WO2002087427A1 - Appareil et procede de mesure de caracteristiques specifiques des yeux - Google Patents

Appareil et procede de mesure de caracteristiques specifiques des yeux Download PDF

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Publication number
WO2002087427A1
WO2002087427A1 PCT/NL2002/000290 NL0200290W WO02087427A1 WO 2002087427 A1 WO2002087427 A1 WO 2002087427A1 NL 0200290 W NL0200290 W NL 0200290W WO 02087427 A1 WO02087427 A1 WO 02087427A1
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Prior art keywords
light
eye
lens
reflectance
pupil
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PCT/NL2002/000290
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English (en)
Inventor
Jan Van De Kraats
Toussaint Theresia Johannes Maria Berendschot
Niels Petrus Antonius Zagers
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Universitair Medisch Centrum Utrecht
Universiteit Utrecht
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Publication of WO2002087427A1 publication Critical patent/WO2002087427A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions

Definitions

  • the invention relates to an apparatus for measurement of specific characteristics of eyes.
  • Such apparatus is known from US 5873831.
  • a laser light source is provided for directing monochromatic light into an eye.
  • a light collecting system is provided for collecting light scattered by the eye, which is then directed to a spectrally highly selective system for separating different types of light.
  • Analysing means are then provided for analysing the light received by said selective means for analyses of macular carotenoid pigment deposition.
  • An object of the present invention is to provide for an apparatus with which at least two characteristics of an eye can be measured.
  • a further object of the present invention is to provide for such apparatus using a single light source.
  • a still further object of the present invention is to provide for such apparatus which enables assessment of at least two of the following three characteristics substantially simultaneously: spatial distribution of the fundus reflectance in a pupil plane of an eye; the part of the retina used for fixation; and - the spectral fundus reflectance along a line in the pupil plane.
  • the present invention further has the object to provide for a method for measurements of specific characteristics of eyes, with which method substantially instantaneously measurement and analyses of at least two characteristics of an eye can be obtained.
  • At least spectro graphic means are provided for analysing the spectral pattern and/or distribution of the light reflected, wherein analysing means are provided for assessment of fundus reflection in the pupil plane and/or spectral fundus reflectance along a line in the pupil plane and/or measurement of the part of the retina used for fixation.
  • substantially white light is transmitted from a light source, from which light red light can be filtered out, whereas the heat of the light can be substantially absorbed. Surprisingly it has been found that light having longer wavelengths may normally be disregarded. Filtering will result in less heating.
  • the remaining light is transferred through a hole in a mirror, from the back side thereof, into an eye, approximately through the centre of the lens system of said eye, accurately focussed by lenses and/or diaphragms. This light is reflected by at least the retina and transmitted back through said lens system, onto the reflecting surface of said mirror, around said hole.
  • Said mirror is preferably angled relative to the direction of the light transferred into said eye, such that it can be transferred to said analysis means. This enables good separation of the going light going into the eye and the less intensive light reflected, which is to be analysed. Interference is substantially obviated.
  • light reflected is directed at will either to a video image system or to a spectrograph, for example by means of an optical switch comprising a movable mirror.
  • Lenses or polarisation means such as filters can be provided for varying a plane of detection and/or imaging, especially between the optical switch and the video image system.
  • Computer means comprising analysing software can be provided for processing digital images of the reflected light, which images can be obtained by for example a C CD -camera, a digital video system or the like. By digitising the images obtained, such as light reflection images and spectrographs accurate analyses can be obtained almost instantaneously by said computer means.
  • Various advantageous embodiments of an apparatus and method according to the present invention are presented in the appending claims. By way of example an advantageous embodiment will be described, with reference to the drawings. These show: fig. 1 schematically an apparatus according to the present invention; fig. 2 schematically a light source of an apparatus according to fig. 1; fig. 3 schematically a ophthalmic mirror system of an apparatus according to fig. 1; fig.
  • FIG. 4 schematically an optical switch of an apparatus according to fig. 1; fig. 5 schematically a video observation system of an apparatus according to fig. 1; fig. 6 schematically a spectrograph and detector of an apparatus according to fig. 1; fig. 7 an experimental set-up combining apparatus of fig. 2-6; fig. 8 an example of a two dimensional dataset; fig. 9 a diagram showing the relation between reflectance and position in the pupil plane at different wavelengths; fig. 10 a diagram showing percentage reflectance versus wavelength; fig. 11 schematically the layout of the experimental apparatus, similar to fig. 1 and the pupil plane and retinal plane configuration; and fig. 12-15 test results obtained with the apparatus according to fig. 11.
  • FIG. 1 shows schematically an apparatus according to the present invention. The different components will in further detail be described with reference to fig. 2 - 6.
  • An apparatus 1 for analysis of characteristics of an eye, comprises a light source 2, an ophthalmic mirror system 3, an optical switch 4, a video observation unit 5, a detector 6 with a spectrograph 7 connected thereto and a computer 8 comprising appropriate software and a monitor.
  • the light source 2 designed such that it emits light of different, multiple wave lengths, especially substantially white light.
  • the light emitted from the light source 2 is focused and passed through said ophthalmic mirror system 3, into an eye 9.
  • the beam 10 of light is emitted into substantially the centre of the lens system of the eye 9, as indicated schematically in fig. 1A, such that it passes substantially straight through a central part 11 of the pupil.
  • Said light is then reflected by inter alia said retina, partly out of said eye 9 through the part 12 of the lens system of the eye surrounding said central part 11.
  • the light reflected, indicated by numerous arrows 13 has a substantially lower intensity then the beam 10 and is somewhat scattered due to the reflection and the reflecting surfaces such as the retina and other surfaces inside the eye. Also contamination of the lens system can influence scattering.
  • the reflected light 13 is deflected by the ophthalmic mirror system 3 towards the light switch 4.
  • the reflected light is either deflected to the video observation unit 5 or to the detector 6 and connected spectrograph 7, for analysing the spatial distribution of the fundus reflection, preferably in the pupil plan, preferably simultaneously, assessment of the part of the retina used for fixation and spectral fundus reflectance along a line in the pupil plane respectively.
  • the video images and spectrographic images which are preferably digitised, are fed into the computer unit 8 for processing and viewing said images and the analysing results on the screen.
  • At least the light source 2, the optical switch, the video observation system 5 and the detector and spectrograph 6, 7 are controlled by the computer unit, which is also used for absloute spectrographic calibration of the apparatus, which is necessary for accurate analysis of the images and spectrographic plots obtained.
  • Fig. 2 schematically shows a light source 2, from which a controlled beam 10 of light is produced.
  • the actual source of light 14 is the rectangular shaped coil of a 30 W halogen lamp.
  • the top lens system 15 consists of two lenses 16. They image the coil on a diaphragm (not shown), which is optically conjugate with the pupil plane of the investigated eye 9. The diaphragm determines the size of the entrance in the lens system of the eye 9. Between the two relay lenses a set of filters absorbing heat and red light can be placed (not shown) for filtering out substantially all red light and/or heat in said beam 10.
  • the bottom lens system 17 again consists of a pair of lenses 18. They are drawn as a single lens. In reality, they are preferably spaced a few cm apart. A plane optically conjugate with the retinal plane of the investigated eye 9 is available in between these two lenses. In this plane a diaphragm (not shown) is placed to control the size of the illuminated region on the retina. The light is focused towards the ophthalmic mirror system 3, as shown in fig. 3 by converting lines 10A, crossing in point F. Fig. 3 shows schematically the ophthalmic mirror system 3 which allows separating the dim light 13 reflected by the eye 9 from the intense beam 10 entering it.
  • the key element is a mirror 19 with a central hole 20 placed optically conjugate with the pupil plane.
  • An image of the coil (beam 10) is focused in the centre of the hole 20 by the light source 2. This image is relayed with a single, aspheric ophthalmic lens 21 to the pupil plane. Because the rays (schematically shown as lines 10B) are focused substantially within the centre 11 of the eye's lens-system 9A, the rays 10B will continue in their original direction towards the retina. This way, a relatively small spot is illuminated on the retina. ⁇ . Light 13 reflected from the retina can be considers as a new, small source of light. When the eye 9 is unaccommodated, the lens system 9A of the eye 9 will image the retina in a plane placed at infinity.
  • a plane optically conjugate to the retina (not specifically shown) is located in between the ophthalmic lens 21 and the mirror 19 with central hole 20, one focal length behind the ophthalmic lens 21. Both this retinal plane and the largest part of the pupil plane are available via the mirror 19.
  • the optic switch 4 as schematically shown in fig. 4 comprises three lenses 22, 23 and 24 respectively, and a moveable mirror 25.
  • the mirror 25 is pivotally connected to an axis 26 and is movable between a position "in place” as shown in fig. 4, enclosing an angle of approximately 45 degrees with the main direction of the light 13 (which is in the drawing substantially perpendicular to the centre of lens 22) and a pivoted position out of reach of said light 13.
  • the mirror 25 "in place" the light 13 is reflected 'upwards' and the right 22 and top lens 23 act as a relay pair (upward, right and left as seen in fig. 4; these can normally be in any desired position).
  • the light 13 is directed towards a video observation channel of the video observation unit 5, as shown in fig. 5.
  • the mirror 25 can be removed from the beam 13 fast, which makes the light available for the detector 6 and spectrograph 7.
  • the right 22 and left lens 24 act as a relay pair.
  • Fig. 5 schematically shows Video observation unit 5.
  • the bottom lens 23 in Figure 5 corresponds to the top lens 23 in Figure 4.
  • the bottom lens 23 relays both the pupil and retinal plane (only two pupil plane rays are drawn). Both planes are available for imaging on the video camera (V).
  • the top lens system 27 contains an insertable lens 28 (not shown specifically). By removing or inserting this lens 28, the imaged plane is selected. Video images obtained can be displayed on a monitor 29.
  • Fig. 6 schematically shows a detector 6 and spectrograph 7.
  • the right lens 24 in Figure 6 corresponds to the left lens 24 in Figure 4.
  • This lens 24 images the pupil plane at infinity.
  • a plane optically conjugate to the retina (not specifically shown) is located between this lens 24 and the lens 30 nearest to it at the left, as seen in fig. 6.
  • a diaphragm is used to limit the observed region of the retina to just within the illuminated region (fig. 1A).
  • the second lens 30 focuses the light on the entrance slit 31 of an imaging spectrograph 7.
  • This slit 31 is in a plane optically conjugate to the pupil plane.
  • the first lens 33 of the spectrograph 7 turns the beam 13D parallel again.
  • the beam 13E traverses a direct vision prism which spectrally decomposes the beam 13E.
  • the light reflected from the eye is divided in light of different wavelengths by said prism, for further analysis.
  • the further lens 34 images the spectrum on a cooled CCD camera 35.
  • the CCD 35 is controlled an read with the computer unit 8.
  • FIG. 7 A schematic representation of the set up as seen from above is depicted in Fig. 7.
  • Retinal and pupil planes are indicated with R and P, conjugate planes with R' and P.
  • the optical path starts with a lamp 14.
  • the lenses L1...L4 and the ophthalmic front-lens Lf define the entrance beam, which illuminates a small spot on the retina.
  • Light reflected from the eye is captured by Lf. Separation of the reflected light from the entrance beam is achieved with an ophthalmic mirror Mh 19.
  • the reflected light is either available for observation with a video camera V, or for analysis with an imaging spectrograph.
  • the mode used depends on the position of an insertable mirror Mi 25.
  • the spectrograph image is captured with a cooled integrating CCD camera. Below a more detailed description is given.
  • the entrance beam is a Maxwellian view system, used for controlled illumination of a small spot on the retina.
  • the light source is a 30 W halogen lamp.
  • An image of the coil of the lamp is relayed in the pupil plane with lens systems LI and L2, L3 and L4, and the ophthalmic front lens Lf.
  • An aperture placed conjugate to the pupil plane in plane P' after L2 controls the size of the entrance beam in the pupil plane to 1 x 1.5 mm.
  • a cross-wire for fixation is placed in plane R' close to the lamp. In between LI and L2 the beam is substantially parallel.
  • spectral filters are placed, with the purpose to increase the ratio of blue over red light. Eye reflectance is far lower in the blue wavelength region than in the red. In between L3 and L4 the beam is also parallel.
  • a retinal conjugate plane R' is available here, where an aperture controls the angle of the illuminated field on the retina. A 3 degrees field is used for measurements. For alignment, the field angle can be increased to for example 10 degrees.
  • Light reflected from the eye is very dim compared to the bright entrance beam. Separating both beams is achieved with an ophthalmic mirror Mh 19. The entrance beam passes through the central hole 20 of the mirror. Light reflected from the eye is captured by the remaining part of the mirror. This configuration allows observation of most of the pupil.
  • Lens Lf is placed slightly out of center and is slightly tilted, to redirect reflections at the front and back glass-air interfaces out of the center of the beam. Remaining stray-light is accounted for in the dark calibration.
  • the retina is imaged at infinity by the eye's lens.
  • Lens Lf images the retinal plane in its focal plane, in between Lf and Mh. Mh is conjugate with the pupil plane. Both planes are relayed to either a video observation channel (up-wards), or an imaging spectrograph (left-wards), depending on the position of the insertable mirror Mi 25.
  • a video observation channel For alignment of the subject a video observation channel is available.
  • lenses L5 and L10 act together as a relay pair. Both retinal and pupil plane are relayed to between lens L10 and Lll.
  • An insertable lens Li controls which plane is focussed on the video camera chip V. Imaging the retinal plane allows observing whether the subject fixates correctly on the entrance beam. Imaging of the pupil enables observing the location of the entrance beam within the pupil, and is also used to achieve a good focus of the entrance beam in the pupil plane.
  • Lenses L5 and L6 combined image the pupil plane at infinity.
  • a retinal plane R' is available, where an aperture controls the size of the sampled region on the retina to approximately 2 degrees.
  • An adjustable slit is placed in the focal plane of lens L7.
  • the slit defines a horizontal, bar shaped exit pupil, which measures 1 x 12 mm in the pupil plane of the eye.
  • the slit is in the focal plane of lens L8, which images it at infinity.
  • the light traverses a direct vision dispersion prism (Prism, Linos, Part No. 33 1120).
  • the spectral image is focussed on the chip of a cooled CCD camera (CCD, SBIG, ST-237).
  • the camera is read out in 3x3 binning mode.
  • the spectral image contains 213 points in spectral direction and about 85 points in spatial direction.
  • Fig. 8-10 show data obtained with an apparatus and a method according to the present invention.
  • Fig. 8 shows an example of a two-dimensional data-set: percentage reflectance versus wavelength and position in the pupil plane.
  • the data was binned to 5 nm bandwidth in the spectral direction.
  • the common spectral shape of fundus reflectance is recognizable at the borders of the spectrum.
  • a single spatial profile at 525 nm is indicated with the fat line.
  • Fig. 9 shows reflectance versus position in the pupil plane at four different wavelengths.
  • the data is subset of the data shown in fig. 8.
  • the spatial intersections were taken near a number of common laser wavelengths.
  • Data was binned to 5 nm bandwidth before the profiles were obtained.
  • the solid lines are fits of a Gaussian curve of the data.
  • Fig. 10 shows a percentage reflectance versus wavelength.
  • the data is a subset of the data shown in figure 8.
  • the spectral intersection was taken where the spatial intersections show a maximum.
  • the solid line is a model fit to the data.
  • An apparatus can be used for example for measurement of both the spatial distribution of the fundus reflectance in the pupil plane and the spectral distribution of the reflectance along a line in the pupil plane.
  • the part of the retina used for fixation should preferably be monitored, to avoid problems because of possible peripheral fixation.
  • the measurements can be made fast and easy resulting in high performance and low cost of the apparatus.
  • the Foveal Reflection Ophthalmoscope according to the present invention will allow study a substantial number of patients in diseases such as age-related macular degeneration and glaucoma, which both ask for a better understanding of their pathogenesis.
  • An apparatus 1 according to the present invention is especially suitable for screening device for photoreceptor densitometry and as a tool for detection of macular and melanin pigment density.
  • Age-related macular degeneration (AMD) is the most common cause of blindness in the Western world. Macular- and melanin pigment possibly protect against AMD. It is therefore of great importance to have a simple device that can measure these pigments, both for screening and follow-up in case of dietary supplementation.
  • an apparatus according to the present invention is especially but not exclusively suitable as a screening device for densitometry.
  • the presently known technique of densitometry is time consuming and can only be applied at a very limited number of laboratories in the world. Therefore, it is of great importance to have a simple screening device, that provides similar information, which is provided for by the present invention.
  • the apparatus was basically set up as follows:
  • FIG. 11A A schematic representation of the experimental set up is depicted in Fig. 11A.
  • Retinal and pupil planes are indicated with R and P, conjugate planes with R' and P. In some cases, adjacent elements or planes are drawn as a single line.
  • the entrance beam emerges from a lamp, and passes the lenses LI through L4 and the ophthalmic front-lens Lf.
  • the entrance beam defines a small entrance pupil in pupil plane P, and illuminates a small spot in the retinal plane R.
  • Light reflected from the eye is captured by lens Lf. Separation of the reflected light from the entrance beam is achieved with an ophthalmic mirror Mh.
  • the reflected light is either available for observation with a video camera V, or for analysis with an imaging spectrograph.
  • the mode used depends on the position of an insertable mirror Mi.
  • the spectrograph image is captured with a cooled integrating CCD camera.
  • the retinal and pupil plane configuration is depicted in Fig. 11B.
  • the illuminated field measures 2.8 degrees.
  • the sampled field is concentric, and measures 1.9 degrees. This overlap assures a complete illumination of the sampled field, despite small errors in focus and aberrations in the optics of the eye.
  • the cross-wire is centered on the illuminated field.
  • the entrance pupil is placed centered with, and below the bar shaped exit pupil. Their separation is 0.7 mm.
  • the bar is defined by the slit of the spectrograph. To avoid confusion: the terms entrance and exit are defined with respect to the eye, not the spectrograph.
  • the entrance beam forms a Maxwellian view system, used for controlled illumination of a small spot on the retina.
  • An image of the coil of the 30 W halogen lamp is relayed to the pupil plane with achromatic pairs LI, L2 and L3, L4, and the ophthalmic front-lens Lf (20 D, Nikon).
  • the front-lens can be moved in the direction of the beam (z-direction) to focus on the retina. Eye reflectance is far lower in the blue wavelength region than in the red.
  • glass filters F are placed (FG3 and BG38, 3 mm both, Schott), with the purpose of increasing the ratio of blue over red light, and to block most of the infrared light.
  • the intensity of the light entering the eye is 1.10 x 10 6 Td.
  • An aperture in plane P' after L2 controls the size of the entrance beam in the pupil plane to 0.8 x 1.2 mm (with the front-lens focussed at infinity).
  • a cross-wire for fixation is placed in plane R' close to the lamp. Between L3 and L4 the beam is again parallel.
  • Another retinal conjugate plane R' is available here, where an aperture controls the visual angle of the illuminated field on the retina. A 2.8 degrees field is used for measurements. For alignment, the field angle is increased to 16 degrees.
  • An additional green filter (VG9, Spindler & Hoyer) is then inserted, to increase contrast of the view.
  • the intensity of the alignment beam is 3.35 x 10 5 Td.
  • Light reflected from the eye is captured by lens Lf.
  • the retinal plane is imaged in the focal plane of Lf, the pupil plane in the plane of Mh.
  • Light reflected from the eye is very dim compared to the bright entrance beam.
  • the entrance and exit light are separated with an ophthalmic mirror Mh conjugate to the pupil plane.
  • the entrance beam which passes through the central hole of Mh, is correctly focussed in the pupil plane, reflections from the cornea largely disappear in the same hole.
  • Light reflected from the eye is captured by the remaining part of the mirror. This configuration allows observation of the entire pupil, except for the part covered by the hole.
  • Lens Lf is placed slightly out of center and is slightly tilted, to redirect reflections at the front and back glass-air interfaces out of the center of the beam. This way, the reflections are blocked by the retinal aperture at R' in the spectrograph, and by a small mask on a glass plate in front of LlO in the observation beam.
  • a video observation channel For alignment of the subject a video observation channel is available.
  • lenses L5 and LlO act together as a relay pair. Both retinal and pupil plane are relayed to between lens LlO and Lll.
  • Lens Li moved in or out of the beam with a magnetic solenoid, controls which plane is focussed on the video camera chip V (VCB-3512P, Sanyo). Imaging the retina allows focussing of the cross-wire, and observing whether the subject fixates correctly. Imaging of the pupil enables observing the location of the entrance beam within the pupil, and is also used to achieve an optimal focus of the entrance beam in the pupil plane.
  • E. Imaging Spectrograph When the mirror Mi is removed from the beam, light is available for the imaging spectrograph. Lenses L5 and L6 combined, image the pupil plane at infinity. In between L6 and L7 a retinal plane R' is available, where an aperture controls the size of the sampled region on the retina to 1.9 degrees.
  • a slit 0.90 mm wide, is placed in the focal plane of lens L7, conjugate to the pupil plane.
  • the slit defines a horizontal bar shaped exit pupil, which measures 0.8 x 12 mm in the pupil plane of the eye (with the front-lens focussed at infinity).
  • the slit is in the focal plane of lens L8, which images it at infinity.
  • the light traverses a direct vision dispersion prism (Prism, Spindler & Hoyer, Part No. 331120).
  • the spectral image is focussed on the chip of a cooled CCD camera (CCD, ST-237, SBIG).
  • the camera is read out in 3 x 3 binning mode.
  • the spectral image contains 213 points in spectral direction and 85 points in spatial direction.
  • Reflectance was routinely calibrated with a surface painted with Eastman 6080 white mounted at the end of a black, anodized tube. 2 This painted surface was calibrated against a freshly pressed BaSO 4 surface, which we considered the gold standard.
  • the white reference was placed at 445 mm behind the pupil plane and illuminated with the measuring light. Front-lens focus was adjusted to place the reference in a retinal conjugate plane.
  • White reference frames calibrate the spectral output of the lamp, transmission of the optics, sensitivity of the CCD camera, as well as sensitivity variations among CCD camera pixels. To account for stray light in the apparatus and dark current in the CCD camera, reference frames of a dark cloth held at about one meter behind the pupil plane were taken.
  • the integration time of the dark frames matched the integration time of the measured spectrum and the white reference frame.
  • White and dark reference frames were obtained prior to each session. In case a refractive correction was required during the session, additional dark frames for the new position of the front-lens were obtained at the end of the session.
  • Each 3 x 3 binned pixel on the CCD is a detective element, measuring counts at a certain wavelength ⁇ within range ⁇ , and at a certain pixel position x in the spatial direction.
  • an expression for calculating reflectance R( ⁇ , x) from the number of counts in the measurement C " M( ⁇ , x), the white reference Cw( ⁇ , x), and matching dark references CMD(X, X) and Cw ⁇ ( ⁇ , x) is derived.
  • R( ⁇ , x) is an equivalent reflectance: all sources contributing to the reflected light are considered as if they were diffuse reflectors.
  • Ph( ⁇ ) be the number of photons per second in the entrance beam, at wavelength ⁇ within range ⁇ , either entering the eye or falling on the white-reference surface. Part of the photons will be reflected and back scattered, forming a source of photons in the retinal plane.
  • the number of counts in a pixel is proportional to the photon flux through its detection area and the integration time. The flux through the area Ap spanned by the detective element in the pupil plane at distance d from the retinal plane, is proportional to Ap / d 2 . In the measurement situation, the number of detected counts is given by:
  • ⁇ is the ratio of the sampled and illuminated area in the retinal plane.
  • S ( ⁇ , x) is a sensitivity factor containing transmission of the optics, quantum efficiency and gain of the CCD pixels.
  • the factor 2 ⁇ accounts for light being reflected into half a sphere. In case of the BaSO 4 white reference surface, 99 % of light in the range 400-800 nm is reflected perfectly diffuse or isotropic into a half sphere. 30 A relation similar to Eq. (1) holds for the white reference images:
  • the factor Aw I AM which accounts for changes in scale of the pupil plane with the front-lens position, is calculated from pixel scale SP ⁇ X as ( «Sp ⁇ ,w / ⁇ SPIX,M) 2 (for calibration of ⁇ S ⁇ , see Section 3C).
  • the axial length of the eye d eye is calculated from the front-lens focal adjustment. It is assumed that the cornea and eye-lens can be treated as a single flat lens with focal distance 22.29 mm, 30 and that all ametropia can be attributed to variation in axial length of the eye.
  • RN the read-noise of the camera in counts, i the number of counts read from the pixel, and B the bias level of the camera in counts.
  • the factor 3 accounts for 3 x 3 on-chip binning. Using the appropriate error propagation mathematics and Eq. (3), an error is attributed to the reflectance.
  • spectral calibration of the spectrograph images of a mercury lamp illuminating the wall opposing the set-up were obtained. Pixel positions of 7 lines were determined (wavelengths in air: 435.8, 491.6, 546.1, (577.0 + 579.1) / 2, 623.4, 690.8, and 772.9 nm). 31
  • the wavelength range covered by the spectrograph was 420-790 nm. Dispersion strongly depended on wavelength. At 420 nm the spectral range covered by one 3 x 3 binned pixel was about 0.4 nm; at 760 nm it was about 6 nm.
  • SPIX For calibration of pixel scale SPIX, a transparent film containing periodic vertical dark bars was placed in the pupil plane.
  • Images of the wall opposing the set-up revealed the periodic pattern, which enabled scaling of the pupil plane to CCD pixels.
  • Scale was calibrated for the complete range of front-lens settings. With the front-lens focussed at infinity, one 3 x 3 binned pixel corresponded to 0.14 mm in the pupil plane. Prior to the calculation of reflectance, the images were binned and interpolated to 5 nm spectral and 0.1 mm spatial resolution, to correct for the non-linear dispersion of the prism and variable scaling of the pupil plane.
  • the research followed the tenets of the Declaration of Helsinki and was approved by the local Medical Ethics Committee. The purpose was explained at the beginning of the experiment, and written informed consent was obtained.
  • the pupil of one eye was dilated with one or two drops tropicamide 0.5 %.
  • the head-rest can be adjusted in 3 dimensions. This allowed focussing on the pupil plane, and positioning of the entrance beam within the pupil. Subjects were instructed to fixate the cross-wire at all times.
  • For adjustment of the head-rest the large field with an additional green filter was used. With the large field the pupil lit up more brightly, focus in the pupil plane was more critical, and a larger part of the retina could be seen.
  • the entrance beam was focused in the pupil plane. Care was taken to avoid reflections from the corneal surface of the eye. Fixation was checked in the retinal image. If required, the front-lens focus was adjusted. During focal adjustment the head-rest was moved as well, to maintain a good focus in the pupil plane.
  • the maximum in the directional reflectance (e.g., the maximum of the Stiles-Crawford effect) was searched for, using the measuring field.
  • continuously spatial profiles near 540 nm were read from the CCD while discarding the remaining part of the data, thereby achieving a short readout time. Integration time was reduced to 0.25 seconds.
  • the directional reflectance shows up prominently.
  • the maximum position is readily observed in a profile plot on a computer display.
  • the maximum in vertical direction was found by a manual search. While scanning vertically, the latest profile was compared by eye to the highest profile till then. The search typically took about 2 minutes.
  • A. Reflectance Spectrum Image An example of an image of two-dimensional reflectance is presented in Fig. 12 (female subject, age 20). The image shows equivalent reflectance of the fovea, expressed as a percentage on a logarithmic scale, versus wavelength and location in the pupil plane. Temporal (T) and nasal (N) side are indicated. The image can be looked upon in two ways: first, as spectral reflectance versus location in the pupil plane, and second, as an optical Stiles-Crawford profile versus wavelength.
  • the characteristics of spectral fundus reflectance are recognized: a decrease towards short wavelengths, with steeper decrements at 590 nm, 510 nm, and at the lowest recorded wavelengths. 2 - 13 - 15 - 32 At the longest wavelengths, ocular pigments, except melanin, are fairly transparent. Below 590 nm, light is efficiently absorbed by blood. The contribution to reflectance from deeper, blood rich layers diminishes, causing the first decrement. Reflectance below 590 nm mainly originates from the receptor cell layer. 2 The second decrement at 510 nm is due to macular pigment. The latter also causes a shallow dip near 460 nm.
  • Absorption by the crystalline lens causes a decline at the shortest recorded wavelengths.
  • the optical SCE is best observed in the region 510-590 nm.
  • the profile near 540 nm, indicated by the thick line in Fig. 2 presents a typical example.
  • Reflectance shows a bell-shaped dependence on position in the pupil plane, with a maximum slightly on the nasal side of the pupil center. 21,23, 2 5 - 27
  • the directional part of the reflectance dissolves in the much larger non-directional part.
  • absorption by the macular pigment and the crystalline lens leave the bell-shape intact, but strongly reduce the amplitude of the directional reflectance.
  • Spectral Intersections For each measurement, the spectrum at the pupil position with the highest reflectance at 540 nm was selected (e.g., the spectrum indicated with a thick line in Fig. 2). The spectra were fitted with the van de Kraats et ⁇ l. fundus reflectance model using a least squares method. 2 - 33 Each data point was assigned a weight one over its error squared. The model describes radiation transfer in the eye with a limited number of reflecting, absorbing, and scattering layers. Spectral properties of the absorbers are taken from the literature.
  • the solid lines represent model fits. The effect of increasing lens absorption with age is apparent from the downward trend with age of the spectra below 500 nm. Deviations between the data and the model are largest below 425 nm. Here, both reflectance and the power of the entrance beam are low, resulting in a low signal to noise ratio.
  • the mean data are also presented in Table 1, together with relative standard deviation, i.e., the standard deviation of the subject means divided by the mean of subject means. Also given is the relative error, which was first calculated for each subject from the mean of the estimated measurement errors and mean of 25 spectra, and then averaged over subjects.
  • Table 2A gives a summary of the results of the spectral model fit.
  • the parameter mean PM is the mean of 21 within subject mean values.
  • the standard deviation ⁇ N is the standard deviation of the subject means with respect to PM.
  • PMW and PMAX are the lowest and highest within subject means. In some cases MIN reached zero. This was the lower limit set in the fit algorithm.
  • the Levenberg-Marquardt method returned 68 % confidence intervals for the fitted parameters. 33
  • the mean of 21 within subject mean confidence interval estimations CI is also shown in Table 2A.
  • the study design of 5 measurement series with 5 replacements allowed an estimation of (1) the total standard deviation o ⁇ , (2) standard deviation with respect to the mean of series ⁇ s, and (3) the standard deviation of the mean of series ⁇ M .
  • the coefficient of repeatability CR is defined as the 95% range for the difference in two repeat measurements. 34 The coefficients followed from the mean values of ⁇ ? ⁇ s, and CJM after multiplication by 2 ⁇ 2.
  • Fig. 14 gives an impression of the model predictions for single measurements.
  • Fig. 14A shows twenty-five macular pigment density (D m ac) estimates for all twenty-one subjects.
  • D m ac is known to vary substantially between subjects. The within subject variability is occasionally large. Six subjects had experience in this type of experiments (1, 3, 12, 13, 17, and 21). They generally showed low variability. In some of the other subjects variability was equally low (e.g., 2, 10 and 11). Others, however, show a large variability (e.g., 9 and 19).
  • Fig. 14B is a similar scatter plot for melanin density (D me ia). For melanin, within-subject variation is much smaller compared to Dmac The stability of the melanin data indicates that the high Dmac variability is not related to instrumental errors or head instability of the subject. A probable explanation is given in the discussion.
  • the solid lines represent fits with Eq. (5).
  • the profiles drop to zero.
  • the edge of the pupil may span numerous pixels when the bar is far below or above the pupil center, since the vertical width of the bar is much larger than the horizontal width of the pixels.
  • the maxima show up near the pupil center, with a tendency to the nasal side.
  • Table 2B gives a summary of the SCE parameter fit results (c.f., explanation in Section 4B).
  • Fig. 13B Mean Spectrum In Fig. 13B, the mean spectrum (solid line) is compared with literature data. Differences between the spectra depend on (at least) three factors: composition of the population, size of the illuminated and sampled retinal field, and configuration of entrance and exit pupil. The large differences between subjects are very apparent from Fig. 13A, with largest variation below 500 nm. There is a strong influence of age on the spectra, as absorption in the crystalline lens increases with age. 35 Delori and Pflibsen measured subjects aged 22-38 years. 15 The lack of older subjects may explain the somewhat higher reflectance below 500 nm.
  • Receptor disc reflectance jRdisc cannot be discerned from a reflecting layer at the level of the retinal pigment ephithelium (RPE) in a single bleached spectrum at the Stiles-Crawford maximum.
  • RPE retinal pigment ephithelium
  • the arguments for attributing reflectance at this level in the retina to the discs in the receptor outer segments are given by van de Kraats et ⁇ l. 2
  • Mean disc reflectance was 2.8 %, similar to van de Kraats et ⁇ l., who found 2.75 %. 2
  • the results can also be compared with RPE reflectance of 2.3 % in the model by Delori and Pflibsen. 15
  • the high mean disc reflectance demonstrates the effectiveness of alignment with the Stiles-Crawford maximum.
  • Mean macular pigment density Dmac was 0.45 at 460 nm, range 0.28-0.64. Van de Kraats et al. found higher values (0.54 at 460 nm, 0.42-0.83). 2 As stated before, this was caused by sampling a smaller retinal field. Delori and Pflibsen found lower values (0.21 at 460 nm, 0.12-0.31). 15 In a more recent paper, Delori et al. reported 0.23 for a reflectometric method (sampled field: 2 degrees). 39 With a method based on the autofluorescence of lipofuscin, a fluorophore posterior to the macular pigment, they found 0.48 (sampled field: 2 degrees).
  • the cause for the low reflectometric values may reside in their model, since it lacks reflectors anterior to the macular pigment, e.g., inner limiting membrane and cornea. Accounting for light reflected posterior to the macular pigment gives a higher macular pigment level.
  • Berendschot et al. studied the effect of lutein supplementation on D mac in 8 male subjects with a reflectometer and a scanning laser ophthalmoscope (SLO). 8 At baseline, mean Dmac was 0.47 for the reflectometric, and 0.26 for the SLO technique.
  • Reflectance from the cornea JRcomea was on average 0.043 %. This is low in absolute sense, but is of equal magnitude as light reflected from the fundus at wavelengths below 500 nm, especially in older subjects, e.g., see Fig 13A.
  • the mean confidence interval CI states how accurately parameters are determined in the model fit. A large confidence interval indicates large measurement errors or bad convergence of the fit. For most parameters, except jRiim and ?comea, CI was smaller than ⁇ isr and the range PMIN to PMAX. Apparently, in some cases i?ii m and ir nea did not strongly contribute to reflectance and were attributed a very large error. The weakness of the current model is that sometimes parameters are optimized in the fit while being insignificant, or that parameters reach the lower (physical) limit set to zero.
  • CRT The coefficient of repeatability derived from the total standard deviation CRT contains the total experimental error.
  • CRT was smaller or hardly larger than ⁇ N and well smaller than the range PMIN to PMAX. This means the measurements discriminate well between subjects.
  • CRT is much larger than CI for Dmac and ?disc . This indicates that the uncertainty in D mac and i?di SC results mainly from experimental errors.
  • a high within series CRs points to errors in fixation and movements of the subject. Between series CRM is mainly connected to errors in the alignment procedure. For ?disc CRM is largest, most variation is due to variation in alignment on the optical Stiles-Crawford maximum. For D ma c CRs is largest. Macular pigment is highly concentrated towards the center of the fovea.
  • ⁇ wavelength
  • R mean reflectance
  • SD relative between subjects standard deviation, i.e., the standard deviation of the subject means divided by the mean
  • RE relative error.

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Abstract

L'invention concerne un appareil de mesure d'au moins deux caractéristiques spécifiques des yeux. Cet appareil comprend une source lumineuse (2), des moyens (3) de transfert de rayonnement de la source lumineuse (2) vers un oeil (9) et des moyens de réception de rayonnement (6) permettant de recevoir le rayonnement réfléchi par l'oeil (9), la source lumineuse (2) comprenant des moyens permettant de fournir un rayonnement à plusieurs longueurs d'ondes, plus précisément de la lumière blanche, et les moyens de réception de rayonnement (6) comprenant des moyens spectrographiques permettant d'analyser le rayonnement réfléchi, ainsi que, de préférence, des moyens d'observation vidéo.
PCT/NL2002/000290 2001-05-02 2002-05-02 Appareil et procede de mesure de caracteristiques specifiques des yeux WO2002087427A1 (fr)

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WO2003058200A2 (fr) 2002-01-07 2003-07-17 The University Of Utah Research Foundation Procede et appareil pour obtenir une image de pigments maculaires par imagerie raman
WO2005044098A1 (fr) * 2003-10-28 2005-05-19 Welch Allyn, Inc. Ophtalmoscope de documentation numerique
EP1793732A2 (fr) * 2004-09-29 2007-06-13 University Of Delaware Spectrographe a infrarouge et methode pour diagnostiquer une maladie
US7311401B2 (en) * 1998-11-24 2007-12-25 Welch Allyn, Inc. Eye viewing device comprising eyepiece and video capture optics
WO2009018953A2 (fr) * 2007-08-03 2009-02-12 Carl Zeiss Meditec Ag Procédé et dispositif de détermination des conditions d'état d'un objet à étudier et de mesure de fluorescence sur l'œil
EP2278909A1 (fr) * 2008-04-22 2011-02-02 Annidis Health Systems Corp. Procédé et appareil de surveillance de fond rétinien
US8350044B2 (en) 2009-05-05 2013-01-08 Dow Agrosciences, Llc. Pesticidal compositions
US8807751B2 (en) 2008-04-22 2014-08-19 Annidis Health Systems Corp. Retinal fundus surveillance method and apparatus
CN106166056A (zh) * 2016-07-11 2016-11-30 孙明斋 多光谱眼底成像系统
WO2017075089A1 (fr) * 2015-10-28 2017-05-04 Loma Linda University Système et procédé pour analyser différentes couches rétiniennes

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Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7311401B2 (en) * 1998-11-24 2007-12-25 Welch Allyn, Inc. Eye viewing device comprising eyepiece and video capture optics
EP1480559A2 (fr) * 2002-01-07 2004-12-01 The University of Utah Research Foundation Procede et appareil pour obtenir une image de pigments maculaires par imagerie raman
WO2003058200A2 (fr) 2002-01-07 2003-07-17 The University Of Utah Research Foundation Procede et appareil pour obtenir une image de pigments maculaires par imagerie raman
EP1480559A4 (fr) * 2002-12-19 2006-04-05 Univ Utah Res Found Procede et appareil pour obtenir une image de pigments maculaires par imagerie raman
WO2005044098A1 (fr) * 2003-10-28 2005-05-19 Welch Allyn, Inc. Ophtalmoscope de documentation numerique
EP1793732A4 (fr) * 2004-09-29 2009-11-11 Univ Delaware Spectrographe a infrarouge et methode pour diagnostiquer une maladie
EP1793732A2 (fr) * 2004-09-29 2007-06-13 University Of Delaware Spectrographe a infrarouge et methode pour diagnostiquer une maladie
WO2009018953A2 (fr) * 2007-08-03 2009-02-12 Carl Zeiss Meditec Ag Procédé et dispositif de détermination des conditions d'état d'un objet à étudier et de mesure de fluorescence sur l'œil
WO2009018953A3 (fr) * 2007-08-03 2009-04-09 Zeiss Carl Meditec Ag Procédé et dispositif de détermination des conditions d'état d'un objet à étudier et de mesure de fluorescence sur l'œil
EP2278909A1 (fr) * 2008-04-22 2011-02-02 Annidis Health Systems Corp. Procédé et appareil de surveillance de fond rétinien
EP2278909A4 (fr) * 2008-04-22 2012-10-31 Annidis Health Systems Corp Procédé et appareil de surveillance de fond rétinien
US8491120B2 (en) 2008-04-22 2013-07-23 Annidis Health Systems Corp. Retinal fundus surveillance method and apparatus
US8807751B2 (en) 2008-04-22 2014-08-19 Annidis Health Systems Corp. Retinal fundus surveillance method and apparatus
US8350044B2 (en) 2009-05-05 2013-01-08 Dow Agrosciences, Llc. Pesticidal compositions
WO2017075089A1 (fr) * 2015-10-28 2017-05-04 Loma Linda University Système et procédé pour analyser différentes couches rétiniennes
CN106166056A (zh) * 2016-07-11 2016-11-30 孙明斋 多光谱眼底成像系统

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