WO2020125435A1 - 一种太赫兹角膜热成形术系统和方法 - Google Patents

一种太赫兹角膜热成形术系统和方法 Download PDF

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WO2020125435A1
WO2020125435A1 PCT/CN2019/123438 CN2019123438W WO2020125435A1 WO 2020125435 A1 WO2020125435 A1 WO 2020125435A1 CN 2019123438 W CN2019123438 W CN 2019123438W WO 2020125435 A1 WO2020125435 A1 WO 2020125435A1
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terahertz
corneal
cornea
temperature
monitoring
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刘文权
鲁远甫
李光元
佘荣斌
焦国华
吕建成
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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Priority claimed from CN201822129470.4U external-priority patent/CN209474947U/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/013—Instruments for compensation of ocular refraction ; Instruments for use in cornea removal, for reshaping or performing incisions in the cornea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/0008—Apparatus for testing the eyes; Instruments for examining the eyes provided with illuminating means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions

Definitions

  • This application relates to the field of biomedical engineering technology and terahertz technology, in particular to a corneal thermoforming technology using terahertz waves.
  • Corneal thermoplasty means that the collagen tissue is heated and contracted and denatured by a certain heat source at an appropriate depth of the corneal stroma layer. This leads to a change in the three-dimensional structure of the corneal stroma layer, which causes the corneal curvature to change to achieve the purpose of changing the corneal refractive power.
  • the collagen tissue of the corneal stroma layer begins to shrink or change its three-dimensional structure when it continues to 55 °C; it reaches its ideal or permanent contraction state at 65 to 70 °C; when the temperature continues to exceed 70 °C, the corneal collagen tissue begins to dissolve,
  • the hydrolysis of the collagen silk sliding cross-linked structure will lead to the destruction of the three-dimensional spiral structure, which makes the collagen fibers elongate and become relaxed; when the temperature exceeds 75-80°C, the collagen tissue will necrosis, the corneal injury reaction will occur, and the corneal cells will proliferate , New collagen production, causing scars and refractive regression.
  • the key to corneal thermoplasty is how to permanently change the three-dimensional structure of the corneal stroma. Therefore, during the implementation of corneal thermoplasty, the temperature within the cornea should be controlled as much as possible within the range of 65 °C ⁇ 70 °C.
  • corneal thermoplasty mainly focuses on probe corneal thermoplasty, conductive corneal thermoplasty, laser corneal thermoplasty, etc., mainly used for the treatment of hyperopia, presbyopia and astigmatism correction.
  • the above-mentioned existing technologies all have certain disadvantages.
  • Probe keratoplasty uses a heated probe to act on the center of the cornea. This procedure has the disadvantages of difficult to control coagulation depth, poor predictability, and obvious postoperative refractive regression.
  • Conductive keratoplasty uses radiofrequency energy as a heat source, uses the electrical properties of corneal tissue, and releases radiofrequency energy to heat collagen and cause collagen contraction; however, due to corneal contact problems, treatment is likely to cause discomfort and postoperative patients. Corneal epithelial cell ulceration; at the same time, because of the problem of hot spot location, it may also cause temporary irregular astigmatism caused by the treatment probe not perpendicular to the corneal surface; moreover, due to system design issues, it is difficult to change the surgical parameters once set .
  • Laser keratoplasty uses a laser to heat the corneal stroma, causing its collagen fibers to contract, thereby changing the corneal refractive power. It is a non-invasive treatment of the cornea.
  • the present application proposes to use the proper penetration depth of the terahertz wave and the cornea to solve the technical problem of insufficient depth of the photocoagulation point, and scan and irradiate the shaped terahertz beam
  • the optimal surgical parameters are formulated according to the real-time feedback of the corneal surface temperature, corneal thickness, corneal refractive power and corneal topography, thereby making the postoperative refractive power and corneal deformation more stable and can be effectively reduced Corneal refractive regression after operation.
  • Terahertz (THz) wave refers to electromagnetic waves with a frequency in the range of 0.1 to 10 THz.
  • the frequency is between microwave and infrared bands. It has the characteristics of microwave and light waves. It has low quantum energy, large bandwidth, and good penetration. And other characteristics, it has great scientific value and application prospects in the fields of basic physics, industrial applications, biomedicine, and national defense security.
  • Water has strong absorption of terahertz waves, so that the penetration depth of terahertz waves in biological tissues is about several hundred microns. When the terahertz wave is irradiated onto the biological tissue, it can be absorbed by the water in the biological tissue and transformed into heat, and the thermal effect of the biological tissue is generated.
  • the corneal tissue is rich in water (75%-85%), and the thickness (400-700 ⁇ m) is equivalent to the terahertz wavelength, so compared with the infrared light source used in the existing corneal thermoplasty, too
  • the wavelength of the Hertz wave is longer, and a deeper penetration depth matching the corneal tissue can be obtained in the corneal tissue, and the corresponding thermal effect is more significant.
  • the energy of the terahertz wave increases, the corneal tissue heats up under the irradiation of the terahertz wave and can completely reach the temperature of the corneal stromal layer thermal deformation. Therefore, terahertz waves can be a new heat source for corneal thermoplasty.
  • a terahertz keratoplasty system which is characterized by including a terahertz laser as a heat source and a collimated scanning module, so as to irradiate a terahertz beam onto the cornea;
  • the collimating scanning module includes a collimator, a power adjustment part and a two-dimensional scanning device.
  • the two-dimensional scanning device is a two-dimensional galvanometer scanning system with beam shaping function. Or a beam shaper and/or a corneal marker are further provided behind the two-dimensional scanning device.
  • the power adjustment part may specifically be a terahertz attenuator; the collimator includes a first terahertz reflector and a second terahertz reflector.
  • the beam after passing through the terahertz attenuator is split by a terahertz beam splitter; one beam is received by the terahertz power meter for power detection, and the other beam is used to illuminate the eyeball.
  • the system further includes a temperature monitoring control unit to obtain the spatial distribution information of the cornea temperature through a high-resolution infrared thermal imager.
  • the temperature monitoring control unit may further include a cooling module for adjusting the temperature of the cornea according to the monitoring result of the high-resolution infrared thermal imager.
  • system further includes a computer control section, through which the two-dimensional scanning device and/or the refrigeration module are controlled; wherein the control of the two-dimensional scanning device and/or the refrigeration module refers to the High-resolution infrared thermal imager monitoring results.
  • the system further includes one or more corneal physiological parameter feedback units, and the monitoring results of the corneal physiological parameter feedback unit are sent to the computer control section for adjusting the terahertz beam irradiated to the cornea.
  • the corneal physiological parameter feedback unit is one or more of an ophthalmic optical coherence tomography scanner, a corneal topograph, and an eyeball follower.
  • the system may also include an operating microscope and an ITO spectroscope for observing the surgical procedure, and the light beam passing through the two-dimensional scanning device is reflected by the ITO spectroscope and irradiated on the cornea of the eyeball; the light beam reflected by the eyeball is transmitted through The ITO spectroscope is used to obtain surgical monitoring information.
  • the present application also proposes a terahertz corneal thermoforming method, which is characterized by using a terahertz laser as a heat source, and irradiating the terahertz beam onto the cornea with a collimating scanning module.
  • the power density of the terahertz laser is 5000-8000W/m 2 , preferably 6000W/m 2 .
  • the cornea is heated for 180 to 720 seconds.
  • the method further includes using a temperature monitoring control unit to obtain corneal temperature spatial distribution information; and referring to the corneal temperature spatial distribution information to adjust the terahertz beam irradiated on the cornea, or directly referring to the corneal temperature spatial distribution information Adjust the temperature of the cornea.
  • the method further includes acquiring monitoring information during the operation, the monitoring information including one or more of corneal thickness information, corneal refractive power information, corneal topography, and the center position of the pupil of the eyeball; and adjusting the irradiation with reference to the monitoring information A terahertz beam onto the cornea, or directly adjust the temperature of the cornea with reference to the monitoring information.
  • the terahertz corneal thermoforming technology proposed in this application has the following technical effects:
  • the terahertz laser Due to the use of a high-power continuous wave terahertz laser with a frequency in the range of 0.1 to 10 THz, compared with the infrared laser used in the prior art, the terahertz laser has a longer wavelength and a deeper penetration depth in the corneal tissue And the power of the terahertz beam is adjustable, and the shaping scan of the terahertz beam is controllable, so that the corneal thermocoagulation depth and the uniformity of heating are significantly improved.
  • the system is equipped with a high-resolution infrared thermal imager. According to the spatial distribution information of the corneal surface temperature provided by the imager, the scanning situation of the terahertz beam can be estimated, and further combined with the real-time feedback of the terahertz beam scanning mirror and the eyeball follower. Greatly improve the accuracy of the control of the position of the corneal operation of the terahertz beam during the operation.
  • the temperature monitoring and control unit composed of a high-resolution infrared thermal imager and a cooling module realizes the prediction and control of the corneal temperature, which can effectively prevent the cornea from being heated too high and too fast during the operation and causing thermal damage.
  • Figure 1 shows a schematic diagram of a corneal thermal analysis model
  • Figure 2 shows the corneal temperature with time under irradiation of THz beams with different power densities (frequency 1THz, beam diameters (a) 2mm, (b) 4mm, (c) 5mm, (d) 6mm and (e) 8mm) Change graph;
  • FIG. 3 shows a prediction map of the stromal coagulation zone after a terahertz beam with a frequency of 1 THz, a beam diameter of 6 mm, and a power density of 6000 W/m 2 is irradiated to the cornea for 1200 seconds;
  • Figure 4 shows a schematic diagram of the prediction of thermal damage after a terahertz beam with a frequency of 1 THz, a beam diameter of 6 mm, and a power density of 6000 W/m 2 after irradiating the cornea for 1200 seconds; the left picture shows the spatial distribution and the right picture shows the corneal surface The thermal damage at the center changes with time;
  • FIG. 5 shows a schematic diagram of the terahertz corneal thermoforming system of the present application.
  • terahertz radiation power level generated by the laboratory is about 10mW ⁇ 100W.
  • the terahertz peak power generated by the energy recovery linear accelerator can reach 10KW (kW), and the free electron laser can even reach MW (million watt). This also cleared the technical barrier for terahertz waves to become a heat source for corneal thermoplasty.
  • the corneal tissue is rich in water (75% to 85%), and the thickness (400 to 700 ⁇ m) is equivalent to the terahertz wavelength, so it is based on the absorption of terahertz waves by water and is used in existing corneal thermoplasty Compared with the infrared light source, the terahertz wave can obtain a deeper penetration depth matching the corneal tissue in the corneal tissue, and the corresponding thermal effect is also more significant. Under the irradiation of terahertz waves with sufficient power, the thermal effect can cause the corneal tissue to heat up to the temperature of thermal coagulation deformation.
  • a thermal analysis model of the cornea is established based on a two-dimensional axisymmetric cylindrical coordinate system, as shown in FIG. 1 of the specification.
  • the model assumes that the cornea and related structures are cylinders with a diameter of 15 mm, which are mainly three-layer structures, including a tear film with a thickness of 10 ⁇ m, a cornea with a thickness of 600 ⁇ m, and an aqueous humor layer with a thickness of 2 mm.
  • T is the temperature field inside the biological tissue (°C)
  • ⁇ is the density of the biological tissue (kg/m3)
  • k is the thermal conductivity of the biological tissue (W/m/K)
  • C is the specific heat capacity of the biological tissue (J /kg/K)
  • q is the terahertz heat source.
  • terahertz beams are generally regarded as Gaussian beams. Without loss of generality, the terahertz heat source is defined as follows:
  • P d is the power density of terahertz beam
  • w 0 is the terahertz beam radius
  • ⁇ is the absorption coefficient of biological tissue
  • r and z represent radial distance and longitudinal thickness, respectively.
  • the thermal performance parameters used in corneal thermal analysis can be obtained by consulting literature reports, as shown in the following table.
  • thermal damage of corneal tissue is determined by the temperature and heating time of the tissue. According to Arrheniusequation, the thermal damage degree factor can be obtained as follows:
  • ⁇ (t) is the thermal injury degree factor of corneal tissue
  • the terahertz beam diameter is generally on the order of millimeters, and the smallest beam diameter under the focus of the commonly used terahertz lens is about 2 mm.
  • the diameter of the photocoagulation zone of laser keratoplasty is generally between 6.0 and 7.5 mm, so the selection range of the terahertz beam diameter is 2 to 8 mm.
  • the initial temperature of the cornea was set to 35 °C
  • the irradiation time was 1200 seconds
  • the finite element method was used to simulate and calculate the center position of the cornea surface in the high-power terahertz beam ( The working frequency of the simulation calculation is set to 1 THz, the beam diameter is 2 to 8 mm, and the power density is 1000 to 10000 W/m 2 )
  • the temperature increase under irradiation is shown in FIG. 2 of the specification. This results in a terahertz beam diameter of 2mm, 4mm, 5mm, 6mm and 8mm.
  • the terahertz beam can reach the power density range of safe photocoagulation temperature (55 ⁇ 75°C) and optimal operation temperature (65 ⁇ 70°C) , See Table 2 for details.
  • the analysis is made for the case where the terahertz beam diameter is 6.0 mm (the diameter of the photocoagulation area of laser corneal thermoplasty is generally between 6.0 and 7.5 mm).
  • the figure shows that, under the condition that the irradiation time and the beam diameter are fixed, the magnitude and speed of the corneal heating depends on the power density of the irradiated terahertz beam. The higher the terahertz beam power, the greater the corneal temperature increase and the faster the temperature increase.
  • the corneal temperature rise range is about 5 ⁇ 64 °C.
  • the temperature of the cornea rises sharply in the first 60 seconds, and the temperature rises gently in 60 to 180 seconds, and reaches a certain steady-state temperature value after 180 seconds (the temperature will not increase even under the long-term irradiation of the terahertz beam).
  • the optimal operation temperature of corneal thermoplasty is 65 ⁇ 70°C, and the terahertz heating of the cornea decreases from the surface to the endothelial surface, according to the heating curve, a terahertz beam with a power density of 4000 ⁇ 6000W/m 2 can Used for corneal thermoplasty, in particular, a terahertz beam of 6000 W/m 2 is preferably used for corneal thermoplasty.
  • the coagulation zone of the matrix (a region capable of degeneration) is estimated. Since the collagen tissue of the corneal stroma begins to contract and change its three-dimensional structure when continuing at 55°C, the area at a temperature of 55 to 75°C can be regarded as the stroma coagulation zone.
  • the gray area in the figure is the matrix solidification area estimated under the above simulation conditions.
  • a collagen-like degeneration zone with a cylindrical shape, a diameter of about 3000 ⁇ m, and a depth of 600 ⁇ m (up to the full cornea) is formed in the cornea along the terahertz propagation direction (corneal depth direction). Therefore, using the terahertz beam can achieve full-thickness and uniform corneal heating.
  • the thermal damage of the cornea under 1200 seconds of terahertz wave irradiation at a frequency of 1 THz, a beam diameter of 6 mm, and a power density of 6000 W/m 2 was also predicted.
  • the left picture shows the spatial distribution of the degree of corneal damage after 1200 seconds of heating.
  • thermal injury degree factor of corneal tissue there are generally the following views: when ⁇ (t) ⁇ 0.1, it can be considered as no thermal injury, which is an ideal situation; when 0.1 ⁇ (t) ⁇ 1, it is mild Thermal injury only causes undesirable reversible deformation of the corneal stroma; when ⁇ (t) ⁇ 1, it is a serious injury, which causes carbonization of the corneal stroma, resulting in irreversible necrosis and permanent destruction of the corneal tissue.
  • the center of the corneal surface is most damaged, and the thermal damage factor ⁇ reaches 0.16. The closer to the center of the corneal surface, the higher the degree of thermal damage, but it is a mild thermal injury.
  • thermal damage is also related to the amount of time accumulated, so the maximum acceptable heating time can be determined according to the time-dependent thermal damage at the center of the corneal surface (where the damage is most severe), and then Effectively avoid thermal damage to corneal tissue.
  • the time when the thermal damage factor ⁇ at the center of the corneal surface reaches 0.1 is about 720 seconds. Therefore, the longest heating time can be determined 720 seconds.
  • the cornea is optimally heated by a terahertz beam with a frequency of 1 THz, a beam diameter of 6 mm, and a power density of 6000 W/m 2 .
  • the time is 180 to 720 seconds.
  • the terahertz source is a heat source very suitable for corneal thermoplasty.
  • the terahertz heat source can be selected from currently available products such as gas lasers, quantum cascade lasers, and free electron lasers that can generate high-power terahertz radiation (0.1-10 THz).
  • this application proposes a terahertz corneal thermoforming system, as shown in FIG. 5 of the specification.
  • the system includes a high-power terahertz laser 1 and a matching collimating scanning module for generating and irradiating a terahertz beam to the human eye for surgery.
  • the laser 1 is a continuous laser with a frequency in the range of 0.1-10 THz.
  • the collimating scanning module includes a collimator composed of a first terahertz mirror 2 and a second terahertz mirror 3, a power adjustment section formed by a terahertz attenuator 4, and beam shaping and XY two-dimensional Scanned device.
  • the beam emitted by the continuous laser 1 is collimated by the first terahertz reflector 2 in the collimator to form parallel light, and the parallel light is split by a terahertz after passing through the terahertz attenuator 4
  • the mirror 5 splits the beam, one beam is received by the terahertz power meter 6 for power detection, and the other beam is reflected by the second terahertz mirror 3, and is realized by the XY two-dimensional galvanometer scanning system 7 with beam shaping function
  • the scanning of the light beam is finally irradiated onto the eyeball 9 after being reflected by the ITO beamsplitter 8 that reflects only the terahertz light beam and passes through the visible light.
  • the energy of the terahertz beam can be evenly distributed through beam shaping.
  • the scanning system 7 may be a general scanner, and a beam shaper is provided immediately after the scanning system 7.
  • a corneal marker suitable for the terahertz band can be provided after the above scanning system.
  • a metal sheet with a hole structure can be used to realize the corneal marker, and the size and shape of the aperture , Quantity, arrangement interval and other parameters are set to meet the needs in the photocoagulation area.
  • the system of the present application is also equipped with a high-resolution infrared thermal imager 10 and a cooling module on both sides of the eyeball 11.
  • the high-resolution infrared thermal imager 10 and the refrigeration module 11 together form a temperature monitoring and control unit, which helps to realize the prediction and control of the corneal temperature, and prevents the cornea from being heated too high and too fast during the surgery to cause thermal damage.
  • Infrared thermal imaging is an accurate, measurable, non-contact diagnostic technique.
  • the high-resolution infrared thermal imager 10 can use commercially available FLIR 655, FLIR T650, FLIR A6700, FLIR GF335, FLIR X8400 and other models to provide information on the spatial distribution of the corneal surface temperature. According to the previous simulation calculation, after the cornea is heated, the highest temperature is at the center of the terahertz beam on the cornea surface, and the temperature is attenuated in the direction of the beam radius. Based on the temperature profile, invisible terahertz beams can be detected and used for identification and target confirmation.
  • the cooling module 11 is, for example, a heat dissipation cooling module, which uses flowing air for cooling and cooling; or it can also use a small volume, light weight and easy to integrate plasma wind heat dissipation cooling, which uses the principle of ion discharge to generate air flow to achieve the cooling effect.
  • the distance between the cooling module 11 and the eyeball is between 5 cm and 15 cm.
  • the temperature monitoring control unit can also be combined with the monitoring results of the Ophthalmic Optical Coherence Tomography (OCT), corneal topography, and eyeball follower And feed back these monitoring result data to the computer control unit 20 to adjust the terahertz beam scanning mirror, so as to realize more precise control of the position of the terahertz beam in the corneal surgery during the operation.
  • Modules such as operating microscopes, ophthalmic optical coherence tomography (OCT), corneal topographs, and eyeball followers are equipped with light sources. After these light sources illuminate the eyeball 9, the light signal will be reflected from the eyeball 9.
  • a first beam splitter 12, a second beam splitter 13 and a third beam splitter 14 are provided in this order on the optical path of the eyeball 9 and the ITO beam splitter 8 after being reflected by the above optical signals to form a beam splitting system .
  • the first beam splitter 12 splits part of the light reflected by the eyeball to the operating microscope 15, and the operating staff can observe the entire surgical process through the operating microscope 15.
  • Ophthalmology OCT 16 is a mature instrument in the prior art. Ophthalmology OCT 16 can obtain corneal thickness information during the entire operation. In the system of the present application, the corneal thickness information obtained through the Ophthalmology OCT 16 is preferably fed back to the computer control unit 20 in real time. Specifically, Ophthalmology OCT can be used to monitor corneal thickness in real time. When the corneal thickness is less than 400 ⁇ m or greater than 700 ⁇ m, an early warning shutdown is required.
  • the size of the diameter according to the photocoagulation zone (region with a temperature greater than 55°C) can be observed in real time.
  • the contraction depth of the photocoagulation point can be obtained. Therefore, the thickness and temperature information can be corroborated with each other, and the two can be combined to evaluate the stromal coagulation area of corneal thermoforming surgery.
  • the scanning galvanometer is controlled to adjust the irradiation position of the terahertz beam, and the temperature of the cornea is controlled by using a corresponding cooling module.
  • the light beam reflected by the second beam splitter 13 and then reflected by the third beam splitter 14 will enter the corneal topograph 17 to detect the corneal topography and corneal diopter in real time.
  • a corneal topograph is used for monitoring, which can measure the corneal curvature in real time and reflect the morphological changes of the entire cornea.
  • the human eye can be roughly regarded as a complex concentric refractive system composed of multiple optical elements.
  • the light passes through the outer surface of the cornea, the corneal stroma, the inner surface of the cornea, the aqueous humor, and the anterior lens
  • the refractive effects of a series of media such as the surface lens matrix and nucleus, the posterior surface of the lens, and the vitreous body finally reach the retina for imaging.
  • the total refractive power of the eyeball is +58.64D
  • the refractive power of the cornea is +43.05D
  • the refractive power of the external corneal surface is 48.83D
  • the refractive power of the cornea accounts for 73.41% of the refractive power of the entire eyeball
  • the refractive power of the external corneal surface accounts for 83.27% of the refractive power of the entire eyeball .
  • the cornea is an important part of the refractive system of the eye, and the radius of curvature of the outer surface of the cornea plays a major role in the refractive power of the eye.
  • the effect of changing the refractive power can be evaluated based on the change in the radius of curvature of the outer surface of the cornea. For example, suppose the radius of curvature of the original outer surface of the cornea is r1. After the terahertz beam irradiates the cornea, the corneal contraction occurs according to the above-mentioned analysis of the corneal heat absorption characteristics, and the radius of curvature decreases to r2. When the radius of curvature changes from r1 to r2, its refractive power increases to ⁇ D, estimated as follows:
  • the light beam transmitted through the third beam splitter 14 and then reflected by the reflecting mirror 18 will be incident on the eyeball follower 19, which tracks and positions the pupil center of the eyeball.
  • the center of the pupil and the corneal surface temperature distribution map may be fused and registered to try to keep the pupil center mark coincident with the bright spot in the temperature distribution map.
  • the scanning system is controlled to adjust the irradiation position of the terahertz beam so that the center of the terahertz beam coincides with the center of the upper surface of the cornea.
  • the scanning system 7, high-resolution infrared thermal imager 10, cooling module 11, ophthalmology OCT 16, corneal topograph 17 and eyeball follower 19 are all connected to the computer control unit 20.
  • the detection results of high-resolution infrared thermal imager 10, ophthalmology OCT 16, corneal topograph 17 and eyeball follower 19 and other instruments are transmitted to the computer control unit, thereby monitoring the operation process in real time.
  • it can be automatically adjusted by the computer or manually by advanced users and staff to make appropriate adjustments to the terahertz heat source and temperature monitoring and control unit, so as to achieve the most optimal surgical effect and achieve the stability of the corneal thermoforming effect. It makes the postoperative refractive power and corneal deformation more stable, and effectively reduces the technical effect of postoperative corneal refractive regression.
  • the terahertz keratoplasty technology of the present application has been described above.
  • the terahertz keratoplasty system mainly includes a terahertz heat source, a temperature monitoring control unit, a corneal physiological parameter feedback, and a computer control unit.
  • the work of the system is realized by computer control.
  • the terahertz heat source unit realizes the energy adjustment, conditioning and scanning of the terahertz beam according to the feedback of the real-time monitoring parameters of the operation.
  • the temperature monitoring and control unit implements temperature monitoring and feedback control of the cornea to prevent thermal damage caused by excessive or rapid corneal temperature increase.
  • Each corneal physiological parameter feedback unit realizes the monitoring of eye state, corneal thickness, corneal refractive power, corneal topography and surgical process, which provides a basis for the optimization of surgical parameters.
  • the computer control unit adjusts the relevant parameters of the terahertz source according to the monitoring of the temperature monitoring control unit and each corneal physiological parameter feedback unit.
  • the user can also feedback the terahertz heat source, corneal temperature monitoring, and corneal physiological parameters according to the needs.
  • Each part of the unit performs corresponding operations to improve the stability of the corneal thermoforming effect as a whole and effectively reduce the incidence of corneal refractive regression after surgery.

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Abstract

一种太赫兹角膜热成形系统和一种太赫兹角膜热成形方法。具体使用太赫兹激光器（1）作为热源，利用相配套的准直扫描模块将太赫兹光束照射到眼球（9）角膜上。进一步使用温度监测控制单元获得角膜温度空间分布信息，并参考角膜温度空间分布信息调整照射到角膜上的太赫兹光束，或者直接调整角膜的温度。同时获取角膜厚度信息、角膜屈光度信息、角膜地形图以及眼球（9）瞳孔中心位置中的一个或者多个手术监测信息，并参考监测信息调整照射到角膜上的太赫兹光束，或者直接调整角膜的温度。角膜热成形手术中的热凝深度和受热均匀性均有明显的提高，有效减少屈光回退的发生。

Description

一种太赫兹角膜热成形术系统和方法 技术领域
本申请涉及生物医学工程技术领域和太赫兹技术领域，特别是涉及一种使用太赫兹波的角膜热成形技术。
背景技术
角膜热成形术即通过某种热源在角膜基质层的适当深度加热，使胶原组织受热收缩、变性，如此导致角膜基质层三维结构的改变，从而使得角膜曲率发生改变以达到改变角膜屈光度的目的。研究证明，角膜基质层的胶原组织在持续55℃时开始收缩或改变其三维结构；65～70℃时达到其理想或永久的收缩状态；当温度持续超过70℃时，角膜胶原组织开始溶解，就会由于胶原丝滑动交联结构的水解而导致三维螺旋结构的破坏，从而使胶原纤维拉长变得松弛；温度超过75～80℃时，胶原组织发生坏死，角膜发生损伤反应，角膜细胞增殖、新生胶原产生，引起瘢痕和屈光回退。如果胶原组织受热但未能达到上述特定的温度，组织将复水，进而重新恢复到原来的结构，同时导致屈光回退。为保持屈光稳定，减少屈光回退，角膜热成形术的关键是如何永久性地改变角膜基质层的三维结构。因此，在角膜热成形术的实施过程中角膜内温度应尽量控制到范围在65℃～70℃之间。
目前，国际上关于角膜热成形术的研究主要集中于探针角膜热成形术、传导性角膜热成形术、激光角膜热成形术等，主要用于治疗远视、老视和散光的矫正。但是上述现有技术均存在一定的缺点。
探针角膜热成形术通过一根受热的探针作用于角膜中央部，该手术存在着凝固深度不易控制、预测性差、术后屈光回退明显的缺陷。
传导性角膜热成形术以射频能量为热源，利用角膜组织的电学特性，通过释放射频能量使胶原产热并引起胶原收缩；但是由于角膜接触问题，治疗易引 起术后患者的不适感且易引发角膜上皮细胞的溃烂；同时，因为热凝点定位问题可能还导致治疗探头不垂直于角膜表面而引起的暂时性不规则散光；而且，由于系统的设计问题，手术参数一旦设定就很难改变。
激光角膜热成形术使用激光对角膜基质加热，使其胶原纤维收缩，从而改变角膜的屈光度，是一种非入侵式治疗角膜的手段。研究发现减少术后屈光回退的关键在于在角膜组织内形成全层而均匀的基质凝固区，只有热凝固深度相宜、受热均匀，并维持持续而稳定的升温作用，才能使角膜基质胶原纤维热凝固,以达到治疗目的。但是现有激光角膜热成形术难以达到与角膜相宜的穿透深度，组织切片研究发现激光角膜热成形术产生的加热深度只达50％，而且全层受热不均匀，无法在角膜组织形成全层而均匀的基质凝固区，因此术后的屈光稳定性较差。此外，现有激光角膜热成形术设备中，通过棱镜将一束激光分成独立的多束激光进行加热，但也往往存在分束后的各加热激光能量不均匀的问题，因而还容易造成角膜局部的热损伤。
基于以上技术问题，为保持屈光稳定，减少屈光回退，学者们在不断寻找更新、更好的热源，优化搭建可靠性更强的系统，以达到更好的治疗效果。
申请内容
有鉴于此，针对上述现有技术存在的技术问题，本申请提出利用太赫兹波与角膜相宜的穿透深度以解决光凝点的深度不足的技术问题，并通过对整形的太赫兹光束扫描照射以解决角膜受热不均的问题，同时，根据角膜表面温度、角膜厚度、角膜屈光度和角膜地形图的实时反馈制定最优的手术参数，由此使得术后屈光度及角膜形变更加稳定，能有效减少术后角膜屈光回退。
太赫兹(THz)波是指频率在0.1～10THz范围内的电磁波，其频率介于微波和红外波段之间，兼有微波和光波的特性，具有低量子能量、大带宽、良好的穿透性等特点，在基础物理、工业应用、生物医学和国防安全等领域具有重大的科学价值和应用前景。水对太赫兹波具有强烈的吸收，使得太赫兹波在生物组织的穿透深度约几百微米。当太赫兹波被照射到生物组织上时，其能够被生物组织里的水吸收而转变为热，生物组织的热效应便由此产生。对于角膜 组织而言，角膜组织富含水分(75％～85％)，厚度(400～700μm)与太赫兹波长相当，因此与现有角膜热成形术中使用的红外波段的光源相比，太赫兹波的波长更长，在角膜组织中能够获得与角膜组织相匹配的更深的穿透深度，相应的热效应也更为显著。随着太赫兹波能量的增大，角膜组织在太赫兹波的照射下升温并完全能够达到角膜基质层热凝形变的温度。因而太赫兹波完全能够成为一种用于角膜热成形术的新型热源。
具体的，本申请提出了一种太赫兹角膜热成形术系统，其特征在于：包括作为热源的太赫兹激光器以及相配套的准直扫描模块，从而将太赫兹光束照射到眼球角膜上；所述准直扫描模块包括准直器、功率调节部和二维扫描器件。
其中所述二维扫描器件为带有光束整形功能的二维振镜扫描系统。或者在所述二维扫描器件后还设置有光束整形器和/或角膜标记器。
所述功率调节部具体可以为太赫兹衰减片；所述准直器包括第一太赫兹反射镜和第二太赫兹反射镜。经过太赫兹衰减片后的光束被一个太赫兹分束镜进行分束；一束被太赫兹功率计接收用于功率检测，另一束用来照射眼球。
优选地，系统还包括温度监测控制单元，通过高分辨红外热成像仪来获得角膜的温度空间分布信息。所述温度监测控制单元还可以包括制冷模块，用于根据所述高分辨红外热成像仪的监测结果调整角膜的温度。
进一步，系统还包括计算机控制部，通过所述计算机控制部控制所述二维扫描器件和/或所述制冷模块；其中对所述二维扫描器件和/或所述制冷模块的控制参考所述高分辨红外热成像仪的监测结果。
进一步优选，系统还包括一个或者多个角膜生理参数反馈单元，所述角膜生理参数反馈单元的监测结果被输送到所述计算机控制部用以调整照射到角膜的太赫兹光束。具体地，所述角膜生理参数反馈单元为眼科光学相干断层扫描仪、角膜地形仪以及眼球跟随仪中的一个或多个。
此外，系统还可以包括用于对手术过程进行观察的手术显微镜、ITO分光镜，经过所述二维扫描器件的光束由所述ITO分光镜反射照射到眼球角膜上；由眼球反射的光束透过所述ITO分光镜后用于获取手术监测信息。
本申请同时还提出一种太赫兹角膜热成形方法，其特征在于：使用太赫兹激光器作为热源，利用相配套的准直扫描模块将太赫兹光束照射到眼球角膜上。其中所述太赫兹激光器的功率密度为5000～8000W/m 2，优选为6000W/m 2。而角膜受热的时间为180～720秒。
优选地，所述方法，还包括使用温度监测控制单元获得角膜温度空间分布信息；以及参考所述角膜温度空间分布信息调整照射到角膜上的太赫兹光束，或者参考所述角膜温度空间分布信息直接调整所述角膜的温度。
进一步所述方法还包括获取手术中的监测信息，所述监测信息包括角膜的厚度信息、角膜屈光度信息、角膜地形图以及眼球瞳孔中心位置中的一个或者多个；以及参考所述监测信息调整照射到角膜上的太赫兹光束，或者参考所述监测信息直接调整所述角膜的温度。
其中所述调整照射到角膜上的太赫兹光束或者所述直接调整所述角膜的温度的操作是通过计算机控制部完成的。
本申请提出的太赫兹角膜热成形技术相对于现有角膜热成形术而言具有如下的技术效果：
1、由于使用了频率在0.1～10THz范围内的高功率连续波太赫兹激光器，与现有技术中所使用的红外激光相比，太赫兹激光波长更长而在角膜组织具有更深的穿透深度，并且太赫兹光束的功率可调，太赫兹光束的整形扫描可控，从而使得角膜热凝深度和受热均匀性均有明显的提高。
2、系统配有高分辨红外热成像仪，根据该成像仪所提供的角膜表面温度空间分布信息能够预估太赫兹光束的扫描情况，进一步结合太赫兹光束扫描镜、眼球跟随仪的实时反馈，大大提高了手术过程中太赫兹光束角膜手术位置控制的精确性。
3、利用高分辨红外热成像仪和制冷模块组成的温度监测控制单元实现了角膜温度的预估和控制，能够有效防止手术过程中角膜受热过高过快而导致热损伤。
4、能够实现实时的手术过程监测，并能够根据反馈数据由计算机控制 或者高级用户做出适当的调整以达到最优化的手术效果，从而进一步提高角膜热成形效果的稳定性，有效减少术后角膜屈光回退。
上述说明仅是本申请技术方案的概述，为了能够更清楚了解本申请的技术手段，并可依照说明书的内容予以实施，以下以本申请的较佳实施例并配合附图详细说明如后。
附图说明
构成本申请的一部分的附图用来提供对本申请的进一步理解，本申请的示意性实施例及其说明用于解释本申请，并不构成对本申请的不当限定。在附图中：
图1示出了角膜热分析模型的示意图；
图2示出了不同功率密度的THz光束(频率1THz,光束直径分别为(a)2mm、(b)4mm、(c)5mm、(d)6mm和(e)8mm)照射下角膜温度随时间变化曲线图；
图3示出了频率为1THz、光束直径为6mm、功率密度为6000W/m 2的太赫兹光束照射角膜1200秒后基质凝固区预估图；
图4示出了频率为1THz、光束直径为6mm、功率密度为6000W/m 2的太赫兹光束照射角膜1200秒后热损伤的预测情况示意图；其中左图为空间分布情况，右图为角膜表面中心处的热损伤随时间变化情况；
图5示出了本申请的太赫兹角膜热成形系统的结构示意图。
具体实施方式
为使本申请的目的、技术方案和优点更加清楚，下面将结合本申请具体实施例及相应的附图对本申请技术方案进行清楚、完整地描述。显然，所描述的实施例仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施 例，都属于本申请保护的范围。
近年来，随着太赫兹科学与技术的发展，太赫兹源的设备水平得到了长足的发展，高功率太赫兹源不断涌现。目前实验室产生的太赫兹辐射功率水平约为10mW～100W。由能量回收直线加速器产生的太赫兹峰值功率可达10KW(千瓦)，而自由电子激光器甚至可达到MW(百万瓦)。这也为太赫兹波成为一种用于角膜热成形术的热源扫清了技术障碍。
对于角膜组织而言，角膜组织富含水分(75％～85％)，厚度(400～700μm)与太赫兹波长相当，因此基于水对太赫兹波的吸收，与现有角膜热成形术中使用的红外波段的光源相比，太赫兹波在角膜组织中能够获得与角膜组织相匹配的更深的穿透深度，相应的热效应也更为显著。在足够功率太赫兹波的照射下，产生的热效应能使角膜组织升温到热凝形变的温度。
根据角膜的对称性，基于二维轴对称的柱面坐标系建立角膜热分析模型，如说明书附图1所示。模型假设角膜及相关结构为直径15mm的圆柱体,其主要为三层机构，包括厚度为10μm的泪膜、厚度为600μm的角膜和厚度为2mm的房水层。假设太赫兹光束垂直照射角膜，由于水对太赫兹波的高吸收，热能由此产生，并通过热传导使得角膜受热升温。若初始时刻(t＝0)角膜的温度为T0，则太赫兹光束作用在角膜表面时，其热传导方程为：
Figure PCTCN2019123438-appb-000001
式中，T为生物组织内部的温度场(℃)，ρ为生物组织的密度(kg/m3)，k为生物组织的导热系数(W/m/K)，C为生物组织的比热容(J/kg/K)，q为太赫兹热源。考虑到目前分析时，太赫兹光束一般被视为高斯光束。为不失一般性，定义太赫兹热源如下式如示：
Figure PCTCN2019123438-appb-000002
式中，R f为太赫兹波在生物组织的反射率(R f＝0.02@1THz)，P d为太赫兹光束的功率密度，w 0为太赫兹光束半径，α为生物组织的吸收系数，r和z分别表示径向距离和纵向厚度。
在角膜热分析中所用到的热性能参数，可通过查阅文献报道得到，如下表所示。
表1角膜热分析中所用到的角膜、泪膜及房水组织的热性能参数
Figure PCTCN2019123438-appb-000003
为防止角膜因为过热而导致受损，有必要对角膜在升温过程中的热损伤进行分析评估。角膜组织的热损伤由组织的温度和加热时间决定，根据Arrhenius equation可以得到其热损伤程度因子，如下式：
Figure PCTCN2019123438-appb-000004
式中Ω(t)为角膜组织的热损伤程度因子，k B为Boltzmann常数(k B＝1.4×10 -23J/K),
Figure PCTCN2019123438-appb-000005
为Planck常数(6.6×10 -34J·s),R为气体常数(R＝8.313J/(mol·K)),ΔS和ΔH分别胶原变性的熵(106kJ/mol)和焓(39J/(mol·K))。
目前太赫兹光束直径一般为毫米量级，且目前常用太赫兹透镜聚焦下的最小光束直径约为2mm。又，目前激光角膜热成形手术的光凝区直径一般在6.0～7.5mm之间，故太赫兹光束直径的选择范围为2～8mm。基于上述分析，在未考虑热对流和热损失的情况下,设定角膜的初始温度为35℃，照射时间为1200秒,利用有限元方法模拟计算了角膜表面中心位置在高功率太赫兹光束(模拟 计算的工作频率设为1THz,光束直径为2～8mm,功率密度为1000～10000W/m 2)照射下的升温情况，如说明书附图2所示。由此可得2mm、4mm、5mm、6mm和8mm的太赫兹光束直径下，太赫兹光束能够达到安全光凝温度(55～75℃)和最佳手术温度(65～70℃)的功率密度范围，具体参见表2所示。
表2不同光束直径下达到安全光凝温度和最佳手术温度的功率密度范围
Figure PCTCN2019123438-appb-000006
进一步，针对太赫兹光束直径为6.0mm(目前激光角膜热成形手术的光凝区直径一般在6.0～7.5mm之间)的情况进行分析。图中显示，在照射时间、光束直径一定的情况下，角膜升温的幅度与速度取决于照射的太赫兹光束功率密度。太赫兹光束功率越高，角膜升温幅度越大，升温速度也越快。角膜升温幅度大约在5～64℃之间。角膜在前60秒温度陡升，在60～180秒升温平缓，180秒后达到某个稳态温度值(即使在太赫兹光束的长期照射下依然不再升温)。由于角膜热成形术的最佳手术温度为65～70℃,且角膜的太赫兹受热从表面到内皮面是递减的，因此根据升温曲线，功率密度为4000～6000W/m 2的太赫兹光束能够用于角膜热成形术，特别地，优选6000W/m 2的太赫兹光束用于角膜热成形术。
进一步，基于频率1THz、直径6.0mm、功率密度6000W/m 2的太赫兹光束加热角膜1200秒后的温度空间分布情况，对基质凝固区(能够产生变性的区域)进行预估。由于角膜基质的胶原组织在持续55℃时开始收缩并改变其三维结构，所以温度处于55～75℃的区域可视为基质凝固区。参见说明书附图3，图中灰色区域即为上述模拟条件下预估的基质凝固区。即在太赫兹所照射的区域，沿太赫兹传播方向(角膜深度方向)在角膜内形成一个类似圆柱形的、直径约3000μm、深度600μm(深达角膜全层)的胶原变性区。因而，利用太赫兹光束能够实现全层而均匀的角膜受热。
此外，还对角膜在频率为1THz、光束直径为6mm、功率密度为6000W/m 2的太赫兹波照射1200秒下的热损伤进行了预测。参见说明书附图4所示，左图为角膜受热1200秒后损伤程度的空间分布情况。对于角膜组织的热损伤程度因子，一般有如下的看法：当Ω(t)≤0.1时，可认为是无热损伤，属于理想的情况；当0.1<Ω(t)<1时，属于轻度热损伤，仅使角膜基质产生不理想的可逆形变影响；当Ω(t)≥1时，属于重度损伤，会使角膜基质产生碳化，导致角膜组织不可逆的坏死和永久性的破坏。从左图中可见，角膜表面中心受损程度最高，热损伤因子Ω达到了0.16。越靠近角膜表面中心处，热损伤程度越高，但属于轻度热损伤。随着深度增加，其受损程度会随之降低。由于热损伤除了受温度的影响外，还与其时间积累量有关，因此可以根据角膜表面中心处(受损程度最严重处)随时间变化的热损伤情况来确定可接受的最长受热时间，进而有效避免角膜组织的热损伤。由说明书附图4的右图可见，角膜表面中心处的热损伤因子Ω达到0.1的时间约为720秒。因此最长的受热时间可确定720秒。同时，结合角膜组织随时间变化的升温曲线(180秒后温度达到稳态)，在频率为1THz、光束直径为6mm、功率密度为6000W/m 2的太赫兹光束照射下，角膜受热的最佳时间为180～720秒。
基于以上分析可知，太赫兹源是一种非常适合角膜热成形术的热源。具体地，太赫兹热源可以选用能够产生高功率太赫兹辐射(0.1～10THz)的气体激光器、量子级联激光器、自由电子激光器等现有可用产品。根据上述工作原理，本申请提出一种太赫兹角膜热成形系统，参见说明书附图5所示。系统包括高功率太赫兹激光器1及相配套的准直扫描模块，用于产生并将太赫兹光束照射至人眼进行手术。其中所述激光器1为频率在0.1～10THz范围内的连续激光器。所述的准直扫描模块包括由第一太赫兹反射镜2和第二太赫兹反射镜3组成的准直器、由太赫兹衰减片4形成的功率调节部、以及实现光束整形和XY二维扫描的器件。具体地，所述连续激光器1发出的光束经所述的准直器中的第一太赫兹反射镜2准直成平行光，该平行光经太赫兹衰减片4后，被一个太赫兹分束镜5进行分束，一束被太赫兹功率计6接收用于功率检测，另一束通过第二太赫兹反射镜3反射后，经由带有光束整形功能的XY二维振镜扫 描系统7实现光束的扫描，最后经过只反射太赫兹光束并透过可见光的ITO分光镜8反射后，照射到眼球9上。
其中，通过光束整形使得太赫兹光束能量能够均匀分布。尽管上述提及XY二维振镜扫描系统7本身可以具有光束整形功能，但并不限于此，扫描系统7可以为一般扫描器，在扫描系统7之后紧随再设置一个光束整形器。此外，为了方便手术操作，在上述扫描系统之后还可以设置一个适用于太赫兹波段的角膜标记器，具体地可以利用一片具有孔结构的金属薄板来实现角膜标记器，并通过对孔径大小、形状、数量、排列间隔等参数的设置来满足在光凝区方面的需求。
为了进一步提高手术过程中太赫兹光束角膜手术位置控制的精确性，以及进一步避免对角膜产生不必要的伤害，本申请的系统中在眼球两边还分别配有高分辨红外热成像仪10和制冷模块11，高分辨红外热成像仪10和制冷模块11共同组成温度监测控制单元，帮助实现角膜温度的预估和控制，防止手术过程中，角膜受热过高过快而导致热损伤。
红外热成像是一种精确、可计量、非接触式的诊断技术。其中高分辨红外热成像仪10可以选用市售FLIR 655,FLIR T650,FLIR A6700,FLIR GF335,FLIR X8400等型号的产品，以提供角膜表面的温度空间分布信息。根据之前的模拟计算，角膜受热后，温度最高点位于角膜表面的太赫兹光束中心位置，温度在光束半径方向上衰减。基于温度分布图，能够检测到无法看见的太赫兹光束，并用于标识和目标确认。根据角膜热成形的温度范围，设定温度的上下限，在此基础上，可实时标记角膜升温的异常情况。而所述制冷模块11例如为散热制冷模块，其采用流动空气制冷降温；或者也可以使用体积小、重量轻且方便集成的等离子风散热制冷，利用离子放电产生空气流动的原理达到制冷的效果。优选地，所述制冷模块11距离眼球的距离为5cm-15cm之间。
进一步，为了获得更优的手术效果，设定更优的手术过程参数，所述温度监测控制单元还可以与眼科光学相干断层扫描仪(OCT)、角膜地形仪、眼球跟随仪的监测结果相结合，将这些监测结果数据反馈到计算机控制部20，以对太赫兹光束扫描镜进行调整，从而实现手术过程中太赫兹光束在角膜手术位 置的更精确的控制。手术显微镜、眼科光学相干断层扫描仪(OCT)、角膜地形仪、眼球跟随仪等模块自身配备有光源，这些光源照射眼球9后光信号将从眼球9反射。
具体参见说明书附图5,在眼球9和ITO分光镜8上述光信号反射后射出的光路上依次设置有第一分光镜12、第二分光镜13和第三分光镜14，以此构成分光系统。其中，第一分光镜12将眼球反射出的光分束一部分到手术显微镜15，手术工作人员可以通过手术显微镜15来观察整个手术过程。
经过第一分光镜12反射后再经第二分光镜13透射的光束将入射到眼科OCT 16。眼科OCT 16是现有技术中已经成熟的仪器设备，通过眼科OCT 16可以获得整个手术过程中角膜的厚度信息。本申请的系统中优选将通过眼科OCT 16获得的角膜厚度信息实时反馈到计算机控制部20。具体地，利用眼科OCT可实时监测角膜厚度，当角膜厚度小于400μm或者大于700μm时则需要预警停机。根据角膜热分析模型，基于角膜表面温度分布，可以实时观测根据光凝区(温度大于55℃区域)直径的大小。通过实时观测角膜厚度变化，可以得到光凝点的收缩深度。因此，厚度与温度信息可以相互印证，并将两者相结合，评估角膜热成形手术的基质凝固区。根据基质凝固区的大小和深度等信息，控制扫描振镜对太赫兹光束照射位置的调整，并利用相应的制冷模块等对角膜的温度进行控制。
此外，经过第二分光镜13反射后进一步经过第三分光镜14反射的光束将入射到角膜地形仪17，从而对角膜地形图、角膜屈光度进行实时检测。采用角膜地形仪进行监测，可以实时测量角膜曲率的变化过程，反映整个角膜的形态变化。根据屈光理论，人的眼球可以大致看作是一套复杂的由多个光学元件所构成的同心共轴屈光系统,光线经过角膜外表面、角膜基质、角膜内表面、房水，晶状体前表面晶状体基质和核、晶状体后表面、玻璃体等一系列介质的屈光作用,才最终到达视网膜成像。据有关数据，眼球总屈光力为+58.64D，而角膜屈光力为+43.05D，角膜外表面屈光力为48.83D，角膜屈光力占整个眼球屈光力的73.41％，角膜外表面屈光力占整个眼球的屈光力的83.27％。可见，角膜是眼屈光系统的重要组成部分，角膜外表面曲率半径对眼球屈光力的影响 起主要作用。因而，可以根据角膜外表面曲率半径的改变来评估屈光力改变效果。例如，假设角膜原始外表面的曲率半径是r1,太赫兹光束照射角膜后，根据上述的角膜热吸收特性分析，角膜发生收缩，其曲率半径减少为r2。当曲率半径从r1变成r2时，其屈光力增加为ΔD,估算如下：
D1＝(n-1)/r1＝(1.376-1)/r1＝0.376/r1
D2＝(n-1)/r2＝(1.376-1)/r2＝0.376/r2
ΔD＝D2-D1＝0.376(r1-r2)/r1×r2
最后经过第三分光镜14透射并随后经过反射镜18反射的光束将入射到眼球跟随仪19，所述眼球跟随仪19对眼球瞳孔中心进行跟踪定位。具体地，可以将瞳孔中心与角膜表面温度分布图相融合并配准，尽量保持瞳孔中心标记与温度分布图中的亮斑处重合。当两者发生偏差时，控制扫描系统实现对太赫兹光束的照射位置调整，以尽量使得太赫兹光束中心与角膜上表面中央处重合。
在整个手术过程中，扫描系统7、高分辨红外热成像仪10、制冷模块11、眼科OCT 16、角膜地形仪17和眼球跟随仪19均与计算机控制部20相连。高分辨红外热成像仪10、眼科OCT 16、角膜地形仪17和眼球跟随仪19等仪器的检测结果传送至计算机控制单元，由此实时监测手术过程。同时基于上述检测结果可以由计算机自动，或者由高级用户及工作人员手动，对太赫兹热源、温度监测控制单元做出适当的调整，从而达到最优化的手术效果，实现提高角膜热成形效果的稳定性，使得术后屈光度及角膜形变更加稳定，有效减少术后角膜屈光回退的技术效果。
以上对本申请的太赫兹角膜热成形技术进行了说明，其中太赫兹角膜热成形术系统主要包括太赫兹热源、温度监测控制单元、角膜生理参数反馈和计算机控制部等单元。系统的工作通过计算机控制实现，太赫兹热源单元根据手术实时监测参数的反馈实现对太赫兹光束的能量调节、调理和扫描。温度监测控制单元实现了角膜的温度监测以及反馈控制，以防角膜升温过高或过快造成的热损伤。各个角膜生理参数反馈单元实现了眼球状态、角膜厚度、角膜屈光度、角膜地形及手术过程的监测，为手术参数优化提供了依据。系统工作时，计算 机控制单元根据温度监测控制单元和各个角膜生理参数反馈单元的监测，调整好太赫兹源的相关参数，用户也可以根据需求，对太赫兹热源、角膜温度监控、角膜生理参数反馈等单元各部分进行相应的操作，从而整体提高角膜热成形效果的稳定性，有效减少了术后角膜屈光回退的发生。
需要说明的是，在不冲突的情况下，本申请中的实施例及实施例中的特征可以相互组合。
以上所述，仅是本申请的较佳实施例而已，并非对本申请作任何形式上的限制，依据本申请的技术实质对以上实施例所作的任何简单修改、等同变化与修饰，均仍属于本申请技术方案的范围内。

Claims (19)

  1. 一种太赫兹角膜热成形系统，其特征在于：
    包括作为热源的太赫兹激光器(1)以及相配套的准直扫描模块，从而将太赫兹光束照射到眼球角膜上；
    所述准直扫描模块包括准直器、功率调节部和二维扫描器件。
  2. 如权利要求1所述的系统，其特征在于：所述二维扫描器件为带有光束整形功能的二维振镜扫描系统(7)。
  3. 如权利要求1所述的系统，其特征在于：
    在所述二维扫描器件后还设置有光束整形器和/或角膜标记器。
  4. 如权利要求1所述的系统，其特征在于：所述功率调节部为太赫兹衰减片(4)；所述准直器包括第一太赫兹反射镜(2)和第二太赫兹反射镜(3)。
  5. 如权利要求1所述的系统，其特征在于：经过太赫兹衰减片(4)后的光束被一个太赫兹分束镜(5)进行分束；一束被太赫兹功率计(6)接收用于功率检测，另一束用来照射眼球。
  6. 如权利要求1所述的系统，其特征在于：还包括温度监测控制单元，通过高分辨红外热成像仪(10)来获得角膜的温度空间分布信息。
  7. 如权利要求6所述的系统，其特征在于：所述温度监测控制单元还包括制冷模块(11)，用于根据所述高分辨红外热成像仪(10)的监测结果调整角膜的温度。
  8. 如权利要求7所述的系统，其特征在于：还包括计算机控制部(20)，所述计算机控制部(20)控制所述二维扫描器件和/或所述制冷模块(11)；
    其中上述对所述二维扫描器件和/或所述制冷模块(11)的控制参考所述高分辨红外热成像仪(10)的监测结果。
  9. 如权利要求8所述的系统，其特征在于：还包括一个或者多个角膜生理参数反馈单元，所述角膜生理参数反馈单元的监测结果被输送到所述计算机控制部(20)用以调整照射到角膜的太赫兹光束。
  10. 如权利要求9所述的系统，其特征在于：所述角膜生理参数反馈单元为眼科光学相干断层扫描仪(16)、角膜地形仪(17)以及眼球跟随仪(19)中的一个或多个。
  11. 如权利要求1、6、9中任一项所述的系统，其特征在于：还包括用于对手术过程进行观察的手术显微镜(15)。
  12. 如权利要求1、6、9中任一项所述的系统，其特征在于：还包括ITO分光镜(8)，经过所述二维扫描器件的光束由所述ITO分光镜(8)反射照射到眼球角膜上；由眼球反射的光束透过所述ITO分光镜(8)后用于获取手术监测信息。
  13. 一种太赫兹角膜热成形方法，其特征在于：
    使用太赫兹激光器(1)作为热源，利用相配套的准直扫描模块将太赫兹光束照射到眼球角膜上。
  14. 如权利要求13所述的方法，其特征在于：
    所述太赫兹激光器(1)的功率密度为5000～8000W/m 2。
  15. 如权利要求14所述的方法，其特征在于：
    所述太赫兹激光器(1)的光束直径为6mm，功率密度为6000W/m 2。
  16. 如权利要求13-15任一项所述的方法，其特征在于：
    角膜受热的时间为180～720秒。
  17. 如权利要求13所述的方法，其特征在于还包括如下操作：
    使用温度监测控制单元获得角膜温度空间分布信息；
    参考所述角膜温度空间分布信息调整照射到角膜上的太赫兹光束，或者参考所述角膜温度空间分布信息直接调整所述角膜的温度。
  18. 如权利要求17所述的方法，其特征在于还包括如下操作：
    获取手术中的监测信息，所述监测信息包括角膜的厚度信息、角膜屈光度信息、角膜地形图以及眼球瞳孔中心位置中的一个或者多个；
    参考所述监测信息调整照射到角膜上的太赫兹光束，或者参考所述监测信息直接调整所述角膜的温度。
  19. 如权利要求17或18所述的方法，其特征在于：
    所述调整照射到角膜上的太赫兹光束或者所述直接调整所述角膜的温度 的操作是通过计算机控制部(20)完成的。
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