GB2378600A

GB2378600A - Retinal function camera to determine retinal blood oxygenation.

Info

Publication number: GB2378600A
Application number: GB0119155A
Authority: GB
Inventors: Patrick Kerr; Jonathan Watts
Original assignee: Individual
Current assignee: Individual
Priority date: 2001-08-06
Filing date: 2001-08-06
Publication date: 2003-02-12
Also published as: GB0119155D0

Abstract

A retinal camera 101 is used to examine an eye 10, the camera including a light source 1 having first and second sources 21, 22 emitting first and second infrared wavelength bands respectively and a physical light source 23 provides diffuse illumination. The first and second light sources are arranged to alternately produce infrared light onto the retina such that the absorptivity of light of the first wavelength band by oxygenated blood is greater than the absorptivity of light of the second wavelength band, and the absorptivity of light of the first wavelength band by deoxygenated blood is less than the absorptivity of light of the second wavelength band. Light is selectively focused from the first and second sources by lens arrangement 30, 50, 60, 80 and 90 and imaging devices 90, 120, 130 produce respective images of a portion of the retina illuminated with the respective wavelength bands. The images obtained by the imaging device is processed 140 to determine retinal function and the images may be displayed using false colours.

Description

RETINAL FUNCTION CAMERA This invention relates to a retinal function camera.

Age-related macular degeneration may cause loss of macula function of an eye due to the death of photoreceptor cells and the retinal pigment epithelium.

This results in the gradual loss of detailed central vision. In addition, small yellow deposits in the centre of the retina, known as drusen, are seen in the early stages of macular degeneration. People aged over 50 who have drusen are at risk of developing choroidal neovascularisation. This refers to small new abnormal blood vessels that appear to form in response to tissue hypoxia. In such neovascular age-related macular degeneration, the abnormal new blood vessels from the choroidal layer grow and proliferate with fibrous tissue within the drusen material. This choroidal neovascularisation may cause acute loss of vision as transudate or haemorrhage accumulates within or beneath the retina. The transudate, haemorrhage or scar tissue may be seen on ophthalmoscopy but fluorescein angiography may be needed to visualise the abnormal blood vessels. The area of choroidal neovascularisation may be treated by either laser photocoagulation or, if the vessels extend under the centre of the retina, by photodynamic therapy.

However, the new blood vessels are difficult to see. Screening for the choroidal new vessels and their complications, which may develop over a short time, is currently done by identifying loss of vision. The diagnosis and assessment requires investigation by an ophthalmologist, who may need to use fluorescein angiography to see the new choroidal vessels. Current screening for choroidal neovascularisation involves a patient observing straight lines on a piece of graph paper and reporting any distortion of the lines or the development of blank spots.

Alternatively, any change of retinal metabolism, such as macular degeneration and diabetic retinopathy, may be assessed by studies of the oxygenation of blood in the retina. Arterial blood is highly oxygenated while

venous blood is deoxygenated. Areas of retinal tissue hypoxia may be recognised before the development of new vessels.

The oxygenation of blood in the retina can be determined by illuminating the blood with infrared light of different wavelengths due to differential absorption of different wavelengths by oxygenated and deoxygenated blood. Deoxygenated blood illuminated at 760nm appears darker than when it is illuminated at 1000nm. Conversely oxygenated blood illuminated at 760nm appears lighter than when illuminated at 1 OOOnm. In illumination at both 760nm and 1 OOOnm partially deoxygenated blood appears on the grey scale.

It is known from US 4, 877, 322 to use this property to measure relative oxygenation saturation of choroidal blood of the eye fundus and more particularly to make such measurements in specifically selected areas of the eyegrounds for the study of glaucoma and macular degeneration. In this prior art disclosure the retina is illuminated simultaneously with white, red and infrared light and the relative absorption of red and infrared light used to determine the oxygenation and, hence, the concentration of capillaries in the regions of the retina. However, because the retina is illuminated with all three wavelengths simultaneously, it is not possible to obtain any detailed view of retinal function.

It is known from US 5,219, 400 to determine the degree of haemoglobin oxygenation in the blood vessels of the retina under conditions of darkadaptation and light adaptation by directing a beam of near-infrared light having a range of wavelengths from 700-1000nm at a blood vessel in the retina, measuring the intensity of the backscattered light from the blood vessel in the range from 700 to 800nm at regularly spaced intervals of wavelength such as 2nm, and determining the degree of haemoglobin oxygenation by reference to a correlation between haemoglobin oxygenation and light absorbance in the nearinfrared spectral range. There is also disclosed an artificial eye model for calibration of haemoglobin oxygenation saturation and near infrared reflective spectral data. However, there is no disclosure of the formation of an image of retinal function.

US 5,400, 791 discloses the use of infrared light between 795nm and 815nm for angiography.

It is an object of the present to at least mitigate the foregoing difficulties.

According to this invention there is provided a retinal function camera comprising: a first source of light of a first wavelength band; a second source of light of a second wavelength band, the absorptivity of light of the first wavelength band by oxygenated blood being greater than the absorptivity of light of the second wavelength band and the absorptivity of light of the first wavelength band by deoxygenated blood being less than the absorptivity of light of the second wavelength band; means for focussing light selectively from the first and second sources on a portion of a retina; imaging means for producing respective images of a portion of the retina illuminated with the respective wavelength bands; and processing means for reviewing images obtained by the imaging means, to determine retinal function.

Conveniently, the processing means comprises means for displaying the images alternately, at a predetermined frequency, such that areas of image having differential absorptivity at the first and second wavelengths flicker.

Preferably, the predetermined frequency is 12Hz.

Advantageously, the source of light is an array of superluminescent diodes producing light in the wavelength band 550nm to 650nm to produce a conventional image and also producing alternating infrared light in a first infrared wavelength band of 700nm to 805nm and a second infrared wavelength band of 805nm to lOOOnm to produce a functional image.

Conveniently, the processing means comprises means for assigning the respective images created with the first infrared wavelength band and the second infrared wavelength band and the conventional image with false colours respectively and combining the three images to form a combined colour image.

Advantageously, the first and second sources of light are infrared, superluminescent diodes provided with narrow band pass filters to restrict the waveband of light emitted.

Conveniently, the light source is a wide spectrum light source emitting wavelengths from near infrared through the visible spectrum and the two infrared light sources are produced by passing the wide spectrum white light through narrow band pass filters.

Advantageously, the means for focusing light selectively from the first source and the second source comprise means for focussing light from the first and second sources and for sequentially switching on and off the two sources alternately.

Conveniently, the means for fbcussing light selectively from the rwo 11 L t-I tL. L, or Lu I i irom tne iwo sources comprise means for focussing light from the first and second sources and shutter means for alternately interrupting light from the first and second sources, respectively.

Advantageously, the processing means includes means for comparing an image with a reference image formed at an earlier time.

Preferably the processing means includes pattern recognition means for aligning the image with the reference image.

Conveniently, the processing means comprises means for alternately displaying the image formed by the first light source and the image formed by the second light source to form a composite image which flickers except at those isoreflective points corresponding to partial oxygenation at which absorption of light from the first light source is equal to absorption of light from the second source.

Preferably the processing means include means for assigning first flickering portions of the image corresponding to portions of the retina having greater oxygenation than the isoreflective points a first false colour and for

assigning second flickering portions of the image corresponding to portions of the retina having less oxygenation than the isoreflective points a second false colour and for generating intensities of the false colours at each point in the image proportional to the difference in oxygenation of that respective point from the oxygenation of the isoreflective points.

Conveniently, the processing means includes means for calibrating oxygenation by identifying a portion of the retina image of maximum oxygenation and a portion of the retina image of maximum de-oxygenation.

Conveniently, the means for focussing light include scanning means for scanning the focussed light across at least a portion of the retina.

Preferably, the scanning means include first scanning means for scanning the focussed light horizontally across the at least a portion of the retina and second scanning means for scanning the focussed light vertically across the at least a portion of the retina.

Conveniently, the first scanning means includes one of a rotatable polygonal mirror and a vibratable plane mirror.

Conveniently, the second scanning means includes a galvanometer scanner.

Preferably, first synchronising means are provided to synchronise the first and second scanning means with selection means for selectively operating the first source of light and the second source of light.

Preferably, second synchronising means are provided to synchronise the first and second scanning means with the imaging means.

Preferably, the first and second scanning means are adapted to de-scan light reflected from the retina and reflecting de-scanned light to the imaging means.

Conveniently, the first and second scanning means operate at frequencies corresponding to television scanning frequencies such that the processing means may be used to form a television image.

Specific embodiments of the invention will now be described by way of example with reference to the accompanying drawings in which: Fig. 1 shows a first embodiment of the invention in schematic form ; Fig. 1A shows a cross-section along the double arrow headed line lA-lA of Fig 1; Fig. 2 shows a second embodiment of the invention in schematic form; Fig. 2A shows a cross-section along the double arrowhead lines 2A-2A of Fig 2; Fig. 3 shows a third embodiment of the invention in schematic form.

In the diagrams, like reference numerals denote like parts.

Referring to Fig. 1, a retinal camera 101 is used to examine an eye 10.

The camera includes a light source 1 comprising an integrating sphere 20 having a first and second source 21,22 disposed at substantially 120 to each other, emitting first and second infrared wavelength bands respectively and a white light source 23, to provide diffuse illumination. The primary function of the integrating sphere is to produce the alternating infrared light from the same point source so that the retinal images, formed by the two infrared sources, are aligned.

The 600nm visible light source 23 is useful in differentiating veins and arteries in the retinal image. It is present to allow the functional image obtained with the infrared sources to be compared with a conventional image.

Possible sources of illumination include an array of superluminescent diodes, producing light in the range 550nm to 650nm, and preferably at 600nm, to produce a conventional image and superluminescent diodes sequentially illuminating a diffuse reflective integrator sphere with infrared light in the region of 758nm (700nm-805nm) and 910nm (805nm-lOOOnm) to provide illumination for a functional image. Narrow band pass filters may be used with the superluminescent diodes to restrict their bandwidth. Alternative optical arrangements for the light source include a beam splitter arrangement for the near infrared superluminescent diodes. The superluminescent diodes may either

switch on and off sequentially or their light may be sequentially blocked with a shutter. Alternative light sources may be used. For example a wide spectrum source emitting radiation from near infrared through the visible spectrum such as a xenon light doped with other gases to provide a near infrared spectrum between 700nm to lOOOnm with narrow band pass filters may be used.

Alternatively, laser diodes may be used as the infrared sources, in which case to avoid the speckle effect of laser light, the integrating sphere 20 converts collimated, coherent, narrow band light from the laser diodes into uncollimated, incoherent, narrow band light.

Light from the light source is collimated by a condenser lens 30 and passed through an annular ring diaphragm 40 before being reflected by a mirror 50 and passing through a relay lens 60. A cross-section of the annular ring diaphragm is shown in Fig 1A, in which is shown an annular transparent portion 41 within an opaque support 42. A cone of light emergent from the annular diaphragm and reflected by the mirror 50 is then reflected by a perforated mirror 80, having a central transmission hole 81, through an objective lens 90 into the eye 10 to produce an evenly illuminated area at the focal plane of the eye 10. An internal fixation target 70 is provided between the relay lens 60 and the perforated mirror 80, on an optical axis defined thereby. The internal fixation target 70 may be a small illuminated object such as cross-wires on which the eye 10 may be focussed. After absorption within the retina, light is reflected from the retina out of the eye back through the objective lens 90 and a portion of the reflected light passes through the central aperture 81 of the perforated mirror 80, and sequentially through an occluding diaphragm 110, a focus lens 120 and an imaging lens 130 to form an image in an image recorder 140. The annular ring diaphragm 40 and the pupil of the eye 10 are arranged in conjugate positions in the illuminating optical system and the pupil of the eye 10, transmission hole 81 of the mirror 80 and the aperture 111 of the occluding diaphragm 110 are arranged in conjugate positions of the objective optical system.

Figure 2 illustrates a further embodiment 102 of the invention in which the integrating sphere of the first embodiment shown in Fig. 1 is replaced by a half silvered mirror 24 and two superluminescent diodes with narrow band pass filters 21', 22' are disposed so that infrared light of a first waveband from the first superluminescent diode 21'passes through the mirror along the optical axis 11 and infrared light of a second waveband from the superluminescent diode 22' is reflected by the half silvered mirror 24 to also pass along the optical axis 11.

Other parts of the embodiment are as described for the first embodiment illustrated in Fig. 1.

The operation of the first two embodiments of the invention is similar.

Taking the second embodiment of Fig 2 as an example, with the patient focusing the eye 10 to be studied on the fixation target 70 the pupil of the eye is located adjacent to the aspheric ophthalmic objective lens 90. This aligns the pupil and the foveola to ensure that when the light source is activated to illuminate the retina, light is transmitted through the pupil rather than reflected from the iris. Without an illuminated object the eye would wander while looking into a black void. The illuminated object is faint in intensity to avoid pupil constriction. A typical illuminated object is a fine cross or concentric circle cut out of an opaque screen in front of a low-powered light-emitting diode. An alternative would be illuminated cross-wires.

Either visible 600nm light from a superluminescent diode 23 or xenon light source (not shown) is used to obtain a conventional image, Alternating infrared illumination in the region of 758nm and 910nm is provided by the superluminescent diodes 21,22 to project infrared light beams onto the retina to obtain a functional image.

The image recorder comprises an imaging device sensitive to light in the designated spectrum, for example a CMOS or CCD array, photodetector, infrared sensor or other infrared image sensor.

In order to analyse the images, account must be taken of residual internal reflection inside the optical system. This is minimised by a black absorptive internal surface and the use of ridging or internal baffles. In addition, the light output from the light source may be variable and light is absorbed by the front surface coatings of the mirrors and the lenses. Further, light may leak into the system from around an eye seal which may produce a light flare and in some patients, vasoconstriction due to drugs and smoking may alter the retinal oxygenation. These problems may be largely obviated by comparing the images produced under different wavelength illuminations or at different times.

A visualisation of altered retinal function or structure may be obtained by comparing individual retinal fiend images with initial reference retinal field images to detect any change. This involves the use of pattern recognition software to obtain a'best fit"superimposition of the reference and new image.

The reference image is then subtracted from the new image leaving the components that have changed. The components that have changed are then superimposed on the new image and identified by, for example, a colour change or flashing image. Alternatively the three images obtained with the visible light and the two infrared wavelengths from the superluminescent diode sequential illumination may be superimposed, after allocating each image a false colour (for example, red, green and blue), to create a colour image.

As indicated above, deoxygenated blood illuminated at 760nm appears darker than when it is illuminated at 1000nm. Conversely oxygenated blood illuminated at 760nm appears lighter than when illuminated at lOOOnm. In both pictures partially deoxygenated blood would appear on the grey scale.

Therefore, if alternating images are displayed, at for example 12Hz, on a screen most of the images of blood vessels will flicker but there will be areas of blood vessels that do not flicker in light intensity. These non-flickering blood vessels at the isoreflective point for equal energy illumination form a reference deoxygenation point. The non-flickering, isoreflective areas may be displayed in

yellow. Areas that flicker have a significant difference in oxygenation from the isoreflective point. The greater the contrast of flicker the more saturated or desaturated the blood is with oxygen. The desaturated blood may be displayed in blue and the colour intensity related to the flicker contrast. The oxygenated blood may be displayed in red and the colour intensity related to the flicker contrast. This produces a subjective image of retinal function with one isoreflective point.

To determine absolute values of oxygenation it is necessary to calibrate the image. A retinal artery with maximum flicker contrast when illuminated with 900nm-1000nm near infrared light is examined. An inspired oxygen concentration Fi02 is increased from 21% to, for example, 50% to ensure that the retinal artery blood is 100% saturated. This provides a reference for 100% oxygen saturation of retinal blood. A retinal haemorrhage with maximum flicker contrast when illuminated with near infrared light in the region of 760nm is examined. The retinal haemorrhage consists of deoxygenated blood. The inspired oxygen concentration Fi02 may be decreased from 21% to 10% to ensure that there is no increase in flicker contrast or the Fi02 may be increased to 50% to ensure that there is no reduction in flicker contrast. This provides a reference for deoxygenated retinal blood. Alternative calibration may be obtained by perfusing either an animal eye or an artificial eye model with haemoglobin of known oxygen saturation and recording infrared images. This technique may be used to obtain a haemoglobin oxygen saturation level for the isoreflective point. The retinal function calibration techniques outlined may be repeated for cytochrome a, a3 with infrared light in the 700nm to 1300nm, to obtain a further isoreflective point and additional calibration, Cytochrome a, a3 is used in addition to haemoglobin oxygen saturation to assess tissue oxygenation states. However, the longer wavelengths used would have greater tissue penetration and a possible degraded image quality.

The scanning laser retinal function camera, illustrated in figure 3, is a further embodiment for producing the sequential near infrared images of the

fundus required to generate the functional image. This comprises a multiple near infrared laser source that is able to direct a narrow beam of infrared laser light in the region of 758nm (700nm-805nm) via a mirror system and focus the light onto the fundus. The light reflected from the fundus is directed to an infrared detector, which produces an electrical output proportional to the intensity of the detected infrared light. By moving the mirror system according to a scanning sequence in a raster fashion and synchronising the detector to the scanning sequence, it is possible to produce an image of the fundus. The electrical output from the infrared detector is processed to display an image of a portion of the fundus. The laser light in the region of 758nm (700nm-805nm) is then switched off and a narrow beam of infrared light in the region of 910nm (805nm-lOOOnm) is focussed via the mirror system onto the fundus. The infrared light in the region of 910nm is reflected from the fundus is directed to the infrared detector which produces an electrical output proportional to the intensity of the detected light.

The electrical output is processed to display an image of a portion of the fundus.

The two images obtained are stored and then processed to be displayed alternately, at a predetermined frequency, to form a composite image such that areas that have a differential absorptivity at the 700nm-805nm and 805nm-lOOOnm wavelengths flicker. Non flickering, isoreflective blood vessels contain partially oxygenated haemoglobin at which the absorption of light from the 700nm-805nm laser is equal to the absorption of light from the 805nm to lOOOnm laser. The non-flickering isoreflective areas may be displayed in yellow. Blood vessels that flicker have a significant difference in oxygenation from the isoreflective point. The greater the contrast of the flicker the more saturated or desaturated the blood is with oxygen. The desaturated blood may be displayed in blue and the colour intensity related to the flicker contrast. The oxygenated blood may be displayed in red and the colour intensity related to the flicker contrast.

This produces a subjective scanning laser image of retinal function with one isoreflective point.

Figure 3 illustrates a scanning laser retinal function camera. This produces sequential images of the fundus from two infrared lasers.

The scanning laser retinal function camera has two separate laser beam sources, a first laser source 26 producing infrared laser light in the region of 758nm (700nm-805nm), and a second laser source 27 producing infrared laser light in the region of 910nm (805nm-lOOOnm).

Infrared laser beams from the first and second sources pass through respective electrooptic

modulators 261,271, which provide individual intensity control of the respective infrared beams.

An optical beam adder 28 located to receive laser beams emergent from the respective electrooptic modulators allows both infrared laser beams access to an optical axis of the scanning laser retinal function camera. This allows the infrared laser sources sequentially to illuminate a retina at the focal plane of an eye 10. The laser beam from the adder passes through focus lens 31, which allows the laser beam to be focused on the retina. The light from the focus lens 31 is reflected by a mirror 50 and passes through central transmission hole 81 in a perforated mirror 80 onto a rotating eighteen-facet polygonal mirror 150 rotatable at about 52,100rpm. The rotatable polygonal mirror reflects the infrared laser light beam onto a mirror 160 as a linear horizontal scan with a repetition rate of 15625 Hz corresponding to the closed circuit television standard, in a horizontal axis of the eye 10. The mirror 160 reflects and focuses the infrared laser light beam onto a movable galvanometer mirror 170. The galvanometer mirror 170 is electrically movable so as to vary the reflection angle to produce a vertical scan with a repetition rate of 50 Hz in a vertical axis of the eye 10. The infrared laser light is reflected by the galvanometer mirror 170 to a mirror 180, which focuses the infrared laser light as a 10 micron diameter spot onto the focal plane of the eye 10.

It will be understood that alternative apparatus for producing a scanning beam may be used, for example, a vibrating mirror and galvanometer two-axis scanner may replace the polygonal mirror and galvanometer scanner.

Light reflected from the retina returns along the same pathway and is de-scanned by the galvanometer mirror 170 and the rotating polygonal mirror 150. The reflected light is then reflected by perforated mirror 80 towards a focussing lens 120 and sequentially through an occluding diaphragm 110 and onto an infrared detector 141, such as an avalanche photodiode. The return signals are detected on a pixel-by-pixel basis and then transferred to a frame grabber card (not shown) to construct a synchronised data frame. The data frame is synchronised to the vertical frame, horizontal line and pixel clock signals from the scanning apparatus. A controller (not shown), that receives horizontal and vertical synchronising signals from the scanning apparatus, activates and deactivates the lasers sequentially.

The scanning laser retinal function camera illustrated in Fig. 3 is similar to the Digital Laser Scanning Fundus Camera, described by Plesch et al. in Applied Optics, Vol. 26, No. 8, page 1480-86, April 15,1987. This device uses a collimated laser beam focussed by the eye to a

spot of 10-15 microns diameter for illumination of a single point of the retina. The light scattered back from the retina, normally 3-5% of the incident light, is collected through the outer 95% of the pupil. Angular scanning of the illuminating laser beam sweep the spot across the retina and results in time resolved sequential imaging of the retina. The device is connected to a digital image buffer and a microcomputer for image storage and processing.

The scanning laser retinal function camera illustrated in Fig. 3 contains an optical beam adder that is used in US 6099127. This uses a red 670nm, green 540nm and blue 488nm laser light sources, with an optical beam adder, which separately illuminate the fundus. The three images obtained are used to construct a colour representation of the fundus.

Optimising the retinal function image The ideal retinal function image contains: A stable non-flickering background of light reflected from retinal and choroidal pigments and cells.

Maximal contrast of light from deoxygenated and oxygenated blood.

Similar depth of infrared light retinal penetration to image the same retinal and choroidal components.

Infrared light in the region of 758nm and lOOOnm may provide maximum contrast for haemoglobin oxygenation. In order to optimise the functional retinal image the 1000nm wavelength illumination may need to be tuned closer to 805nm. A retinal background isoreflective non-flickering point will be determined when the light energy reflected from retinal and choroidal pigment cells by the 700nm-805nm and 805nm-lOOOnm sources is equal. This will provide a stable non-flickering background on which to contrast the functional image. The light source wavelength or power may be variable to allow tuning of the image.

The individual light source intensity may be controlled by altering the supply power using a current limiting technology. Alternatively the light output may be controlled with either a variable aperture diaphragm or an electrooptic modulator.

Alternative light wavelengths Alternative wavelengths of the light spectrum where there are significant differences of light absorption between oxyhaemoglobin and deoxyhaemoglobin may be used to generate the functional image. Light between 488nm and 700 nm may be used. Suitable wavelengths would be 488nm and 600nm, 488nm and 635nm or 488nm and 670nm. The visible light, between 488nm and 700nm, would have less retinal tissue penetration than the near infrared light.

Alternative imaging technology Alternative imaging arrangements may be used to generate the separate wavelength retinal and choroidal images needed to generate the functional retinal image. The scanning laser retinal function camera may have a confocal filter positioned upstream of the detector to allow the retinal surface image to be detected while blocking the deeper choroidal image. An anticonfocal filter may be positioned upstream of the detector to block the retinal surface image and allow the deeper choroidal image to be detected.

The scanning laser retinal function camera may have an orthogonal polarising filter positioned upstream of the detector. The function of the orthogonal polarising filter is to block the surface reflected light that has the same linear polarisation as the laser illumination light. This will allow orthogonally polarised light that has been scattered and reflected from deeper layers to be detected and form the image.

The retinal function camera may have a linear polarising filter on the illuminating axis and an orthogonal polarising filter on the imaging axis. The orthogonal polarising filter will block the reflected light from the retinal surface that has the same linear polarisation as the illumination light. This will allow light from deeper layers, that contain haemoglobin oxygenation information, to be detected and form the image.

The scanning laser retinal function camera controller sequentially activates the different wavelength lasers, which the scanner scans across a portion of the retina to form a complete data frame with each laser. Alternatively, a portion of the retina scan, such as sequential scan lines may be illuminated. This would form an interlaced data frame. The data frame would need to be deinterlaced to form the two separate images prior to constructing the retinal function image.

Simultaneous illumination of the retina with two separate wavelengths of light is possible by either using the integrating sphere or a dichroic beam combiner. The separate wavelength images may be obtained with a dichroic beam splitter and separate imaging optics.

The invention provides the advantages of

Sequential illumination of the same retinal field with light, between 488nm and lOOOnm, selected to differentiate the oxygen saturation of haemoglobin, allowing the construction of a tissue function retinal image.

The use of isoreflective points for retinal function calibration.

An intensity of flicker contrast compared with an isoreflective point related to the relative haemoglobin oxygen saturation.

A retinal and choroidal pigment isoreflective background, on which to contrast the functional image, is obtained by tuning the intensity of the individually controlled light sources.

A retinal and choroidal function image formed from sequential illumination of the retina with linearly polarised light, filtering of the reflected light with an orthogonal polarising filter upstream of the detector in the scanning laser retinal function camera or upstream of the imaging device of the retinal

function camera.

Evaluation of effectiveness and safety of drug compounds. The infrared light fundus images, infrared sensor data or fundus functional data or image may be used to assess change of retinal metabolism, toxic reactions and other biological processes after drug administration.

Claims

CLAIMS 1. A retinal function camera comprising: a first source of light of a first wavelength band; a second source of light of a second wavelength band, the absorptivity of light of the first wavelength band by oxygenated blood being greater than the absorptivity of light of the second wavelength band and the absorptivity of light of the first wavelength band by deoxygenated blood being less than the absorptivity of light of the second wavelength band; means for focusing light selectively from the first and second sources on a portion of a retina; imaging means for producing respective images of a portion of the retina illuminated with the respective wavelength bands; and processing means for reviewing images obtained by the imaging means, to determine retinal function.
2. A retinal function camera as claimed in claim 1, wherein the processing means comprises means for displaying the images alternately, at a predetermined frequency, such that areas of image having differential absorptivity at the first and second wavelengths flicker.
3. A retinal function camera as claimed in claim 2, wherein the predetermined

frequency is 12Hz.
4. A retinal function camera as claimed in claims 1 or 2, wherein there is provided an array of superluminescent diodes producing light in the wavelength band 550nm to 650nm to produce a conventional image and the first infrared wavelength band is 700nm to 805nm and the second infrared wavelength band is 805nm to lOOOnm to produce a functional image.
5. A retinal function camera as claimed in claim 4, wherein the processing means comprises means for assigning the respective images created with the first infrared wavelength band and the second infrared wavelength band and the conventional image with false colours respectively and combining the three images to form a combined colour image.

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6. A retinal function camera as claimed in claim 1, wherein the first and second sources of light are infrared, superluminescent diodes provided with narrow band pass filters to restrict the waveband of light emitted.
7. A retinal function camera as claimed in claim 1, wherein a wide spectrum light source is provided emitting wavelengths from near infrared through the visible spectrum and the two infrared light sources are produced by passing the wide spectrum white light through narrow band pass filters.
8. A retinal function camera as claimed in any of the preceding claims, wherein the means for focusing light selectively from the first source and the second source comprise means for focusing light from the first and second sources and for sequentially switching on and off the two sources alternately.
9. A retinal function camera as claimed in any of claims 1 to 7, wherein the means for focusing light selectively from the first and second sources comprise means for focusing light from the first and second sources and shutter means for alternately interrupting light from the first and second sources, respectively.
10. A retinal function camera as claimed in any of the preceding claims, wherein the processing means includes means for comparing an image with a reference image formed at an earlier time.
11. A retinal function camera as claimed in any of claims 1 to 9, wherein the processing means includes pattern recognition means for aligning the image with the reference image.
12. A retinal function camera as claimed in any of claims 1 to 9, wherein the processing means comprises means for alternately displaying the image formed by the first light source and the image formed by the second light source to form a composite image which flickers except at those isoreflective points corresponding to partial oxygenation at which absorption of light from the first light source is equal to absorption of light from the second source.

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13. A retina ! function camera as claimed in claim 12, wherein the processing means includes means for assigning first flickering portions of the image corresponding to portions of the retina having greater oxygenation than the isoreflective points a first false colour and for assigning second flickering portions of the image corresponding to portions of the retina having less oxygenation than the isoreflective points a second false colour and for generating intensities of the false colours at each point in the image proportional to the difference in oxygenation of that respective point from the oxygenation of the isoreflective points.
14. A retinal function camera as claimed in any of the preceding claims, wherein the processing means includes means for calibrating oxygenation by identifying a portion of the retina image of maximum oxygenation and a portion of the retina image of maximum de-oxygenation.
15. A retinal function camera as claimed in claim 1, wherein the means for focusing light include scanning means for scanning the focused light across at least a portion of the retina.
16. A retinal function camera as claimed in claim 14, wherein the scanning means include first scanning means for scanning the focused light horizontally across the at least a portion of the retina and second scanning means for scanning the focused light vertically across the at least a portion of the retina.
17. A retinal function camera as claimed in claim 16, wherein the first scanning means includes one of a rotatable polygonal mirror and a vibratable plane mirror.
18. A retinal function camera as claimed in claims 16 or 17, wherein the second scanning means includes a galvanometer scanner.
19. A retinal function camera as claimed in claims 16,17 or 18, wherein first synchronising means are provided to synchronise the first and second scanning means with selection means for selectively operating the first source of light and the second source of light.

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20. A retinal function camera as claimed in claim 19, wherein second synchronising means are provided to synchronise the first and second scanning means with the imaging means.
21. A retinal function camera as claimed in claim 16, wherein the first and second scanning means are adapted to de-scan light reflected from the retina and reflecting de-scanned light to the imaging means.
22. A retinal function camera as claimed in claims 16 or 21, wherein the first and second scanning means operate at frequencies corresponding to television scanning frequencies such that the processing means may be used to form a television image.
23. A retinal function camera substantially as hereinbefore described with reference to and as shown in Figures 1 and 1A, or 2 and 2A, or 3 of the accompanying drawings.