Device and method for non-invasive monitoring of retinal tissue temperature

Abstract

A method and device for non-invasive monitoring of the temperature of the retina and the retinal pigment epithelium inside the eye, particularly during heating of the bottom of the eye, wherein alternating probing short-duration pulses of light, one at wavelength close to the absorption maximum of the photoreceptor cell type and the other at wavelength in the near-infrared region, are directed at the retinal tissue at appropriate time intervals.

Photoreceptor cell electrical signals, photoresponses, are recorded using electroretinography (ERG) and the changes in retinal temperature are determined from changes in photoresponse kinetics and changes in photoreceptor sensitivity to the stimuli. The method is especially applicable at temperatures up to 45 C. for humans and for other animals.

Claims

1. A method for non-invasive determination of a retinal tissue temperature inside an eye, wherein the method comprises steps of: providing an electromagnetic radiation stimulation to interact with the retinal tissue, measuring electrical responses of the retinal tissue to the electromagnetic radiation stimulation as a function of time, where the response is a temperature-dependent electrical response of the retinal tissue to the used electromagnetic radiation stimulation, and determining a first and a second parameter of the measured response, where the first parameter relates to kinetics of the measured electrical responses of the retinal tissue to the electromagnetic radiation stimulation, and the second parameter relates to a photoreceptor sensitivity of the measured electrical responses of the retinal tissue to the electromagnetic radiation stimulation, determining the temperature of the retinal tissue based on the determined first and second parameter of the measured responses by: comparing at least the determined first parameter to previously determined first reference parameter, where the dependency of said previously determined first reference parameter on the temperature is known, and comparing a ratio of said determined second parameter being the electrical response to a first wavelength of the stimulation to another second parameter being an electrical response to the second wavelength of the stimulation, where the dependency of said ratio of said second parameters on the temperature is known.

2. The method of claim 1, wherein the electromagnetic radiation stimulation comprises: one or more wavelengths, comprising white light or a visible wavelength, or an infrared wavelength, a first wavelength or a first wavelength range changing to a second wavelength or to a second wavelength range, alternating short-duration pulses, continuous radiation with fluctuating or continuously changing intensity or wavelength, continuous radiation comprising sequences of pseudorandom, sinusoidal, sawtooth, or stepwise electromagnetic radiation stimuli, or sequences of pulses.

3. The method of claim 1, wherein the wavelength of the first electromagnetic radiation stimulation is in the range of the absorption maximum of the photoreceptor cell type.

4. The method of claim 1, wherein the wavelength of the second electromagnetic radiation stimulation is in the near-infrared region.

5. The method of claim 1, wherein the electromagnetic radiation stimulation comprises first and second electromagnetic radiation alternating pulses, directed at the retinal tissue at time intervals in the range of 0.5-5 ms.

6. The method of claim 1, wherein the first parameter relating to the kinetics reflects changes in a response kinetics and is time-to-peak or the time to the maximal slope of the measured wave from the electromagnetic radiation pulse stimulus.

7. The method of claim 1, wherein the determination of a retinal tissue temperature is a continuously monitor determination and the electromagnetic radiation stimulation is given or changed at constant time intervals.

8. A device for non-invasive determination of a retinal tissue temperature inside an eye, wherein the device comprises: an electromagnetic radiation source for providing electromagnetic radiation stimulation to interact with the retinal tissue, a measuring member for measuring an electrical response of the retinal tissue to the electromagnetic radiation stimulation as a function of time, where the electrical response is a temperature-dependent response of the retinal tissue to the used electromagnetic radiation stimulation, and a first determination unit for determining a first and/or second parameter of the measured response, where the first parameter relates to kinetics of the measured electrical responses of the retinal tissue to the electromagnetic radiation stimulation, and the second parameter relates to a photoreceptor sensitivity of the measured electrical responses of the retinal tissue to the electromagnetic radiation stimulation, a second determination unit for determining the temperature of the retinal tissue based on the determined first and second parameter of the measured responses by: comparing at least the determined first parameter to previously determined first reference parameter, where the dependency of said previously determined first reference parameter on the temperature is known, and comparing a ratio of said determined second parameter being the electrical response to a first wavelength of the stimulation to another second parameter being an electrical response to the second wavelength of the stimulation, where the dependency of said ratio of said second parameters on the temperature is known.

9. The device of claim 8, wherein the device with the electromagnetic radiation source are configured to provide: one or more wavelengths, comprising white light or a visible wavelength, or infrared wavelength, a first wavelength or a first wavelength area changing to a second wavelength or to a second wavelength area, alternating short-duration pulses, continuous radiation with fluctuating or continuously changing intensity or wavelength, continuous radiation comprising sequences of pseudorandom, sinusoidal, sawtooth, or stepwise electromagnetic radiation stimuli, or sequences of pulses.

10. The device of claim 8, wherein the wavelength provided by the electromagnetic radiation source is in the range of 500-600 nm.

11. The device of claim 8, wherein the wavelength provided by the second electromagnetic radiation source is in the near-infrared region and above 600 nm.

12. The device of claim 8, wherein the device comprises also a controller for controlling said electromagnetic radiation stimulation so that the stimulation is provided as alternating pulses at time intervals, where said time intervals are controlled to be in the range of 0.5-15 s.

13. The device of claim 8, wherein said electromagnetic radiation source is implemented by LED-diodes or laser sources.

14. The device of claim 8, wherein the device comprises optical members for directing the provided electromagnetic radiation pulses to the retinal tissue.

15. The device of claim 8, wherein the measuring member is implemented by an zo electroretinography (ERG) device.

16. The device of claim 10, wherein the device comprises also a reference electrode for measuring an electrical response of the reference retinal tissue to the electromagnetic radiation stimulation as a function of time, where the electrical response is a temperature-dependent response of the retinal tissue to the used electromagnetic radiation stimulation and where the temperature of said reference retinal tissue is known, whereupon the second determination unit is configured to determine the temperature of the retinal tissue by comparing the determined first and second parameter to the determined first and second reference parameter related to the second reference retinal tissue.

17. An arrangement for controlling heating power of a heating apparatus used for heating a retinal tissue inside an eye, wherein the arrangement comprises a device for non-invasive determination of the retinal tissue temperature inside the eye, wherein the device comprises: an electromagnetic radiation source for providing electromagnetic radiation stimulation to interact with the retinal tissue, a measuring member for measuring an electrical response of the retinal tissue to the electromagnetic radiation stimulation as a function of time, where the electrical response is a temperature-dependent response of the retinal tissue to the used electromagnetic radiation stimulation, and a first determination unit for determining a first and second parameter of the measured response, where the first parameter relates to kinetics of the measured electrical responses of the retinal tissue to the electromagnetic radiation stimulation, and the second parameter relates to a photoreceptor sensitivity of the measured electrical responses of the retinal tissue to the electromagnetic radiation stimulation, a second determination unit for determining the temperature of the retinal tissue based on the determined first and second parameter of the measured responses by: comparing at least the determined first parameter to previously determined first reference parameter, where the dependency of said previously determined first reference parameter on the temperature is known, and comparing a ratio of said determined second parameter being the electrical response to a first wavelength of the stimulation to another second parameter being an electrical response to the second wavelength of the stimulation, where the dependency of said ratio of said second parameters on the temperature is known, and a power controller for controlling the heating power of said heating apparatus based on the measured retinal tissue temperature so that the temperature is kept in a predetermined range.

18. (canceled)

19. The method of claim 3, wherein the wavelength of the first electromagnetic radiation stimulation is in the range of 500-600 nm.

20. A method of claim 4, wherein the wavelength of the second electromagnetic radiation stimulation is above 600 nm.

21. A method of claim 7, where the time intervals are in the range of 0.5-15 s.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Next the invention will be described in greater detail with reference to exemplary embodiments in accordance with the accompanying drawings, in which:

[0025] FIG. 1 illustrates a principle of an exemplary ERG signal recorded from a mouse retina showing the a-wave and the b-wave according to an advantageous embodiment of the invention,

[0026] FIG. 2 illustrates exemplary ERG signals recorded from a mouse retina showing the effects of temperature on b-wave kinetics and on rod photoreceptor sensitivity at long wavelengths (780 nm) according to an advantageous embodiment of the invention,

[0027] FIG. 3 illustrates an exemplary graph showing comparison of measured temperature data with temperature data determined by combining photoresponse kinetics and long-wavelength sensitivity data from one isolated mouse retina according to an advantageous embodiment of the invention, and

[0028] FIG. 4 illustrates an exemplary device for non-invasive determination of retinal tissue temperature inside an eye as well as an arrangement using the device for controlling heating power of a heating apparatus used for heating retinal tissue inside an eye according to an advantageous embodiment of the invention.

DETAILED DESCRIPTION

[0029] FIG. 1 illustrates a principle of an exemplary ERG signal recorded from a mouse retina showing the a-wave and the b-wave according to an advantageous embodiment of the invention. According to an embodiment, the temperature of the photoreceptor layer and/or the retinal pigment epithelium can be determined combining temperature information deduced from changes in photoresponse kinetics and changes in photoreceptor sensitivity. When gaining temperature estimates from long-wavelength sensitivity best resolution is achieved when short-duration pulses of light weak enough to produce linear range b-wave responses are used, i.e. the amplitude of the responses should not be larger than approximately 15% of the maximal amplitude attainable with strong stimuli.

[0030] For gaining temperature estimates from photoresponse kinetics, changes in a-wave or b-wave kinetics or in both can be analyzed. Best resolution is achieved with linear-range b-wave responses, because in the linear range the photoresponse kinetics does not depend on stimulus strength but depends only on temperature. Several features or combinations of features reflecting changes in photoresponse kinetics can be used, e.g. the time-to-peak of the a-wave or b-wave from the light pulse, the time to the maximal slope of the a-wave or the b-wave etc.

[0031] In order to continuously monitor the temperature, the electromagnetic radiation stimulation is given as pulses or changed (e.g. intensity or wavelength is changed) essentially at constant time intervals, where the time intervals are in the range of 1-15 s, more advantageously in the range of 1-5 s. Another possibility is to use continuous light stimuli with fluctuating stimulus strength (e.g. sequences of pseudorandom, sinusoidal, sawtooth, or stepwise light stimuli).

[0032] FIG. 2 illustrates exemplary ERG signals recorded from a mouse retina showing the effects of temperature on b-wave kinetics and on rod photoreceptor sensitivity at long wavelengths (780 nm) according to an advantageous embodiment of the invention, where the changes in kinetics (rate or response time) as well as also in photoreceptor sensitivity (the amplitude) can be clearly seen, when the retina is heated.

[0033] FIG. 3 illustrates an exemplary graph showing comparison of measured temperature data with temperature data determined by combining photoresponse kinetics and long-wavelength sensitivity data from one isolated mouse retina according to an advantageous embodiment of the invention.

[0034] FIG. 4 illustrates an exemplary device 100 for non-invasive determination of the retinal tissue 101, 102 temperature inside an eye 103 as well as an arrangement 150 using the device 104 for controlling the heating power of a heating apparatus (e.g. an IR LED) 105 used for heating a retinal tissue inside an eye according to an advantageous embodiment of the invention. The device 100 for non-invasive determination of a retinal tissue (including also the retinal pigment epithelium) temperature inside an eye comprises a first and/or second electromagnetic radiation sources 106, 107 (with suitable controller 108) for providing the electromagnetic radiation stimulation, such as first and/or second electromagnetic radiation stimuli 106a, 107a to interact with the retinal tissue 101, 102. It is to be noted that the all kinds of stimulation can be provided, as is depicted elsewhere in this document. In addition the device comprises a measuring member 109, such as an electroretinography device, for measuring electrical photoresponses of the retinal tissue 101, 102 to the electromagnetic radiation stimulation as a function of time.

[0035] The measuring member 109 may be implemented by an electroretinography device, such as a corneal electroretinography device. The device may comprise an ERG electrode 114 located on the surface of the eye under study and a reference electrode 115 located somewhere else in contact with the body. According to an embodiment the changes in potentials (voltage) between these electrodes (114, 115) are then measured as a response to the stimulation.

[0036] The device also comprises a first determination unit 111, such as a computer with suitable software, for determining a first and/or second parameter of the measured photoresponse. In addition the device comprises also a second determination unit 112, such as a computer with suitable software (can be the same as the first determination unit), for determining the temperature of the retinal tissue based on the determined first and/or second parameter of the measured photoresponse. The determination can be implemented as depicted elsewhere in this description. In addition the device advantageously comprises suitable electronics, such as an amplifier and A/D converters 110.

[0037] The device advantageously comprises also a controller 108 for controlling the second electromagnetic stimulation, such as its intensity, fluctuation, duration as well other parameters. For example the stimulation can be controlled so to provide e.g. the first and second electromagnetic radiation pulses/stimuli so that they are provided as alternating pulses/stimuli at appropriate time intervals, where said appropriate time intervals are controlled to be e.g. in the range of 1-15 s, for example. The first and second electromagnetic radiation sources 106, 107 are advantageously implemented by LED-diodes and/or laser sources, but also other and suitable electromagnetic radiation sources can be used.

[0038] The device may also comprise optical members 113, such as lenses and/or prisms, for directing the provided electromagnetic radiation stimuli 106a, 107a to the retinal tissue 101, 102.

[0039] The invention has been explained above with reference to the aforementioned embodiments, and several advantages of the invention have been demonstrated. It is clear that the invention is not only restricted to these embodiments, but comprises all possible embodiments within the spirit and scope of the inventive thought and the following patent claims. In particularly it should be noted that the provided electromagnetic radiation stimulation may comprise e.g. alternating short-duration pulses or continuous fluctuating illumination, consisting e.g. sequences of pulses, or having continuously changing intensity, having one or more wavelengths, or wavelength area or areas, as described in the document.

[0040] The features recited in dependent claims are mutually freely combinable unless otherwise explicitly stated.