peT
`WORLD INTElLECTUAL PROPERTY ORGANIZATION
`International Bureau
`INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`WO 94/25107
`
`(11) International Publication Number:
`
`(51) International Patent Classification 5 :
`A6lN 5/02
`
`Al
`
`(43) International Publication Date:
`
`10 November 1994 (10.11.94)
`
`(21) International Application Number:
`
`PCTIUS94/04362
`
`.. ~
`
`(22) International Filing Date:
`
`20 April 1994 (20.04.94)
`
`(30) Priority Data:
`051,033
`
`20 April 1993 (20.04.93)
`
`US
`
`(81) Designated States: AT, AU, BB, BG, BR, BY, CA, CH, CN,
`CZ, DE, DK, ES, Fl, GB, GE, HU, JP, KG, KP, KR, KZ,
`LK, LU, LV, MG, MN, MW, NL, NO, NZ, PL, PT, RO,
`RU, SD, SE, SK, TJ, IT, UA, UZ, VN, European patent
`(AT, BE, CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC,
`NL, PT, SE), OAPI patent (BF, BJ, CF, CG, CI, eM, GA,
`GN, ML, MR, NE, SN, TD, TG).
`
`(71) Applicant: NOVATEC LASER SYSTEMS, INC. [USIUS]; Published
`2237 Faraday Avenue, Carlsbad, CA 92008 (US).
`With international search report.
`Before the expiration of the time limit for amending the
`claims and to be republished in the event of the receipt of
`amendments.
`
`(72) Inventor: LA!, Shui, T.; 1223 Orchard Glen Circle, Encinitas,
`CA 92024 (US).
`
`(74) Agents: GREENHAUS, Bruce et al.; Spensley Hom Jubas &
`Lubitz, 5th floor, 1880 Century Park East, Los Angeles, CA
`90067 (US).
`
`(54) Title: IMPROVED OPHTHALMIC SURGICAL LASER AND METHOD
`
`(57) Abstract
`
`A laser-based method and apparatus for corneal and intraocular surgery.
`The preferred method of performing a surface ablation of cornea tissue or other
`organic materials uses a laser source which has a low ablation energy density
`threshold and extremely short laser pulses to achieve precise control of tissue
`removal. The laser beam cross-sectional area is preferably about 10J.£m in diameter.
`The preferred laser system includes a broad gain bandwidth laser (102) such as
`ThAlih Cr:LiSrAlf6. Nd:YLF, or similar lasers, with a preferred wavelength of .
`about 830 nm, which is generally transmissive in eye tissue. The invention can be
`used to excise or photoablate regions within the cornea, capsule, lens, vitreoretinal
`membrane, and other structures within the eye. The invention provides an
`improved method of eye surgery which has accurate control of tissue removal, and
`flexibility of ablating tissue at any desired location with predetermined ablation
`depth.
`
`" ':\
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`SYSTEM
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 1
`
`

`

`FOR THE PURPOSES OF INFORMATION ONLY
`
`Codes used to identify States party to the PCT on the front pages of pamphlets publishlng international
`applications under the PCT.
`
`AT
`AU
`BB
`BE
`BF
`BG
`BJ
`BR
`BY
`CA
`CF
`CG
`CD
`cr
`CM
`CN
`CS
`CZ
`DE
`DK
`ES
`FI
`FR
`GA
`
`Austria
`Australia
`Barbados
`Belgium
`Burkina Paso
`Bulgaria
`Benin
`Brazil
`Belarus
`Canada
`Central African Republic
`Congo
`Switzerland
`CI)te d'!voire
`Cameroon
`China
`Czechoslovakia
`Czech Republic
`Germany
`Denmark:
`Spain
`Fmland
`France
`Gabon
`
`GD
`GE
`GN
`GR
`HU
`m
`IT
`JP
`KE
`KG
`KP
`
`KR
`KZ
`U
`LK
`LV
`LV
`MC
`MD
`MG
`ML
`MN
`
`United Kingdom
`Georgia
`Guinea
`Greece
`Hungary
`Ireland
`Italy
`lapan
`Kenya
`Kyrgystan
`Democratic People's Republic
`of Korea
`Republic of Korea
`Kazakbstan
`Liechtenstein
`Sri Lanka
`Luxembourg
`Latvia
`Monaco
`Republic of Moldova
`Madagascar
`Mali
`Mongolia
`
`MR
`Mauritania
`MW Malawi
`NE
`Nigc:l'
`NL
`Netberlands
`Norway
`NO
`New Zea1and
`NZ
`PL
`Poland
`PT
`Portugal
`Rolllllllia
`RO
`Russian Federation
`RU
`SD
`Sudan
`SE
`Swedeu
`SI
`Slovenia
`SK
`Slovakia
`Senegal
`SN
`TD
`Chad
`TG
`Togo
`Tajikistan
`TJ
`IT
`Trinidad and Tobago
`UA
`Uk:ra.ine
`US
`United States of America
`UZ
`Uzbekistan
`VietNam
`VN
`
`"
`
`....
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 2
`
`

`

`wo 94/25107
`
`PCT /uS94/04362
`
`-1-
`
`IMPROVED OPHTHALMIC SURGICAL LASER AND METHOD
`
`If
`
`BACKGROUND OF THE INVENTION
`
`1.
`
`Field of the Invention
`
`This invention relates to methods of, and apparatus for, eye surgery, and more
`
`5
`
`particularly to a laser-based method and apparatus for corneal and intraocular
`
`surgery.
`
`2.
`
`Related Art
`
`The concept of correcting refractive errors by changing the curvature of the eye was
`
`initially implemented by mechanical methods. These mechanical procedures involve
`
`10
`
`removal of a thin layer of tissue from the cornea by a microkeratome, freezing the
`
`tissue at the temperature of liquid nitrogen, and re-shaping the tissue in a specially
`
`designed lathe. The thin layer of tissue is then re-attached to the eye by suture. The
`
`drawback of these methods is the lack of reproducibility and hence a poor
`
`predictability of surgical results.
`
`15
`
`With the advent of lasers, various methods for the correction of refractive errors and
`
`for general eye surgery have been attempted, making use of the coherent radiation
`
`properties of lasers and the precision of the laser-tissue interaction. A CO2 laser was
`one of the first to be applied in this field. Peyman, et aI., in Ophthalmic Surgery, vol.
`
`11, pp. 325-9, 1980, reported laser burns of various intenSity, location, and pattern
`
`20
`
`were produced on rabbit corneas. Recently, Horn, et aI., in the Journal of Cataract
`
`Refractive Surgery, vol. 16, pp. 611-6, 1990, reported that a curvature change in rabbit
`
`corneas had been achieved with a Co:MgF2 laser by applying specific treatment
`patterns and laser parameters. The ability to produce burns on the cornea by either
`
`a CO2 laser or a Co:MgF2 laser relies on the absorption in the tissue of the thermal
`energy emitted by the laser. Histologic studies of the tissue adjacent to burn sites
`
`25
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 3
`
`

`

`WO 94/25107
`
`PCT ruS94/04362
`
`-2-
`
`caused by a CO2 laser reveal extensive damage characterized by a denaturalized
`zone of 5-1 0 pm deep and disorganized tissue region extending over 50 pm deep.
`
`Such lasers are thus ill-suited to eye surgery.
`
`..
`
`In U.S. Patent No, 4,784,135, Blum et al. discloses the use of far-ultraviolet excimer
`
`5
`
`laser radiation of wavelengths less than 200 nm to selectively remove biological
`
`materials. The removal process is claimed to be by photoetching without using heat
`
`as the etching mechanism. Medical and dental applications for the removal of
`
`damaged or unhealthy tissue from bone, removal of skin lesions, and the treatment
`
`of decayed teeth are cited. No specific use for eye surgery is suggested, and the
`
`1 0
`
`indicated etch depth of 150 pm is too great for most eye surgery purposes.
`
`In U.S. Patent No. 4,718,418, L'Esperance, Jr. discloses the use of a scanning
`
`ultraviolet laser to achieve controlled ablative photodecomposition of one or more
`
`selected regions of a cornea. According to the disclosure, the laser beam from an
`
`excimer laser is reduced in its cross-sectional area, through a combination of optical
`
`15
`
`elements, to a 0.5 mm by 0.5 mm rounded-square beam spot that is scanned over
`
`a target by deflectable mirrors. TQ ablate a corneal tissue surface with such an
`
`arrangement, each laser pulse would etch out a square patch of tissue. An etch
`
`depth of 14 pm per pulse is taught for the illustrated embodiment. This etch depth
`
`would be expected to result in an unacceptable level of eye damage.
`
`20
`
`Another technique for tissue ablation of the cornea is disclosed in U.S. Patent No.
`
`4,907,586 to Bille et al. By focusing a laser beam into a small volume of about 25-30
`
`Jim in diameter, the peak beam intensity at the laser focal point could reach about
`1012 watts per cm2
`
`, At such a peak power level, tissue molecules are "pulled" apart
`
`under the strong electric field of the laser light, which causes dielectric breakdown of
`
`25
`
`the material. The conditions of dielectric breakdown and its applications in
`
`ophthalmic surgery had been described in the book "VAG Laser OphthalmiC
`
`Microsurgery" by Trokel. Transmissive wavelengths near 1.06 Jim and a frequency-
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 4
`
`

`

`WO 94/25107
`
`PeT fUS94/04362
`
`-3-
`
`r
`
`doubled laser wavelength near 530 nm are typically used for the described method.
`
`Near the threshold of the dielectric breakdown, the laser beam energy absorption
`
`characteristics of the tissue changes from highly transparent to strongly absorbent.
`
`The reaction is very violent, and the effects are widely variable. The amount of tissue
`
`5
`
`removed is a highly non-linear function of the incident beam power. Hence, the
`
`tissue removal rate is difficult to control. Additionally, accidental exposure of the
`
`endothelium by the laser beam is a constant concern. This method is not optimal for
`
`cornea surface or intraocular ablation.
`
`An important issue that is largely overlooked in all the above-cited references is the
`
`10
`
`fact that the eye is a living organism. Like most other organisms, eye tissue reacts
`
`to trauma, whether it is inflicted by a knife or a laser beam. Clinical results have
`
`shown that a certain degree of haziness develops in most eyes after laser refractive
`
`surgery with the systems taught in the prior art. The principal cause of such haziness
`
`is believed to be roughness resulting from cavities, grooves, and ridges formed while
`
`15
`
`laser etching. Additionally, clinical studies have indicated that the extent of the haze
`
`also depends in part on the depth of the tissue damage, which is characterized by
`
`an outer denatured layer around which is a more extended region of disorganized
`
`tissue fibers. Another drawback due to a rough corneal surface is related to the
`
`healing process after the surgery: clinical studies have confirmed that the degree of
`
`20
`
`haze developed in the cornea correlates with the roughness at the stromal surface.
`
`The prior art also fails to recognize the benefits of ablating eye tissue with a laser
`
`beam having a low energy density. A gentle laser beam, one that is capable of
`
`operating at a lower energy density for a surgical procedure, will clearly have the
`
`advantage of inflicting less trauma to the underlying tissue. The importance of this
`
`25
`
`point can be illustrated by considering the dynamiCS of the ablation process on a
`
`microscopic scale: the ablation process is basically an explosive event. During
`
`ablation, organiC materials are broken into their smaller sub-units, which cumulate a
`
`large amount of kinetic energy and are ejected away from the laser interaction point
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 5
`
`

`

`WO 94/25107
`
`peT /uS94/04362
`
`-4-
`
`at a supersonic velocity. The tissue around the ablated region absorbs the recoil
`..
`forces from such ejections. The tissue is further damaged by acoustic shock from
`
`the expansion of the superheated plasma generated at the laser interaction point.
`
`Accordingly, a shallower etch depth or smaller etch volumes involves less ejected
`
`5
`
`mass and acoustic shock, and hence reduces trauma to the eye.
`
`It is therefore desirable to have a method and apparatus for performing eye surgery
`
`that overcomes the limitations of the prior art.
`
`In particular, it is desirable to provide
`
`an improved method of eye surgery which has accurate control of tissue removal,
`
`flexibility of ablating tissue at any desired location with predetermined ablation depth
`
`10
`
`or volume, an optically smooth finished surface after the surgery, and a gentle
`
`surgical beam for laser ablation action.
`
`The present invention provides such a method and apparatus.
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 6
`
`

`

`WO 94/25107
`
`peT IUS94/04362
`
`-5-
`
`SUMMARY OF THE INVENTION
`
`The present invention recognizes that an optically smooth corneal surface and a clear
`
`intraocular light path (including post-operative clarity) are all critical to successful
`
`ophthalmic surgery. The effects of eye surgery on all of the intraocular elements
`
`5
`
`encountered by light traversing the optical path from the cornea to the retina must be
`
`considered. The invention was developed with a particular view to preserving these
`
`characteristics.
`
`The preferred method of performing a surface ablation of cornea tissue or other
`
`organiC materials uses a laser source which has the characteristics of providing a
`
`10
`
`shallow ablation depth or region (about 0.2 pm to about 5.0 pm), a low ablation
`
`energy density threshold (about 0.2 to 5 J,lJ/(1 0J,lm)2) and extremely short laser pulses
`
`(having a duration of about 0.01 picoseconds to about 2 picoseconds per pulse) to
`
`achieve precise control of tissue removal. The laser beam cross-sectional area is
`
`preferably about 10 J,lm in diameter.
`
`15
`
`The preferred laser system includes a broad gain bandwidth laser, such as Ti3AI20 3,
`Cr:LiSrAIF6, Nd:YLF, or similar lasers, with a preferred wavelength of about 400 nm
`to about 1900 nm, which is generally transmissive in eye tissue.
`
`Each laser pulse is directed to its intended location in or on the eye through a laser
`
`beam control means, such as the type described in a co-pending, commonly-owned
`
`20
`
`patent application for an invention entitled "Method of" and Apparatus for, Surgery of
`
`the Cornea" (U.S. Patent Application Serial No. 07/788,424).
`
`Various surgical procedures can be performed to correct refractive errors or to treat
`
`eye diseases. The surgical beam can be directed to remove cornea tissue in a
`
`predetermined amount and at a predetermined location such that the cumulative
`
`25
`
`effect is to remove defective or non-defective tissue, or to change the curvature of the
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 7
`
`

`

`WO 94/25107
`
`peT ruS94/04362
`
`cornea to achieve improved visual acuity. Excisions on the cornea can be make in
`
`any predetermined length and depth, and in straight line or in curved patterns.
`
`Alternatively, circumcisions of tissue can be made to remove an extended area, as in
`
`a cornea transplant. The invention can be used to excise or photoablate regions
`
`5
`
`within the cornea, capsule, lens, vitreoretinal membrane, and other structures within
`
`the eye.
`
`The present invention provides an improved method of eye surgery which has
`
`accurate control of tissue removal, flexibility of ablating tissue at any desired location
`
`with predetermined ablation depth, an optically smooth finished surface after the
`
`10
`
`surgery, and a gentle surgical beam for laser ablation action.
`
`The details of the preferred embodiments of the present invention are set forth in the
`
`accompanying drawings and the description below. Once the details of the invention
`
`are known, numerous additional innovations and changes will become obvious to one
`
`skilled in the art.
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 8
`
`

`

`WO 94/25107
`
`peT fUS94/04362
`
`-7-
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`FIGURE 1 A is a diagram showing the power density of a square laser pulse versus
`
`time for a 5 ns pulse.
`
`FIGURE 1 B is a diagram showing the power density of a square laser pulse versus
`
`5
`
`time for a 2.5 ns pulse.
`
`FIGURE 1 C is a diagram showing the power density of a square laser pulse versus
`
`time for a 2 ps pulse.
`
`FIGURE 2 is a diagram showing the excited state electron density of eye tissue at a
`
`laser beam interaction point.
`
`10
`
`FIGURE 3 is a diagram showing eye tissue ablation energy threshold versus pulse
`
`width.
`
`FIGURE 4 is a diagram showing the relative diameters of tissue regions removed by
`
`laser pulses at the ablation threshold for pulses of approximately 1 ns, 10 ps, and 1
`
`ps duration.
`
`15
`
`FIGURE 5 is a diagram showing the interaction pOint of a laser beam.
`
`FIGURE 6 is a block diagram of the preferred embodiment of the inventive apparatus.
`
`FIGURE 7 is a cross-sectional side view of a cornea showing some of the resulting
`
`incisions which can be formed in a stroma by the present invention.
`
`FIGURE 8A is a top view of a cornea, showing the use of the present invention to
`
`20
`
`make radial excisions on the cornea .
`..
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 9
`
`

`

`WO 94/25107
`
`peT /uS94/04362
`
`-8-
`
`FIGURE 88 is a top view of a cornea, showing the use of the present invention to
`
`make transverse-cut excisions on the cornea.
`
`FIGURE 9A and 98 are cross-sectional side views of a cornea, showing the use of
`
`the present invention to remove tissue to a desired depth d over an area on the
`
`5
`
`cornea, and an alternative method for performing a cornea transplant.
`
`FIGURE 10 is a cross-sectional side view of a cornea, showing the use of the present
`
`invention to correct myopia.
`
`FIGURE 11 is a cross-sectional side view of a cornea, showing the use of the present
`
`invention to correct hyperopia.
`
`10
`
`FIGURE 12 is a cross-sectional side view of a cornea, showing the use of the present
`
`invention to correct myopia using an alternative method.
`
`FIGURE 13A is a cross-sectional side view of a cornea, showing the use of the
`
`present invention to correct hyperopia using an alternative method.
`
`FIGURE 138 is a top view of the cornea of FIGURE 13A, showing the use of the
`
`15
`
`perimeter radial cuts to help correct hyperopia.
`
`FIGURE 14A is a cross-sectional side view of a convex applanator plate applied to
`
`an eye.
`
`FIGURE 148 is a cross-sectional side view of a concave applanator plate applied to
`
`an eye.
`
`20
`
`Like reference numbers and designations in the various drawings refer to like
`
`elements.
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 10
`
`

`

`WO 94/25107
`
`PCT /uS94/04362
`
`-9-
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`Throughout this description, the preferred embodiment and examples shown should
`
`be considered as exemplars, rather than limitations on the method and apparatus of
`
`the present invention.
`
`5
`
`The laser apparatus and method disclosed in this invention is for achieving two
`
`principal objectives:
`
`(1)
`
`The damage zone around the material ablated by the inventive laser system
`
`must be substantially reduced in comparison to prior art laser systems.
`
`(2)
`
`For each laser pulse deposited in or on the eye, a definite predetermined
`
`10
`
`depth or volume of tissue is to be ablated. The ablated depth per laser pulse must
`
`be controllable and about 5 pm or less, and preferably about 0.5 pm or less.
`
`To achieve these objectives, the present invention uses short duration laser pulses
`
`from about 0.01 to 2 picoseconds to reduce inflicted damage to target tissues. The
`preferred laser system includes a Ti3A120 3, Cr:LiSrAIF6, Nd:YLF, or similar laser with
`a preferred wavelength of about 400 nm to about 1900 nm. The laser beam cross(cid:173)
`
`15
`
`sectional area is preferably about 10 pm in diameter. The importance of these
`
`characteristics is explained below.
`
`Laser Pulse Duration
`
`A fundamental problem of prior art ophthalmic surgical laser systems is that such
`
`20
`
`systems fail to adequately take into account the interaction of the laser beam with
`
`organic tissue in the ablation process, particularly when using relatively transmissive
`
`laser wavelengths. Laser ablation occurs when the laser beam intensity, or energy
`
`level, is increased beyond a certain threshold level, causing dielectric breakdown.
`
`However, the actual ablation conditions vary depending on the characteristics of a
`
`25
`
`wide range of laser parameters and the composition of the material to be ablated.
`
`When laser energy is absorbed in an organic material, on the most basic level, the
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 11
`
`

`

`WO 94/25107
`
`PCT fUS94/04362
`
`-10-
`
`electronic configuration of the target polymer molecules makes a transition to one of
`
`its excited electronic states. Each polymer is made of hundreds or more of sub-units
`
`of smaller molecules called monomers. The monomers are made of even smaller
`
`units of radicals consisting of combinations of hydrogen, carbon, oxygen, and
`
`5
`
`nitrogen atoms. Depending on the energy level of the laser photons, a polymer can
`
`be broken into constituent monomers, radicals, or ionized atoms.
`
`For a laser having a wavelength near about 830 nm, a single laser photon is not
`
`sufficiently energetic to break any molecular bond. Breaking such a bond is a highly
`
`non-linear multi-photon process. After absorbing an initial photon, a molecule is
`
`10
`
`promoted to an excited electronic state configuration, with its electrons in higher
`
`energy orbits. This state will decay, or "relax", if additional photons are not absorbed
`
`to maintain the excited electronic state configuration.
`
`As the laser beam intensity increases further towards the ablation threshold, additional
`
`photons are absorbed, and the excited electron density reaches a critical volume
`
`15
`
`density such that the electronic orbitals can pair and transfer the sum of their energy
`
`to a single electron orbital. This process breaks the molecule into two or more
`
`pieces, and releases an energetic electron. At this point, the organic medium is
`
`damaged but not yet ablated.
`
`With increased power levels of the laser beam, further photons are absorbed, and the
`
`20
`
`excited electron density increases correspondingly. At the same time, the excited
`
`electrons migrate down the polymeric chain of the organic material, and spread
`
`towards the bulk volume with lower excited state density. The present invention
`
`recognizes that the excited state electronic orbitals are the means for energy storage
`
`that will eventually fuel the ablation process, and the electronic energy state migration
`
`25
`
`process plays a key role in the dynamics controlling the initiation of the laser ablation.
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 12
`
`

`

`WO 94/25107
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`PeT /uS94/04362
`
`-11-
`
`Because photoablation requires multiple photons interacting with organic tissue
`
`molecules, "ignition" of ablative action near the threshold condition is determined by
`
`a statistical process. That is, determination of the average etch depth or volume for
`
`laser beam energies near the ablation energy threshold are derived by measuring
`
`5
`
`actual etch depth or volume after hundreds or sometimes'thousands of laser pulses
`
`over the same location, and determining an average etch amount per pulse. On a
`
`single shot basis, however, the etch depth or volume could vary significantly, and
`
`most of the laser pulses may not ablate any material at all.
`
`In general, the ablation
`
`threshold for a particular wavelength is the total integrated energy required for 50%
`
`1 0
`
`of laser pulses to have an effect.
`
`Because of the statistical nature of laser pulse ablation, it is important to note that a
`
`reproducible etch depth or volume will not necessarily be attained at reduced levels
`
`of laser energy per pulse, especially when the energy level is close to being at an
`
`arbitrarily small value above the ablation energy threshold. Thus, in order to ensure
`
`15
`
`a reliable etch depth or etch volume for each single laser pulse, the operating energy
`
`per pulse is conventionally set at a multiple of the ablation energy threshold level; a
`
`factor of 3 to 4 times the ablation energy threshold is usually considered sufficient to
`
`achieve satisfactory results. For an excimer laser, the ablation threshold level is at
`about 50 mJ/cm2
`
`; basically no ablative action is observed at a laser energy density
`
`20
`
`below this threshold level. Accordingly, the typical energy density in an excimer surgi(cid:173)
`cal laser beam required for cornea ablation is about 150-250 mJ/cm2
`
`•
`
`Consider now the geometriC distribution of the excited state orbitals in an organic
`
`material. As the laser light is absorbed in the organic material, by Beer's law, the
`
`front surface where the material is first exposed encounters most of the laser photons,
`
`25
`
`and the beam intensity decreases exponentially as it traverses deeper into the
`
`material. Hence, the spatial distribution of the excited state density also decreases
`
`accordingly, characteristic of the absorption coefficient of the material at the laser
`
`wavelength.
`
`It follows that the slope of the distribution curve of the excited state
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 13
`
`

`

`WO 94/25107
`
`peT /uS94/04362
`
`-12-
`
`electron density is directly related to the absorption coefficient. Additionally, the
`
`steeper the slope of the excited state density distribution curve, the more spatially
`
`localized is the excited state density.
`
`Thus, to maintain a small laser beam interaction point (e.g:, about 1 J.1m to about 30
`
`5
`
`J.1m, and preferably about 10 J.1m), the slope of the excited state density distribution
`
`curve must be steep. To obtain a steep slope, the pulse width of the impinging laser
`
`beam should be kept narrow.
`
`It is known that if ablation is found to occur at a particular laser peak power,
`
`narrowing the laser pulse increases the ablation threshold. For example, FIGURE 1 A
`
`10
`
`is a diagram showing the power density of a square laser pulse versus time for a 5
`
`ns pulse.
`
`If the ablation threshold is found to occur. at a particular power density
`
`(arbitrarily considered to have a value of "1" in FIGURE 1), then a higher ablation
`
`threshold is required when the pulse is narrowed. That is, the total integrated energy
`
`of the shorter laser pulse must approach the total integrated energy of the longer
`
`15
`
`laser pulse. However, it is also known that halving the pulse duration does not
`
`require a doubling of the power density of the pulse. For example, FIGURE 1 B is a
`
`diagram showing the power density of a square laser pulse versus time for a 2.5 ns
`
`pulse. The ablation threshold is less than twice the ablation threshold of a 5 ns
`
`pulse.
`
`20
`
`Empirical results obtained from materials damage indicate that a particular ablation
`
`threshold can be reached with a pulsed laser beam 100 times shorter in duration than
`
`a longer duration pulse when the total integrated energy of the shorter laser pulse is
`
`at about 10% of the total integrated energy of the longer pulse.
`
`Conventional teaching requires an increase in the ablation threshold energy density
`
`25
`
`as pulse widths are decreased. However, it has been recognized in the present
`
`invention that the reason halving the pulse width of a laser does not require a
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 14
`
`

`

`WO 94125107
`
`peT /uS94/04362
`
`-13-
`
`doubling of the ablation threshold energy density is related to the build-up and
`
`relaxation of the excited state electron density. FIGURE 2 is a diagram showing the
`
`excited state electron density of eye tissue at a laser beam interaction point. The
`
`diagram shows that the excited state electron density is related to the energy density
`
`5
`
`of the incident laser beam. As photons from a laser beam interact with tissue, the
`
`electron state of the molecules undergo "charging" to a steady state. The "charging"
`
`time tR is related to the electron migration rate. The discharge time is also equal to
`
`tR. The charge/discharge time tR is approximately 0.5 to 1 picoseconds.
`
`After the initial photons of a laser pulse charge the excited state electron density to
`
`10
`
`a steady state, the remaining photons of the pulse have essentially no effect on such
`
`density. The steady state arises because energy migrates away from the beam
`
`interaction point. When using longer duration pulses, the energy migration process
`
`is counter-balanced by additional laser beam pumping to build up the critical excited
`
`state electron denSity. However, with a longer laser pulse, the excited state orbitals
`
`15
`
`diffuse from the laser interaction point into the depth of the material (along the laser
`
`beam direction). Hence, the excited state distribution curve will have less steep a
`
`slope compared to the curve from a shorter pulse. The present invention recognizes
`
`that the depth of the tissue layer which has sufficient excited state orbitals to satiSfy
`
`the ablation threshold condition will be correspondingly deepened. Therefore, the
`
`20
`
`damage inflicted by a longer duration laser pulse is more extensive than the damage
`
`inflicted with a shorter duration pulse.
`
`As noted above, for a laser pulse having a low energy density, a longer pulse dura(cid:173)
`
`tion is required to achieve sufficient photon interactions to charge the excited state
`
`electron density to a steady state. Conversely, for a laser pulse having a shorter
`
`25
`
`duration, a higher energy density is required. However, because of the higher energy
`
`density, more photon interactions per unit of time occur, thereby more rapidly
`
`charging the excited state electron density to the steady state. Less energy migrates
`
`away from the laser interaction point. Consequently, the total integrated energy of
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 15
`
`

`

`WO 94/25107
`
`PCT ruS94/04362
`
`-14-
`
`a narrower pulse need not be as great as the total integrated energy of a longer
`
`pulse to achieve the ablation threshold.
`
`Importantly, it has been discovered in the present invention that the power density for
`
`the ablation threshold reaches an approximately constant level as the laser pulse
`
`5
`
`width decreases and closely approaches the charge/discharge time tR• For example,
`as shown in FIGURE 1 C, a 2 picosecond pulse may have about the same ablation
`
`threshold as a much shorter pulse. FIGURE 3 is a diagram showing eye tissue
`
`ablation energy threshold versus pulse width. As the laser pulse width reaches about
`
`2 picoseconds, and the energy density of the beam is about 1.0 J.lJ/(10J.lm)2 for an
`
`10
`
`830 nm wavelength, the number of photons is sufficient to maintain a steady state
`
`excited state electron density without significant decay. This relationship between
`
`, pulse duration and constant ablation threshold has been found to exist from about
`
`2 picoseconds down to at least 0.01 picoseconds.
`
`Thus, ablation can be achieved at a low ablation threshold energy using such
`
`15
`
`extremely short duration laser pulses. Further, tissue damage from acoustic shock
`
`and kinetic action from dissociated matter is directly proportional to energy deposited
`
`at the laser interaction point.
`
`If the ablation threshold is achieved at less than the
`
`total pulse energy, the remaining energy in the pulse is completely absorbed by the
`
`generated plasma, thereby contributing to the explosive effect of the tissue ablation.
`
`20
`
`Both acoustic shock and kinetic action are decreased by reducing the pulse duration.
`
`Another benefit from reducing the pulse duration is limitation of damage to tissue
`
`surrounding the laser interaction pOint due to energy migration. FIGURE 4 is a
`
`diagram showing the relative diameters of tissue regions removed by laser pulses at
`
`the ablation threshold for pulses of approximately 1 nanosecond, 10 picoseconds,
`
`25
`
`and 0.1 picosecond duration. As can be seen, the range of tissue removal and
`
`surrounding tissue damage is substantially less for the shorter pulses (the volume of
`
`Alcon Research, Ltd.
`Exhibit 1017 - Page 16
`
`

`

`WO 94/25107
`
`PCT /uS94/04362
`
`-15-
`
`tissue removed is proportional to energy deposited, which falls off from the center of
`
`the interaction pOint proportionally to the radius cubed).
`
`Transmissive Wavelengths
`
`In order to perform intraocular surgical procedures, the laser beam necessarily must
`
`5
`
`pass through overlying tissue to the desired location without damage to the overlying
`
`tissue. Accordingly, the illustrated embodiment of the present invention uses an 830
`
`nm wavelength for the laser beam, which is generally transmissive in eye t!ssue.
`
`Such a wavelength can be generated in known fashion from a broad gain bandwidth
`(I.e., 1:.). > t'V 1 mm) laser, such as a Ti3A120 3, Cr:LiSrAIF 6' Nd:YLF, or similar laser.
`One such laser is described in co-pending U.S. Patent Application Serial No.
`
`10
`
`07/740,004, filed August 2, 1991, entitled "Two Dimensional Scanner-Amplifier Laser"
`
`and assigned to the assignee of the present invention.
`
`Other wavelengths could be used as desired, since absorption and transmission in
`
`the eye is a matter of degree. Thus, less transmissive wavelengths can be used for
`
`15
`
`procedures at or near the front of the eye, such as the cornea.
`
`In general,
`
`acceptable wavelengths include the ranges of about 400 nm to about 1900 nm, about
`
`2.1 pm to about 2.8 pm, an