Introducing bubbles to improve cornea reshaping without the creation of a flap

Abstract

Ultra-short pulsed laser radiation is applied to a patient's eye to create a row of bubbles oriented perpendicular to the axis of vision. The row of bubbles leads to a region of the eye to be ablated. In a second step, a femtosecond laser beam guided through the row of bubbles converts it to a channel perpendicular to the axis of vision. In a third step, a femtosecond laser beam is guided through the channel to ablate a portion of the eye. Using a femtosecond laser with intensity in the range of 10.sup.11-10.sup.15 W/cm.sup.2 for the second and third steps facilitates multi-photon ablation that is practically devoid of eye tissue heating. Creating bubbles in the first step increases the speed of channel creation and channel diameter uniformity, thereby increasing the precision of the subsequent multi-photon ablation.

Claims

1. A method of removing material from an internal portion of organic tissue, comprising: creating a plurality of bubbles below the surface of the organic tissue with one or more laser beams, wherein the plurality of bubbles include a first row of bubbles which are linearly aligned; creating a channel through the linearly aligned first row of bubbles with the one or more laser beams; and ablating material located along or at the end of the channel with the one or more laser beams.

2. The method of claim 1 wherein the channel is created from 10.sup.−9 seconds to 10.sup.−6 seconds after the first row of bubbles is created.

3. The method of claim 2 wherein the one or more laser beams creating the first row of bubbles has a pulse intensity of from 10.sup.8 to 10.sup.9 W/cm.sup.2; the one or more laser beams creating the channel through the first row of bubbles has a pulse intensity of from 10.sup.11 to 10.sup.15 W/cm.sup.2; and the one or more laser beams ablating the material has a pulse intensity from 10.sup.12 to 10.sup.15 W/cm.sup.2.

4. The method of claim 3 wherein the one or more laser beams creating the first row of bubbles has a pulse energy of from 1 to 10 μJ; the one or more laser beams creating the channel through the first row of bubbles has a pulse energy of from 0.1 mJ to 1 mJ; and the one or more laser beams ablating the material has an energy level from 0.1 mJ to 5 mJ.

5. The method of claim 4 wherein the one or more laser beams creating the channel through the first row of bubbles has a focus diameter from 10 μm to 100 μm.

6. The method of claim 4 wherein the ablation of material is conducted with pulses having a repetition rate of 1 KHz or greater.

7. The method of claim 4 wherein pulses of the one or more laser beams that creates a first row of bubbles below the surface of the organic tissue are delivered parallel to a first axis; and wherein the first row of bubbles are created perpendicular to the first axis.

8. The method of claim 4 wherein the first row of bubbles are created at a depth from 150 μm to 250 μm below the surface of the organic tissue.

9. The method of claim 4 wherein the pulses of the one or more laser beams has a duration from 30 to 200 fsec.

10. The method of claim 4 wherein the pulses of the one or more laser beams has a repetition rate from 100 to 10,000 Hz.

11. The method of claim 4 wherein a single initial laser beam is divided to create the one or more laser beams that creates the first row of bubbles and the one or more laser beams that creates the channel and ablates the material.

12. The method of claim 4 wherein more than one row of bubbles are created, and the creation of the channel is through more than one row of bubbles.

13. The method of claim 2 wherein the channel extends from an outer surface of the organic tissue to an end point within the organic tissue.

14. The method of claim 2: wherein the row of bubbles is created below the surface of the organic tissue; wherein creating the channel through the row of bubbles with the one or more laser beams comprises creating a temporary micro-channel extending from a surface of the organic tissue to a micro-channel end point located within the organic tissue by delivering a first plurality of ultra-short laser pulses through the row of bubbles; and wherein ablating the material located along or at the end of the channel with the one or more laser beams comprises delivering a second plurality of ultra-short laser pulses with pulse energies of 20 μJ or greater and focused down to a pulse intensity in a range of 10.sup.12 to 10.sup.15 W/cm.sup.2 and thereby generating a void.

15. A method of removing material from an internal portion of organic tissue, comprising: creating a plurality of bubbles below the surface of the organic tissue with one or more laser beams, wherein the plurality of bubbles include a first row of bubbles which are linearly aligned; and creating a channel through the linearly aligned first row of bubbles with the one or more laser beams; wherein the channel is created from 10.sup.−9 seconds to 10.sup.−6 seconds after the first row of bubbles is created; wherein the one or more laser beams creating the first row of bubbles has a pulse intensity of from 10.sup.8 to 10.sup.9 W/cm.sup.2; the one or more laser beams creating the channel through the first row of bubbles has a pulse intensity of from 10.sup.11 to 10.sup.15 W/cm.sup.2; wherein the one or more laser beams creating the first row of bubbles has a pulse energy of from 1 to 10 μJ; the one or more laser beams creating the channel through the first row of bubbles has a pulse energy of from 0.1 mJ to 1 mJ; and wherein the first row of bubbles are created at a depth from 150 μm to 250 μm below the surface of the organic tissue.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Other objects and advantages of the invention may become apparent upon reading the following detailed description and upon reference to the accompanying drawings.

(2) FIG. 1 shows a schematic side view of prior art cornea laser ablation after creating a flap.

(3) FIG. 2 shows a schematic side view of creating a row of bubbles by laser induced photo-disruption, a step in a process for removing material from an interior portion of a cornea of the present invention.

(4) FIG. 3 shows a schematic side view of creating a row of bubbles by laser induced photo-disruption using a cylindrical lens.

(5) FIG. 4 shows a schematic side view of creating a row of bubbles by laser induced photo-disruption using a combination of a spherical lens and a cylindrical lens.

(6) FIG. 5 shows a schematic side view of converting a row of bubbles into a micro-channel by laser induced ablation or multi-photon ablation, another step in a process for removing material from an interior portion of a cornea of the present invention.

(7) FIG. 6 shows a schematic side view of creating a void within an interior portion of a cornea by removing material using laser induced multi-photon ablation enabled by a laser directed down the temporary micro-channel, yet another step in a process for removing material from an interior portion of a cornea of the present invention.

(8) FIG. 7 shows a schematic plan view of creating a void within an interior portion of a cornea by removing material using laser induced multi-photon ablation enabled by a laser directed down the temporary micro-channel.

(9) While the invention is subject to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and the accompanying detailed description. It should be understood, however, that the drawings and detailed description are not intended to limit the invention to the particular embodiment which is described. This disclosure is instead intended to cover all modifications, equivalents and alternatives falling within the scope of the present invention as defined by the appended claims. Further, the drawings may not be to scale, and may exaggerate one or more components in order to facilitate an understanding of the various features described herein.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

(10) One or more embodiments of the invention are described below. It should be noted that these and any other embodiments described below are exemplary and are intended to be illustrative of the invention rather than limiting.

(11) The preferred embodiments of the present invention will now be described with reference to the drawings. Identical elements in the various figures are identified with the same reference numerals.

(12) Reference will now be made in detail to embodiments of the present invention. Such embodiments are provided by way of explanation of the present invention, which is not intended to be limited thereto. In fact, those of ordinary skill in the art may appreciate upon reading the present specification and viewing the present drawings that various modifications and variations can be made thereto.

(13) FIG. 1 shows a schematic side view of prior art cornea LASIK laser ablation after creating a flap. With the flap 105 lifted aside, a laser beam 115 may ablate the interior of the cornea 110 directly, removing material from an ablated area 130 by photo-ablation, a heat mediated process. In such surgery, the laser beam 115 may be directed substantially along the optical axis, a.k.a. the axis of vision 125.

(14) The present invention improves on both the LASIK, and the prior Flapless LASIK method by, as an initial step, creating bubbles under the surface of the cornea in order to increase the speed of the laser beam penetrating into the area of corneal ablation. This improved Flapless LASIK procedure is a three-step procedure.

(15) In the first step, shown in FIG. 2, a laser beam oriented near parallel, or at a greater angle, to the axis of vision creates one or more long and narrow rows of bubbles in the cornea of the eye. Such a bubble row or rows may lead to the regions that are to be ablated in subsequent steps.

(16) In the second step, shown in FIG. 5, a femtosecond laser beam, directed through such bubble rows, reaches the stroma, between the inner (endothelial) and outer (superficial) cornea, creating a channel that is about perpendicular to the axis of vision or at a lesser or greater angle.

(17) In the third step, shown in FIG. 6, a femtosecond laser beam, after reaching the stroma, ablates the stroma at targeted spots.

(18) While the present invention is directed toward creating a channel within the cornea to reach the stroma, it can be applied to other areas of the eye.

(19) The steps of bubble creation, channel creation, and ablation of material can be accomplished by using one, two or three laser beams, whereby one or more laser sources may be used to generate the laser beams. For instance, a single laser source can be used that generates a single laser beam, preferably a femtosecond laser beam, that is divided into two beams, where the first beam performs the bubble creation and the second beam creates the channel and then ablates the target material. A second alternative would utilize two separate laser sources, where the first source generates the laser beam that creates the bubbles and the second source generates the laser beam that creates the channel and then ablates the target material. A third alternative would utilize a single laser source that emits a single laser beam at any given time and without splitting the beam, whereby the beam would initially be directed to create the bubbles, and once the bubbles were complete, the beam would be directed to create the channel and then ablate the material. A fourth alternative would utilize three separate laser beams, that would emit from one, two or three laser sources, whereby the first laser beam creates the bubbles, the second laser beam creates the channel, and the third laser beam ablates the target material.

(20) The preferred laser beams consist of pulses in the range of 30 to 200 fsec duration, which could be longer or shorter, at repetition rates of 100 to 10,000 Hz, which could be higher or lower, and with varying intensities depending on the process or step being undertaken.

The First Step

(21) In this initial step, shown in FIG. 2, a laser beam 115 of very low pulse energy, preferably in the range of 1 to 10 μA, though it may, with diminishing efficacy, be higher or lower, and with a focused intensity that is preferably in the range of 10.sup.8-10.sup.9 W/cm.sup.2, may be used. Any other such parameters that are sufficient to initiate a photo-disruption process may also be used, but may have significantly diminished efficacy. In one embodiment, a plurality of ultra-short laser pulses 115 are delivered to the eye approximately along, or parallel to, the vision axis 170, hence approximately perpendicular to the second laser beam used in the later steps shown in FIGS. 4 and 5. The laser may also be directed at different angles to the vision axis, though other angles tend to require more complex optical arrangements to achieve consistently good results. These pulsed may be used to create at least one row of bubbles 155 at depths of 150-250 μm below the surface of the cornea, although it could be shallower or deeper, that creates a string or row of bubbles, which may be created in an approximately straight line. A femtosecond or picosecond laser could be used to create the bubbles. This line of bubbles 155 is a precursor for the channel that is created in the second step.

(22) FIG. 2 shows a schematic side view of this step of creating a row of bubbles 155 by laser induced photo-disruption. As seen in FIG. 2, a laser amplifier and power supply 140 may be interfaced to programmable control circuitry 145, and may be used to generate a pulsed laser beam 115 that may be focused down to produce a pulse intensity in a range of 108 to 109 W/cm2 within a vicinity of the focal point. The laser beam 115 may, for instance, be focused by optical elements 150 such as, but not limited to, concave and convex spherical lenses, cylindrical lenses, prisms, beam-splitters, adjustable diaphragms, minors or some combination thereof. A bubble formed by photo-disruption 155 may be similar in diameter to the focus diameter 220 of the laser pulse, i.e., in a range from 10 μm to 100 μm. While creating the row of bubbles 135, the laser beam 115 may be directed substantially parallel to the optical axis, a.k.a. the axis of vision 125, thought the row of bubbles 135 may lie substantially perpendicular to this axis. This may be achieved by, for instance, by translating the optical elements 150 perpendicular to the axis of vision 125 in small incremental steps by means of a micro-transducer such as, but not limited to, a piezo-electric drive, a stepper motor controlled micrometer thread, or some combination thereof, all of which may be manipulated via the control circuitry 145. The row of bubbles may also be created by related methods such as, but not limited to, tilting the optics, using one or more steering mirrors, or some combination thereof.

(23) The bubbles are created using photo-disruption and their creation does not damage the cornea, and in particular does not damage the thin area of cornea corresponding to the flap area of regular LASIK. The bubbles are created in the range of between tens of nanoseconds [1 nanosecond (1 nsec)=10.sup.−9 sec] and tens of microseconds [1 microsecond (1 μsec)=10.sup.−6 sec] before the main ablation channel is created, although that time span could be shorter or longer. Bubbles are typically created in one to two rows, but there can be more rows, next to each other on a plane approximately parallel to the surface of the cornea. The focused laser beam spot may be moved along the stroma, at a speed of approximately 0.25 mm/s or faster, to form a bubble region.

(24) In another embodiment of creating the bubble row or rows, shown in FIG. 3, a cylindrical lens 215 can be implemented with the laser 140 oriented approximately parallel to the axis of vision 125, which creates one row of bubbles 135 per single pulse from the laser. Thus one or more rows of bubbles can be created, stretching from the edge of the eye's cornea to the point of ablation in the stroma, in a shorter period of time than without the use of a cylindrical lens.

(25) FIG. 3 shows a schematic side view of creating a row of bubbles by laser induced photo-disruption using a cylindrical lens 215. The laser amplifier and power supply 140 overseen by control circuitry 145 may generate a suitably shaped and powered beam that may be focused by the cylindrical lens 215 to form a focal line 225. The focal line may create the row of bubbles 135 in a single step, or may be stepped perpendicular to the axis of vision 125, creating the row of bubbles 135 in two or more steps. Using a focal line may increase the speed of the row creating process, but may require a higher powered laser to produce the required focused intensity to produce photo-disruption.

(26) In another embodiment, a laser beam oriented approximately perpendicular to the axis of sight can sequentially create bubbles at varying depths, thereby creating a bubble row or rows.

(27) In the event that the creation of the bubble row 135 or rows requires a shorter channel length without losing laser beam energy, an additional spherical lens can be applied. Such lens, with a diameter that can be approximately equal to the length of the cylindrical lens, is placed just above or below the cylindrical lens. The combination of these lenses both placed in the path of the laser beam can change the elongation of the laser beam to better match a distance from the entrance of the ablation laser beam into the cornea up to the desired area of stromal ablation.

(28) FIG. 4 shows a schematic side view of creating a row of bubbles by laser induced photo-disruption using a combination of one or more spherical lenses 210 and a cylindrical lens 215. The spherical lenses 210 may, for instance, act as beam shaping elements that may optimize the beam shape so that the spherical lens 210 may create a focal line 225 optimized for creating the row of bubbles 135 by photo-disruption.

(29) In another embodiment, more than one bubble row may be created approximately parallel to one another in order to create a wider diameter channel. This may provide improved control of the channel's perpendicular size as well as a channel with improved uniformity, compared to a channel of the same diameter that is created using a single row of bubbles. The resulting channel may be ellipsoidal in shape with a width in the range of 50 to 100 μm, which may be smaller or greater.

(30) While the focus size of a cylindrical lens dcyl without the use of a spherical lens may be in the range of 10 to 100 μm and elongated along the cylindrical lens axis, for example ζcyl=5 mm, using a cylindrical lens in conjunction with a spherical lens of long focal length, hence large focal spot diameter, for example d=2 mm, will produce a focal spot length ζcyl−d=2 mm practically without significant change of dcyl−d≈dcyl.

The Second Step

(31) In the second step, as shown in FIG. 5, a laser beam 190 creates the channel 180 by means of multi-photon ablation through the row or rows of bubbles by connecting by multi-photon ablation said row or rows of bubbles, where the channel typically extends from an outer (superficial) surface of the cornea 110 to a channel end point 185 located within said cornea (the endothelial cornea). The channel allows for ablation or removal of material at the channel end point as well as along the channel.

(32) This channel creating laser beam has a preferred pulse energy range of 0.1 mJ to 1 mJ and a focus diameter range of 10 μm to 100 μm, although each of these variables could be less than or greater than specified herein. The channel is created using multi-photon ablation, which requires a pulse intensity of 10.sup.12 watts/cm.sup.2 or greater, although a pulse intensity in the range of 10.sup.13-10.sup.15 W/cm.sup.2 is preferred. As the pulse intensity increases, the probability of initiating multi-photon ablation on a given pulse increases. However, higher energies will create wider channels, which may be less desirable. Use of lower pulse intensity that creates the channel via photo-ablation is possible, but this would result in thermal damage that would cause a longer channel closure and a longer healing time.

The Third Step

(33) Once the channel is created, the energy level of the laser beam may be kept constant or it may be increased, preferably by a factor of from 2 to 5 in comparison to the laser pulse energy for creation of the channel, or a different laser beam may be used at such energy levels. The pulse intensity is preferably increased to or maintained in the range of 10.sup.13-10.sup.15 W/cm.sup.2, and by focusing the laser at targeted tissue, the tissue is removed by multi-photon ablation. Keeping the energy of each laser pulse at approximately a constant value for the given pulse duration and the focal spot size is important to reach and maintain the approximately constant intensity for multi-photon ablation of live tissue. The channel may, for instance, also provide a means of removal of the ablated material in the form of a gas or a liquid, or a combination thereof. The removal of the ablated material may, for instance, occur as the result of a pressure differential between the void and the ambient room pressure. The procedure may, for instance, be conducted in a reduced pressure environment to provide improved removal of the ablated material. A separate channel or channels may alternatively be provided for the removal of the ablated material.

(34) FIG. 6 shows a schematic side view of this step of creating a void 195 within an interior portion of the cornea 110 by removing material using laser induced multi-photon ablation enabled by laser beam consisting of a second plurality of ultra-short laser pulses 205 directed down the temporary micro-channel 180. The laser amplifier and power supply 140, under control of programmable circuitry 145, may, for instance, produces pulses having energies in a range of 0.1 mJ to 5 mJ. These pulses may be focused down by optical elements 150 to produce pulse intensities in a range of 10.sup.12 to 10.sup.15 W/cm.sup.2. These high intensity pulses may induce multi-photon ablation within the temporary micro-channel 180 or in a vicinity of the micro-channel end point 185.

(35) By changing the position of the focusing lens or focusing minor, the location of the ablation spot can be moved along the channel. Controlling the number of laser pulses for each spot controls the amount of ablated material in each spot. By increasing the number of laser pulses more material will be ablated per unit of time, and by decreasing the number of laser pulses less material will be ablated per unit of time.

(36) By maintaining the pulse repetition rate, preferably in the range of 1 kHz or greater during this third step, the channel opening can be controlled or maintained until the desired ablations and procedures can be completed. Once the procedures are complete, the channel will spontaneously close and heal within several minutes, most of the time in less than 3 minutes, whereby smaller diameter channels may heal faster than larger diameter channels.

Multi-Photon Ablation

(37) The second and third steps are preferably accomplished using “multi-photon ablation”.

(38) Multi-photon ablation is a completely different method of material removal than photo-ablation. Multi-photon ablation requires a high laser pulse intensity, equal to or higher than 10.sup.12 W/cm.sup.2 and preferably in the range of 10.sup.13-10.sup.15 W/cm.sup.2, in order to remove particles, i.e. molecules and atoms, from targets. Multi-photon ablation operates by means of instantaneous absorption of several photons, faster than the molecule's or atom's relaxation time, and creates an ultra-high electric field in the vicinity of such particles. This causes a non-thermal ablation of matter, whereas other laser based ablation methods are thermal.

(39) For example, a 5 mJ pulse with 50 femtosecond pulse duration focused down to a diameter of 10 to 100 μm provides a pulse intensity in the range of 10.sup.13-10.sup.15 W/cm.sup.2. At such intensities particles (molecules, atoms) at the surface of the target material, for instance tissue, are under a very high electric field, which may exceed the work force, or bounding, of a molecule or atom to the target such as tissue material, therefore freeing them from the target surface and creating the effect of ablation but practically without heating the target material.

(40) Initiating multi-photon ablation with a given laser pulse is based on probability that is most affected by the pulse intensity. So, while multi-photon ablation may be possible below an intensity of 10.sup.12 W/cm.sup.2, the probability that a given pulse causes multi-photon ablation at lower intensities is significantly lower. As such, descriptions herein of multi-photon ablation processes do not preclude the possibility that certain laser pulses within such processes will fail to invoke multi-photon ablation and that certain pulses may thereby invoke photo-ablation.

(41) FIG. 7 shows a schematic plan view of creating a void 195 within an interior portion of a cornea 110 by removing material using laser induced multi-photon ablation enabled by a laser 140 directed down the temporary micro-channel 180.

Benefits of Bubble Creation

(42) The second and third steps can alternatively be performed as described without initially performing the first step of bubble creation. However, creating the bubbles prior to creating the channel provides several benefits in addition to those benefits provided in creating the channel without first creating the bubbles. First, implementing the bubble creation step increases the speed of the ablation channel's creation in the cornea. For example, the speed of creation of a 3 mm channel from the edge of the cornea to the area required for ablation was 1.5-2 times faster than without bubbles, all other conditions being the same. Second, the bubble creation provides for a more uniform channel diameter, which significantly increases the uniformity of the laser beam from shot-to-shot while traveling to the spot of ablation, improving the precision of the ablation. As seen from comparing the ablation times between ablation of material where the channel was created with and without the initial bubble creation step, this increased channel uniformity decreases losses of energy of the laser pulses, which allows for the effective and practical use of a lower level of pulse intensity for the multi-photon ablation of target materials by as much as about an order of magnitude.

Other Applications

(43) While the procedures disclosed herein are described as they apply to the eye, they may alternatively be applied to create channels in material or organic tissue, for example whereby the bubbles are initially created in the organic tissue using photo-disruption, fsec laser pulses then create the channel through the bubbles using multi-photon ablation, and if ablation is desired fsec laser pulses ablate matter using multi-photon ablation or other ablation techniques.

(44) Additionally, once a channel is created via steps 1 and 2, or via step 2, described herein, procedures other than ablation may be implemented through the channel, or material, drugs, or devices may be inserted through the channel.

(45) Although this invention has been described with a certain degree of particularity, it is to be understood that the present disclosure has been made only by way of illustration and that numerous changes in the details of construction and arrangement of parts may be resorted to without departing from the spirit and the scope of the invention.