(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY(PCT)
`
` (10) International Publication Number
`
`WO 2008/008330 A2
`
`(19) World Intellectual Property Organization
`International Burcau
`
`(43) International Publication Date
`17 January 2008 (17.01.2008)
`
`(51) International Patent Classification:
`A61IB 18/18 (2006.01)
`
`(21) International Application Number:
`PCT/US2007/015718
`
`(22) International Filing Date:
`
`10 July 2007 (10.07.2007)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`(30) Priority Data:
`60/830,292
`11/825,816
`
`English
`
`English
`
`12 July 2006 (12.07.2006)
`9 July 2007 (09.07.2007)
`
`US
`US
`
`(71) Applicant (for afl designated States except US): NTK EN-
`TERPRISES, INC. [US/US]; 2800 North Dallas Parkway,
`Suite 100, Plano, Texas 75093 (US).
`
`(72) Inventor; and
`(75) Inventor/Applicant (for US only): BERRY, Michael, J.
`[US/US]; 10448 Fairway Lane, Carmel, California 93923
`(US).
`
`(81) Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AT, AU, AZ, BA, BB, BG, BH, BR, BW,BY, BZ, CA, CH,
`CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG,
`ES, FI, GB, GD, GE, GI, GM, GT, TIN, IIR, ITU, ID,IL,
`IN,IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK,
`LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, Mw,
`MX, MY, MZ, NA, NG, NI, NO, NZ, OM,PG,PII, PL,
`PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY,
`TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA,
`ZM, ZW.
`
`(84) Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM,
`ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI,
`FR, GB, GR, HU,IE, IS, IT, LT, LU, LV, MC, MT, NL, PL,
`PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM,
`GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
`
`Published:
`
`— without international search report and to be republished
`upon receipt of that report
`
`(74) Agents: MUNCK, William A.et al.; Munck Butrus, P.C.,
`900 Three Galleria Towerll13155 Noel Road, Dallas, Texas
`75240 (US).
`
`For two-letter codes and other abbreviations, refer to the "Guid-
`ance Notes on Codes and Abbreviations" appearing at the begin-
`ning of each regular issue of the PCT Gazette.
`
`(54) Titles DEUTERATED OCULAR SOLUTIONS FOR LIK AND OTHER SURGICAL EYE PROCEDURES
`
`1200
`
`<a
`
`START
`
`1202
`
`
`NY | PREPARE PATIENT'S EYE FOR SURGICAL PROCEDURE
`
`APPLY DEUTERATED OCULAR SOLUTION TO SURFACE OF
`
`PATIENT’S EYE
`
`APPLY PROTECTIVE CORNEAL APPLANATOR DEVICE
`
`1208
`
`SY GENERATE LASER LIGHTAND IRRADIATESURFACEOF PATIENT'S
`EYE
`—
`REMOVE PROTECTIVE CORNEAL APPLANATOR DEVICE
`
`1210
`
`
`
`(57) Abstract: A deuterated ocular solution is applied (1204) to an eye. The deuterated ocular solution includes deuterated water
`and one or more ocular drugs (such as proparacaine). A protective corneal device (102) is applied (1 206) to a cornea of the eye. The
`device (102) includes a window (210) configured to contact at least a portion of the cornea. At least part of the corneais irradiated
`(1208) using light energy that passes through the window (210) during a cornea reshaping procedure, where the window (210)is
`substantially transparent to the light energy. The window (210) of the protective corneal device (102) and the deuterated ocular
`solution may preventclinically significant damage to a corneal epithelium of the cornea during the cornea reshaping procedure, such
`as by preventing a temperature of the corneal epithelium from exceeding approximately 70°C during the cornea reshaping procedure.
`This may help to avoid a wound healing response in the eye and an associated regression of refractive correction.
`
`
`
`2008/008330A2/IINIMIANINAINAININMIATTMITIATAAA
`
`
`
`
`
`

`

`WO 2008/008330
`
`PCT/US2007/015718
`
`1
`
`DEUTERATED OCULAR SOLUTIONS FOR
`LTK AND OTHER SURGICAL EYE PROCEDURES
`
`CROSS-REFERENCE TO RELATED APPLICATIONS
`
`[0001] This application claims priority under 35 U.S.C.
`
`§
`
`119(e)
`
`to U.S. Provisional Patent Application No.
`
`60/830,292
`
`filed on
`
`July 12,
`
`2006,
`
`and U.S. Patent
`
`Application No.
`
`filed July 9, 2007 (Attorney
`
`10
`
`Docket No. UNIV0O3-00005) which are hereby incorporated by
`
`reference.
`
`{09002} This application is related to the following U.S.
`
`Patent Applications:
`
`15
`
`AND METHOD FOR CORNEA APPLANATION AND EPITHELIUM PROTECTION
`
`Serial No. 60/684,749 entitled “DEVICE, SYSTEM,
`
`DURING CORNEA RESHAPING” filed on May 26, 2005;
`
`Serial No. 60/695,175 entitled “DEVICE, SYSTEM,
`
`AND METHOD
`
`FOR
`
`ENHANCED
`
`PROTECTION
`
`OF
`
`THE
`
`CORNEAL
`
`EPITHELIUM DURING CORNEA RESHAPING” filed on June 29, 2005;
`
`20
`
`and
`
`Serial No. 11/440,794 entitled “DEVICE, SYSTEM,
`
`AND METHOD
`
`FOR
`
`EPITHELIUM PROTECTION
`
`DURING
`
`CORNEA
`
`RESHAPING” filed on May 25, 2006;
`
`all of which are hereby incorporated by reference.
`
`

`

`WO 2008/008330
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`PCT/US2007/015718
`
`2
`
`TECHNICAL FIELD
`
`[0003] This disclosure is generally directed to ocular
`solutions. More specifically,
`this disclosure is directed
`to
`deuterated
`ocular
`solutions
`for
`laser
`thermal
`
`keratoplasty (LTK) and other surgical eye procedures.
`
`BACKGROUND
`
`(0004] Today,
`
`there are hundreds of millions of people
`
`in the United States
`
`and around the world who wear
`
`eyeglasses or contact
`
`lenses to correct ocular refractive
`
`errors.
`
`The most common ocular refractive errors include
`
`myopia
`
`(nearsightedness),
`
`hyperopia
`
`(farsightedness),
`
`astigmatism, and presbyopia.
`
`[0005] Myopic vision can
`
`be modified,
`
`reduced,
`
`or
`
`corrected by flattening the cornea axisymmetrically around
`
`the visual axis to reduce its refractive power. Hyperopic
`
`vision can be modified,
`
`reduced, or corrected by steepening
`
`the cornea axisymmetrically around the visual axis
`
`to
`
`increase its refractive power. Regular astigmatic vision
`
`can be modified,
`
`reduced, or corrected by flattening or
`
`steepening
`
`the
`
`cornea with
`
`the
`
`correct
`
`cylindrical
`
`curvatures
`
`to compensate
`
`for
`
`refractive errors
`
`along
`
`various meridians.
`
`Irregular astigmatism often requires
`
`correction by a more complex refractive surgical procedure.
`
`Presbyopic vision can be modified,
`
`reduced, or corrected
`
`by rendering the cornea multifocal by changing its shape
`
`annularly so that one annular zone focuses distant rays of
`
`light properly while another annular zone focuses near rays
`
`of light properly.
`
`[0006] There are various procedures that have been used
`
`to correct ocular refractive errors, such as laser thermal
`
`keratoplasty (LTR).
`
`LTK uses
`
`laser
`
`light
`
`to heat
`
`the
`
`cornea, causing portions of the cornea to shrink over time.
`
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`
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`3
`
`For example,
`
`human corneal stromal collagen may shrink
`
`when heated to a temperature above approximately 55°C.
`
`stroma is the central,
`
`thickest layer of the cornea.
`
`The
`
`The
`
`stroma is formed mainly of keratocytes embedded in an
`
`extracellular matrix
`
`composed
`
`of
`
`— collagen
`
`fibers,
`
`proteoglycans, water, and other materials.
`
`If the pattern
`
`ef stromal collagen shrinkage is properly selected,
`
`the
`
`cornea is reshaped to reduce or eliminate one or more
`
`ecular refractive errors.
`
`LTK typically does not
`
`remove
`
`10
`
`corneal tissue and does not penetrate the cornea physically
`
`with a needle or other device.
`
`[0007] A problem with LTK and other procedures
`
`is
`
`regression of refractive correction, meaning the correction
`
`induced during a procedure is reduced or eliminated over
`
`15
`
`time and an ocular refractive error returns. Corneal wound
`
`healing may be one cause of this regression, and a corneal
`
`wound healing response may be triggered by damage to the
`
`corneal epithelium in the cornea.
`
`The corneal epithelium
`
`20
`
`is heated to a.
`it
`if
`example,
`for
`damaged,
`can be
`temperature of approximately 70°C or greater, even if only
`
`for a period of a few seconds or less.
`
`fOOO8) Moreover, during reshaping of a cornea using LTK
`
`or another procedure,
`
`it may be desirable to use one or
`
`more ocular or ophthalmic solutions,
`
`such as
`
`a
`
`topical
`
`25
`
`anesthetic. However,
`
`these ophthalmic solutions may often
`
`interfere with the LTK or other procedure,
`
`such as by
`
`interfering with the corneal reshaping.
`
`

`

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`
`PCT/US2007/015718
`
`4
`
`SUMMARY
`
`[0009] This
`
`disclosure
`
`provides
`
`deuterated
`
`ocular
`
`solutions for LTK and other surgical eye procedures.
`
`(0010)
`
`In a first embodiment, a method includes applying
`
`a deuterated ocular solution to an eye.
`
`The eye includes a
`
`cornea,
`
`and
`
`the deuterated ocular
`
`solution includes
`
`deuterated water and one or more ocular drugs.
`The method
`also includes applying a device to the cornea of the eye,
`where the device includes a window configured to contact at
`
`least a portion of the cornea.
`
`The method further includes
`
`irradiating at least part of the cornea using light energy
`
`that passes through the window during a cornea reshaping
`
`procedure.
`
`The window is substantially transparent to the
`
`light energy.
`
`[0011]
`
`In particular embodiments,
`
`the one or more ocular
`
`drugs include proparacaine.
`[0012]
`In other particular
`
`embodiments,
`
`the method
`
`further
`
`includes preventing, using the window and the
`
`deuterated ocular solution, clinically significant damage
`
`to a corneal epithelium of
`
`the cornea during the cornea
`
`reshaping procedure.
`
`For example,
`
`the method could include
`
`the corneal epithelium from
`temperature of
`preventing a
`‘exceeding approximately 70°C during the cornea reshaping
`
`procedure.
`
`[0013]
`
`In a second embodiment, an apparatus includes a
`
`suction ring configured to attach the apparatus to an eye,
`
`where
`
`the eye includes a cornea.
`
`The apparatus also
`
`includes a window configured to contact at least a portion
`
`of the cornea.
`
`The window is substantially transparent to
`
`light energy that
`
`irradiates the cornea during a cornea
`
`reshaping procedure.
`
`The window is also configured to cool
`
`at least a portion of a corneal epithelium in the cornea
`
`during the cornea reshaping procedure.
`
`In addition,
`
`the
`
`10
`
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`
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`
`5
`
`apparatus
`
`includes
`
`a
`
`reservoir
`
`configured to hold a
`
`deuterated ocular solution.
`
`The deuterated ocular solution
`
`includes deuterated water and one or more ocular drugs and
`
`is for application to the eye before the cornea reshaping
`
`procedure.
`
`[0014]
`
`In a third embodiment, a system includes a light
`
`source configured to generate light energy for a cornea
`
`reshaping procedure.
`
`The system also includes a device
`
`configured to be applied to an eye that includes a cornea.
`
`The device includes a window configured to contact at
`
`least a portion of the cornea.
`
`The window is substantially
`
`transparent
`
`to the light energy.
`
`The window is also
`
`configured to cool at
`
`least
`
`a portion of
`
`a
`
`corneal
`
`epithelium in the
`
`cornea during the
`
`cornea
`
`reshaping
`
`procedure.
`
`In addition,
`
`the system includes a container
`
`holding a deuterated ocular solution.
`
`The deuterated
`
`ocular solution includes deuterated water and one or more
`
`ecular drugs and is for application to the eye before the
`
`cornea reshaping procedure.
`
`[90015] Other technical features may be readily apparent
`
`to one skilled in the art
`
`from the following figures,
`
`descriptions, and claims.
`
`10
`
`15
`
`20
`
`

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`PCT/US2007/015718
`
`6
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0016] For
`
`a more
`
`complete
`
`understanding
`
`of
`
`this
`
`disclosure and its features,
`
`reference is now made to the
`
`following description,
`
`taken in conjunction with the
`
`in which:
`accompanying drawings,
`£0017] FIGURE 1 illustrates an example system for cornea
`
`reshaping according to one embodiment of this disclosure;
`
`[0018] FIGURE
`
`2
`
`illustrates
`
`an
`
`example protective
`
`corneal applanator device according to one embodiment of
`
`10
`
`this disclosure;
`
`{0019] FIGURES 3A and 3B illustrate example uses of a
`
`protective corneal applanator device
`
`according to one
`
`embodiment of this disclosure;
`
`(0020] FIGURE 4
`
`illustrates an example microlens that
`
`15
`
`could be mounted in a protective corneal applanator device
`
`according to one embodiment of this disclosure;
`
`[0021] FIGURES
`
`5
`
`through
`
`8
`
`illustrate
`
`example
`
`temperature distributions within corneal
`
`tissue during a
`
`cornea reshaping procedure according to one embodiment of
`
`20
`
`this disclosure;
`
`[0022] FIGURES
`
`9A through 9D illustrate example beam
`
`splitting systems according to one
`
`embodiment of
`
`this
`
`disclosure;
`
`[0023] FIGURE 10 illustrates an example linear four-beam
`
`25
`
`array matching a fiber optic array in a beam distribution
`
`system according to one embodiment of this disclosure;
`
`[0024] FIGURES
`
`11A through
`
`11C
`
`illustrate example
`
`patterns of treatment during a cornea reshaping procedure
`
`according to one embodiment of this disclosure; and
`[0025] FIGURE 12 illustrates an example method for using
`
`30
`
`a deuterated ocular solution during a cornea reshaping
`
`procedure according to one embodiment of this disclosure.
`
`

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`PCT/US2007/015718
`
`7
`
`DETAILED DESCRIPTION
`
`[0026] FIGURE 1 illustrates an example system 100 for
`
`cornea
`
`reshaping according to one
`
`embodiment of
`
`this
`
`disclosure.
`
`The embodiment of
`
`the system 100 shown in
`
`FIGURE 1
`
`is for illustration only. Other embodiments of
`
`the system 100 may be used without departing from the scope
`
`of this disclosure.
`
`[0027]
`
`In this
`
`example,
`
`the
`
`system 100
`
`includes
`
`a
`
`protective corneal applanator device 102.
`
`The protective
`
`corneal
`
`applanator
`
`device
`
`102
`
`is pressed against
`
`a
`
`patient’s eye 104 during a cornea reshaping procedure.
`
`For
`
`example,
`
`the protective corneal applanator device 102 may
`
`be used during laser thermal keratoplasty ({(LTK) or other
`
`procedure meant
`
`to correct one or more ocular refractive
`
`errors in the patient’s eye 104.
`
`[0028] Among other
`
`things,
`
`the protective
`
`corneal
`
`applanator device 102 helps to reduce or eliminate damage
`
`to the corneal epithelium of the patient’s eye 104 during
`
`the
`
`cornea
`
`reshaping
`
`procedure.
`
`For
`
`example,
`
`the
`
`protective corneal applanator device 102 could act as a
`
`heat sink to conduct heat away from the patient’s eye 104
`
`during the procedure. This helps to reduce the temperature
`
`of
`
`the corneal epithelium, which may help to reduce or
`
`eliminate damage
`
`to the corneal epithelium and avoid a
`
`corneal wound
`
`healing
`
`response
`
`that
`
`could
`
`lead
`
`to
`
`regression
`
`of
`
`refractive
`
`correction.
`
`One
`
`example
`
`embodiment of the protective corneal applanator device 102
`
`is shown in FIGURE 2, which is described below.
`
`In this
`
`document,
`
`the phrase “cornea reshaping procedure” refers to
`
`any procedure involving a patient’s eye 104 that results in
`
`a
`
`reshaping of
`
`the cornea in the eye 104, whether
`
`the
`
`reshaping occurs immediately or over time.
`
`[0029] The system 100 also includes a laser 106.
`
`The
`
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`8
`
`laser 106 provides laser light that is used to irradiate
`
`the patient’s
`
`eye
`
`104
`
`during
`
`the
`
`cornea
`
`reshaping
`
`procedure.
`
`The
`
`laser 106 represents any suitable laser
`
`capable of providing laser light
`
`for a cornea reshaping
`
`procedure.
`
`For example,
`
`the laser 106 could represent a
`
`continuous wave laser, such as a continuous wave hydrogen
`
`fluoride chemical laser or a continuous wave thulium fiber
`
`laser.
`
`In other embodiments,
`
`the laser 106 could represent
`
`a pulsed laser, such as a pulsed holmium:yttrium aluminum
`
`garnet
`
`(Ho:YAG)
`
`laser.
`
`Any other suitable laser or non-
`
`laser light source capable of providing suitable radiation
`
`for a cornea reshaping procedure could also be used in the
`
`system 100.
`
`[0030] The
`
`laser
`
`light produced by the laser 106 is
`
`provided to a beam distribution system 108.
`
`The beam
`
`distribution system 108 focuses the laser light
`
`from the
`
`laser 106.
`
`For example,
`
`the beam distribution system 108
`
`could include optics that focus the laser light
`
`from the
`
`laser 106 to control
`
`the geometry, dose,
`
`and irradiance
`
`level of the laser light as it is applied to the cornea of
`
`the patient’s
`
`eye
`
`104
`
`during
`
`the
`
`cornea
`
`reshaping
`
`procedure.
`
`The beam distribution system 108 could also
`
`include a shutter for providing a correct exposure duration
`of the laser light.
`In addition,
`the beam distribution
`system 108
`could include a
`beam splitting system for
`
`splitting the
`
`focused laser
`
`light
`
`into multiple beams
`
`(which may be
`
`referred to ‘as “laser beams,” “treatment
`
`beams,” or “beamlets”).
`
`The beam distribution system 108
`
`includes any suitable optics, shutters, splitters, or other
`
`or additional structures for generating one or more beams
`
`for a cornea reshaping procedure.
`
`Examples of
`
`the beam
`
`splitting system in the beam distribution system 108 are
`
`shown in FIGURES 9A through 9D, which are described below.
`
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`9
`
`[0031] One or more beams
`
`from the beam distribution
`
`system 108
`
`are
`
`transported to the protective corneal
`
`applanator device 102 using a fiber optic array 110.
`
`The
`
`fiber optic array 110 includes any suitable structure(s)
`
`for transporting one or multiple laser beams or other light
`
`energy to the protective corneal applanator device 102.
`
`The
`
`fiber optic array 110 could,
`
`for example,
`
`include
`
`multiple groups of
`
`fiber optic cables,
`
`such as groups
`
`containing four fiber optic cables each.
`
`The fiber optic
`
`array 110 could also include attenuators that
`
`rebalance
`
`fiber outputs so as to make up for differences in optical
`
`fiber transmission through the array 110.
`
`[0032] A translation stage 112 moves
`
`the fiber optic
`
`array 110 so that
`
`laser light
`
`from the laser 106 enters
`
`different ones of the fiber optic cables in the fiber optic
`
`array 110.
`
`For example,
`
`the beam distribution system 108
`
`could produce four laser beams, and the translation stage
`
`112 could move the fiber optic array 110 so that the four
`
`beams enter different groups of four fiber optic cables.
`
`Different fiber optic cables could deliver laser light onto
`
`different areas of
`
`the cornea in the patient’s eye 104.
`
`The translation stage 112 allows the different areas of the
`
`cornea to be irradiated by controlling which fiber optic
`
`cables are used to transport the laser beams from the beam
`
`distribution
`
`system 108
`
`to
`
`the
`
`protective
`
`corneal
`
`applanator device 102.
`
`The translation stage 112 includes
`
`any suitable structure for moving a
`
`fiber optic array.
`
`While the use of four laser beams and groups of four fiber
`
`optic cables has been described,
`
`any suitable number of
`
`laser beams and any suitable number of fiber optic cables
`
`could be used in the system 100.
`
`[0033] A position controller 114 controls the operation
`
`of the translation stage 112.
`
`For example,
`
`the position
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`
`controller 114 could cause the translation stage 112 to
`
`translate,
`
`thereby repositioning the fiber optic array 110
`
`so that the laser beams from the beam distribution system
`
`108 enter a different set of fiber optic cables in the
`
`array 110..
`
`The position controller
`
`114
`
`includes
`
`any
`
`hardware,
`
`software,
`
`firmware, or combination thereof for
`
`controlling the positioning of a fiber optic array.
`
`[0034] A controller 116 controls the overall operation
`
`of the system 100.
`
`For example,
`
`the controller 116 could
`
`ensure that the system 100 provides predetermined patterns
`
`and doses of laser light onto the anterior surface of the
`
`cornea in the patient’s eye 104. This allows the controller
`
`116 to ensure that an LTK or other procedure is carried out
`
`properly on the patient’s eye 104.
`
`In some embodiments,
`
`the controller 116 includes all of the controls necessary
`
`for a surgeon or other physician to have complete control
`
`of
`
`the cornea
`
`reshaping procedure,
`
`including suitable
`
`displays of operating variables showing what parameters
`
`have been preselected and what parameters have actually
`
`been used.
`
`AS a particular example,
`
`the controller 116
`
`could allow a surgeon to select, approve of, or monitor a
`
`If a
`the patient’s eye 104.
`irradiation of
`pattern of
`pulsed laser 106 is used, the controller 116 could also
`
`allow the surgeon to select, approve of, or monitor
`
`the
`
`pulse duration,
`
`the number of pulses to be delivered,
`
`the
`
`number of pulses
`
`actually delivered to a particular
`
`location on the patient’s eye 104, and the irradiance of
`
`each pulse.
`
`In
`
`addition,
`
`the
`
`controller
`
`116 may
`
`synchronize the actions of various components in the system
`
`100 to obtain accurate delivery of laser light onto the
`
`cornea of
`
`the patient's eye 104.
`
`The controller
`
`116
`
`includes any hardware, software,
`
`firmware, or combination
`
`thereof for controlling the operation of the system 100.
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`il
`
`As
`
`an
`
`example,
`
`the controller
`
`116
`
`could represent
`
`computer
`
`(such as
`
`a desktop or
`
`laptop computer) at
`
`a
`
`a
`
`surgeon's location capable of displaying elements of
`
`the
`
`cornea reshaping procedure that are or may be of interest
`
`to the surgeon.
`
`[0035] A power supply 118 provides power
`
`to the laser
`
`106.
`
`The power
`
`supply 118
`
`is also controlled by the
`
`controller 116. This allows the controller 116 to control
`
`if and when power is provided to the laser 106.
`
`The power
`
`supply 118 represents any suitable source(s) of power for
`the laser 106.
`
`[0036] As
`
`shown
`
`in FIGURE
`
`1,
`
`the
`
`system 100 also
`
`includes one or more ocular diagnostic tools 120.
`
`The
`
`ocular diagnostic tools 120 may be used to monitor
`
`the
`
`condition of the patient’s eye 104 before, during,, or after
`
`the cornea reshaping procedure.
`
`For example,
`
`the ocular
`
`diagnostic tools 120 could include a keratometer or other
`
`corneal
`
`topography measuring device, which is used to
`
`measure the shape of the cornea in the patient’s eye 104.
`
`By comparing the shape of the cornea before and after the
`
`procedure,
`
`this tool may be used to determine a change in
`
`the shape of
`
`the cornea. After
`
`treatment, keratometric
`
`measurements
`
`may
`
`be
`
`performed
`
`to
`
`produce
`
`corneal
`
`10
`
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`
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`
`topographic maps
`been obtained.
`
`that verify the desired correction has
`In some embodiments,
`the keratometer may
`
`25
`
`provide a digitized output from which a visual display is
`
`producible to show the anterior surface shape of the cornea
`
`204.
`
`As another example,
`
`the ocular diagnostic tools 120
`
`could include a mechanism for viewing the cornea in the
`
`30
`
`patient's eye 104 during the procedure, such as a surgical
`
`microscope or
`
`a slit-lamp biomicroscope.
`
`Any other or
`
`additional ocular diagnostic tools 120 could be used in the
`
`system 100.
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`
`{0037]
`
`In addition,
`
`the system 100 may include a beam
`
`diagnostic tool 122.
`
`The beam distribution system 108
`
`could include a beam splitter that samples a small portion
`
`(such as a few percent) of one or more laser beams.
`
`A
`
`sampled laser beam could represent the beam that is to be
`
`split or one of the beams after splitting.
`
`The sampled
`
`portion of the beam is directed to the beam diagnostic tool
`
`122, which measures laser beam parameters such as power,
`
`spot size, and irradiance distribution.
`
`In this way,
`
`the
`
`controller 116 can verify whether the patient’s eye 104 is
`
`receiving a proper
`
`amount of
`
`laser
`
`light
`
`and whether
`
`various
`
`components
`
`in the
`
`system 100
`
`are
`
`operating
`
`properly.
`
`[0038]
`
`In one aspect of operation,
`
`a patient may lie
`
`down on a table that
`
`includes a head mount for accurate
`
`positioning of the patient’s head.
`
`The protective corneal
`
`applanator device 102 may be attached to an articulated arm
`
`that holds the device 102 in place.
`
`The articulated arm
`
`may be attached to a stable platform,
`
`thereby helping to
`
`restrain the patient’s eye 104 in place when the protective
`
`corneal applanator device 102 is attached to the patient’s
`
`eye 104.
`
`The patient may look up toward the ceiling during
`
`the procedure, and the laser beams transported by the fiber
`
`optic array 110 may be directed vertically downward onto
`
`the patient’s eye 104. Other procedures may vary from this
`
`example.
`
`For example,
`
`the protective corneal applanator
`
`device 102 may have a small permanent magnet mounted on the
`
`center of its front surface.
`
`This magnet may be used to
`
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`
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`
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`
`25
`
`fiber optic holder shaft on the
`attach and centrate a
`protective corneal applanator device 102 using another
`
`30
`
`small permanent magnet that is mounted on the fiber optic
`
`holder shaft.
`
`In addition, as described in more detail
`
`below, one or more deuterated ocular/ophthalmic solutions
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`13
`
`can be used during the procedure.
`
`{0039] A surgeon or other physician who performs
`
`the
`
`cornea reshaping procedure may use a
`
`tool
`
`(Such as an
`
`ophthalmic surgical microscope, a slit-lamp biomicroscope,
`
`oer other
`
`tool 120),
`
`together with one or more visible
`
`tracer laser beams
`
`(from a Low energy visible laser such as
`
`a helium-neon laser) collinear with the treatment beams,
`
`to
`
`verify the proper positioning of the treatment beams.
`
`The
`
`surgeon or other physician also uses the controller 116 to
`
`control
`
`the system 100
`
`so as
`
`to produce
`
`the correct
`
`pattern,
`
`irradiance, and exposure duration of the treatment
`
`The controller 116 could be used by the surgeon or
`beams.
`other physician as
`the focal point
`for controlling all
`
`variables and components
`
`in the system i100.
`
`During the
`
`procedure,
`
`the laser 106 produces functionally effective
`
`laser light, which is processed to produce the correct
`
`pattern and dose of functionally effective light on the
`
`anterior surface of the cornea in the patient’s eye 104.
`
`[0040] As described in more detail below,
`
`the protective
`
`corneal applanator device 102 provides various features or
`
`performs various
`
`functions during the cornea reshaping
`
`procedure.
`
`Among other
`
`things,
`
`the protective corneal
`
`applanator device 102 helps to provide thermal protection
`
`for the corneal epithelium in the cornea of the patient’s
`
`eye 104 during the procedure.
`
`For example,
`
`the protective
`
`corneal applanator device 102 may conduct heat away from
`
`the cornea in the patient’s eye 104 during the procedure.
`
`This may help to reduce the temperature of
`
`the corneal
`
`epithelium in the patient’s eye 104.
`
`By
`
`reducing the
`
`temperature of the corneal epithelium during the procedure,
`
`the protective corneal applanator device 102 may help to
`
`the corneal epithelium from reaching a threshold
`prevent
`temperature at which clinically significant damage to the
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`
`corneal epithelium occurs.
`
`The
`
`threshold temperature
`
`could,
`
`for
`
`example,
`
`occur at approximately 70°C.
`
`By
`
`keeping
`
`the
`
`corneal
`
`epithelium below this
`
`threshold
`
`temperature, clinically significant damage to the corneal
`
`epithelium may be avoided.
`
`In this document,
`
`the phrase
`
`“clinically significant
`
`damage”
`
`refers
`
`to damage
`
`that
`
`triggers a sufficient corneal wound healing that
`
`leads to
`
`significant regression of refractive correction. Alithough
`
`some damage may be
`
`inherent
`
`in particular embodiments,
`
`10
`
`clinically insignificant
`
`damage would
`
`not
`
`trigger
`
`a
`
`sufficient
`
`corneal wound
`
`healing
`
`and
`
`is
`
`therefore
`
`acceptable.
`
`[0041]
`
`In some
`
`embodiments,
`
`the
`
`reshaping procedure
`
`104
`the eye
`in the stroma of
`produces ocular changes
`without
`inducing clinically significant
`damage
`to the
`
`15
`
`viability of ocular structures. Although some damage may
`
`be
`
`inherent
`
`in
`
`particular
`
`embodiments,
`
`clinically
`
`insignificant damage means
`
`that
`
`the eye 104 continues to
`
`function optically and that the cellular layers continue to
`
`live and regenerate.
`
`For example, normal undamaged corneal
`
`stroma contains keratocytes, which are specialized cells
`
`that maintain stromal integrity and health by synthesizing
`
`collagen and proteoglycans
`
`(among other things).
`
`These
`
`“quiescent” keratocytes can be activated and transformed
`
`into repair phenotypes (fibroblasts and myofibroblasts) if
`
`triggered by,
`
`for
`
`example,
`
`significant
`
`damage
`
`to the
`
`epithelial basement membrane by corneal wounding.
`
`The
`
`repair phenotypes secrete collagenase to degrade damaged
`
`collagen,
`
`synthesize
`
`new collagen,
`
`and
`
`cause
`
`stromal
`
`remodeling (among other things). Clinicaily insignificant
`
`damage may not
`
`include a fibrotic wound healing response,
`
`including activation and transformation of keratocytes into
`
`their
`
`repair phenotypes, which leads
`
`to regression of
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`refractive correction.
`
`15
`
`[0042} In this example, heating the collagen of
`
`the
`
`stroma to a temperature of at least 55 to 58°C and up toa
`
`Maximum of about
`
`80°C causes
`
`the collagen to shrink,
`
`thereby changing the shape of the cornea of the eye 104.
`
`The main
`
`structural
`
`change occurring during collagen
`
`shrinkage may
`
`be denaturation by
`
`a helix-coil
`
`phase
`
`transition in which Type I collagen molecules rearrange
`
`from a triple helix conformation to a random coil form due
`
`to the breakage of hydrogen bonds that maintain the triple
`
`helix.
`
`Other structural
`
`changes
`
`to the extracellular
`
`matrix may also be caused by heating. For example,
`
`the
`
`proteoglycans and the hydration state of the stroma may be
`
`changed,
`
`thereby contributing to corneal reshaping.
`
`In some
`
`embodiments,
`
`the maximum temperature
`
`of photothermal
`
`modification
`
`of
`
`the
`
`stroma
`
`could
`
`be
`
`restricted to
`
`approximately 75°C,
`
`the approximate threshold temperature
`
`for stromal keratocyte damage and necrosis,
`
`in order to
`
`reduce the possibility of clinically significant damage
`
`that
`leads
`to
`corneal wound
`healing
`regression of refractive correction.
`
`responses
`
`and
`
`[0043]
`
`In these embodiments,
`
`the heating process can be
`
`caused by directing light energy onto the cornea of the eye
`
`104
`
`to cause absorption of
`
`the energy, which heats the
`
`stroma to the desired temperature.
`
`This may be done by
`
`providing a light source (such as laser 106)
`
`that radiates
`
`light
`
`energy
`
`characteristically
`
`deposited within
`
`specified range of depths of
`
`the
`
`corneal
`
`tissue.
`
`a
`
`[In
`
`particular
`
`embodiments,
`
`for photothermal keratoplasty,
`
`wavelengths of
`
`light energy that are absorbed primarily
`
`within the anterior region (approximately one-third to one-
`
`half the thickness) of the cornea may be used.
`
`[0044] The selection and control of the source of light
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`16
`
`energy that
`
`induces the thermal changes to the cornea of
`
`the eye 104 may be important.
`
`The variables used to select
`
`the appropriate amount and type of light energy may include
`
`wavelength,
`
`irradiance level, and time (duration).
`
`These
`
`three variables may be selected so that the amount of light
`
`energy is functionally effective to produce a predetermined
`
`change in the anterior portion only of
`
`the stroma. The
`
`light source can be a
`
`laser or a non-laser light source
`
`appropriate wavelengths,
`the
`of
`radiation
`providing
`irradiances, and durations to be absorbed within the stroma
`
`10
`
`without penetrating deeply into the eye 104 in a manner
`
`that can damage the endothelium of
`
`the cornea or other
`
`structures of the eye 104. Additionally,
`
`the light source
`
`may accomplish the desired modification of the stroma by
`
`15
`
`photothermal keratoplasty on a timescale in which thermal
`
`diffusion from the heated stroma into adjacent tissue does
`
`not damage the endothelium or other ocular structures.
`
`The
`
`light energy may also be of a type that can be directed
`
`onto the cornea and controlled to produce the appropriate
`
`29
`
`thermal changes.
`
`[0045] The following represents particular examples of
`
`lasers 106 that could be used in the system 100.
`
`The use
`
`of
`
`these particular examples does not
`
`limit
`
`the light
`
`energy
`
`source,
`
`preferred wavelength,
`
`irradiance,
`
`or
`
`duration of exposure in any way.
`
`As examples,
`
`thulium
`
`based lasers producing light within a wavelength range of
`
`approximately 1.8 to 2.1 microns can be effectively used.
`
`Thulium based lasers include a Tm:YAG laser
`
`(in which
`
`thulium ions are doped into a crystalline matrix of yttrium
`
`aluminum garnet) or a thulium fiber laser (in which thulium
`
`fiber matrix).
`ions are doped into a glass
`fluoride chemical
`lasers could also be used.
`
`Hydrogen
`In the
`
`following description,
`
`the term “wavelength” generally
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`17
`
`includes wavelengths of slightly greater
`
`and
`
`slightly
`
`smaller value and is often described in this disclosure as
`
`"one or more wavelengths."
`
`[0046]
`
`In particular embodiments,
`
`the wavelength range
`
`of light energy from the laser 106 is about 2.4 microns to
`
`about
`
`2.67 microns,
`
`such
`
`as
`
`approximately
`
`2.5
`
`to
`
`approximately 2.6 microns, for a hydrogen fluoride chemical
`
`laser. Light within this range of wavelengths is absorbed
`
`primarily in the anterior of
`
`the
`
`stroma.
`
`In other
`
`particular embodiments,
`
`light having wavelength