EP2616025A1 - Method for performing a reversible refractive procedure - Google Patents
Method for performing a reversible refractive procedureInfo
- Publication number
- EP2616025A1 EP2616025A1 EP11824649.5A EP11824649A EP2616025A1 EP 2616025 A1 EP2616025 A1 EP 2616025A1 EP 11824649 A EP11824649 A EP 11824649A EP 2616025 A1 EP2616025 A1 EP 2616025A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- refractive
- lenticule
- refractive lenticule
- procedure
- eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F9/00825—Methods or devices for eye surgery using laser for photodisruption
- A61F9/00834—Inlays; Onlays; Intraocular lenses [IOL]
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F9/00825—Methods or devices for eye surgery using laser for photodisruption
- A61F9/00831—Transplantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/145—Corneal inlays, onlays, or lenses for refractive correction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/16—Intraocular lenses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
- A61F2009/00872—Cornea
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F2009/00878—Planning
- A61F2009/0088—Planning based on wavefront
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F2009/00885—Methods or devices for eye surgery using laser for treating a particular disease
- A61F2009/00895—Presbyopia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/013—Instruments for compensation of ocular refraction ; Instruments for use in cornea removal, for reshaping or performing incisions in the cornea
Definitions
- Various embodiments relate to the field of refractive procedures or surgeries, in particular, reversible refractive procedures on refractive lenticules.
- Surgical correction for refractive errors may be performed by a number of procedures.
- Laser correction involves procedures such as EpiLASIK, LASIK or conductive keratoplasty, while lens based corrections involve the use of phakic intraocular lenses.
- LASIK is still the procedure of choice for both patients and refractive surgeons.
- LASIK consists of two steps: the first step involves the formation of a corneal flap and the second step is when the excimer ablation is performed in the corneal stromal bed.
- Femtosecond lasers FL have been widely used in LASIK surgery to fashion the corneal flap. The laser will cut a lamellar flap followed by a vertical corneal incision. A vertical cut may be produced since the femtosecond laser can deliver laser pulses of 1 micron diameter at a preselected depth in the cornea, which then expands to 20/30 microns with the formation of a cavitation bubble.
- Femto-LASIK Even though Femto-LASIK has demonstrated good efficacy, it can still be associated with side effects found in standard LASIK, for example, glare, haloes, dry eye and still requires the use of two separate laser machines, one for the flap the other for the excimer ablation. This increases the length of time of the overall procedure and the costs.
- Refractive Lenticular Extraction (ReLEx) has been proposed. It consists of performing the entire refractive procedure without an excimer laser. ReLEx surgery involves 2 different surgical approaches, Femtosecond Lenticule Extraction (FLEx), and Small Incision Lenticule Extraction (SMILE).
- FLEx Femtosecond Lenticule Extraction
- SMILE Small Incision Lenticule Extraction
- FLEx mimics conventional LASIK surgery by performing a LASIK type hinged flap to extract the lenticule.
- the femtosecond laser creates four stromal incisions to create a corneal lenticule and a corneal flap.
- the size and shape of the lenticule is calculated based on the patient refractive error.
- the lenticule is separated from the flap above and the rest of the cornea below using a small spatula. Following this, the lenticule is grasped with a forceps and extracted from the eye. Finally, the flap is repositioned and the interface washed. At this time the refractive error is already corrected without the use of a second laser.
- the SMILE procedure is a flap-less form of small incision surgery, in which the lenticule is extracted through a small superior pocket incision, without the formation or lifting of a full flap, which has the advantages of minimal incision or disturbance to the corneal surface, greater wound strength as a full flap is not raised, the possibility of less flap-related optical aberrations, with enhanced visual quality and less loss of contrast sensitivity, and less neurotrophic keratopathy or dry eye, as less corneal nerves may be disrupted at the corneal periphery when a full flap is used. Both procedures come under the umbrella term of Refractive Lenticule Extraction (ReLEx).
- ReLEx Refractive Lenticule Extraction
- the present invention relates to a method for performing a reversible refractive procedure by reimplanting a refractive lenticule that has been obtained by a refractive procedure on the eye, the method comprising the steps of preparing the refractive lenticule for reimplantation, creating a corneal flap in an eye of an acceptor, transferring the refractive lenticule under the corneal flap, and repositioning and covering the acceptor's corneal flap; thereby reimplanting the refractive lenticule.
- the present invention relates to a refractive lenticule obtained by a refractive procedure on the eye of a donor for use in a method for subsequent reimplantation in a reversible refractive procedure on an acceptor, wherein the refractive lenticule is stored at a temperature below 0°C.
- Figure 1 shows a flow diagram illustrating the processes performed for short term study of FLEx vs LASI , in accordance to various embodiments
- Figure 2 shows in vivo confocal microscopy of keratocyte activation, according to various embodiments
- Figure 3a shows immunohistochemistry images of fibronectin expression of the central cornea, according to various embodiments
- Figure 3b shows immunohistochemistry images of fibronectin expression of the periphery of flap, according to various embodiments
- Figure 4a shows immunohistochemistry images of inflammation of the central cornea, according to various embodiments
- Figure 4b shows immunohistochemistry images of inflammation of the periphery of flap, according to various embodiments
- Figure 5 shows light microscopy of an extracted lenticule at (a) lOOx magnification; (b) 400x magnification of the anterior edge; (c) 400x magnification of the posterior edge; and (d) 5600x magnification of a keratocyte, according to various embodiments;
- Figure 6a shows slit lamp (SL) images of the lenticule following re-implantation, in accordance to various embodiments
- Figure 6b shows confocal microscopic images of the lenticule following reimplantation in accordance to various embodiments
- Figure 6c shows a plot of corneal thickness, in accordance to various embodiments.
- Figure 7 shows in vivo confocal microscopy of the lenticule, according to various embodiments
- Figure 8 shows topography results 28 days after re-implantation of the lenticule, in accordance to various embodiments
- Figure 9 shows immunohistochemistry images of inflammation of the eye 28 days after re-implantation of the lenticule compared against a control (in the rightmost column), according to various embodiments;
- Figure 10 shows confocal microscopic images of inflammation similar to Figure 9 using various labels and stains, in accordance to various embodiments;
- Figure 11a shows a light microscopic image of extracted stromal lenticules, according to various embodiments
- Figure 1 lb shows a magnified light microscopic image of the extracted stromal lenticules, according to various embodiments
- Figure 11c shows a light microscopic image of a cell culture of the extracted stromal lenticules, according to various embodiments
- Figure 1 Id shows a light microscopic image of the cell culture of Figure 1 1c after adding the stock freezing solution, according to various embodiments
- Figure l ie shows a light microscopic image of the cell culture following a culture of a fresh lenticule, according to various embodiments
- Figure l lf shows a light microscopic image of the cell culture after 1 month of cryopreservation, according to various embodiments.
- Figure l lg shows gel electrophoresis for real-time PCR, in accordance to various embodiments.
- the present invention relates to a method for performing a reversible refractive procedure by reimplanting a refractive lenticule that has been obtained by a refractive procedure on the eye.
- the method comprising the steps of preparing the refractive lenticule for reimplantation, creating a corneal flap in an eye of an acceptor, transferring the refractive lenticule under the corneal flap, and repositioning and covering the acceptor's corneal flap; thereby reimplanting the refractive lenticule.
- the term "refractive procedure” may generally refer to any eye surgery used to improve the refractive state of the eye. This may include methods of surgical remodeling of the cornea or cataract surgery. For example, use of excimer lasers to reshape curvature of the cornea is a refractive procedure.
- the term "reversible refractive procedure” may refer to a procedure to invert or undo the refractive procedure.
- the term "refractive lenticule”, as used herein, relates to a piece of stromal corneal tissue that is removed to correct refractive error of the eye.
- the refractive lenticule may be peeled off the corneal bed.
- the refractive lenticule may have any shape and can, for example, be lense-shaped.
- the refractive lenticule has been stored at a temperature below 0 °C.
- the refractive lenticule may have been stored at about -80 °C.
- the refractive lenticule may be freezed and the frozen refractive lenticule may be stored in a freezer or a cryopreserving environment.
- the refractive lenticule may be held by a support to maintain a curved surface comparable to a corneal surface.
- the support may be a rigid gas permeable contact lens or a mounting structure comprising a curved surface.
- the term "mounting structure" may refer to any structure or mechanism to hold the refractive lenticule in place.
- the mounting structure may include a right and left mount to hold the refractive lenticule at each end such that the refractive lenticule is spreaded like a flat sheet.
- the mounting structure may also allow for easy removal of the refractive lenticule without damage.
- the step of preparing the refractive lenticule for reimplantation may comprise thawing the refractive lenticule in a water bath of about 37 °C.
- the refractive lenticule may be washed in a buffer solution.
- the buffer solution may be selected from the group consisting of morpholinepropanesulfonic acid, a Phosphate Buffered Solution (PBS), a trehalose buffer, and a sucrose buffer.
- the step of preparing the refractive lenticule for reimplantation may further comprise enzymatically digesting the thawed refractive lenticule for culture of corneal stromal fibroblast.
- the step of preparing the refractive lenticule for reimplantation may also further comprise adjusting refractive errors of the refractive lenticule to restore near vision, or to correct presbyopia, or to treat complications of keratectasia.
- the step of repositioning and covering the acceptor's corneal flap may comprise placing a bandage contact lens over the repositioned corneal flap.
- the refractive lenticule for reimplantation may have been obtained by a method comprising the steps of creating an incision in an eye of a donor, and extracting the refractive lenticule through the incision.
- the incision may be made using a one-laser refractive surgery.
- the one-laser refractive surgery may be Refractive Laser Extraction (ReLEx).
- the ReLEx may comprise Small Incision Lenticule Extraction (SMILE).
- SMILE Small Incision Lenticule Extraction
- the incision may comprise one or two or three or four stromal incisions.
- the four stromal incisions may further create a corneal flap in the donor's eye.
- the ReLEx in this embodiment may be Femtosecond Lenticule Extraction (FLEx).
- the donor and the acceptor may be the same subject. In other embodiments, the donor and the acceptor may be different subjects.
- the present invention relates to a refractive lenticule obtained by a refractive procedure on the eye of a donor for use in a method for subsequent reimplantation in a reversible refractive procedure on an acceptor, wherein the refractive lenticule is stored at a temperature below 0°C.
- the refractive lenticule may be snap-freezed in liquid nitrogen for about 10 minutes.
- the snap-freezing process may be carried out for about 5 minutes to about 15 minutes, or about 5 minutes to about 8 minutes, or about 12 minutes to about 15 minutes.
- the refractive lenticule may be stored at about -80 °C.
- the refractive lenticule may be cryopreserved.
- the refractive lenticule may be suspended in a serum-containing medium in a vessel, a freezing solution of about 10% serum and about 20% organic solvent is added in a dropwise manner into the vessel to form a mixture of about 10% serum and about 10% organic solvent, the vessel containing the mixture is placed in a -80 °C freezer for at least 4 hours; and the frozen mixture is transferred into liquid nitrogen for storage.
- the organic solvent may be selected from the group consisting of organic solvent is selected from the group consisting of hexane, heptane, cyclohexane, benzene, pyridine, dichloromethane, chloroform, carbon tetrachloride, carbon disulfide, tetrahydrofuran, dioxane, diethyl ether, diisopropylether, ethylene glycol monobutyl ether, methyl ethyl ketone, methyl isobutyl ketone, acetone, cyclohexanone, ethyl acetate, isobutyl isobutyrate, ethylene glycol diacetate, dimethylformamide, acetonitrile, N,N-dimethyl acetamide, nitromethane, acetonitrile, N-methylpyrrolidone, dimethylsulfoxide water, methanol, ethanol, butyl alcohol and formic acid.
- the serum
- the refractive lenticule may be obtained by creating an incision in an eye of the donor; and extracting the refractive lenticule through the incision.
- the incision may be created using a one-laser refractive surgery.
- the one-laser refractive surgery is Refractive Laser Extraction (ReLEx).
- the ReLEx may comprise Small Incision Lenticule Extraction (SMILE) or Femtosecond Lenticule Extraction (FLEx).
- the donor and the acceptor may be the same subject. In another embodiment, the donor and the acceptor may be different subjects.
- the stored refractive lenticule may be processed to adjust its refractive errors to restore near vision, or to correct presbyopia, or to treat complications of keratectasia.
- the term "about” or “approximately” as applied to a value may encompass the exact value and a variance of +/- 5% of the value.
- the phrase “at least substantially” may include “exactly” and a variance of +/- 5% thereof.
- “A is at least substantially same as B” may encompass embodiments where A is exactly the same as B, or where A may be within a variance of +/- 5%, for example of a value, of B, or vice versa.
- Various embodiments provides the storage of refractive lenticules following the FLEx or SMILE ReLEx or other similar stromal lenticule extraction procedures to make these completely reversible or modifiable refractive procedures.
- FLEx/SMILE The main advantage of FLEx/SMILE is that in theory it may be able to correct higher refractive powers with removal of less tissue and also it is a potentially reversible procedure.
- a FLEx model in an animal is firstly established.
- a rabbit model is chosen since this has been previously chosen to study refractive surgical procedure, for example, LASI and PRK so as to provide basis for comparison.
- Example A Comparison to LASIK - Establishing ReLEx model
- Rabbits are anesthesized with a combination of xylazine hydrochloride (20 mg/kg) and kentamine hydrochloride (40 mg/kg) intramuscularly.
- preservative-free oxybuprocain hydrochloride eyedrops (Benoxinat SE 0.4%) are applied to each eye just before the surgery. After the surgery, the eyelids are closed with a temporary tarsorrhaphy placed with a 6-0 suture.
- the rabbits are then sacrificed under anesthesia by intracardiac injection of 5 ml embutramine 0.2 g/ml, mebezonium iodide 0.05 g/ml, and tetracaine hydrochloride 0.005 g/ml. All rabbits are treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The experimental protocol is approved by the Institutional Animal Care and Use Committee of SingHealth.
- Example B Storage and re-implantation of stromal lenticule
- the extracted stromal lenticules are carefully transferred on the Rigid Gas Permeable (RGP) contact lens. A marking at 6 o'clock position is made on the lens to indicate the anatomical position of the lenticule on the cornea before extraction. A drop of 10% DMSO (Sigma, St. Louis, MI) is applied on the lenticule before a 10-minute snap freezing in the liquid nitrogen (N 2 ). The lenticule is stored in -80 °C until further use.
- RGP Rigid Gas Permeable
- the re-implantation of the lenticule is performed 28 days after the initial ReLEx procedure.
- a Siebel spatula is inserted under the flap near the hinge and the flap is then lifted.
- the lenticule is transferred onto the exposed stromal bed by a sliding motion from the RGP contact lens.
- a bandage contact lens (Bausch & Lomb, Rochester, NY) is placed over the flap and the eyelid is closed with a temporary tarsorraphy for 3 days.
- Post-operative follow up is done on day 3, 14, and 28 after the re-implantation.
- Gentamycin and Dexamethasone of 1 ml each are injected subconjunctivally following the re-implantation procedure and each post-operative follow up.
- Figure 1 shows a flow diagram illustrating the processes performed for short term study (sacrifice 1 day after surgery in Example A) and long term study (sacrifice 28 days after surgery in Example B) of FLEx vs LASIK.
- the term "OCT” for example in Figure 1 refers to optical coherence tomography.
- immunofluorescent staining may generally refer to fluorescent dyeing for detection and imaging of biological samples using light microscopy with a fluorescence microscope.
- TUNEL may generally refer to terminal deoxynucleotidyl transferase dUTP nick end labeling for detecting DNA fragmentation by labeling the terminal end of nucleic acids.
- in vivo confocal refers to in vivo confocal microscopy (IVCM), wherein confocal microscopy may generally refer to a microscopy for obtaining increased resolution by limiting the illumination and observation systems to a single point.
- the term "refractive states” may generally refers to a determining procedure for the purpose of obtaining glasses and includes specification of lens type (monofocal, bifocal, other), lens power, axis, prism, absorptive factor, impact resistance, and other factors.
- Example C Lenticule Viability - Before and after Cryopreservation
- Extracted stromal lenticules from clinical patients and also from human cadaver eyes have undergone TUNEL assay, transmission electron microscopy (TEM), cell culture and real-time PCR.
- Extracted human stromal lenticule is washed twice (about 10 minutes each) in a phosphate buffered saline (PBS) buffered antibiotic/antimycotic solution.
- PBS phosphate buffered saline
- the lenticule is then transferred into a cryovial and resuspended in 500 ⁇ medium containing 10% fetal bovine serum (FBS, Invitrogen, Carlsbad, CA, USA).
- FBS fetal bovine serum
- a stock freezing solution containing 10% FBS and 20% dimethyl sulfoxide (DMSO, Sigma, St. Louis, MO, USA.) are added slowly in a dropwise manner to an equal volume ratio, to make a final volume of 1 ml freezing solution containing 10% FBS and 10% DMSO.
- Freezing of the cryovial containing the stromal lenticule is carried out in a cryo- container ("Mr. Frosty", Nalgene, Denmark), within a -80 °C freezer overnight, and transferred into liquid nitrogen the following day for long-term storage.
- Thawing of frozen stromal lenticule is carried out after one month of cryopreservation where the vial containing the frozen stromal lenticule is rapidly thawed in water bath at 37 °C. Immediately after thawing, the stromal lenticule is rinsed twice in a PBS solution to remove the cryoprotectant agents. Thawed lenticules are either enzymatically digested for the culture of corneal stromal fibroblast, or immersed in a tissue-freezing compound and frozen for cryosection to be analyzed with TEM and TUNEL assay. Discussion
- Table 1 shows the data extracted from topography results for various refractive procedures as carried out in the short term study of Example A.
- Kh and Kv represent horizontal Keratometry readings and vertical Keratometry readings, respectively, to determine the exact curvature (steepness) of an eye with respective standard deviations. That is, the larger the Keratometry reading, the steeper or the more curved is the eye.
- the control procedure is an unoperated eye. For the same myopic correction, less corneal flattening using the FLEx procedure as compared to using the LASIK procedure is observed. For example, with -3.00D correction, using the FLEx procedure Kh is about 37.16 diopter, while using the LASIK procedure Kh is 37.00 diopter.
- the Kh using the FLEx procedure is larger than that using the LASIK procedure; thus the eye using the FLEx procedure is steeper or more curved, therefore less flattening.
- Figures 3a and 3b show immunohistochemistry images of increasing fibronectin expression with increasing power of myopic correction with both ReLEx and LASIK.
- the term "ReLEx” may be interchangeably referred to as "FLEx”.
- the myopic correction of -6.00D is of a larger or increased power as compared to the myopic correction of -3.00D.
- increasing fibronectin expression in term of higher intensity shades are observed as indicated by the arrows.
- Figures 4a and 4b show immunohistochemistry images of inflammation.
- FIG 4b it is observed that there are similar levels of inflammation at low correction (i.e., at -3.00D) between LASIK and ReLEx (as indicated by the area enclosed by the double-dashed rectangle).
- higher corrections i.e., at -6.00D
- there is more inflammation in the LASIK group as indicated by the arrows in Figure 4a and the area enclosed by the single-dashed ellipse in Figure 4b).
- Slit lamp (SL) images in Figure 6a and the confocal microscope images of Figures 6b show clearing of lenticule following re-implantation in accordance to various embodiments, for example, in Example B.
- Figure 6c shows an increase in corneal thickness back to preoperative stat on OCT.
- Figure 9 shows immunohistochemistry images of inflammation of the eye 28 days after re-implantation of the lenticule compared against a control (in the rightmost column).
- the leftmost column of Figure 9 shows lOOx magnified immunohistochemistry images of the eye 28 days after re-implantation of the lenticule while the center column shows respective 200x magnified images of the enclosed rectangular areas correspondingly marked out in each of lOOx magnified images in the leftmost column. It is shown from the images of the eye 28 days after re-implantation of the lenticule, more clearly in the enlarged images of the center column that new extracellular matrix formation and minimal inflammation are present, as indicated by the light shades within the area enclosed by the dashed ellipses.
- Figure 10 shows confocal microscopic images of inflammation similar to Figure 9 using various labels (TUNEL) and stains (Ki-67 and Phalloidin).
- Figure 11a shows a light microscopic image of extracted stromal lenticules as described in Example C.
- Figure l ib shows a magnified light microscopic image of the extracted stromal lenticules before cryopreservation following collagenase digestion as described in Example C.
- Figure 1 1c shows a cell culture of the extracted stromal lenticules. After adding the stock freezing solution containing 10% FBS and 20% DMSO to the cell culture, longish cells (fibroblasts) are observed in Figure l id.
- Figure l ie shows the cell culture following a culture of a fresh lenticule, and Figure 1 If shows cell culture after 1 month of cryopreservation.
- Figure 1 lg shows the gel electrophoresis for real-time PCR of the extracted stromal lenticules after cryopreservation, wherein KERA refers to keratoctyes, ALDH31A refers to Aldehyde dehydrogenase 31 A, GAPDH refers to glyceraldehyde-3 -phosphate dehydrogenase, and the leftmost band of the gel electrophoresis being a marker.
- KERA refers to keratoctyes
- ALDH31A refers to Aldehyde dehydrogenase 31 A
- GAPDH refers to glyceraldehyde-3 -phosphate dehydrogenase
- the leftmost band of the gel electrophoresis being a marker.
- the presence of keratocyte mRNA is observed.
- the object of various embodiments is to store the lenticule following extraction for an indefinite period (or for at least the lifetime of a patient) in a freezing manner.
- Freezing may include all forms of cryobiology from fast freezing to vitrification. Following preservation, the lenticule is stored by freezing. Storage is required so that re-implantation of the lenticule at a later date can be carried out. The re-implantation is able to correct the original refractive error that has been removed by the lenticule; thereby reversing the procedure, or to enable further adjustment of the refractive errors, including restoration of near vision, This allows for solving presbyopia at a subsequent date, or to treat the potential complication of keratectasia due to, for example, inadequate stromal bed thickness and strength, which may be associated with collagen cross-linking of the lenticule and/or stromal recipient bed. This makes the ReLEx procedures reversible forms of corneal refractive surgery, which offers considerable advantages over current techniques.
- the reversible refractive procedure allows for (i) the reimplantation of the lenticule if needed to treat future presbyopia, or (ii) the correction of the refractive error if the patient wants the procedure reversed, or (iii) the treatment of keratectasia, or (iv) more accurate calculation of intraocular lens power for cataract surgery if the patient needs this as he/she gets older.
- the lenticules are allowed to be stored for the lifetime of the patient so that it may be replaced at anytime.
- the lenticules may also be modified by surgical or excimer laser techniques to alternative refractive powers.
- Various clinical scenarios are: Scenario 1 : Total reversal of refractive procedure in the same patient
- the unmodified lenticule is re-implanted back into the same patient either through the original flap or via a new femtosecond ablation procedure, potentially for treatment of keratectasia.
- Scenario 2 Reimplantation into the same patient to treat subsequent alterations in refractive error
- the lenticule may be modified (e.g. by excimer ablation) to suit the required refractive error, e.g. hyperopia or astigmatism.
- Scenario 3 Reimplantation to treat onset of presbyopia in the same patient
- the lenticule may be modified to a low hyperopic power (e.g. about 1.00D or about 1.50D) and reimplanted in the non-dominant eye of a presbyopic patient to effect monovision correction.
- a low hyperopic power e.g. about 1.00D or about 1.50D
- the lenticule may be donated by the patient (with appropriate informed consent and donor serology testing) to be used as a lamellar corneal stromal allograft transplant to effect refractive treatments for other patients in the same situations as Scenarios 1 to 3 above.
- the lenticules may be donated by the patient (with appropriate informed consent and donor serology testing) to be used as a lamellar corneal stromal allograft transplant for treating a variety of other corneal refractive, tectonic or therapeutic conditions, such as keratoconus, corneal thinning and irregularities, descemetoceles, and corneal perforations.
- the lenticules may be donated by the patient (with appropriate informed consent and donor serology testing) to be used as a lamellar corneal stromal allograft transplant for treating presbyopia in other patients by standardized modification of the lenticules to presbyopic designs, such as multifocal designs, wavefront guided designs, diffractive designs, aspheric profile designs, and a small (e.g. about 3-5 mm) "centre near" presbyopic implant to effect a bifocal cornea effect.
- presbyopic designs such as multifocal designs, wavefront guided designs, diffractive designs, aspheric profile designs, and a small (e.g. about 3-5 mm) "centre near" presbyopic implant to effect a bifocal cornea effect.
- RGP contact lens or similar devices or a mounting structure which has a curved surface replicating the corneal surface radius to ensure correct shape for storage.
- the patients' lenticules may be stored in such a bank underwritten costs by the patient for possible reimplantation at a future date.
Abstract
Description
Claims
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US38203710P | 2010-09-13 | 2010-09-13 | |
PCT/IB2011/002125 WO2012035403A1 (en) | 2010-09-13 | 2011-09-13 | Method for performing a reversible refractive procedure |
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EP2616025A1 true EP2616025A1 (en) | 2013-07-24 |
EP2616025A4 EP2616025A4 (en) | 2015-02-18 |
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EP (1) | EP2616025A4 (en) |
AU (1) | AU2011303580B2 (en) |
SG (1) | SG188466A1 (en) |
WO (1) | WO2012035403A1 (en) |
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US9622911B2 (en) | 2010-09-30 | 2017-04-18 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
EP2830637A4 (en) | 2012-03-29 | 2016-03-16 | Cxl Ophthalmics Llc | Compositions and methods for treating or preventing diseases associated with oxidative stress |
US9555111B2 (en) | 2012-03-29 | 2017-01-31 | Cxl Ophthalmics, Llc | Ocular cross-linking system and method for sealing corneal wounds |
EP2830627A4 (en) | 2012-03-29 | 2015-10-14 | Cxl Ophthalmics Llc | Ocular treatment solutions, delivery devices and delivery augmentation methods |
DE102013218415A1 (en) | 2012-09-14 | 2014-04-10 | Carl Zeiss Meditec Ag | Eye surgery procedure |
US10092393B2 (en) | 2013-03-14 | 2018-10-09 | Allotex, Inc. | Corneal implant systems and methods |
CN103892938A (en) * | 2014-04-01 | 2014-07-02 | 薛春燕 | Corneal lamellar piece and production method thereof |
US10449090B2 (en) | 2015-07-31 | 2019-10-22 | Allotex, Inc. | Corneal implant systems and methods |
DE102016208012A1 (en) * | 2016-05-10 | 2017-11-16 | Carl Zeiss Meditec Ag | Eye surgery procedure |
DE102021124087A1 (en) * | 2021-09-17 | 2023-03-23 | Carl Zeiss Meditec Ag | Correction of the refraction of an eye by corneal modification |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996024018A1 (en) * | 1995-01-30 | 1996-08-08 | Organogenesis, Inc. | Method and package design for cryopreservation and storage of cultured tisse equivalents |
CN101463340A (en) * | 2008-12-31 | 2009-06-24 | 大连理工大学 | Two-step temperature-reducing method for eliminating cryogenic fracture in biological tissue preserved by vitrification method |
WO2009158723A2 (en) * | 2008-06-27 | 2009-12-30 | Amo Development, Llc. | Intracorneal inlay, system, and method |
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US6989008B2 (en) * | 2001-03-23 | 2006-01-24 | Minu Llc | Adjustable ablatable inlay |
US6630001B2 (en) * | 1998-06-24 | 2003-10-07 | International Heart Institute Of Montana Foundation | Compliant dehyrated tissue for implantation and process of making the same |
US7960098B2 (en) * | 2007-07-12 | 2011-06-14 | Warsaw Orthoperic, Inc. | Methods and compositions for the preservation of cells and tissues |
-
2011
- 2011-09-13 WO PCT/IB2011/002125 patent/WO2012035403A1/en active Application Filing
- 2011-09-13 AU AU2011303580A patent/AU2011303580B2/en not_active Ceased
- 2011-09-13 EP EP11824649.5A patent/EP2616025A4/en not_active Ceased
- 2011-09-13 SG SG2013017330A patent/SG188466A1/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996024018A1 (en) * | 1995-01-30 | 1996-08-08 | Organogenesis, Inc. | Method and package design for cryopreservation and storage of cultured tisse equivalents |
WO2009158723A2 (en) * | 2008-06-27 | 2009-12-30 | Amo Development, Llc. | Intracorneal inlay, system, and method |
CN101463340A (en) * | 2008-12-31 | 2009-06-24 | 大连理工大学 | Two-step temperature-reducing method for eliminating cryogenic fracture in biological tissue preserved by vitrification method |
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WO2012035403A1 (en) | 2012-03-22 |
AU2011303580B2 (en) | 2016-03-10 |
AU2011303580A1 (en) | 2013-05-02 |
WO2012035403A8 (en) | 2012-09-20 |
EP2616025A4 (en) | 2015-02-18 |
SG188466A1 (en) | 2013-05-31 |
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