KR100904252B1 - Ultrafast laser device and method for selective ablation of angiogenetic blood vessels - Google Patents

Abstract

The present invention relates to a surgical device for selective neovascularization and a neovascular selective removal method to selectively and safely remove neovascularization by focusing on neovascularization using an existing ultra-fast laser ultra-fine processing technology and optical method. As, the surgical device for neovascular selective removal using an ultra-fast laser according to the present invention comprises a laser system for generating a laser beam; An optical system for focusing the laser beam from the laser light source; A stage for positioning the focused object including the neovascular vessel; And a monitoring device for monitoring tissue including neovascularization; Includes, the laser beam system includes a laser control unit for adjusting the laser beam fluence satisfying the following equation.

D _n <F <D _t (1)

[F is the laser beam fluence to be irradiated, D _n is the laser beam fluence to the extent that neovascularization can be removed by laser beam irradiation, and D _t is the normal blood vessel damaged by the laser beam irradiation process spontaneously. It is a laser beam fluence of normal regeneration and the extent to which tissue cells except neovascular and normal blood vessels are not damaged by laser beam irradiation.]

Ultra Fast Laser, Neovascularization, Neovascularization, Fluence, Single Pulse, Femtosecond

Description

Ultrafast laser device and method for selective ablation of angiogenetic blood vessels}

1 is a block diagram of the ultra-fast laser surgical apparatus of the present invention.

FIG. 2 is a confocal image of an embryonic stage of changes in the state of blood vessels after irradiation of a blood vessel region of a zebra-fish embryo with an ultrafast laser; FIG.

Figure 3 is an optical photograph of the developmental stage of the embryo for the state of the embryo after removing the neovascularization of the zebrafish embryo using ultrafast laser.

4 and a graph of the state of blood vessels classified according to the developmental stage of the embryo after the ultrafast laser irradiation to the blood vessels of zebrafish embryos.

5 is another graph classifying the state of blood vessels according to the developmental stage of the embryo after irradiating ultrafast laser to blood vessels of zebrafish embryo.

6 is a statistical data graph of the fluence of lasers used in surgery for the developmental stages of zebrafish embryos.

7 is a graph of the dependence of the average laser fluence used according to the developmental stage of the embryo of zebrafish.

* Detailed description of the main parts of the drawings *

(1): Ti: sapphire laser system

(2): IBM compatible PC and laser beam scan program

(3): high speed optical shutter (4): galvanometer scanner

(5): Objective lens (6): Beam splitter

(7) CCD camera (8) Photomultiplier

(9) argon ion laser (10) pinhole

(11) 45 deg dichroic mirror (800 nm) (12) 45 deg dichroic mirror (488 nm)

(13) 45 deg total reflection mirror

The present invention relates to a surgical device for selective neovascularization and a neovascular selective removal method to selectively and safely remove neovascularization by focusing on neovascularization using an existing ultra-fast laser ultra-fine processing technology and optical method. will be.

Ultra-fast laser ablation surgery and process method is known to have a large number of applications, particularly excellent in ultra-fine process technology because the thermal-mechanical damage can be minimized compared to the various removal techniques using a relatively long laser pulse. In addition, micromachining techniques based on high energy particles such as electron beams and plasmas are not free from thermal, chemical, and physical damages of the material constituting the target object, and in particular, processing is not possible at all depending on the type of processed material. As part of the effort to develop a response technology, the development efforts of the ultra-fast laser ablation technique have been actively progressed. In particular, objects such as living bodies cannot be applied to these methods because they cannot be subjected to a micro process by placing them in a vacuum. However, various forms of optical methods, such as endoscopy and nonlinear spectroscopic techniques such as various forms of optical coherence tomography (OCT), or various 2-D and 3-D bio-duals due to ultrasonic and nuclear magnetic resonance principles, Advances in imaging and clinical diagnostics are accelerating advances in the early detection of pathologically abnormal tissue in smaller areas. However, with the rapid development of this diagnostic technique, the clinically necessary surgical removal technique is precisely achieved by mechanical methods such as scalpels or laser surgery techniques that can be oscillated in the laser region of the ultra-long pulse or the ultra-nanosecond pulse that have been used conventionally. There is a limit to the invention of a new technology that can overcome this situation is urgent.

In particular, laser surgery techniques for specific tissues are very well known, but most of them induce photothermal effects by irradiating a laser to a specific site or by adsorbing a specific pigment to a specific tissue to photoexcitation it to induce a photochemical reaction. The method of eliminating or eliminating biological function was used. In this case, side effects affecting parts other than the intended ones by inevitable secondary photoinduced reactions, such as thermal diffusion into other tissues or additional chemical reactions other than the desired part, as well as specific target areas. The accompanying harms have always been pointed out. The prerequisite for overcoming these limitations is that new laser surgery and removal methods that are free from thermal and mechanical damage must be developed, while at the same time selective and safe removal techniques must be developed.

On the other hand, the treatment of macular degeneration caused by neovascularization occurring in the intraocular retina is largely surgery and drug therapy. In macular degeneration, however, it is known that the treatment of neovascularization of the choroid (eye vessel) covering the outer retina is the key to treatment, but there is no cure. Among the recently proposed methods, pharmacotherapy is based on macular degeneration, one of the diseases caused by neovascularization, which is a photodynamic therapy in which a laser is irradiated after the injection of a drug called bijudine, sold by Novartis, a multinational pharmaceutical company. It is effectively known in some cases of the disease. On the other hand, there is no known drug treatment for dry patients, the most common case. Surgical methods include laser photocoagulation and resection, and some of the retinas using a gas laser (Ar ion, Kr ion lasers) are used to cause scars by causing a kind of burn to prevent the growth of new blood vessels. Since the size of the coagulated powder is so large that it cannot be neglected compared with the size of the macula, new methods of treatment are required because it does not eliminate severe vision disorders and the underlying etiology.

The present inventors surprisingly, when irradiating a laser beam to neovascularization using a ultrafast laser device under specific conditions, the neovascularization is removed within a certain range of fluence, but due to its proximity to the neovascularization, Even if damaged, it was confirmed that the spontaneous recovery to normal blood vessels that function again to complete the present invention.

Therefore, in the present invention, a surgical device for selective removal of neovascularization using ultrafast laser and ultrafast laser that can remove neovascularization while minimizing the degree of damage and surgical-induced disorder that cannot be reached by the conventional surgery or drug therapy. To provide a neovascular selective removal method using. In addition, another object of the present invention is to damage the normal blood vessels of the tissues or regions around the neovascularization and to selectively remove only the neovascularization by minimizing the additional disorder that is a problem in the existing technical methods. By using the advantage of free from mechanical thermal damage that could not be avoided in the conventional removal technique, the present invention uses an ultrafast laser to target an abnormally grown or pathological target in a tissue or a specific part of a living individual. It provides a new way to remove selectively and safely.

The present invention relates to a surgical device for selective neovascularization and a neovascular selective removal method to selectively and safely remove neovascularization by focusing on neovascularization using an existing ultra-fast laser ultra-fine processing technology and optical method. As, the surgical device for neovascular selective removal using an ultra-fast laser according to the present invention comprises a laser system for generating a laser beam; An optical system for focusing the laser beam from the laser light source; A stage for positioning the focused object including the neovascular vessel; And a monitoring device for monitoring tissue including neovascularization; Includes, the laser beam system includes a laser control unit for adjusting the laser beam fluence satisfying the following equation.

D _n <F <D _t (1)

[F is the laser beam fluence to be irradiated, D _n is the laser beam fluence to the extent that neovascularization can be removed by laser beam irradiation, and D _t is the normal blood vessel damaged by the laser beam irradiation process spontaneously. It is a laser beam fluence of normal regeneration and the extent to which tissue cells except neovascular and normal blood vessels are not damaged by laser beam irradiation.]

The range of the laser beam fluence (F) to be irradiated should be such that the neovascularization can be removed, but inevitably the laser beam is irradiated to the tissue or the normal blood vessel adjacent to the neovascularization during the laser beam irradiation to the neovascularization. Therefore, when the laser beam fluence for irradiating the neovascularization to the laser beam is above a certain range, the neovascularization is removed, but the normal blood vessel damaged by the laser beam irradiation due to adjacent to the neovascularization is returned to normal function after the laser beam irradiation. Surgical device for selective removal of neovascularization according to the present invention because it fails to recover to normal blood vessels, and damages neovascular blood cells or tissues other than normal blood vessels when irradiated with a laser beam, thereby causing irreparable damage of the tissues. The range of application of the fluence F of the laser beam irradiated in The most important component in achieving what the purpose of the patients surgical devices.

The range of the laser beam fluence according to the present invention may vary depending on the type and region of the animal to be treated, but if the laser beam fluence is in the range of 10 to 200 J / cm ² , the neovascularization according to the present invention can be removed. It is a laser beam fluence of the degree, and the damaged normal blood vessels spontaneously recover during the removal of the neovascularization, and the laser beam flu that does not cause damage to tissue cells except neovascular blood and normal blood vessels when the laser beam is irradiated. It's Enshi.

Even more preferred range of 30 to 170 J / cm ² as laser beam fluence of normal blood vessel recovery and intact range of tissue cells.

The laser beam employed in the neovascular selective surgical removal apparatus according to the present invention is a laser beam in the near infrared region, preferably a single pulse laser beam, more preferably a femtosecond single pulse laser beam. If the tissue is repeatedly irradiated with pulses, a rise in temperature due to continued accumulation of heat will occur if a constant temperature rise is caused by the immediately irradiated pulse and does not return to thermal equilibrium prior to the arrival of the continuing pulse. There may be. The method of minimizing the accumulation of photo-thermodynamic damage and photochemical damage is to use a single pulse laser beam, more preferably to use a femtosecond single pulse laser beam.

 Surgical apparatus for selective neovascularization removal using ultrafast laser according to the present invention comprises a stage and neovascularization for positioning a focused object including an optical system and neovascularization for focusing the laser beam from the ultrafast laser beam group laser light source. It includes a monitoring device for monitoring the tissue containing.

The optical system is adopted to process the beam generated from the ultra-fast laser light source and adjust the path to focus, and may include all of the conventional laser beam optical systems, and a dichroic mirror for selectively reflecting light according to the wavelength. ), The optical filter including the objective lens and the notch filter can be used to control and focus the path of the pure short wavelength laser beam, and the intensity of the laser beam can be controlled using the neutral density filter. In addition, only a single pulse can be extracted from the pulse train of the laser beam using a fast optical shutter.

The stage for positioning the focused object including the neovascular vessel is employed to control the irradiation position setting of the laser beam for accurate laser beam irradiation to the site where the neovascularization is located, and the position control stage is applied to the neovascular vessel. It is driven using galvanoscopy or angiography. In order to control the irradiation position setting of the laser beam, it is preferable to include a device that can observe the object to be focused in real time image. As a real-time imaging device, a common confocal imaging device can be used, which is a light source of a visible light beam, preferably an argon ion laser beam, a galvano-scanner mirror for two-dimensional irradiation of the light source, a total mirror and dichroism Preferably, a mirror including a dichroic mirror, a lens including a correction lens, a filter including an interference filter, a photodetector including a pinhole, a photoconductive element and a photomultiplier tube are provided. Do.

The real-time imaging device may be used as a monitoring device for monitoring tissues including neovascularization, and a charge coupled device (CCD) camera may be provided to detect a photoluminescence signal split by a beam splitter.

At this time, the galvano scan (galvano-scanner mirror), the photodetector, the optical shutter, and the CCD camera are preferably controlled in conjunction with a control program driven by the digital processor.

The neovascular vessel that can be removed by the surgical device for selective removal of neovascular vessels using the ultrafast laser according to the present invention is applied to various diseases in which neovascular vessels are very seriously involved, including neovascular vessels generated in the choroid covering the outer retina. can do.

The present invention includes a method for selectively removing neovascularization of animals other than humans using an ultrafast laser, and the method for selectively removing neovascularization according to the present invention is characterized by the following steps.

a) irradiating a laser beam satisfying the following formula (1) to a surgical site including neovascular and normal blood vessels;

D _n <F <D _t (1)

[F is the laser beam fluence to be irradiated, D _n is the laser beam fluence to the extent that neovascularization can be removed by laser beam irradiation, and D _t is the normal blood vessel damaged by the laser beam irradiation process spontaneously. It is a laser beam fluence of normal regeneration and the extent to which tissue cells except neovascular and normal blood vessels are not damaged by laser beam irradiation.]

b) spontaneously regenerating normal blood vessels damaged during the removal of the neovascularization.

The laser beam irradiated in step a) is a laser beam in the near infrared region, and is characterized by a femtosecond single pulse laser beam, and the fluence (F) of the irradiated laser beam is preferably in the range of 10 to 200 J / cm ² . Even more preferred is a range from 30 to 170 J / cm ² .

In the step of focusing the laser beam on the neovascularization, the control of the position of the neovascularization to be focused is preferably performed by galvanoscopy or angiography for the neovascularization.

Hereinafter, the neovascularization selective removal apparatus and the neovascularization selective removal method for selectively and safely removing neovascularization according to the present invention will be described with specific examples, but the following description does not limit the scope of the present invention.

1 is a block diagram of an ultrafast laser surgical device designed to selectively and safely remove neovascularization, and FIG. 2 is an embryonic step-by-step view of changes in the state of blood vessels after irradiation of a blood vessel region of a zebra-fish embryo with an ultrafast laser. Focused image, Figure 3 is an optical photo of the developmental stage of the embryo for the state of the embryo after removing the neovascularization of the zebrafish embryo using ultrafast laser, Figure 4 and Figure 5 is a high-speed laser irradiation to the blood vessels of zebrafish embryo Later, the state of blood vessels is a graph classified according to the developmental stage of the embryo, Figure 6 is a histogram of the statistical data of the fluence of the laser used in the operation for the developmental stage of the embryo of zebrafish, Figure 7 is a zebrafish embryo This is a graph of the dependence of the laser fluence mean used over different stages of development.

In the present invention, angiogenesis using the ultrafast laser according to the present invention is performed based on the process of irradiating and removing the target neovascularization part with an ultrafast laser according to the formation of blood vessels in each developmental stage of a zebrafish embryo, which is relatively well known. An embodiment of a surgical device and a method for vascular selective removal will be described.

In the embodiment exemplified for implementing the present invention, the progress of ablation surgery under the early developmental state of zebrafish embryos under all identical ablation surgery experimental conditions, such as the same laser power and irradiation time for the same site and the optical device used for irradiation Selection of neovascularization by ultra-fast laser irradiation according to the development of neovascularization by experimentally observing the progress of removal surgery by laser irradiation as the degree of development of blood vessels progressed along with the condition and embryo development In this study, we obtained optical images of how blood vessels in the area irradiated with the laser beam responded to the passage of time during the embryo development of zebrafish. Ultrafast laser neovascularization by acquiring Information on the selectivity and safety of the surgery was collected.

In order to evaluate the effect of local vascular injury on the development of whole embryos as the development of blood vessels progressed, all the embryos with laser beam irradiation were examined for the growth of embryos.

Example 1

The zebra-fish ( Tg (fli1: EGFP) ^y1 ) used as the subject of an embodiment according to the present invention is readily available through the ZIRC (The zebrafish international resource center, USA). The zebrafish can manipulate the gene to express Green fluorescent protein (GFP) in the fil1 promoter, which regulates endothelial cells, allowing sensitive long-term imaging of blood vessels in living eggs (Lawson, NK and Weinstein, BM (2002), Dev. Biol. 248, 307-318). In addition, since previous observations and studies on the formation of blood vessels at each developmental stage are relatively small (Isogai, S. et al (2003), Dev. Biol. 130 (21): 5218-5290 ) It is a very good in-vivo experimental material for the design and the experimental realization of selective ablation of ultrafast laser in the formation of neovascularization. For example, about 16.5 hours after fertilization under normal temperature and conditions, the embryo's condition is named 15 somite stages, and in the trunk midline, neovascular cells are clearly visible in a linear state and form arteries. It is known that the inside of the tube begins to form at the 28 somite stage.

The ultrafast laser surgical apparatus used in this embodiment and Example 2 has the configuration of FIG. 1, and the ultrafast laser of FIG. 1 is a Ti: Sapphire amplifier system having a pulse width of 150 fs, a repetition rate of 1 kHz, and a wavelength of 800 nm. The laser beam was controlled by using an ND filter, and an optical shutter with an opening delay of more than 0.5 ms was used to extract only a single pulse from a laser pulse train of 1 kHz. This femtosecond laser single pulse was adjusted to a focal length of 3 mm and 63 times objective lens to focus on neovascularization of a specific region, so that the microscopic removal process could be performed.

A self-contained confocal imaging device combined with a surgical device was used to image the site of neovascularization of zebrafish embryos in real time. In order to observe fluorescence in GFP-expressing endothelial cells, an argon ion laser beam was scanned in two dimensions through a galvano-scanner mirror as shown in FIG. The point of change was corrected through a correction lens placed at two calculated distances. The unchanged point of the corrected laser beam is mounted at the entrance of the objective lens so that the naturally focused laser beam can be scanned two-dimensionally in the corrected state. The focused laser beam operates at high speed through the galvano-scanner mirror, where the laser photoluminescence signal generated at the focused area is collimated-focused through the same optical device and path and used as a photodetector. The signal was detected by a photomultiplier tube. At this time, the laser beam signal of the argon ion laser used as a light source among the detected optical signals was effectively removed by using an interference type optical filter. The signal detected in the above manner is synchronized with the scanning signal of the laser beam by the galvano-scanner mirror operation, which is operated by the signal processor of the computer to obtain a maximum of 7 images per second. In addition, the optical system is designed to be free from interference with the femtosecond laser during the operation of the imaging system, so that selective and safe neovascularization can be efficiently performed.

In the developmental stages of genetically engineered zebrafish embryos, the vascular site was selectively irradiated with an ultrafast laser and then monitored rapidly for changes in vascular status. Using a total of 445 zebrafish embryos, a total of 445 embryos were screened at the Somite 14, Somite 20, Somite 25, Prim 16, and Prime 20 stages, respectively, and the ultrafast laser was selectively irradiated to the vessels while imaging the vessels in real time. In the case of all embryos, blood vessels were removed and the state of the blood family was recorded in the term of the denominator. The molecular term was recorded in the molecular term when the embryo failed to complete its development after blood and surgery. . At this time, the postoperative state of the vessel was divided into three stages as defined above: Complete Disruption, Half recovery, and Perfect Recovery. It was. Table 1 describes the results, FIGS. 2 and 3 are optical photographs of the results of the procedure, and FIGS. 4 and 5 graphically show the results.

[Table 1] Total 445 Embryonic Surgery Results (Total Number of Embryos / Early Embryos)

Figure 2 is obtained by confocal fluorescence image, Figure 2 (a) is a result of observing the process of changing the shape of the blood vessels before and after irradiating the ultra-fast laser in step 14 somite. The intensity of the photo-luminescent signal observed at this time is the portion where the amount of signal is small in the blue area, and the signal counts toward the red color. In other words, the long edge from the upper right side to the lower left side of the pre-operative image shows the endothelial cells forming a colony and having the shape of new blood vessels. Based on the acquired image, the ultrafast laser is indicated by a black arrow. The site was selectively irradiated and the removed surgical site was observed with a time interval of 1 second. As shown in (a) of FIG. 2, in the case of Somite 14, which has a rapid development stage, it is clear that the shape of the blood vessel is very clearly removed from the laser irradiated portion, and the shape of the blood vessel is separated over time. Was observed. (Hereinafter, the procedure is called "disruption of blood vessels.")

Figure 2 (b) is the result of the ultrafast laser ablation procedure in Somite 20 stages zebrafish more advanced than Somite 14 stages. Irradiation of the femtosecond laser under the same conditions to the areas indicated by the black arrows at a time interval of one second shows that the photoluminescence signal was significantly reduced by the removal of endothelial cells at the irradiation site immediately after the irradiation. . After a few seconds, however, the shape of the laser-irradiated area was changed, and the clear removal traces previously seen were somewhat disappeared. Ultimately, the shape of the blood vessel was not exactly the same as the image before the removal, but it still had the shape of the blood vessel. It can be confirmed, and partially shows the phenomenon of spontaneous recovery of the surgical site of the blood vessels. (Hereinafter, the procedure of this operation is called "Half Recovery of Blood Vessel.")

Figure 2 (c) shows a typical photoluminescence fluorescence image showing the time course of the progress before and after the removal of blood vessels generated in Somite 25, the more advanced embryo development stage, from which the ultrafast laser In the case of focusing and irradiating the part indicated by the color arrow under the same conditions as in the above case, it is confirmed that the irradiated part is clearly removed immediately after the irradiation. However, within a few seconds after the removal by laser beam irradiation, the shape of blood vessels is recovered to the same shape as before laser irradiation. (Hereinafter, this procedure is referred to as "perfect recovery of blood vessels.")

When the development starts through the irradiation of the local ultrafast laser to the blood vessels during the formation of blood vessels in which the degree of development is confirmed with the developmental stage of the embryo from the result of Example 1, the blood vessels can be efficiently removed. After the removal, the vessels can be observed to be destroyed without reconstruction. On the other hand, as the development of the vessels progresses, the vessels can be removed as efficiently as in the immature vessels. It can be seen that phenomena at least resemble or recover to exactly the same form. From this, by using the surgical device and the removal method for neovascular selective removal using ultrafast laser according to the present invention, neovascularization can be selectively removed, even if the blood vessels are sufficiently developed, even if the damage is caused by the laser beam. It can be seen that the voluntary recovery can ensure the safety that ultimately prevents damage. This selective and safe neovascular removal method is characterized by the fact that ultra-fast lasers can achieve It is shown that a pulsed laser, continuous wave laser, or laser in the ultraviolet region can be realized by a completely free removal operation from inevitable thermal-mechanical additional damage.

FIG. 3 is a diagram illustrating the state of an embryo after angiovascular removal at each developmental stage after the removal of neovascularization using ultrafast laser at each developmental stage of zebrafish embryos. The embryo development stage is somite 14, and the vessel's condition is early neovascularization. If the embryo is removed, the embryo does not develop at all. (B) develops after a certain degree of development. It shows the case where it stopped and died. Figure 3 (c) shows that in certain cases after the development stage of the embryo reaches the somite 20, the development of the complete fry after complete operation of the blood vessels, but the form is not ordinary In the case of the modified case and (d), after the development of the embryo has been progressed to some extent (for example, somite 25), the development of the embryo continues without any signs of damage after the vessel is removed with the ultrafast laser. A typical case is shown with a complete pom-pom. These results clearly show that the embryos can not continue their development because ultrafast laser ablation under ultra-fast laser removal under the condition of blood vessels has a strong correlation with the developmental stage of the embryo. .

In addition, when the development of the embryos progressed, the more mature blood vessels were removed with ultra-fast laser, although the target area of the blood vessels could be successfully removed within a few seconds immediately after the surgery. This shows that the development of the embryo itself can be safely and effectively done without damaging the development of the embryo itself.

Figure 4 is a result showing the degree of response of the blood vessels after surgery on the total 445 embryos treated according to the developmental stage of the embryo, that is, the degree of blood vessel development. As the developmental stage of the target embryo progresses from Somite 14 to Somite 20, Somite 25, Prim 16, Prime 20, etc., it clearly shows that the removal and damage of blood vessels after surgery is significantly reduced. The blood vessels of the embryos have been shown to completely overcome damage and regenerate within a few seconds under the same conditions.

Figure 5 shows the results of Table 1 in order to know the abnormality of the development process of the embryo itself for the postoperative state of the blood vessels, 94.75% or more of the embryos when the vessels completely overcome damage and regenerated In the case of embryos that have completely broken blood vessels, more than 25% of them are dying without completing the developmental process.

Example 2

In order to determine the dependence of laser fluence used for the procedure and spontaneous recovery of neovascular vascular and normal vessels using the apparatus of FIG. 1, minimal damage to blood vessels on confocal microscope imaging monitored in real time during the procedure Was measured and the results are shown in FIGS. 6 and 7.

Based on Figures 6 and 7, the laser fluence used can cause neovascularization within the Somite 25 region in Somite 14 to damage in fluence in the range of 30-50 J / cm ² , more In embryos Prim 16 and Prim 20, more than 170-180 fluences are needed. In the early developmental stages of embryos, it is possible to sufficiently damage neovascularization with a very low 50 J / cm ² fluence. As shown in FIG. 6, the surgical neovascularization ultimately undergoes permanent damage and can be successfully removed. Shows that it can. On the other hand, in the highly developed Prim16 and Prim 20-stage embryos, which were damaged in the high 170 J / cm ² fluence region, the vessels successfully re-sponsored successfully under these extreme conditions. Therefore, it shows the significance and reliability of the effect of the neovascular selective and selective removal of the neovascular vessels and the normal vessels spontaneously regenerate the surgical device and surgical method using the femtosecond laser-based ultrafast laser according to the present invention .

Surgical device and method for selective removal of neovascularization using ultrafast laser according to the present invention can remove only neovascularization by selective and safe method while at the same time maintaining various damages in other tissues, especially existing normal blood vessel It can be applied to the treatment of vascular diseases, and it can be applied to ultra-precision surgery with precision that has not been achieved by conventional scalpel or relatively long pulsed nano laser, continuous wave laser and ultraviolet laser surgery.

Claims (15)

A laser light source for generating a femtosecond single pulse laser beam; An optical system for focusing the laser beam from the laser light source; A stage for positioning the focused object including the neovascular vessel; And A monitoring device for monitoring tissue including neovascularization; Including; The neovascularization is removed and the laser beam fluence is adjusted to satisfy Equation (1) below, in which normal blood vessels damaged by the laser beam are spontaneously repaired and tissue cells excluding neovascular blood and normal blood vessels are not damaged by the laser beam. Surgical device for selective removal of neovascularization using an ultra-fast laser comprising a laser controller. 10 J / cm ² ≤ F ≤ 200 J / cm ² (1) [F is the laser beam fluence to be irradiated.] The method of claim 1, The laser beam is a surgical device for selective neovascular removal using an ultra-fast laser, characterized in that the laser beam in the near infrared region. delete delete delete The method of claim 1, Fluence (F) of the irradiated laser beam is a surgical device for neovascular selective removal using an ultra-fast laser, characterized in that 30 to 170 J / cm ² . The method according to claim 1 or 2, The stage for positioning the focused object including the neovascular vessel is a surgical device for selective removal of neovascular vessels using ultra-fast laser, characterized in that by the galvano scan or angiography for the neovascular vessels. The method according to claim 1 or 2, The neovascularization is a surgical device for selective neovascularization removal using ultra-fast laser, characterized in that the neovascularization is generated in the choroid covering the outer region of the retina. a) The neovascularization is removed at the surgical site including neovascularization and normal blood vessels, and the normal blood vessels damaged by the laser beam are spontaneously repaired and tissue cells except neovascular and normal blood vessels are not damaged by the laser beam. Irradiating a femtosecond single pulse laser beam that satisfies 1); 10 J / cm ² ≤ F ≤ 200 J / cm ² (1) [F is the laser beam fluence to be irradiated.] b) spontaneously regenerating normal blood vessels damaged by the laser beam irradiation; Neovascular vessel selective removal method of an animal except a human using an ultrafast laser comprising a. The method of claim 9, The laser beam irradiated in the step a) is a neovascular selective removal method of the animal, except for humans using ultra-fast laser, characterized in that the laser beam in the near infrared region. delete delete delete The method of claim 9, Fluence (F) of the laser beam irradiated in the step a) is 30 to 170 J / cm ² characterized in that the neovascular selective removal method of the animal, except for humans using an ultra-fast laser. The method of claim 10, Irradiation of the laser beam in step a) is the neovascularization selective removal method of the animal, except for humans, using ultrafast laser, characterized in that the position control by galvanoscopy or angiography for the neovascularization.

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