer and/or the Henle fiber layer is then accurately measured, and the thickness of these structure can be estimated. 
     While the particular SYSTEM AND METHOD FOR DETERMINING BIREFRINGENCE OF ANTERIOR SEGMENT OF A PATIENT&#39;S EYE as herein shown and described in detail is fully capable of attaining the above-described objects of the invention, it is to be understood that it is the presently preferred embodiment of the present invention and is thus representative of the subject matter which is broadly contemplated by the present invention, that the scope of the present invention fully encompasses other embodiments which may become obvious to those skilled in the art, and that the scope of the present invention is accordingly to be limited by nothing other than the appended claims, in which reference to an element in the singular is not intended to mean “one and only one” unless explicitly so stated, but rather “one or more”. All structural and functional equivalents to the elements of the above-described preferred embodiment that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the present claims. Moreover, it is not necessary for a device or method to address each and every problem sought to be solved by the present invention, for it to be encompassed by the present claims. Furthermore, no element, component, or method step in the present disclosure is intended to be dedicated to the public regardless of whether the element, component, or method step is explicitly recited in the claims. No claim element herein is to be construed under the provisions of 35 U.S.C. §112, sixth paragraph, unless the element is expressly recited using the phrase “means for” or, in the case of a method claim, the element is recited as a “step” instead of an “act”.