Methods and devices for holding, positioning and controlling the temperature of a corneal implant

Abstract

The invention relates to methods and devices for holding, positioning and controlling the temperature of a corneal implant or corneal transplant made of human donor tissue or artificial tissue. The invention relates to a corneal implant holder (1), methods for controlling the temperature of an implant or transplant, and methods for processing tissue at the dew point or frozen tissue.

Description

[0001] Methods and devices for holding, positioning and temperature control of a corneal implant

[0002] The invention relates to methods and devices for holding, positioning, and temperature-controlling a corneal implant made from human donor tissue or artificial tissue. The invention thus relates to a corneal implant holder and methods for temperature-controlling an implant or graft. This corneal implant holder can be used before, during, and after tissue reshaping by means of a processing device, for example, a processing laser.

[0003] A tissue sample from human donor cornea or artificial tissue can be transformed from a known initial shape into a known target shape using a processing device, for example, a processing laser. The target shape should be suitable for inducing therapeutic and / or refractive changes to the overall corneal geometry after implantation into a human cornea. For precisely controlled tissue ablation, critical temperatures must not be exceeded, depending on the tissue type. This could include, for example, significantly exceeding the dew point or a melting point. Furthermore, for precisely controlled processing, such as tissue ablation or sectioning, the hydration state and, in the case of frozen samples, the degree of freezing must be monitored.Furthermore, precise processing requires the exact positioning and alignment of a tissue sample relative to the processing device and later relative to the patient's eye.

[0004] The invention solves the problem of storing a fabric in such a way that it suffers no damage, or only acceptably minor damage, during processing. This includes maintaining the necessary temperature limits during processing.

[0005] These temperature limits are maintained by the corneal implant holder because, according to the invention, it has a temperature control unit. The temperature control unit is designed to regulate the temperature of a tissue holder within the corneal implant holder, i.e., to adjust, maintain, lower, or raise its temperature. "Regulating" here refers to any type of temperature adjustment.

[0006] The corneal implant holder comprises at least one tissue holder for receiving a corneal implant or corneal graft, a tissue holder base and at least one temperature control unit, wherein the at least one temperature control unit is arranged in the tissue holder base and is configured to temperature control the at least one tissue holder.

[0007] The corneal implant holder can be further modified and improved by additional optional features. These additional features can be combined and / or omitted as desired.

[0008] Thus, one design of the cornea implant holder can include a cold reservoir and optionally a curved contact surface.

[0009] In other words, the temperature unit of the cornea implant holder can include at least one body serving as a cold reservoir (also: passive cooling element) or be a body serving as a cold reservoir.

[0010] Optionally or additionally, the temperature unit of the cornea implant holder may include at least one active cooling element or be an active cooling element.

[0011] Another purpose of the cornea implant holder can be to maintain information about tissue position and orientation before, during, and after processing. In this configuration, the cornea implant holder can therefore be used for temperature control as well as for positioning and registration.

[0012] As mentioned above, one form of temperature control can be achieved passively using a cold reservoir.

[0013] If the corneal implant holder uses a passive cooling element, the cooling element can comprise or consist of a material with a specific heat capacity greater than or equal to approximately 300 joules per kilogram per kelvin (J / (kg K)). Alternatively or optionally, the passive cooling element can be accommodated in a correspondingly designed pocket or recess of the tissue holder, with the accommodation occurring without any mechanical play. Optionally or alternatively, the height of the corneal implant holder can be essentially determined by the height of the passive cooling element.

[0014] Such a cold reservoir can, purely by way of example and without limitation, consist of or comprise a copper body with good thermal conductivity. Where a copper body is mentioned or described in this disclosure, this refers to any body that serves as a cold reservoir and is made of any material. During processing, the temperatures that may arise, particularly in the remaining, i.e., unprocessed, reshaped fabric immediately during and after processing by a laser pulse, must remain below a permissible maximum temperature, and at least local melting of frozen fabric material or drying out of fabric material processed in an unfrozen state at the dew point must be prevented.

[0015] In the case of frozen tissue material, moisture from the ambient air must not condense and freeze on the tissue surface, as an ice layer inherently has different processing properties (ablation or cutting properties) and impairs the targeted reshaping of the tissue. Simultaneously, the ablation products of a laser pulse (which are purely illustrative examples) must be efficiently and promptly removed from the space between the tissue and the laser exit point, typically in the immediate vicinity above the tissue, before the arrival of the next pulse. The ablation products, which rise above the sample in the form of a plume, can also contain water, which can lead to ice formation on a frozen tissue surface, thus preventing precise processing of the implant. According to the invention, such an influence of released water is to be minimized or, ideally, completely eliminated.

[0016] The passively cooled corneal implant holder described above can, for example, be tempered in a refrigerator or freezer and then functions as a passively cooled holder during application.

[0017] The invention can also prevent icing of frozen sample material.

[0018] For processing to be effective, it is important that this only takes place after the fabric temperature has reached a target range (also depending, for example, on the humidity) and after freezing. The invention can also enable synchronization between temperature control and fabric processing.

[0019] In order to achieve the intended refractive and / or therapeutic effect, the tissue must have the correct shape after processing.

[0020] In one possible implementation, a processing program ("pattern") for a scanning spot laser (a modern medical excimer laser being used as a purely illustrative example, without limitation) with precisely defined, spatially and temporally ordered processing pulses is applied to the source tissue. For this to work, the tissue must be positioned correctly relative to the processing laser so that the pre-calculated positions of the processing pulses are achieved relative to the tissue shape. This is achieved through a registration process.

[0021] Furthermore, after processing, the processed tissue must be able to be positioned at the predetermined location and in the predetermined orientation within the target eye. Markings are required for this purpose. This disclosure further describes a corneal implant holder that additionally includes aids for marking the tissue relative to the holder, as well as markings on the holder for positioning relative to the processing device, e.g., a processing laser, and enables the precise marking of the tissue at predetermined positions after processing.

[0022] It is known to adjust the temperature of a tissue sample for processing, in particular to cool the sample below freezing or to the dew point. It is also known to temperature-control a sample holder accordingly.

[0023] The solution presented here goes further by eliminating the problem of heating during processing at the dew point, either through the optionally applied supply air to the processing device or through the laser pulses themselves, thus ensuring the tissue remains at the dew point even during processing. In the case of processing below the freezing point, the solution presented here prevents the potential freezing of a frozen sample by means of the optional controlled supply of dry air, which is essential for precise processing. Methods for detecting freezing are also presented.

[0024] It is well known to mark tissue, particularly during surgery, using a surgical aid. Special felt-tip pens are commercially available in many variations. The methods and corneal implant holder presented here go further, as they provide a fixed reference to the tissue holder, which in turn, via optional alignment structures, provides a fixed reference to the processing device, such as a laser (registration). These inventive tissue marking methods enable even inexperienced users to achieve precise marking.

[0025] Mounts for fabric holding, positioning, temperature control, and environmental condition monitoring are presented, and their features are described. A distinction is first made between two application scenarios: one involving fabric that should not dry out during processing (dew point), and the other involving fabric that should be processed in a frozen state (frozen). Design versions of the mount are conceivable that support both scenarios equally, as well as versions for only one of these scenarios.

[0026] The mounts or cornea implant holders can be used in particular for storage during the transport of an implant, as they can, for example, provide a constant temperature that is compatible and necessary for the implant.

[0027] Definitions of terms

[0028] In this context, "mount" refers to all the elements that are connected to the user and laser system for temperature control, support, positioning, and interfacing. A mount can also be called a corneal implant holder.

[0029] The icing of a sample refers to the adsorption and successive freezing of water from the ambient air onto the surface of a tissue lamella that has a surface temperature below the freezing point of water. In contrast, freezing refers to the phase transition between the soft and solid phases of a tissue or hydrogel.

[0030] A temperature ramp refers to a time-varying temperature, where the temperature changes continuously between the initial and final values ​​of the ramp. In the simplest case, a temperature ramp is linear, meaning it exhibits a constant change in temperature, but non-linear functions are also conceivable as ramps (e.g., logarithmic ramps with initially high and continuously decreasing cooling rates).

[0031] Supply air refers to the airflow directed by a processing laser into the working plane, originally introduced to remove ablation products from the processing zone. This supply air is typically supplemented by devices and methods for exhaust air extraction.

[0032] Dry air refers to process air according to the invention (controlled by the mount presented here) that flows around a fabric to be processed.

[0033] The cornea implant holder can therefore include at least one device for providing and / or monitoring and / or controlling or adjusting process parameters of dry air surrounding tissue on the tissue holder or of an inert protective gas surrounding tissue on the tissue holder.

[0034] For temperature control: If the cornea implant holder uses an active cooling element, the active cooling element can comprise at least one heat exchanger and / or at least one Peltier element and / or at least one refrigeration machine in any combination and / or number.

[0035] Alternatively or additionally, the active cooling element can include a temperature sensor designed to determine the temperature of the tissue holder and to provide a temperature value representing this determined temperature.

[0036] Alternatively or additionally, the active cooling element can include or be connected to a temperature controller, wherein the temperature controller is designed to regulate the temperature of the tissue holder to the predetermined temperature by comparing a measured temperature of the tissue holder with a predetermined temperature of the tissue holder.

[0037] Alternatively or additionally, the active cooling element can include at least one humidity sensor or be connectable to at least one humidity sensor, wherein the humidity sensor is designed to determine the water content of the air or gas or gas mixture arranged around a fabric resting on the fabric holder and to provide a humidity value representing the moisture content.

[0038] Alternatively or additionally, the active cooling element can include at least one control system or be connectable to at least one control system, wherein the control system is designed to act as an interface for human-machine interaction and to provide appropriate input and output means.

[0039] Tissue holder: A holder for the tissue to be processed. The tissue is in direct mechanical contact with the tissue holder and is preferably held in place by gravity and adhesion forces between the tissue and the material of the tissue holder. The tissue holder is advantageously a sterile, single-use item or sterilizable (steam sterilization). The holder is also preferably biocompatible and has a very high thermal transmittance coefficient. Furthermore, the holder should be unaffected, or only minimally affected, by the radiation of the processing laser, i.e., damaged or abraded. Any abraded material from the holder should preferably also be biocompatible.

[0040] Possible materials that possess these properties include, in particular, titanium alloys, silicon carbide, stainless steel, silicon nitride, aluminum oxide, and aluminum nitide. A material that meets the normative requirements for implants is preferred, and preferably the material is certified as an implant material.

[0041] In another embodiment, calcium fluoride (CaF₂; also CaF₂ in this disclosure) can be used as a material for storing the graft or implant. CaF₂ also exhibits good thermal conductivity and inertness.

[0042] The corneal implant holder, and in particular the tissue holder of the corneal implant holder, can therefore comprise or consist of at least one material from the above-mentioned list of materials.

[0043] Furthermore, a contact surface with the implant or graft can have a lens, for example made of CaF₂ with a suitable radius of curvature. This enables optimal attachment and placement of the implant or graft while maintaining good thermal conductivity.

[0044] The tissue holder may also include a plastic frame. Optionally, the tissue holder has a skirt that surrounds the CaF lens in such a way that fluid cannot freely drain from the edge of the graft or implant. This can ensure continuous moistening of the implant or graft.

[0045] The copper body can be received in a pocket or recess of the fabric holder that is designed complementarily to the copper body. In particular, the fabric holder and / or the fabric holder base can receive the copper body without play, preferably in an interference fit, so that heat conduction from the fabric holder to the copper body can occur without insulating air gaps.

[0046] In this case, the overall height of the corneal implant holder can be essentially determined by the height of the copper body. The copper body can be designed as a cube, purely as an example; however, other shapes, such as a prism with a versatile base and top surface, are advantageously conceivable to provide an effective surface for heat exchange between the heat sink and the tissue holder base.

[0047] Tissue Holder Base: The tissue holder (abbreviated: GH) itself can be mechanically and thermally connected to the tissue holder base. The tissue holder base does not come into contact with the tissue and, in this configuration, does not need to be biocompatible or sterilizable. Preferably, however, the tissue holder base is made of a material suitable for wipe disinfection. Not shown, but optionally available, is at least one additional cover element for the tissue holder base. This allows the two functions (heat transfer and infection protection) to be separated. This cover element can additionally fulfill at least one of the following tasks: positioning the holder on the holder base, fixing the holder on the holder base, easy cleaning / suitability for wipe disinfection. This element can optionally be designed as a sterile, single-use item or be sterilizable.

[0048] Tissue holder and tissue holder base can also be a single unit (the separation between tissue holder and tissue holder base is optional, but simplifies compliance with sterility requirements). The GH base and cooler can also be a single unit.

[0049] For sterility reasons, the thermal contact between GH and GH base is achieved either through optimal mechanical contact (polishing, lapping, superpolishing), i.e., preventing air from entering between the contact surfaces, or through the use of a sterile contact medium. This can also include liquid thermal contact media.

[0050] These statements regarding thermal contact can also be applied to the previously described design of the cornea implant holder with passive cooling (with a cooling or cold reservoir, for example in the form of a copper body).

[0051] In other words, the corneal implant holder can be designed such that the at least one passive and / or active cooling element has a first contact surface which, to improve thermal conductivity and / or heat transfer between the cooling element and the tissue holder, indirectly contacts a second contact surface of the tissue holder, facing away from a support surface for the placement or reception of a corneal implant, via a (preferably sterile) contact medium; and / or directly contacts the second contact surface via a first contact surface machined to minimize surface roughness and / or a second contact surface machined to minimize an air gap between the first and second contact surfaces.

[0052] Temperature sensor: A temperature transducer that is in very good thermal contact with the tissue holder or—since it is itself in very good thermal contact with the tissue holder base—with the tissue holder base. The temperature sensor can be an electronic component (NTC, PT100 / PT1000) or, alternatively, an optoelectronic sensor that measures the thermal radiation of the tissue holder without contact. The sensor can be integrated into the tissue holder base or into the tissue holder itself. For non-contact temperature determination via thermal radiation, this sensor can also be designed as part of the processing or laser system, and the measurement data can be transmitted to the temperature controller via the interface and control system.

[0053] Temperature controller: This can be, for example, a PID controller that actively regulates the performance of the cooler and thus keeps the temperature measured at the temperature sensor at the set value T_set.

[0054] Ambient air humidity sensor: A sensor for the water content of the room air in the vicinity of the sample.

[0055] Supply air humidity sensor: An additional sensor can also be used to measure the humidity of the supply air and use this value to determine the dew point. This sensor can also be part of the processing or laser system if the supply air is provided by the processing or laser system.

[0056] Control system (which can also be part of the temperature controller or integrated into the processing laser, in which case appropriate interfaces must be provided on the mount side): The control system determines the setpoint of the temperature controller and provides sensor monitoring data to the user and the laser system. The setpoint temperature can be specified either via the user interface, determined by the laser system, or autonomously by the control system. To determine the setpoint temperature, sensor information, particularly from the ambient air and / or supply air humidity sensors, can be used. The dew point temperature can be calculated from the humidity data and used directly or with an offset as the setpoint temperature.

[0057] In particular, the control system can also switch between different set temperatures for the temperature controller or transmit defined time profiles of the set temperatures to the temperature controller.

[0058] The control system can also regulate dry supply air for ventilation of the tissue holder's surroundings via suitable valves and flow restrictors. The control parameters can be set or modified either autonomously or via the user interface or the processing or laser system. Temperature offset: T_set = T_dew point + T_offset. The temperature offset describes the difference between the set temperature and the dew point temperature. A temperature offset is provided, according to the invention, to parameterize and maintain the finite heat transfer and the associated temperature differences between the temperature sensor and the tissue surface. In this case, T_offset is negative. However, positive values ​​for T_offset are also possible, for example, for calibration purposes.

[0059] Functional description

[0060] The inventive method for processing a corneal implant or a corneal graft at the dew point comprises the following process steps:

[0061] Providing the corneal implant or corneal graft in a processing area of ​​the processing device on the tissue holder of a corneal implant holder;

[0062] Measuring environmental parameters to determine the dew point and determining the dew point based on the environmental parameters;

[0063] Setting a target temperature, possibly taking into account a temperature offset;

[0064] Starting the temperature control process while continuously measuring the humidity and continuously adjusting the target temperature depending on the humidity;

[0065] Positioning the corneal implant or corneal graft;

[0066] Adopting a working temperature as the new target temperature under continuous temperature monitoring;

[0067] Editing the corneal implant or corneal graft upon reaching the new target temperature; and optionally

[0068] Setting a storage temperature to be achieved for storing the processed corneal implant or the processed corneal graft; and optionally

[0069] Applying a marker to the modified corneal implant or corneal transplant. The interaction of the functional blocks is described below using a typical, exemplary, and non-restrictive scenario of modification at {dew point}:

[0070] 1) To process a fabric, the dew point of the ambient air (T_dew point) is first determined by measuring its humidity using a humidity sensor. The set temperature T_set of the temperature controller is then adjusted by the control system so that the surface temperature of the fabric holder is within + / - 0.5°C of this dew point. Optionally, the difference between the sensor temperature and the surface temperature (due to the finite thermal conductivity of the materials and / or interfaces between the sensor and the surface) can be taken into account by a derived offset value T_offset. In the simplest case, this offset is derived by setting T_offset equal to the difference between the sensor temperature and the surface temperature. Preferably, the offset temperature deviates from this simplest case by less than 3°C, and particularly preferably by less than 1°C.Since the dew point depends not only on the absolute humidity but also on the atmospheric pressure, this pressure can also be determined, for example, via another sensor and included in the calculation of the dew point.

[0071] The start of the temperature control to the dew point can be triggered via the corresponding interfaces either by the user or by the excimer laser system from a higher-level process control for tissue processing.

[0072] During the preparatory steps before tissue removal - e.g., positioning the tissue or the mount - the temperature is actively controlled and adjusted to the changing dew point in case of changing room humidity.

[0073] 2) Immediately before the start of processing, the set temperature can be adjusted to the changed situation during the processing of the implant or transplant (working temperature, T_processing):

[0074] In the case of processing with supplied air, the measured humidity from the supplied air (supply air humidity sensor) can be used to determine the corresponding dew point of the supplied air and passed to the temperature controller as a new set value.

[0075] Additionally, or independently of this, the temperature offset can be adjusted to the situation during processing: for example, if the processing laser heats the fabric and / or the flow of the supply air leads to a different thermal coupling of the fabric to the ambient air. Both can result in a changed temperature difference between the temperature sensor and the fabric surface.

[0076] The change in the set temperature, via the calculated dew point temperature and / or via a modified temperature offset to the working temperature, can be triggered (via the corresponding interfaces) either by the user or by the processing laser from a higher-level control system for fabric processing. The value of the temperature offset for the working temperature can advantageously be transmitted from the processing laser to the control system in a processing-specific manner.

[0077] It is not strictly necessary to use the supply air for processing. In one possible configuration, the processing laser blocks the supply air or does not activate it at all when in fabric processing mode. Alternatively, this can also be controlled by the control system via data exchange between the control system and the processing laser.

[0078] 3) After processing, the set temperature can be adjusted back to the dew point temperature of the ambient air.

[0079] Functional description in the {Frozen} scenario: Processing fabric in a frozen state is carried out with slight deviations from the above scheme. Step 2) is modified accordingly:

[0080] The inventive method for processing a frozen corneal implant or a frozen corneal graft comprises the following process steps:

[0081] Providing the corneal implant or corneal graft in a processing area of ​​the processing device on the tissue holder of a corneal implant holder;

[0082] Measuring environmental parameters to determine the dew point and determining the dew point based on the environmental parameters;

[0083] Setting a target temperature, possibly taking a temperature offset into account; starting the temperature control process while continuously measuring the humidity and continuously adjusting the target temperature depending on the humidity;

[0084] Positioning the corneal implant or corneal graft;

[0085] Adopting a working temperature as the new target temperature under continuous temperature monitoring;

[0086] Supply of dry air or an inert gas, at least in an area around the corneal implant or corneal graft;

[0087] Checking starting conditions regarding the freezing of the corneal implant or corneal graft;

[0088] Processing of the corneal implant or corneal graft upon reaching the new target temperature;

[0089] Discontinuation of the supply of dry air or inert gas after completion of the processing of the corneal implant or corneal graft; and optionally

[0090] Setting a storage temperature to be achieved for storing the processed corneal implant or the processed corneal graft; and optionally

[0091] Placing a mark on the modified corneal implant or corneal transplant.

[0092] This will be explained in more detail below.

[0093] 2a) Starting the temperature ramp to freeze the tissue: To start the treatment, the set temperature is lowered from the dew point temperature (plus offset) to the working temperature. This reduction preferably occurs within 40 seconds, more preferably within 10 seconds. The rate of temperature change is preferably at least 0.5 K / s, more preferably more than 2 K / s. In contrast to the {dew point} scenario, the working temperature here is significantly below the freezing point of the tissue (preferably between -30°C and -20°C). In an alternative embodiment, the temperature is below -50°C and the cooling rate is greater than 10 K / s.

[0094] The temperature drop to the operating temperature can be initiated either by the user or by the processing laser. This drop can be achieved as quickly as possible by maximizing cooling capacity (typically 15-30 seconds) or controlled by the control system in predetermined time-based ramps. Preferably, the fabric is frozen with temperature changes of approximately -1 K / s, which enables rapid and homogeneous freezing. (Simply maintaining a constant temperature below 0°C is insufficient to bring the fabric into a predictably or detectably frozen state.)

[0095] 2b) Start of dry air supply: The control system switches on the supply of dry air. This can be triggered synchronously with the start of temperature control to operating temperature or when a temperature threshold (e.g., the dew point of the ambient air) is undershot by a certain value by the control system.

[0096] 2c) Processing can begin when several conditions are met: The fabric must be frozen, which can preferably be detected by suitable sensors and evaluated by the control system, or alternatively, determined by time and temperature measurements after the temperature has continuously fallen below the freezing point compared to reference times and temperatures stored in the control system. Furthermore, the measured temperature must have reached the target operating temperature range, or have already reached it for a specific period of time. The control system can monitor these conditions and, if they are met, signal this to the user and / or the processing laser, thus enabling processing.

[0097] 2d) After processing, the fabric can be thawed again and brought to the dew point or briefly to temperatures above the dew point, and the supply of dry air can be stopped.

[0098] In the {Frozen} scenario, the operating temperature is chosen to be significantly below the melting point to prevent thawing even during continuous processing and thus continuous heat input from the processing laser, and to ensure that it remains reliably below the melting point. Specifically, it is chosen so that individual laser processing pulses, or a few processing pulses that overlap in time and space (and are therefore only one pulse period apart), do not raise the sample above the freezing point for a duration greater than 1.5 ms, even locally within the pulse area. For IR radiation measurement, this corresponds to a specific camera-laser delay and a specific camera integration time. Significantly higher temperatures may be measured for other measurement parameters, but this is not relevant for processing. Preferably, the temperature of the tissue holder is in the range of -5 to -15°C, and particularly preferably in the range of -15 to -25°C.Properties of the tissue holder.

[0099] The fabric holder itself may preferably have the following material and surface properties to enable the processing scenarios, with particular emphasis on the thermal requirements for the {Frozen} scenario (tempering at dew point is less demanding):

[0100] The material should preferably be biocompatible and sterilizable by common methods (steam sterilization, autoclaving). The material should preferably be resistant to the chosen method of processing the implant or graft and, purely by way of example (if laser processing takes place), should not be ablatable with the laser radiation used and should not change its material composition; i.e., ablation only occurs at a laser fluence > 250 mJ / cm². A2 instead. To keep the cooling capacity within an acceptable range of 50–100 W (including power loss), the heat capacity of the heated materials (fabric holder and fabric holder base) can be < 5 J / K, but preferably < 2 J / K, and the heat transfer between the fabric holder and fabric holder base is preferably greater than 10 kW / (m²). 2 K). This heat transfer should be achieved without thermal pastes or pads for reasons of sterility and biocompatibility. This can be achieved by mechanical means, such as a very smooth polish of the interfaces or, preferably, by the use of sterile and / or biocompatible liquids (e.g., BSS, water, dextran solution, glycerin, ethanol) to compensate for small surface roughnesses (with a roughness of Ra = 3.2 or less) and to establish good thermal contact.

[0101] Material constants for the materials preferably used here: Heat capacity:

[0102] Ti: 520 J / kg / K; Stainless steel: -500 J / kg / K; SiC: -600 J / kg / K; Aluminum: 888 J / kg / K Thermal conductivity:

[0103] Ti: 20 W / m / K; Stainless steel: -50 W / m / K; SiC: -100 W / m / K; Aluminum: 160-180 W / m / K Specific density:

[0104] Ti: 4.5 g / cm A 3; Stainless steel: -8 g / cm² A 3; SiC: < 3.2 g / cm A 3; Aluminium: 2.7 g / cm A 3

[0105] Since each laser pulse can locally raise the temperature by a few degrees, and since even the spatiotemporal overlap of a few pulses (< 5 pulses within a time interval of 10 ms) should not raise the temperature of the frozen tissue above freezing (for a time > 1.5 ms after the processing pulse), very good thermal contact between the tissue holder and the tissue must be achieved with coupling constants preferably > 1000 W / m². A 2 / K, preferably > 2000 W / m A 2 / K and even more preferably > 3000 W / m A 2 / K.

[0106] The limitations mentioned here can be met with titanium alloys, stainless steel, silicon carbide, aluminum oxide, and, to a limited extent, also with silicon nitride and aluminum nitride. Calcium fluoride (CaF₂) can optionally be used, as mentioned above.

[0107] dry air

[0108] The fabric holder cannot have a complete curvature on its top side. The top side is therefore only curved in sections, and any ratio between the curved surface and the smooth surface of the fabric holder on the top side can be selected; for example, the curved surface can be 30%, 40%, 50%, 60%, or 70%.

[0109] The dry air should have a pressure dew point below the fabric temperature at the operating point (e.g., < -25°C) and should flow laminarly around the fabric (to prevent turbulence with more humid ambient air). It is sufficient if the flow is laminar in the area of ​​the fabric.

[0110] The dry air prevents condensation and subsequent freezing of water from the ambient air on the frozen fabric surface. Water and ice alter the effect of the processing laser and thus disrupt the targeted processing of the fabric. At the same time, the dry air ensures the efficient removal of processing products (e.g., ablation plume), which could otherwise accumulate above the fabric and continuously absorb subsequent laser pulses more strongly, or whose aqueous components could condense on the surface. This removal, as well as the laminar airflow, can be supported by an intake system, which is also integrated into the mount or, preferably, into the processing laser itself.

[0111] Instead of dry air, an inert protective gas such as nitrogen, helium, argon, or SF6 can also be used, as long as it does not absorb the radiation from the processing laser. The dry air is controlled and its quality monitored by the control system using suitable sensors and actuators. This can include, for example, sensors for flow rate, flow velocity, overpressure, temperature, and humidity.

[0112] The cornea implant holder may also include flow-shaping and / or flow-shielding elements to generate a laminar flow of dry air or inert protective gas in the area of ​​tissue positioned on the tissue holder or to shield against turbulence caused by other air currents.

[0113] The generation of laminar flow can optionally be advantageously supported by suitable means, such as a wall or hood that directs the air around the tissue holder and shields it from turbulence caused by other airflows (CCA, operating room ventilation). This hood can enclose the tissue on all sides, provided that the part facing the processing laser is made of a material that transmits this laser radiation, for example, quartz glass, CaF2, or MgF2.

[0114] Instead of a continuous laminar airflow around the fabric, it is also possible to surround the fabric with a protective gas that is significantly heavier than ambient air. This gas is introduced in small quantities into the fabric area before freezing and contained within a container structure. Possible protective gases include SF6 or argon.

[0115] Shot fade-out

[0116] The cornea implant holder may further comprise at least one radiation trap for absorbing therapeutic radiation, and may further comprise a control device configured to direct a subset of individual processing pulses of the therapeutic radiation into the at least one radiation trap.

[0117] The device can therefore incorporate a beam dump: To keep the tissue temperature below the upper limit required for the respective processing mode {dew point} or {frozen}, the heating of the tissue sample can be limited by reducing the effective repetition rate acting on the tissue. This can be achieved, for example, by directing individual processing pulses not directly onto the sample, but intermittently onto a predetermined part of the tissue holder (beam dump, beam trap, in which the laser radiation is almost completely absorbed and does not escape). To further reduce the heating of the tissue holder, this dump can advantageously be designed as a depression in the tissue holder to dissipate the generated heat more quickly via the underlying structures.Furthermore, this depression can be filled with water or BSS prior to processing to increase heat dissipation through evaporation and thus remove latent heat. The position and size of the beam dump can encompass the entire area of ​​the fabric holder outside the maximum area intended for fabric processing, plus a safety margin of at least one spot diameter, and / or encircle the lamella in a ring shape. One or more circular areas with a minimum diameter equal to one spot diameter are also possible as beam dumps. Alternatively, the beam dump can be designed as a hole in the fabric holder, so that laser pulses directed into this area strike the underlying material rather than the fabric holder itself.

[0118] Functionality Positioning

[0119] The tissue can be preferably processed by the processing laser at predetermined points; for this, a fixed relative position of the tissue to the processing laser must be set and maintained. This is achieved by first precisely positioning the tissue in relation to the tissue holder and, in a second step, precisely positioning the tissue holder with the tissue attached in relation to the laser.

[0120] Positioning of the tissue relative to the tissue holder

[0121] To position the fabric on the fabric holder, the fabric holder has the following features, which can be implemented individually or in any combination.

[0122] These features include markings centered on the apex (the highest point of the curvature, visible in the side view in Fig. 8d) of the curved part of the tissue holder, and consisting of one or more rings concentric to the apex, with ring diameters typically in the range of 3–10 mm.

[0123] These features also include single lines or crossed lines (crosshairs) that pass through the apex of the spherically curved part of the tissue holder. (In the case of crossed lines, the intersection point also lies on the apex.)

[0124] The markings can be achieved through the application of paint or through localized surface modification by mechanical or laser processing, such as laser engraving of the tissue holder. Markings can also be achieved without a visually perceptible color change to the tissue holder material if, for example, grooves or locally structured surface roughness modulate the intensity of light scattering towards suitable viewing positions during positioning (preferably from above), or create local shadows when illuminated from the side.

[0125] Another solution for achieving precise fabric positioning involves structuring the fabric holder so that a ring-shaped counterpart (cylindrical shape) fits precisely into a circular groove on the holder. The inner diameter of this cylinder is matched to the diameter of the fabric being processed, ensuring that when the fabric rests on the curved holder, it contacts the cylinder's inner wall. It is advantageous for the cylinder to have strategically placed holes that allow water (or liquids of similar viscosity) to be supplied or removed via capillary action. This facilitates controlled removal of the liquid between the fabric and the holder through the cylinder, without altering the fabric's position.Once such a fluid film has been removed, does the adhesion between the tissue and the tissue holder ensure that the position is not changed even when the positioning cylinder is removed, and that the tissue remains in the predetermined position on the tissue holder?

[0126] Positioning of the tissue relative to the processing laser

[0127] Two prerequisites are necessary for positioning the tissue holder in relation to the processing laser: On the one hand, the tissue holder must be able to move in a controlled manner relative to the processing laser, and on the other hand, its position (location in space and orientation) must be recognizable.

[0128] The mount containing the tissue holder can itself have positioning degrees of freedom that are mechanically and / or motor-adjustable. (In the case of motor-adjustable positioning, it is advantageous to allow the user to control the position via operating elements and also to enable the processing laser to control the motor adjusters via a data interface (e.g., to use tracker signals for automatic adjustment).

[0129] Another option is to incorporate a mechanical interface on the mount, allowing it to be rigidly coupled to a patient table (especially its head section) that is already part of the laser processing system. This way, the table's positioning devices can be used directly for the mount and thus the tissue holder.

[0130] The corneal implant holder may further comprise c) at least one reference structure for referencing or positioning a corneal implant or corneal graft to the tissue holder; and / or d) at least one referencing device for referencing or positioning a corneal implant or corneal graft to the tissue holder; and / or e) at least one alignment structure for referencing or positioning the implant holder to a processing device.

[0131] An improvement to the previously described corneal implant holder is possible

[0132] If at least one reference structure according to c) exists, this reference structure:

[0133] (C1) include at least one color marking and / or marking obtained by surface modification of the tissue holder; and / or

[0134] (C2) include individual lines intersecting in an imaginary extension, or intersecting lines, and / or at least one, preferably at least two, concentric circles as a marker; and / or

[0135] (C3) be centered on an apex of a curved part of the tissue holder facing a processing device.

[0136] Optionally or additionally, if at least one referencing device according to d) is present, this referencing device

[0137] (D1) Have a ring-shaped centering element that can be precisely fitted to or placed on the tissue holder; and / or

[0138] (D2) Be able to be inserted into a recess or raised area provided on the fabric holder without mechanical play; and / or (D3) Have an inner diameter that corresponds to the diameter of a fabric to be processed; and / or

[0139] (D4) Have inlets and outlets designed to supply fluid to or from tissue.

[0140] Optionally or additionally, if at least one alignment structure according to e) is present, this alignment structure can be used.

[0141] (E1) On a support area for the application of a tissue, at least one structure from the list of structures comprising a pupil structure; an iris structure; and a varied iris structure whose iris elements have been replaced by a pattern; and / or

[0142] (E2) Have at least one peripheral alignment structure on a peripheral edge area of ​​the tissue holder located outside the support area.

[0143] For precise position detection of the tissue holder, the structures described above are generally sufficient, especially for manual positioning relative to the processing laser. However, particularly in conjunction with a processing laser that has devices for machine image processing and especially for the detection of pupils, iris, limbus and / or scleral vessels, further marking structures are advantageous. a) A pupil structure centered on the apex of the tissue holder, which can be detected by the processing laser, is possible.This allows a lateral offset between the tissue holder and the processing center to be detected and corrected. b) An iris structure is also possible, which, in addition to the pupil, makes not only a lateral offset but also an angular offset between the processing system and the tissue holder detectable and correctable. c) Furthermore, a variant of the iris structure is conceivable where the iris elements have been replaced by a pattern that can, for example, additionally encode information about the type of tissue holder or the tissue. d) Structures at the edge of the processing area, where no tissue to be processed (i.e., approximately 5 mm distance to the apex of the tissue holder) is in contact with the surface, can also be advantageous.

[0144] When the structures are detected by the processing laser, for example, by an eye-tracking system integrated into the laser, the position information can either be output to the user for manual positioning. Alternatively, with motorized controls (whether mounted or lying down), this positioning can be performed by the processing system itself (via a data interface). Another option, particularly for small deviations (< 3 mm) between the target and actual position of the detected tissue holder, is to have the processing laser track the positions of the individual processing pulses (analogous to eye tracking in refractive surgery). This can even be done during the processing itself to compensate for vibrations or camera shake.

[0145] When processing frozen tissue, a problem arises because the tissue's transmission decreases significantly upon freezing, making the detection of underlying marker structures impossible. This problem is solved by also applying peripheral alignment structures to the tissue holder for position and orientation detection—that is, structures located outside the tissue. In a combination of alignment structures, artificial pupils and / or iris structures can be detected initially, and then, upon freezing the tissue, the detection switches to the outer alignment structures.

[0146] Marking positions for the fabric after processing

[0147] The processed tissue must be implanted in the correct location, position, and orientation. For this purpose, tissue is typically marked with clear indicators before being inserted into the recipient eye. These indicators can be applied manually using suitable pens without any additional tools.

[0148] In one embodiment of the cornea implant holder, it further comprises a marking template which can be uniquely positioned and attached to the tissue holder in a predetermined position and rotation, and which allows access to the cornea implant or cornea graft positioned on the tissue holder for the purpose of applying a marking at predetermined marking positions.

[0149] Preferably, however, the tissue orientation relative to the tissue holder—known precisely by the methods described above—is marked directly on the tissue holder. For this purpose, precisely manufactured stamps or stencils for common surgical marking instruments (a), trypan blue marking pens frequently used in ophthalmology (b), or stencils with more complex marking patterns for structuring a surface application of trypan blue (c) are conceivable. The stencils must have unambiguous orientation structures relative to the tissue holder so that they can be aligned with each other. Preferably, however, this is achieved by precisely fitting mechanical structures that are designed as counterparts and are integrated into the stencil and tissue holder, or into the stencil and the structures surrounding the tissue holder (e.g., the mounting housing).

[0150] Support for implant measurement or thickness measurement

[0151] Optionally, markings can be applied in the form of a color or surface modification that strongly absorbs or strongly reflects at the common wavelengths of OCT measuring devices.

[0152] The markings can also serve to increase the visibility of the tissue in the OCT scan or to reduce artifacts. For this purpose, the markings can be designed to cover such a large area that the entire lamella can be measured in a single OCT scan.

[0153] For the purpose of thickness measurement, the tissue holder or tissue holder base can be equipped with an ultrasonic transducer and receiver.

[0154] Functionality: Freezing detection

[0155] The corneal implant holder can further comprise at least one device for detecting a phase transition of tissue arranged on the tissue holder, wherein the device is configured to: simultaneously detect at least one first detector signal representing specular reflection and at least one second detector signal representing diffuse scattering, evaluate a relative change of the detected detector signals to each other, and detect a phase transition depending on the relative change of the detected detector signals to each other; and / or is configured to evaluate an image of at least one central marking located beneath the tissue when the tissue is placed on the tissue holder with respect to the contrast of the marking, and detect a phase transition depending on a change in the contrast of the central marking;and / or designed to determine the temperature profile of the fabric holder and thus indirectly the temperature profile of a fabric arranged on the fabric holder, and to detect a phase transition depending on a temperature change attributable to the release of latent heat. For processing fabric in the frozen state, it must be ensured that it has actually undergone a phase transition to a frozen state after falling below the freezing point. It is possible to keep a fabric in a supercritical state below freezing for an extended period (>20 s) without it undergoing a phase transition to a solid state.

[0156] Either the user must ensure that the fabric is frozen at the start of processing. However, it is preferable to detect this state via the mount or to support this task with a detection system in the processing laser by structuring the fabric holder. Possible detection methods that enable machine-assisted detection of the phase transition from the gelatinous, unfrozen to the solid, frozen phase are presented below.

[0157] The approaches presented can be used individually or in combination to detect the phase transition.

[0158] Diffuse vs. Specular Reflection

[0159] In one embodiment of the method, the process step of checking initial conditions can include the process step of detecting the freezing of the cornea implant or cornea graft, wherein this process step can further include acquiring a first detector signal representing a specular reflection; acquiring a second detector signal representing a diffuse scattering; evaluating a relative change of the detected detector signals to each other; and detecting a phase transition as a function of the relative change of the detected detector signals to each other.

[0160] An arrangement and method for detecting the phase transition can be based on the analysis of the ratio of specular to diffuse reflection at the tissue surface. A light source (LED or laser) generates a focused beam of light that is reflected at the surface of the unfrozen tissue towards a photodetector (photodiode), where the intensity of the incident beam is detected. Suitable lenses and aperture arrangements can be used in the photodetector to increase selectivity, and wavelength-sensitive filters can be used to reduce interference from stray light.

[0161] At least one, and preferably several, other photodetectors collect scattered light from the detection beam. These photodetectors are preferably not located in the plane of incidence of the detection beam. In the case of an unfrozen sample, the signal from these detectors is not caused by the detection beam, but only by background light. (For higher collection efficiency, suitable lenses and aperture arrangements can be used in these detectors, and wavelength-sensitive filters can be used for insensitivity to stray light.) At the moment of the phase transition, the largely specular reflection changes, and incident light is diffusely scattered by the frozen surface.

[0162] The detection of icing is achieved by simultaneously recording the detector signals, which change significantly at the moment of icing: The signal of the specular reflection becomes significantly weaker, while signals of the diffuse scattering become slightly stronger, or remain the same.

[0163] It is irrelevant for the design whether the reflective mirror image originates from the fabric surface or the fabric holder surface, which is easily possible in the case of a transparent fabric.

[0164] The light source for the detection light does not necessarily have to be part of the mount; in particular, it is possible to integrate it into the processing laser itself (this would allow, for example, the use of the alignment lasers of an excimer laser, such as the MEL, which illuminate the tissue).

[0165] Alternatively or additionally, in an embodiment of the inventive method, the process step of detecting the freezing of the cornea implant or the cornea graft can include recording at least one central marker located under the tissue when the tissue is resting on the tissue holder; evaluating the contrast of the marker; and detecting a phase transition depending on the change in the contrast of the central marker.

[0166] - Differential attenuation of structures below and beside the tissue

[0167] To detect the phase transition, markings can also be placed on the tissue holder as before (“positioning”) and these can be recorded and analyzed by the video system of the processing device (the processing laser) or another suitable monitoring device.

[0168] The tissue holder can be marked so that suitable high-contrast structures are placed both in the area beneath the tissue being processed ("central") and in an area not covered by the tissue ("peripheral"). Due to the phase transition, the transmission of the tissue changes significantly, and the central structures are no longer perceptible or only visible with significantly reduced contrast. This change in contrast can be detected by the processing laser's image processing system and transmitted to the control system, where it can be analyzed and evaluated, for example, in relation to the temperature signal. It is sufficient to detect the rapid change in contrast in correlation with a tissue holder temperature at or below the freezing point of the sample and to infer that the sample is freezing.Preferably, because it is more robust against false detection, the contrast loss of the central structures is compared with the contrast of the peripheral structures, which does not change or changes only slightly when the sample is frozen. The freezing of the lamella can thus be inferred from the change in the contrast difference.

[0169] Temperature measurement

[0170] Alternatively or additionally, in an embodiment of the inventive method, the process step of detecting the freezing of the cornea implant or the cornea graft can include determining a temperature profile of the tissue holder and thus indirectly a temperature profile of tissue arranged on the tissue holder; and detecting a phase transition as a function of a temperature change attributable to the release of latent heat.

[0171] Another way to detect the phase transition is to precisely measure the tissue temperature during cooling. With rapid cooling (~1 °C / s), the tissue remains in a supercooled, supercritical state for an extended period. It has already fallen below the freezing point, but the phase transition has not yet occurred. As soon as the phase transition begins, latent heat (enthalpy of fusion) is released, which warms the tissue (but not above the freezing point). This warming can be detected using suitable temperature measurement methods, thus enabling the detection of the phase transition. The temperature can be determined using contact methods with a sensor, even on the underside of the tissue, or by detecting the blackbody radiation emitted by the tissue surface using an IR camera or pyrometer.

[0172] In particular, it is possible to use the temperature sensor of the temperature control system for this detection, even if it is implemented as a contact sensor in the tissue holder base, provided that the heat flow between the tissue and this sensor is large enough. With the aforementioned materials and heat capacities, this is possible; it is advantageous to also record the cooling performance of the cooler itself and relate it to the temperature changes.

[0173] The above describes in particular the following aspects of the present invention:

[0174] Detailing the properties of the mounting materials which are suitable to meet the requirements for sterility and heat transfer.

[0175] A specific assembly of the mount consisting of fabric holders, temperature-controlled elements, and control elements.

[0176] Options for placing markings on the tissue holder, which can be used by the processing laser to detect and correct the position and orientation of the mount relative to the processing laser.

[0177] Fluid management under the sample through the tissue holder (removing the fluid film to achieve adhesion, good thermal contact and a defined processing regime).

[0178] - Devices on the mount to mark the position of the tissue relative to the mount.

[0179] - Displaying the temperature or reaching the target temperature corridor to the operator so that processing can be started by him in the correct temperature regime, or alternatively, communicating the temperature or reaching the target temperature corridor to the processing laser for synchronization of processing.

[0180] An automatic switch-on of water-free air supply when the temperature drops below freezing prevents icing of the tissue surface. This can be controlled either by the user or by the processing laser, allowing integration into a complex process control system via the treatment laser.

[0181] An automatic control system adjusts to the fabric's dew point to keep the fabric in a hydrated state. A switch to a different temperature, corresponding, for example, to a different dew point in the supply air at the moment of processing, or to maintain the heat input from the laser and / or the supply air and keep the temperature at the dew point.

[0182] An (automatic) switch to a temperature below freezing with synchronous control of the dry supply air prevents icing. The mount also allows a significantly larger radius of curvature than the eye; in particular, the radius of curvature of the target implant may also be used. Toric shapes (astigmatic) should also not be excluded. Larger radii (i.e., flatter curvatures) than those of the human cornea allow for treatment with less energy input to the surface, due to lower ablation efficiency losses.

[0183] Detection of icing by the mount or the processing laser is made possible by structures on the tissue holder.

[0184] Relevant aspects of the present invention:

[0185] - The most efficient possible heat exchange is required between the corneal implant holder and the cooling element of the mount. This is achieved through optimal surface contact and preferably not through thermal contact agents (thermal paste, Apad, etc.) between the mount and the underlying element to ensure the sterility of the holder. Suitable materials that can be manufactured to a very smooth finish, are themselves sterile, and exhibit high thermal conductivity and a good heat transfer coefficient between the sample holder and tissue include, for example, titanium, stainless steel, silicon carbide, aluminum nitride, and possibly also aluminum oxide (corundum) and calcium fluoride (CaF2).

[0186] - It is advantageous to measure the mount temperature using a temperature sensor that is in good thermal contact with the mount, or that measures the mount temperature without contact. Good contact means either direct contact or via an intermediate element that exhibits very high heat transfer between the mount and the intermediate element.

[0187] Furthermore, feedback of the temperature and / or the achievement of a target temperature range to the operator or to the processing or laser processing device is particularly preferred. The following aspects are particularly optional. These can improve the corneal implant holder.

[0188] A division of the various functions – sterile tissue support, temperature conduction, temperature measurement and active cooling – into different components that are mechanically and thermally combined into a complete system is advantageous, but these functions can also be partially or completely combined.

[0189] The connection between the control system and the processing laser is advantageous, but not necessary. If it is not present, the user must manually switch between temperature control regimes and / or manually enable processing after icing.

[0190] The following section will explain the aspects of the present invention in more detail with reference to the accompanying drawings. The drawings merely illustrate possible embodiments of the present invention, and the described features can be combined or omitted as desired. Identical features or features with the same function are further indicated by the same reference numerals. Repetitive descriptions of features are avoided, so explanations of features described in preceding figures are also applicable to other figures unless differences are explicitly indicated.

[0191] Explanations of the procedure can be applied to the device. Likewise, explanations of the device can be applied to the computer-implemented procedure.

[0192] They show:

[0193] Fig. 1 schematic representation of a design of a cornea implant holder;

[0194] Fig. 2 Block diagram of functional elements of a cornea implant holder for use in tissue processing at the dew point;

[0195] Fig. 3-7 shows a further embodiment of the cornea implant holder in different views;

[0196] Fig. 8 schematic flow chart of a procedure for processing a corneal implant or a corneal graft at the dew point;

[0197] Fig. 9 Block diagram of functional elements of a corneal implant holder for use in the processing of frozen tissue; Fig. 10 Schematic flow chart for the procedure for processing a frozen corneal implant or a frozen corneal graft;

[0198] Fig. 11 schematic side view of the tissue holder in a further embodiment;

[0199] Fig. 12 schematic representation of the tissue holder in a further embodiment;

[0200] Fig. 13 schematic representation of possible positioning aids;

[0201] Fig. 14 schematic representation of possible positioning aids for fine positioning;

[0202] Fig. 15 schematic representation of the use of templates;

[0203] Fig. 16 Diagram for the detection of a phase transition (freezing of a tissue) according to a first embodiment;

[0204] Fig. 17 Diagram for the detection of a phase transition (freezing of a tissue) according to a second embodiment; and

[0205] Fig. 18 Diagram for the detection of a phase transition (freezing of a tissue) according to a third embodiment.

[0206] Figure 1 shows a schematic diagram of a corneal implant holder 1 in one embodiment. The corneal implant holder includes an active cooling element 3, which can regulate the temperature of a tissue holder base 7 by means of a thermal contact medium 5. In the embodiment shown, a temperature sensor 9 is mounted in the tissue holder base 7; in other embodiments, this sensor may be located in a different position and in a different number. Furthermore, the corneal implant holder 1 includes a tissue holder 11, and a thermal contact medium 5 may also be located between the tissue holder 11 and the tissue holder base 7.

[0207] In some embodiments this is not necessary, especially in those which have polished or superpolished surfaces, so that thermal heat equalization between the fabric holder 11 and the fabric holder base 7 takes place solely via such smooth contact surfaces.

[0208] Figure 2 shows a block diagram of functional elements of a temperature-controlled corneal implant holder 1 for use in the processing of tissue, i.e., a corneal implant or a corneal graft, at the dew point. The arrows with double lines indicate heat exchange, whereas single lines represent electrical and / or control signals.

[0209] The fabric holder 11 is shown, which is in thermal exchange with the fabric holder base 7 and the active cooling element 3. The temperature sensor 9 also participates in the heat exchange. Furthermore, a Kontra II system 13 is shown, which is electrically and / or control-connected to a temperature controller 15, a humidity sensor for the ambient air 17, a humidity sensor for the supply air 19, an interface to the processing laser 21, and a user interface 23.

[0210] Figures 3 to 7 show a further embodiment of the corneal implant holder 1 from different views. In the embodiment shown, the corneal implant holder 1 also comprises a tissue holder 11 and a tissue holder base 7, wherein a passive cooling element 24 is accommodated in a complementary pocket 27 of the tissue holder base 7. The passive cooling element 25 is a cold reservoir 27 and, in the embodiment shown, a copper body 29. In other embodiments, a different material with high specific heat capacity can be used for the passive cooling element 25.

[0211] The copper body 29 can cool a contact surface 33 via contact surfaces 31 (see Figures 5 and 7) if the copper body 29 has been stored in a refrigerator or freezer before use. The contact surface 33 can be lenticular, i.e., convex towards a vertical direction 35. This curvature can, in particular, correspond to a curvature of a corneal implant or a corneal graft. The contact surface 33 can, in particular, consist of or comprise calcium fluoride 37 (CaF₂).

[0212] The tissue holder 11 shown can comprise a plastic frame 39 and the previously mentioned calcium fluoride lens 36 37. Furthermore, a skirt 41 is shown, which surrounds the lens 36 in a ring-like manner and thus prevents any fluid in which the corneal implant or corneal graft may be stored from flowing out at the edge of the graft or implant, thereby ensuring continuous moistening of the implant or graft.

[0213] Figure 8 schematically illustrates the process flow of a procedure for processing a corneal implant or a corneal graft at the dew point.

[0214] To process a fabric, the dew point of the ambient air (T_dew point) is first determined by measuring its humidity using a humidity sensor. The set temperature T_set of the temperature controller is then adjusted by the control system so that the surface temperature of the fabric holder lies within ±0.5°C of this dew point. Optionally, the difference between the sensor temperature and the surface temperature (due to the finite thermal conductivity of the materials and / or interfaces between the sensor and the surface) can be accounted for by a derived offset value T_offset. In the simplest case, this offset is derived by setting T_offset equal to the difference between the sensor temperature and the surface temperature. Preferably, the offset temperature deviates from this simplest case by less than 3°C, and particularly preferably by less than 1°C.Since the dew point depends not only on the absolute humidity but also on the atmospheric pressure, this pressure can also be determined, for example, via another sensor and included in the calculation of the dew point.

[0215] The start of the temperature control to dew point can be triggered via the corresponding interfaces either by the user or by the excimer laser system from a higher-level process control for tissue processing.

[0216] During the preparatory steps before tissue removal - e.g., positioning the tissue or the mount - the temperature is actively controlled and adjusted to the changing dew point in case of changing room humidity.

[0217] Immediately before the start of processing, the set temperature can be adjusted to the changed situation during the processing of the implant or transplant (working temperature, T_processing):

[0218] In the case of processing with supplied air, the measured humidity from the supplied air (supply air humidity sensor) can be used to determine the corresponding dew point of the supplied air and passed to the temperature controller as a new set value.

[0219] Additionally, or independently of this, the temperature offset can be adjusted to the situation during processing: for example, if the processing laser heats the fabric and / or the flow of the supply air leads to a different thermal coupling of the fabric to the ambient air. Both can result in a changed temperature difference between the temperature sensor and the fabric surface.

[0220] The change in the set temperature, via the calculated dew point temperature and / or via a modified temperature offset to the working temperature, can be triggered (via the corresponding interfaces) either by the user or by the processing laser from a higher-level control system for fabric processing. The value of the temperature offset for the working temperature can advantageously be transmitted by the processing laser to the control system in a processing-specific manner. It is not strictly necessary to use the supply air for processing. In one possible configuration, the processing laser blocks the supply air or does not activate it at all when operating in fabric processing mode. Alternatively, this can also be controlled by the control system via data exchange between the control system and the processing laser.

[0221] After processing, the set temperature can be adjusted back to the dew point temperature of the ambient air.

[0222] Figure 9 shows a block diagram of functional elements of the corneal implant holder 1 for use in processing frozen tissue, i.e., a frozen corneal implant or a frozen corneal graft. In this block diagram, double-line arrows indicate heat exchange, while single lines represent electrical and / or control signals. The tissue holder 11 is shown, which is in thermal exchange with the tissue holder base 7 and the active cooling element 3. The temperature sensor 9 also participates in the heat exchange. A control system 13 is also shown, which is electrically and / or control-connected to a temperature controller 15, an ambient air humidity sensor 17, an interface to the processing laser 21, and a user interface 23. Furthermore, in this embodiment, the control system 13 is connected to a dry air controller 43 and an icing detector 45.

[0223] Figure 10 schematically illustrates a flowchart for the procedure of processing a frozen corneal implant or a frozen corneal graft. Processing of tissue in the frozen state is carried out with slight deviations from the scheme shown in Figure 8.

[0224] Initiation of the temperature ramp to freeze the tissue: To start the treatment, the set temperature is lowered from the dew point temperature (plus offset) to the working temperature. This reduction preferably occurs within 40 seconds, more preferably within 10 seconds. The rate of temperature change is preferably at least 0.5 K / s, more preferably more than 2 K / s. In contrast to the {dew point} scenario, the working temperature here is significantly below the freezing point of the tissue (preferably between -30°C and -20°C). In an alternative embodiment, the temperature is below -50°C and the cooling rate is greater than 10 K / s.

[0225] The temperature drop to the operating temperature can be initiated either by the user or by the processing laser. This drop can be achieved as quickly as possible by maximizing cooling capacity (typically 15-30 seconds) or controlled by the control system in predetermined time-based ramps. Preferably, the fabric is frozen with temperature changes of approximately -1 K / s, which enables rapid and homogeneous freezing. (Simply maintaining a constant temperature below 0°C is insufficient to bring the fabric into a predictably or detectably frozen state.)

[0226] Dry air start: The control system switches on the supply of dry air. This can be triggered synchronously with the start of temperature control to operating temperature or when a temperature threshold (e.g., the dew point of the ambient air) is undershot by a certain value by the control system.

[0227] Processing can begin when several conditions are met: The fabric must be frozen, preferably detected by suitable sensors and evaluated by the control system, or alternatively, frozen by measuring time and temperature after the fabric has continuously fallen below the freezing point compared to reference times and temperatures stored in the control system. Furthermore, the measured temperature must have reached the target operating temperature range, or have reached it for a specific period of time. The control system can monitor these conditions and, if they are met, signal this to the user and / or the processing laser, thus enabling processing.

[0228] After processing, the fabric can be thawed again and brought to the dew point or briefly to temperatures above the dew point, and the supply of dry air can be stopped.

[0229] Figure 11 schematically shows a side view of the fabric holder 11. For the sake of clarity, other elements are not shown in this and the following figures.

[0230] The figure shows a laminar flow 47 around a tissue 49 on the tissue holder 11. Dry air 51 flows in from the left along a flow direction 53 and is converted into a laminar flow field 55 (shown schematically as dotted lines). The flow and laminarization are part of the cornea implant holder 1 and are controlled by the Kontra II system 13 (e.g., flow rate 57 or flow velocity 59). The outflow can be cleaned of processing products 65, for example, by a suction 61 and downstream particle filters 63, which can either also be part of the cornea implant holder 1 or part of the processing laser. Figure 12 shows the tissue holder 11 schematically in a side view (a) and a top view (b). The fabric holder 11 includes a schematically drawn hood 67, which guides the laminar airflow 47 around the fabric 49 and shields it from other airflows 69.The top view shows a schematic representation of a transparent wall 71.

[0231] The wall 71 is interrupted in a region of the laser entry 73. Alternatively, this opening is closed by a window (e.g., quartz glass) that transmits the processing laser. The laminar flow 47 around the tissue 49 shown in Figure 12 is less susceptible to other air currents 69 than the type of flow shown in Figure 11.

[0232] Figure 13 schematically illustrates different configurations of possible positioning aids on the corneal implant holder 1. a) The (optional) curved area 75 of the tissue holder 11 is shown in a different color 77 in these illustrations. The color is represented as hatching in the drawing and is not a marking. b) Concentric rings 79 can be used as an alternative or additional positioning aid, with the rings 79 arranged concentrically to an apex 81 of the holder's curvature. c) Another possible positioning aid is the use of a crosshair 83, with the intersection point 85 arranged concentrically to the apex 81 of the holder's curvature. d) shows a sectional drawing of the side view of the tissue holder 11 with a notch 87 (see also the enlargement 89) and matching ring template 91, wherein the notch 87 is arranged in an annular shape and concentric to the apex 81 of the holder curvature.

[0233] Figure 14 schematically illustrates possible positioning aids on the cornea implant holder 1 for fine positioning.

[0234] These structures can be evaluated using machine image recognition via the processing laser. The (optional) curved area of ​​the tissue holder 11 is shown in a different color (hatching) in these illustrations; however, this color is not intended to be a marking, and all markings are shown in black. (The structures shown can also be combined.) (a) Shows a pupil structure 93 centered on the apex 81 of the tissue holder 11, which can be detected by the processing laser. This allows a lateral offset between the tissue holder 11 and a processing center to be detected and corrected. (b) Shows an iris structure 95, which, in addition to the pupil 93, makes not only a lateral offset but also an angular offset between the processing system and the tissue holder 11 detectable and correctable.c) shows a variant of the iris structure 95 in which iris elements 95a have been replaced by a pattern 95b, which can, for example, additionally encode information 95c about the type of tissue holder 11 or the tissue 49. d) shows peripheral structures 97 at the edge of the processing area 75, where no tissue 49 to be processed (i.e., approximately 5 mm distance to the apex 81 of the tissue holder 11) is located.

[0235] Figure 15 schematically shows possibilities for marking the tissue alignment using templates 99 precisely manufactured to fit the tissue holder 11 or cornea implant holder 1.

[0236] This allows the orientation of the tissue 49 relative to the tissue holder 11, which is known exactly by the methods described above, to be marked directly on the tissue holder 11.

[0237] (a) For this purpose, precisely manufactured stamps or stencils 99, 101 for common surgical marking instruments 107 such as a cornea marker 109 can be used.

[0238] (b) shows trypan blue marker pens 107a commonly used in ophthalmology for marking tissue 49 using a template 103 for such a cornea marker 109

[0239] (c) shows a stencil 105 for a marking pen 107 with more complex marking patterns for structuring a flat application of trypan blue.

[0240] The templates 99 can have unique orientation structures relative to the tissue holder 11 so that they can be aligned with each other. Preferably, however, this is achieved by precisely fitting mechanical structures 111 and 113, which are designed as counterparts and are integrated into template 99 and tissue holder 11, or into template 99 and the surrounding structures (e.g., housing) of the tissue holder 11. Figure 16 schematically illustrates a diagram for the detection of a phase transition via specular reflection 115 and diffuse reflection 117. a) shows the beam path 119 of the detection light 121 from a light source 122 towards the detector “S” for specular reflection 115. The upper image shows a side view, the lower image a top view of the tissue holder 11. b) illustrates diffuse scattering 117 after icing, which now partly reaches the detectors 123 for diffuse scattered light 125 “D1” and “D2”.c) shows the change in the detector signals at time 127 of the phase transition129.

[0241] Figure 17 schematically illustrates another possibility for detecting the freezing of tissue 49 (i.e., the phase transition 129 of the material of tissue 49).

[0242] Shown is a detection of the contrast 131 of central 133 and peripheral markers 97. Due to the phase transition 129, the contrast 131 of the markers 133 obscured by the tissue 49 decreases significantly from a first contrast 131a before freezing to a second contrast 131b, while a third contrast 131c of peripheral markers 97 remains essentially constant before freezing and corresponds to a fourth contrast 131d after freezing.

[0243] Figure 18 schematically illustrates another possibility for detecting a phase transition 129. It shows thermal imaging camera measurement data 135 of the phase transition 129 of a freezing sample 49. The temperature 145 is shown as a function of time 147.

[0244] Cooling occurs at an average rate of -1°C per second. The tissue remains well below freezing for several seconds (time span 139) before the phase transition occurs at t=22s. The temperature measurement then shows the released latent heat as a brief warming (up to 150°C / s for < 60 ms).

Claims

1. Cornea implant holder (1) comprising at least one tissue holder (11) for receiving a cornea implant or cornea graft, a tissue holder base (7) and at least one temperature control unit (3, 24), wherein the at least one temperature control unit (3, 24) is arranged in the tissue holder base (7) and is configured to temperature control the at least one tissue holder (11).

2. Cornea implant holder (1) according to claim 1, wherein the temperature control unit (3) a) comprises at least one body serving as a cold reservoir (27) (also: passive cooling element 24) or is a body serving as a cold reservoir (27); and / or b) comprises at least one active cooling element (3) or is an active cooling element (3).

3. Cornea implant holder (1) according to claim 2, wherein the at least one passive (24) and / or active cooling element (3) has a first contact surface (31) which is designed to improve thermal conductivity and / or heat transfer between the cooling element (3, 24) and the tissue holder (11). - indirectly, via a (preferably sterile) contact medium (5), a second contact surface of the tissue holder (11) facing away from a support surface for the placement or reception of a corneal implant; and / or - directly through a first contact surface (31) machined to minimize surface roughness and / or a second contact surface machined to minimize an air gap between the first and second contact surfaces, the second contact surface is contacted.

4. Cornea implant holder (1) according to claim 2 or 3, wherein in case a) a passive cooling element (24): A1 ) the cooling element (24) comprises or consists of a material with a specific heat capacity greater than or equal to approximately 300 joules per kilogram per kelvin (J / (kg K)); and / or A2) the passive cooling element (24) in a complementary pocket (27) or recess of the tissue holder (1) is receptive or recorded, with the recording taking place without mechanical play; and / or A3) the height extent of the cornea implant holder (1) is essentially determined by the height extent of the passive cooling element (24); and in case b) of an active cooling element (3): B1) this comprises, in any combination and / or number, at least one heat exchanger and / or at least one Peltier element and / or at least one refrigeration unit; and / or B2) this includes a temperature sensor (9) which is configured to determine the temperature of the tissue holder (11) and to provide a temperature value representing this determined temperature; and / or B3) this includes or is connectable to a temperature controller (15), wherein the temperature controller (15) is configured to regulate the temperature of the tissue holder (11) to the predetermined temperature by comparing a measured temperature of the tissue holder (11) with a predetermined temperature (T_set) of the tissue holder (11); and / or B4) this comprises or is connectable to at least one humidity sensor (17, 19), wherein the humidity sensor (17, 19) is configured to determine the water content of the air or gas or gas mixture arranged around a fabric (49) resting on the fabric holder and to provide a humidity value representing the moisture content; and / or B5) this includes or is connectable to at least one control system (13), wherein the control system (13) is designed to act as an interface for human-machine interaction and to provide appropriate input and output means.

5. Cornea implant holder (1) according to any one of claims 1 to 4, wherein the tissue holder (11) comprises or consists of at least one material from the following list of materials: - A titanium compound; - Stainless steel; - Silicon carbide; - Aluminum oxide; - Silicon nitride; - Aluminum nitride; and - Calcium fluoride (CaF).

6. Cornea implant holder (1) according to one of claims 1 to 5, further comprising at least one device for providing and / or monitoring and / or controlling or adjusting process parameters of dry air (51) surrounding tissue on the tissue holder or of an inert protective gas surrounding tissue on the tissue holder.

7. Cornea implant holder (1 ) according to claim 6, further comprising flow-shaping and / or flow-shielding elements for generating a laminar flow (47) of the dry air (51 ) or the inert protective gas in the area of ​​a tissue (49) positioned on the tissue holder (11 ) or for shielding against turbulence caused by other air currents (69).

8. Cornea implant holder (1) according to one of claims 1 to 7, further comprising at least one radiation trap for absorption of therapeutic radiation, wherein a control device is provided which is configured to direct a subset of individual processing pulses of the therapeutic radiation into the at least one radiation trap.

9. Cornea implant holder (1) according to any one of claims 1 to 8, further comprising at least one device for detecting a Phase transition (129) of a tissue (49) arranged on the tissue holder (11), wherein the device: - is designed to simultaneously detect at least one first detector signal representing a specular reflection (115) and at least one second detector signal representing a diffuse scattering (117), to evaluate a relative change of the detected detector signals to each other, and to detect a phase transition (129) as a function of the relative change of the detected detector signals to each other; and / or - is designed to record at least one central (133) marking located under the tissue (49) when the tissue (49) is placed on the tissue holder (11), to evaluate the contrast (131) of the marking (133) and to detect a phase transition (129) depending on a change in the contrast (131) of the central marking (133); and / or - is designed to determine a temperature profile of the tissue holder (11 ) and thus indirectly a temperature profile of a tissue (49) arranged on the tissue holder (11 ) and to detect a phase transition (129) depending on a temperature change (143) attributable to the release of latent heat.

10. Cornea implant holder (1) according to any one of claims 1 to 9, further comprising c) at least one reference structure for referencing or positioning a cornea implant or cornea graft to the tissue holder (11); and / or d) at least one referencing device for referencing or positioning a cornea implant or cornea graft to the tissue holder (11); and / or e) at least one alignment structure for referencing or positioning the implant holder (1) to a processing device.

11. Cornea implant holder (1) according to claim 10, wherein - If at least one reference structure according to c) exists, these: (C1) includes at least one color marking and / or marking obtained by surface modification of the tissue holder; and / or (C2) comprises individual lines intersecting in an imaginary extension, or intersecting lines, and / or at least one, preferably at least two, concentric circles (79) as a marker; and / or (C3) is centered on an apex (81) of a curved part (75) of the tissue holder (11) facing a processing device; wherein - If at least one referencing device according to d) is present, these (D1) A ring-shaped centering element that can be precisely fitted to or placed on the tissue holder; and / or (D2) Can be inserted into a recess (87) provided on the tissue holder (11) or into a raised area provided on the tissue holder (11) without mechanical play; and / or (D3) Has an inner diameter that corresponds to the diameter of a fabric to be processed (49); and / or (D4) has inlets and outlets designed to supply a fluid to the tissue (49) or to discharge it away from the tissue (49); and wherein - If at least one alignment structure according to e) is present, this (E1) On a support area for the application of a tissue (49) at least one structure from the list of structures comprising a pupil structure (93); an iris structure (95); and a varied iris structure (95) whose iris elements (95a) have been replaced by a pattern (95b); and / or (E2) Has at least one peripheral alignment structure (97) on a peripheral edge area of ​​the tissue holder located outside the support area.

12. Cornea implant holder (1) according to one of claims 1 to 11, further comprising a marking template (99) which can be uniquely positioned and attached to the tissue holder (11) in a predetermined position and rotation, and which allows access to the cornea implant or cornea graft positioned on the tissue holder (11) for the purpose of applying a marking at predetermined marking positions.

13. Procedure for processing a corneal implant or a corneal graft, at the dew point, comprising the following procedural steps: - Providing the corneal implant or corneal graft in a processing area of ​​the processing device on the tissue holder (11) of a corneal implant holder (1) - Measuring environmental parameters to determine the dew point and determining the dew point based on the environmental parameters; - Setting a target temperature (T_set), possibly taking into account a temperature offset (T_offset); - Starting the temperature control process while continuously measuring the humidity and continuously adjusting the target temperature (T_set) depending on the humidity; - Positioning the corneal implant or corneal graft; - Adopting a working temperature as the new target temperature under continuous temperature adjustment; - Editing the corneal implant or corneal graft upon reaching the new target temperature (T_set); and optionally - Setting a storage temperature to be achieved for storing the processed corneal implant or the processed corneal graft; and optionally - Placing a mark on the processed corneal implant or corneal graft.

14. Method for processing a frozen corneal implant or a frozen corneal graft, comprising the following process steps: - Providing the corneal implant or corneal graft in a processing area of ​​the processing device on the tissue holder (11) of a corneal implant holder (1) - Measuring environmental parameters to determine the dew point and determining the dew point based on the environmental parameters; - Setting a target temperature (T_set), possibly taking into account a temperature offset (T_offset); - Starting the temperature control process while continuously measuring the humidity and continuously adjusting the target temperature (T_set) depending on the humidity; - Positioning the corneal implant or corneal graft; - Adopting a working temperature as the new target temperature under continuous temperature adjustment; - Supply of dry air (51 ) or an inert gas, at least in an area around the corneal implant or corneal graft; - Checking starting conditions regarding the freezing of the corneal implant or corneal graft; - Processing of the corneal implant or corneal graft upon reaching the new target temperature; - Termination of the supply of dry air (51) or inert gas after completion of the processing of the corneal implant or corneal graft; and optionally - Setting a storage temperature to be achieved for storing the processed corneal implant or the processed corneal graft; and optionally - Placing a mark on the processed corneal implant or corneal graft.

15. The method of claim 14, wherein the method step of checking starting conditions comprises the method step of detecting the freezing of the cornea implant or cornea graft, wherein this method step further comprises: - Detecting a first detector signal representing a specular reflection (115); detecting a second detector signal representing a diffuse scattering (117); evaluating a relative change of the detected detector signals to each other; and detecting a phase transition (129) as a function of the relative change of the detected detector signals to each other; or - Recording at least one central (133) marker located under the tissue (49) when the tissue (49) is resting on the tissue holder (11); evaluating the contrast (131) of the marker (133); and detecting a phase transition (129) as a function of the change in the contrast (131) of the central marker (133); or - Determining a temperature profile of the tissue holder (11 ) and thus indirectly a temperature profile of a tissue (49) arranged on the tissue holder (11 ); and detecting a phase transition (129) as a function of a temperature change (143) attributable to the release of latent heat.

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