Patent Description:
The macula is the central part of the retina responsible for the majority of central vision. It is comprised of the fovea, a small, cone-dominated region, which is surrounded by the rod-dominated parafovea. Photoreceptor density decreases extending out from the macula, with an almost complete loss of cone receptors outside of the inner ten degrees.

Photoreceptors are dependent on the health of the Retinal Pigment Epithelium (RPE) and Bruch's membrane complex. This complex is responsible for nutrient and waste exchange, keeping the photoreceptors healthy and clearing substances such as opsin, which is a by-product of bleaching. As the function of the RPE and Bruch's membrane complex deteriorates, or is otherwise impaired, the photoreceptors suffer from a deficient supply of nutrients and reduced clearing of toxins and by-products of bleaching. This results in a reduction in the health and function of photoreceptors.

Rod photoreceptors are responsible for vision in dim light, while cone receptors allow for responses to bright light and colors. Rods are particularly vulnerable to the effects of reduced function of the RPE and Bruchs membrane complex and as such, this decay results in reduced scotopic, or dark-adapted vision.

Dark-adaptation can be defined as the recovery of light sensitivity by the retina in the dark after exposure to a bright light (bleaching). As such, dark adaptation provides a useful assessment of the health of the RPE and/or Bruch's membrane complex.

Rod receptors seem to be effected by damage to the RPE and/or Bruch's membrane prior to serious deterioration of cone receptors. This is significant as the early detection of impaired dark adaptation could allow novel treatment options for a range of disease before the serious visual impairment associated with cone defects becomes apparent. As there are no treatment options currently available to reverse damage associated with most retinal diseases, providing treatment before damage is done, is crucial to a successful outcome.

The RPE complex slowly deteriorates with age, but accelerated deterioration is the major cause of early stage AMD. In most eyes, debris that is not cleared through the membrane complex builds up between the Bruch's membrane and the RPE to form drusen. Early or dry AMD progresses to wet AMD when this drusen causes inflammation that sets off a chain reaction resulting in the growth of many small blood vessels up into the RPE. These delicate vessels are prone to bursting, which causes blood to leak into the retina. Both the growth and the leaking blood causes severe damage to the retina and this is the stage of AMD that is most serious. Preventing progression to this stage and treating it when it does occur is the major target for currently marketed pharmaceuticals.

The measurement of dark adaption of the human eye has been known for some time. In more recent years, research has investigated abnormal dark adaption and found a high correlation with the presence of Age-related Macular Degeneration (AMD) and structural changes in the Bruch's membrane. Research has also found that dark adaption anomalies indicate the presence of AMD much earlier than other detectable irregularities.

A study in <NUM> found rod recovery to be the best way to detect early AMD but because of the difficulties in measuring rod recovery they ranked it much lower than other techniques (<NPL>).

A <NUM> study found that dark adaptation showed a strong ability to detect early functional changes that could lead to AMD, but becomes significantly poorer as a monitoring tool after the onset of AMD. Steady state tests such as flicker perimitry (<NUM> flicker) showed a continuous decline as eye function deteriorates and offer a better quality test of disease progression (<NPL>).

The methods known in the prior art involve bleaching the retina of a subject with a bright light source and generating a stimulus with a specific spectrum and intensity to be seen by the subject. When the stimulus is seen the subject acknowledges this. The time delay from the time of bleaching to the time of stimulus and the level of intensity is recorded and further analysed to establish the physiological parameters characteristic for the disease. Multiple measurements of the stimulus point can be taken to increase accuracy of measurement.

A publication by Jackson & Edwards contains a description of a short duration dark adaptation protocol for assessment of age-related maculopathy (ARM) using a Dark Adaptometer called the AdaptDX ("<NPL>). The AdaptDX presents a stimulus point at the line of sight. This publication notes that using the twenty minute procedure in combination with the AdaptDx dark adaptometer allows the differentiation of early AMD and normal patients. As the severity of AMD increases, rod recovery rate and rod intercept drop very quickly.

Another known device is based on retinal imaging overlaying the retinal image surface to a projected light pattern. A third apparatus uses a tilting mirror system to produce the stimulus point at desired position.

Improved methods and apparatuses to quickly and efficiently measure dark-adaptation in a patient are highly desirable.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge.

It is a preferred object of the embodiments of the present invention to provide an apparatus and method that addresses or at least ameliorates one or more of the aforementioned problems of the prior art and/or provides a useful commercial alternative.

The article entitled "<NPL>, discloses an automated static perimeter/adaptometer designed to measure thresholds with lights of two wavelengths. The use of two LEDs with different peak emission wavelengths (<NUM> and <NUM>) is taught to permit an assessment of the relative state of rod and cone mechanisms in a particular region of the retina either during dark adaptation or when the eye is fully dark adapted.

<CIT> discloses a device for testing the macula of the eye of a human subject. The device comprises an adapting light to bleach the retina and a stimulus light source which is exposed for detecting the threshold on the photoreceptors. The stimulus light source may comprise a plurality of colored lights.

Generally, separate embodiments of the present invention relate to a dark adapted perimetry device and a dark adapted perimetry method. The photobleaching aspects of the present invention are of particular advantage because they provide a substantially even illumination at a known quantity of exposure to the retina over a wide or substantially full field of view. Advantageously, the photobleaching aspects of this invention may incorporate a high level of bleaching. Also of significant advantage are the dark adapted perimetry device and dark adapted perimetry methods of the invention which may achieve a large dynamic range and optionally a large field of view.

In a first aspect, the invention resides in a dark adapted perimetry device comprising:.

In a second aspect, the invention provides a dark adapted perimetry method comprising:.

In one embodiment of the second aspect, the method further comprises applying a normative data set that has been statistically derived though clinical trials to establish normal response characteristics of stimuli. The normative data may be compared with noise reduced response data.

In one embodiment of the first or second aspects, only one light source is illuminated at a time. Each time a light source is illuminated it may be illuminated with known exposure parameters for one or more of intensity, spectrum and location relative to a fixation axis. The luminance of a light source may be increased until an input is received. In one particular embodiment, illumination comprises known exposure parameters for all of intensity, spectrum and location relative to a fixation axis.

In another embodiment of the first or second aspects, the dark adapted perimetry device comprises a field of view greater than <NUM> deg eccentricity. In other embodiments the field of view comprises more than <NUM>; more than <NUM>; more than <NUM>, or more than <NUM> deg eccentricity. In one particular embodiment the field of view comprises <NUM> deg eccentricity.

In still another embodiment of the first or second aspects, a dynamic range of measurement is about <NUM> dB. In other embodiments, the dynamic range may be about <NUM> dB; about <NUM> dB; about <NUM> dB; about <NUM> db; about <NUM> dB; or about <NUM> dB.

In yet another embodiment of the first or second aspects, the dark adapted perimetry device is able to detect a visual threshold of about <NUM>-<NUM> cd/m<NUM>.

In another embodiment of the first or second aspects, each stimulus target light source comprises an optical transmissive element with diffusing light propagation properties, and a circular exit diaphragm which forms the stimulus surface.

In still another embodiment of the first or second aspects, each stimulus target light source is connected to a respective optical fibre. Each respective optical fibre may be illuminated by a respective light source. The respective light source comprises a respective LED complex light source. The LED complex light source illuminates one or more light guide which illuminates a respective optical fibre.

In another embodiment of the first or second aspects, luminance of each stimulus target light source is modulated using one or more of pulse width modulation (PWM), LED current level modulation and multi source modulation of the light source.

In still another embodiment of the first or second aspect, the on level of the PWM is the LED current of a first LED within the LED complex source.

In yet another embodiment of the first or second aspect, the wavelength of the high intensity LED and the low intensity LED may comprise red.

The light power range of the high intensity LED and the low intensity LED may overlap, however the maximum intensity of the high intensity LED is higher than the maximum intensity of the low intensity LED. The maximum intensity of the high intensity LED may be <NUM> dB higher than the low intensity LED.

In another embodiment the LED complex source may further comprise a LED of a second wavelength. The second wavelength LED may comprise green.

In another embodiment of the first or second aspect, the device may further comprise a fixation target, wherein the intensity of the fixation target may be changed with the bleaching recovery of the subject.

The dark adapted perimetry device of the first or second aspect may further comprise a shield.

The dark adapted perimetry device of the first or second aspect may further comprise a processing unit. The processing unit may correlate neighbouring stimulus signals. The correlation may comprise at least two neighbouring stimulus target light sources. The correlation may comprise a weighting function. The weighting function may be dependent on the distance between the points and the statistical confidence of the data points.

The device of the first aspect or the method of the second aspect may be used to detect a visual disease or condition such as AMD.

In one embodiment, the concave array guide may be spherical or substantially spherical.

In one embodiment of the first or second aspect, the plurality of light sources display a spectral distribution with a dominant wavelength that coincides with the peak sensitivity of the rod and the cone receptors (L, M and S receptors). In another embodiment only one wavelength is displayed at a time.

In one embodiment of the first or second aspect, at least three measurements are performed at three different wavelengths. The three wavelengths may comprise one that is sensitive to scatter (blue); one that is less sensitive to scatter (red); with the third one between these two (yellow or blue (cyan) at the visual axis of the retina. The at least three measurements and different wavelengths may comprise four.

In one embodiment of the first or second aspect, the device further comprise an alignment illumination source, wherein the reflection of the alignment illumination source may be used in a captured image of the eye to provide information on the alignment of the eye.

In another embodiment of the first aspect, the photobleaching device may comprise a bleaching device comprising:.

In another embodiment of the second aspect, the photobleaching may comprise a method comprising:.

Further aspects and/or features of the present invention will become apparent from the following detailed description.

In order that the invention may be readily understood and put into practical effect, reference will now be made to embodiments of the present invention with reference to the accompanying drawings, wherein like reference numbers refer to identical elements. The drawings are provided by way of example only, wherein:.

Skilled addressees will appreciate that elements in the drawings are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the relative dimensions of some elements in the drawings may be distorted to help improve understanding of embodiments of the present invention.

Separate embodiments of the present invention relate to a photobleaching device, a method of photobleaching, a dark adapted perimetry device and a method for dark adapted perimetry. The methods and devices of the present invention may be used to detect a visual disease or condition such as, AMD.

Advantageously, the present invention may allow early retinal disease detection and/or physiological parameter determination of the human eye.

The photobleaching device usable in the present invention provide improved diagnostic accuracy and resolution, by producing a substantially even illumination at a known quantity of exposure to the retina over a wide or substantially full field of view. Hitherto, this has not been achieved. The present inventors have made this possible by applying a bleach control device within the photobleaching device.

<FIG> show some embodiments of a photobleaching device <NUM> usable in the invention. <FIG> show a light guide <NUM> bleaching embodiment. <FIG> show a light guide <NUM> bleaching with a curved light source <NUM> embodiment. <FIG> and <FIG> show an integrating sphere <NUM> bleaching embodiment.

Regardless of embodiment, photobleaching device <NUM> comprises an eye piece <NUM> for positioning eye <NUM>. As shown in <FIG> a locator <NUM> is provided for moving device <NUM> into and out of the optical path. The locator <NUM> may be located on any part of device <NUM> and may comprise any mechanical or electromechanical means of movement. As shown with arrows in <FIG>, locator <NUM> can move in two planes, clockwise and anti-clockwise to rotate into and out of the optical path and proximally and distally with respect to eye <NUM>. Once photobleaching device <NUM> is in position, eye <NUM> may be illuminated with illumination source <NUM>.

In the embodiments shown in <FIG>, <FIG> and <FIG> device <NUM> comprises an imaging system <NUM> for tracking the gaze direction. Imaging system <NUM> comprises a lens <NUM> and an imaging sensor <NUM>.

In the other embodiments, instead of an imaging system <NUM>, device <NUM> comprises a fixation target <NUM> which may comprise a black opaque coating that is not illuminated. The fixation target does not provide bleaching to the retina. In another embodiment the fixation target <NUM> may comprise a lens aperture of a gaze tracking device <NUM>. The fixation target <NUM> may be located at the centre of the illumination source <NUM>. The fixation target <NUM> may be limited in size to be equivalent to the fovea or to about two degrees of visual field. Advantageously, the retinal fixation area focused on fixation target <NUM> remains unexposed or partially unexposed during bleaching, which means the unbleached photoreceptors may respond to low level illumination and identify the fixation target <NUM>, while the bleached receptors remain unresponsive to the low level illumination.

Each of the light guide <NUM> bleaching embodiments (<FIG>); light guide <NUM> bleaching with a curved light source <NUM> embodiment (<FIG>) and integrating sphere <NUM> bleaching embodiments (<FIG> and <FIG>) also comprise an illumination source <NUM>. The light guide <NUM> bleaching embodiments and light guide <NUM> bleaching with a curved light source <NUM> embodiments are shown to comprise a light guide <NUM>, while <FIG> shows an embodiment comprising an integrating sphere <NUM>.

Light guide <NUM> comprises a light guide optical medium <NUM>. The light guide optical medium <NUM> may be comprised of acrylic and may comprise a reflective or a total reflective surface <NUM> on the parts if its exterior that do not provide light to eye <NUM>. The light guide <NUM> is illuminated by light source <NUM>. The light guide <NUM> embodiment shown in <FIG> also comprises a concave surface <NUM>. <FIG> and <FIG> show the concave surface <NUM> of light guide <NUM> to comprise facets <NUM>. In the embodiments shown in <FIG> the concave surface <NUM> does not comprise facets.

The illumination source <NUM> in the light guide <NUM> bleaching embodiments (<FIG>) and light guide <NUM> bleaching with a curved light source <NUM> embodiments (<FIG>) comprises an illumination panel <NUM> comprising a plurality of LEDs <NUM> disposed on a surface of panel <NUM>. All illustrated embodiments of light guide <NUM> comprise symmetrical illumination panels <NUM>.

The illumination panels <NUM> shown in <FIG> comprise an aperture or orifice <NUM> for the transmission of light to imaging sensor <NUM> or fixation target <NUM>. <FIG> and <FIG> show LEDs <NUM> to be spaced over substantially the entire surface of planar, circular panel <NUM>. <FIG> and <FIG> also show LEDs <NUM> to be spaced over substantially the entire surface of arcuate light source <NUM>. The curved or arcuate light source <NUM> comprises an unfolded spherical shape <NUM> comprising a plurality of petals or wings <NUM>. Arcuate light source <NUM> comprises or is disposed on a flexible printed circuit board (PCB) <NUM>.

As will be readily understood by a skilled person, illumination source <NUM> may comprise a Köhler illumination source. As used herein "Köhler illumination" is also known for ophthalmic applications as Maxwellian Viewing Systems. The main characteristic of this concept is that an illumination source is imaged onto the pupil plane of the eye. With this, spacial features of the light source are not visible on the retinal plane and highly even illumination is achieved. More sophisticated versions can be derived wherein the apertures at the conjugate planes can control sharp edges of the illuminated field as well as control the brightness.

The embodiments shown in <FIG> illustrate an embodiment comprising an integrating sphere <NUM> comprising a white diffuse coating <NUM>, a baffle <NUM>, an entry port <NUM> and an exit port <NUM>. The illumination source <NUM> shown in <FIG> comprises a xenon flash lamp. In other embodiments, one or more high intensity LED may be used.

An integrating sphere, also known as an Ulbricht sphere, is an optical component consisting of a hollow spherical cavity with its interior covered with a diffuse white reflective coating, with small holes for entrance and exit ports. Its relevant property is a uniform scattering or diffusing effect. Light rays incident on any point on the inner surface are, by multiple scattering reflections, distributed equally to all other points. The effects of the original direction of light are minimized. An integrating sphere may be thought of as a diffuser which preserves power but destroys spatial information.

The device <NUM> may also comprise a bleach control device <NUM> to control the brightness and pulse form of the illumination source <NUM>. The brightness and pulse form of the illumination source <NUM> is controlled with bleach control device <NUM>. The bleach control device <NUM> may be connected to or comprised within a perimetry device <NUM> such as dark adapted perimetry device <NUM> described below. The connection may be to control unit <NUM>. The bleach control device <NUM> may comprise a printed circuit board.

Bleaching device <NUM> may also comprise a spectral filter <NUM> to filter the light incident upon the eye. Although not shown in <FIG>, the integrating sphere <NUM> may also be used with a spectral filter <NUM>. In the integrating sphere <NUM> embodiments the spectral filter may be located between eye <NUM> and sphere <NUM>. In the light guide <NUM> bleaching embodiments (<FIG>) and light guide <NUM> bleaching with a curved light source <NUM> embodiments (<FIG>) the spectral filter <NUM> may be located between illumination source <NUM> and a light guide <NUM> or between a light guide <NUM> and the eye <NUM>.

The spectral filter <NUM> should not cover the imaging system <NUM> or the fixation target <NUM>. The spectral filter <NUM> may comprise an aperture for the imaging system <NUM> or the fixation target <NUM>.

In one embodiment, the present invention is distinguished from other retinal bleaching methods by providing a selective and substantially even illumination over a large portion of the retina (Ganzfeld). The present invention may provide selective illumination over an area on the order of <NUM> degrees field of view or more. This is of significant advantage because it is known that specific spectral exposure for the stimulus is desired to discriminate AMD sensitive test results. This is also true for initial bleaching.

Of significant advantage is that the present invention provides measurements within a field of view comprising a substantial area of the retina with up to <NUM> deg eccentricity. In another embodiment of the field of view is greater than <NUM> deg eccentricity. In other embodiments the field of view comprises more than <NUM>; more than <NUM>; more than <NUM>, or more than <NUM> deg eccentricity.

The present invention may utilise a bleaching level of <NUM>-<NUM>%, depending on the application. Once the bleaching has been performed, the bleaching device is removed from the optical path.

In one embodiment, the invention presents a bleaching device <NUM> that is able to provide substantially even illumination over a large portion of the retina and a known bleaching level. As noted above, bleaching device <NUM> may be equipped with a spectral filter <NUM>. This can be advantageous for achieving a specific bleaching behaviour to reduce measuring time to the rod cone break. Additionally, a diaphragm (not shown) may be applied to the bleaching device <NUM> to illuminate desired portions of the retina and correspondingly prevent exposure of other areas on the retina. The diaphragm may comprise an aperture, whose conjugate image on the retina produces a sharp edge of the illuminated area.

The present invention is the first to provide illumination of such large portions of the retina, and the first to do so with a high level of accuracy.

The illumination source <NUM> may further comprise an image forming system (not shown) disposing radiation of the object plane into the image plane of the bleaching device <NUM>. The aperture size of the imaging forming device may be conjugate to the retinal observable field. The object plane size of the bleaching device <NUM> is conjugate to the entrance pupil size of eye <NUM>. The bleaching device <NUM> may further comprise a filter (not shown) placed in the image path of the bleaching device disposing filtered radiation onto the retina.

Conventional displays are constrained to approximately three log units of luminance and are unable to produce very low light levels. The range of cone and rod recovery spans between five to six log units and may be three to four units below the capacity of conventional CRT displays. While this capacity may be lowered using neutral density (ND) filters, visual acuity (VA) remains a poor measurement for detecting AMD. This is because early AMD does not often show functional changes despite structural changes.

According to one embodiment of the invention, stimulus exposure may start shortly after bleaching with bleaching device <NUM>. The stimulus is recorded via acknowledging the signal seen through an input unit <NUM>, preferably a button or switch. The values are recorded and related to a time reference point, which in a preferred embodiment coincides with the bleaching pulse.

The subject's eye <NUM> may be exposed with a plurality of spatially separated stimulus target light sources <NUM>, with only one stimulus light source <NUM> illuminated at a time. Known exposure parameters for intensity, spectrum and location relative to a fixation axis which forms the origin of the instrument coordinate system for each stimulus target light source <NUM> intensity may be used.

One embodiment of a dark adapted perimetry device <NUM> according to the invention is shown in <FIG>. The body <NUM> houses an array guide <NUM> comprising stimulus target array <NUM> which is comprised of individual stimulus target light sources <NUM>. In the embodiment shown, the array guide <NUM> absorbs visual radiation and to do this is black.

Light sources <NUM> comprise an optical transmissive element with diffusing light propagation properties, and a circular exit diaphragm which forms the stimulus surface. The exit diaphragm disposes the radiation to eye <NUM>.

Device <NUM> also comprises one or more fixation targets <NUM> (not shown) which assists with the alignment of subjects visual axis of the subject's observed eye with instrument reference axis. Preferably respective fixation targets <NUM> are located in the centre of array guide <NUM> and one each located in the left part and in the right part of array guide <NUM>.

An alignment illumination source <NUM> is shown on a front surface of body <NUM>. The reflection of alignment illumination source <NUM> may be used in a captured image of eye <NUM> to provide information on the alignment of eye <NUM>. In one embodiment illumination source <NUM> is an infrared illumination source. Alignment illumination source may comprise a ring or point light source.

Further a tracking device <NUM> is comprised to correlate the activated stimulus target light source <NUM> to a location on the retina of eye <NUM> where the measurements of both locations have been acquired at the time of the subject response.

A control unit <NUM> (see <FIG>) is also comprised to present controlled and selective stimulus target light source <NUM> illumination at a specific location, record exposure parameters at the time of subject response through the input unit <NUM>, and record the time relative to a time reference point for the measurement. The control unit <NUM> may comprise a programmable logic controller.

The exposure parameters at subject's response to said exposure of each activated stimulus may be recorded and related in time to a time reference point.

As discussed below, accuracy improvement may be achieved by processing the exposure parameters to reduce measurement uncertainty. The processing may be performed using said recorded exposure parameters with at least two different locations relative to the instrument coordinate system.

The method may further include processing of the accuracy improved data to establish characteristic adaption parameters of eye <NUM>.

A further step in the method may be a comparison of the characteristic adaption parameters of eye <NUM> with said normative reference.

The captured data can be noisy. In order to provide highly accurate data that can be used for diagnostic purposes, the invention also provides an accuracy improvement method. One shortcoming of prior art methods is that only a single stimulus point is observed over time and then noise reduction is performed along these data points. The present invention correlates the responses of neighbouring stimulus points with the single point data and performs noise reduction thereon. A curve or set of curves may be formed to express the relationship between responses of neighbouring points on the retina. The skilled person will realise that only one point can be obtained at one time and that said response time is used as one of the parameters in said relationship.

From the teaching herein, a skilled person is readily able to select a suitable noise reduction algorithm. While any of the known methods of noise reduction can be applied, suitable ones include least square fitting, generalised cross validation or maximum likelihood estimation. The noise reduction may comprise reduction at a common intensity level or across a surface normal.

In one embodiment, the present invention uses a normative data set that has been statistically derived though clinical trials to establish normal response characteristics of stimuli. The normative data is compared with the noise reduced response data derived from the accuracy improvement methods. Significantly, this comparison may in turn be used in the diagnosis of diseases of the retina and preferably for the diagnosis of early AMD.

The light sources <NUM> have the capacity to display a spectral distribution with a dominant wavelength that coincides with the peak sensitivity of the rod and the cone receptors (L, M and S receptors). In one embodiment only one wavelength is displayed at a time.

Another embodiment has a spectral distribution of the dominant wavelengths that coincide with the isoluminant responses of two said receptors of the normal scotopic viewer. This has the advantage of detecting receptor differences directly through direct comparison, and produces overall lower noise in the measurements.

The comparison between the normative data and the measurement data may be displayed in a novel method topographically onto the retinal coordinate system displaying derived characteristics with additional numerical, color or graphical means representing a third dimension. The display may be a <NUM>-D visualization by intensity or by response time.

Additionally by overlaying this display, an additional level of detail may be displayed, for example temporal data may be visualized with an overlay.

The complexity of the information of a retinal coordinate system includes information of response sensitivity, response time, rate of change in response sensitivity achieved through determining a derivative of the response function, and other derived characteristics including cone break. These are preferred characteristics, but the invention is not limited to these.

Sudden changes in response from neighbouring points on the retina may also indicate retinal defects. Additionally, characteristics like rod-cone ratio may be derived by applying different spectral stimuli to the same stimulus location, which are substantially coincident in the spectral sensitivity to the receptor sensitivities.

Combining these different stimulus responses gives additional information in regards to rod-cone behaviour and rod-cone density, helping further in the diagnosis of disease. This accuracy of the different spectral responses may be further improved by determining the lens density of the subject's ocular media. The lens density is measured by performing at least three measurement at least three different wavelength. One that is sensitive to scatter (blue); one that is less sensitive to scatter (red); with the third one between these two (yellow or blue (cyan) at the visual axis of the retina.

In other embodiments, the device <NUM> uses a minimum of two colours or four colours to discriminate lens density. The use of at least three colours is more robust and reliable and provides a common reference to the two. Lens density defects may be detected in different colour shades, depending on the underlying cause, for this possibly the fourth color can be used. A four point ratio will be also more accurate than a two point ratio.

In order to perform accurate correlation of measurements to the actual retinal positions, tracking device <NUM> is used. The tracking device <NUM> correlates a characteristic of the eye that is unique relative to the location of the retina. The perimetry device <NUM> presents an activated stimulus target light source <NUM> relative to the instrument axis. The tracking device <NUM> records at least two of these unique characteristics at the time of stimulus response and a control unit <NUM> correlates these sets of points to determine the location of the retina that was exposed by the stimulus target light source <NUM>.

Three methods are presented to acquire the characteristics of the eye <NUM>. One is to project a pattern of at least three points or a ring pattern onto the cornea or other ocular surfaces and capture the image of this reflection. This first method is well known as purkinje images, where the invention makes use of the brightest purkinje images for analysis of gaze which are the 1st purkinje image which is derived from the anterior corneal surface and the <NUM>rd purkinje image, which is derived from the anterior lens surface. Another method is to capture patterns (at least <NUM> points) on the iris or pupil together with information on the surrounding area of the eye not being part of the eye (at least <NUM> points). The third method is to illuminate at capture with a retinal imaging device at least one small portion of the retina. The rotation of at least one of the characteristic location points is captured against the fixation axis at the time of response. The difference of the two locations is the measure of deviation from the instrument axis.

Ambient light can contaminate the measurement noticeably, as the measurements are performed at extremely low light levels. Ambient light needs to be eliminated as much as possible. The invention presents a shield <NUM> (not shown) which provides a means of shielding the measuring system from unintended light by surrounding the functional components with a baffle that is incorporated or attached to the perimetry device <NUM>.

Further a pupil measuring device <NUM> (<FIG>) is comprised in perimetry device <NUM> to capture and measure the size of the pupil at the time of stimulus response by the subject. This value is used to correct the measured response values to retinal exposure levels, commonly known as troland.

As noted above, one or more fixation target <NUM> is presented at the instrument coordinate origin or at an offset position in the horizontal plane intersecting the origin depending on which portions of the retina are measured, with the visual axis representing one of the coordinate axes. As the bleaching recovery progresses and hence the visual sensitivity increases, the brightness of the fixation target <NUM> is adjusted as a function of this recovery and changes from initially a bright level to a dimmer level in order to present maintain substantially the same exposure level relative to the expected stimulus target light source <NUM> level.

The invention may also comprise accuracy improvement wherein the stimulus exposure parameters are processed to reduce measuring uncertainty, the processing may be performed using said recorded exposure parameters with at least two different locations relative to the instrument coordinate system.

The invention may also comprise the processing of accuracy improved data to establish characteristic adaption parameters of said subject's eye.

The invention may further comprise a comparison of said subject's characteristic adaption parameters with said normative reference.

The present invention also provides a method of topographically displaying the comparison of rod and cone characteristics, the method comprising comparing said subject's characteristic adaption parameters; a two dimensional coordinate system and coordinates representing the retinal locations; allocation of adaption parameter values to said retinal coordinates; a color scale where colors are associated to adaption parameters; Representation of the adaption parameters as planar graphical display values with the retinal coordinates in the viewing plane, where these values are displayed with at least one or in combination as said color, as a numerical value, contours of equal value.

The method of topographically displaying the comparison of rod and cone characteristics may further comprise presenting information of more than three dimensions, comprising: a rotated planar topographical display where coordinate origin is not normal to viewing plane, wherein an additional dimension is represented as a coordinate value normal to the retinal coordinates; and the additional dimensional information is represented by displaying a section of the said topographical display simultaneously as a 2D planar display with retinal coordinates as one ordinate, the adaption parameter as a second ordinate, and the additional dimensional information as a colour, numerical or graphical display. The colour, numerical or graphical display may comprise one or more of contours, dots and/or vectors.

In another embodiment, the additional dimensional information may be overlayed with numerical, graphical and color information. The overlay may comprise one or more of black/white weighting of color, coloring of numerical values and contours and vectors. The present invention also provides a method to eliminate the effects of transmissive ocular properties (lens density LD) from the measurement of the stimulus responses. This method comprises the subject fixating at a known stimulus (LD) wherein the LD stimulus emits at least three dominant wavelengths. At least one of these wavelengths is sensitive to scattering properties of the subject's ocular medium. Another of the wavelengths is substantially insensitive to said scattering properties. The stimuli are presented at different times and said exposure is increased from low intensity level that is undetectable by subject until the stimulus is seen. The subject's response to the observed stimulus is then recorded and a determination of transmissive ocular properties is made by combining said recorded LD stimulus measurements. Any transmissive effects may be eliminated by combining this response with the methods described above.

This highlights yet another advantage of the present invention which is the detection of visual thresholds in the order of <NUM>-<NUM> cd/m<NUM>.

The perimetry device <NUM> may further comprise, a processing unit <NUM> for performing accuracy improvement of as described herein wherein the stored measurement points are processed into graphical and numerical data outputs and characteristic values, where the outputs include the dark adaptation response of cones and rods.

The device <NUM> may further comprise a storage unit <NUM> storing one or more of predetermined normative references, image data, analysis results and characteristic parameters of the stimulus targets.

The perimetry device <NUM> may further comprise a display unit <NUM> presenting the outputs of the processing unit <NUM>.

The device may further comprise a fixation structure <NUM> supporting and stabilising the patient's head and its position relative to the perimetry device reference axis during a test. As shown in <FIG>, the fixation structure <NUM> may also provide a base for attachment of locator <NUM>.

In one embodiment, the dominant wavelength of the spectrum of each of the plurality of stimulus target light sources <NUM> may be selected to coincide with peak responses of the visual receptors in the human eye/retina.

The control unit <NUM> delivers the full dynamic range of stimulus luminance in the order of <NUM> dB (ratio of ><NUM> x106:<NUM>) through electronic means. The minimum visual threshold is in the order of <NUM>-<NUM>cd/m<NUM> and requires the novel methods of the control unit <NUM> to achieve required accuracy and resolution.

In order to achieve the said dynamic range of stimulus luminance, at least two means of modulations are used. The first comprises a pulse width modulation (PWM) of the light intensity signal by varying the on/off period of the stimulus target light source <NUM>.

The second comprises LED current level modulation. In this embodiment, as shown for example in <FIG> a light well <NUM> (see <FIG> and <FIG>) is used. Light well <NUM> comprises an array of LED sources <NUM> complementary to the stimulus target array <NUM>. Each LED complex source <NUM> provides the illumination used to activate a complementary stimulus target light source <NUM>. Each LED complex source <NUM> is connected to the stimulus target light source <NUM> through a respective fibre optic cable <NUM>. Each respective optical fibre <NUM> may be illuminated by a respective light source <NUM>. The respective light source <NUM> comprises a LED complex light source. The LED complex light source <NUM> may illuminate one or more light guide <NUM> which illuminates the respective optical fibre <NUM>.

In this second method of modulation the on level of the PWM is the LED current of a first LED (LED A) <NUM> within the LED complex source. The off level LED current of the PWM is at zero in the preferred embodiment, however a LED-LOW current level that is greater than zero and lower than the LED current may be also used.

A third means of modulation is advantageous but not essential to the invention. The third means increases the dynamic range of the stimulus luminance by utilising a second LED (LED B) <NUM> of the same wavelength to the first LED (LED A) <NUM> for each stimulus target light source <NUM>. This third means, or dual light source modulation, allows for switching between first LED <NUM> which comprises a high intensity <NUM> and second LED <NUM> which comprises a low intensity LED to produce a light output on the stimulus substantially lower than with the first LED (LED A) <NUM> alone. The same modulations apply of the first <NUM> and second LEDs <NUM> (LEDs A and B).

That is, first LED <NUM> may comprise a high intensity LED and can be powered to get the brightest light and second LED <NUM> may comprise a low intensity LED to show the lowest light. As such, by utlising an LED complex source <NUM> comprising two or more LED light sources, perimetry device <NUM> can generate a much larger range of outputs than a single LED. First LED <NUM> and second LED <NUM> are never activated at the same time, so there is still always only one LED running.

The wavelength of the high intensity LED and the low intensity LED may comprise red.

The light power range of the high intensity LED <NUM> and the low intensity LED <NUM> may overlap, however the maximum intensity of the high intensity LED <NUM> is higher than the maximum intensity of the low intensity LED <NUM>. The maximum intensity of the high intensity LED <NUM> may be <NUM> dB higher than the low intensity LED <NUM>.

In another embodiment the LED complex source <NUM> may further comprise a LED of a second wavelength <NUM>. The second wavelength LED <NUM> may comprise green.

<FIG> shows another embodiment which does not use fibre optic cables <NUM>. Instead LED complex source <NUM> illuminates one or more light guide <NUM> which illuminates a respective stimulus target light source <NUM>.

The control unit <NUM> may apply the stored characteristics of the stimulus target light source <NUM> to control said luminance at the required magnitude and precision into the said modulations and corresponding magnitudes.

Another significant advantage of the present invention is that the dynamic range of measurement with this invention has been largely increased to about <NUM> dB dynamic range. In another embodiment, the dynamic range of measurement is about <NUM> dB. In other embodiments, the dynamic range may be about <NUM> dB; about <NUM> dB; about <NUM> dB; about <NUM> db; about <NUM> dB; or about <NUM> dB.

A fixation target <NUM> of the perimetry device <NUM>, where the intensity of the fixation target <NUM> may be controlled by the control unit <NUM> and may be changed with the bleaching recovery of the subject. The preferred method maintains a luminance ratio between the target illumination and the expected luminance response at the line of sight level of the subject at the point of time during the test. The preferred method may use a range of discrete brightness levels corresponding to the levels of recovery.

The device may comprise a processing unit <NUM> that cross correlates neighbouring stimulus signals. The prior art apparatus and method measure the temporal rod-cone recovery of only a single stimulus. The present invention may consider at least two neighbouring stimuli points. Each stimulus may be characterised with a different temporal rod-cone recovery curve, as the rod cone density changes with eccentricity from the fovea. Each stimulus response may be correlated to the neighbouring stimulus response(s) with a weighting function that is dependent on the distance between the points and the statistical confidence of the data points. The preferred embodiments include a plurality of stimuli points. This may be performed as a series of lines or curves along the retinal coordinates, or as a topographical correlation between points of retinal coordinates.

To further improve the parameters of temporal rod cone response graph (reduction of least square deviation), known statistical methods for curve fitting methods may be applied. These include but are not limited to the below mentioned methods like MLE (maximum likelihood estimator), GCV (generalised cross validation), least squares, moving averaging, (note, the mathematical dimension of rod-cone response model is two for the temporal rod cone response and increased by one for a line scan or two for an aerial scan for the retinal coordinates and curves may be presented as clusters of lower orders). The systematic uncertainties and accuracy is further improved as the increased number of measuring points (cross correlated stimuli points) help reducing measuring uncertainty. Further, the said responses of neighbouring stimuli target light sources <NUM> are subtracted or as preferred embodiment a partial derivate to each of the said dimensions formed. Characteristics of portions of the derivative space are used to describe physiological properties and diseases of the eye <NUM>.

Such physiological properties include rod-cone ratio for each stimulus target light source <NUM> location in particular when the stimulus target light source <NUM> are exposed to at least two dominant wavelengths that are largely different to the exposed rod or cones respectively. Correlation of the multispectral stimulus responses with the rod cone ratio in the processing unit <NUM> is used as means for the said disease detection.

The perimetry device <NUM> may also include a shield <NUM> (not shown) comprising an occluding barrier that partly surrounds the perimetry device <NUM>. The shield <NUM> acts to prevent external light stimulating the test subject.

In one embodiment the shield <NUM> is opaque in the visible electromagnetic spectrum, and comprises an absorbing surface and a diffusing surface so no direct radiation from an undesired ambient light source and no reflections from a stimulus point or any other ambient radiation can be detected by the subject.

The shield <NUM> may be comprised as an integral component of the device <NUM> or may be removably attached to device <NUM>.

The skilled person readily understands that the shield <NUM> should be positioned to surround a substantial portion of the array guide <NUM> and to enclose the direct light paths between all stimulus target light sources <NUM> and the test subject's eye.

A tracking device <NUM> of the perimetry device <NUM> comprises a fixation target <NUM> as described above; an amplitude beam splitter diaphragm <NUM> (not shown), with an aperture <NUM> (not shown) covering the whole field of view for the stimulus target light sources <NUM>; a collimating mirror <NUM> (not shown); an imaging objective lens system <NUM> (not shown); and an imaging camera <NUM> (not shown), viewing a portion of the retina. The skilled person readily understands that the fixation target <NUM> should be positioned so that the gaze of the subject's eye is directed toward the centre of said fixation target <NUM>.

In another embodiment the tracking device <NUM> comprises a fixation target <NUM> as described above as well as a light pattern disposing infrared illumination onto the cornea of the test subject. The light pattern may be distributed substantially symmetrically around the test pattern. The light pattern may comprise at least one light point or thin circular section for each direct horizontally and vertically. The circular section may extend to a closed circular ring wherein the illuminated circular section or ring is located outside the said stimulus target array <NUM>. A camera <NUM> (not shown) with an imaging lens <NUM> (not shown) may be located in the centre of the stimulus target array <NUM> forming an image of the reflected light pattern off the subject's cornea and the fixation target <NUM>.

Tracking device processing unit <NUM> (not shown) may calculate the location and rotational coordinates of the subject's eye from the said image of the light pattern. The tracking device processing unit <NUM> uses image information of said camera <NUM> with orientation of the gaze of the subject's eye <NUM> (e.g. reference to known stimulus points) at known positions in space of the reference point of the subject's eye <NUM>. With the known location of the eye relative to the instrument axis and the known gaze, all information of the spatial location of the eye <NUM> and rotational state relative to the instrument coordinate system is sufficiently defined. Commonly known geometric rules may be used to calculate through said algorithm these parameters and establish registration of the retinal coordinates to the instrument coordinates.

A third type of tracking device <NUM> may also be used with perimetry device <NUM>. This third type comprises a fixation target <NUM> as described above and a camera <NUM> with an imaging lens <NUM> with its entrance pupil located in proximity of the stimulus target array <NUM> The camera <NUM> is used to detect at least one detectable feature near the subject's eye pupil plane (EPP) of the examined eye <NUM>, features like the iris or pupil and at least two features on the subject's head and an illumination emitting infrared radiation towards the EPP and features on the head.

The camera <NUM> is used to obtain an image of the EPP and features taken at the time of stimulus response. A tracking device processing unit <NUM> is used to determine the rotational coordinates from the said image of the subject's EPP and features on the head and establish registration of the stimulus coordinates to the rotation coordinates relative to said reference axis.

At least one image of the EPP and features on the head taken at a known rotational coordinates as the fixation axis, which is used to determine physiological rotational parameters of the eye.

Device <NUM> may also comprise a pupil measuring device <NUM> (not shown) to record the subject's pupil size. The pupil measuring device <NUM> may conveniently comprise the imaging camera <NUM>.

Of significant advantage, the recorded rod-cone response value may be corrected with the measure pupil size at the time of patient response to the corresponding stimulus luminance with said processing unit <NUM> to provide means for expressing rod-cone response as the portion of stimulus radiation disposed on the retina.

Device <NUM> may also comprise a means for determining the lens density of the ocular lens of the test subject's ocular media comprising at least one stimulus disposing radiation of at least three different dominant wavelengths.

Preferably, only one dominant wavelength is presented at a time and the difference in response to the different dominant wavelengths is used in the processing unit to determine the lens density parameters.

The present invention provides a high quality, highly specific solution to the issue of measuring rod recovery.

In this specification, the terms "comprises", "comprising" or similar terms are intended to mean a non-exclusive inclusion, such that an apparatus that comprises a list of elements does not include those elements solely, but may well include other elements not listed.

Claim 1:
A dark adapted perimetry device (<NUM>) comprising:
a photobleaching device (<NUM>);
a concave, array guide (<NUM>) the guide comprising a stimulus target array (<NUM>) comprising a plurality of stimulus target light sources (<NUM>) positioned within the guide (<NUM>) wherein each stimulus target light source (<NUM>) is connected and is illuminated by a respective LED complex light source (<NUM>) wherein each respective LED complex light source (<NUM>) comprises a high intensity LED (<NUM>) and a low intensity LED (<NUM>) of the same wavelength; and
a control unit configured to selectively illuminate light sources comprised in the plurality of stimulus target light sources (<NUM>) at a predetermined luminance.