Electroretinography system, stimulation device for an electroretinography system, method of electroretinography, control device for an electroretinography system and computer program product

Abstract

The present invention relates to the field of medical engineering and in particular to the field of electroretinography (ERG). An electroretinography system (1) is proposed, having: a first signal generator (11) for creating a first stimulation signal; a first light source (12) for creating first optical stimuli in a visible spectral range on the basis of the first stimulation signal; a second signal generator (21) for creating a second stimulation signal; a second light source (22) for creating second optical stimuli in a UV spectral range on the basis of the second stimulation signal; a detection unit (31) for detecting a common ERG response signal; and an evaluation unit (41) that is configured to extract from the common ERG response signal a first ERG response signal component, which corresponds to the first stimulation signal, and a second ERG response signal component, which corresponds to the second stimulation signal. A stimulation device for an electroretinography system, a method of electroretinography, a control device for an electroretinography system and a computer program product are also provided.

Description

Electroretinography system, stimulation device for an electroretinography system, method for electroretinography, control device for an electroretinography system and computer program product.

[0001] The present invention relates to an electroretinography (ERG) system. The present invention further relates to a corresponding stimulation device for an electroretinography system, a method for electroretinography, a control device for an electroretinography system, and a corresponding computer program product.

[0002] Electroretinography (ERG) systems are used to examine retinal function. Light stimuli are applied and the electrical responses produced by the retina during the visual process are recorded. Electroretinography can be considered a method in the field of ophthalmological electrodiagnostics in humans, animals, and ex vivo retinal preparations.

[0003] With an ERG system, electrical potentials generated by the retina can be recorded using one or more electrodes. These are transient potentials that reflect the electrical activity of the cones, rods, and bipolar cells. The electrical potentials can be derived from an electrode applied to the cornea or conjunctiva. A counter electrode is located near the eye, for example, on the lateral canthus (angle of the eyelid). A ground electrode to reduce electrical interference can also be attached, for example, to the forehead or earlobe. A distinction can be made between scotopic (dark-adapted) and photopic (light-adapted) conditions. Under scotopic conditions, the retina is tuned for dark vision, i.e., the rod system dominates both vision itself and the electrical signals. Under photopic conditions, i.e.After light adaptation with a defined background light, the rod system is desensitized and the cone system dominates. Therefore, rod function is primarily tested under scotopic conditions, while cone function is tested under photopic conditions. ERG testing is used, for example, in the follow-up of retinitis pigmentosa, in which the rods are primarily affected and later the cones. The electroretinogram is also used in zoology—specifically in the sensory physiology of animals—to examine the eyes of vertebrates and invertebrates.

[0004] The inventor has recognized that the development and preclinical evaluation of therapeutic strategies for use in human retinal diseases is predominantly based on murine models with genetic defects homologous to humans. However, mice, in particular, have a significantly differently organized cone system than humans. The rod system and the sparsely occurring "true" blue cones (also known as "true blue" in English, visual pigment S-opsin), on the other hand, are, according to current knowledge, very similarly organized. The majority of cones in Humans are composed of green cones (visual pigment M-opsin) and red cones (visual pigment L-opsin). In mice, however, these cones contain a mixture of the visual pigments mS-opsin and mM-opsin; an analogous mL-opsin is missing (the prefix m is intended to distinguish mouse opsins from those of humans). The ratio of opsins in the cones is not evenly distributed in the mouse retina; rather, there is a distinct dorsoventral gradient, which, according to current knowledge, is due to the living conditions (upper hemifield visualizes the ground, lower hemifield the sky, with correspondingly diverging visual requirements). In addition, the maximum spectral sensitivity of mS-opsin is shifted to the UV range at 360nm compared to that of human S-opsin (approx. 420nm).

[0005] A disadvantage of conventional ERG systems is that they are designed for measurements in the range of the spectrum visible to humans. The inventor recognized that conventional systems are inadequate for measurements in nocturnal animals, e.g., mice, with a deviating light sensitivity curve (V-lambda curve), particularly in the UV range. The inventor recognized that, for example, the functional measurement of a mouse's cones using electroretinography (ERG) with commercially available equipment does not capture the UV-sensitive component of the cones, even though mS opsin makes up a large portion of the mixed visual pigment. Therefore, the measurements performed to date are inefficient in this respect, and the results of preclinical substance tests fall short of the potential.

[0006] Starting from conventional ERG systems, one object of the invention may be to provide an improved ERG system.

[0007] The inventors recognized that it would be particularly desirable to expand conventional ERG systems to include measurements in the UV range, for example, to test the function of the retinal cones in nocturnal animals. Alternatively, or in addition, it would be desirable to provide an ERG system that enables more meaningful measurements in different spectral ranges in a simpler manner.

[0008] The inventors further recognized that it would be desirable to provide an ERG system that enables simple measurements of test objects (e.g., mice) with a luminosity curve that deviates from human luminosity. In particular, it would be desirable to enable simplified system calibration. Alternatively or additionally, it would be desirable to be able to cost-effectively retrofit existing ERG systems.

[0009] According to a first aspect of the present invention, an electroretinography system is provided comprising: a first signal generator for generating a first stimulation signal; a first light source for generating first optical stimuli in a visible spectral range based on the first stimulation signal; a second signal generator for generating a second stimulation signal; a second light source for generating second optical stimuli in a UV spectral range based on the second stimulation signal; a detection unit for detecting a common ERG response signal; and an evaluation unit configured to extract a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal from the common ERG response signal.

[0010] It is therefore proposed, compared to a conventional ERG system, which is only designed for measurements in the range of the spectrum visible to humans, to additionally provide a second light source which is configured to generate second optical stimuli in a UV spectral range. This not only provides a second light source, but also a second signal generator for generating a second stimulation signal. The second light source is configured to generate second optical stimuli in the UV spectral range based on the second stimulation signal. This advantageously makes it possible to provide both optical stimuli in the visible spectral range and optical stimuli in the UV spectral range, enabling parallel or alternating application of optical stimuli in the visible spectral range and in the UV spectral range.One advantage may be that more meaningful measurement results can be achieved. Adaptation effects or a degrading measurement quality, which could occur if measurements... Measurements with visible stimuli on the one hand and UV stimuli on the other hand would be measured with a significant time interval can be advantageously avoided.

[0011] In the proposed solution, the ERG response signal acquired by the acquisition unit includes both contributions caused by the stimulation in the optical spectral range and contributions caused by the stimulation in the UV spectral range. The evaluation unit is therefore configured to extract from the joint ERG response signal a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal. In other words, the evaluation unit can be configured to extract the degree of physiological interaction of the respective signals in the retina of the eye from the joint ERG response signal caused by the first ERG signal component corresponding to the first stimulation signal and the second ERG signal component corresponding to the second stimulation signal.

[0012] A further advantage of the proposed solution is that conventional ERG systems can also be subsequently expanded to include a second signal generator for generating a second stimulation signal and a second light source for generating second optical stimuli in a UV spectral range based on the second stimulation signal. A first signal generator for generating a first stimulation signal and a first light source for generating first optical stimuli in a visible spectral range based on the first stimulation signal already present in a conventional ERG system can still be used. An existing detection unit, for example with a signal amplifier and A / D converter connected to a measuring electrode, can also still be used. However, the response signal now also contains additional signal components.According to the proposed solution, an evaluation unit is therefore provided, which is configured to extract from the common ERG response signal a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal. The corresponding evaluation can preferably be implemented as a computer-implemented solution and thus in a simple manner. They can also be added later to expand the functionality of conventional ERG systems. This allows for cost-effective retrofitting.

[0013] Against this background, according to a further aspect of the present disclosure, a stimulation device for an electroretinography (ERG) system is proposed. The ERG system comprises a first signal generator for generating a first stimulation signal; a first light source for generating first optical stimuli in a visible spectral range based on the first stimulation signal; a second signal generator for generating a second stimulation signal; a second light source for generating second optical stimuli in a UV spectral range based on the second stimulation signal; a detection unit for detecting a common ERG response signal; and an evaluation unit configured to extract from the ERG response signal a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal.Here, the proposed stimulation device comprises the second signal generator for generating the second stimulation signal and the second light source for generating the second optical stimuli in a UV spectral range based on the second stimulation signal.

[0014] An advantage of this design may be that such a stimulation device enables cost-effective retrofitting of an existing ERG system and / or retrofitting with minimal technical effort. A particular advantage may be that no intervention in the existing interaction between the first signal generator and the first light source is necessary.

[0015] Furthermore, according to a further aspect of the present disclosure, a method for electroretinography is proposed, comprising the steps of: generating a first stimulation signal; generating first optical stimuli in a visible spectral range based on the first stimulation signal; generating a second stimulation signal; generating second optical stimuli in a UV spectral range based on the second stimulation signal; detecting a common ERG response signal; and extracting a first ERG response signal component corresponding to the first Stimulation signal and a second ERG response signal component corresponding to the second stimulation signal from the common ERG response signal.

[0016] It is understood that the above-mentioned stimulation device, the method, the control device and the computer program product according to the above-mentioned and subsequently described further aspects of the present disclosure may have identical or similar configurations and / or advantages as the electroretinography system according to the first aspect of the present disclosure.

[0017] Some terms and designations used in the present disclosure are defined and explained in more detail below.

[0018] In the context of the present disclosure, a visible spectral range can be understood as a range of the spectrum that is usually visible to humans, in particular a spectral range between 380 nm and 780 nm, in particular between 400 nm and 780 nm. A UV spectral range is understood as light or electromagnetic radiation in the optical frequency range with shorter wavelengths than the light visible to humans, in particular in the UV-A, UV-B and / or UV-C spectral range, in particular in a spectral range between 315 nm and 380 nm.

[0019] The acquisition unit can be a functional unit configured to record an ERG response signal. Electrical potentials generated by the retina can be recorded using one or more electrodes. The electrical potentials could, for example, be derived from a reference electrode using an electrode applied to the cornea or conjunctiva. The one or more electrodes can, for example, be coupled to an analog-to-digital converter via an optional signal amplifier to record the ERG response signal. Signal processing can be analog or digital.

[0020] Preferably, the electroretinography system is configured such that the first signal generator together with the first light source and the second signal generator together with the second light source are set up to be operated in parallel. In other words, a measurement can be carried out in which both light sources are active. One advantage can be that the measurements in the visible spectral range and in the UV spectral range can be carried out with a comparable state of adaptation of the test subject or test object. Adaptation effects or other changes in measurement quality therefore do not distort the measurement. Adaptation effects could occur, for example, if visible stimuli and UV stimuli were measured with a significant time interval. With simultaneous stimulation in the visible spectral range and in the UV spectral range, the associated response components can be separated again by the subsequent signal processing using the evaluation unit and assigned to the stimuli.The evaluation unit can further be configured to extract the degree of physiological interaction of the signals in the retina of the eye from the joint ERG response signal, induced by the first ERG signal component corresponding to the first stimulation signal in the visible spectral range, and the second ERG signal component corresponding to the second stimulation signal in the UV spectral range. This is particularly relevant when both light sources are active during the measurement and generate pulsed stimulation signals, also known as flicker stimuli, which in particular produce alternating light pulses in the visible spectral range and the UV spectral range.

[0021] Accordingly, the electroretinography system can be configured to alternate between an optical stimulus in the visible spectral range and an optical stimulus in the UV spectral range. One advantage of this configuration can be that the evaluation unit can separate the response signal components in the time domain, despite parallel measurements in the UV and visible spectral ranges, i.e., with joint detection of a common ERG response signal. The electroretinography system can be configured to generate the first and second optical stimuli in an interleaved operating mode, wherein an alternating sequence of optical stimuli in the visible spectral range and optical stimuli in the UV spectral range is generated. An optical stimulus can be a light pulse or flash.

[0022] The first or second signal generator can have an adjustable delay element and be configured to delay the second optical stimuli relative to the first optical stimuli (by a defined amount). By delaying the first and second optical stimuli relative to one another, it can be ensured that the first and second optical stimuli do not impinge on the eye at the same time and thus generate temporally separated contributions to the response signal. It is also possible for both the first signal generator and the second signal generator to have a delay element. An advantage of this configuration can be that the desired interactions of the response signal components can be obtained in a targeted manner and thus more quickly than is possible with a series of measurements with a random time difference between the two stimuli. This can facilitate subsequent signal processing.Furthermore, the adjustable delay element can also be used to determine the assignment of the ERG response signal components, i.e., whether they are elicited by the first optical stimuli or the second optical stimuli. For example, if the delay element is set such that the generation of the second stimulation signal is delayed, it is possible to observe how this affects the combined ERG response signal. The response signal component that was detected with the corresponding delay can be assigned to the second stimulation signal.

[0023] The first signal generator for generating the first stimulation signal and the second signal generator for generating the second stimulation signal can have independent clocks. In other words, the first signal generator in conjunction with the first light source and the second signal generator in conjunction with the second light source can be configured to generate the first optical stimuli and the second optical stimuli independently of one another. Independent of one another can mean that a frequency and / or phase position of the first and second optical stimuli is not synchronized with one another.For example, the first optical stimuli can be generated using a first signal generator and a first light source of a conventional ERG system, and the second optical stimuli can be generated using a second signal generator and a second light source of a retrofitted stimulation device according to one aspect of the present disclosure. This facilitates the retrofitting of conventional ERG systems.

[0024] In one development, the detection unit can be synchronized either with the first signal generator or with the second signal generator. The detection unit can be configured to sample the common ERG response signal in synchronization with the first stimulation signal generated by the first signal generator. Alternatively, the detection unit can be configured to sample the common ERG response signal in synchronization with the second stimulation signal generated by the second signal generator. According to one embodiment, the detection unit is therefore synchronized only with the first signal generator or the second signal generator. By synchronizing the detection unit with one of the signal generators, the signal generation and the signal detection are correlated with one another.For example, the first signal generator and the detection unit can be integral components of an existing ERG system, which are configured such that signal generation and signal detection are strictly correlated with each other. In this case, the signal generator and detection unit can be synchronized with a common clock. The second signal generator, however, can be part of a retrofitted or supplemented stimulation device. The first ERG response signal component, corresponding to the first stimulation signal generated by the first signal generator, is therefore strictly correlated with the timing or sampling by the detection unit, whereas ERG response signal components corresponding to the second stimulation signal generated by the second signal generator do not exhibit such a strict correlation, for example, they may vary randomly in phase or temporal position between the two optical stimuli.The evaluation unit can be configured to use this information to distinguish and extract the first and second response signal components.

[0025] The electroretinography system can be configured such that the first stimulation signal and the second stimulation signal do not have a fixed phase relationship to one another. The electroretinography system can be configured such that random delays occur between the first and second stimulation signals. A fixed phase relationship between the first stimulation signal and the second stimulation signal is also possible, but not required. Synchronization can be omitted, particularly in an ERG system that is created by retrofitting an existing ERG system. This can make retrofitting This can be done considerably easier, as no major hardware modifications to the existing components are required. Rather, it may be sufficient if a stimulation device with the second signal generator and the second light source is started at approximately the same time as, for example, an already existing internal first signal generator with the first light source. The acquisition unit acquires the common ERG response signal. The evaluation unit can again differentiate between the different ERG signal components, for example because only the first ERG signal component based on an internal first signal generator has a fixed phase relationship with a detection (e.g., sampling) by an internal acquisition unit.

[0026] The electroretinography system may further comprise a control device, wherein the control device is configured to: determine a first measured value (e.g., amplitude and / or latency information of the signal) of the first ERG response signal component and a second measured value of the second ERG response signal component; and adapt the first optical stimuli and / or the second optical stimuli such that the first and second ERG response signal components have the predefined interaction signs. The first measured value of the first ERG response signal component and the second measured value of the second ERG response signal component may each have amplitude and / or latency information. The first measured value of the first ERG response signal component may be an amplitude of the first ERG response signal component. The second measured value of the second ERG response signal component may be an amplitude of the second ERG response signal component.Alternatively or additionally, the first measured value of the first ERG response signal component can be or comprise latency information of the signal. Accordingly, the second measured value of the first ERG response signal component can alternatively or additionally be or comprise latency information of the signal. Alternatively or additionally, the first measured value of the first ERG response signal component can comprise amplitude and latency information of a scalar product of the first ERG response signal component with a predetermined signal template. Accordingly, the second measured value of the second ERG response signal component can comprise amplitude and latency information of a scalar product of the second ERG response signal component with a predetermined (same or different) signal template. One advantage can be that a flexible approach to. Determination of a species-specific equivalent biological efficacy of first optical stimuli in a visible spectral range and second optical stimuli in a UV spectral range can be provided. One advantage can be that calibration can be simplified. The ERG responses to (a) stimulation in the visible spectral range (e.g. with white light) and (b) stimulation with UV light are evaluated. The intensity of the stimuli can be adjusted so that both stimuli elicit the same (or an equally strong) ERG response. One advantage can be that in this way calibration can be carried out with simultaneous or alternating pulsed exposure to white light and UV light. As described above, pulses with white light and UV light can be measured alternately. Synchronization is not absolutely necessary, since separation is possible, for example, by evaluating different phase positions.For example, the intensity of the first and second optical stimuli is adjusted such that the first and second stimuli each elicit equally strong ERG response signal components.

[0027] In a further development, the control device can be configured for step-by-step, repeated adjustment of the first optical stimuli and / or the second optical stimuli until the first and second ERG response signal components exhibit the predefined interaction signs. This allows the first and second optical stimuli to be adjusted iteratively until the first and second ERG response signal components exhibit the desired interaction signs. This can be particularly advantageous when the effect of adjusting the first and / or second optical stimuli on the first and second ERG response signal components is not known in advance, i.e., it is not yet conclusively known which respective adjustment is required to achieve the desired interaction signs, such as, for example, an identical amplitude of the first and second ERG response signal components.

[0028] The control device may be configured to: determine a first amplitude of the first ERG response signal component and a second amplitude of the second ERG response signal component; and adjust the first optical stimuli and / or the second optical stimuli such that the first and second ERG response signal components have an equal amplitude. One advantage may be that a flexible approach for determining a species-specific equivalent The biological effectiveness of first optical stimuli in a visible spectral range and second optical stimuli in a UV spectral range can be determined. The amplitude of the first and / or second optical stimuli is thus varied or adjusted until they elicit the same amplitude and thus equivalent biological effect with respect to the first and second ERG response signal components. A step-by-step adjustment can be made. It is not necessary to know a luminosity curve (V-lambda curve) in the respective spectral ranges in advance. One advantage can be that the system can be used flexibly for measurements in different species.

[0029] In particular, the control device can be configured to: determine a first amplitude and first phase position of the first ERG response signal component and a second amplitude and second phase position of the second ERG response signal component; and adapt the first optical stimuli and / or the second optical stimuli such that the ERG response signal, i.e. the jointly generated ERG response signal, has a maximum amplitude at a first, defined phase difference between the first and second response signal components and a minimum amplitude at twice the frequency at a second, defined phase difference, for example at a phase difference of 180°. The respective phase values ​​can depend on the curve shape of the ERG response signal components.

[0030] The electroretinography system can be configured such that the first optical stimuli and the second optical stimuli have different radiometric intensities. In particular, the different radiometric intensities of the first optical stimuli and the second stimuli can be configured to each elicit an ERG response signal component from the rod and / or cone system with the same characteristics (e.g., amplitude, curve shape). In other words, the first and second optical stimuli are configured to elicit first and second ERG response signal components with the same characteristics, for example, with the same amplitude. One advantage can be that the response signal is used as the criterion, rather than the same radiometric intensity.Despite different luminosity curves in the visible spectral range and in the UV spectral range, an ERG response signal can be provided with the same amplitude for each. first and second optical stimuli. A further advantage may be that measurements can be made flexibly for different species with possibly different luminosity curves (also known as V-lambda curves).

[0031] The electroretinography system can be configured such that the first and / or second optical stimuli are a pulse sequence with a pulse frequency between 0.3 Hz and 100 Hz, in particular between 1 Hz and 50 Hz, in particular between 3 Hz and 30 Hz, in particular with a pulse frequency of 6 Hz. The first and / or second light source can be configured to generate repetitive stimuli with a predetermined repetition frequency. Such stimuli can also be referred to as flicker stimuli. For example, a pulse sequence of short, in particular narrow-band UV light pulses with a predetermined repetition frequency or pulse frequency of, for example, 6 Hz can be used.

[0032] The second light source can comprise one or more UV LEDs, in particular in conjunction with a (narrow-band) bandpass filter configured to allow light at a wavelength in the range from 360 nm to 365 nm (and not in the visible range) to pass through. One advantage can be that, during a measurement, influences of SWS opsin and MWS opsin in the murine cones can be distinguished. One advantage of the additional specific bandpass filter can be that a measurement is performed at a maximum sensitivity of SWS opsin while simultaneously avoiding stimulation of the MWS opsin, thus enabling a particularly meaningful measurement while simultaneously reducing energy input into the eye. The second light source can be part of a retrofit solution with an additional module. The second light source can be part of a stimulation device according to one aspect of the present disclosure.

[0033] The stimulation device, for example in the form of an additional module for an existing ERG system, also referred to as a host system, can preferably be configured to generate an additional, independent ERG signal component, wherein the resulting total ERG response signal, originally consisting only of a first signal component generated by a host system based on stimulation with light in a visible spectral range, is amplified or extended. by the second signal component based on stimulation with light of a different quality, such as in the UV spectral range. This allows a modified response characteristic of the resulting overall ERG response signal, originally consisting only of a first signal component generated by a host system based on transient and optionally constant stimulation (background light) with light in a visible spectral range, to be achieved by means of a second signal component generated by an additional module based on transient stimulation and optionally constant stimulation (background light) with light of a different quality, such as in a UV spectral range.A measurable physiological interaction in the visual system can be determined between the ERG signal component generated by the stimulation device, which has an initially unknown physiological effect, and the signal component generated by the host system, which has a known physiological effect, for calibrating the stimulus generated by the stimulation device. Equivalence of effect (for stimuli of the same frequency) is present, for example, if stimulation with a specific phase difference results in an increase in amplitude and with another specific phase difference, for example, stimulation in antiphase, a decrease in amplitude when the frequency is doubled. The respective phase values ​​depend on the curve shape of the ERG response signal components.

[0034] According to a further aspect of the present disclosure, a control device for an electroretinography system is proposed, wherein the control device is configured to: receive a common ERG response signal, wherein the common ERG response signal has a first ERG response signal component corresponding to a first stimulation signal and based on first optical stimuli with light in a visible spectral range and a second ERG response signal component corresponding to a second stimulation signal and based on second optical stimuli with light in a UV spectral range; extract the first ERG response signal component and the second ERG response signal component from the received common ERG response signal; determine a first measured value (e.g.Amplitude and / or latency information of the signal), in particular a first amplitude, of the first ERG response signal component and a second measured value, in particular a second amplitude, of the second ERG response signal component; and generating a control signal for adapting the first optical stimuli and / or the. second optical stimuli such that by (stepwise, repeated) adjusting the first optical stimuli and / or the second optical stimuli, the first and second ERG response signal components have the desired or predefined interaction signs, in particular such that the first and second ERG response signal components have the same amplitude. The control device can have the configurations and advantages described above with regard to the control device.

[0035] According to a further aspect of the present disclosure, a computer program product is proposed, comprising instructions which, when executed by a computer, cause the computer to carry out the following steps: receiving a common ERG response signal, wherein the common ERG response signal has a first ERG response signal component corresponding to a first stimulation signal and based on first optical stimuli with light in a visible spectral range and a second ERG response signal component corresponding to a second stimulation signal and based on second optical stimuli with light in a UV spectral range; extracting the first ERG response signal component and the second ERG response signal component from the received common ERG response signal; determining a first measured value (e.g.Amplitude and / or latency information of the signal), in particular a first amplitude, of the first ERG response signal component and a second measured value, in particular a second amplitude, of the second ERG response signal component; and generating a control signal for adapting the first optical stimuli and / or the second optical stimuli such that, by (stepwise, repeatedly) adapting the first optical stimuli and / or the second optical stimuli, the first and second ERG response signal components have the desired or predefined interaction signs, in particular such that the first and second ERG response signal components have the same amplitude.

[0036] In other words, the proposed signal processing can also be carried out on a computer that is accordingly configured by the proposed computer program product. It is understood that in this context, receiving an ERG response signal means receiving data that response signal. For example, the data can be acquired by a detection unit, for example with a detector or an electrode arrangement, an optional signal amplifier and an analog-to-digital converter, and made available as a digital ERG response signal for further processing by a computer. Accordingly, generating a control signal can be understood as generating data that represents a control signal or control commands. In the context of the present disclosure, a computer can be understood as a data processing device and can also refer to an office computer, a laboratory computer, a microcontroller, a server, a cloud-based data processing device and / or (integrated) circuits as well as application-specific circuits or ASICs.A further advantage of this design is that the functionality of conventional ERG systems can be easily extended subsequently with the proposed solution.

[0037] Further advantages are evident from the description and the attached drawings.

[0038] It is understood that the features mentioned above and those to be explained below can be used not only in the combination specified in each case, but also in other combinations or on their own, without departing from the scope of the present invention.

[0039] Embodiments of the invention are illustrated in the accompanying drawings and explained in more detail in the following description. They show: Fig. 1 is a schematic representation of an electroretinography system according to an embodiment of the disclosure; Fig. 2 is a schematic representation of an electroretinography system according to another embodiment of the disclosure with a stimulation device and a control device according to further aspects of the present disclosure; Fig. 3 graphical representations of ERG response signals with first and second ERG response signal components from experimental measurement data, from a simulation and as an overlay; Fig. 4 is a flowchart showing method steps for adapting the first and / or second optical stimuli; Fig. 5 is a graphical representation of experimental measurement data; Fig. 6 is a further graphical representation with experimental measurement data associated with Fig. 5, wherein the first optical stimuli and second optical stimuli are adapted such that the first and second ERG response signal components have an equal amplitude; Fig. 7 shows a graphical representation of experimental data from a mouse model lacking sensitivity in the white light range (Opnlmw mutant); Fig. 8 is a flow chart of an electroretinography procedure.

[0040] Fig. 1 shows a schematic representation of an electroretinography (ERG) system 1 according to an embodiment of the disclosure. The ERG system 1 is used in particular to examine the retinal function of a subject 200. The ERG system 1 is configured to record electrical potentials generated by the retina of the eye 201 of the subject 200 using one or more electrodes.

[0041] The ERG system 1 comprises a first signal generator 11 for generating a first stimulation signal and a first light source 12 for generating first optical stimuli in a visible spectral range based on the first optical stimulation signal. In the example shown in Fig. 1, the first signal generator 11 and the first light source 12 are connected to each other via a connection 13. The first Light source 12 may, for example, comprise one or more white LEDs or other light sources that emit visible light in a spectral range typically visible to humans between 380 nm and 780 nm, in particular between 400 nm and 780 nm.

[0042] The ERG system 1 further comprises a second signal generator 21 for generating a second stimulation signal and a second light source 22 for generating second optical stimuli in a UV spectral range based on the second stimulation signal. In the example shown in Fig. 1, the second signal generator 21 and the second light source 22 are connected to one another via a connection 23. The second light source 22 can, for example, comprise one or more UV LEDs or other light sources configured to emit UV light. Optionally, the second light source 22 can comprise a bandpass filter configured to allow light at a wavelength in a range from 360 nm to 365 nm, but not in the visible range, to pass through.The second optical stimuli, unlike conventional systems, make it possible not only to take measurements in the range of the spectrum visible to humans, but also to take measurements on test objects, such as nocturnal animals, especially mice, with a different luminosity curve (V-lambda curve).

[0043] The ERG system 1 further comprises a detection unit 31 configured to detect an ERG response signal. The detection unit can preferably comprise a measuring amplifier or preamplifier 32, which can be provided as part of the detection unit 31 or as a separate element. In Fig. 1, the preamplifier is illustrated by way of example as an external operational amplifier. The ERG response signal is preferably detected by means of an electrode 33 applied to the cornea or conjunctiva. A counterelectrode 34 is preferably provided in the vicinity of the eye, for example, in the canthus of the eyelid. However, a counterelectrode at another location in the vicinity of the eye is also conceivable, such as on the temple 202 or on the earlobe 203. The evaluation unit 31 is configured to detect a common ERG response signal.The common ERG response signal has a first ERG response signal component corresponding to the first stimulation signal in response to first optical stimuli from the first. light source 12 and a second ERG response signal component corresponding to the second stimulation signal in response to second optical stimuli from the second light source 22.

[0044] The ERG system 1 further comprises an evaluation unit 41. The evaluation unit 41 is configured to extract the first ERG response signal component corresponding to the first stimulation signal and the second ERG response signal component corresponding to the second stimulation signal from the common ERG response signal. In the proposed solution, the ERG response signal acquired by the acquisition unit includes both contributions caused by stimulation in the visible spectral range and contributions caused by stimulation in the UV spectral range. The evaluation unit 41 is configured to evaluate the ERG response signal such that the respective ERG response signal components caused by stimulation in the visible spectral range and by stimulation in the UV spectral range can be separated from one another, or to determine the degree of physiological interaction of the respective stimuli in the retina of the eye.

[0045] Preferably, the first signal generator 11 together with the first light source 12 and the second signal generator 21 together with the second light source 22 are configured to be operated in parallel. This allows measurements to be taken in the visible spectral range and in the UV spectral range with a comparable adaptation state of the test subject or test object. Adaptation effects or other changes in measurement quality therefore do not distort the measurement. For example, so-called flicker stimuli can be emitted. The first and / or second optical stimuli can be a pulse sequence with a pulse frequency between 0.3 Hz and 100 Hz, in particular between 1 Hz and 50 Hz, in particular between 3 Hz and 30 Hz, in particular with a pulse frequency of 6 Hz. An optical stimulus or light pulse in the visible spectral range and an optical stimulus or light pulse in the UV spectral range preferably alternate.

[0046] In the embodiment shown, the ERG system 1 further comprises a control device 42. The control device 42 is configured to determine a first measured value, for example an amplitude and / or latency information, of the first ERG response signal component and a second measured value, for example, an amplitude and / or latency information, of the second ERG response signal component. Furthermore, the control device 42 is configured to adapt the first optical stimuli and / or the second optical stimuli such that the first and second ERG response signal components have predefined interaction symbols. An iterative approach is possible here, as described below by way of example with reference to Fig. 4.

[0047] In the example shown in Fig. 1, the first signal generator 11, the second signal generator 12, the detection unit 31, the evaluation unit 41, and the control device 42 are arranged together. For example, these elements can be provided as a common arrangement 10, for example, in a common housing. This facilitates synchronization of the elements. For example, a common clock generator can be provided, which enables synchronized operation.

[0048] The first light source 12 and the second light source 22 can also be integrated into the common housing. To enable a flexible experimental setup, however, the light sources are preferably provided as separate elements that can be flexibly positioned to apply the first and second stimuli in a targeted manner to the eye 201 of the test object or subject 200.

[0049] In contrast, the example shown in Fig. 2 shows a different arrangement with a separate stimulation device 20. This enables cost-effective retrofitting of existing systems. Elements designated by the same reference numerals in Fig. 2 correspond to the corresponding elements in Fig. 1. Therefore, the differences are primarily highlighted below.

[0050] In the example shown in Fig. 2, the first signal generator 11 connected to the first light source and the detection unit 31 form a common arrangement 10 and can, for example, be arranged in a common housing. In this case, the signal generator and detection unit from an existing ERG system can also be used. However, an additional stimulation device 20 is provided. The second signal generator 21 and the second light source 22 are arranged separately and form a separate stimulation device 20. The stimulation device 20 has the second signal generator 21 for generating the second stimulation signal and the second light source 22 for generating the second optical stimuli in a UV spectral range based on the second stimulation signal.

[0051] In the example shown in Fig. 2, the evaluation unit 41 is also arranged separately. However, it is also possible for the evaluation unit 41 to be part of the stimulation device 20 or to be provided as part of the common arrangement 10. Preferably, the evaluation unit 41 can be implemented by means of a computer or a computing device. The common ERG response signal detected by the detection unit 31 can in this case be provided, for example, in the form of digitized measurement data for evaluation by the computer. The computer is specially configured in terms of software and in this case serves as an evaluation unit 41, which is configured to extract a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal from the common ERG response signal.This enables cost-effective implementation and flexible evaluation of the measurement data.

[0052] The stimulation device 20 can be implemented as a completely independent device. This enables particularly simple retrofitting of an existing ERG system. For measurements in the UV spectral range, the stimulation device can be put into operation at approximately the same time as the common arrangement 10. In this case, the first signal generator 11 for generating the first stimulation signal and the second signal generator 21 for generating the second stimulation signal can have clock generators 15, 25 that are independent of one another. In particular, the first stimulation signal and the second stimulation signal do not have a fixed phase relationship to one another, whereby random delays arise between the first and second stimulation signals. This can prevent the first and second optical stimuli caused by the first and second stimulation signals from always being generated at the same time orwith a fixed phase relationship to each other on the eye 201 of the subject 200 and possibly always hit at the same time.

[0053] The detection unit 31 can be synchronized with the first signal generator 11. This is schematically illustrated in Fig. 2 by the connection of the clock generator 15 to both the first signal generator 11 and the acquisition unit 31. In this case, the acquisition unit 31 can sample the common ERG response signal in synchronization with the first stimulation signal generated by the first signal generator. By correlating the signal generation of the first stimulation signal and the signal sampling, the first ERG response signal component in the common ERG response signal can be separated from the second ERG response signal component. However, the separation and extraction of the first and second ERG response signal components is not limited to this.

[0054] Alternatively, the acquisition unit 31 can also be synchronized with the second signal generator 21, as schematically illustrated by the dashed connection between the clock generator 15 and the second signal generator 21. In this case, the acquisition unit 31 can be configured to sample the common ERG response signal in synchronization with the second stimulation signal generated by the second signal generator 21.

[0055] Furthermore, it is possible to synchronize both the first signal generator 11 and the second signal generator 21 with the acquisition unit. As a result, the first and second ERG response signal components evoked in response to the first and second stimuli are always located at a defined temporal position in the joint ERG response signal acquired by the acquisition unit.

[0056] Optionally, the ERG system 1 can have an adjustable delay element 26, which is configured to delay the second optical stimuli relative to the first optical stimuli by a defined amount. In the example shown in Fig. 2, the delay element 26 is schematically shown in a control line from the first evaluation unit 41 or the control device 42 to the second signal generator. A delay element in an incoming or outgoing control or connection line of a signal generator can be understood as part of the signal generator within the scope of the present disclosure. In principle, the first and / or second signal generator can have an adjustable delay element and for this purpose be configured to delay the second optical stimuli relative to the first optical stimuli by a defined amount. If, for example, there is an overlap of the first ERG response signal component and the second ERG response signal component, the response signal components can be separated by delaying the first or second optical stimuli. Furthermore, the adjustable delay element can be used to perform comparison measurements at different delays. From the comparison, it can be determined which part of the ERG response signal was shifted, and thereby an assignment of the response signal components to the first and second optical stimuli can be made.

[0057] Fig. 3 shows graphical representations of ERG response signals with first and second ERG response signal components from experimental measurement data, from a simulation, and as an overlay. The horizontal axis represents a time axis. The vertical axis represents an amplitude of the combined ERG response signal. The first column shows experimental measurement data from an ERG measurement of a mouse. The second column shows a model of the ERG response signals. The third column shows an overlay of the measurement data from column 1 and the model from column 2.

[0058] In Fig. 3, the first row shows a first case, also referred to as Case 1, wherein the first light source emits first optical stimuli in a visible spectral range, here white light, and is set to an intensity “A”. This can be a white light source from a conventional ERG device. The second light source generates second optical stimuli in a UV spectral range with an initially unknown intensity X. Even if the optical intensity is known, the amplitude of the evoked ERG response signal can initially be unknown. The graph with the experimental measurement data is labeled 311. The graph with the modeling is labeled 312. The graph with the overlay is labeled 313.

[0059] In Fig. 3, a second case, also referred to as case 2, is shown in the second line, where the first light source emits first optical stimuli in a visible spectral range, here white light, and is set to an intensity “B”, where “B”>“A”, ie the Intensity "B" is greater than intensity "A." The second light source generates second optical stimuli in a UV spectral range with the initially unknown intensity X, as in Case 1. The graph with the experimental measurement data is labeled 321. The graph with the modeling is labeled 322. The graph with the overlay is labeled 323.

[0060] In Fig. 3, the third row shows a third case, also referred to as Case 3, wherein the first light source emits first optical stimuli in a visible spectral range, here white light, and is set to an intensity “C”, where “C”>“B”, i.e. the intensity “C” is greater than the intensity “B”. The second light source generates second optical stimuli in a UV spectral range with the initially unknown intensity X, as in Case 1. The graph with the experimental measurement data is labeled 331. The graph with the modeling is labeled 332. The graph with the overlay is labeled 333.

[0061] In case 1, the (biological effect of) intensity A is much smaller than X. Curves 314 and 315 represent separate measurements of the common ERG response signal. Corresponding simulations are shown in the second column with curves 316, 317. Curves 314, 315 and 316, 317 are not temporally correlated with the detection unit 31 of the ERG system 1, since they are all caused or dominated by the second light source 22 of the stimulation device 20 of the ERG system 1, and the stimuli from the first light source 21 of the ERG system 1 are negligible. In the example shown, the first signal generator 11 and the second signal generator 21 are not synchronized with each other or have independent clock generators 15, 25. However, the detection unit 31 is synchronized with the first signal generator 11.

[0062] In case 2, the (biological effect of) intensity A is comparable to X. Curves 324 and 325 represent separate measurements of the common ERG response signal. Corresponding simulations are shown in the second column with curves 326, 327. Curves 324, 325 and 326, 327 are at least partially temporally correlated with the detection unit 31 of the ERG system 1, since they represent response signal components evoked by the first optical stimuli from the first light source 11 of the ERG System 1 (this component is correlated) and response signal components evoked by the second optical stimuli from the second light source 21 of the (unsynchronized) second light source 22 of the ERG System 1 (this component is uncorrelated). An interference or superposition of the two response signal components takes place. If both response signal components happen to occur simultaneously (curve 324 in the measured data, curve 326 in the model), this leads to a maximum amplitude with an unchanged curve shape. If both signals occur in antiphase (roughly the case with curve 325 in the measured data, curve 327 in the model), the positive and negative components partially cancel each other out, resulting in a minimum amplitude with twice the frequency (i.e. twice as many "peaks").

[0063] In case 3, the (biological effect of) intensity A is much greater than X. Curves 334 and 335 represent separate measurements of the common ERG response signal. Corresponding simulations are shown in the second column with curves 336, 337, with curves 336 and 337 superimposed. Curves 334, 335 and 336, 337 are all temporally correlated with the detection unit 31 of the ERG system 1, since they are all evoked or dominated by the first light source 11, and the second optical stimuli from the second light source 22 of the ERG system are negligible.

[0064] Fig. 4 shows a flowchart with method steps for adapting the first and / or second optical stimuli. An exemplary algorithm for determining equivalence between the two stimuli (UV stimulus of unknown intensity vs. white light stimulus of known intensity) is explained using graphical representations of ERG response signals with first and second ERG response signal components from a simulation. The graph in the left column of Fig. 4 corresponds to the scenario in graph 312 in Fig. 3. The graph in the middle column of Fig. 4 corresponds to the scenario in graph 322 in Fig. 3. The graph in the right column of Fig. 4 corresponds to the scenario in graph 332 in Fig. 3.

[0065] In step 410, a common ERG response signal is received, wherein the common ERG response signal includes (a) a first ERG response signal component corresponding to a first stimulation signal and based on first optical stimuli with light in a visible spectral range and (b) a second ERG response signal component corresponding to a second stimulation signal and based on second optical stimuli with light in a UV spectral range. As described with reference to Fig. 3, different scenarios can arise.

[0066] The left column shows the case, referred to as Case 1 in Fig. 3, in which the (biological effect of the) intensity of the first optical stimuli A is much smaller than the (biological effect of the) intensity of the second optical stimuli X. In step 411, an evaluation is carried out to the effect that the common ERG response signal or the position of the curves 317, 318, 319 is uncorrelated with a time window of the acquisition unit for acquiring the common ERG signal. In step 412, an adjustment of the first optical stimuli and / or the second optical stimuli is carried out. Since the (uncorrelated) second optical stimuli dominate in the present case, an intensity of the second optical stimuli can be reduced or an intensity of the first optical stimuli can be increased, or both.The algorithm returns to step 410, where the joint ERG response signal is measured again using the adjusted first and / or second optical stimuli.

[0067] The right-hand column shows the case, referred to as Case 3 in Fig. 3, in which the (biological effect of) intensity C of the first optical stimuli is much greater than the (biological effect of) intensity X of the second optical stimuli. In step 431, an evaluation is carried out to the effect that the common ERG response signal or the position of the curves 336, 337 correlates completely with a time window of the detection unit for detecting the common ERG signal. In step 432, an adjustment of the first optical stimuli and / or the second optical stimuli is therefore carried out. Since the correlated first optical stimuli dominate in the present case, an intensity of the first optical stimuli can be reduced or an intensity of the second optical stimuli can be increased, or both.The algorithm returns to step 410, where the joint ERG response signal is measured again using the adjusted first and / or second optical stimuli.

[0068] The middle column shows the case, designated as Case 2 in Fig. 3, in which the (biological effect of the) intensity of the first optical stimuli and the (biological Effect of the) intensity of the second optical stimuli elicits ERG response signals with the same amplitude. This is considered to be an at least approximately equivalent physiological effect. In particular, curves 326, 327, 328 can result from successive measurements, whereby the ERG response signals (a) correlate with the time window of the detection unit that uses visible light as a stimulus, and (b) vary depending on the phase difference of the first and second optical stimuli between increased amplitude and frequency corresponding to the stimulus (curve 326) and reduced amplitude at twice the frequency (curve 327), and mixed forms in between (curve 328). The algorithm ends in step 422, wherein the first optical stimuli and / or the second optical stimuli are adjusted such that the first and second ERG response signal components have an equal amplitude or produce an equal biological effect.

[0069] Fig. 5 and Fig. 6 are graphical representations based at least in part on the same experimental data. Fig. 5 is another graphical representation, wherein the first optical stimuli and second optical stimuli are adjusted such that the first and second ERG response signal components have an equal amplitude. This is an exemplary representation of a successful determination of the physiological effectiveness of UV stimuli using the equivalence method described with reference to Fig. 4. The flash intensity [log (cd*s / m 2 The horizontal axis labeled "b-wave amplitude [pV]" indicates the intensity of an optical stimulus. The vertical axis labeled "b-wave amplitude [pV]" indicates the amplitude of the measured ERG response signal.

[0070] The measurements were performed in a rhodopsin knockout mouse under dark-adapted (scotopic) conditions, as this mouse possesses normal cone function with complete absence of rod function, thus reliably ruling out any influence of the rods on the measurements. A measurement of cone function would otherwise only be possible under light-adapted (photopic) conditions, although adaptation also affects cone function (reduces responses), and this also occurs spectrally differently for white and UV, since the standard adaptation background consists of white light.

[0071] Fig. 5 shows a so-called "intensity response" function. The "intensity response" function is a representation method for statistical ERG data of multiple entities at different intensities. Shown are so-called "box-and-whisker plots" (representing the 5%, 25%, 50%, 75%, and 95% quantiles of measurement data) of one group (here, UV data) compared with the limiting 5% and 95% quantiles of the other, typically a control group (here, white light data). Curve 521 represents a line connecting the 50% quantiles of the ERG response signals in response to second optical stimuli in the UV spectral range. Curve 511 represents the 5% quantile of the ERG response signals in response to first optical stimuli in the visible spectral range. Curve 512 indicates the 95% quantile of the ERG response signals in response to first optical stimuli in the visible spectral range.

[0072] The data here represent the statistical results of multiple measurements as shown in Fig. 6. In the left graph in Fig. 6, labeled "dark adapted, UV flash," the ERG response signals 621 under dark-adapted conditions to a second optical stimulus in the UV spectral range are shown. In the right graph in Fig. 6, labeled "dark adapted, white flash," the ERG response signals 611 under dark-adapted conditions to a first optical stimulus in the visible spectral range are shown. The multiple curves arranged one above the other each represent the ERG response signals at different stimulus intensities. The intensity increases from top to bottom.

[0073] An exemplary procedure for the measurements shown in Fig. 5 and Fig. 6 can be described as follows:

[0074] (a) First, for example, using the method described with reference to Fig. 4, the first optical stimuli and / or the second optical stimuli can be adapted such that the first and second ERG response signal components exhibit predefined interaction signs, in this case providing an equal ERG response signal amplitude. During the equivalence determination, an equivalent value B (white light) is determined for the unknown value X (UV light).

[0075] (b) From tabulated radiometric measurements of the UV light source, the desired relative values ​​related to X are determined (here logarithmic and semi-logarithmic steps up and down, as shown on the horizontal axis in Fig. 5 and illustrated for example ERG response signals in Fig. 6). From the table, it was then determined which setting (larger or smaller current through the LEDs) would then yield values ​​such as 1 / 10 X, 1 / 100 X, etc., or 10 X, 100 X, etc. Since radiometric and photometric quantities behave proportionally in this context, equivalents to, for example, 1 / 10 B, 1 / 100 B, etc., or 10 B, 100 B, etc., can be obtained without further measurement. In the example, equivalence was approximately B = 1 cd*s / m 2 This corresponds logarithmically to the value "0". With the existing setup, the range of -2 log (cd*s / m 2 ) corresponding to 1 / 100 X to 1 log (cd*s / m 2) corresponding to 10 X in a total of seven steps (Fig 5, X-values ​​for the black curve and the grey boxes).

[0076] (c) With the first signal generator and the first light source, measurements are performed at the various desired intensities of the first stimulus (white light, calibrated) (here B / 100 to 10 B, see Fig. 6, right). With the second signal generator and the second light source, measurements are performed at the desired equivalent intensities using the second stimulus (UV light, equivalence calibrated) (here X / 100 to 10 X, see Fig. 6, left).

[0077] From the illustration in Fig. 6, it is readily apparent that the measurements shown as examples in Fig. 5 and Fig. 6 yield virtually the same result. This underlines, on the one hand, that the equivalence determination was correct, and, on the other hand, that the extension to other intensities is indeed feasible and productive.

[0078] d) The measurements according to c) are repeated for different entities until a meaningful amount of data is available. An example result is illustrated in Fig. 5. The so-called flash intensity (x-axis) represents the equivalent values ​​for the measurement data using UV light (second stimulus), and the actual, calibrated values ​​for the measurement data using white light (first stimulus).

[0079] Fig. 6 shows graphs with experimental measurement data from a model lacking sensitivity in the white light range (Opnl mw mutant) illustrating the gain in response capacity by UV stimulation, based on ERG response signals generated by first optical stimuli in the visible spectral range (white stimulus 1) or second optical stimuli in the UV spectral range (UV stimulus 2).

[0080] Using the first signal generator and the first light source, which can be provided, for example, by a conventional ERG device, measurements were performed at the various desired intensities of the first optical stimulus (white light, calibrated) (here B / 100 to 10 B, analogous to Fig. 6, right).

[0081] With the second signal generator and the second light source, which can be provided, for example, by a stimulation device proposed herein, measurements were performed at the desired equivalent intensities using the second optical stimulus (UV light, equivalence calibrated) (here X / 100 to 10 X, analogous to Fig. 6, left).

[0082] In normal mice, designated C56BL / 6 Normal Control in Fig. 7, and the Opnl mw mutants, designated Opnlmw no MW opsin in Fig. 7, regular rod function is present. Therefore, rod responses dominate in the scotopic (dark-adapted) measurements using single flashes (no flicker) (top row, "scotopic flash," see, for example, curves 713, 711, 721, 723). However, the missing cone component in the Opnl mw mutants during white-light stimulation is evident from an amplitude reduction immediately after the positive peak (see arrows in Fig. 7), which causes the descending part to become convex instead of concave.

[0083] In the photopic ERG (bottom row in Fig. 7), the functional gain due to the equivalence-calibrated UV-ERG is particularly evident.

[0084] Firstly, the response of the mouse without M-opsin (Opnlmw mutant) to UV stimulation, see e.g. curve 724, is comparable to the normal mouse (Fig. 7, bottom left, see e.g. curve 722), while in contrast to the control, with white light stimulation in the used intensity range no response is discernible, see e.g. comparison of curve 714 with curve 712 in Fig. 7, bottom right.

[0085] Second, the response of the normal mouse (C57BL / 6) is more sensitive to UV stimulation (onset at lower intensity, higher amplitude at a given intensity) than to white light stimulation, because the background for suppressing rod influences by adaptation is spectrally white by default and thus only affects the M-opsin of the cones.

[0086] From the illustration in Fig. 7, it is readily apparent that the measurements shown as examples in the lower left panel of Fig. 7 yield virtually the same result. This underscores, firstly, that the equivalence determination was correct and, secondly, that an extension to the photopic range is also applicable without further measurement. A key finding is the lack of a response of the Opnlmw mutant upon stimulation with white light.

[0087] Fig. 8 shows a flowchart of a method 800 for electroretinography. In a step S801, a first stimulation signal is generated, and in a step S802, based on the first stimulation signal, first optical stimuli in a visible spectral range are generated. In a step S803, a second stimulation signal is generated, and in a step S804, based on the second stimulation signal, second optical stimuli in a UV spectral range are generated.

[0088] In step S805, a common ERG response signal is acquired. In step S806, a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal are extracted from the common ERG response signal. The extracted first and second ERG response signal components can be used as measurement results, or optionally, further method steps can be performed.

[0089] In step S807, a first measured value, in particular a first amplitude, of the first ERG response signal component and a second measured value, in particular a second Amplitude of the second ERG response signal component can be determined. In a likewise optional step S808, a control signal can be generated for adapting the first optical stimuli and / or the second optical stimuli such that, by (stepwise, repeated) adapting the first optical stimuli and / or the second optical stimuli, the first and second ERG response signal components have predefined interaction signs, in particular such that the first and second ERG response signal components have the same amplitude. By way of example, Fig. 8 shows the adaptation of the first optical stimuli by a feedback path 809 to step S801 of generating the first stimulation signal. Alternatively or additionally, however, a corresponding feedback path to steps S802, S803, and / or S804 can also be provided.

[0090] In summary, the present disclosure enables conventional ERG systems to be expanded to include measurements in the UV range, for example, for testing the function of the retinal cones in nocturnal animals. According to a further aspect of the present disclosure, an ERG system can be provided that enables more meaningful measurements in different spectral ranges in a simpler manner. Furthermore, it is possible to provide an ERG system that enables measurements of test objects (e.g., mice) with a brightness sensitivity curve that deviates from human brightness sensitivity in a simple manner. In particular, simplified system calibration can be enabled. Furthermore, existing ERG systems can be cost-effectively retrofitted according to aspects of the present disclosure.

Claims

Patent claims 1. Electroretinography system (1) comprising: a first signal generator (11) for generating a first stimulation signal; a first light source (12) for generating first optical stimuli in a visible spectral range based on the first stimulation signal; a second signal generator (21) for generating a second stimulation signal; a second light source (22) for generating second optical stimuli in a UV spectral range based on the second stimulation signal; a detection unit (31) for detecting a common ERG response signal; and an evaluation unit (41) configured to extract a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal from the common ERG response signal.

2. Electroretinography system (1) according to claim 1, wherein the first signal generator (11) together with the first light source (12) and the second signal generator (21) together with the second light source (22) are adapted to be operated in parallel with one another.

3. Electroretinography system (1) according to one of the preceding claims, wherein the electroretinography system is configured to alternate between an optical stimulus in the visible spectral range and an optical stimulus in the UV spectral range.

4. Electroretinography system (1) according to one of the preceding claims, wherein the first or second signal generator (11, 21) has an adjustable delay element (26) and is designed to generate the second optical stimuli to be delayed relative to each other by a defined amount compared to the first optical stimuli.

5. Electroretinography system (1) according to one of the preceding claims, wherein the first signal generator (11) for generating the first stimulation signal and the second signal generator (21) for generating the second stimulation signal have clock generators (15, 25) independent of one another.

6. The electroretinography system (1) according to claim 5, wherein the acquisition unit (31) is synchronized either with the first signal generator (11) or with the second signal generator (21); in particular, wherein the acquisition unit (31) is configured either to sample the common ERG response signal in synchronization with the first stimulation signal generated by the first signal generator (11), or wherein the acquisition unit (31) is configured to sample the common ERG response signal in synchronization with the second stimulation signal generated by the second signal generator (21).

7. Electroretinography system (1) according to one of the preceding claims, wherein the first stimulation signal and the second stimulation signal do not have a fixed phase relationship to one another, whereby random delays arise between the first and second stimulation signals.

8. Electroretinography system (1) according to one of the preceding claims, further comprising a control device (42), wherein the control device is arranged to: Determining a first measured value of the first ERG response signal component and a second measured value of the second ERG response signal component; and Adapting the first optical stimuli and / or the second optical stimuli such that the first and second ERG response signal components have predefined interaction signs.

9. Electroretinography system (1) according to claim 8, wherein the first measured value of the first ERG response signal component and the second measured value of the second ERG response signal component each comprise amplitude and latency information of the signal.

10. Electroretinography system (1) according to 8 or 9, wherein the control device (42) is arranged to gradually, repeatedly adjust the first optical stimuli and / or the second optical stimuli until the first and second ERG response signal components have the predefined interaction signs.

11. Electroretinography system (1) according to one of claims 8 to 10, wherein the control device (42) is arranged to: Determining a first amplitude of the first ERG response signal component and a second amplitude of the second ERG response signal component; and Adjusting the first optical stimuli and / or the second optical stimuli such that the first and second ERG response signal components have an equal amplitude.

12. Electroretinography system (1) according to one of the preceding claims, wherein the first optical stimuli and the second optical stimuli have a different radiometric intensity, in particular wherein the different radiometric intensity of the first optical stimuli and the second stimuli are each configured to elicit an ERG response signal component of the rod and / or cone system with the same characteristic.

13. Electroretinography system (1) according to one of the preceding claims, wherein the first and / or second optical stimuli are a pulse sequence with a pulse frequency between 0.3 Hz and 100 Hz, in particular between 1 Hz and 50 Hz, in particular between 3 Hz and 30 Hz, in particular with a pulse frequency of 6 Hz.

14. Electroretinography system (1) according to one of the preceding claims, wherein the second light source (22) comprises one or more UV LEDs, in particular in conjunction with a bandpass filter which is designed to allow light at a wavelength in a range of 360 nm to 365 nm, and not in the visible range, to pass through.

15. Stimulation device (20) for an electroretinography system (1) with a first signal generator (11) for generating a first stimulation signal; a first light source (12) for generating first optical stimuli in a visible spectral range based on the first stimulation signal; a second signal generator (21) for generating a second stimulation signal; a second light source (22) for generating second optical stimuli in a UV spectral range based on the second stimulation signal; a detection unit (31) for detecting a common ERG response signal; and an evaluation unit (41) configured to extract from the ERG response signal a first ERG response signal component corresponding to the first stimulation signal and a second ERG response signal component corresponding to the second stimulation signal.wherein the stimulation device (20) comprises the second signal generator (21) for generating the second stimulation signal and the second light source (22) for generating the second optical stimuli in a UV spectral range based on the second stimulation signal; 16. Method (800) for electroretinography comprising the steps: Generating a first stimulation signal (S810); Generating first optical stimuli in a visible spectral range based on the first stimulation signal (S802); Generating a second stimulation signal (S803); Generating second optical stimuli in a UV spectral range based on the second stimulation signal (S804); Acquiring a common ERG response signal (S805); and extracting a first ERG response signal component corresponding to the first stimulation signal and a second ERG Response signal component corresponding to the second stimulation signal from the common ERG response signal (S806).

17. Control device (42) for an electroretinography system (1 ), wherein the control device is arranged to Receiving a common ERG response signal, the common ERG response signal comprising a first ERG response signal component corresponding to a first stimulation signal and based on first optical stimuli with light in a visible spectral range and a second ERG response signal component corresponding to a second stimulation signal and based on second optical stimuli with light in a UV spectral range; Extracting the first ERG response signal component and the second ERG response signal component from the received common ERG response signal (S806); Determining a first measured value, in particular a first amplitude, of the first ERG response signal component and a second measured value, in particular a second amplitude, of the second ERG response signal component (S807); and Generating a control signal for adapting the first optical stimuli and / or the second optical stimuli such that, by stepwise, repeated adaptation of the first optical stimuli and / or the second optical stimuli, the first and second ERG response signal components have predefined interaction signs, in particular such that the first and second ERG response signal components have an equal amplitude (S808).

18. A computer program product comprising instructions which, when executed by a computer, cause the computer to perform the following steps: Receiving a common ERG response signal, wherein the common ERG response signal comprises a first ERG response signal component corresponding to a first stimulation signal and based on first optical stimuli with light in a visible spectral range and a second ERG response signal component corresponding to a second stimulation signal and based on second optical stimuli with light in a UV spectral range; Extracting the first ERG response signal component and the second ERG response signal component from the received common ERG response signal (S806); Determining a first measured value, in particular a first amplitude, of the first ERG response signal component and a second measured value, in particular a second amplitude, of the second ERG response signal component (S807); and Generating a control signal for adapting the first optical stimuli and / or the second optical stimuli such that, by stepwise, repeated adaptation of the first optical stimuli and / or the second optical stimuli, the first and second ERG response signal components have predefined interaction signs, in particular such that the first and second ERG response signal components have an equal amplitude (S808).

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