Method and devices for determining a disruption threshold value or multi-photon absorption threshold value

Abstract

The present invention relates to: a method for determining a disruption threshold value (37) or a multi-photon absorption threshold value of a cornea (17) of a patient's eye (9) to be treated with a femtosecond laser (5); a computer program product (71); a laser therapy device (10); a data signal (77); and a computer-readable storage medium (79). The method comprises: activating a scanner element (1) such that a treatment beam path (3) of the femtosecond laser (5) moves along a trajectory (11) outside an optical zone (7) to be treated of the eye (9) to be treated; incrementally increasing a power (P) emitted by the femtosecond laser (5) without interrupting the movement of the treatment beam path (3) along the trajectory (11); carrying out at least one examination step for detecting a threshold value range along the trajectory (11), in which range the disruption threshold value (37) or the multi-photon absorption threshold value was reached; and reading out the laser power (P) that was used in the threshold value range; and defining said laser power (P) as a disruption threshold value (37) or as a multi-photon absorption threshold value.

Description

[0001] Methods and devices for determining a disruption or multiphoton absorption threshold

[0002] The present invention relates to a method for determining a disruption or multiphoton absorption threshold value of a cornea of ​​a patient's eye to be treated with a femtosecond laser, as well as a computer program product, a laser therapy device, a data signal and a computer-readable non-volatile storage medium.

[0003] When using a femtosecond laser in refractive surgery, optimal laser pulse energy is crucial for treatment success. Laser pulse energies that are too low do not trigger photodisruption or multiphoton absorption, and the desired effect of the femtosecond laser is not achieved. Using photodisruption at energies that are too high, there is a risk of an opaque bubble layer (OBL) forming and, on the other hand, the risk of tissue deformation due to the resulting gas, resulting in a slower visual recovery. This should be avoided at all costs.

[0004] When performing laser-induced refractive index changes or laser-induced crosslinking, there is a risk of blistering if the energy used is too high, which is not desired with these treatment options.

[0005] For the purposes of this disclosure, the term patient includes a person to be treated of any gender.

[0006] Since the disruption or multiphoton absorption threshold of the cornea can vary from patient to patient, and the transmission losses of the laser beam can also vary, treatments can occur in which the applied laser pulse energy falls outside the optimal range. If photodisruption occurs in a tissue, this manifests itself as bubbles appearing at the focus of the femtosecond laser. Multiphoton absorption occurring in the tissue can manifest itself as changes in the tissue structure or in tissue parameters such as the refractive index or elastic modulus.

[0007] The aim of the present invention is to enable treatment with optimally adjusted laser pulse energy and to enrich state-of-the-art solutions in this regard.

[0008] The present invention achieves this object for the method mentioned at the outset by comprising the following method steps: controlling a scanner element such that a processing beam path of the femtosecond laser moves along a trajectory outside an optical zone of the eye to be treated; incrementally increasing the power emitted by the femtosecond laser without interrupting the movement of the processing beam path along the trajectory; and

[0009] Performing at least one examination step to detect a threshold range along the trajectory in which the disruption threshold or the multiphoton absorption threshold has been reached. Specifically, this means:

[0010] In case of (a) a photodisruption-based treatment of the eye: taking an image of the eye to be treated; checking those image areas that represent areas of the eye to be treated in which laser emission has occurred; detecting the area of ​​incipient blistering in the cornea of ​​the patient's eye, i.e. determining the area in which blistering is detected (this area is the threshold area); and reading out the laser power that was used in the corresponding area of ​​incipient blistering, i.e. in the threshold area

[0011] In case (b) of a multiphoton absorption-based treatment of the eye such as, but not limited to, LIRIC or crosslinking: performing at least one measurement method from the list of measurement methods comprising:

[0012] High-resolution optical coherence tomography;

[0013] - autofluorescence;

[0014] Optical coherence elastography;

[0015] Brioullin spectroscopy; or

[0016] Ultrasound imaging,

[0017] Checking those image areas which represent areas of the eye to be treated in which a laser emission has occurred; detecting the area of ​​incipient tissue modification in the cornea of ​​the patient's eye, i.e. determining the area in which a change in at least one tissue parameter of the cornea is detected (this is the threshold value area), such as, purely by way of example, a change in the refractive index or Young's modulus; and reading out the laser power which was used in the corresponding area of ​​incipient change in the at least one tissue parameter of the cornea, i.e. in the threshold value area.

[0018] In both case (a) and case (b), the laser power used in the threshold range is then read out and this laser power is set as the disruption threshold or as the multiphoton absorption threshold.

[0019] This means, in case (a): defining this laser power as the disruption threshold, or in case (b), defining this laser power as the multiphoton absorption threshold. An area of ​​incipient or beginning bubble formation (for case (a)) is understood as an area in which bubbles generated by the photodisruption of the femtosecond laser have been detected in the tissue. It is conceivable that a minimum number of bubbles are necessary within a defined area of ​​the area to be able to speak of reaching the disruption threshold. Ideally, each laser pulse generates a bubble in the material.If the set laser pulse energy of the femtosecond laser is so close to the disruption threshold that, depending on slightly different local tissue parameters, a bubble does not form with every laser pulse (but only at the next higher selected laser pulse energy), it is conceivable that the disruption threshold is interpolated as a value between two laser pulse energies. A simple and non-restrictive way to ensure this is, for example, to calculate the average of two adjacent laser pulse energy levels. The terms laser pulse energy, laser energy, and pulse energy should be understood as synonyms herein, with all three units being the joule, J (for pulsed lasers commonly used in ophthalmology, this value is in the picojoule to nanojoule range).

[0020] The procedural step of detecting the area of ​​incipient blistering in the cornea is thus to be understood as detecting bubbles generated in the cornea and marking or defining the area in which the bubbles were detected. This procedural step can be modified such that a minimum number of bubbles must be detected to define the corresponding area as the area of ​​incipient blistering.

[0021] An area of ​​incipient or beginning change in at least one tissue parameter of the cornea (for case (b)) is to be understood as an area in which a modification of at least one parameter generated in the tissue by the multiphoton absorption of the femtosecond laser has been detected. It is conceivable that within a defined area of ​​the area, a minimum proportion with measured modification is necessary to be able to speak of reaching the multiphoton absorption threshold. Ideally, each laser pulse creates an area in the material in which a change in at least one tissue parameter of the cornea is measurable.If a set laser pulse energy of the femtosecond laser is so close to the multi-photon absorption threshold that, depending on slightly different local tissue parameters, a change in at least one tissue parameter of the cornea does not occur with every laser pulse (but only with the next higher selected laser pulse energy), it is conceivable that the multi-photon absorption threshold is interpolated as a value between two laser pulse energies. A simple and non-restrictive way of ensuring this is, for example, averaging two adjacent levels of laser pulse energy. The method step of detecting the area of ​​incipient change in at least one tissue parameter of the cornea is thus defined as detecting areas created in the cornea with a measured change in at least one tissue parameter of the cornea and marking orDefining the area in which the change was detected.

[0022] This means that before the actual laser treatment begins, test shots of the femtosecond laser with different energies are applied in a specific pattern into the peripheral cornea.

[0023] A bubble image (for case (a)) of these test shots can be captured with a suitable camera and analyzed by a computer program.

[0024] For case (b), a corresponding measurement result can be obtained using a suitable measuring device. Even in the case of measurements using high-resolution optical coherence tomography, autofluorescence, optical coherence elastography, Brioullin spectroscopy, or ultrasound imaging, the obtained measurement result can be analyzed using a computer program.

[0025] The computer program product according to the invention comprises instructions which, when executed on or by a laser therapy device, cause the laser therapy device to carry out an embodiment of the method presented.

[0026] The data signal according to the invention transmits such a computer program product.

[0027] The laser therapy device according to the invention is accordingly designed to carry out a method described herein and / or to execute a computer program product described herein and / or to receive a data signal described herein.

[0028] A corresponding computer-readable non-transitory storage medium according to the disclosure stores a computer program product described herein.

[0029] The method and devices according to the invention can be improved by further optional features described in more detail below. These optional features can be combined with one another as desired. Furthermore, features described in the course of the method can be transferred to the corresponding configuration of the laser therapy device, the computer program product, the data signal, or the computer-readable non-volatile storage medium.

[0030] The laser therapy device can be equipped with an additional camera to capture the bubble image, or a camera already present in the laser therapy device can be used. Analysis of the images captured by the camera can yield the disruption threshold for case (a). This can represent the ideal pulse energy for treating the respective patient's eye in its current condition.

[0031] Alternatively, in case (b), the laser therapy device may comprise an additional device which is designed to comprise at least one measuring method from the list of measuring methods:

[0032] High-resolution optical coherence tomography;

[0033] - autofluorescence;

[0034] Optical coherence elastography;

[0035] Brioullin spectroscopy; and ultrasound imaging. It is thus conceivable that the laser therapy device comprises a high-resolution optical coherence tomograph, an autofluorescence detector, an optical coherence elastograph, a Brioullin spectroscope, or an ultrasound imaging measuring device. Analysis of the measurements obtained using one of the aforementioned measuring devices can yield the multiphoton absorption threshold for case (b). This can represent the ideal pulse energy for treating the respective patient's eye in its current condition.

[0036] Furthermore, this energy value can be transmitted to the control software of the femtosecond laser of the laser therapy device and used to set the energy value for the subsequent treatment. The determined energy value can thus either be used directly or optionally added to a user-selectable and stored offset, so that the energy value for the subsequent treatment corresponds to the sum of the determined disruption threshold or the determined multiphoton absorption threshold and the offset.

[0037] Preferably, the test shots and the calculation of the disruption or multiphoton absorption threshold value take place immediately before the actual treatment of the eye. If the patient's eye is fixed, for example, using a patient interface, the test shots and the calculation of the disruption or multiphoton absorption threshold value can take place while the patient's eye is suctioned in, i.e., connected to the laser therapy device via the patient interface. The method presented here is independent of whether the patient's eye is fixed using any patient interface or whether the eye is treated without fixation. In any case, the test shots take place before and, in particular, independently of the actual treatment of the patient's eye. The method presented therefore neither represents a surgical procedure nor is it a sub-step of such a surgical procedure.Rather, the procedure should be understood as a test procedure for determining optimal parameters.

[0038] A laser therapy device can have the appropriate means to carry out the individual process steps.

[0039] For example, a scanner element can be provided that consists of or includes at least one scanning mirror. Other known scanner elements such as rotating prisms or mirrors or deformable mirror elements (DMDs) are also conceivable.

[0040] The processing beam path can be understood as the optical path along which the laser radiation of the femtosecond laser propagates. The processing beam path thus exists even when the femtosecond laser is not emitting. Furthermore, the processing beam path can be characterized by a target laser that preferentially emits in the visible spectral range. The laser radiation of the target laser can propagate collinearly with the processing beam path.

[0041] Various known laser types can be used as femtosecond lasers, which can be based, for example, on a disk laser or a fiber laser, or can have a classically constructed laser resonator with an end mirror, output mirror and a laser crystal arranged between these two elements.

[0042] What all laser types have in common is that they emit pulsed laser radiation whose pulses have a temporal mean half-width (FWHM) in the femtosecond range, i.e. between a few and several hundred femtoseconds.

[0043] The wavelength of the therapy light can be around 1 micrometer or even in the UV range. Precise threshold setting is particularly important when using therapy radiation in the UV range, as UV light can quickly become toxic at too high a dose, for example, to the corneal endothelium. In such a wavelength range, the photodisruption or multiphoton absorption threshold should be reached during a treatment, but not exceeded.

[0044] The optical zone to be treated is the area of ​​the cornea in which refractive correction of the patient's eye is to be performed. This exact area is not used or treated by the test procedure presented here, and therefore is not modified or influenced.

[0045] Thus, the optical zone can be described as the optically effective zone of a refractive correction (both in case (a) and in case (b)). Purely by way of example, in the specific case of a SMILE operation, this optical zone can be understood as the outer region of the lenticule incision. The test shots outside the optical zone can thus also be the first shots of a clearance to be created in the corneal tissue or a transition zone (both clearance and transition can be assigned to the lenticule incision). Both the clearance and the transition zone lie outside the optically effective zone within which a refractive correction is performed.

[0046] The trajectory can preferably be determined by or during the treatment of the patient's eye and represent part of the treatment planning. The trajectory can preferably be circular or spiral, but can also have other shapes. Thus, the trajectory for the method presented here can represent the path of the processing beam path before the actual eye surgery. This path can be followed by a path of the processing beam path during the eye surgery, i.e., an ablation pattern or an irradiation pattern, in the subsequent eye surgery not described here.

[0047] During the procedure, the processing beam path is moved along the trajectory, and the femtosecond laser is switched on at at least one predetermined position along the trajectory, thus emitting laser radiation. The processing beam path then continues to move along the trajectory, irradiating the cornea, until the power emitted by the femtosecond laser is increased at one or more predetermined points in time. Thus, two, three, four, or more subregions along the trajectory are irradiated or exposed to laser pulses of different pulse energies. Other parameters of the femtosecond laser preferably remain approximately unchanged, such as the pulse repetition rate, the pulse duration, the wavelength (more precisely, the central wavelength and the emitted spectrum), as well as the divergence and convergence of the laser radiation.The parameters are approximately unchanged, since nonlinear effects (SPM, self-focusing, Ml, FWM, etc.) can occur, especially in a femtosecond laser, when the laser pulse energy is changed.

[0048] The laser therapy device can, in particular, have an existing camera or, more generally, a recording device for optically capturing the patient's eye to be treated (case (a)), or it can provide an additional camera. The camera can also provide appropriate illumination of the patient's eye. The illumination can be in the visible spectral range, preferably in the near infrared spectral range. The latter option can reduce or eliminate glare for the patient.

[0049] Accordingly, in case (b), the laser therapy device may already have one of the aforementioned measuring devices and utilize it. In some embodiments, such a measuring device will be provided additionally. Since the trajectory is predetermined and the time at which the femtosecond laser is switched on or the laser pulse energy of the femtosecond laser is increased is known, and furthermore, the patient's eye can be aspirated using a patient interface, the area of ​​the recorded camera image or the area of ​​the measurement result in which the cornea of ​​the patient's eye was irradiated is known. The treated areas along the trajectory therefore do not have to be located separately, but are known in advance.

[0050] To detect the area of ​​incipient blistering in the patient's cornea, known image processing methods can be used, such as detecting changing backscatter, detecting a gradual change in image content and / or image brightness and / or other image parameters, and / or object recognition. It is also conceivable that an artificial intelligence-based model obtained through machine learning could be used to detect incipient blistering in the cornea.

[0051] In case (b), ie in a treatment of the corneal tissue based on multiphoton absorption, the detection of the area of ​​incipient change of at least one corneal tissue parameter depends on the selected measurement method.

[0052] For example, when using a high-resolution OCT, a local measurement of a change in refractive index can form the basis of the measurement. If autofluorescence is measured, it can be stimulated by the treatment itself or by another light source in a measurement focus following the treatment focus. Optical coherence elastography can evaluate the elasticity and / or viscosity of the examined tissue (the cornea) based on OCT data. It is also conceivable that tissue vibrations can be stimulated by ultrasound, or that phase OCT and / or pulsed ultrasound pulses can be used to evaluate lens elasticity. Brioullin spectroscopy measures spatially resolved Brioullin scattering to determine viscoelastic parameters of the eye.

[0053] A model based on artificial intelligence can, in particular, be one created using machine learning. In machine learning, an artificial system or model can learn from a large number of examples and, using algorithms, build a statistical model that evaluates the input data, for example, in a weighting matrix, to determine output data. After training, such a model is tested or validated with test or validation data. An artificial intelligence model is not based on memorized examples, but rather recognizes patterns and regularities in the training data and can apply these recognized patterns or regularities to unknown data.In particular, image data showing the cornea of ​​the patient's eye, on which the beginning of blistering or the beginning of a change in at least one tissue parameter of the cornea is to be detected, can serve as input data for the model. Such input data is processed by the model during execution of the computer program product, for example, by a data processing device or the laser therapy device itself, in such a way that the output data is generated. The output data includes the detection of an area of ​​incipient blistering in the acquired images or the detection of an area of ​​incipient change in at least one tissue parameter of the cornea.

[0054] Based on this acquired knowledge, the artificial intelligence-based model can also react to input data that has not previously occurred.

[0055] The model based on artificial intelligence thus allows the complex process of detecting the beginning of blistering or the detection of an incipient change in at least one tissue parameter of the cornea to be modeled automatically and taking into account the input data.

[0056] To train the artificial intelligence-based model, data sets of corneal images or data sets of measurement results of changes in at least one corneal tissue parameter from different patient eyes can be used. These are preferably annotated, i.e., areas in which blistering is detectable or a change in at least one corneal tissue parameter is measurable are marked. This allows for supervised learning of the model. Furthermore, it is advantageous if the model is validated with validation data, which can be taken from the training data set before the model is learned and can correspond to approximately 10% to 30% of the data set.Corresponding images of patient eyes are input into the model, and areas of incipient blistering in the images or areas of incipient change in at least one tissue parameter of the cornea are identified by the model. These identified areas are compared with marked areas of blistering or incipient parameter change stored in the validation data. If the model successfully identifies the areas of incipient blistering or incipient parameter change, the model can be referred to as a trained model. Furthermore, it is possible for the artificial intelligence-based model to be further trained during operation using data generated during the model's operation. This can further increase the model's recognition accuracy.The artificial intelligence-based model used for this purpose can be a convolutional neural network (CNN), which allows for feature extraction. Subsequent object classification can be performed using linear support vector machine classifiers, for example. Training a CNN can be achieved using backpropagation, for example.

[0057] The input layer is capable of receiving image data or measurement data, which is then subjected to discrete convolution using a deconvolution matrix, the so-called filter kernel. A pooling layer can be provided downstream, which can significantly reduce the amount of data to be processed. The output is preferably provided via a fully connected layer. Since the primary goal of this application is to detect the onset of bubble formation or the onset of parameter changes, i.e., only one class of objects (air bubbles created by photodisruption or parameter changes created by multiphoton absorption) is detected, this last layer can have a single neuron. However, models with a different number of neurons are also conceivable.

[0058] When using such a model, it can be provided to pre-process the acquired images or measurement data in order, for example, to use an aperture describing the trajectory to input only those image data or image regions or measurement data that are located on the trajectory into the model. For example, with a circular or spiral trajectory, a (virtual) inverted ring aperture can be used to prepare the input data for input into the model in such a way that image regions or measurement data that are not located on the trajectory are not input into the model or are filled with a constant value, e.g. a pixel value corresponding to black. As soon as the area of ​​incipient blistering or the area of ​​incipient change in at least one tissue parameter of the cornea is identified, the laser pulse energy assigned to this area can be set as the disruption threshold or multiphoton absorption threshold.

[0059] It is particularly preferred if the trajectory describes a circular arc whose center approximately corresponds to the apex of a contact lens placed on the patient's eye to be treated. The preoperative measurement can thus be easily performed before the actual treatment by utilizing a trajectory or movement pattern of the laser therapy device already used for the treatment. This also allows the measurement to be integrated before the actual treatment in such a way that the actual treatment is not further delayed and can still be performed with the optimal laser parameters, i.e., the correct laser pulse energy.Avoiding a delay is particularly relevant because the phase in which the patient's eye is sucked onto the contact lens (also contact interface) is referred to as the critical phase, since a loss of contact during this phase can have negative effects on the treatment.

[0060] In one embodiment of the method, the incremental increase of the power emitted by the femtosecond laser can be carried out only in at least one circular arc and no laser power can be emitted on the remaining trajectory.

[0061] This has the advantage that the area within which the cornea is irradiated by the femtosecond laser for testing purposes can be minimized.

[0062] Particularly preferably, the processing beam path can traverse two or four or more circular arcs around the optical zone to be processed, along which the power emitted by the femtosecond laser is repeatedly incrementally increased.

[0063] Preferably, the circular arcs are rotationally symmetrical to the apex of the contact lens and, more preferably, always arranged in the same angular segment. Particularly preferably, the two, three, four, or more circular arcs are evenly distributed around the optical zone.

[0064] More preferably, the incremental increase in the power emitted by the femtosecond laser can occur in equidistant power steps. Furthermore, the different power steps or power levels can be identical in each circular arc. In particular, the power steps can be oriented to a predetermined threshold, which can be set by a technician, for example, during setup of a laser therapy device. This means that, purely by way of example and not by way of limitation, one laser pulse energy below the set threshold, one laser pulse energy corresponding to the set threshold, and one or two laser pulse energies above the set threshold can be defined as power steps. The step size between the individual power steps can be, for example and not by way of limitation, 10 nanojoules.

[0065] Furthermore, it is conceivable that the parameters of the femtosecond laser and / or an optical system through which the femtosecond laser passes and is focused and / or the parameters of the scanner element are selected such that each section of the constant energy trajectory of the femtosecond laser has dimensions of approximately 0.5 mm along the trajectory and approximately 0.2 mm transverse to the trajectory.

[0066] Such dimensions are small enough to allow rapid recovery of the irradiated corneal tissue, yet large enough to be detectable by a camera or measuring device. To enable better differentiation of the energy levels, the sub-areas of different energies, i.e., the sections of the constant-energy trajectory of the femtosecond laser, can be spaced apart by a distance of, for example, and not limited to, 0.2 mm. Thus, the different sections of the constant-energy trajectory of the femtosecond laser are not adjacent to one another and can be more easily distinguished, for example, through or during computer-assisted analysis of acquired images.

[0067] In a further advantageous embodiment, for case (a), the detection of the area of ​​incipient blistering can include evaluating the brightness progression along the trajectory. With appropriate illumination, it is conceivable that incipient blistering may become noticeable through a sudden increase in brightness, i.e., an increase in reflectivity (more precisely: a change in the scattering characteristics) of the observed area due to the incipient blistering. If, in particular, a decrease in brightness is observed along the trajectory after the increase in brightness, it can be assumed that blistering has occurred in this area.

[0068] In another embodiment, it is further advantageous if, in the case of locally spaced-apart sections of the trajectory with applied laser power and different determined disruption or multiphoton absorption thresholds, the highest of these disruption or multiphoton absorption thresholds is defined as the common disruption or multiphoton absorption threshold. The locally spaced-apart sections can be referred to as test regions.

[0069] Thus, deviations of the disruption or multiphoton absorption threshold in different areas of the cornea can be taken into account.

[0070] For example, if a different disruption or multiphoton absorption threshold is determined in four circular arcs, the highest of these different disruption or multiphoton absorption thresholds can be defined as the common disruption or multiphoton absorption threshold. This has the advantage that photodisruption or multiphoton absorption, such as laser-induced refractive index changes or laser-induced crosslinking, always occurs during the actual treatment of the patient's eye with the set laser pulse energy, and ideally, no follow-up treatment of the patient's eye is necessary.

[0071] The method can be further improved by the trajectory being composed of a plurality of tracks spaced apart from one another by a track pitch, wherein the image regions (or the regions of the measurement data) comprise at least two or at least ten or at least thirty or approximately fifty tracks.In this embodiment, the detection of the area of ​​incipient blistering (an incipient change in at least one tissue parameter) in the cornea of ​​the patient's eye can occur for at least two of the tracks located in an image area (in a region of the measurement data); the readout of the laser power used in the corresponding area of ​​incipient blistering (an incipient change in at least one tissue parameter) can occur for at least two of the tracks located in an image area; and an average value of the laser power used in the corresponding area of ​​incipient blistering (an incipient change in at least one tissue parameter) can be determined from at least two tracks. The determined average value can then be defined as the disruption or multiphoton absorption threshold.

[0072] For example, the trajectory can be meandering or spiral. With a spiral trajectory, the radius of the approximately circular path can decrease gradually and continuously. Two such paths lying next to each other can each be referred to as a track. These are separated by a track distance that can be, without restriction, in the range of a few micrometers (pm), for example, 4 micrometers. Assuming an assumed size of the area to be treated of approximately 8-9 millimeters, the differences in the radius of an individual circular path considered along this path, but also between neighboring paths, are in the thousandths range and are therefore negligible.

[0073] In the method, laser emission can thus occur for consecutive tracks along an angular range, so that several so-called bubble lines (when the disruption threshold is reached) or lines with an incipient change in at least one tissue parameter (when the multi-photon absorption threshold is reached) can be generated. The laser emission can occur in adjacent tracks, or every two tracks, or with a certain number of tracks without laser emission between two tracks with laser emission, e.g., every two, every five, or every ten tracks. Thus, a large number of tracks can be present in a predetermined image area. All or a subset of these tracks can be used to detect bubble formation (to detect an incipient change in at least one tissue parameter), so that the disruption or multi-photon absorption threshold can be calculated by averaging.This design of the method also allows the detection of strongly deviating disruption or multi-photon absorption threshold values, so-called outliers, to which a user can be alerted by the method.

[0074] The laser therapy device can, in particular, comprise a controller that controls and / or triggers the individual method steps and / or performs the evaluation. Particularly since the determination of the disruption or multiphoton absorption threshold is time-critical (since it occurs while the patient's eye is being suctioned through the contact interface), it is advantageous if this is performed directly by the laser therapy device itself or its controller or its computing device (or a data processing device).

[0075] Nevertheless, it is conceivable that the disruption or multi-photon absorption threshold is determined by a data processing device designed separately from the laser therapy device.

[0076] Parts of the method presented in this disclosure may represent a computer-implemented method for detecting incipient blistering (an incipient change in at least one tissue parameter) and may be executable on any data processing device.

[0077] For this purpose, the process can read input data representing an image or measurement data of an eye to be treated. Furthermore, in addition to the actual image data or measurement data, this input data can also contain location-dependent information that represents the locations of the eye to be treated—that is, the locations in the image data or measurement data where irradiation with a femtosecond laser was performed, and the power used. All of this information can be stored in the input data.

[0078] In a subsequent step, the image areas in which irradiation has occurred can be examined, and these areas can be checked for the onset of blistering (a beginning change in at least one tissue parameter), thus detecting the onset of blistering (a beginning change in at least one tissue parameter). If the onset of blistering (change) has been detected, the laser pulse energy or laser power assigned to this image area can be defined and provided as a disruption or multiphoton absorption threshold. The image area represents the area of ​​the patient's eye in which the blistering (the beginning change in at least one tissue parameter) was detected.

[0079] In a further embodiment of the method, in addition to incrementally increasing a power emitted by the femtosecond laser, at least one further parameter from the list of parameters comprising:

[0080] A spot spacing parameter, which represents a spacing between adjacent laser spots; A spot mode parameter, which represents a laser emission as a multi-spot or as a single spot; and

[0081] A beam mode parameter, which represents the beam shape of the laser beam, can be varied without interrupting the movement of the processing beam path along the trajectory, wherein the threshold range along the trajectory in which the disruption threshold or the multi-photon absorption threshold was reached can additionally be detected as a function of at least one further parameter.

[0082] A threshold value to be determined can depend on the distance between neighboring spots. Thus, it can be planned to conduct test shots with different spot spacings. In this case, the spot spacings are, in particular, those used in scan patterns. The spot spacing parameter can represent these distances between neighboring spots.

[0083] Constant spot spacing is conceivable for the entire treatment, or, purely as an example and not as a limitation, constant spot spacing for the surface incisions and smaller spot spacing for an access incision. The spot spacing can range from approximately 1.0 μm to approximately 4.5 μm. Any value between 1.0 μm and 4.5 μm is configurable and conceivable for the spot spacing.

[0084] The spot mode parameter, for example, includes a multispot mode: Since the threshold value can depend on the spatial AND temporal distance between the neighboring spots, it is conceivable to apply part (or the entire) test pattern in multispot mode.

[0085] In a planned treatment, it is possible to cut the surface cuts in multi-spot mode and one edge cut in single-spot mode. Alternatively, an exclusive multi-spot operation is also conceivable.

[0086] Multi-spot operation refers to laser irradiation at multiple foci. The multi-spot can thus consist of two, three, four, or any number of foci. In single-spot operation, the therapeutic radiation is focused on a single focus.

[0087] The beam mode parameter describes the beam shape in which the therapeutic radiation is delivered to the tissue. The beam shape refers to the lateral intensity distribution perpendicular to the propagation direction. Common beam shapes are Gaussian, Bessel, or vortex. Since the threshold can depend on the shape of the spot, this is also taken into account. When selecting the test pattern, it is conceivable that a laser can switch between multiple modes within a pattern. In such a setup, the thresholds for both modes in the test pattern are preferably determined beforehand. However, it is conceivable that only vortex modes are used.

[0088] The aspects of the present invention will be explained in more detail below with reference to the accompanying drawings. The drawings show possible exemplary embodiments of the present invention purely by way of example, whereby the described features can be combined with one another or omitted as desired. Identical features or features with the same function are further identified by the same reference numerals. Repetitive descriptions of features are omitted, so that explanations of features described in previous figures can also be applied to other figures, unless differences are explicitly pointed out.

[0089] They show:

[0090] Fig. 1 shows a schematic flow of the method presented in this disclosure;

[0091] Fig. 2 shows a schematically illustrated laser therapy device;

[0092] Fig. 3 is a schematic representation of a patient’s eye;

[0093] Fig. 4 different schematically represented forms of the trajectory;

[0094] Fig. 5 schematically shows a possible process for detecting incipient bubble formation; and

[0095] Fig. 6 is a schematic representation of a data processing device.

[0096] The figures are intended to describe, purely schematically and non-limitingly, methods and devices relating to the treatment of an eye based on photodisruption. In these methods and devices, blistering occurs in the cornea of ​​the eye, which, more precisely, first appears at the disruption threshold and cannot be detected at lower energies.

[0097] However, the invention also encompasses further embodiments of methods and devices based on multiphoton absorption, for example, two-photon absorption. In these ocular procedures, no blistering occurs, but rather a change in at least one tissue parameter of the cornea, for example, a change in the refractive index generated by the irradiated laser, or a crosslinking of fibers in the corneal tissue.

[0098] The corresponding statements regarding photodisruption-based methods and devices can be transferred to the (not shown) embodiments of the methods and devices based on multiphoton absorption. Accordingly, the (not shown) embodiments of the device can comprise the (previously mentioned) necessary (measuring) devices instead of a camera for detecting the change in at least one tissue parameter of the cornea.

[0099] Figure 1 shows the schematic sequence of the method presented in this disclosure. Reference is also made to Figures 2 and 3, which schematically show the laser therapy device 10 and an eye 9, respectively.

[0100] In a first method step S1, a scanner element 1 is controlled such that a processing beam path 3 of a femtosecond laser 5 moves along a trajectory 11 outside an optical zone 7 of the eye 9 to be treated.

[0101] In a second process step S2, a pulse power P emitted by the femtosecond laser 5 is incrementally increased. During this process, a movement of the processing beam path 3 along the trajectory 11 is not interrupted.

[0102] This results in subregions 13 along the trajectory 11 being subjected to different pulse powers P, i.e., irradiated or illuminated. By synchronizing the movement of the processing beam path 3 along the trajectory 11 with the incremental increase in the pulse power P, the position of the subregions 13-1, 13-2, 13-3, and 13-4 on the eye 9 is fixed. In other embodiments, a different number of subregions 13 may be provided. The number four selected here is purely exemplary.

[0103] Depending on the number of stages of incremental increase of the pulse power P, a plurality of sub-areas 13 can thus be defined. The four sub-areas 13 shown in Fig. 3 can be combined into a test area 15. The test areas 15 can also be referred to as locally spaced sections 15.

[0104] Furthermore, several test areas 15 can be generated in the course of the presented method. In the example shown in Fig. 3, these are four test areas 15, which are arranged at equal angular intervals, ie, equidistantly with two opposing test areas 15 outside the optical zone 7 on or in the cornea 17 of the eye 9 to be treated.

[0105] In other embodiments (not shown), a different number of test areas 15 and / or a different number of sub-areas 13 and / or a different orientation or arrangement of these areas 13, 15 may be provided.

[0106] With reference to Figs. 1 and 2, in a third method step S3, an image 21 of the eye 9 to be treated is recorded. This can be done using a recording device 20, such as a camera 20a. The camera 20a can already be provided in the laser therapy device 10 or can be provided additionally. Purely by way of example, the camera 20a is arranged to the side of a laser output 43 on an application arm 41. The image 21 is transmitted purely by way of example to a controller 39, which can include a data processing device 61.

[0107] In the subsequent process step S4, those image areas are examined that represent areas of the eye 9 to be treated in which a laser emission has occurred, i.e., in which the femtosecond laser 5 has irradiated the cornea 17. These image areas correspond to the subareas 13 of the respective test area 15.

[0108] In this recorded image 21 (see also Fig. 5), the eye 9, including the iris 25 and sclera 27, as well as the eyelids 29, can be visible. Due to the fact that the eye 9 can be suctioned onto the laser therapy device 10 by means of a contact lens 31 in order to determine a disruption threshold 37, and due to the data from the scanner element 1, it is known in which areas of the image 21 irradiation by the femtosecond laser 5 took place, namely in the defined partial areas 13. The image 21 shown here is used merely for better explanation. Since the determination of the disruption threshold 37 occurs after suction, in an image 21 (not shown) taken after suction, only the cornea and the iris 25 in a central area of, but not limited to, approximately 8-9 mm can be visible and / or recorded by the camera.The size of this central area may depend on the size of the contact lens used. In some embodiments, this central area may be larger, allowing the sclera 27 to be at least partially visible in image 21.

[0109] In a subsequent method step S5, the partial area 13 in which the incipient blistering 33 is visible in the cornea 17 of the eye 9 is detected. The incipient blistering 33 is shown in Fig. 3. Here, the test area 15 is visible with four partial areas 13, wherein the partial areas 13 differ in that they were irradiated with different pulse powers P.

[0110] Finally, in a method step S6, the pulse power P used in the area of ​​incipient bubble formation 33 is defined as the disruption threshold value 37.

[0111] With reference to Fig. 2, the laser therapy device 10 will be briefly discussed. This device comprises a femtosecond laser 5, a control unit or controller 39, an application arm 41 (which can be fixed or movable), and a laser output 43.

[0112] Furthermore, a contact interface 45 in the form of a contact lens 31 is shown, which is attached to the laser output 43 and can establish contact with the eye 9 by means of suction. Also shown is a schematically illustrated scanner element 1, whereby the number of individual elements and / or the position of the scanner element 1 in the laser therapy device 10 can vary in other embodiments. The scanner element 1 allows movement of the processing beam path 3.

[0113] Referring to Fig. 3, a patient's eye 9 is schematically depicted. An apex 47 of the contact interface 45 or contact lens 31 (not shown in Fig. 3, see Fig. 2) is schematically represented by a cross. The apex 47 represents a center point 49 of a circle (not shown) along which the trajectory 11 runs.

[0114] Four test areas 15 are shown along the trajectory 11, each comprising four sub-areas 13. For simplified representation, the sub-areas 13 are marked by a rectangle. A radial width 13a of the sub-areas 13 is determined at least by the focus size of the femtosecond laser 5, whereas a tangential extension 13b results from a speed of the illumination beam path 3 and the duration of the laser emission of the femtosecond laser 5.

[0115] Thus, a radial width 13a of a partial area 13 can correspond to the focus size of the femtosecond laser 5, but a radial width 13a can be selected larger than the focus size for reasons of simplified detection.

[0116] If the pulse energy P emitted in a sub-area 13 is below a threshold value for disruption, no bubbles 34 form in this sub-area 13. This is shown purely by way of example in Fig. 3 in sub-areas 13-1 and 13-2. Purely by way of example, the processing beam path 3 traverses the trajectory 11 counterclockwise. This determination is arbitrary. Bubble formation 33 can be seen in sub-areas 13-3 and 13-4 of each test area 15.

[0117] Thus, the respective subregions 13-3 represent the subregion 13 in which incipient bubble formation 33, i.e., bubbles 34, is / are detectable. The pulse energy P applied in this subregion 13-3 is thus defined as the disruption threshold 37. An enlargement 14 further shows that individual bubbles 34 can form even before the disruption threshold 37 is reached. This is shown for subregion 13-2. For the sake of clarity, not all bubbles 34 are provided with a reference symbol.

[0118] The bubbles 34 are generated along a bubble line 35, which can also be referred to as a track 35. Since adjacent tracks 35 can be generated along a trajectory 11 (as shown below in Fig. 4), a further scanning parameter is a track spacing 36 between individual adjacent tracks 35. The tracks 35, as well as the track spacing 36, can also be defined for a meandering trajectory 11a. This is schematically illustrated in an enlargement in Fig. 4. If, for detection reasons, a radial width 13a of (non-limiting) 0.2 mm is selected, then approximately 50 tracks 35 are located in each sub-area, assuming a (non-limiting) track spacing 36 of approximately 4 pm.

[0119] This also makes it possible to calculate the average across multiple tracks 35 along which the femtosecond laser 5 emitted laser radiation at an identical angular position. The laser emission can occur along adjacent tracks 35 or all 2, 5, or 10 tracks 35.

[0120] Should irregularities or varying parameters of the cornea 17 along the trajectory 11 result in the partial area 13-3 in one test area 15 showing the beginning of blistering, but in another test area 15 a partial area 13-4, whereby a higher pulse energy P was applied in the partial area 13-4 than in the partial area 13-3, the pulse energy P applied in the partial area 13-4 is defined as the disruption threshold 37.

[0121] In Fig. 3, the optical zone 7 to be processed and the trajectory 11, which lies outside this optical zone 7 to be processed, are also shown.

[0122] Fig. 4 schematically illustrates various forms of the trajectory 11. In particular, the distances between individual regions of the two shown forms of the trajectory 11 are not drawn to scale. Firstly, there is a meandering trajectory 11a, the individual meanders 12 of which extend partly outside the optical zone 7 to be processed and partly within it. With such a trajectory 11a, the femtosecond laser 5 can be switched on, for example, near or at the reversal points 51, and its pulse energy P can be incrementally increased. In such a case, the test regions 15 and their subregions 13 are not in the form of a circular arc segment, but rather in the form of the meandering trajectory 11a, ideally in the rectilinear region of the meandering trajectory 11a.

[0123] Furthermore, Fig. 4 schematically illustrates a spiral trajectory 11b, wherein the trajectory 11 shown in Fig. 3 may be a part of such a spiral trajectory 11b, namely the outermost approximately annular section 53 of such a spiral trajectory 11b. For reasons of clarity, a track spacing 36 is shown that is not to scale and is too large (see the explanations for Fig. 3).

[0124] In addition to the possible forms of a trajectory 11 shown in Fig. 4, further trajectories 11 are conceivable.

[0125] Fig. 5 shows a schematic diagram of a possible process for detecting the beginning of bubble formation 33.

[0126] Shown schematically is the image 21 of an eye 9, which was recorded after the eye 9 was suctioned onto the contact lens 31. According to the explanations for Fig. 2, it should be noted that, since the determination of the disruption threshold 37 occurs after suction, in an image 21 (not shown) recorded after suction, only the cornea and the iris 25 in a central area of, but not limited to, approximately 8-9 mm may be visible and / or recorded by the camera. The eyelids are not visible when the eye 9 is suctioned onto the contact lens. The image of the eye shown can nevertheless be used for explanation.

[0127] Furthermore, an annular aperture 57 is shown, the center point 59 of which is aligned with the apex 47 of the contact lens 31. Such an annular aperture 57 can reduce the relevant image data for detecting incipient bubble formation 33, since after its application, only image data located on the trajectory 11 remains.

[0128] Due to the synchronization of the femtosecond laser 5 and the movement of the scanner element 1, the position of the test areas 15 as well as the sub-areas 13 of each test area 15 is known. Locating the test areas 15 or their sub-areas 13 is not necessary.

[0129] This is followed by the detection of incipient bubble formation 33 for the individual sub-areas 13 of each test area 15, i.e., purely by way of example, an examination of the scattering 16 of illumination light (not shown). The intensity of scattered light 16 increases with the incipient bubble formation 33. This situation is schematically illustrated for sub-area 13-3 for all four test areas 15 by increased scattering 16.

[0130] It is conceivable that a threshold value 18 of the scatter 16 must be exceeded in order to define the respective sub-area 13 (here, sub-area 13-3) as the area of ​​incipient blistering 33. The scatter 15 can differ quantitatively in all test areas 15.

[0131] Fig. 6 schematically illustrates a data processing device 61. This device comprises, purely by way of example, a model 63 based on artificial intelligence, which can be stored, for example, in a memory unit 65. In other embodiments, the memory unit 65 can store only a computer program product 71 that is not based on artificial intelligence and executes the method described herein when started on the data processing device 61.

[0132] The data processing device 61 has a data input 67, via which, for example, the image 21 and laser data 69 correlated with it can be input. The laser data 69 can assign a pulse power P emitted by the femtosecond laser 5 in a respective sub-area 13 of each test area 15 to a coordinate in the image 21. The data processing device 61 executes a previously written method and determines the disruption threshold 37 from the input data 21, 69. The disruption threshold 37 can be output at a data output 68.

[0133] The artificial intelligence-based model 63 or the computer program product 71 can also be stored on a remote PC 73 or in a cloud 75 and can be requested and received by the data processing device 61 from at least one of these sources 73, 75 in the form of a data signal 77.

[0134] It is also conceivable for the data processing device 61 to load the computer program product 71 from a non-volatile storage medium 79 on which the computer program product 71 is stored. The non-volatile storage medium 79 can be connectable to the data processing device 61 or readable by it and can be an optical storage medium 79a, a magnetic storage medium 79b, or a storage medium based on flash memory 79c.

[0135] List of reference symbols

[0136] 1 scanner element

[0137] 3 Processing beam path

[0138] 5 femtosecond lasers

[0139] 7 optical zone to be processed

[0140] 9 eye to be treated

[0141] 10 laser therapy device

[0142] 11 T rajectory

[0143] 11a meandering t rajectory

[0144] 11b spiral trajectory

[0145] 12 meanders

[0146] 13 sub-area

[0147] 13-1 Sub-area

[0148] 13-2 Sub-area

[0149] 13-3 Sub-area

[0150] 13-4 Sub-area

[0151] 13a radial width of the subareas

[0152] 13b tangential extension of the sub-areas

[0153] 14 Magnification

[0154] 15 Test area

[0155] 16 Scattering

[0156] 18 Threshold of scatter

[0157] 17 Cornea

[0158] 20 Recording device

[0159] 20a Camera 20a

[0160] 21 Image

[0161] 25 Iris

[0162] 27 sclera

[0163] 29 Eyelid

[0164] 31 contact glass

[0165] 33 Area of ​​incipient blistering

[0166] 34 Bladder

[0167] 35 bubble line / track

[0168] 36 T rack distance 37 Disruption threshold

[0169] 39 controllers

[0170] 41 Application arm

[0171] 43 Laser output

[0172] 45 Contact interface

[0173] 47 Apex

[0174] 49 Center

[0175] 51 Turning point

[0176] 53 annular section

[0177] 57 annular aperture

[0178] 59 Center

[0179] 61 Data processing device

[0180] 63 artificial intelligence-based model

[0181] 65 storage unit

[0182] 67 Data input

[0183] 68 Data output

[0184] 69 laser data

[0185] 71 Computer program product

[0186] 73 Remote PC

[0187] 75 Cloud

[0188] 77 data signal

[0189] 79 non-volatile storage medium

[0190] 79a optical storage medium

[0191] 79b magnetic storage medium

[0192] 79c storage medium based on flash memory

[0193] P Pulse power

[0194] 51 first procedural step

[0195] 52 second procedural step

[0196] 53 third procedural step

[0197] 54 fourth procedural step

[0198] 55 fifth procedural step

[0199] 56 sixth procedural step

Claims

1. A method for preoperatively determining a disruption threshold value (37) or a multiphoton absorption threshold value of a cornea (17) of a patient's eye (9) to be treated with a femtosecond laser (5), comprising - controlling a scanner element (1) such that a processing beam path (3) of the femtosecond laser (5) moves along a trajectory (11) outside an optical zone (7) of the eye (9) to be treated; incrementally increasing a power (P) emitted by the femtosecond laser (5) without interrupting the movement of the processing beam path (3) along the trajectory (11); Carrying out at least one examination step for detecting a threshold range along the trajectory (11) in which the disruption threshold (37) or the multi-photon absorption threshold has been reached; and - Reading out the laser power (P) used in the threshold range and defining this laser power (P) as a disruption threshold (37) or as a multi-photon absorption threshold.

2. The method according to claim 1, wherein in case (a) of a procedure based on photodisruption in the cornea, the at least one examination step comprises: - taking an image (21) of the eye (9) to be treated; Checking those image areas (13) which represent areas of the eye (9) to be treated in which a laser emission has taken place; Detection of the area of incipient blistering (33) in the cornea (17) of the patient’s eye (9); and - reading out the laser power (P) used in the threshold range, ie in the corresponding range of incipient blistering (33), and wherein in case (b) of an intervention based on multi-photon absorption in the cornea, the at least one examination step comprises: Carrying out at least one measurement method from the list of measurement methods comprising: o High-resolution optical coherence tomography; o Autofluorescence; o Optical coherence elastography; o Brioullin spectroscopy; or o Ultrasound imaging, Checking those image areas that represent areas of the eye to be treated in which laser emission has occurred; Detection of the area of incipient tissue modification in the cornea of the patient's eye, i.e. determination of the area in which a change in at least one tissue parameter of the cornea is detected; and - Reading out the laser power used in the corresponding area of onset of change in at least one tissue parameter of the cornea.

3. Method according to claim 1 or 2, wherein the trajectory (11) describes a circular arc whose center point (49) approximately corresponds to an apex (47) of a contact lens (31) which is placed on the patient's eye (9) to be treated.

4. Method according to one of claims 1 to 3, wherein the incremental increase of the power (P) emitted by the femtosecond laser (5) is carried out only in at least one circular arc and no laser power (P) is emitted on the remaining trajectory (11).

5. Method according to claim 4, wherein the processing beam path (3) traverses two or four or more circular arcs around the optical zone (7) to be processed, along which the power (P) emitted by the femtosecond laser (5) is repeatedly incrementally increased.

6. The method according to any one of claims 1 to 5, wherein the incremental increase of the power (P) emitted by the femtosecond laser (5) takes place in equidistant power steps.

7. Method according to one of claims 1 to 6, wherein the parameters of the femtosecond laser (5) and / or the parameters of an optical system traversed by the femtosecond laser and / or the parameters of the scanner element (1) are selected such that each section of the trajectory of constant energy of the femtosecond laser (5) has dimensions (13a, 13b) of approximately 0.5 mm along the trajectory (11) and approximately 0.2 mm transverse to the trajectory (11).

8. Method according to one of claims 2 to 7, wherein in case (a) the detection of the region (13) of incipient bubble formation (33) comprises an evaluation of the brightness profile along the trajectory (11).

9. The method according to one of claims 1 to 8, wherein furthermore, in the case of locally spaced-apart sections (15) of the trajectory (11) with applied laser power (P) and in these different disruption threshold values (37) or multi-photon absorption threshold values determined, the highest of these disruption threshold values (37) or multi-photon absorption threshold values is defined as a common disruption threshold value (37) or as a common multi-photon absorption threshold value.

10. The method according to any one of claims 1 to 9, wherein the trajectory 11 is composed of a plurality of tracks 35 spaced apart from one another by a track spacing 36, wherein the image areas 13 (for case (b) the areas of the measurement data) comprise at least two and / or at least ten and / or at least thirty and / or approximately fifty tracks, and wherein The detection of the area of incipient blistering (33) (for case (b) the area of an incipient change in at least one tissue parameter) in the cornea (17) of the patient's eye (9) is carried out for at least two of the tracks 35 located in an image area 13; The reading of the laser power (P) used in the corresponding area of incipient blistering (33) (for case (b) in the area of an incipient change in at least one tissue parameter) is carried out for at least two of the tracks 35 located in an image area 13; and An average value of the laser power (P) which is determined in the corresponding area of incipient blistering (33) (for case (b) in the area of an incipient change in at least one tissue parameter) from at least two tracks (35) and the determined average value is defined as the disruption threshold value (37) (for case (b) as the multi-photon absorption threshold value).

11. The method according to any one of claims 1 to 10, wherein in addition to incrementally increasing a power (P) emitted by the femtosecond laser (5), at least one further parameter from the list of parameters comprising: A spot spacing parameter, which represents a distance between adjacent laser spots; A spot mode parameter that allows laser emission as multi-spot or single- Spot represents; and A beam mode parameter that represents the beam shape of the laser beam without interrupting the movement of the processing beam path (3) along the trajectory (11), and wherein the threshold range along the trajectory (11) in which the disruption threshold (37) or the multi-photon absorption threshold was reached is additionally detected as a function of the at least one further parameter.

12. A computer program product (71) comprising instructions which, when executed on or by a laser therapy device (10), cause the device (10) to perform a method according to any one of claims 1 to 11.

13. Data signal (77) which transmits the computer program product (71) according to claim 12.

14. Laser therapy device (10) which is designed to carry out a method according to one of claims 1 to 11 and / or to execute a computer program product (71) according to claim 12 and / or to receive a data signal (77) according to claim 13.

15. A computer-readable non-volatile storage medium (79) on which a computer program product (71) according to claim 12 is stored.

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