GB2252403A

GB2252403A - Ocular measurements

Info

Publication number: GB2252403A
Application number: GB9101530A
Authority: GB
Inventors: Peter Alan Howarth
Original assignee: Individual
Current assignee: Individual
Priority date: 1991-01-24
Filing date: 1991-01-24
Publication date: 1992-08-05
Also published as: WO1992012667A1; GB9101530D0; AU1179392A

Abstract

The retina of an eye (1) is stimulated by means of a light source (15). The pupil (3) of that eye (1) or the other eye of the subject is simultaneously monitored by means of a pupillometer (7) and the constrictions and/or dilations of the pupil (3) in response to the light source are analysed.

Description

OCULAR MEASUREMENTS This invention relates to apparatus and methods for determining the condition of the retina of a human or animal eye and/or of associated physiological systems, in particular neural pathways associated with the pupillary and visual systems.

For a normal person, a flash of light falling on the retina of the eye causes the pupil to constrict. If there is damage somewhere in the pathway, as can be caused by diseases such as glaucoma, this response will be either reduced or absent.

The relative sensitivity of various parts of the neural pathway can potentially be measured by examifllr.g pupil responses. The integrity of different parts of the retina can be assessed by examining how well the pupil responds to a light flashed at that part of the retina This assessment could take the form of evaluating c large a response is produced by a given stimulus. The size of the response would indicate the normality or otherwise of the nervous pathway. Similarly, examination of the time delay between a stimulus an tre pupil response can also aid in the evaluation of the integrity of the nervous pathways, and diseases such as multiple sclerosis, which can affect the transmissior.

time of nervous signals, may be assessed in this way.

The use of pupil responses to measure aspects of the nervous system has been proposed, but previous proposals have suffered from practical disadvantages, in particular being either of limited scope or very time-consuming.

According to one aspect of the present invention, I propose to stimulate the eye using a repetitive stimulus, in particular, repeated flashes of light.

Thus, there may be provided apparatus comprising a light source, means for repetitively energising the light source, and means for monitoring the response of the pupil of an eye exposed to the light source.

According to another aspect of the present invention, it is proposed that the eye be stimulated at different retinal positions by a plurality of concurrent stimuli, for example, two or more light sources at different positions and energised at different times or different frequencies, and the pupil response be monitored.

By this means, a plurality of points on the retina and/or a plurality of neural pathway portions can be investigated simultaneously.

The aforesaid aspects of the invention may be practised simultaneously and means for effecting them may be incorporated in a single instrument or apparatus.

Thus, there may be provided, in accordance with the invention, an instrument or apparatus comprising: A. Means for stimulating different points on the retina of an eye B. Means for recording the response of the pupil of the eye to such stimuli C. Means for analysing the response and its relationship to the stimulus, for determining the condition of the eye or associated neural pathways.

The invention will now be presented in further detail.

1. The use of repetitive stimuli: Instead of using a single flash of light, the instrument uses a repetitive stimulus. The pupil' 5 repetitive response is then recorded using a pupillometer. This is of particular interest because two aspects of this response can be used for the assessment of the integrity of the nervous pathway at each of the stimulated retinal points - the amplitude, and the phase of the response relative to the stimulus.

Amplitude: this is effectively the amount of variation in pupil size in response to the variation in the stimulus. With a reduced pupil response (which might come about, for example, because of physiological damage within the pathway) the amplitude of the pupil oscillation could be reduced.

Phase: this reflects the time delay between the stimulus and the pupil' 5 response. Damage to the neural pathway could lead to an abnormal time delay, and hence an abnormal phase lag".

There are two ways that either of these measures could be used for the assessment of the integrity of the nervous pathway. If a single trial is used, then the value itself (amplitude or the phase) could be the measure used; if multiple trials are used then either the average value or else the variation in the value (e. g. the standard deviation) could be used as the measure.

Any one, or any combination, of these measures could be used to determine whether the pupil' 5 response was normal or abnormal.

The above description relates to fixed amplitude lights, and examines the pupil' 5 response to them. An alternative approach incorporating the use of repetitive stimuli would be to use variable amplitude lights, and determine the amplitude necessary to achieve a criterion pupil response - either at threshold or at a suprathreshold level. Here instead of looking at the response to a given stimulus we are looking at the size of the stimulus needed to produce a given response.

In addition, the techniques described here can be used in two ways. First, the absolute threshold for the pupil could be determined. Second, the relative thresholds for the pupil can be determined. Also, the thresholds for eliciting pupil reponses, absolute or relative, for different coloured lights can be determined, and in this way any disease process differentially affecting different receptor types or different neural pathways can be assessed.

2. The use of multiple stimuli: In a normal person, two lights flashed at different frequencies (each within the range that the pupil will follow) will elicit a composite pupil response. Analysis of the response will show that the pupil is, in effect, oscillating at both frequencies simultaneously.

Similarly three, four, or more lights flickered simultaneously will elicit a pupil response which has a component at each of the source frequencies.

Using the fact that the pupil response reflects activity at different frequencies simultaneously, multiple points on the retina can be tested at the same time in that each light at each location is flashed at a different frequency, and hence the pupil' 5 response at that frequency signals the response at a particular position on the retina.

Four measures can be used to evaluate the pupil response, and hence assess the neural pathway: 1. the amplitude of the response at each frequency 2. the phase lag of the response at each frequency 3. the variation in amplitude when multiple trials are performed 4. the variation in phase when multiple trials are performed.

In addition, each retinal point can be assessed by either examining the measure itself and comparing it with known "normal" values, or by comparing the pupil response at any one retinal location with the responses at other retinal locations. The second form of assessment has the advantage that if a portion of the retina is less responsive than another portion, the relative difference could show this to be the case irrespective of any individual variation in the pupi responsiveness - which might themselves come about because of the experimental conditions or because of individual idiosyncrasies of the particular person.

comparing data taken at the same time from different portions of the retina the adverse effects of between-trial variation are minimised.

The use of multiple stimuli can be implemented either for assessing the size of responses at different retinal positions, or for assessing time delays within the nervous pathway. The comparison between the responses at different locations can be used to check the person' 5 fixation. This is important because if the person is not fixating the desired place then the location of the retina stimulated will not be the required location.

The fixation can be checked by having one flickering light imaged at the blind spot (on the optic nerve head). The optic nerve head contains no photoreceptors, and so if the person' 5 fixation is correct, there will be no response at the flicker frequency of this light.

On the other hand, if the fixation is incorrect then a pupil oscillation will be seen at the flicker frequency because a responsive portion of the retina will have been stimulated.

The apparatus to be used may conveniently be as shown schematically in the accompanying drawing. It essentially consists of: 1. A means of stimulating different points on the retina 2. A means of recording the pupil response 3. A means of analysing the response and its relationship to the stimulus.

The diagram shows, very schematically, an eye 1 with a pupil 3, a multiple-stimulus array board or panel 5, a pupillometer 7, means 9 for processing signals obtained from the pupillometer, for example a video camera and picture analyser, a microprocessor 13 for analysing the pupil response, comparing the response with the imposed stimuli and with standardised responses, and providing a suitable output of data, and control means 11 controlled by the microprocessor, for regulating the luminance of the individual elements of the stimulus array.

For stimulating different points on the retina of the eye, an array of individual light sources 15 is provided, each being essentially a point source, for example a LED. The array also incorporates a fixation spot or light 17, which is, conveniently, placed at or near the centre of the array.

The support for the lights is shown as being a flat 2-dimensional surface, but this is not a prerequisite; in fact, there are advantages in using a curved or hemispherical surface in that the lights would be equidistant from the eye. Irrespective of the way that the support is made, or the lights are presented to the eye, an important feature is that there must be more than one light, in known positions relative to the fixation point.

The lights 15 must be controllable so that more than one can be lit simultaneously. In this way, more than one position on the retina can be stimulated at the same time. To this end there are means 11 for controlling the luminance of each light and varying the luminance over time. The luminance of each light need not be identical, but can be provided in a number of ways, for example by a signal generator or by a microprocessor controlling the light output. The control system should be able to vary the luminance of each light in a known manner, so that for each light a specified luminance waveform can be produced - for example a sine wave or a square wave.

The individual lights 15 are caused to flash or flicker repetitively, producing a corresponding repetitive response in the pupil size. Each light source will affect only a limited region of the retina and the corresponding neural pathway. If two or more light sources are caused to flash repetitively at different frequencies, the pupil will produce a composite response, having a frequency component corresponding to the frequency of each individual light source. These freqency components can be analysed and monitored individually. Since the different light sources affect different regions of the retina and neural pathways, the response at each individual frequency will correspond to the condition of the respective region of the retina and neural pathway.

Consequently, by subjecting the eye to multiple concurrent stimuli at different positions and at different frequencies, measurements can be obtained very quickly, relating to identifiable different regions of the retina and associated neural pathways.

The pupil size is measured with a pupillometer.

This pupillometer either records pupil size continuously, or samples the size at a known sampling rate. In either case, an important feature is that the pupillometer should be able to record changes in pupil size in such a way that its output can be analysed to examine the pupil's response in terms of the amplitude and phase.

The instrument comprises analysis means, in particular the microprocessor 13, which operates to analyse the composite response of the pupil to the multiple stimuli comprising flashes of light from different source positions presented simultaneously or in a particular spatial or temporal pattern such as to enable the responses to be correlated with the positions of the respective light sources 15 and thus with the respective positions on the retina and associated neural pathways.

By way of example only, a digital signal could be produced by the pupillometer, which could then be analysed (e.g. by Fourier analysis or cross-correlation) to produce the amplitude and the phase of the pupil response at each of the frequencies of interest.

Knowledge of the stimulus and signal phases would then allow a relative response phase to be determined.

Claims

1. Apparatus for performing ocular measurements comprising a light source for direction at the retina of an eye, means for energising the said light source and means for monitoring the constrictions and/or dilations of the pupil of an eye in response to the light source.

2. Apparatus according to claim 1, wherein the said apparatus comprises means for repetitively energising the said light source.

3. Apparatus according to any preceding claim, wherein the said apparatus comprises a plurality of light sources for direction at respectively different parts of the retina.

4. Apparatus according to claim 3, wherein during use the said light sources are energised at respectively different times.

5. Apparatus according to claim 3, wherein the said light sources are energised concurrently during use.

6. Apparatus according to claim 3, 4 or 5, wherein the said light sources are energised at respectively different frequencies.

7. Apparatus according to any one of claims 3 to 6, wherein the said apparatus comprises means for recording the response of the pupil to the repective stimuli applied to the retina by the said plurality of light sources and means for analysing the said response.

8. Apparatus according to any preceding claim, wherein the said apparatus comprises means for measuring the phase of the pupil response in relation to a stimulus applied to the retina by a light source.

9. Apparatus according to any preceding claim, wherein the said apparatus comprises means for measuring the amplitude of the pupil response in relation to a stimulus applied to the retina by a light source.

10. Apparatus according to any preceding claim, wherein the said apparatus comprises means for determining the average phase and/or the average amplitude of the pupil response in relation to stimuli applied to the retina by a light source.

11. Apparatus according to claim 3 or any one of claims 4 to 10 when dependent on claim 3, comprising a plurality of light sources of different colours.

12. Apparatus according to claim 3 or any one of claims 4 to 11 when dependent on claim 3, wherein the said plurality of light sources are arranged as an array upon a support structure.

13. Apparatus according to claim 12, wherein the said support structure is curved to match the curvature of the surface of an eye.

14. Apparatus according to claim 7 or any subsequent claim dependent thereon, wherein the said means for recording the response of a pupil is a video camera and the said means for analysing the said response is a microprocessor.

15. Apparatus according to any preceding claim, wherein the waveform of a stimulus provided by the said light source is substantially that of a square wave.

16. Apparatus according to any one of claims 1 to 14, wherein the waveform of a stimulus provided by the said light source is substantially that of a sine wave.

17.Apparatus according to any preceding claim, wherein the said means for monitoring the constrictions of a pupil moniters pupil size continuously.

18. Apparatus according to any one of claims 1 to 16, wherein the said means for monitoring the constrictions of a pupil makes sampled measurements of pupil size.

19. Apparatus according to claim 12 or any claim dependent thereon, wherein the said light sources are energised according to a spatial pattern.

20. Apparatus according to claim 3 or any claim dependent thereon, wherein the said light sources are energised simultaneously.

21. Apparatus according to claim 12 or any one of claims 13 to 19 when dependent thereon, wherein the said light sources are energised according to a temporal pattern.

22. Apparatus according to claim 7 or any claim dependent thereon, wherein said means for analysing the response of the said pupil uses Fourier analysis or cross-correlation.

23. Apparatus according to claim 12 or any claim dependent thereon, wherein the said array includes a fixation spot.

24. Apparatus for performing ocular measurements substantially as herein described with reference to the accompanying drawing.

25. A method of performing ocular measurements, comprising the steps of: (i) stimulating the eye using a light source; (ii) monitoring the response of the pupil of the eye; and (iii) analysing the response.

26. A method of performing ocular measurements using apparatus in accordance with any one of claims 1 to 24.